Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Histosurgical mapping of endoscopic endonasal surgery of sinonasal tumours to improve radiotherapy guidance.

PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

Radiotherapy of salivary gland tumours.

Primary tumours of the salivary glands account for about 5 to 10% of tumours of the head and neck. These tumours represent a multitude of situations and histologies, where surgery is the mainstay of treatment and radiotherapy is frequently needed for malignant tumours (in case of stage T3-T4, nodal involvement, extraparotid invasion, positive or close resection margins, histological high-grade tumour, lymphovascular or perineural invasion, bone involvement postoperatively, or unresectable tumours). The diagnosis relies on anatomic and functional MRI and ultrasound-guided fine-needle aspiration for the diagnostic of benign or malignant tumors. In addition to patient characteristics, the determination of primary and nodal target volumes depends on tumor extensions and stage, histology and grade. Therefore, radiotherapy of salivary gland tumors requires a certain degree of personalization, which has been codified in the recommendations of the French multidisciplinary network of expertise for rare ENT cancers (Refcor) and may justify a specialised multidisciplinary discussion. Although radiotherapy is usually recommended for malignant tumours only, recurrent pleomorphic adenomas may sometimes require radiotherapy based on multidisciplinary discussion. An update of indications and recommendations for radiotherapy for salivary gland tumours in terms of techniques, doses, target volumes and dose constraints to organs at risk of the French society for radiotherapy and oncology (SFRO) was reported in this article.

A new model outperforming RPA and DS-GPA scores for individualized survival prediction of patients following whole brain irradiation for brain metastasis.

PURPOSE: Survival after whole brain radiation therapy (WBRT) in patients with multiple brain metastases (BM) is currently predicted by group-based scoring systems with limited usability for decision. We aimed to develop a more relevant individualized predictive model than Radiation Therapy Oncology Group - Recursive Partitioning Analysis (RTOG-RPA) and Diagnosis - Specific Graded Prognostic Assessment (DS-GPA) for patients with limited life-expectancy. METHODS: Based on a Discovery cohort of patients undergoing WBRT, multivariable piecewise Cox regression models with time cut-offs at 1 and 3 months were developed to predict overall survival (OS). A final parsimonious model was defined, and an external validation cohort was used to assess its discrimination and calibration at one, six, and 12 months. RESULTS: In the 173-patient Discovery cohort, the majority of patients had primary lung cancer (56%), presence of extracranial disease (ECD) (75%), Eastern Cooperative Oncolgy Group - Performance Status (ECOG-PS) score 1 (41%) and no intracranial hypertension (ICH) (74%). Most patients were classified as the RPA class II (48%). The final piecewise Cox model was based on primary site, age, ECD, ECOG-PS and ICH. An external validation of the model was carried out using a cohort of 79 patients. Individualized survival estimates obtained with this model outperformed the RPA and DS-GPA scores for overall survival prediction at 1-month, 6-months and 12- months in both Discovery and Validation cohorts. A R/Shiny web application was developed to obtain individualized predictions for new patients, providing an easy-to-use tool for clinicians and researchers. CONCLUSION: Our model provides individualized estimates of survival for poor prognosis patients undergoing WBRT, outperforming actual scoring systems.

Psychological and physical impact in women treated for breast cancer: Need for multidisciplinary surveillance and care provision.

PURPOSE: Cancer survivors often experience adverse physical and psychosocial effects. Fear of recurrence is a difficulty very commonly reported in post-cancer life. The primary objective of this study was to describe post-cancer supportive care needs in patients treated for breast cancer. PATIENTS AND METHODS: In this monocentric observational study, cancer survivors aged≥18years, diagnosed with breast cancer and treated in 2017 (cohort A) and in 2015 (cohort B) were administered a post-cancer needs questionnaire, and the Fear of Cancer Recurrence Inventory (severity subscale). RESULTS: The study included 139 patients. Pain (51.9%), fatigue (51.9%), weight gain during treatment (35.1%), psychological difficulties (20.5%), and difficulties in marriage and sexual life (13.1%) were the complaints in the post-cancer period. There were no differences between the two cohorts. The severity subscale of the Fear of Cancer Recurrence Inventory showed 35.8% patients with a score>13. The fear of recurrence was a source of social difficulties, psychological disorders, and difficulties in marriage and sexual life. CONCLUSIONS: Not only FCR, but also issues such as fatigue, pain, psychological difficulties, and difficulties in marriage and sexual life all call for a psycho-oncological follow-up. Clinical and radio-senological surveillance is essential, but it absolutely must be accompanied by a multidisciplinary follow-up, with central importance to psychological care.

