A biophysical model of cell evolution after cytotoxic treatments: Damage, repair and cell response.

We present a theoretical agent-based model of cell evolution under the action of cytotoxic treatments, such as radiotherapy or chemotherapy. The major features of cell cycle and proliferation, cell damage and repair, and chemical diffusion are included. Cell evolution is based on a discrete Markov chain, with cells stepping along a sequence of discrete internal states from 'normal' to 'inactive'. Probabilistic laws are introduced for each type of event a cell can undergo during its life: duplication, arrest, senescence, damage, reparation, or death. We adjust the model parameters on a series of cell irradiation experiments, carried out in a clinical LINAC, in which the damage and repair kinetics of single- and double-strand breaks are followed. Two showcase applications of the model are then presented. In the first one, we reconstruct the cell survival curves from a number of published low- and high-dose irradiation experiments. We reobtain a very good description of the data without assuming the well-known linear-quadratic model, but instead including a variable DSB repair probability. The repair capability of the model spontaneously saturates to an exponential decay at increasingly high doses. As a second test, we attempt to simulate the two extreme possibilities of the so-called 'bystander' effect in radiotherapy: the 'local' effect versus a 'global' effect, respectively activated by the short-range or long-range diffusion of some factor, presumably secreted by the irradiated cells. Even with an oversimplified simulation, we could demonstrate a sizeable difference in the proliferation rate of non-irradiated cells, the proliferation acceleration being much larger for the global than the local effect, for relatively small fractions of irradiated cells in the colony.

[Five-fraction radiotherapy for breast cancer]. / Radiothérapie du cancer du sein en cinq fractions.

Extreme hypofractionation in adjuvant breast radiotherapy currently generates a lot of interest. We propose here a synthesis of hypofractionation trials and present the DESTHE COL and DESTHE GR projects, encouraged by the French National Cancer Institute (INCa), which experiment care pathways in order to deploy effective strategies to de-escalate the therapeutics and to reduce sequelae after cancer treatment.

[Braindrive: Who can drive among patients undergoing brain radiation therapy?] / Braindrive : qui peut conduire parmi les patients pris en charge pour une radiothérapie cérébrale ?

PURPOSE: Brain tumors can be associated with various neurological symptoms impairing driving ability. We sought to assess patients' knowledge on the French driving legislation. MATERIALS AND METHODS: This is a prospective descriptive epidemiological study carried out at the Oscar Lambret center in Lille, among driving license holders treated by radiotherapy for one or more primary cerebral tumor or brain metastasis. The survey was carried out by hetero-administered questioners. The primary endpoint was the frequency of patients informed on the French driving legislation at the initial radiotherapy consultation, given with a 95% confidence interval by the Clopper-Pearson exact binomial method. RESULTS: From the 1st February to March 31st, 2022, 33 patients with brain tumors were evaluated. Three of them were excluded because they did not have a driving license. Among the 30 patients analyzed, 12 patients (40% IC95 [22.7; 59.4]) had been informed of the existence of a possible contraindication to drive before the radiotherapy consultation. Among the 30 patients, 21 (70%) had a contraindication to drive. Of the eight patients (26.6%) who drove, four (13.3%) should not. CONCLUSION: Most patients have a contraindication to drive, but only 40% of the patients questioned stated that they had been informed of the existence of a possible contraindication before the radiotherapy consultation.

[Stereotactic body radiation therapy for primary kidney cancer]. / Radiothérapie stéréotaxique des carcinomes rénaux primitifs.

The incidence of primary renal cancer is increasing, particularly in elderly patients who may have comorbidities and/or a surgical contraindications. Stereotactic body radiotherapy has primarily been evaluated retrospectively to date. The most commonly used dose schedules are 40Gy in five fractions, 42Gy in three fractions, and 26Gy in one fraction. The results in terms of local control and toxicity are very encouraging. The advantages of stereotactic body radiotherapy compared to thermal ablative treatments are its non-invasive nature, absence of general anesthesia, ability to treat larger lesions, and those close to the renal hilum. Prospective evaluations are still necessary.

[Androgen deprivation therapy for prostate cancer and osteoporotic risk]. / Suppression androgénique dans le cancer de la prostate et risque ostéoporotique.

Androgen deprivation therapy represents an important part of the management of prostate cancer. However, epidemiological data have shown that it is a well-established cause of osteoporosis and increased risk of fracture. So far no consensus guidelines have been published regarding the screening and treatment of osteoporosis in men with prostate cancer. Here we report the design of a new questionnaire, derived from the FRAX(®) ("Fracture Risk Assessment Tool") algorithm, to evaluate the risk of fracture in those patients. In accordance with recent reviews and on the basis of their experience, our French board of experts recommends systematic screening for osteoporosis with dual energy x- ray absorptiometry scans, practice of exercise and calcium and vitamin D supplementation, and selective treatment with bisphosphonates in men at greatest osteoporotic risk.

