See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/357271365

Organs at risk radiation dose constraints

Article in Cancer/Radiothérapie · December 2021

DOI: 10.1016/j.canrad.2021.11.001

CITATIONS READS

50 2,746

2 authors:

Ge Noël Dedi Antoni

University of Strasbourg Universitas HKBP Nommensen
654 PUBLICATIONS 8,884 CITATIONS 17 PUBLICATIONS 79 CITATIONS

SEE PROFILE SEE PROFILE

All content following this page was uploaded by Ge Noël on 04 February 2022.

The user has requested enhancement of the downloaded file.

G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Disponible en ligne sur

ScienceDirect
www.sciencedirect.com

Clinical practice guidelines

Organs at risk radiation dose constraints

Doses limites de radiations dans les organes à risque
G. Noël ∗ , D. Antoni
Département de radiothérapie-oncologie, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, BP 23025, 67033 Strasbourg, France

a r t i c l e i n f o a b s t r a c t

Keywords: Dose constraints are essential for performing dosimetry, especially for intensity modulation and for radio-
Dose constraints therapy under stereotaxic conditions. We present the update of the recommendations of the French
Stereotactic radiotherapy society of oncological radiotherapy for the use of these doses in classical current practice but also for
IMRT
reirradiation.
3D-RT
© 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All
Radiation therapy
rights reserved.
Guidelines
French Society for Radiation Oncology

r é s u m é

Mots clés : Les contraintes de dose sont primordiales pour effectuer les planimétries, tout particulièrement pour la
Contraintes de dose radiothérapie avec modulation d’intensité et pour la radiothérapie en conditions stéréotaxiques. Nous
Radiothérapie en conditions stéréotaxiques présentons la mise à jour des recommandations de la Société française de radiothérapie oncologique pour
RT-3D l’utilisation de ces doses dans la pratique courante, mais aussi pour la réirradiation.
RCMI
© 2021 Société française de radiothérapie oncologique (SFRO). Publié par Elsevier Masson SAS. Tous
Réirradiation
droits réservés.
Radiothérapie
Recommandations
Société française de radiothérapie
oncologique

1. Introduction practices, preparation, and dosimetry while raising new questions

concerning long-term safety and tolerance to treatments, but also
The dose to administer in organs at risk is becoming increasingly by combination treatments with new medicinal products [11].
better known. The rate of adverse events has decreased with devel- These changes raise the question of the real equivalence of the
opment of intensity modulation radiotherapy (IMRT) [1]. However, dose calculated with the quadratic linear model even though cal-
the low doses cover more healthy volume [2]. Therefore, radiother- culations of the Normal Tissue Complication Probability (NTCP) are
apy is in a dilemma, which is to avoid acute adverse events related still awaited [12].
to the total dose received by organs at risk and to prevent unknown Because the volumes irradiated in IMRT with high and medium
adverse events related to stochastic reactions [3]. doses are smaller, reirradiation of patients is possible [13]. Then
More and more therapies are being developed such as hypofrac- the questions arise of “forgetting” the dose delivered previously,
tionated treatments, moderately increased doses in breast cancer, the “cumulative” total of doses delivered with different fractiona-
and prostate cancer and with very high doses in stereotactic radi- tions, the validation of protocolised dose constraints with the first
ation therapy with ablative doses for which the extension of irradiations and not of reirradiations.
indications appears unlimited [4–10]. Results of these treatments
are good to excellent and have markedly changed prescribing 2. Reflections on dose constraints

Dose constraints have become increasingly necessary as the

∗ Corresponding author. result of development of IMRT and of stereotactic radiotherapy.
E-mail address: [email protected] (G. Noël). Many studies have been published on the risks of acute or late-onset

https://doi.org/10.1016/j.canrad.2021.11.001
1278-3218/© 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Please cite this article as: Noël G, Antoni D, Organs at risk radiation dose constraints, Cancer Radiother,
https://doi.org/10.1016/j.canrad.2021.11.001
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Fig. 1. Method to calculate doses for a reirradiation. BED: biologically effective dose; RecoRadTM : Recommendations for practice of external beam radiotherapy and
brachytherapy.

complications with distribution of dose–volume histogrammes. 3. Advice for use of dose constraints
Certain studies have developed NTCP modules, the risk/irradiated
volume relations with a given dose or the risk/doses delivered in a It is important to understand that this involves physical doses
given volume. In spite of the utility, the relevance and the mathe- delivered and not a 2 Gy equivalent dose. This raises real problems
matical accuracy of these studies, currently, it is essential to have a when irradiation is hypofractionated. Therefore, if a dose constraint
threshold value for evaluation of dose–volume histogrammes gen- for a given organ is V45Gy < 150 cm3 , it means that the volume of
erated based on proposals for dosimetry made in routine practice the organ in the volume surrounded by the 45 Gy isodose should
[14]. be less than 150 cm3 . It is impossible to determine if this limit
It is possible to find a group of articles that report on different has been obtained in patients treated for a tumour volume who
dose constraints and limits that it is also possible to discuss for received 70 Gy in 35 fractions, 60 Gy in 30 fractions, 50 Gy in 25 frac-
each of them; in fact, this involves a characteristic of the specialty tions or 45 Gy in 15 fractions. Doses per fraction in this organ then
of being especially attentive to this culture of risk [15–24]. are 1.28 Gy, 1.5 Gy, 1.8 Gy and 3 Gy, respectively. Consequently, the
The reader should consider the fact that these studies, even with 2 Gy equivalent dose for an organ with an ␣/␤ ratio of 3 Gy rises
a threshold dose, suffer from two possible major biases, delineation to 38.5 Gy, 40.5 Gy, 43.2 Gy and 54 Gy. In addition, it is necessary
of the target volume can be discussed and primarily in a retrospec- to consider the doses given (unless there are specific details on
tive study. The latter can be very different from one radiotherapist hypofractionation) such as doses given by 2 Gy fractions. If the dose
to another. Moreover, the evaluation of complications, even if based per fraction delivered is less than 2 Gy and that the dose is less than
on established rating scales from the Radiation Therapy Oncol- or equal to 45 Gy, it is possible to state that we are in a safe range. On
ogy group (RTOG), the European Organisation for Research and the contrary, if the dose per fraction is greater than 2 Gy, it is neces-
Treatment of Cancer (EORTC), or the Common Terminology Cri- sary to recalculate the dose constraint for a fraction such as the one,
teria for Adverse Events (CTCAE), has not often been the subject which surrounds the volume of 150 cm3 in the patient considered.
of validation of correspondence between the radiotherapists who Advisable values are to be taken with caution in patients who
have used them. These data can explain why values are different have multiple concomitant disorders, vascular disorders, cere-
from one published report to another. Lastly, these data are not brovascular accidents (stroke), arterial hypertension, diabetes,
always related to factors that can interact with a given complica- chronic lung disease, chronic digestive disorders such as Crohn’s
tion, individual radiosensitivity, radiosusceptibility, genomics, or disease, smoking, etc. [16,20,31,32].
mechanisms set up by the microenvironment or combination use The values should be taken with circumspection because the
with different systemic combination therapies [11,25–30]. techniques can vary and have different tolerance [33].
Consequently, the majority of these studies are retrospective, It is classical to remember to write protocols in radiotherapy
in fact, it is extremely difficult to commit to a clinical trial with an departments. In this regard, the Recommendations for practice of
objective of complications, they could be even non-ethical, yet a external beam radiotherapy and brachytherapy (RecoRadTM ) vol-
reflection must be developed in order to truly obtain the objective ume is a major support. It is essential to adhere to it and to record
values. In addition, in the tables, values can be different or even cases where it has not been followed and to note the reasons for this
differ widely, such as a confidence interval that may be built based change. Let us note that, in retrospective studies, the doses deliv-
on different articles. No value is erroneous, but it is to be evaluated ered are often in a sometime wide range. It then is not surprising
in its study context. to observe relapses in treated volumes that are underdosed and

2
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 1
Dose constraints for normofractionated or moderate hypofractionated radiotherapy (dose per fraction < 6 Gy) schedules for organs at risk located in skull and base of the
skull.

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adapted based on context)

Brain Risk of complications at 5 years of 5% V60 Gy < 33% [40] D33% < 72 Gy [40]
V60 Gy < 33% [40]
EPTN: V60 Gy < 3 mL [41]
Scalp Risk of alopecia < 50% if Permanent alopecia
Dmax < 43 Gy [42] V25 Gy < 0.03 mL [42]
Optic chiasma Risk of blindness if Dmax > 54 Gy [43] Dmax 54 Gy [44] V50Gy ≤ 10% [45]
V55 Gy ≤ 0.03 mL [41]
Dmax PRV ≤ 60 Gy as needed [44]
Cochlea Risk of deafness if Dmean ≤ 40–45 Gy [41,46] Dmean ≤ 10 Gy [46]
Dmax > 60 Gy [46] V50 Gy < 0.03 mL [47]
Risk of tinnitus if If conservation of hearing is essential:
Dmean > 32 Gy [46] Dmean ≤ 35 Gy [47]
Cornea Risk of corneal abrasions and Dmax = 30–50 Gy [50]
ulcerations if
V50 Gy > 0.03 mL [41,48,49]
Lens Risk of cataract at 5 years Dmax < 10 Gy–15 Gy V10 Gy ≤ 0.03 mL [41]
100%: Dmax = 20–40 Gy [51]
70%: 10 Gy/1 fraction [52]
50%: Dmax = 18 Gy [40]
18%: Dmax = 14 Gy [52]
5%: Dmax = 10 Gy [40]
Lachrymal gland Kerato-conjunctivitis: Dmean < 32 Gy [53]
EPNT: Dmean < 25 Gy [41]
Hippocampus 2 hippocampuses + 5 mm
Dmax < 16 Gy [54]
Sum total of the 2 hippocampuses
D40% ≤ 7.3 Gy [55,56]
Pituitary gland Dmax = 45–50 Gy [57] Panhypopituitarism
Dmean ≤ 45 Gy [41]
Deficit of GH
Dmean ≤ 20 Gy [41]
Temporal lobe Risk of necrosis < 5% at 5 years or at 10
years if:
BED = (108–119 Gy) [58]
Optic nerve Risk of blindness at 5 years Dmax 54 Gy [44] V60 Gy < 25% [43,62]
0%–5%: Dmax = 50–60 Gy [40,45,59] V55 Gy ≤ 0.03 mL [58] V54 Gy < 1% [63]
50%: Dmax = 65 Gy [41] Dmax PRV ≤ 60 Gy if necessary [44] V < 50–60 Gy = 5–30% [61]
5% risk of Neuropathy at 10 years if
Dmax > 60 Gy [60]
Risk of unusual neuritis at 5 years
3–7%: Dmax = 55–60 Gy [61]
7–20%: Dmax > 60 Gy [61]
Total eye V30 Gy < 50%
V50 Gy < 30%
Retina Risk of blindness at 5 years Dmean ≤ 45 Gy V45 Gy < 50% [50]
5%: Dmean = 45 Gy [41] V45 Gy ≤ 0.03 mL [65] V50 Gy < 60% [66]
50%: Dmean = 65 Gy [41]
Risk of retinopathy at 5 years
0%: Dmean < 40–45 Gy [62–64]
50%: Dmean = 45–55 Gy [62]
83%: Dmean = 55–65 Gy [62]
100%: Dmean > 65 Gy [62]

Dx% : dose in x% of volume; VxGy : recipient volume x Gy; EPTN: European Particle Therapy Network; Dmax : maximum dose; PRV: planned target dose of organs at risk; Dmean :
mean dose; GH: growth hormone; BED: biologically effective dose.

Table 2
Dose constraints for normofractionated or moderate hypofractionated radiotherapy (dose per fraction < 6 Gy) schedules for organs at risk located in the head and neck.

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adapted depending on context)

Temporomandibular Risk of trismus above 50 Gy [39] Dmax < 50 Gy [68] D33% < 65 Gy [41]
joint Dmean < 40 Gy [67] D66% < 60 Gy [41]
D100% < 60 Gy [41]
Oral cavity V30 Gy < 65% [69]
V35 Gy < 35% [69]
Parotid gland 2 parotid glands V15 Gy < 66–67% [70,71]
Dmean ≤ 26 Gy [70] V30 Gy < 43–45% [70,71]
V45 Gy < 24–26% [70,71]
Submaxillary gland Dmean < 32 Gy [53]
Dmean < 39 Gy [72]

3
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 2 (Continued)

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adapted depending on context)

Larynx Risk of voice dysfunction for doses Dmax < 63–66 Gy [73,74] V50 Gy < 27% [75]
greater than 60–65 Gy Dmean < 43.5 Gy [75]
Risk of laryngeal oedema for doses Glottis and supraglottic area
greater than 45 Gy Dmean < 40–48 Gy [69]
V50 Gy < 21% [69]
Mandible 5% risk of radionecrosis at 5 years if: Dmax < 65 Gy Implantation rejection 0% if
Edentate patient Dmean < 60 Gy Dmax < 40 Gy [76,77]
Dmean > 60–65 Gy
Non edentate patient
Dmean > 60 Gy
Pharyngeal constrictor Risk of dysphagia if Upper and middle constrictor muscles V40 Gy < 90% [80]
muscles Dmean > 45–66 Gy [78] Dmean < 63 Gy [69] V50 Gy < 80% [80]
V55 Gy < 80% [69] V60 Gy < 70% [80]
V65 Gy < 30% [69] V65 Gy < 50% [80]
Lower constrictor muscles
Dmean < 54 Gy [69]
V40Gy ≤ 41% [79]
V50 Gy < 51% [69]
Thyroid Dmean < 30 Gy [40]
V40 Gy < 85% [81]
V50 Gy < 30% [82]
V50 Gy < 60% [83]
V25 Gy < 60% [84]
and V35 Gy < 55% [84]
and V45 Gy < 45% [84]

VxGy : recipient volume x Gy; Dx % : dose in x% of volume; Dmax : maximum dose; Dmean : mean dose.

Table 3
Dose constraints for normofractionated or moderate hypofractionated radiotherapy (dose per fraction < 6 Gy) schedules for thoracic organs at risk.