[Clinical trials that have changed our practices 2010-2020]. / Les essais cliniques en radiothérapie qui ont changé les pratiques 2010­2020.

PURPOSE: This article aims to describe and list the clinical trials that have changed our practices in breast cancer, urological cancer, gynecological cancer, cancer of the upper aerodigestive tract and digestive cancer in the last ten years. MATERIAL AND METHODS: We listed and selected the studies published between 2010 and 2020. The articles were identified on the basis of a Medline search with PubMed and knowledge of the authors. RESULTS: Five to six trials were selected in breast cancer, urological cancers, gynecological cancers, cancers of the upper aerodigestive tract and digestive cancers asking the different fundamental questions in radiotherapy. CONCLUSION: Depending on the pathologies, the questions raised over the past 10 years remain fundamental questions such as the place of neoadjuvant treatment, the place of hypofractionation or the type of chemotherapy concomitant with radiotherapy.

Efficacy and safety of panitumumab alone or in association with radiotherapy in unresectable cutaneous squamous cell carcinoma.

BACKGROUND: The prognosis of unresectable cutaneous squamous cell carcinomas is very poor. OBJECTIVE: To evaluate the efficacy and safety of panitumumab alone or in association with radiotherapy in the treatment of unresectable cutaneous squamous cell carcinoma. METHODS: This was a monocentre retrospective study of all consecutive patients having received at least two courses of panitumumab, alone or in association with radiotherapy, between 2016 and 2019. The primary endpoint was the rate of best overall response, evaluated according to the RECIST 1.1 criteria. The secondary endpoints were the response and disease control rates at 6 weeks and 6 months, progression-free survival, overall survival and safety. RESULTS: A total of 25 patients were included; their median age was 86 years, and 17 (86%) had a WHO performance status over 2. The best overall response rate was 52%, including four complete responses (16%) and nine partial responses (36%). All patients with complete response and five out of nine patients with partial response had received concurrent radiotherapy, in most cases in moderate to low doses (<40 Gray, 67%). The response rates at 6 weeks and 6 months were 12% and 28%, respectively. The control rates at 6 weeks and 6 months were 84% and 32%, respectively. Median progression-free survival was 6.9 months, and median overall survival was 10.5 months. Grade 3 side-effects, mostly dermatological, occurred in 16 patients (64%). CONCLUSION: These results suggest that panitumumab remains pertinent in the treatment of unresectable cutaneous squamous cell carcinoma, in particular in association with radiotherapy, despite recent advances with anti-PD-1 antibodies. It presents several advantages: it can be used in very elderly or feeble patients, it does not provoke anaphylactic or other irreversible or life-threatening side-effects, and our study observed some long-term responses. Further prospective investigation of anti-EGFR antibodies, in association with anti-PD-1 antibodies and/or chemotherapy, should be conducted.

Cancer of the oesophagus and lymph nodes management in the neoadjuvant or definitive radiochemotherapy setting.

Despite representing a 1% of diagnosed cancer cases in the USA and up to 5% in eastern Asia and Africa, oesophageal cancer still holds numerous questions concerning the best therapeutic management. For squamous cell carcinoma, while radiochemotherapy has proven itself to be the gold standard as part of the trimodality or alone as a definitive treatment, radiotherapy modalities are still debated especially regarding lymph node irradiation. Involved nodes irradiation was developed with the aim of maintaining clinical outcomes and enhancing quality of life but lacks grade 1 evidence. In this article, we aim to summarize the state of art regarding lymph node irradiation, discuss the impact of target definition, delivery techniques, concomitant treatment and the perspectives. Being highly connected to the lymph vessels, lymphatic metastases are frequent and can locate from the neck to the coeliac area with each node having a different prognostic significance. Regarding the comparison between elective nodal irradiation and involved nodes irradiation, evidence-based medicine mostly relies on retrospective studies. Pooled, it suggests similar clinical outcomes with lower acute toxicities in favour of involved nodes irradiation. However, delivery techniques, doses and concomitant treatment were not consensual. Studies are ongoing evaluating the impact of radiation delivery techniques and the choice of concomitant treatment, i.e. immunotherapy. Modern techniques of imaging, radiation therapy progressing each day and alternative treatment modalities being tested, the need of randomized controlled trials has never been so high. Elective nodal irradiation should remain the standard of care while phase 3 trials explore the safety of involved nodal irradiation.

[Siriade 2.0: An e-learning platform for radiation oncology contouring]. / Siriade 2.0 : outil de formation en ligne à la délinéation en radiothérapie.