[The role of radiotherapy to the primary tumor and metastases in patients with oligometastatic prostate cancer]. / Place de la radiothérapie de la tumeur primitive et/ou des métastases du cancer de la prostate oligométastatique.

Oligometastatic prostate cancer is among the most studied oligometastatic cancers in the literature. However few prospective studies have assessed stereotactic body radiotherapy (SBRT) for prostate cancer oligometastases. Two randomised phase II trials show a progression-free survival benefit compared with observation. Prospective registry data show very good local control and low toxicity too. Inclusion in ongoing trials should be strongly encouraged to define the role of SBRT in addition to systemic therapy. Radiation therapy to the primary tumour has been studied in randomised trials and provides an overall survival benefit in patients with low metastatic burden. The benefit is inversely correlated with the number of bone lesions using conventional imaging, up to three metastases. Radiotherapy to the primary tumour is recommended by the learned societies for patients with low metastatic burden. Its role in combination with second generation anti androgen therapy needs to be clarified.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.

[Place and modalities of postoperative radiotherapy in the management of cerebral metastases]. / Place et modalités de l'irradiation postopératoire dans la prise en charge des métastases cérébrales.

Metastases are the most common brain tumors. After surgery, stereotactic radiotherapy (SRT) of the resection cavity is the standard of care. Data from two randomized trials indicate that SRT to the surgical bed is an effective treatment in reducing local failure as compared with observation, while reducing the risk of cognitive deterioration and maintaining quality of life as compared with whole brain radiation therapy. Local control appears higher after hypofractionated SRT compared to single-fraction SRT. Several questions such as target volumes, the optimal regimen in particular for large tumor bed, strategies to reduce the risk of lepto-meningeal recurrence, and the treatment sequence still need to be answered.

[Left-sided breast cancer locoregional radiation therapy with rotational intensity-modulated irradiation and deep inspiration breath hold: Dosimetric comparison]. / Irradiation mammaire locorégionale gauche avec modulation d'intensité rotationnelle et inspiration profonde : comparaison dosimétrique.

PURPOSE: Adjuvant left-sided breast cancer locoregional radiotherapy can be accounted for long-term cardiac toxicity. The deep inspiration breath hold techniques can reduce cardiac doses. Only a few studies have investigated rotational intensity-modulated radiotherapy with deep inspiration breath hold. MATERIAL AND METHODS: We conducted a dosimetric study comparing rotational intensity-modulated radiotherapy in free breathing with deep inspiration breath hold for irradiation of left breast cancer and locoregional lymph nodes. Doses to organs at risk were compared, as well as doses to coronary arteries, left anterior descending coronary artery region, and aortic valve. RESULTS: The data from nine patients were included in the study. Treatment plans were comparable for target volumes. The deep inspiration breath hold delivery technique, compared with free breathing, reduced radiation dose to the heart (mean dose 4.8Gy vs. 6.6Gy, p=0.008; dose in 2% of the volume 16.8Gy vs. 23.3Gy, p=0.008; volume receiving 25Gy 0.8% vs. 2,2%, p=0.008; volume receiving 30Gy 0.4% vs. 1.2%, p=0.009), as well as to the right coronary artery (mean dose 6Gy vs. 8.9Gy, p=0.028), to the left anterior descending artery (mean dose 9.6Gy vs. 14.6Gy, p=0.021), to the left anterior descending coronary artery region (dose in 2% of the volume 17.4Gy vs. 24.6Gy, p=0.021), and to the aortic valve (mean dose 4.8Gy vs. 7Gy, p=0.028). Other doses to organs at risk were similar. CONCLUSION: Rotational intensity-modulated radiotherapy with deep inspiration breath hold is associated with better sparing of the heart, on the right and left anterior descending coronary arteries, and on the aortic valve, compared with free breathing techniques, for adjuvant left breast cancer locoregional irradiation.

[Stereotactic body radiotherapy. How to better protect normal tissues?] / Radiothérapie stéréotaxique extra crânienne. Comment mieux protéger les tissus sains ?

