Multicriteria optimization of radiation therapy: Towards empowerment and standardization of reverse planning for head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers. MATERIAL AND METHODS: We performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method. RESULTS: Median age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was -2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was -4.6Gy (P<0.001). CONCLUSION: Multicriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.

[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.

Radiotherapy for cancers of the oesophagus, cardia and stomach.

We present the updated recommendations of the French society for radiation oncology on radiotherapy of oesophageal cancer. Oesophageal cancer still remains a malignant tumour with a poor prognosis. Surgery remains the standard treatment for localized cancers, regardless of histology. For locally advanced stages, surgery remains a standard for adenocarcinomas after neoadjuvant treatment with chemotherapy or chemoradiotherapy. However, it is a therapeutic option after initial chemoradiotherapy for stage III squamous cell carcinomas, given the increased morbidity and mortality with a multimodal treatment, which results in an equivalent overall survival with or without surgery. Preoperative or exclusive chemoradiotherapy should be delivered according to validated regimens with an effective total dose (50Gy), if surgery is not planned or if the tumour is deemed resectable before chemoradiotherapy. Intensity-modulated radiotherapy significantly reduces irradiation of the lungs and heart and may reduce the morbidity of this treatment, especially in combination with surgery. In case of exclusive chemoradiotherapy, dose escalation beyond 50Gy is not currently recommended. Some technical considerations still remain questionable, such as the place of prophylactic lymph node irradiation, adaptive radiotherapy, evaluation of response during and after chemoradiotherapy and the value of proton therapy.

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] / Radiothérapie du carcinome épidermoïde du larynx de stade précoce, étage glottique : intérêt de l'hypofractionnement ?

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

[Stereotactic body radiotherapy for locally advanced pancreatic cancer: A systemic review]. / Radiothérapie stéréotaxique dans le cancer du pancréas localement avancé : revue de la littérature.

Stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) is an emerging treatment option. Most studies showed local control of approximately 75% with no evidence of improved overall survival. Gastrointestinal toxicities could be significant, ranging up to 22% for acute toxicities≥grade 3+ and 44% for late toxicities≥grade 3+. Currently, no standardized guidelines for treatment and management scheme. We conducted a systemic review of published prospective and retrospective trials to evaluate the efficacy, safety, technical data, and discuss future directions.

[Stereotaxic radiotherapy of primary extracranial tumors]. / Radiothérapie stéréotaxique des tumeurs primitives extracrâniennes.

Stereotactic radiotherapy is a fundamental change from the conventional fractionated radiotherapy and represents a new therapeutic indication. Stereotactic radiotherapy is now a standard of care for inoperable patients or patients who refuse surgery. The results are encouraging with local control and survival rates very high in selected populations. The rate of late toxicity remains acceptable. Good tolerability makes it appropriate even for elderly and frail patients. In these fragile patients or in certain specific clinical situations, different surgical, radiotherapy or interventional radiology attitudes can be discussed on a case-by-case basis. These situations are considered in this article for the pulmonary, hepatic and prostatic localizations.

[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.

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.

Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer.

BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.

Use of an in-house Monte Carlo platform to assess the clinical impact of algorithm-related dose differences on DVH constraints.

PURPOSE: The aim of the present work is to evaluate a semi-automatic prescription and validation system of treatment plans for complex delivery techniques, integrated in a Monte Carlo platform, and to investigate the clinical impact of dose differences due to the calculation algorithms, by assessing the changes in DVH constraints. METHODS: A new prescription module was implemented into the Moderato system, an in-house Monte Carlo platform, with corresponding dose constraints generated depending on the anatomical region and fractionation scheme considered. The platform was tested on 83 cases treated with Cyberknife and Tomotherapy machines, to assess whether dose variations between the re-calculated dose and the Treatment Planning System might impact the dose constraints on the sensitive structures. RESULTS: Dose differences were small (within 3%) between calculation algorithms in most of the thoracic, pelvic and abdominal cases, both for the Cyberknife and Tomotherapy machines. On the other hand, spinal and head and neck treatments presented a few significant dose deviations for constraints on small volumes, such as the optic pathways and the spinal cord. These differences range from -11% to +6%, inducing constraint violations of up to 8% over the dose limit. CONCLUSIONS: The Moderato platform offers an interesting tool for plan quality validation, with a prescription module highlighting crucial features in the structures list, and a Monte Carlo dose re-calculation for complex modern techniques. Due to the high number of warnings appearing in some situations, display optimization is required in practice.

[Spinal stereotactic body radiotherapy: French assessment in 2016]. / État des lieux de la radiothérapie en conditions stéréotaxiques vertébrale en France en 2016.

PURPOSE: Stereotactic body radiotherapy to vertebral column remains uncommon practice and only relevant in selected group of patients. The main objective of the study was to describe the current state of medical practices of stereotactic body radiotherapy to vertebral column in France in 2016 and to assess the diversity of practices to identify areas for improvement and establish a common database set for this technique. MATERIALS AND METHODS: A questionnaire was written with contribution of a medical physicist, a radiation oncologist, an information technologist and a radiotherapy resident. The questionnaire was distributed online to a radiation oncologists and a medical physicists partner of selected French radiotherapy specialized centres that provide stereotactic body radiotherapy to vertebral metastasis from April to June 2016. The questionnaire surveyed the following topics: patients' selection, simulation, targeted volume and organs at risk delineation, prescription, dosimetric implementation and image guidance. RESULTS: A total of 31 centres were surveyed. Seventy eight per cent of centres (n=21) completed the questionnaire. The "ideal" patient for spine stereotactic radiotherapy according to these institutions has a good performance status, a long life expectancy, controlled primary tumour with oligometastatic spread. The most prescribed protocol was 30Gy in three fractions. For clinical target volume delineation, about two thirds of centres used the International Spine Radiosurgery Consortium (ISRC) recommendations (Noël G et al.,2006). CONCLUSION: This study identified some consistency of practices in some aspects despite the lack of consensus guidelines. Nevertheless, further studies are needed to establish consensus of planning and treatment.

French updated recommendations in Stage I to III melanoma treatment and management.

As knowledge continues to develop, regular updates are necessary concerning recommendations for practice. The recommendations for the management of melanoma stages I to III were drawn up in 2005. At the request of the Société Française de Dermatologie, they have now been updated using the methodology for recommendations proposed by the Haute Autorité de Santé in France. In practice, the principal recommendations are as follows: for staging, it is recommended that the 7th edition of AJCC be used. The maximum excision margins have been reduced to 2 cm. Regarding adjuvant therapy, the place of interferon has been reduced and no validated emerging medication has yet been identified. Radiotherapy may be considered for patients in Stage III at high risk of relapse. The sentinel lymph node technique remains an option. Initial examination includes routine ultrasound as of Stage II, with other examinations being optional in stages IIC and III. A shorter strict follow-up period (3 years) is recommended for patients, but with greater emphasis on imaging.

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.