PURPOSE: In 2008, the French national society of radiation oncology (SFRO) and the association for radiation oncology continued education (AFCOR) created Siriade, an e-learning website dedicated to contouring. MATERIAL AND METHODS: Between 2015 and 2017, this platform was updated using the latest digital online tools available. Two main sections were needed: a theoretical part and another section of online workshops. RESULTS: Teaching courses are available as online commented videos, available on demand. The practical section of the website is an online contouring workshop that automatically generates a report quantifying the quality of the user's delineation compared with the experts'. CONCLUSION: Siriade 2.0 is an innovating digital tool for radiation oncology initial and continuous education.

[Hypofractionated radiotherapy in rectal cancer for elderly patients]. / Radiothérapie hypofractionnée des cancers du rectum chez le sujet âgé.

Rectal cancer is a common pathology in the elderly. The standard for advanced rectal tumors is a chemoradiotherapy regimen combined 50Gy with concomitant chemotherapy followed by a surgery. This treatment induces interruptions of chemoradiotherapy and toxicities G3-4 more important in people over 70 years of age. Hypofractionated radiotherapy 5×5Gy with surgery following week is an alternative. All retrospective studies on this fractionation report an excellent immediate and chronic tolerance. The randomized phase III NACRE trial, comparing these 2 radiotherapy, followed by surgery at 6-8 week, established a standard in the management of the elderly patients.

Adjuvant radiation therapy for malignant Abrikossoff's tumor: a case report about a femoral triangle localisation.

BACKGROUND: Granular cell or Abrikossoff's tumors are usually benign however rare malignant forms concern 1 to 3% of cases reported. Pelvic locations are exceptional. CASE PRESENTATION: We report a case of a 43-years-old patient who had a benign Abrikossoff's tumor localized in the right femoral triangle diagnosed at the biopsy. The patient underwent a surgical tumorectomy and inguinal lymph nodes resection. Histologically, the tumor showed enough criteria to give diagnosis of malignancy: nuclear pleomorphism, tumor cell spindling, vesicular nuclei with large nucleoli. Moreover, five lymph nodes were metastatic. Immunohistochemistry findings confirmed the diagnosis of granular cell tumor which is positive for S100 protein and CD68 antibodies. The mitotic index was nevertheless low with a Ki67 labeling index of 1-2%. A large surgical revision with an inguinal curage following radiotherapy were decided on oncology committee. Adjuvant radiotherapy on the tumor bed and right inguinal area of ​​50 Gy in conventional fractionation was delivered with the aim of reducing local recurrence risk. There was no recurrence on longer follow-up (10 months post radiotherapy). CONCLUSIONS: Adjuvant radiotherapy seems an appropriate therapeutic approach, even if controversial, given that some authors report effectiveness on local disease progression.

[Doses to organs at risk in conformational radiotherapy and stereotaxic irradiation: The heart]. / Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : le cœur.

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries.

[Technique of complex mammary irradiation: Mono-isocentric 3D conformational radiotherapy and helical tomotherapy]. / Techniques d'irradiation mammaire complexe : radiothérapie conformationelle tridimensionnelle mono-isocentrique et nomothérapie hélicoïdale.

PURPOSE: To evaluate the dosimetric contribution of helical tomotherapy for breast cancers compared with conformal radiotherapy in mono-isocentric technique. PATIENTS AND METHOD: For 23 patients, the dosimetric results in mono-isocentric 3D conformational radiotherapy did not satisfy the constraints either of target volumes nor organs at risk. A prospective dosimetric comparison between mono-isocentric 3D conformational radiotherapy and helical tomotherapy was therefore carried out. RESULTS: The use of helical tomotherapy showed a benefit in these 23 patients, with either an improvement in the conformity index or homogeneity, but with an increase in low doses. Of the 23 patients, two had pectus excavatum, five had past thoracic irradiation and two required bilateral irradiation. The other 14 patients had a combination of morphology and/or indication of lymph node irradiation. For these patients, helical tomotherapy was therefore preferred to mono-isocentric 3D conformational radiotherapy. CONCLUSIONS: Tomotherapy appears to provide better homogeneity and tumour coverage. This technique of irradiation may be justified in the case of morphological situations such as pectus exavatum and in complex clinical situations. In other cases, conformal radiotherapy in mono-isocentric technique remains to be favoured.

[Rectal squamous cell carcinoma treatment: Retrospective experience in two French university hospitals, review and proposals]. / Prise en charge du carcinome épidermoïde du rectum : expérience de deux centres universitaires français, revue de la littérature et recommandations.