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adjusted depending on context)

Left anterior V20 Gy < 0% [85]

descending coronary
artery
Heart base (right RT3D and IMRT
atrium, right Dmax < 8.5 Gy [86]
coronary artery and Dmax < 23 GyEQD2 [87]
ascending aorta)
Heart Breast cancer: Breast cancer Lung cancer
Increase in risk of a cardiac event by 1% Dmean ≤ 5 Gy [88] V40 Gy ≤ 100% [89]
per Gray if Other thoracic cancers Breast cancer
Dmean > 5 Gy [88] Dmax 30 Gy if heart is irradiated in V20 Gy ≤ 20% [92]
totality V20 Gy ≤ 10% [85]
V45 Gy ≤ 66% [89] V40 Gy ≤ 5% [85]
V60 Gy ≤ 33% [89] Droit: V5 Gy ≤ 40% [92]
Risk of valvular heart disease at 1.6% if Gauche V5 Gy ≤ 50% [92]
Dmean valve ≤ 30 Gy [90,91] Gastric cancer
V25 Gy < 50% [93]
V40 Gy < 30% [93]
Oesophagus Risk of severe oesophagitis if RT only V20 Gy ≤ 35% [97]
RT only Dmax < 69 Gy [95] V20 Gy ≤ 45% [15]
V60 Gy ≥ 30% [94] Grade 2 limited oesophagitis V40 Gy < 36.6% ± 11.7 [98]
Chemoradiotherapy V35Gy < 50% [96] V45 Gy < 34.0% ± 11.4 [98]
V50 Gy ≥ 30% [15] Chemoradiotherapy V45 Gy < 40% [15]
Dmax < 69 Gy [95] V50 Gy < 31.0% ± 12.7 [98], ≤ 32% [99]
V60 Gy ≤ 30% [94] V55 Gy < 27.3% ± 13.7 [98]
Grade 2 limited oesophagitis V57.5 Gy < 25.7% ± 13.7 [98]
V35 Gy < 31% [96] V60 Gy < 23.7% ± 13.4 [98]
V62 Gy < 18.0% ± 13.6 [98]
V65 Gy < 15.4% ± 12.6 [98]
V67.5 Gy < 12.3% ± 12.3 [98]
V70 Gy < 8.8% ± 11.3 [98]
Left atrium RT3D and IMRT
Dmax < 64 Gy [100]
Pericard RT3D
V50 Gy ≤ 17% [101]
V55 Gy ≤ 21% [102]
Brachial plexus Dmax < 54 Gy [85]
If necessary Dmax < 60–66 Gy [103]

4
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 3 (Continued)

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adjusted depending on context)

Lung Irradiation of intrathoracic cancers Lung cancer: total for two lungs
Total amount for 2 lungs V < 5 Gy > 2300 mL [93]
V20 Gy ≤ 35–37% [89] V20 Gy < 20% [93]
Dmean ≤ 20 Gy [89] Risk of lung disorder ≥ grade 2
Recorad article 2021 0%: V20 Gy ≤ 22% [107]
V20 Gy ≤ 30–35% 7%: V20 Gy = 22–31% [107]
V30 Gy ≤ 20% Risk of lung disorder ≥ grade 3
V13 Gy ≤ 42% 4%: V25 Gy ≤ 30% (in [108])
Mean dose ≤ 15–20 Gy Risk of lung disorder all grades
Homolateral lung 4%: V30 Gy ≤ 18% (in [108])
V20 Gy < 20% Homolateral lung
IMRT: Risk of lung disorder ≥ grade 2
V5 Gy < 60% [104] 9%: V20 Gy ≤ 52% [109]
V5 Gy < 70% [105] 8%: V30 Gy ≤ 39% [109]
Irradiation of breast cancer Opposite lung
Dmean ≤ 15 Gy Risk of lung disorder ≥ grade 3
Breast alone: V20 Gy ≤ 14% [106] 0%: V5 Gy ≤ 60% [110]
Breast + nodes: V20 Gy ≤ 22% [106] 3%: V5 Gy ≤ 42% [110,111]
Dmean ≤ 18 Gy [85] 4%: V5 Gy ≤ 75% [110]
Breast alone: V20 Gy ≤ 25% [85] Breast cancer:
Breast + nodes: V20 Gy ≤ 35% [85] Homolateral lung
V20 Gy ≤ 45% [92]
V30 Gy < 35% [92]
V30 Gy < 10% [112]
Breast V5 Gy ≤ 15% [92]
Trachea Dmax < 70 Gy
Right ventricle V10 Gy < 4% [113]
Left ventricle V60 Gy < 0% [59]
V30 Gy < 10% [114]

VxGy : recipient volume x Gy; Dmax : maximum dose; Dmean : mean dose.

Table 4
Dose constraints for normofractionated or moderate hypofractionated radiotherapy (dose per fraction < 6 Gy) schedules for abdominal organs at risk.

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adjusted depending on context)

Duodenum V15 Gy < 120 mL (intestinal loop only)

[20,115]
V25 Gy ≤ 45% [116]
V35 Gy ≤ 20% [116]
V45 Gy < 190 mL (peritoneal cavity)
Late onset
V55 Gy < 1 mL [117]
V55 Gy < 15 mL [118]
Stomach Risk of ulcer above one dose of 45 Gy Dmax < 54 Gy [119]
Dmean < 45 Gy [119]
Liver GTV-Liver: D100% ≤ 28–30 Gy [120]
Dmean < 28–32 Gy [120] V5 Gy < 86% [121]
Liver: Dmean < 26 Gy [121] V10 Gy < 68% [121]
Abnormal liver: V15 Gy < 59% [121]
Dmean < 22 Gy [122] V16 Gy < 66% [121]
Vtotal-V30 Gy > 700 mL [121] V20 Gy < 49% [121]
V25 Gy < 35% [121]
V30 Gy < 30% [93,123]
V32 Gy < 33% [121]
V35 Gy < 25% [121]
V40 Gy < 20% [121]
V47.6 Gy < 33% [124]
Pancreas Exocrine secretion
Dmean < 20–25 Gy [125]
Endocrine secretion (tail)
Dmean < 25 Gy [125]
Digestive tract RTOG late onset toxicity
grade ≥ 2 < 25% (intestinal loops)
V30 Gy < 178 mL [126]
V40 Gy < 151 mL [126]
V45 Gy < 139 mL [126]
V60 Gy < 98 mL [126]
V65 Gy < 40 mL [126]

5
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 4 (Continued)

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adjusted depending on context)

Kidney Dmean < 16.2 Gy [127] One or both kidneys

Total two kidneys: V5 Gy < 50% [127]
V20 Gy < 50% [93,128] V10 Gy < 30% [127]
In a single kidney V20 Gy < 10% [127]
V20 Gy < 30% [93,128–130] V20 Gy < 100 mL [127]
If irradiation of both kidneys Creatinine clearance and renal atrophy
V20 Gy < 70% in one kidney and V20 Gy < 26.6% [131]
V20 Gy < 30% in the second kidney D30% < 19 Gy [131]
[93,128–130]

VxGy : recipient volume x Gy; Dmax : maximum dose; Dmean : mean dose; Dx% : dose in x % volume; RTOG: Radiation Therapy Oncology Group.

Table 5
Dose constraints for normofractionated or moderate hypofractionated radiotherapy (dose per fraction < 6 Gy) schedules for pelvic organs at risk.

Organ at risk Dosimetric limits associated with Usual planning constraints (to be Other published constraints
potential risk of complication adjusted depending on context)

Bulb of penis Dmean ≤ 38.2 Gy [40,132]

Dmean ≤ 52.5 Gy [133,134]
D30% < 67 Gy [133]
D45% < 63 Gy [133]
D60% < 42 Gy [133]
D75% < 20 Gy [133]
D95% < 50 Gy [135]
Anal canal Limit the dose to 55 Gy in the entire Dmean < 40–45 Gy [136]
canal Dmean < 40–47 Gy [14]
Faecal incontinence
V35 Gy < 60% [137]
V40 Gy < 40% [137]
Colon/sigmoid Late onset effects
V15 Gy < 250 mL [138]
V30 Gy < 100 mL [138]
V40 Gy < 90 mL [138]
Late onset effects grade 1 diarrhoea
V40 Gy < 10% [139]
V30 Gy < 16% [139]
Small bowel (peritoneal Risk of diarrhoea grade 3 Small bowel loops: Diarrhoea < grade 2 (intestinal loops)
cavity or sac) 2% risk: V45 Gy < 100 mL [140] V15 Gy < 275 mL [141] Reference: [143]
10% risk: V45 Gy < 200 mL [140] Peritoneal cavity: V40 Gy < 124 mL
V15 Gy < 830 mL [141] V45 Gy < 71 mL
V45 Gy < 150 mL [142] V60 Gy < 0.5 mL
Reference: [144]
V5 Gy < 276 mL (204–332)
V10 Gy < 244 mL (136–263)
V15 Gy < 194 mL (106–349)
V20 Gy < 94 mL (65–115)
V25 Gy < 70 mL (47–93)
V30 Gy < 65 mL (5–74)
V35 Gy < 23 mL (3–50)
V40 Gy < 23 mL (3–50)
V > 42.75 Gy < 10 mL (0–41)
Diarrhoea < grade 3 (intestinal loops) [142,145]
V5 Gy < 425–500 mL
V10 Gy < 265–300 mL
V15 Gy < 120–150 mL
V20 Gy < 112–145 mL
V25 Gy < 105–140 mL
V30 Gy < 92–135 mL
V35 Gy < 85–130 mL
V40 Gy < 71–125 mL
Digestive toxicity (abdominal cavity) [142]
V20 Gy < 554 mL
V30 Gy < 311 mL
V35 Gy < 241 mL
V40 Gy < 188 mL
V50 Gy < 105 mL
Late onset toxicity
V40 Gy < 340 mL [146]
V15 Gy < 275 mL [138]
Bone marrow Bone marrow
Dmean ≤ 32 Gy [147]
Pelvis: ≤ 28 Gy [147]
Lumbosacral ≤ 35 Gy [147]

6
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 5 (Continued)

Organ at risk Dosimetric limits associated with Usual planning constraints (to be Other published constraints
potential risk of complication adjusted depending on context)

External genital organs V20 Gy < 50% [148]

V30 Gy < 35% [148]
V50 Gy < 5% [148]
Iliac bone V40 Gy < 37% V10 Gy < 90% (in [23])
Inner cavity of bone (cortical bone V20 Gy < 75% (in [23])
removal) grade 2 haematopoietic V30 Gy < 50% [147]
group AE V40 Gy < 35% [147]
V40 Gy < 40% [149] V40 Gy < 37% (in [23])
V50 Gy < 5% [147]
Dmax < 50 Gy [150]
V10 Gy < 90% [150]
V20 Gy < 75% [150]
V40 Gy < 37% [150]
IMRT + cisplatin
V10 Gy < 95% [151]
V20 Gy < 80% [151]
V30 Gy < 64% [151]
Ovary Dmean = 6–10 Gy [152]
Lumbosacral plexus Dmax ≤ 50 Gy [153–155]
Rectum Prostate Rectum in totality
RT normofractionated Dmax ≤ 52.5 Gy [147]
V60 Gy < 50% V40 Gy < 50% [147]
V70 Gy < 25% V65 Gy < 30% [157]
V75 Gy < 35% V70 Gy < 15% [157]
(Gétug) V75 Gy < 3% [157]
RT hypofractionated (20 × 3 Gy) Male
Dmean as low as possible [156] V40 Gy < 40% [158]
V46 Gy ≤ 30% [156] V65 Gy < 20% [158]
V37 Gy ≤ 50% [156] V70 Gy < 10% [158]; < 15% [159]
Female
V40 Gy < 80% [158]
V65 Gy < 40% [158]
V70 Gy < 20% [158]
Toxicity ≥ grade 2
V40 Gy < 60% [160]
V50 Gy < 50% [160]
V60 Gy < 40% [161]; < 25% [160]
V70 Gy < 25% [161]
V72 Gy < 15% [160]
V75.6 Gy < 15% [161]
V76 Gy < 5% [160]
V78 Gy < 5% [161]
Proctorrhagia < grade 2–3
V50 Gy < 60–65% [162]
V60 Gy < 50–55% [162]
V65 Gy < 40% [163]
V70 Gy < 25–30% [162]; < 30% [163]
V75 Gy < 5% [163]
Wall of rectum
NTCP proctorrhagia ≥ 2
< 5%: V73.7 Gy < 40% [164]
Rectal toxicity
V60 Gy < 54% [165]
V70 Gy < 44% [165]
V75 Gy < 39% [165]
Late onset rectal toxicity
V30 Gy ≤ 80% [166]
V40 Gy ≤ 65% [166]
V50 Gy ≤ 55% [166]
V60 Gy ≤ 40% [166]
V65 Gy ≤ 30% [166]
V70 Gy ≤ 15% [166]
V75 Gy ≤ 3% [166]
Sacrum Dmax < 50 Gy [150]
Femoral head V50 Gy < 2% [147] V30 Gy < 50% [148]
V52 Gy < 10% [167] V40 Gy < 35% [148]
V44 Gy < 5–10% [148]

7
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 5 (Continued)

Organ at risk Dosimetric limits associated with Usual planning constraints (to be Other published constraints
potential risk of complication adjusted depending on context)

Uterus D100% < 45 Gy [168]

Bladder Prostate Bladder in totality
RT, normofractionated V20 Gy < 96% [169]
V60 Gy < 50% V35 Gy < 50% [148]
V70 Gy < 25% V40 Gy < 35% [148]
(Gétug) V45 Gy < 35% [147]
RT, hypofractionated (20 × 3 Gy) V50 Gy < 50% [157]; 5% [148]
V60 Gy ≤ 5% [156] V60 Gy < 25% [157]
V48 Gy ≤ 25% [156] V65 Gy < 50% [134]
V41 Gy ≤ 50% [156] V70 Gy < 5% [157]; < 35% [134]
V75 Gy < 25% [134]
Bladder wall
V20 Gy < 99% [169]

VxGy : recipient volume x Gy; Dmax : maximum dose; Dmean : mean dose; Dx%: dose in x % volume; NTCP: Normal Tissue Complication Probability; Gétug: Study group of
genitourinary tumours.

Table 6
Dose constraints for normofractionated or moderate hypofractionated radiotherapy (dose per fraction < 6 Gy) schedules for organs at risk located in the whole body.

