[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.

[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.

[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.

[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.

[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.

[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.

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.

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).

[Intraprostatic fiducials in stereotactic radiotherapy for prostate cancer]. / Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate.

PURPOSE: Image-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility. PATIENTS AND METHODS: Over a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25Gy and 11 patients five fractions of 6.25Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients. RESULTS: The tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4-113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment. CONCLUSIONS: Intraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.

Clinical implementation of a Monte Carlo based treatment plan QA platform for validation of Cyberknife and Tomotherapy treatments.

PURPOSE: The main focus of the current paper is the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, without adding additional tasks to the dosimetry department. METHODS: The Monte Carlo platform consists of C++ classes for the actual functionality and a web based GUI that allows accessing the system using a web browser. Calculations are based on BEAMnrc/DOSXYZnrc and/or GATE and are performed automatically after exporting the dicom data from the treatment planning system. For Cyberknife treatments of moving targets, the log files saved during the treatment (position of robot, internal fiducials and external markers) can be used in combination with the 4D planning CT to reconstruct the actually delivered dose. The Monte Carlo platform is also used for calculation on MRI images, using pseudo-CT conversion. RESULTS: For Tomotherapy treatments we obtain an excellent agreement (within 2%) for almost all cases. However, we have been able to detect a problem regarding the CT Hounsfield units definition of the Toshiba Large Bore CT when using a large reconstruction diameter. For Cyberknife treatments we obtain an excellent agreement with the Monte Carlo algorithm of the treatment planning system. For some extreme cases, when treating small lung lesions in low density lung tissue, small differences are obtained due to the different cut-off energy of the secondary electrons. CONCLUSIONS: A Monte Carlo based treatment plan validation tool has successfully been implemented in clinical routine and is used to systematically validate all Cyberknife and Tomotherapy plans.

[Stereotactic body radiation therapy for spinal metastases]. / Radiothérapie stéréotaxique des métastases osseuses vertébrales.

After the liver and lungs, bones are the third most common sites of cancer metastasis. Palliative radiotherapy for secondary bone tumours helps relieve pain, improve the quality of life and reduce the risk of fractures. Stereotactic body radiotherapy can deliver high radiation doses with very tight margins, which has significant advantages when treating tumours close to the spinal cord. Strict quality control is essential as dose gradient at the edge of the spinal cord is important. Optimal schedule is not defined. A range of dose-fractionation schedules have been used. Pain relief and local control are seen in over 80%. Toxicity rates are low, although vertebral fracture may occur. Ongoing prospective studies will help clarify its role in the management of oligometastatic patients.

Low-dose brachytherapy for early stage penile cancer: a 20-year single-institution study (73 patients).

PURPOSE/OBJECTIVES: The aim of this study is to analyze the results of exclusive interstitial brachytherapy (IBT) as a conservative approach in the treatment of penile cancer confined to the glans or the shaft with long-term follow-up in a single institution. MATERIALS/METHODS: Between July 1992 and November 2013, 73 consecutive patients with non-metastatic invasive penile cancer were treated by Low dose rate (LDR) IBT in our institution. The localization of the primary lesion was glands in 67 patients (91.8 %) and shaft in 6 patients (8.2 %). All 73 patients presented with squamous cell carcinoma with grades of differentiation as follows: 34 patients with grade 1 (44.7 %), 9 patients with grade 2 (11.8 %), 9 patients with grade 3 (11.8 %) and 21 patients unknown (28.8 %). Six patients (7.8 %) presented with in situ carcinoma, 55 patients (75,3 %) presented with T1, 11 patients (15 %) presented with T2, and one patient (1.3 %) presented with Tx. Inguinal nodal dissection was performed in 29 patients (38.2 %); 13 patients (17.8 %) presented with histologically confirmed positive ganglion. After circumcision, IBT was performed using a hypodermic needle. The median dose delivered was 60 Gy (range, 40 to 70 Gy). The median activity of the iridium-192 wire was 1.12 mCi/cm, and the median reference isodose rate was 0.4 Gy/h (range, 0.2-1.2). Patients with histological inguinal metastases received external beam radiotherapy to the selected inguinal affected area with a median dose of 45 Gy (30-55 Gy). RESULTS: The median follow-up time was 51.8 months (range 34.4 to 68.7). The 5-year overall survival was 82.0 %, with eight deaths from cancer and five non-cancer-related deaths. Disease-specific survival was 91.4 %, relapse-free survival was 64.4 %, and local relapse-free survival as 74 %. Total or partial penile preservation was 87.9 % at 5-years. Complications rates at 5 years were 6.6 % urethral stenosis (five patients), two patients (2.6 %) with pain related to sexual intercourse and four patients (5.3 %) with dysuria grade 2. Five patients (6.8 %) required penile amputation for necrosis. CONCLUSIONS: IBT provides good local control with organ preservation, excellent tolerance and low complication rates in early-stage penile cancers.

[Repeated radiation dose effect and DNA repair: Importance of the individual factor and the time interval between the doses]. / Effets de répétitions de doses d'irradiation et réparation de l'ADN : importance du facteur individuel et de l'intervalle de temps entre les doses.

The dose fractionation effect is a recurrent question of radiation biology research that remains unsolved since no model predicts the clinical effect only with the cumulated dose and the radiobiology of irradiated tissues. Such an important question is differentially answered in radioprotection, radiotherapy, radiology or epidemiology. A better understanding of the molecular response to radiation makes possible today a novel approach to identify the parameters that condition the fractionation effect. Particularly, the time between doses appears to be a key factor since it will permit, or not, the repair of certain radiation-induced DNA damages whose repair rates are of the order of seconds, minutes or hours: the fractionation effect will therefore vary according to the functionality of the different repair pathways, whatever for tumor or normal tissues.

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.

[Positron emission tomography and stereotactic body radiation therapy for lung cancer: From treatment planning to response evaluation]. / TEP et radiothérapie stéréotaxique pulmonaire : rôles dans la préparation du traitement et le suivi de la maladie.

Stereotactic body radiation therapy is the standard treatment for inoperable patients with early-stage lung cancer. Local control rates range from 80 to 90 % 2 years after treatment. The role of positron emission tomography in patient selection is well known, but its use for target definition or therapeutic response evaluation is less clear. We reviewed the literature in order to assess the current state of knowledge in this area.

[Implementing new technology in radiation oncology: The French agency for nuclear safety (ASN) report]. / Conditions de mise en œuvre des « nouvelles techniques et pratiques ¼ en radiothérapie. Synthèse du rapport du groupe de travail issu du groupe permanent d'experts en radioprotection médicale de l'Autorité de sûreté nucléaire.

In August 2013, the French nuclear safety agency (ASN) requested the permanent group of experts in radiation protection in medicine (GPMED) to propose recommendations on the implementation of new technology and techniques in radiation oncology. These recommendations were finalized in February 2015 by the GPMED. In April 2015, the ASN sent a letter to the French ministry of health (DGS/DGOS), and its national health agencies (ANSM, INCa, HAS). In these letters, ASN proposed that, from the 12 recommendations made by the GPMED, an action plan should be established, whose control could be assigned to the French national cancer institute (INCa), as a pilot of the national committee for radiotherapy and that this proposal has to be considered at the next meeting of the national committee of radiotherapy.