After publishing a retrospective series of 23 patients treated for a rectal squamous cell carcinoma with exclusive curative and conservative intent chemoradiation, we aim to propose a review of the literature about this rare tumour. We identified 11 retrospective studies, on 106 patients, treated between 2007 and 2016. Treatment of rectal squamous cell carcinoma should be similar to anal carcinoma, based on exclusive chemoradiation, displaying a 5-year overall survival rate over 80%, while it was 32% in surgical series. Baseline explorations should be similar as for anal carcinoma, with an interest in PET-CT at diagnosis and monitoring, after a delay over 6 weeks after chemoradiation. Intensity-modulated radiotherapy is legitimate, to a prophylactic dose between 36 and 45Gy, and over 54Gy to the tumour. Concomitant chemotherapy should combine an antimetabolite (5-fluorouracil or capecitabine) and mitomycin C, or cisplatin. This treatment seems well tolerated, associated with grade 2 or above toxicity below 30%. Follow-up should be established on anal squamous cell carcinoma schedule, with endoscopic ultrasonography and PET-CT. Rectal squamous cell carcinoma is a rare tumour; it management should be based on anal curative and conservative intent chemoradiation.

[Definition of accurate planning target volume margins for esophageal cancer radiotherapy]. / Détermination des marges du volume cible anatomoclinique au volume cible prévisionnel pour la radiothérapie conformationnelle des cancers de l'œsophage.

More than 4000 cases of esophagus neoplasms are diagnosed every year in France. Radiotherapy, which can be delivered in preoperative or exclusive with a concomitant chemotherapy, plays a central role in treatment of esophagus cancer. Even if efficacy of radiotherapy no longer has to be proved, the prognosis of esophagus cancer remains unfortunately poor with a high recurrence rate. Toxicity of esophageal radiotherapy is correlated with the irradiation volume, and limits dose escalation and local control. Esophagus is a deep thoracic organ, which undergoes cardiac and respiratory motion, making the radiotherapy delivery more difficult and increasing the planning target volume margins. Definition of accurate planning target volume margins, taking into account the esophagus' intrafraction motion and set up margins is very important to be sure to cover the clinical target volume and restrains acute and late radiotoxicity. In this article, based on a review of the literature, we propose planning target volume margins adapted to esophageal radiotherapy.

[Clinical to planning target volume margins in prostate cancer radiotherapy]. / Détermination des marges du volume cible anatomoclinique au volume cible prévisionnel pour la radiothérapie du cancer prostatique.

The knowledge of inter- and intrafraction motion and deformations of the intrapelvic target volumes (prostate, seminal vesicles, prostatectomy bed and lymph nodes) as well as the main organs at risk (bladder and rectum) allow to define rational clinical to planning target volume margins, depending on the different radiotherapy techniques and their uncertainties. In case of image-guided radiotherapy, prostate margins and seminal vesicles margins can be between 5 and 10mm. The margins around the prostatectomy bed vary from 10 to 15mm and those around the lymph node clinical target volume between 7 and 10mm. Stereotactic body radiotherapy allows lower margins, which are 3 to 5mm around the prostate. Image-guided and stereotactic body radiotherapy with adequate margins allow finally moderate or extreme hypofractionation.

[Radiotherapy of hypopharynx cancers]. / Radiothérapie des cancers de l'hypopharynx.

The intensity-modulated radiotherapy is the gold standard in the treatment of hypopharynx cancers. Early T1 and T2 tumours could be treated by exclusive radiotherapy or surgery. For tumours requiring total pharyngolaryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy are possible. For T4 tumours, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, curative dose is 70Gy and prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used for locally advanced cancers with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation is based on guidelines.

[Radiotherapy of oropharynx carcinoma]. / Radiothérapie des cancers de l'oropharynx.

Indication, doses, technique of radiotherapy and concomitant chemotherapy for oropharynx carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

[Radiotherapy of larynx cancers]. / Radiothérapie des cancers du larynx.

Intensity-modulated radiotherapy is the gold standard in the treatment of larynx cancers (except T1 glottic tumour). Early T1 and T2 tumours may be treated by exclusive radiation or surgery. For tumours requiring total laryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy is possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, the curative dose is 70Gy and the prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation was based on guidelines.

[Radiotherapy of carcinoma of the salivary glands]. / Radiothérapie des tumeurs des glandes salivaires.

Indication, doses, and technique of radiotherapy for salivary glands carcinoma are presented, and the contribution of neutrons and carbon ions. The recommendations for delineation of the target volumes and organs at risk are detailed.