Organ at risk Dosimetric limits associated with Usual constraints of planning (to be Other published constraints
potential risk of complication adjusted depending on context)

Bone marrow Risk of radiation myelitis Dmax ≤ 45 Gy [85,170]

Dmax = 50–50.4 Gy [89] Dmax ≤ 50 Gy
If combination with chemotherapy
Dmax 40–45 Gy [93] If combination with
chemoradiotherapy
Dmax ≤ 45 Gy
Long bones Dmax < 59 Gy [68,170] Risk of fracture
V40 Gy < 64% [170]
Skin Late onset reaction ≥ 3 if Breast fibrosis
Dmean > 60 Gy in over 20 cm2 [171] D100% < 60 Gy [103]

VxGy : recipient volume x Gy; Dmax : maximum dose; Dx%: dose in x % volume.

complications in volumes that have received excess doses. This is reference articles [35] or the list in the model for computer cal-
expected and is logical. In addition, the rigorousness of the protocol culation linear quadratic model (iLQ) developed by the French
makes it possible to avoid multiplying such cases without eliminat- society of young oncological radiotherapists (SFjRO) with the sup-
ing radiosensitivity, the cause of complications with doses below port from the French Society of Oncological Radiotherapy (SFRO;
the expected dose and relapses with unexpected doses. It is with http://www.sfjro.fr›ilq›modelelq).
this method that each radiotherapist can also define the dose con- Nevertheless, it is necessary to remain very cautious for doses
straints and, in particular, can verify with time, the relevance of the in stereotactic radiotherapy for which validation of the quadratic
choice taken in drafting of protocols. linear model is still debated [36,37]. The first objective is to cal-
In principle, dose constraints should always be the lowest pos- culate the BED of the dose constraint based on tables provided.
sible. In addition, in dosimetry, the objective of achieving optimum Then, it is necessary to calculate the BED (compared to the dose
tumour coverage is clear. The objective for organs at risk is less so. per fraction of planned treatment) of previously received doses by
In fact, the constraints of doses proposed in the tables are not the organs at risk concerned by the new irradiation. There remains the
doses to reach; they are doses to not be exceeded, which means notion of the dose forgotten. The latter can be evaluated based on
that the dose should be lower, whenever possible. two models; one is the so-called rapid recovery, and the other, the
slow recovery. The first one takes into account two periods, one of
4. Planning organ at risk volume 6 months with a decrease in the dose previously received by 25%
and the second one at one year with a “recovered dose” of 50%,
Planning organ at risk volume (PRV) has been proposed by the possible maximum recovery [38]. The second method consists of
International Commission on Radiation Units and Measurements recovery with 5% per year, out of a total maximum of 10 years, and
(ICRU) although neither the definition nor the purpose have been therefore not exceeding 50%. Based on this calculation, it is possible
clearly defined [34]. However, this concept can be useful primarily to obtain a remaining dose based on the dose constraint available
for stereotactic radiotherapy where it can make it possible to be in the tables. The two methods do not yield the same results if
reassured on dose distribution. However, to date, no focalised dose the interval between the two sessions of irradiation is less than ten
constraints exist in PRV. years, caution should be developed, in particular, by considering the
following organs: the spinal cord, brain stem, optic chiasma as hav-
ing to be irradiated with the lowest possible dose. For other organs,
5. Reirradiation
caution and discussion with the patient is unavoidable (Fig. 1).
Dose constraints in reirradiation are difficult to consider. A
simple method then consists of calculating the biologically effec- 6. Dose constraints
tive dose (BED) received per organ at risk, by taking as the
maximum dose, the one deposited in 0.035 mL of the organ, Dose constraints are listed in two separate sets of tables,
and for dose per fraction, this dose divided by the number normofractionated or moderately hypofractionated protocols
of fractions received. The value of ␣/␤ can be chosen in the (Tables 1–6) and stereotactic treatments (Tables 7–12).

8
 G. Noël, D. Antoni

CANRAD-4270; No. of Pages 17

G Model
Table 7
Dose constraints for ablative hypofractionated radiotherapy (dose per fraction > 6 Gy) schedules for organs at risk located in the skull and base of the skull.

Organ Number of fractions

1 2 3 4 5 ≥8

Brain V10 Gy < 10 mL [172] V20 Gy ≤ 20 mL [174,175] V24 Gy ≤ 20 mL [174,175]

V12 Gy < 5–10% [173] V23.1 Gy < 7 mL [176] V28.8 Gy < 3–7 mL [177]
V12 Gy < 7.9–8.5 mL [173]
V12 Gy ≤ 5 mL [174,175]
Optic tracts Dmax < 8 Gy [178,179] Dmax < 13.7 Gy [178] Dmax < 10.5 Gy [176] Dmax < 21.2 Gy [178] Dmax < 25 Gy [178] Dmax < 29.6 Gy [178]
Dmax < 10–12 Gy [172] V11.7 Gy < 0.2 mL [178] Dmax < 17.4 Gy [178] V19.2 Gy < 0.2 mL [178] Dmax < 15 Gy [177] V27.2 Gy < 0.2 mL [178]
Dmax > 12 Gy [174,180] Dmax < 20 Gy [174,180] Dmax < 25 Gy [174,180]
V8 Gy < 0.2 mL [178] V15.3 Gy < 0.2 mL [178] V23 Gy < 0.2 mL [178]
Cochlea Dmax < 6 Gy [172] Dmax < 11.7 Gy [178] Dmax < 14.4 Gy [178] Dmax < 18 Gy [178] Dmax < 22 Gy [178] Dmax < 26.4 Gy [178]
Dmax < 9 Gy [178]
Hippocampus Dmax < 6.65 Gy [181]
V4.21 Gy < 100% [181]

ARTICLE IN PRESS
Brain stem Dmax < 10–12 Gy [172] Dmax < 19.1 Gy [178] Dmax < 23.1 Gy [178] Dmax < 27.2 Gy [178] Dmax < 31 Gy [178] Dmax < 37.6 Gy [178]
Dmax < 15 Gy [178,182] V13 Gy < 0.5 mL [178] Dmax < 24 Gy [182] V20.8 Gy < 0.5 mL [178] V23 Gy < 0.5 mL [178] V27.2 Gy < 0.5 mL [178]
V10 Gy < 0.5 mL [178] V15.9 Gy < 0.5 mL [178] V30 Gy < 5% [182]
Spinal Dmax < 10 Gy [182] Dmax < 18.3 Gy [178] Dmax < 20.3 Gy [182] Dmax < 25.6 Gy [178] Dmax < 25 Gy [182] Dmax < 33.6 Gy [178]
cord + medulla Dmax < 12.4 Gy [182] V13 Gy < 0.35 mL [178] Dmax < 21 Gy [182] V18 Gy < 0.35 mL [178] Dmax < 25.3 Gy [182] V26.4 Gy < 0.35 mL [178]
oblongata Dmax < 13 Gy [182] Dmax < 22.5 Gy [178] 6 mm on either side PTV Dmax < 28 Gy [178]
Dmax < 14 Gy [178] V15.9 Gy < 0.35 mL [178] Dmax < 26 Gy [182] V22 Gy < 0.35 mL [178]
[182,183] 6 mm on either side PTV 6 mm on either side PTV
V7 Gy < 1.2 mL [182,183] V18 Gy < 10% [182] V10 Gy < 10% [182]
V10 Gy < 0.35 mL
[172,182,183]
9

V14 Gy < 0.035 mL [172,182]

6 mm on either side PTV
V10 Gy < 10% [182]

VxGy : recipient volume x Gy; Dmax : maximum dose.

Table 8
Dose constraints for ablative hypofractionated radiotherapy (dose per fraction > 6 Gy) schedules for organs at risk located in head and neck area.

Organ Number of fractions

Cancer/Radiothérapie xxx (xxxx) xxx–xxx

1 2 3 4 5 ≥8

Carotid artery Dmax < 20–30 Gy

[174,184]
Dmax < 32.5 Gy [185]
V20 Gy < 0.5 mL [184]
Cochlea Dmax < 6 Gy [172] Dmax < 11.7 Gy [178] Dmax < 14.4 Gy [178] Dmax < 18 Gy [178] Dmax < 22 Gy [178] Dmax < 26.4 Gy [178]
Dmax < 9 Gy [178]
Larynx Dmean < 15 Gy [185]
Mandible Dmax < 20 Gy [185]

Dmax : maximum dose; Dmean : mean dose.

 G. Noël, D. Antoni

CANRAD-4270; No. of Pages 17

G Model
Table 9
Dose constraints for ablative hypofractionated radiotherapy (dose per fraction > 6 Gy) schedules for thoracic organs at risk.

Organ Number of fractions

1 2 3 4 5 ≥8

Oesophagus Dmax < 15.4 Gy [182] Dmax < 28.3 Gy [178] Dmax < 27 Gy [186] Dmax < 30 Gy [185] Dmax < 35 Gy [186] Dmax < 43.2 Gy
Dmax < 24 Gy [178] V24.3 Gy < 5 mL [178] Dmax < 30 Gy [182] Dmax < 35.6 Gy [178] Dmax < 38 Gy [178] [178]
V11.9 Gy < 5 mL [182] Dmax < 32.4 Gy [178] V18.8 Gy < 5 mL [187] Dmax < 50 Gy [182] V36.8 Gy < 5 mL [178]
V14 Gy < 2.5 mL [182] V27 Gy < 5 mL [186] V30.4 Gy < 5 mL [178] V14 Gy < 2 mL [186]
V14 Gy < 2 mL [186] V27.9 Gy < 5 mL [178] V27.5 Gy < 5 mL [182]
V20 Gy < 5 mL [178] V32.5 Gy < 5 mL [178]
Brachial plexus Dmax < 16.4 Gy [178] Dmax < 21.2 Gy [178] Dmax < 26 Gy [178] Dmax < 29.6 Gy [178] Dmax < 32.5 Gy [178] Dmax < 39.2 Gy
Dmax < 24 Gy [182] V17.8 Gy < 3 mL [178] Dmax < 30 Gy [182] V24.8 Gy < 3 mL [178] Dmax < 35 Gy [182] [178]
V13.6 Gy < 3 mL [178] V22 Gy < 3 mL [178] V27 Gy < 3 mL [178] V32.8 Gy < 3 mL [178]
V14 Gy < 3 mL [182]
Heart/pericardium Dmax < 22 Gy Dmax < 26 Gy [178] Dmax < 30 Gy [178] Dmax ≤ 32 Gy [185] Dmax < 38 Gy [178] Dmax < 40 Gy [178]
[178,182] V20 Gy < 15 mL [178] V24 Gy < 15 mL [178] Dmax < 34 Gy [178,188] Dmax < 50 Gy [182] V34.4 Gy < 15 mL

ARTICLE IN PRESS
V16 Gy < 15 mL V28 Gy < 15 mL [178,188] V32 Gy < 15 mL [178] [178]
[178,182]
Large blood vessels Dmax < 37 Gy [178] Dmax < 41 Gy [178] Dmax < 45 Gy [178] Dmax < 49 Gy [178,186] Dmax < 53 Gy [178] Dmax < 62 Gy [178]
V31 Gy < 10 mL [178] V35 Gy < 10 mL [178] V39 Gy < 10 mL [178] Lung art.: Dmax < 52.5 Gy Lung art.: V55.2 Gy < 10 mL
[186] Dmax < 52.5 Gy [186] [178]
Aorta: Dmax < 60 Gy Aorta: Dmax < 60 Gy
[186] [186]
V43 Gy < 10 mL [178,188] V47 Gy < 10 mL [178]
Trachea/bronchi Dmax < 30 Gy [178] Dmax < 38 Gy [178] Dmax < 43 Gy [178] Dmax: 34.8 Gy [188] Dmax < 50 Gy [178] Dmax < 56 Gy [178]
V27.5 Gy < 4 mL [178] V34.5 Gy < 4 mL [178] V39 Gy < 5 mL [178] Dmax < 47 Gy [178] Dmax < 52.5 Gy [186] V50 Gy < 5 mL [178]
Dmax < 52.5 Gy [186] V33.5 Gy < 4 mL [186]
10

V15.6 Gy < 4 mL [188] V45 Gy < 4 mL [178]

V33.5 Gy < 4 mL [186]
V42.4 Gy < 5 mL [178]
Secondary bronchus Dmax < 22.2 Gy [178] Dmax < 25.1 Gy [178] Dmax < 30 Gy [178] Dmax < 34.8 Gy [178] Dmax < 40 Gy [178] Dmax < 48.8 Gy
V17.4 Gy < 0.5 mL [178] V21.6 Gy < 0.5 mL [178] V25.8 Gy < 0.5 mL [178] V28.8 Gy < 0.5 mL [178] V32 Gy < 0.5 mL [178] [178]
V38.4 Gy < 0.5 mL
[178]
Rib Dmax < 30 Gy [23] Dmax < 41.5 Gy [178] Dmax < 39.6 Gy [23] Dmax < 40 Gy [188] Dmax < 43 Gy [23] Dmax < 63 Gy [178]
Dmax < 33 Gy [178] V35 Gy < 5 mL [178] Dmax < 50 Gy [178] Dmax < 54 Gy [178] Dmax < 57 Gy [178] V50 Gy < 5 mL [178]
V22 Gy < 1 mL [23] V10 Gy < 30 mL [188] V32 Gy < 1 mL [188] V35 Gy < 1 mL [23]
V28 Gy < 5 mL [178] V28.8 Gy < 1 mL [23] V43 Gy < 5 mL [178] V45 Gy < 5 mL [178]
V40 Gy < 5 mL [178] Entire wall
Entire wall V30 Gy < 0.7% [189]
V30 Gy < 0.7% [189] V35 Gy < 0.39% [189]
V35 Gy < 0.39% [189] V40 Gy < 0.19% [189]
V40 Gy < 0.19% [189]
Dmean ≤ 8 Gy [174]a Dmean ≤ 8 Gy [174]a Dmean ≤ 8 Gy [174]a

Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Lung (R + L) V8 Gy < 37% [178] V10 Gy < 37% [178] V15.2 Gy < 37% [178]
M: V7.2 Gy < 1500 mL M: V9.4 Gy < 1500 mL V11.4 Gy < 37% [178] V12.8 Gy < 37% [178] V20 Gy < 10–15% [174]a M: V14.4
[178] [178] V20 Gy < 10–15% [174]a V20 Gy < 10% [186] V13.5 Gy < 37% [178] Gy < 1500 mL [178]
F: V7.2 Gy < 950 mL F: V9.4 Gy < 950 mL M: V10.8 Gy < 1500 mL [178] V20Gy < 10–15% [174]a M: V12.5 Gy < 1500 mL F: V14.4 Gy < 950 mL
[178] [178] F: V10.8 Gy < 950 mL [178] V30 Gy < 15% [186] [178] [178]
M: V12 Gy < 1500 mL [178] F: V12.5 Gy < 950 mL
F: V12 Gy < 950 mL [178] [178]
Homolat. lung:
Dmean < 6 Gy [186]

Art.: artery; F: female; M: male; VxGy : recipient volume x Gy; Dmax : maximum dose; Dmean : mean dose.
a
2 lungs minus.
 Table 10
Dose constraints for ablative hypofractionated radiotherapy (dose per fraction > 6 Gy) schedules for abdominal organs at risk.

