Michel Lapeyre

Bio: Michel Lapeyre is an academic researcher from University of Auvergne. The author has contributed to research in topics: Radiation therapy & Brachytherapy. The author has an hindex of 28, co-authored 136 publications receiving 2670 citations.

Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): An open-label phase 3 randomised trial

Abstract: Summary Background Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. Methods In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0–2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. Findings Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9–6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84–1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69–1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67–0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1–43·4) after conventional chemoradiotherapy, 34·1% (28·7–39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0–37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3–4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). Interpretation Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. Funding French Ministry of Health.

Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer.

Abstract: Purpose: To evaluate the prognostic value of tumor downstaging after preoperative radiation for resectable rectal cancer. Methods and Materials: Eighty-eight patients with non-metastatic resectable rectal cancers (76 T3 and 12 T4) were treated with preoperative irradiation. Median dose was 40 Gy (30–46 Gy) delivered over 32 days (range 11–40). Seventeen patients received preoperative chemotherapy, two courses of 5-fluorouracil (5FU) 350 mg/m2/day and folinic acid 20 mg/m2/day; 5 days per week during the first and fifth weeks of radiotherapy. Surgery was performed with a mean delay of 46 days after completion of irradiation and included 66 abdominoperineal resections and 22 anal sphincter-preserving procedures. Postoperative chemotherapy was administered in 44 patients. Results: Histological tumor stages were: complete histological response in 7%, pT2N0 in 19%, pT3N0 in 46%, and pT2-3N1 in 28%. Tumor downstaging occurred in 26%. No predictive factor of downstaging was statistically significant. The median follow-up was 33 months. The 3- and 5-year cancer-specific survival rates were 100% for the pT0N0 and pT2N0, respectively, 89% and 68% for pT3N0, and 64% and 0% for pT2T3N1. After preoperative irradiation, the pathological tumor stages remained a prognostic factor. Patients with downstaging (pT0T2N0) had significantly higher cancer-specific survival rates than the group without downstaging: 100% and 80% at 3 years, and 100% and 45% at 5 years; respectively (p = 0.011). The 3- and 5-year recurrence free-survival rates were 94% for the group with downstaging and 56% and 50%, respectively, for the group without downstaging (p = 0.002). Conclusion: Downstaging after preoperative irradiation in this retrospective study results in an improvement in local control and survival.

Phase III Randomized Trial of Very Accelerated Radiation Therapy Compared With Conventional Radiation Therapy in Squamous Cell Head and Neck Cancer: A GORTEC Trial

Abstract: Purpose With the aim to increase the dose intensity of radiation therapy (RT), and subsequently the locoregional control rate, a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma (HNSCC). Patients and Methods Between 1994 and 1998, 268 patients with T3 or T4, N0 to N3 HNSCC (staged by 1997 International Union Against Cancer criteria) that was not eligible for surgery were randomly assigned to receive either conventional RT, delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days, or to receive very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days (2 Gy/fraction bid). Results The most common tumor site was the oropharynx and most of the patients (70%) had T4 and N1 to N3 tumors in 72% of patients. The main patient and tumor characteristics were well-balanced between the two arms. The median total doses were 63 Gy (accelerated) and 70 Gy (conventional), with a ...

Impact of Intensity-Modulated Radiotherapy on Health-Related Quality of Life for Head and Neck Cancer Patients: Matched-Pair Comparison with Conventional Radiotherapy