The use of stereotactic body radiotherapy (SBRT) has increased rapidly over the past decade. Optimal preservation of normal tissues is a major issue because of their high sensitivity to high doses per session. Extreme hypofractionation can convert random errors into systematic errors. Optimal preservation of organs at risk requires first of all a rigorous implementation of this technique according to published guidelines. The robustness of the imaging modalities used for planning, and training medical and paramedical staff are an integral part of these guidelines too. The choice of SBRT indications, dose fractionation, dose heterogeneity, ballistics, are also means of optimizing the protection of normal tissues. Non-coplanarity and tracking of moving targets allow dosimetric improvement in some clinical settings. Automatic planning could also improve normal tissue protection. Adaptive SBRT, with new image guided radiotherapy modalities such as MRI, could further reduce the risk of toxicity.

[The radiation oncologist, one of the actors in the patient's path after cancer. Follow up after prostate cancer]. / L'oncologue radiothérapeute, un des acteurs du parcours du patient après cancer. Surveillance après cancer de la prostate.

Prostate cancer is the most common cancer of men over 50 years old. Localized prostatic cancer treatment may be responsible of a decline of patient's quality of life. The main actors of treatment are now focused on minimizing functional consequences of treatments. The radiation oncologist has a central role in patient monitoring. The follow-up is codified by official recommendations of learned societies to enhance the post-cancer period. The main objective of this article is to review the recommendations for clinical and biological follow-up. An inventory of the functional consequences of the various treatments will be detailed, and particularly those caused by androgen deprivation therapy, with a review of precautions before implementation, adverse effects and their management, as well as monitoring recommendations. The analysis of quality of life after curative treatment and suggestions to improve monitoring will also be discussed.

Adjuvant management of operated uterine sarcomas: A single institution experience.

PURPOSE: The purpose of this study was to describe the adjuvant management of high grade uterine sarcoma and highlight prognostic factors for overall survival and progression-free survival. MATERIAL AND METHODS: Between 01/2000 and 01/2015, 91 patients undergoing surgery were presented at the multidisciplinary team meeting of our institution. The type of surgery, the anatomopathological features, adjuvant treatments, dates and sites of recurrence were collected. The prognostic value of the various factors was evaluated with the multivariate Cox model. RESULTS: A total of 50 women with uterine sarcoma were identified and lesions included 43 leiomyosarcomas (86%) and seven high grade sarcomas (14%). Eighteen patients received adjuvant pelvic radiotherapy (36%) and six adjuvant systemic therapy (12%). The median follow-up time was 63 months. Thirty-nine patients (78%) had a recurrence: 22 had only metastatic recurrence (58%), two had isolated pelvic recurrence (5%) and 15 had pelvic and metastatic recurrence (38%). Adjuvant radiotherapy was associated with survival without pelvic recurrence in univariate analysis (P=0.005, hazard ratio [HR]=0.15); age greater than 55 years and adjuvant radiotherapy were associated with metastatic free survival in multivariate analysis (P=0.015, HR=2.37, and P=0.013, HR=0.41 respectively) CONCLUSION: According to the results of our series, there is a benefit of radiotherapy after surgery in terms of local control of uterine sarcoma. It is necessary to identify the subgroup of patients who will benefit from an adjuvant radiotherapy in order to provide them with more optimal care.

Harmonization of practices between radiotherapy centres in the Nord and Pas-de-Calais regions (France): A three-year evaluation.

PURPOSE: The delineation of volumes of interest can be a source of significant interobserver variability. The purpose of this study was to improve the homogeneity of delineation between oncologist-radiotherapists in the territorial departments of Nord and Pas-de-Calais (France) through discussions of clinical cases and the adoption of common published reference documents. MATERIALS AND METHODS: All eleven radiotherapy centres in the Nord and Pas-de-Calais departments of France participated. The localizations assessed to date included prostate, head and neck, breast and brain cancers. For each localization, the junior or senior physician(s) in charge of pathology delineated the volumes of interest according to their usual practices. Validated indices, including the Dice similarity coefficient, were used to quantify the delineation differences. The anonymized results were presented at two to three annual meetings. A second delineation of the clinical cases was then carried out to quantify homogenization. An evaluation of dosimetry practices was also conducted for prostate cancer. Wilcoxon assay matched data were used. RESULTS: Our work showed either satisfactory delineation concordance after the initial assessment or improved delineation concordance. For prostate cancer, the Dice similarity coefficient values were greater than 0.6 initially in two of the three clinical cases. For head and neck cancers, a statistically significant improvement was observed for only one of the clinical target volumes. More than half of the Dice similarity coefficient values were greater than 0.6 in the first comparison. The study of clinical cases of breast cancer allowed a homogenization of the delineation of five of the six lymph node clinical target volumes. The dosimetry study of prostate cancer allowed for a homogenization of practices. CONCLUSION: This work makes it possible to harmonize the delineation practices around validated standards. An extension to the entire Hauts-de-France region is planned.

[The Oxygen effect: an old new target?]. / L'effet Oxygène, une cible ancienne toujours d'actualité ?