G. Noël, D. Antoni

CANRAD-4270; No. of Pages 17

G Model
Organ Number of fractions

1 2 3 4 5 6 ≥8

Stomach Dmax < 12.4 Gy [182,183] Dmax < 26 Gy [178] Dmax < 30 Gy [178] Dmax < 27.2 Gy [188] Dmax < 35 Gy [178] Dmax < 42 Gy [178]
Dmax < 15 Gy [182] V20 Gy < 5 mL [178] V22.5 Gy < 5 mL [178] Dmax < 29 Gy [187] V26.5 Gy < 5 mL [178] V31.2 Gy < 5 mL [178]
Dmax < 22 Gy [178] Dmax < 33.2 Gy [178] V30 Gy < 5 mL [182]
V11.2 Gy < 10 mL [182,183] V17.6 Gy < 10 mL [188]
V17.4 Gy < 5 mL [178] V23 Gy < 5 mL [187]
V25 Gy < 5 mL [178]
Duodenum Dmax < 12.4 Gy [183] Dmax < 26 Gy [178] Dmax 30 < Gy [178] Dmax < 33.2 Gy [178] Dmax < 35 Gy [178] Dmax < 42 Gy [178]
Dmax < 22 Gy [178] V 12.5 Gy < 30 mL [190] V 15 Gy < 50% [190] V 15.5 Gy < 50% [190] V 16 Gy < 50% [190] V31.2 Gy < 5 mL [178]
V9 Gy < 10 mL [183] V 14 Gy < 50% [190] V 15 Gy < 30 mL [190] V 17.5 Gy < 30 mL [190] V 20 Gy < 30 mL [190]
V 9 Gy < 30 mL [190] V 16.1 Gy < 5 mL [190] V16.2 Gy < 5 mL [191] V 23.4 Gy < 5 mL [190] V 25.8 Gy < 5 mL [190]
V 11.2 Gy < 5 mL [183,190] V20 Gy < 5 mL [178] V 21 Gy < 5 mL [190] V25 Gy < 5 mL [178] V26.5 Gy < 5 mL [178]
V 12.5 Gy < 50% [190] V 21.5 Gy < 1 mL [190] V22.5 Gy < 5 mL [178] V 27 Gy < 1 mL [190] V 28 Gy < 1 mL [190]
V 16 Gy < 0.035 mL [190] V 25 Gy < 0.035 mL [190] V 25.3 Gy < 1 mL [190] V 31 Gy < 0.035 mL [190] V 32 Gy < 0.035 mL [190]
V 17 Gy < 1 mL [190] V25.3 Gy < 5 mL [190] V35 Gy < 1 mL [186]
V17.4 Gy < 5 mL [178] V 30 Gy < 0.035 mL [190]
V30 Gy < 1 mL [186]

ARTICLE IN PRESS
Jejunum/ileum Dmax < 15.5 Gy [183] Dmax < 24 Gy [178] Dmax < 28,5 Gy [178] Dmax < 27 Gy [187] Dmax < 29 Gy [187] Dmax < 40 Gy [178]
Dmax < 20 Gy [178] V19.2 Gy < 30 mL [178] V20.7 Gy < 30 mL [178] Dmax < 31.6 Gy [178] Dmax < 34.5 Gy [178] V28.8 Gy < 30 mL [178]
V11 Gy < 5 mL [183] V21 Gy < 5 mL [186] V22.4 Gy < 30 mL [178] V24 Gy < 30 mL [178]
V17.6 Gy < 30 mL [178] V24.5 Gy < 2 mL [186] V23 Gy < 3 mL [187] V25 Gy < 5 mL [187]
V 25 Gy < 5 mL [186]
V 30 Gy < 2 mL [186]
Biliary tract Dmax < 30 Gy [178] Dmax < 33 Gy [178] Dmax < 36 Gy [178] Dmax < 38.4 Gy [178] Dmax < 41 Gy [178] Dmax < 48 Gy [178]
V32 Gy < 24 mL [192] V21 Gy < 37 mL [186]
V33.8 Gy < 21 mL [192] V26 Gy < 40 mL [186]
V33.7 Gy < 24 mL [192]
V40 Gy < 21 mL [192]
11

Dmean < 19 Gy [186]

Liver V9.1 Gy < 700 mL [183] V15.1 Gy < 700 mL [178] Primary tumour: V15 Gy < 700 mL V15 Gy < 700 mL [187,193] Dmean < 20 Gy [193] V24.8 Gy < 700 mL [178]
V9.6 Gy < 700 mL [182] Dmean ≤ 13 Gy [174]a [182,187,193] V15–17 Gy < 700 mL [174]a Primary tumour
V11.6 Gy < 700 mL [178] Metastasis: V15–17 Gy < 700 mL [174]a V21 Gy < 700 mL [186] Dmean < 17.5 Gy [199]
Dmean ≤ 15 Gy [174]a V19.6 Gy < 700 mL [178] V21.5 Gy < 700 mL [178] Dmean ≤ 18 Gy [174]a
V15–17 Gy < 700 mL [174]a V21 Gy < 33% [198] CHILD class B Secondary tumour
V15 Gy < 700 mL V12 Gy < 500 mL [197] Dmean < 16.9 Gy [199]
[186,187,193,194] V18 Gy < 33% [197] Dmean ≤ 20 Gy [174]a
V15 Gy < 50% [195]
V17.1 Gy < 700 mL [21]
V17.7 Gy < 700 mL [178]
V18 Gy ≤ 800 mL [196]
V21 Gy < 33% [195]
Dmean < 15 Gy [193]
Child class A
V7 Gy < 500 mL [197]
V10 Gy < 33% [197]

Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Colon Dmax < 16 Gy [182] Dmax < 39 Gy [178] Dmax 45 < Gy [178] Dmax < 28 Gy [187] Dmax < 52.5 Gy [178] Dmax < 57.5 Gy [178]
Dmax < 18.4 Gy [183] V25.8 Gy < 20 mL [178] V28.8 Gy < 20 mL [178] Dmax < 48.5 Gy [178] V30 Gy < 5 mL [182] V35.2 Gy < 20 mL [178]
Dmax < 31 Gy [178] V24 Gy < 5 mL [187] V32.5 Gy < 20 mL [178]
V11.2 Gy < 5 mL [182] V30.8 Gy < 20 mL [178]
V12 Gy < 5 mL [182]
V14.3 Gy < 20 mL [183]
V20.5 Gy < 20 mL [178]
Renal hilum V14 Gy < 15 mL [178] V16.8 Gy < 15 mL [178] V19.5 Gy < 15 mL [178] V21.5 Gy < 15 mL [178] V23 Gy < 15 mL [178] V28 Gy < 15 mL [178]
Renal cortex V9.5 Gy < 200 mL [178] V12.5 Gy < 200 mL [178] V14.7 Gy < 200 mL [178] V16 Gy < 200 mL [178] V15 Gy < 33% [195] V20 Gy < 200 mL [178]
V10 Gy < 35% [182] (2 kidneys) V15 Gy < 35% [182] (2 V16 Gy < 33% [187] V17.5 Gy < 200 mL [178]
V10.6 Gy < 66% [182] (2 kidneys) V18 Gy < 35% [182]
kidneys) V15 Gy < 33% [195] V18 Gy < 33% [187] (2 kidneys)
Ureter Dmax < 35 Gy [178] Dmax < 37.5 Gy [178] Dmax 40 < Gy [178] Dmax < 43 Gy [178] Dmax < 45 Gy [178] Dmax < 53 Gy [178]

VxGy : recipient volume x Gy; Dmax : maximum dose; Dmean : mean dose.
a
Liver – GTV.
 G. Noël, D. Antoni

CANRAD-4270; No. of Pages 17

G Model
Table 11
Dose constraints for ablative hypofractionated radiotherapy (dose per fraction > 6 Gy) schedules for pelvic organs at risk.

Organ Number of fractions

1 2 3 4 5 ≥8

Bulb of penis V16 Gy < 3 mL [178] V20.5 Gy < 3 mL [178] V25 Gy < 3 mL [178] V27 Gy < 3 mL [178] Dmax ≤ 36.25 Gy [200] V35 Gy < 3 mL [178]
V19.9 Gy ≤ 3 mL [201]
V20 Gy ≤ 3 mL [200]
V29.5 Gy < 3 mL [202]
V30 Gy < 3 mL [178]
V36.25 Gy ≤ 3 mL [201]
Rectum Dmax < 15 Gy [182] Dmax < 41.3 Gy [178] Dmax 47 < Gy [178] Dmax < 35–38 Gy [174] Dmax < 35–38 Gy [174] Dmax < 61.5 Gy [178]
Dmax < 33.7 Gy [178] V38 Gy < 3.5 mL [178] V43 Gy < 3.5 mL [178] Dmax < 38 Gy [202] Dmax < 41.8 Gy [182] V56 Gy < 3.5 mL [178]
V18 Gy < 0.03 mL [182] V26.7 Gy < 20 mL [178] V30.3 Gy < 20 mL [178] Dmax < 51.6 Gy [178] Dmax < 55 Gy [178] V45 Gy < 20 mL [178]

ARTICLE IN PRESS
V30 Gy < 3.5 mL [178] Wall V30 Gy < 33% [178] Wall V34 Gy < 33% [178] V47.2 Gy < 3.5 mL [178] V18.13 Gy ≤ 50% [200,201] Wall V45 Gy < 33% [178]
Wall V24 Gy < 33% [178] V34 Gy < 20 mL [178] V29 Gy ≤ 20% [199]
Wall V37 Gy < 33% [178] V32.63 Gy ≤ 10% [200,201]
V34.4 Gy ≤ 3 mL [200,201]
V36 Gy < 1 mL [202]
V37.5 Gy < 20 mL [178]
V38.06 Gy ≤ 1 mL [200]
V38.06 Gy ≤ 0.03 mL [201]
V50 Gy < 3.5 mL [178]
Wall V39 Gy < 33% [178]
Bladder wall Dmax < 25 Gy [178] Dmax < 29 Gy [178] Dmax 33 < Gy [178] Dmax < 35.6 Gy [178] Dmax < 38 Gy [178] Dmax < 44.8 Gy [178]
12

V12 Gy < 15 mL [178] V14.5 Gy < 15 mL [178] V17 Gy < 15 mL [178] V18.5 Gy < 15 mL [178] V20 Gy < 15 mL [178] V22.4 Gy < 15 mL [178]
Bladder Vdose prescribed < 5–10 mL [174] Vdose prescribed < 5–10 mL [174]
Dmax < 45.6 Gy [202] V37 Gy < 10 mL [202]
V41.8 Gy < 10 mL [202] V38.78 Gy ≤ 0.03 mL [201]
V38.78 Gy ≤ 1 mL [200]
V32.63 Gy ≤ 10% mL [200]
V18.12 Gy ≤ 10% [201]
V18.13 Gy ≤ 50% mL [200]
Femoral head V14 Gy < 10 mL [39] V19.5 Gy < 10 mL [178] V21.9 Gy < 10 mL [39] V27 Gy < 10 mL [178] V30 Gy < 10 mL [39,178] V35 Gy < 10 mL [178]
V15 Gy < 10 mL [178] V24 Gy < 10 mL [178]
Cauda equina Dmax < 12.4–14 Gy Dmax < 17–19.3 Gy Dmax < 20.3–23.1 Gy Dmax < 23–26.2 Gy [174] Dmax < 25.3–28.8 Gy [174] Dmax < 38.4 Gy [178]
[174] [174] [174] Dmax < 28.8 Gy [178] Dmax < 30 Gy V34 Gy < 5 mL [178]
Dmax < 16 Gy [170,178] Dmax < 20.8 Gy [178] Dmax < 24 Gy [182] V26 Gy < 5 mL [178] Dmax < 31.5 Gy [178]
Dmax < 18 Gy [182] V18 Gy < 5 mL [178] Dmax < 25.5 Gy [178] V30 Gy < 5 mL [178]
V14 Gy < 5 mL V21.9 Gy < 5 mL [178]
[170,178,182]

Cancer/Radiothérapie xxx (xxxx) xxx–xxx

V16 Gy < 0.03 mL [182]
Sacral plexus Dmax < 16 Gy [178] Dmax < 20.8 Gy [178] Dmax 25.5 < Gy [178] Dmax 28.8 < Gy [178] Dmax < 32 Gy [178] Dmax < 38.4 Gy [178]
V14.4 Gy < 5 mL [178] V18.5 Gy < 5 mL [178] V22.5 Gy < 5 mL [178] V26 Gy < 5 mL [178] V30 Gy < 5 mL [178] V34 Gy < 5 mL [178]
Prostatic urethra Dmax < 38–42 Gy [174] Dmax < 35–38 Gy [174]
Dmax < 40 Gy [202] V38.78 Gy ≤ 0.03 mL [201]
V38.78 Gy ≤ 0.03 mL [200]
V42 Gy ≤ 0.03 mL [202]

VxGy : recipient volume x Gy; Dmax : maximum dose.

G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

Table 12
Dose constraints for ablative hypofractionated radiotherapy (dose per fraction > 6 Gy) schedules for organs at risk located in the whole body.

Organ Number of fractions

1 2 3 4 5 6 ≥8

Skin Dmax < 26 Gy [183] Dmax < 30.3 Gy [178] Dmax < 33 Gy [178] Dmax < 36 Gy [178] Dmax < 38.5 Gy [178] Dmax < Gy Dmax < 45.6 Gy [178]
Dmax < 27.5 Gy [178] V28.3 Gy < 10 mL [178] V31 Gy < 10 mL [178] V33.6 Gy < 10 mL [178] V36.5 Gy < 10 mL [178] Vx Gy < 10 mL V43.2 Gy < 10 mL [178]
V23 Gy < 10 mL [183]
V25.5 Gy < 10 mL [178]

VxGy : recipient volume x Gy; Dmax : maximum dose.

