[Practice changing clinical trials in radiation oncology in 2022]. / Les essais qui changent les pratiques : le point en 2022.

This section highlights selected specific new recommendations and/or updates that have been published during the very last years in the fields of stereotactic radiotherapy, pediatrics, lung cancer, gynecologic and breast cancer, as well as in the area of radiation oncology of urogenital cancer.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Role of radiotherapy in the treatment of primary vaginal cancer: Recommendations of the French society for radiation oncology.

Primary vaginal cancers are rare tumours, for which external beam radiotherapy and brachytherapy are major treatment tools. Given the complexity of brachytherapy techniques, the treatment should be performed in specialised centres. We present the recommendations of the French society for radiation oncology on the indications and techniques for external beam radiotherapy and brachytherapy for primary vaginal cancer.

Radiotherapy of cervical cancer.

External beam radiotherapy and brachytherapy are major treatments in the management of cervical cancer. For early-stage tumours with local risk factors, brachytherapy is a preoperative option. Postoperative radiotherapy is indicated according to histopathological criteria. For advanced local tumours, chemoradiation is the standard treatment, followed by brachytherapy boost, which is not optional. We present the update of the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for cervical cancer.

Radiotherapy for endometrial cancer.

The first intent upfront treatment of endometrial cancer is surgery. External radiotherapy and brachytherapy; however, are important tools in adjuvant setting, according to histopathological risk factors for locoregional recurrence or in the event of an inoperable tumor. We present the update of the recommendations of the French society of oncological radiotherapy on the indications and technical methods of performing radiotherapy and brachytherapy for endometrial cancer.

Role of radiotherapy in the management of vulvar cancer: Recommendations of the French society for radiation oncology.

Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer.

[Hodgkin lymphoma and target definition guidelines]. / Radiothérapie « involved node ¼ et « involved site ¼ des lymphomes hodgkiniens : quels volumes cible ?

Treatment for stage I and II Hodgkin lymphoma is based on a combination of chemotherapy and radiotherapy, with a high successful cure rate. Now, the aim is to decrease toxicity rates. Positron-emission tomography scan is recommended as pretreatment baseline and is very useful to define precisely target volumes for planning radiation therapy. Based on these changes were developed guidelines for modern radiation therapy called involved node and « involved site ¼.

Evaluation at 3 years of concurrent bevacizumab and radiotherapy for breast cancer: Results of a prospective study.

PURPOSE: To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. MATERIAL AND METHODS: This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. RESULTS: Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18-77 months). Median age was 53 years old (range: 23-68 years). The 3-years overall survival was 93% (range: 87-100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. CONCLUSIONS: Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

[Radiotherapy of cervix and endometrial carcinoma]. / Radiothérapie des cancers du col et de l'endomètre.

External irradiation and brachytherapy still have a major place in the treatment of cervix and endometrial carcinoma. This review presents the French guidelines in terms of preparation and choice of irradiation techniques of these gynecological malignancies.

Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer.

OBJECTIVE: To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). METHODS: Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. RESULTS: From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1-2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). CONCLUSION: The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. ADVANCES IN KNOWLEDGE: The largest series of this association.

[Economic assessment of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution for cervix carcinoma]. / Evaluation économique de la curiethérapie de débit pulsé gynécologique (PDR) avec optimisation de la dose pour les cancers du col utérin.

PURPOSE: Our study aims at evaluating the cost of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution versus traditional treatments (iridium wires, cesium, non-optimized PDR). Issues surrounding reimbursement were also explored. MATERIALS AND METHODS: This prospective, multicentre, non-randomised study conducted in the framework of a project entitled "Support Program for Costly Diagnostic and Therapeutic Innovations" involved 21 hospitals. Patients with cervix carcinoma received either classical brachytherapy or the innovation. The direct medical costs of staff and equipment, as well as the costs of radioactive sources, consumables and building renovation were evaluated from a hospital point of view using a microcosting approach. Subsequent costs per brachytherapy were compared between the four strategies. RESULTS: The economic study included 463 patients over two years. The main resources categories associated with PDR brachytherapy (whether optimized or not) were radioactive sources (1053euro) and source projectors (735euro). Optimized PDR induced higher cost of imagery and dosimetry (respectively 130euro and 367euro) than non-optimized PDR (47euro and 75euro). Extra costs of innovation over the less costly strategy (iridium wires) reached more than 2100euro per treatment, but could be reduced by half in the hypothesis of 40 patients treated per year (instead of 24 in the study). CONCLUSION: Aside from staff, imaging and dosimetry, the current hospital reimbursements largely underestimated the cost of innovation related to equipment and sources.

Preoperative radiochemotherapy for resectable localised oesophageal cancer: a controversial strategy.

Preoperative chemoradiation (P-CRT) remains a controversial strategy in the treatment of squamous cell cancer (SCC) and adenocarcinoma (ADC) of the oesophagus. Until recently, randomised studies mixed the two, often without any distinction. In randomised studies involving exclusively SCC, P-CRT increases the rate of local control, R0 resection, pCR and disease-free survival. The absence of any impact on overall survival may be linked to the toxic effects of this treatment. Meta-analyses have revealed a survival benefit of approximately +13% at 2 years. However, the methodology used was perhaps questionable. Five randomised trials involving ADC patients compared P-CRT with surgery alone. The results were contradictory with insufficient statistical power in selected positive studies to answer this issue once and for all. P-CRT is unsatisfactory as a standard treatment. Although local control rates were increased with P-CRT, it should be considered only for selected patients in selected centres.

Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary.