The Oxygen effect plays a key role in cellular response to ionizing radiations. From many years, tumour hypoxia is a limiting treatment factor. Multiple ways to interact with free radicals have been developed. The increase in tissue oxygenation has a limited impact. Radiosensitizing agents as nimorazole or gadolinium have a clinical benefit. Tirapazamine or AQ4N, bioreductive agents, are not routinely used. New agents through the HIF-1 and the endothelial cell pathways are currently being developed. Studies on the expression of endogenous markers of hypoxia could be useful tools to predict tumour response to the treatment.

[Dosimetric evaluation of an automatic segmentation tool of pelvic structures from MRI images for prostate cancer radiotherapy]. / Evaluation dosimétrique d'un outil de délinéation automatique des organes pelviens à partir d'images IRM pour la radiothérapie du cancer prostatique.

PURPOSE: An automatic segmentation tool of pelvic structures from MRI images for prostate cancer radiotherapy was developed and dosimetric evaluation of differences of delineation (automatic versus human) is presented here. MATERIALS AND METHODS: CTV, rectum and bladder were defined automatically and by a physician in 20 patients. Treatment plans based on "automatic" volumes were transferred on "manual" volumes and reciprocally. Dosimetric characteristics of PTV (V(95), minimal, maximal and mean doses), rectum (V(50), V(70), maximal and mean doses) and bladder (V(70), maximal and mean doses) were compared. RESULTS: Automatic delineation of CTV did not significantly influence dosimetric characteristics of "manual" PTV. Rectal V(50) and V(70) were not significantly different; mean rectal dose is slightly superior (43.2 versus 44.4Gy, p=0.02, Student test). Bladder V(70) was significantly superior too (19.3 versus 21.6, p=0.004). Organ-at-risk (OAR) automatic delineation had little influence on their dosimetric characteristics; rectal V(70) was slightly underestimated (20 versus 18.5Gy, p=0.001). CONCLUSION: CTV and OAR automatic delineation had little influence on dosimetric characteristics. Software developments are ongoing to enable routine use and interobserver evaluation is needed.

[Increasing quality and safety of external radiation treatments: actions of the French Society of Radiation Oncology (SFRO)]. / Qualité en radiothérapie: les actions de la société française de radiothérapie oncologique (SFRO).

Accidents which recently occured in external radiotherapy led the French Ministry of Health to implement a programme aimed at increasing quality and safety of treatments. We report the actions of the French society of radiation oncology in the field of this programme called Feuille de route.

[Experience feed back committee in radiotherapy (CREx): a compulsory tool for security management evaluation at two years]. / La cellule de retour d'expérience (CREx) en radiothérapie: un outil indispensable au management de la sécurité. Une évaluation après deux ans d'activité au centre Oscar-Lambret.

After working on treatment organisation in radiotherapy (bonne pratiques organisationnelles en radiothérapie - action pilote MEAH 2003), the development of a security policy has become crucial. With the help of Air France Consulting and the MEAH, three cancer centers in Angers, Lille and Villejuif worked together on the implantation of experience feed back committees (CREx) dedicated to the registration, analysis and correction of precursor events. After two years, we report the centre Oscar-Lambret experience in Lille and try to get the recommendations for generalisation of the process. This seems now to be compulsory for security management in oncology.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Hypofractionated Stereotactic Radiotherapy for Patients with Intracranial Meningiomas: impact of radiotherapy regimen on local control.

We evaluated efficacy and tolerance of hypofractionated stereotactic radiation treatment (hFSRT) in the management of intracranial meningiomas. Between December 2008 and June 2016, 126 patients with 136 intracranial meningiomas were treated with robotic hFSRT. hFSRT was performed as primary irradiation and as a salvage option for the local recurrence after prior radiotherapy. The median prescription dose was 25 Gy (12-40) with a median number of fractions of 5 (3-10). After a median follow-up of 20.3 months (range 1-77 months), the 24-months local control (LC) rate was 81% in the primary hFSRT group and 39% after hFSRT in the re-irradiation group (p=0.002). The clinical control rate of symptoms in the overall population was 95% (95% CI: 89-98%). Progression-free survival (PFS) in the overall population at 24 months was 70% (95% CI: 60%-79%). In the primary hFSRT group, PFS was significantly lower with the most hypofractionated schedules of 21-23 Gy in 3 fractions vs. 25-40 Gy in 5-10 fractions: 62% vs. 92% (p = 0.0006). The incidence of radionecrosis at 24 months was significantly lower in the primary hFSRT group, at 2% vs. 20% in the re-irradiation hFSRT group (p = 0.002).