It is not within the purpose of this review to discuss the rele- [9] Noël G, Bauer N, Clavier JB, Guihard S, Lim O, Jastaniah Z. [Stereotactic radio-
vance or the clinical accuracy of the values taken from the literature. therapy of intracranial benign tumors]. Cancer Radiother 2012;16:410–7,
http://dx.doi.org/10.1016/j.canrad.2012.07.179.
Some of them seem contradictory, but the references enable the [10] Noël G, Daisne JF, Thillays F. [Stereotactic radiotherapy for
reader to consult the original article. brain metastasis]. Cancer Radiother 2012;16 Suppl.:S101–10,
Certain values can be changed or adjusted. We recommend this http://dx.doi.org/10.1016/j.canrad.2011.02.008.
[11] Dhermain F, Noël G, Antoni D, Tallet A. Role of radiation ther-
review for dose constraints in comparison to the one proposed apy in brain metastases management. Cancer Radiother 2020;24:463–9,
previously in Recorad I [39]. http://dx.doi.org/10.1016/j.canrad.2020.06.013.
[12] Defraene G, Schuit E, De Ruysscher D. Development and internal vali-
dation of a multinomial NTCP model for the severity of acute dyspnea
Disclosure of interest after radiotherapy for lung cancer. Radiother Oncol 2019;136:176–84,
http://dx.doi.org/10.1016/j.radonc.2019.03.034.
[13] Nguyen MN, Noël G, Antoni D. [Reirradiation of brain metastasis:
The authors did not disclose relationships/activities/interests. review of the last five years]. Cancer Radiother 2019;23:531–40,
http://dx.doi.org/10.1016/j.canrad.2019.07.144.
[14] Jadon R, Higgins E, Hanna L, Evans M, Coles B, Staffurth J. A sys-
Author contribution tematic review of dose-volume predictors and constraints for late
bowel toxicity following pelvic radiotherapy. Radiat Oncol 2019;14:57,
The authors did not provide this information. http://dx.doi.org/10.1186/s13014-019-1262-8.
[15] Bera G, Pointreau Y, Denis F, Orain I, Dupuis O, Créhange G. [Normal tissue
tolerance to external beam radiation therapy: esophagus]. Cancer Radiother
Acknowledgements 2010;14:327–35, http://dx.doi.org/10.1016/j.canrad.2010.02.008.
[16] Blais E, Pichon B, Mampuya A, Antoine M, Lagarde P, Kantor G,
et al. [Lung dose constraints for normofractionated radiotherapy and for
The authors wish to thank Albert Lisbona and Philippe Giraud stereotactic body radiation therapy]. Cancer Radiother 2017;21:584–96,
for their careful reviewing and proofreading. http://dx.doi.org/10.1016/j.canrad.2017.07.046.
[17] Debbi K, Janoray G, Scher N, Deutsch É, Mornex F. [Doses to organs at risk in
conformational and stereotactic body radiation therapy: liver]. Cancer Radio-
Appendix 1. ther 2017;21:604–12, http://dx.doi.org/10.1016/j.canrad.2017.07.042.
[18] Duvergé L, Castelli J, Lizée T, de Crevoisier R, Azria D. [Doses to organs at risk
for conformational and stereotactic radiotherapy: bladder]. Cancer Radiother
Digital RecoRadTM tool: http://www.sfro-recorad.fr/ 2017;21:597–603, http://dx.doi.org/10.1016/j.canrad.2017.07.038.
[19] Gérard M, Jumeau R, Pichon B, Biau J, Blais E, Horion J, et al. [Hippocampus,
brainstem and brain dose–volume constraints for fractionated 3-D radiother-
References apy and for stereotactic radiation therapy: limits and perspectives]. Can-
cer Radiother 2017;21:636–47, http://dx.doi.org/10.1016/j.canrad.2017.08.
[1] Barillot I, Tavernier E, Peignaux K, Williaume D, Nickers P, Leblanc-Onfroy 108.
M, et al. Impact of postoperative intensity-modulated radiotherapy on acute [20] Goupy F, Chajon E, Castelli J, Le Prisé É, Duvergé L, Jaksic N, et al. [Dose
gastrointestinal toxicity for patients with endometrial cancer: results of constraints to organs at risk for conformational and stereotactic radio-
the phase II RTCMIENDOMETRE French multicentre trial. Radiother Oncol therapy: small bowel and duodenum]. Cancer Radiother 2017;21:613–8,
2014;111:138–43, http://dx.doi.org/10.1016/j.radonc.2014.01.018. http://dx.doi.org/10.1016/j.canrad.2017.07.036.
[2] Antoni D, Natarajan-Ame S, Meyer P, Niederst C, Bourahla K, Noël G. Contribu- [21] Janoray G, Chapet S, Ruffier-Loubière A, Bernadou G, Pointreau Y, Calais G.
tion of three-dimensional conformal intensity-modulated radiation therapy Robotic stereotactic body radiation therapy for tumors of the liver: radiation-
for women affected by bulky stage II supradiaphragmatic Hodgkin disease. induced liver disease, incidence and predictive factors. Cancer Radiother
Radiat Oncol 2013;8:112, http://dx.doi.org/10.1186/1748-717X-8-112. 2014;18:191–7, http://dx.doi.org/10.1016/j.canrad.2014.03.009.
[3] Tubiana M. Can we reduce the incidence of second primary malig- [22] Lacornerie T, Rio E, Mahé MA. [Stereotactic body radiation therapy for hepatic
nancies occurring after radiotherapy? A critical review. Radiother Oncol malignancies: organs at risk, uncertainties margins, doses]. Cancer Radiother
2009;91:4–15, http://dx.doi.org/10.1016/j.radonc.2008.12.016 [discussion 2017;21:574–9, http://dx.doi.org/10.1016/j.canrad.2017.07.028.
1–3]. [23] Schernberg A, Hennequin C. [Normal tissue tolerance to external beam radi-
[4] Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. ation therapy: bone marrow and cortical bone structures]. Cancer Radiother
The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy 2017;21:619–25, http://dx.doi.org/10.1016/j.canrad.2017.06.005.
hypofractionation for treatment of early breast cancer: 10-year follow-up [24] Vandendorpe B, Servagi Vernat S, Ramiandrisoa F, Bazire L, Kirova
results of two randomised controlled trials. Lancet Oncol 2013;14:1086–94, YM. [Doses to organs at risk in conformational radiotherapy and
http://dx.doi.org/10.1016/S1470-2045(13)70386-3. stereotaxic irradiation: the heart]. Cancer Radiother 2017;21:626–35,
[5] de Crevoisier R, Pommier P, Latorzeff I, Chapet O, Chauvet B, Hennequin http://dx.doi.org/10.1016/j.canrad.2017.07.044.
C. [Prostate cancer external beam radiotherapy]. Cancer Radiother 2016;20 [25] Azria D, Riou O, Castan F, Nguyen TD, Peignaux K, Leman-
Suppl.:S200–9, http://dx.doi.org/10.1016/j.canrad.2016.07.037. ski C, et al. Radiation-induced CD8 T-lymphocyte apoptosis as
[6] Barillot I, Antoni D, Bellec J, Biau J, Giraud P, Jenny C, et al. [Ref- a predictor of breast fibrosis after radiotherapy: results of the
erence bases of radiotherapy under stereotaxic conditions for prospective multicenter French trial. EBioMedicine 2015;2:1965–73,
bronchopulmonary, hepatic, prostatic, upper aero-digestive, cerebral http://dx.doi.org/10.1016/j.ebiom.2015.10.024.
and bone tumors or metastases]. Cancer Radiother 2018;22:660–81, [26] Ferlazzo ML, Bourguignon M, Foray N. Functional assays for individ-
http://dx.doi.org/10.1016/j.canrad.2018.08.001. ual radiosensitivity:a critical review. Semin Radiat Oncol 2017;27:310–5,
[7] Keller A, Doré M, Cebula H, Thillays F, Proust F, Darie I, et al. http://dx.doi.org/10.1016/j.semradonc.2017.04.003.
Hypofractionated stereotactic radiation therapy to the resection bed for [27] Seibold P, Auvinen A, Averbeck D, Bourguignon M, Hartikainen JM, Hoeschen
intracranial metastases. Int J Radiat Oncol Biol Phys 2017;99:1179–89, C, et al. Clinical and epidemiological observations on individual radi-
http://dx.doi.org/10.1016/j.ijrobp.2017.08.014. ation sensitivity and susceptibility. Int J Radiat Biol 2020;96:324–39,
[8] Menoux I, Antoni D, Mazzara C, Labani A, Charloux A, Quoix É, http://dx.doi.org/10.1080/09553002.2019.1665209.
et al. Radiation-induced lung toxicity predictors: retrospective analy- [28] Rosenstein BS. Radiogenomics: identification of genomic predic-
sis of 90 patients treated with stereotactic body radiation therapy for tors for radiation toxicity. Semin Radiat Oncol 2017;27:300–9,
stage I non-small-cell lung carcinoma. Cancer Radiother 2020;24:120–7, http://dx.doi.org/10.1016/j.semradonc.2017.04.005.
http://dx.doi.org/10.1016/j.canrad.2019.11.003.

13
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

[29] Citrin DE, Mitchell JB. Mechanisms of normal tissue injury [54] Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. Preservation
from irradiation. Semin Radiat Oncol 2017;27:316–24, of memory with conformal avoidance of the hippocampal neural stem-cell
http://dx.doi.org/10.1016/j.semradonc.2017.04.001. compartment during whole-brain radiotherapy for brain metastases (RTOG
[30] Bourgier C, Castan F, Riou O, Nguyen TD, Peignaux K, Lemanski 0933): a phase II multi-institutional trial. J Clin Oncol 2014;32:3810–6,
C, et al. Impact of adjuvant hormonotherapy on radiation-induced http://dx.doi.org/10.1200/JCO.2014.57.2909.
breast fibrosis according to the individual radiosensitivity: results of [55] Gondi V, Hermann BP, Mehta MP, Tome WA. Hippocampal dosimetry predicts
a multicenter prospective French trial. Oncotarget 2018;9:15757–65, neurocognitive function impairment after fractionated stereotactic radio-
http://dx.doi.org/10.18632/oncotarget.24606. therapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol
[31] Appelt AL, Vogelius IR, Farr KP, Khalil AA, Bentzen SM. Towards Phys 2012;83:e487–93, http://dx.doi.org/10.1016/j.ijrobp.2011.10.021.
individualized dose constraints: adjusting the QUANTEC radiation pneu- [56] Gondi V, Mehta MP, Pugh S, Tome WA. Memory preservation with conformal
monitis model for clinical risk factors. Acta Oncol 2014;53:605–12, avoidance of the hippocampus during whole-brain radiotherapy (WBRT) for
http://dx.doi.org/10.3109/0284186X.2013.820341. patients with brain metastases: primary endpoint results of RTOG 0933. Int J
[32] Giuranno L, Ient J, De Ruysscher D, Vooijs MA. Radiation-induced lung injury Radiat Oncol Biol Phys 2013;87:1186.
(RILI). Front Oncol 2019;9:877, http://dx.doi.org/10.3389/fonc.2019.00877. [57] Haberer S, Assouline A, Mazeron JJ. [Normal tissue tolerance to external beam
[33] Joseph K, Vos LJ, Gabos Z, Pervez N, Chafe S, Tankel K, et al. Skin toxicity in early radiation therapy: brain and hypophysis]. Cancer Radiother 2010;14:263–8,
breast cancer patients treated with field-in-field breast intensity-modulated http://dx.doi.org/10.1016/j.canrad.2010.02.005.
radiotherapy versus helical inverse breast intensity-modulated radiotherapy: [58] Lawrence YR, Li XA, el Naqa I, Hahn CA, Marks LB, Merchant TE, et al. Radiation
results of a phase III randomised controlled trial. Clin Oncol (R Coll Radiol) dose-volume effects in the brain. Int J Radiat Oncol Biol Phys 2010;76:S20–7,
2021;33:30–9, http://dx.doi.org/10.1016/j.clon.2020.07.005. http://dx.doi.org/10.1016/j.ijrobp.2009.02.091.
[34] Stroom JC, Heijmen BJ. Limitations of the planning organ at risk vol- [59] Jiang GL, Tucker SL, Guttenberger R, Peters LJ, Morrison WH, Garden AS,
ume (PRV) concept. Int J Radiat Oncol Biol Phys 2006;66:279–86, et al. Radiation-induced injury to the visual pathway. Radiother Oncol
http://dx.doi.org/10.1016/j.ijrobp.2006.05.009. 1994;30:17–25.
[35] Gay HA, Jin JY, Chang AJ, Ten Haken RK. Utility of normal tissue- [60] Danesh-Meyer HV. Radiation-induced optic neuropathy. J Clin Neurosci
to-tumor ␣/␤ ratio when evaluating isodoses of isoeffective radiation 2008;15:95–100, http://dx.doi.org/10.1016/j.jocn.2007.09.004.
therapy treatment plans. Int J Radiat Oncol Biol Phys 2013;85:e81–7, [61] Mayo C, Martel MK, Marks LB, Flickinger J, Nam J, Kirkpatrick J. Radiation
http://dx.doi.org/10.1016/j.ijrobp.2012.09.021. dose–volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys
[36] Brenner DJ. The linear-quadratic model is an appropriate methodology for 2010;76:S28–35, http://dx.doi.org/10.1016/j.ijrobp.2009.07.1753.
determining isoeffective doses at large doses per fraction. Semin Radiat Oncol [62] Parsons JT, Bova FJ, Fitzgerald CR, Mendenhall WM, Million RR. Radiation
2008;18:234–9, http://dx.doi.org/10.1016/j.semradonc.2008.04.004. retinopathy after external-beam irradiation: analysis of time–dose factors.
[37] Kirkpatrick JP, Meyer JJ, Marks LB. The linear-quadratic model is inappropriate Int J Radiat Oncol Biol Phys 1994;30:765–73 [0360-3016(94)90347-6 (pii)].
to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol [63] Daly ME, Chen AM, Bucci MK, El-Sayed I, Xia P, Kaplan MJ, et al.
2008;18:240–3, http://dx.doi.org/10.1016/j.semradonc.2008.04.005. Intensity-modulated radiation therapy for malignancies of the nasal cav-
[38] Abusaris H, Storchi PR, Brandwijk RP, Nuyttens JJ. Second reirradia- ity and paranasal sinuses. Int J Radiat Oncol Biol Phys 2007;67:151–7,
tion: efficacy, dose and toxicity in patients who received three courses http://dx.doi.org/10.1016/j.ijrobp.2006.07.1389.
of radiotherapy with overlapping fields. Radiother Oncol 2011;99:235–9, [64] Bessell EM, Henk JM, Whitelocke RA, Wright JE. Ocular morbidity after radio-
http://dx.doi.org/10.1016/j.radonc.2011.03.010. therapy of orbital and conjunctival lymphoma. Eye (Lond) 1987;1:90–6,
[39] Noël G, Antoni D, Barillot I, Chauvet B. [Delineation of organs at http://dx.doi.org/10.1038/eye.1987.14.
risk and dose constraints]. Cancer Radiother 2016;20Suppl:S36–60, [65] Petersen IA, Kriss JP, McDougall IR, Donaldson SS. Prognostic factors in
http://dx.doi.org/10.1016/j.canrad.2016.07.032. the radiotherapy of Graves’ ophthalmopathy. Int J Radiat Oncol Biol Phys
[40] Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Toler- 1990;19:259–64.
ance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys [66] Takeda A, Shigematsu N, Suzuki S, Fujii M, Kawata T, Kawaguchi O, et al.
1991;21:109–22. Late retinal complications of radiation therapy for nasal and paranasal malig-
[41] Lambrecht M, Eekers DBP, Alapetite C, Burnet NG, Calugaru V, Coremans nancies: relationship between irradiated-dose area and severity. Int J Radiat
IEM, et al. Radiation dose constraints for organs at risk in neuro- Oncol Biol Phys 1999;44:599–605.
oncology; the European Particle Therapy Network consensus. Radiother [67] Wu VW, Ying MT, Kwong DL. A study on the postradiotherapy changes of
Oncol 2018;128:26–36, http://dx.doi.org/10.1016/j.radonc.2018.05.001. temporomandibular joint in nasopharyngeal carcinoma patients. Br J Radiol
[42] Lawenda BD, Gagne HM, Gierga DP, Niemierko A, Wong WM, 2017;90:20170375, http://dx.doi.org/10.1259/bjr.20170375.
Tarbell NJ, et al. Permanent alopecia after cranial irradiation: [68] Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ. Impact of
dose–response relationship. Int J Radiat Oncol Biol Phys 2004;60:879–87, intensity-modulated radiotherapy on acute hematologic toxicity in women
http://dx.doi.org/10.1016/j.ijrobp.2004.04.031. with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002;54:1388–96,
[43] Martel MK, Sandler HM, Cornblath WT, Marsh LH, Hazuka MB, Roa WH, http://dx.doi.org/10.1016/s0360-3016(02)03801-4.
et al. Dose-volume complication analysis for visual pathway structures of [69] King SN, Dunlap NE, Tennant PA, Pitts T. Pathophysiology of radiation-
patients with advanced paranasal sinus tumors. Int J Radiat Oncol Biol Phys induced dysphagia in head and neck cancer. Dysphagia 2016;31:339–51,
1997;38:273–84. http://dx.doi.org/10.1007/s00455-016-9710-1.
[44] Kruser TJ, Bosch WR, Badiyan SN, Bovi JA, Ghia AJ, Kim MM, et al. NRG brain [70] Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and
tumor specialists consensus guidelines for glioblastoma contouring. J Neu- function relationships in parotid salivary glands following conformal and
roOncol 2019;143:157–66, http://dx.doi.org/10.1007/s11060-019-03152-9. intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol
[45] Maingon P, Mammar V, Peignaux K, Truc G, Barillot I. [Constraints to organs at Biol Phys 1999;45:577–87.
risk for treatment of head and neck cancers by intensity-modulated radiation [71] Deasy JO, Moiseenko V, Marks L, Chao KS, Nam J, Eisbruch A. Radiotherapy
therapy]. Cancer Radiother 2004;8:234. dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys
[46] Hitchcock YJ, Tward JD, Szabo A, Bentz BG, Shrieve DC. Relative contri- 2010;76:S58–63, http://dx.doi.org/10.1016/j.ijrobp.2009.06.090.
butions of radiation and cisplatin-based chemotherapy to sensorineural [72] Murdoch-Kinch CA, Kim HM, Vineberg KA, Ship JA, Eisbruch A. Dose–effect
hearing loss in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys relationships for the submandibular salivary glands and implications for their
2009;73:779–88, http://dx.doi.org/10.1016/j.ijrobp.2008.05.040. sparing by intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys
[47] Bhandare N, Jackson A, Eisbruch A, Pan CC, Flickinger JC, Antonelli P, et al. Radi- 2008;72:373–82, http://dx.doi.org/10.1016/j.ijrobp.2007.12.033.
ation therapy and hearing loss. Int J Radiat Oncol Biol Phys 2010;76:S50–7, [73] Debelleix C, Pointreau Y, Lafond C, Denis F, Calais G, Bourhis JH.
http://dx.doi.org/10.1016/j.ijrobp.2009.04.096. Dose–tolérance à l’irradiation des tissus sains : larynx et pharynx. Cancer
[48] Gore SK, Plowman NP, Dharmasena A, Verity DH, Rose GE. Corneal Radiother 2010;14:301–6.
complications after orbital radiotherapy for primary epithelial malig- [74] Dornfeld K, Simmons JR, Karnell L, Karnell M, Funk G, Yao M, et al. Radiation
nancies of the lacrimal gland. Br J Ophthalmol 2018;102:882–4, doses to structures within and adjacent to the larynx are correlated with
http://dx.doi.org/10.1136/bjophthalmol-2017-311134. long-term diet- and speech-related quality of life. Int J Radiat Oncol Biol Phys
[49] Nakissa N, Rubin P, Strohl R, Keys H. Ocular and orbital complications follow- 2007;68:750–7, http://dx.doi.org/10.1016/j.ijrobp.2007.01.047.
ing radiation therapy of paranasal sinus malignancies and review of litera- [75] Sanguineti G, Adapala P, Endres EJ, Brack C, Fiorino C, Sormani MP, et al.
ture. Cancer 1983;51:980–6 [10.1002/1097-0142(19830315)51:6<980::aid- Dosimetric predictors of laryngeal edema. Int J Radiat Oncol Biol Phys
cncr2820510603>3.0.co;2-y]. 2007;68:741–9, http://dx.doi.org/10.1016/j.ijrobp.2007.01.010.
[50] Marchand V, Dendale R. Tolérance à l’irradiation des tissus sains : l’œil. Cancer [76] Colella G, Cannavale R, Pentenero M, Gandolfo S. Oral implants in radiated
Radiother 2010;14:277–83. patients: a systematic review. Int J Oral Maxillofac Implants 2007;22:616–22.
[51] Henk JM, Whitelocke RA, Warrington AP, Bessell EM. Radiation dose to the [77] Hindorf C, Glatting G, Chiesa C, Linden O, Flux G, Committee ED.
lens and cataract formation. Int J Radiat Oncol Biol Phys 1993;25:815–20. EANM Dosimetry Committee guidelines for bone marrow and whole-
[52] Deeg HJ, Flournoy N, Sullivan KM, Sheehan K, Buckner CD, Sanders JE, et al. body dosimetry. Eur J Nucl Med Mol Imaging 2010;37:1238–50,
Cataracts after total body irradiation and marrow transplantation: a sparing http://dx.doi.org/10.1007/s00259-010-1422-4.
effect of dose fractionation. Int J Radiat Oncol Biol Phys 1984;10:957–64. [78] Rancati T, Schwarz M, Allen AM, Feng F, Popovtzer A, Mittal B, et al. Radiation
[53] Strigari L, Benassi M, Arcangeli G, Bruzzaniti V, Giovinazzo G, Marucci L. A dose-volume effects in the larynx and pharynx. Int J Radiat Oncol Biol Phys
novel dose constraint to reduce xerostomia in head-and-neck cancer patients 2010;76:S64–9, http://dx.doi.org/10.1016/j.ijrobp.2009.03.079.
treated with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys [79] Vlacich G, Spratt DE, Diaz R, Phillips JG, Crass J, Li CI, et al. Dose to
2010;77:269–76, http://dx.doi.org/10.1016/j.ijrobp.2009.07.1734. the inferior pharyngeal constrictor predicts prolonged gastrostomy tube