PURPOSE: To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP). METHODS AND MATERIALS: Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80 years (median 59 years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only. RESULTS: After a median follow-up of 3.3 years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy (p=0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy (p=0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p=0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status (p=0.013) and the radiation technique (2D vs.3D-CRT or IMRT; p=0.029). There was no difference in loco-regional control (p=0.639) and no difference in survival (p=0.493) when chemotherapy was associated. CONCLUSIONS: Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient's local regional control and survival are significantly improved after 3D-CRT or IMRT.

[Stage I endometrial carcinoma]. / Cancer de l'endomètre de stade I.

Most endometrial cancers are diagnosed at stage I (disease limited to the uterine corpus). The definitive treatment for endometrial carcinoma consists in total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy. The decision of adjuvant treatment depends on risk factors. Postoperative radiotherapy plays a major role in the management of stage I endometrial cancer but the respective place of external radiotherapy and vaginal brachytherapy remains controversial. Adjuvant external beam radiotherapy reduces locoregional recurrences, but carries a risk of toxicity without overall survival benefits. Recent data suggest that vaginal brachytherapy is effective in preventing vaginal recurrence with lower toxicity and should be the treatment of choice for intermediate risk endometrial cancer.

[Potential combination of target therapy and radiation therapy in GI tract cancers]. / Place potentielle des thérapies ciblées en association avec la radiothérapie dans les cancers digestifs.

At cellular level, signalization pathway activated by ErbB receptors participate to the proliferation, migration and differenciation of many cellular types. Observed alterations are mutations, overexpressions with or without gene amplification or abnormal stimulation by their ligands. The most frequently observed mutation is an extracellular deletion aiming to activate tyrosine kinase activity without ligand. Strategies to target the EGFr receptor include antisens oligonucleotids, antibodies directed to extracellular component of tyrosine kinase receptor. Only monoclonal antibodies and TKI have been developed in clinical research, mainly for oesophageal and rectal carcinomas. Solid tumor proliferation is under control of tumoral mechanisms and the interaction between tumor and microenvironment. In particular, angiogenesis is important during invasive and metastasis phases. The major role of Vasculoendothelial Growth Factor (VEGF) in angiogenesis is useful for tumor growth, which has been demonstrated by many convergent studies. Radiosensitivation or reversion of radioresistance could be obtained by inhibition of VEGF pathway. Antibodies directed against this molecule have been introduced in GI tract malignancies for the treatment of pancreatic and colic carcinomas.

[Is a linac able to do better than tomotherapy or Cyberknife?]. / Un accélérateur linéaire peut-il faire aussi bien qu'un appareil de tomothérapie ou un Cyberknife?

Tomotherapy is a new external beam radiation therapy technique using helicoidal intensity modulated radiation principle. It is able to avoid multiple isocenters requested to irradiate large volumes. This machine integrates image acquisition, treatment planning, positioning of the patient and irradiation into a sole engine. Six degrees of freedom robot coupled with a 6 MV linear accelerator, InCA has installed the Cyberknife in France in 3 sites chosen. The last generation of linac is a multifunction machine able to deliver conformal irradiations with or without intensity modulated radiation therapy, cranial or extracranial stereotactic irradiation with or without arctherapy or modulation. Performances of each machine have to be measured and compared in a medical and economical procedure.

[Implementation of transabdominal ultrasound image guided conformal intensity modulated radiotherapy]. / Mise en oeuvre de la radiothérapie conformationnelle par modulation d'intensité guidée par échographie transabdominale.

PURPOSE: Optically guided ultrasound imaging has been used in our department since 2003 in order to implement an on line correction scheme in intensity modulated radiation therapy of prostate carcinoma. PATIENTS AND METHODS: The corrections observed during the initial time period of the system (17 patients) are compared to those observed more recently (10 patients). Treatment margins are calculated. RESULTS: Overall systematic errors decreased between 2003 and 2006, and are presently statistically not different from zero. Random errors remain the same (max 4.3 mm). Proposed margins are 7 mm both in lateral and longitudinal direction and 8.4 mm in anteroposterior. CONCLUSION: Ultrasound can be used for on line correction of both positioning and internal organs motion errors and allows reduction of the margins between clinical and planning volume.

[High precision radiotherapy with ultrasonic imaging guidance]. / Radiothérapie de haute précision guidée par échographie.

Conformal radiation therapy with or without intensity modulation is the standard treatment of localized prostate cancer and facilitates dose escalation. The implementation of three-dimensional conformal radiotherapy necessitates focusing on target volume delineation, dosimetry, reproducibility of treatment and quality control. Recently, ultrasound systems that allow direct daily visualization of the prostate have become available. This non-invasive technique can be used to correct both prostate organ motion and set-up error and leads to increase treatment accuracy.

[Conformal radiation therapy with or without intensity modulation in the treatment of localized prostate cancer]. / La radiothérapie de conformation avec et sans modulation d'intensité dans le traitement du cancer localisé de la prostate.

Conformal radiation therapy has now to be considered as a standard treatment of localized prostatic adenocarcinomas. Using conformational methods and intensity modulated radiation therapy requires a rigorous approach for their implementation in routine, focused on the reproducibility of the treatment, target volume definitions, dosimetry, quality control, setup positioning. In order to offer to the largest number of patients high-dose treatment, the clinicians must integrate as prognostic factors accurate definition of microscopic extension as well as the tolerance threshold of critical organs. High-dose delivery is expected to be most efficient in intermediary risks and locally advanced diseases. Intensity modulated radiation therapy is specifically dedicated to dose escalation. Perfect knowledge of classical constraints of conformal radiation therapy is required. Using such an approach in routine needs a learning curve including the physicists and a specific quality assurance program.