Implementation of volumetric-modulated arc therapy for locally advanced breast cancer patients: Dosimetric comparison with deliverability consideration of planning techniques and predictions of patient-specific QA results via supervised machine learning.

PURPOSE: The aim of this study was to implement a clinically deliverable VMAT planning technique dedicated to advanced breast cancer, and to predict failed QA using a machine learning (ML) model to optimize the QA workload. METHODS: For three planning methods (2A: 2-partial arc, 2AS: 2-partial arc with splitting, 4A: 4-partial arc), dosimetric results were compared with patient-specific QA performed with the electronic portal imaging device of the linac. A dataset was built with the pass/fail status of the plans and complexity metrics. It was divided into training and testing sets. An ML metamodel combining predictions from six base classifiers was trained on the training set to predict plans as 'pass' or 'fail'. The predictive performances were evaluated using the unseen data of the testing set. RESULTS: The dosimetric comparison highlighted that 4A was the highest dosimetric performant method but also the poorest performant in the QA process. 2AS spared the best heart, but provided the highest dose to the contralateral breast and lowest node coverage. 2A provides a dosimetric compromise between organ at risk sparing and PTV coverage with satisfactory QA results. The metamodel had a median predictive sensitivity of 73% and a median specificity of 91%. CONCLUSIONS: The 2A method was selected to calculate clinically deliverable VMAT plans; however, the 2AS method was maintained when the heart was of particular importance and breath-hold techniques were not applicable. The metamodel provides promising predictive performance, and it is intended to be improved as a larger dataset becomes available.

Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial.

PURPOSE: Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. PATIENTS AND METHODS: The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. RESULTS: Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). CONCLUSION: Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

Multicenter Randomized Double-Blind, Placebo-Controlled Trial GORTEC (Groupe Oncologie Radiotherapie Tete et Cou) 2009-01 Evaluating the Effect of the Regenerating Agent on Radiodermatitis of Head and Neck Cancer Patients.

PURPOSE: Concomitant cetuximab and radiation therapy (RT) can induce severe radiodermatitis in patients with head and neck cancer (HNC). OTD70DERM, a regenerating agent (RGTA), is a structural and functional analogue of glycosaminoglycans. Preclinical studies have shown that topical RGTA can markedly reduce radiation-induced mucosal and cutaneous toxicities without tumor protection. The present study aimed to evaluate the effect of topical RGTA on radiodermatitis in patients with HNC undergoing RT and cetuximab, for whom RT-induced skin reactions are frequent and/or severe. The primary endpoint was the incidence of grade ≥2 radiodermatitis. METHODS AND MATERIALS: We performed a multicenter, randomized, double-blind, placebo-controlled trial of patients with newly diagnosed HNC undergoing conventionally fractionated RT (70 Gy in 35 fractions) and weekly cetuximab. Patients were randomized 1:1 to receive topical OTD70DERM or placebo on irradiated skin once daily. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to evaluate radiodermatitis (photographs of radiation zone). The Dermatology Life Quality Index score was also evaluated. All the skin reactions seen on the photographs were scored independently by 2 outside experts. RESULTS: Of the 76 randomized patients (38 in each arm), 72 were available for the final radiodermatitis evaluation (37 in the RGTA arm and 35 in the placebo arm). No significant difference was observed concerning the incidence or duration of grade ≥2 radiodermatitis between the 2 arms (81% for RGTA vs 80% for placebo; P=.9). Also, no significant difference was found between the 2 arms regarding grade ≥2 radiodermatitis evaluated by the 2 experts using the photographs of 68 patients (76% vs 74%; P=.78). Finally, no significant difference was found in the Dermatology Life Quality Index score (score >10, 15% vs 20%; P=.45). CONCLUSIONS: Despite the good preclinical rationale, RGTA did not reduce the incidence and severity of radiodermatitis in patients with HNC.

[Respiratory gated radiotherapy: the 4D radiotherapy]. / La radiothérapie asservie à la respiration: la radiothérapie 4D.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breath hold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices (CCD camera for the GEMS/Varian system tested at Curie Institute) to predict the phase of the respiration cycle while the patient breaths freely. A new strategy is currently developed: the 4D Respiration correlated CT. It consists of retrospectively reconstruct CT slices at different phases of the breathing cycle allowing to measure residual movements and to choose the optimal patient's breathing phase where tumor movements are lower. These techniques presently investigated in several medical centers worldwide. The first results are very promising.

[Prostate cancer diagnosed before 55: a retrospective study from the Rare Cancer Network]. / Cancers de la prostate diagnostiqués avant 55 ans: une étude rétrospective du groupe des cancers rares.

This retrospective study on a large number of cases offers a vision of the modalities of care in prostate cancer diagnosed before the age of 55, according to different policies, aiming to propose other directions for 2005. Between January 1974 and December 2001, 365 patients had a pathological diagnosis of prostate cancer occurring before the age of 55. These patients were referred to the departments of radiation therapy affiliated to the Rare Cancer Network. A questionnaire was filled in retrospectively to allow further analysis of medical and surgical data. The treatments were those recommended at the time of analysis and progressed according to new accepted standards. Clinical and pathological features of the patients were as follows: 36% of the tumours were Gleason > 7 scored, 56% of the patients had a T3-T4 and 31 had metastases at the time of diagnosis. As far as treatment was concerned, 4 groups were considered: 83 patients had a radical prostatectomy, 155 received radiation therapy with a curative intent, 87 were treated by hormonal manipulation, and the remaining 40 patients received palliative care. The free of disease survival rate at 10 years was 38% for patients without immediate metastases, only 1% of patients with metastases were alive. The multivariate analysis demonstrated the significant impact of radiotherapy on both local and distant failure rates and of T stage on distant failure rate. Survival was affected by nodal involvement and local failure. A separate analysis of two periods of time (1974-1989 and 1990-2001) did not show any differences in terms of treatment results. This retrospective study suggests that age is not a negative prognostic factor as far as adequate curative treatments are carried out. Therapeutic modalities having considerably evolved in prostate cancer, a further analysis with a longer follow up may allow the evaluation of these treatments on rates of failures and survival. Screening for prostate cancer in family histories is likely to increase the number of cases diagnosed before 55. Therefore, a complete information on morbidity associated to the different means of treatment would lead to a better acceptance of late side effects.