14
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

dependence with concurrent intensity-modulated radiation therapy and [101] Ogino I, Watanabe S, Sakamaki K, Ogino Y, Kunisaki C, Kimura
chemotherapy for locally-advanced head and neck cancer. Radiother Oncol K. Dosimetric predictors of radiation-induced pericardial effu-
2014;110:435–40, http://dx.doi.org/10.1016/j.radonc.2013.12.007. sion in esophageal cancer. Strahlenther Onkol 2017;193:552–60,
[80] Feng FY, Kim HM, Lyden TH, Haxer MJ, Feng M, Worden FP, et al. http://dx.doi.org/10.1007/s00066-017-1127-8.
Intensity-modulated radiotherapy of head and neck cancer aiming [102] Xue J, Han C, Jackson A, Hu C, Yao H, Wang W, et al. Doses of radia-
to reduce dysphagia: early dose-effect relationships for the swal- tion to the pericardium, instead of heart, are significant for survival in
lowing structures. Int J Radiat Oncol Biol Phys 2007;68:1289–98, patients with non-small cell lung cancer. Radiother Oncol 2019;133:213–9,
http://dx.doi.org/10.1016/j.ijrobp.2007.02.049. http://dx.doi.org/10.1016/j.radonc.2018.10.029.
[81] Sommat K, Ong WS, Hussain A, Soong YL, Tan T, Wee J, et al. Thyroid V40 pre- [103] Johansson S, Svensson H, Denekamp J. Dose response and latency for
dicts primary hypothyroidism after intensity-modulated radiation therapy radiation-induced fibrosis, edema, and neuropathy in breast cancer patients.
for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2017;98:574–80, Int J Radiat Oncol Biol Phys 2002;52:1207–19.
http://dx.doi.org/10.1016/j.ijrobp.2017.03.007. [104] Yom SS, Liao Z, Liu HH, Tucker SL, Hu CS, Wei X, et al. Initial evalu-
[82] Berges O, Belkacémi Y, Giraud P. [Normal tissue tolerance to exter- ation of treatment-related pneumonitis in advanced-stage non-small-cell
nal beam radiation therapy: thyroid]. Cancer Radiother 2010;14:307–11, lung cancer patients treated with concurrent chemotherapy and intensity-
http://dx.doi.org/10.1016/j.canrad.2010.03.005. modulated radiotherapy. Int J Radiat Oncol Biol Phys 2007;68:94–102,
[83] Sachdev S, Refaat T, Bacchus ID, Sathiaseelan V, Mittal BB. Thyroid V50 highly http://dx.doi.org/10.1016/j.ijrobp.2006.12.031.
predictive of hypothyroidism in head-and-neck cancer patients treated with [105] Liao ZX, Komaki RR, Thames Jr HD, Liu HH, Tucker SL, Mohan R,
intensity-modulated radiotherapy (IMRT). Am J Clin Oncol 2017;40:413–7, et al. Influence of technologic advances on outcomes in patients with
http://dx.doi.org/10.1097/COC.0000000000000165. unresectable, locally-advanced non-small-cell lung cancer receiving con-
[84] Huang CL, Tan HW, Guo R, Zhang Y, Peng H, Peng L, et al. Thy- comitant chemoradiotherapy. Int J Radiat Oncol Biol Phys 2010;76:775–81,
roid dose–volume thresholds for the risk of radiation-related hypothy- http://dx.doi.org/10.1016/j.ijrobp.2009.02.032.
roidism in nasopharyngeal carcinoma treated with intensity-modulated [106] Teh AY, Park EJ, Shen L, Chung HT. Three-dimensional volumetric analysis of
radiotherapy – A single-institution study. Cancer Med 2019;8:6887–93, irradiated lung with adjuvant breast irradiation. Int J Radiat Oncol Biol Phys
http://dx.doi.org/10.1002/cam4.2574. 2009;75:1309–15, http://dx.doi.org/10.1016/j.ijrobp.2008.12.077.
[85] Nielsen MH, Berg M, Pedersen AN, Andersen K, Glavicic V, Jakobsen EH, [107] Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, et al. Clin-
et al. Delineation of target volumes and organs at risk in adjuvant radio- ical dose-volume histogram analysis for pneumonitis after 3D treatment for
therapy of early breast cancer: national guidelines and contouring atlas by non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1999;45:
the Danish Breast Cancer Cooperative Group. Acta Oncol 2013;52:703–10, 323–9.
http://dx.doi.org/10.3109/0284186X.2013.765064. [108] Marks LB. Dosimetric predictors of radiation-induced lung injury. Int J Radiat
[86] McWilliam A, Kennedy J, Hodgson C, Vasquez Osorio E, Faivre-Finn Oncol Biol Phys 2002;54:313–6.
C, van Herk M. Radiation dose to heart base linked with poorer [109] Ramella S, Trodella L, Mineo TC, Pompeo E, Stimato G, Gaudino D, et al. Adding
survival in lung cancer patients. Eur J Cancer 2017;85:106–13, ipsilateral V20 and V30 to conventional dosimetric constraints predicts radi-
http://dx.doi.org/10.1016/j.ejca.2017.07.053. ation pneumonitis in stage IIIA-B NSCLC treated with combined-modality
[87] McWilliam A, Khalifa J, Vasquez Osorio E, Banfill K, Abravan A, Faivre- therapy. Int J Radiat Oncol Biol Phys 2010;76:110–5.
Finn C, et al. Novel methodology to investigate the effect of radiation dose [110] Song CH, Pyo H, Moon SH, Kim TH, Kim DW, Cho KH. Treatment-related pneu-
to heart substructures on overall survival. Int J Radiat Oncol Biol Phys monitis and acute esophagitis in non-small-cell lung cancer patients treated
2020;108:1073–81, http://dx.doi.org/10.1016/j.ijrobp.2020.06.031. with chemotherapy and helical tomotherapy. Int J Radiat Oncol Biol Phys
[88] Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, et al. 2010;78:651–8, http://dx.doi.org/10.1016/j.ijrobp.2009.08.068.
Risk of ischemic heart disease in women after radiotherapy for breast cancer. [111] Wang S, Liao Z, Wei X, Liu HH, Tucker SL, Hu CS, et al. Analy-
N Engl J Med 2013;368:987–98, http://dx.doi.org/10.1056/NEJMoa1209825. sis of clinical and dosimetric factors associated with treatment-related
[89] Kong FM, Ritter T, Quint DJ, Senan S, Gaspar LE, Komaki RU, et al. pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC)
Consideration of dose limits for organs at risk of thoracic radiother- treated with concurrent chemotherapy and three-dimensional conformal
apy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, radiotherapy (3D-CRT). Int J Radiat Oncol Biol Phys 2006;66:1399–407,
ribs, and brachial plexus. Int J Radiat Oncol Biol Phys 2011;81:1442–57, http://dx.doi.org/10.1016/j.ijrobp.2006.07.1337.
http://dx.doi.org/10.1016/j.ijrobp.2010.07.1977. [112] Kim HJ, Jang WI, Kim TJ, Kim JH, Kim SW, Moon SH, et al. Radiation-induced
[90] Cutter DJ, Schaapveld M, Darby SC, Hauptmann M, van Nimwegen FA, Krol AD, pulmonary toxicity and related risk factors in breast cancer. J Breast Cancer
et al. Risk of valvular heart disease after treatment for Hodgkin lymphoma. J 2009;12:67–72.
Natl Cancer Inst 2015;107:djv008, http://dx.doi.org/10.1093/jnci/djv008. [113] Chan ST, Ruan D, Shaverdian N, Raghavan G, Cao M, Lee P. Effect of radiation
[91] Ratosa I, Ivanetic Pantar M. Cardiotoxicity of mediastinal doses to the heart on survival for stereotactic ablative radiotherapy for early-
radiotherapy. Rep Pract Oncol Radiother 2019;24:629–43, stage non-small-cell lung cancer:an artificial neural network approach. Clin
http://dx.doi.org/10.1016/j.rpor.2019.09.002. Lung Cancer 2020;21, http://dx.doi.org/10.1016/j.cllc.2019.10.010 [136–144
[92] Rudra S, Al-Hallaq HA, Feng C, Chmura SJ, Hasan Y. Effect of RTOG breast/chest e1].
wall guidelines on dose–volume histogram parameters. J Appl Clin Med Phys [114] Mansouri I, Allodji RS, Hill C, El-Fayech C, Pein F, Diallo S, et al.
2014;15:4547, http://dx.doi.org/10.1120/jacmp.v15i2.4547. The role of irradiated heart and left ventricular volumes in heart fail-
[93] Matzinger O, Gerber E, Bernstein Z, Maingon P, Haustermans K, Bosset ure occurrence after childhood cancer. Eur J Heart Fail 2019;21:509–18,
JF, et al. EORTC-ROG expert opinion: radiotherapy volume and treatment http://dx.doi.org/10.1002/ejhf.1376.
guidelines for neoadjuvant radiation of adenocarcinomas of the gastroe- [115] Marks LB, Yorke E.D., Jackson A, Ten Haken RK, Constine LS, Eis-
sophageal junction and the stomach. Radiother Oncol 2009;92:164–75, bruch A, et al. Use of normal tissue complication probability
http://dx.doi.org/10.1016/j.radonc.2009.03.018. models in the clinic. Int J Radiat Oncol Biol Phys 2010;76:S10–9,
[94] Kim TH, Cho KH, Pyo HR, Lee JS, Han JY, Zo JI, et al. Dose–volumetric http://dx.doi.org/10.1016/j.ijrobp.2009.07.1754.
parameters of acute esophageal toxicity in patients with lung cancer treated [116] Huang J, Robertson JM, Ye H, Margolis J, Nadeau L, Yan D. Dose–volume
with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys analysis of predictors for gastrointestinal toxicity after concurrent
2005;62:995–1002, http://dx.doi.org/10.1016/j.ijrobp.2004.12.025. full-dose gemcitabine and radiotherapy for locally-advanced pancre-
[95] Singh AK, Lockett MA, Bradley JD. Predictors of radiation-induced atic adenocarcinoma. Int J Radiat Oncol Biol Phys 2012;83:1120–5,
esophageal toxicity in patients with non-small-cell lung cancer treated with http://dx.doi.org/10.1016/j.ijrobp.2011.09.022.
three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys [117] Kelly P, Das P, Pinnix CC, Beddar S, Briere T, Pham M, et al. Duo-
2003;55:337–41. denal toxicity after fractionated chemoradiation for unresectable
[96] Belderbos J, Heemsbergen W, Hoogeman M, Pengel K, Rossi M, Lebesque pancreatic cancer. Int J Radiat Oncol Biol Phys 2013;85:e143–9,
J. Acute esophageal toxicity in non-small cell lung cancer patients http://dx.doi.org/10.1016/j.ijrobp.2012.09.035.
after high dose conformal radiotherapy. Radiother Oncol 2005;75:157–64, [118] Fokdal L, Honore H, Hoyer M, von der Maase H. Dose–volume his-
http://dx.doi.org/10.1016/j.radonc.2005.03.021. tograms associated to long-term colorectal functions in patients
[97] Wei X, Liu HH, Tucker SL, Liao Z, Hu C, Mohan R, et al. Risk factors for acute receiving pelvic radiotherapy. Radiother Oncol 2005;74:203–10,
esophagitis in non-small-cell lung cancer patients treated with concurrent http://dx.doi.org/10.1016/j.radonc.2004.11.001.
chemotherapy and three-dimensional conformal radiotherapy. Int J Radiat [119] Oberdiac P, Mineur L. [Normal tissue tolerance to external beam
Oncol Biol Phys 2006;66:100–7. radiation therapy: the stomach]. Cancer Radiother 2010;14:336–9,
[98] Chapet O, Kong FM, Lee JS, Hayman JA, Ten Haken RK. Normal tissue com- http://dx.doi.org/10.1016/j.canrad.2010.04.005.
plication probability modeling for acute esophagitis in patients treated with [120] Pan CC, Kavanagh BD, Dawson LA, Li XA, Das SK, Miften M, et al. Radiation-
conformal radiation therapy for non-small cell lung cancer. Radiother Oncol associated liver injury. Int J Radiat Oncol Biol Phys 2010;76:S94–100,
2005;77:176–81, http://dx.doi.org/10.1016/j.radonc.2005.10.001. http://dx.doi.org/10.1016/j.ijrobp.2009.06.092.
[99] Maguire PD, Sibley GS, Zhou SM, Jamieson TA, Light KL, Antoine PA, et al. [121] Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ, et al. Radiation-induced liver
Clinical and dosimetric predictors of radiation-induced esophageal toxicity. disease in three-dimensional conformal radiation therapy for primary liver
Int J Radiat Oncol Biol Phys 1999;45:97–103. carcinoma: the risk factors and hepatic radiation tolerance. Int J Radiat Oncol
[100] Vivekanandan S, Landau DB, Counsell N, Warren DR, Khwanda A, Rosen Biol Phys 2006;65:426–34, http://dx.doi.org/10.1016/j.ijrobp.2005.12.031.
SD, et al. The impact of cardiac radiation dosimetry on survival after radi- [122] Rio E, Mornex F, Peiffert D, Huertas A. [Hepatic tumors
ation therapy for non-small cell lung cancer. Int J Radiat Oncol Biol Phys and radiotherapy]. Cancer Radiother 2016;20 Suppl.:S174–8,
2017;99:51–60, http://dx.doi.org/10.1016/j.ijrobp.2017.04.026. http://dx.doi.org/10.1016/j.canrad.2016.07.019.

