Harnessing drug/radiation interaction through daily routine practice: Leverage medical and methodological point of view (MORSE 02-17 study).

BACKGROUND: Safety profile of the interaction between anticancer drugs and radiation is a recurrent question. However, there are little data regarding the non-anticancer treatment (NACT)/radiation combinations. The aim of the present study was to investigate concomitant NACTs in patients undergoing radiotherapy in a French comprehensive cancer center. METHODS: A prospective cross-sectional study was conducted. All cancer patients undergoing a palliative or curative radiotherapy were consecutively screened for six weeks in 2016. Data on NACTs were collected. RESULTS: Out of 214 included patients, a NACT was concomitantly prescribed to 155 patients (72%), with a median number of 5 NACTs per patient (range: 1-12). The most prescribed drugs were anti-hypertensive drugs (101 patients, 47.2%), psychotropic drugs (n = 74, 34.6%), analgesics (n = 78, 36.4%), hypolipidemic drugs (n = 57, 26.6%), proton pump inhibitors (n = 46, 21.5%) and antiplatelet drugs (n = 38, 17.8%). Although 833 different molecules were reported, only 20 possible modifiers of cancer biological pathways (prescribed to 74 patients (34.5%)) were identified. Eight out of the 833 molecules (0.9%), belonging to six drug families, have been investigated in 28 ongoing or published clinical trials in combo with radiotherapy. They were prescribed to 63 patients (29.4%). CONCLUSION: Drug-radiation interaction remains a subject of major interest, not only for conventional anticancer drugs, but also for NACTs. New trial designs are thus required.

Navigating the highlights of phase III trials: a watchful eye on evidence-based radiotherapy.

BACKGROUND: Phase III randomized controlled trials (RCTs) are the cornerstone of evidence-based oncology. However, there is no exhaustive review describing the radiotherapy RTCs characteristics. The objective of the present study was to describe features of all phase III RCTs including at least a radiation therapy. METHODS AND MATERIALS: Requests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase III as topic', 'radiotherapy', 'brachytherapy', as keywords. RESULTS: A total of 454 phase III RCTs were identified. Studies were mainly based on open (92.1%) multicenter (77.5%) designs, analyzed in intend to treat (67.6%), aiming at proving superiority (91.6%) through overall survival assessment (46.5%). Most frequently studied malignancies were head and neck (21.8%), lung (14.3%) and prostate cancers (9.9%). Patients were mainly recruited with a locally advanced disease (73.7%). Median age was 59 years old. Out of 977 treatment arms, 889 arms experienced radiotherapy, mainly using 3D-conformal radiotherapy (288 arms, 32.4%). Intensity-modulated techniques were tested in 12 arms (1.3%). The intervention was a non-cytotoxic agent addition in 89 studies (19.6%), a radiation dose/fractionation modification in 74 studies (16.3%), a modification of chemotherapy regimen in 63 studies (13.9%), a chemotherapy addition in 63 studies (13.9%) and a radiotherapy addition in 53 trials (11.7%). With a median follow-up of 50 months, acute all-grade and grade 3-5 toxicities were reported in 49.6% and 69.4% of studies, respectively. Radiotherapy technique, follow-up and late toxicities were reported in 60.1%, 74%, and 31.1% of studies, respectively. CONCLUSION: Phase III randomized controlled trials featured severe limitations, since a third did not report radiotherapy technique, follow-up or late toxicities. The fast-paced technological evolution creates a discrepancy between literature and radiotherapy techniques performed in daily-routine, suggesting that phase III methodology needs to be reinvented.

Bilateral Breast Cancer After Prophylactic Bilateral Pulmonary Irradiation.

The purpose of this article is to report a new case of a probably radio-induced bilateral breast cancer occurred after prophylactic bilateral pulmonary irradiation in the treatment of osteosarcoma. A 42-year-old woman, treated at the age of 12 years for osteosarcoma at the right lower limb with chemotherapy (methotrexate, adriamycin and cisplatin) followed by non-conservative surgery and adjuvant radiotherapy. Eighteen years after, she developed her first breast cancer, and five years later, her second contralateral breast cancer. The patient was treated for her two non-metastatic cancers and is currently in complete remission. This publication adds to several previous publications the very probable effect of ionizing radiation in the occurrence of secondary cancers.

[Ototoxicity in head and neck cancers after radiotherapy and chemoradiotherapy: From primary prevention to tertiary prevention]. / Ototoxicité radio-induite et chimio-induite dans les cancers ORL : de la prévention primaire à la prévention tertiaire.

Each year, 15,000 head and neck cancer are treated in France. Prognosis is steadily improving. Consequently, limitation of late toxicities becomes essential. Ototoxicity is common, disabling and undervalued. We aimed to inventory primary, secondary and tertiary prevention measures to reduce ototoxicity induced by radiotherapy and chemotherapy, as well as its impact on quality of life of patients treated for head and neck cancer. External radiation therapy induced 30 to 40% of ototoxicity, including irreversible sensorineural hearing loss. Primary prevention of this risk is based on limiting the dose to the cochlea: 40Gy in case of radiotherapy alone, 10Gy during concomitant chemoradiotherapy with cisplatin. Dose gradients allowed by intensity-modulated radiotherapy help respecting these limits. Concurrent chemotherapy with high dose cisplatin (100mg/m2) also causes hearing loss by cochlear damages. Prescription of carboplatin-5-fluorouracil combination or cetuximab should be preferred in case of high risk of ototoxicity. This risk must be precisely evaluated before treatment. Ototoxicity monitoring during treatment allows early management, and lower long-term impact. Radiosensitivity predictive tests and research of genetic factors predisposing to chemo-induced ototoxicity should enable optimization of therapeutic choices and monitoring.