15
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

[123] Dawson LA, Ten Haken RK, Lawrence TS. Partial irradiation of the liver. Semin for inverse planning. Int J Radiat Oncol Biol Phys 2006;66:505–13,
Radiat Oncol 2001;11:240–6. http://dx.doi.org/10.1016/j.ijrobp.2006.05.005.
[124] De Bari B, Pointreau Y, Rio E, Mirabel X, Mornex F. [Normal tissue tolerance [145] Baglan KL, Frazier RC, Yan D, Huang RR, Martinez AA, Robertson JM. The
to external beam radiation therapy: liver]. Cancer Radiother 2010;14:344–9, dose–volume relationship of acute small bowel toxicity from concurrent 5-
http://dx.doi.org/10.1016/j.canrad.2010.02.013. FU-based chemotherapy and radiation therapy for rectal cancer. Int J Radiat
[125] Gemici C, Yaprak G, Ozdemir S, Baysal T, Seseogullari OO, Ozyurt H. Volumetric Oncol Biol Phys 2002;52:176–83.
decrease of pancreas after abdominal irradiation, it is time to consider pan- [146] Isohashi F, Yoshioka Y, Mabuchi S, Konishi K, Koizumi M, Takahashi Y, et al.
creas as an organ at risk for radiotherapy planning. Radiat Oncol 2018;13:238, Dose–volume histogram predictors of chronic gastrointestinal complications
http://dx.doi.org/10.1186/s13014-018-1189-5. after radical hysterectomy and postoperative concurrent nedaplatin-based
[126] McDonald F, Waters R, Gulliford S, Hall E, James N, Huddart RA. chemoradiation therapy for early-stage cervical cancer. Int J Radiat Oncol Biol
Defining bowel dose volume constraints for bladder radiother- Phys 2013;85:728–34, http://dx.doi.org/10.1016/j.ijrobp.2012.05.021.
apy treatment planning. Clin Oncol (R Coll Radiol) 2015;27:22–9, [147] Bao Z, Wang D, Chen S, Chen M, Jiang D, Yang C, et al. Opti-
http://dx.doi.org/10.1016/j.clon.2014.09.016. mal dose limitation strategy for bone marrow sparing in intensity-
[127] Diavolitsis VM, Rademaker A, Boyle J, Kang Z, Kiel K, Mulcahy M, et al. Change modulated radiotherapy of cervical cancer. Radiat Oncol 2019;14:118,
in creatinine clearance over time following upper abdominal irradiation: a http://dx.doi.org/10.1186/s13014-019-1324-y.
dose-volume histogram multivariate analysis. Am J Clin Oncol 2011;34:53–7, [148] RTOG RTOG 0529. http://www.rtog.org/ClinicalTrials/ProtocolTable/Study
http://dx.doi.org/10.1097/COC.0b013e3181d27080. Details.aspx?study=0529.
[128] Wong Hee Kam S, Huguet F. [Normal tissue tolerance to exter- [149] Mahantshetty U, Krishnatry R, Chaudhari S, Kanaujia A, Engineer R,
nal beam radiation therapy: kidney]. Cancer Radiother 2010;14:340–3, Chopra S, et al. Comparison of 2 contouring methods of bone mar-
http://dx.doi.org/10.1016/j.canrad.2010.02.004. row on CT and correlation with hematological toxicities in non-bone
[129] Dewit L, Verheij M, Valdes Olmos RA, Arisz L. Compensatory renal response marrow-sparing pelvic intensity-modulated radiotherapy with concur-
after unilateral partial and whole volume high-dose irradiation of the human rent cisplatin for cervical cancer. Int J Gynecol Cancer 2012;22:1427–34,
kidney. Eur J Cancer 1993;29A:2239–43. http://dx.doi.org/10.1097/IGC.0b013e3182664b46.
[130] Jansen EP, Boot H, Saunders MP, Crosby TD, Dubbelman R, Bartelink H, [150] Kuntz L, Noël G. [Pelvic irradiation and hematopoietic toxic-
et al. A phase I–II study of postoperative capecitabine-based chemoradio- ity: a review of the literature]. Cancer Radiother 2021;25:77–91,
therapy in gastric cancer. Int J Radiat Oncol Biol Phys 2007;69:1424–8, http://dx.doi.org/10.1016/j.canrad.2020.05.018.
http://dx.doi.org/10.1016/j.ijrobp.2007.05.004. [151] Mutyala S. Dose constraints recommendations and a predictive nomogram
[131] Inaba K, Okamoto H, Wakita A, Tsuchida K, Kashihara T, Kobayashi K, et al. of incidence of haematological toxicity in anal cancer patients treated with
Long-term observations of radiation-induced creatinine clearance reduction concurrent cisplatin and intensity-modulated radiation therapy (IMRT). Int J
and renal parenchymal volume atrophy. Radiother Oncol 2016;120:145–9, Radiat Oncol Biol Phys 2008;72:S298–9.
http://dx.doi.org/10.1016/j.radonc.2016.04.022. [152] Herrmann T. [Radiation reactions in the gonads: importance in patient coun-
[132] Selek U, Cheung R, Lii M, Allen P, Steadham RE, Vantreese Jr TR, seling]. Strahlenther Onkol 1997;173:493–501.
et al. Erectile dysfunction and radiation dose to penile base structures: [153] Badin S, Iqbal A, Sikder M, Chang VT. Persistent pain in anal cancer survivors. J
a lack of correlation. Int J Radiat Oncol Biol Phys 2004;59:1039–46, Cancer Surviv 2008;2:79–83, http://dx.doi.org/10.1007/s11764-008-0051-4.
http://dx.doi.org/10.1016/j.ijrobp.2003.12.028. [154] Frykholm GJ, Sintorn K, Montelius A, Jung B, Pahlman L, Glimelius B. Acute
[133] Roach M, Winter K, Michalski JM, Cox JD, Purdy JA, Bosch W, et al. Penile lumbosacral plexopathy during and after preoperative radiotherapy of rectal
bulb dose and impotence after three-dimensional conformal radiotherapy adenocarcinoma. Radiother Oncol 1996;38:121–30.
for prostate cancer on RTOG 9406: findings from a prospective, multi- [155] Yi SK, Mak W, Yang CC, Liu T, Cui J, Chen AM, et al. Development of a standard-
institutional, phase I/II dose-escalation study. Int J Radiat Oncol Biol Phys ized method for contouring the lumbosacral plexus: a preliminary dosimetric
2004;60:1351–6, http://dx.doi.org/10.1016/j.ijrobp.2004.05.026. analysis of this organ at risk among 15 patients treated with intensity-
[134] RTOG RTOG 0415. http://www.rtog.org/ClinicalTrials/ProtocolTable/Study modulated radiotherapy for lower gastrointestinal cancers and the incidence
Details.aspx?study=0415. of radiation-induced lumbosacral plexopathy. Int J Radiat Oncol Biol Phys
[135] Roach 3rd M, Nam J, Gagliardi G, El Naqa I, Deasy JO, Marks LB. Radia- 2012;84:376–82, http://dx.doi.org/10.1016/j.ijrobp.2011.11.074.
tion dose–volume effects and the penile bulb. Int J Radiat Oncol Biol Phys [156] Langrand-Escure J, de Crevoisier R, Llagostera C, Créhange G, Delaroche
2010;76:S130–4, http://dx.doi.org/10.1016/j.ijrobp.2009.04.094. G, Lafond C, et al. Dose constraints for moderate hypofraction-
[136] Mavroidis P, al-Abany M, Helgason AR, Agren Cronqvist AK, Wersall P, Lind H, ated radiotherapy for prostate cancer: the French Genito-Urinary
et al. Dose–response relations for anal sphincter regarding fecal leakage and Group (Gétug) recommendations. Cancer Radiother 2018;22:193–8,
blood or phlegm in stools after radiotherapy for prostate cancer. Radiobiolog- http://dx.doi.org/10.1016/j.canrad.2017.11.004.
ical study of 65 consecutive patients. Strahlenther Onkol 2005;181:293–306, [157] Vaarkamp J, Adams EJ, Warrington AP, Dearnaley DP. A comparison of forward
http://dx.doi.org/10.1007/s00066-005-1313-y. and inverse planned conformal, multi segment and intensity-modulated
[137] al-Abany M, Helgason AR, Cronqvist AK, Lind B, Mavroidis P, Wersall P, et al. radiotherapy for the treatment of prostate and pelvic nodes. Radiother Oncol
Toward a definition of a threshold for harmless doses to the anal-sphincter 2004;73:65–72, http://dx.doi.org/10.1016/j.radonc.2004.07.015.
region and the rectum. Int J Radiat Oncol Biol Phys 2005;61:1035–44, [158] Pederson AW, Fricano J, Correa D, Pelizzari CA, Liauw SL. Late toxicity
http://dx.doi.org/10.1016/j.ijrobp.2004.07.706. after intensity-modulated radiation therapy for localized prostate cancer:
[138] Chopra S, Dora T, Chinnachamy AN, Thomas B, Kannan S, Engi- an exploration of dose–volume histogram parameters to limit genitourinary
neer R, et al. Predictors of grade 3 or higher late bowel toxicity and gastrointestinal toxicity. Int J Radiat Oncol Biol Phys 2012;82:235–41,
in patients undergoing pelvic radiation for cervical cancer: results http://dx.doi.org/10.1016/j.ijrobp.2010.09.058.
from a prospective study. Int J Radiat Oncol Biol Phys 2014;88:630–5, [159] Michalski JM, Yan Y, Watkins-Bruner D, Bosch WR, Winter K, Galvin
http://dx.doi.org/10.1016/j.ijrobp.2013.11.214. JM, et al. Preliminary toxicity analysis of 3-dimensional conformal
[139] Fonteyne V, De Neve W, Villeirs G, De Wagter C, De Meerleer G. radiation therapy versus intensity-modulated radiation therapy on
Late radiotherapy-induced lower intestinal toxicity (RILIT) of intensity- the high-dose arm of the Radiation Therapy Oncology Group 0126
modulated radiotherapy for prostate cancer: the need for adapting prostate cancer trial. Int J Radiat Oncol Biol Phys 2013;87:932–8,
toxicity scales and the appearance of the sigmoid colon as coresponsi- http://dx.doi.org/10.1016/j.ijrobp.2013.07.041.
ble organ for lower intestinal toxicity. Radiother Oncol 2007;84:156–63, [160] Greco C, Mazzetta C, Cattani F, Tosi G, Castiglioni S, Fodor A, et al.
http://dx.doi.org/10.1016/j.radonc.2007.06.013. Finding dose–volume constraints to reduce late rectal toxicity following
[140] Roeske JC, Bonta D, Mell LK, Lujan AE, Mundt AJ. A dosimetric analysis of acute 3D-conformal radiotherapy (3D-CRT) of prostate cancer. Radiother Oncol
gastrointestinal toxicity in women receiving intensity-modulated whole- 2003;69:215–22.
pelvic radiation therapy. Radiother Oncol 2003;69:201–7. [161] Huang EH, Pollack A, Levy L, Starkschall G, Dong L, Rosen I, et al. Late rectal
[141] Banerjee R, Chakraborty S, Nygren I, Sinha R. Small bowel dose param- toxicity: dose–volume effects of conformal radiotherapy for prostate cancer.
eters predicting grade ≥ 3 acute toxicity in rectal cancer patients Int J Radiat Oncol Biol Phys 2002;54:1314–21.
treated with neoadjuvant chemoradiation: an independent validation [162] Fiorino C, Sanguineti G, Cozzarini C, Fellin G, Foppiano F, Menegotti L,
study comparing peritoneal space versus small bowel loop con- et al. Rectal dose–volume constraints in high-dose radiotherapy of localized
touring techniques. Int J Radiat Oncol Biol Phys 2013;85:1225–31, prostate cancer. Int J Radiat Oncol Biol Phys 2003;57:953–62.
http://dx.doi.org/10.1016/j.ijrobp.2012.09.036. [163] Boersma LJ, van den Brink M, Bruce AM, Shouman T, Gras L, te Velde A, et al.
[142] Robertson JM, Lockman D, Yan D, Wallace M. The dose–volume relationship Estimation of the incidence of late bladder and rectum complications after
of small bowel irradiation and acute grade 3 diarrhea during chemora- high-dose (70–78 GY) conformal radiotherapy for prostate cancer, using dose-
diotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2008;70:413–8, volume histograms. Int J Radiat Oncol Biol Phys 1998;41:83–92.
http://dx.doi.org/10.1016/j.ijrobp.2007.06.066. [164] Sohn M, Yan D, Liang J, Meldolesi E, Vargas C, Alber M. Incidence of late rec-
[143] Guerrero Urbano T, Khoo V, Staffurth J, Norman A, Buffa F, Jackson A, et al. tal bleeding in high-dose conformal radiotherapy of prostate cancer using
Intensity-modulated radiotherapy allows escalation of the radiation dose to equivalent uniform dose-based and dose–volume-based normal tissue com-
the pelvic lymph nodes in patients with locally-advanced prostate cancer: plication probability models. Int J Radiat Oncol Biol Phys 2007;67:1066–73,
preliminary results of a phase I dose escalation study. Clin Oncol (R Coll Radiol) http://dx.doi.org/10.1016/j.ijrobp.2006.10.014.
2010;22:236–44. [165] Nguyen PL, Chen RC, Hoffman KE, Trofimov A, Efstathiou JA, Coen JJ,
[144] Tho LM, Glegg M, Paterson J, Yap C, MacLeod A, McCabe M, et al. et al. Rectal dose–volume histogram parameters are associated with
Acute small bowel toxicity and preoperative chemoradiotherapy long-term patient-reported gastrointestinal quality of life after conven-
for rectal cancer: investigating dose–volume relationships and role tional and high-dose radiation for prostate cancer: a subgroup analysis

16
G Model
CANRAD-4270; No. of Pages 17 ARTICLE IN PRESS
G. Noël, D. Antoni Cancer/Radiothérapie xxx (xxxx) xxx–xxx

of a randomized trial. Int J Radiat Oncol Biol Phys 2010;78:1081–5, artery blowout and other bleeding events in hypofractionated head
http://dx.doi.org/10.1016/j.ijrobp.2009.09.015. and neck retreatments. Int J Radiat Oncol Biol Phys 2021;110:147–59,
[166] Gulliford SL, Foo K, Morgan RC, Aird EG, Bidmead AM, Critchley H, et al. http://dx.doi.org/10.1016/j.ijrobp.2020.12.037.
Dose–volume constraints to reduce rectal side effects from prostate radio- [185] Gogineni E, Zhang I, Rana Z, Marrero M, Gill G, Sharma A, et al.
therapy: evidence from MRC RT01 Trial ISRCTN 47772397. Int J Radiat Oncol Quality of life outcomes following organ-sparing SBRT in previously
Biol Phys 2010;76:747–54, http://dx.doi.org/10.1016/j.ijrobp.2009.02.025. irradiated recurrent head and neck cancer. Front Oncol 2019;9:836,
[167] Bedford JL, Khoo VS, Webb S, Dearnaley DP. Optimization of coplanar six-field http://dx.doi.org/10.3389/fonc.2019.00836.
techniques for conformal radiotherapy of the prostate. Int J Radiat Oncol Biol [186] Pollom EL, Chin AL, Diehn M, Loo BW, Chang DT. Normal tissue constraints for
Phys 2000;46:231–8. abdominal and thoracic stereotactic body radiotherapy. Semin Radiat Oncol
[168] Teh WT, Stern C, Chander S, Hickey M. The impact of uterine radia- 2017;27:197–208, http://dx.doi.org/10.1016/j.semradonc.2017.02.001.
tion on subsequent fertility and pregnancy outcomes. Biomed Res Int [187] Huang WY, Jen YM, Lee MS, Chang LP, Chen CM, Ko KH, et al. Stereotactic body
2014;2014:482968, http://dx.doi.org/10.1155/2014/482968. radiation therapy in recurrent hepatocellular carcinoma. Int J Radiat Oncol
[169] Park JH, Kim YS, Park J, Ahn H, Kim CS, Kim M, et al. Incidence and dose–volume Biol Phys 2012;84:355–61, http://dx.doi.org/10.1016/j.ijrobp.2011.11.058.
analysis of acute bladder toxicity following pelvic radiotherapy. Tumori [188] RTOG RTOG 0915. http://www.rtog.org/ClinicalTrials/ProtocolTable/Study
2014;100:195–200, http://dx.doi.org/10.1700/1491.16413. Details.aspx?study=0915.
[170] Haas RL, Delaney TF, O’Sullivan B, Keus RB, Le Péchoux C, Olmi P, [189] Creach KM, El Naqa I, Bradley JD, Olsen JR, Parikh PJ, Drzymala
et al. Radiotherapy for management of extremity soft tissue sarcomas: RE, et al. Dosimetric predictors of chest wall pain after lung
why, when, and where? Int J Radiat Oncol Biol Phys 2012;84:572–80, stereotactic body radiotherapy. Radiother Oncol 2012;104:23–7,
http://dx.doi.org/10.1016/j.ijrobp.2012.01.062. http://dx.doi.org/10.1016/j.radonc.2012.01.014.
[171] Yanagi T, Kamada T, Tsuji H, Imai R, Serizawa I, Tsujii H. Dose–volume [190] Goldsmith C, Price P, Cross T, Loughlin S, Cowley I, Plowman N. Dose–volume
histogram and dose–surface histogram analysis for skin reactions to car- histogram analysis of stereotactic body radiotherapy treatment of pan-
bon ion radiotherapy for bone and soft tissue sarcoma. Radiother Oncol creatic cancer: a focus on duodenal dose constraints. Semin Radiat Oncol
2010;95:60–5, http://dx.doi.org/10.1016/j.radonc.2009.08.041. 2016;26:149–56, http://dx.doi.org/10.1016/j.semradonc.2015.12.002.
[172] Milano MT, Usuki KY, Walter KA, Clark D, Schell MC. Stereotactic radio- [191] LaCouture TA, Xue J, Subedi G, Xu Q, Lee JT, Kubicek G, et al. Small bowel
surgery and hypofractionated stereotactic radiotherapy: normal tissue dose dose tolerance for stereotactic body radiation therapy. Semin Radiat Oncol
constraints of the central nervous system. Cancer Treat Rev 2011;37:567–78, 2016;26:157–64, http://dx.doi.org/10.1016/j.semradonc.2015.11.009.
http://dx.doi.org/10.1016/j.ctrv.2011.04.004. [192] Toesca DA, Osmundson EC, Eyben RV, Shaffer JL, Lu P, Koong
[173] Minniti G, D’Angelillo RM, Scaringi C, Trodella LE, Clarke E, AC, et al. Central liver toxicity after SBRT: an expanded analy-
Matteucci P, et al. Fractionated stereotactic radiosurgery for sis and predictive nomogram. Radiother Oncol 2017;122:130–6,
patients with brain metastases. J Neurooncol 2014;117:295–301, http://dx.doi.org/10.1016/j.radonc.2016.10.024.
http://dx.doi.org/10.1007/s11060-014-1388-3. [193] Goodman KA, Kavanagh BD. Stereotactic body radiother-
[174] Grimm J, Marks LB, Jackson A, Kavanagh BD, Xue J, Yorke E. High apy for liver metastases. Semin Radiat Oncol 2017;27:240–6,
Dose per Fraction, Hypofractionated Treatment Effects in the Clinic http://dx.doi.org/10.1016/j.semradonc.2017.02.004.
(HyTEC): an overview. Int J Radiat Oncol Biol Phys 2021;110:1–10, [194] Rusthoven KE, Kavanagh BD, Cardenes H, Stieber VW, Burri SH, Feigen-
http://dx.doi.org/10.1016/j.ijrobp.2020.10.039. berg SJ, et al. Multi-institutional phase I/II trial of stereotactic body
[175] Milano MT, Grimm J, Niemierko A, Soltys SG, Moiseenko V, Redmond radiation therapy for liver metastases. J Clin Oncol 2009;27:1572–8,
KJ, et al. Single- and multifraction stereotactic radiosurgery dose/volume http://dx.doi.org/10.1200/JCO.2008.19.6329.
tolerances of the brain. Int J Radiat Oncol Biol Phys 2021;110:68–86, [195] Mendez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen
http://dx.doi.org/10.1016/j.ijrobp.2020.08.013. BJ, Nowak PC, et al. Stereotactic body radiation therapy for primary and
[176] Inoue HK, Seto K, Nozaki A, Torikai K, Suzuki Y, Saitoh J, et al. Three-fraction metastatic liver tumors: a single-institution phase I–II study. Acta Oncol
CyberKnife radiotherapy for brain metastases in critical areas: referring to 2006;45:831–7, http://dx.doi.org/10.1080/02841860600897934.
the risk evaluating radiation necrosis and the surrounding brain volumes [196] Son SH, Choi BO, Ryu MR, Kang YN, Jang JS, Bae SH, et al. Stereo-
circumscribed with a single dose equivalence of 14 Gy (V14). J Radiat Res tactic body radiotherapy for patients with unresectable primary
2013;54:727–35, http://dx.doi.org/10.1093/jrr/rrt006. hepatocellular carcinoma: dose–volumetric parameters predicting the
[177] Inoue HK, Sato H, Seto K, Torikai K, Suzuki Y, Saitoh J, et al. Five-fraction hepatic complication. Int J Radiat Oncol Biol Phys 2010;78:1073–80,
CyberKnife radiotherapy for large brain metastases in critical areas: impact http://dx.doi.org/10.1016/j.ijrobp.2009.09.009.
on the surrounding brain volumes circumscribed with a single dose equiva- [197] Lasley FD, Mannina EM, Johnson CS, Perkins SM, Althouse S, Maluccio M,
lent of 14 Gy (V14) to avoid radiation necrosis. J Radiat Res 2014;55:334–42, et al. Treatment variables related to liver toxicity in patients with hepato-
http://dx.doi.org/10.1093/jrr/rrt127. cellular carcinoma, Child–Pugh class A and B enrolled in a phase 1–2 trial
[178] Kim DWN, Medin PM, Timmerman RD. Emphasis on repair, not just avoidance of stereotactic body radiation therapy. Pract Radiat Oncol 2015;5:e443–9,
of injury, facilitates prudent stereotactic ablative radiotherapy. Semin Radiat http://dx.doi.org/10.1016/j.prro.2015.02.007.
Oncol 2017;27:378–92, http://dx.doi.org/10.1016/j.semradonc.2017.04.007. [198] Dewas S, Mirabel X, Kramar A, Jarraya H, Lacornerie T, Dewas-
[179] Tishler RB, Loeffler JS, Lunsford LD, Duma C, Alexander 3rd E, Kooy HM, et al. Vautravers C, et al. [Stereotactic body radiation therapy for liver primary
Tolerance of cranial nerves of the cavernous sinus to radiosurgery. Int J Radiat and metastases: the Lille experience]. Cancer Radiother 2012;16:58–69,
Oncol Biol Phys 1993;27:215–21. http://dx.doi.org/10.1016/j.canrad.2011.06.005.
[180] Milano MT, Grimm J, Soltys SG, Yorke E, Moiseenko V, Tome WA, [199] Lee MT, Kim JJ, Dinniwell R, Brierley J, Lockwood G, Wong R, et al. Phase I
et al. Single- and multifraction stereotactic radiosurgery dose tolerances study of individualized stereotactic body radiotherapy of liver metastases. J
of the optic pathways. Int J Radiat Oncol Biol Phys 2021;110:87–99, Clin Oncol 2009;27:1585–91, http://dx.doi.org/10.1200/JCO.2008.20.0600.
http://dx.doi.org/10.1016/j.ijrobp.2018.01.053. [200] Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS. Incidence
[181] Birer SR, Olson AC, Adamson J, Hood R, Susen M, Kim G, et al. Hippocampal of programmed cell death 1 inhibitor-related pneumonitis in patients with
dose from stereotactic radiosurgery for 4 to 10 brain metastases: risk factors, advanced cancer: a systematic review and meta-analysis. JAMA Oncol
feasibility of dose reduction via re-optimization, and patient outcomes. Med 2016;2:1607–16, http://dx.doi.org/10.1001/jamaOncol2016.2453.
Dosim 2017;42:310–6, http://dx.doi.org/10.1016/j.meddos.2017.06.007. [201] Robbins ME, Brunso-Bechtold JK, Peiffer AM, Tsien CI, Bailey JE,
[182] Katsoulakis E, Kumar K, Laufer I, Yamada Y. Stereotactic body radiotherapy Marks LB. Imaging radiation-induced normal tissue injury. Radiat Res
in the treatment of spinal metastases. Semin Radiat Oncol 2017;27:209–17, 2012;177:449–66, http://dx.doi.org/10.1667/rr2530.1.
http://dx.doi.org/10.1016/j.semradonc.2017.03.004. [202] Wang K, Mavroidis P, Royce TJ, Falchook AD, Collins SP, Sapareto S,
[183] Meyer JJ, Foster RD, Lev-Cohain N, Yokoo T, Dong Y, Schwarz RE, et al. Prostate stereotactic body radiation therapy: an overview of tox-
et al. A phase I dose-escalation trial of single-fraction stereotactic radi- icity and dose response. Int J Radiat Oncol Biol Phys 2021;110:237–48,
ation therapy for liver metastases. Ann Surg Oncol 2016;23:218–24, http://dx.doi.org/10.1016/j.ijrobp.2020.09.054.
http://dx.doi.org/10.1245/s10434-015-4579-z.
[184] Grimm J, Vargo JA, Mavroidis P, Moiseenko V, Emami B, Jain S, et al.
Initial data pooling for radiation dose–volume tolerance for carotid

17

View publication stats