Abstract: Purpose: To assess the benefit of intensity-modulated radiotherapy (IMRT) compared with conventional RT for the quality of life (QOL) of head and neck cancer survivors. Methods and Materials: Cross-sectional QOL measures (European Organization for Research and Treatment of Cancer QOL questionnaire C30 and head and neck cancer module) were used with a French multicenter cohort of patients cured of head and neck cancer (follow-up ≥ 1 year) who had received bilateral neck RT (≥ 45 Gy) as a part of their initial treatment. We compared the QOL mean scores regarding RT modality (conventional RT vs. IMRT). The patients of the two groups were matched (one to one) according to the delay between the end of RT and the timing of the QOL evaluation and the T stage. Each QOL item was divided into two relevant levels of severity: "not severe" (responses, "not at all" and "a little") vs. "severe" (responses "quite a bit" and "very much"). The association between the type of RT and the prevalence of severe symptoms was approximated, through multivariate analysis using the prevalence odds ratio. Results: Two comparable groups (67 pairs) were available. Better scores were observed on the head and neck cancer module QOL questionnaire for the IMRT group, especially for dry mouth and sticky saliva ( p p = 0.04) for dry mouth, 3.16 ( p = 0.02) for sticky saliva, 3.58 ( p = 0.02) for pain in the mouth, 3.35 ( p = 0.04) for pain in the jaw, 2.60 ( p = 0.02) for difficulties opening the mouth, 2.76 ( p = 0.02) for difficulties with swallowing, and 2.68 ( p = 0.03) for trouble with eating. Conclusion: The QOL assessment of head and neck cancer survivors demonstrated the benefit of IMRT, particularly in the areas of salivary dysfunction and oral discomfort.

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival.

Abstract: Summary Background Previous results from our phase 3 randomised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN) at 3 years. Here we report the 5-year survival data, and investigate the relation between cetuximabinduced rash and survival. Methods Patients with LASCCHN of the oropharynx, hypopharynx, or larynx with measurable disease were randomly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 6–7 weeks or radiotherapy plus weekly doses of cetuximab: 400 mg/m² initial dose, followed by seven weekly doses at 250 mg/m². Randomisation was done with an adaptive minimisation technique to balance assignments across stratifi cation factors of Karnofsky performance score, T stage, N stage, and radiation fractionation. The trial was un-blinded. The primary endpoint was locoregional control, with a secondary endpoint of survival. Following discussions with the US Food and Drug Administration, the dataset was locked, except for queries to the sites about overall survival, before our previous report in 2006, so that an independent review could be done. Analyses were done on an intention-to-treat basis. Following completion of treatment, patients underwent physical examination and radiographic imaging every 4 months for 2 years, and then every 6 months thereafter . The trial is registered at www.ClinicalTrials.gov , number NCT00004227. Findings Patients were randomly assigned to receive radiotherapy with (n=211) or without (n=213) cetuximab, and all patients were followed for survival. Updated median overall survival for patients treated with cetuximab and radiotherapy was 49·0 months (95% CI 32·8–69·5) versus 29·3 months (20·6–41·4) in the radiotherapy-alone group (hazard ratio [HR] 0·73, 95% CI 0·56–0·95; p=0·018). 5-year overall survival was 45·6% in the cetuximab-plus-radiotherapy group and 36·4% in the radiotherapy-alone group. Additionally, for the patients treated with cetuximab, overall survival was signifi cantly improved in those who experienced an acneiform rash of at least grade 2 severity compared with patients with no rash or grade 1 rash (HR 0·49, 0·34–0·72; p=0·002). Interpretation For patients with LASCCHN, cetuximab plus radiotherapy signifi cantly improves overall survival at 5 years compared with radiotherapy alone, confi rming cetuximab plus radiotherapy as an important treatment option in this group of patients. Cetuximab-treated patients with prominent cetuximab-induced rash (grade 2 or above) have better survival than patients with no or grade 1 rash.

Clinical practice guidelines in oncology

Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results.

Abstract: Multimodality approach is the preferred treatment strategy for distal rectal cancer, including radical surgery, radiotherapy and chemotherapy. A significant proportion of patients managed by surgery, performed according to established oncological principles, appear to benefit from chemoradiation (CRT) therapy either pre- or postoperatively in terms of survival and recurrence rates. Preoperative CRT may be associated with less acute toxicity, greater tumor response/sensitivity, and higher rates of sphincter-saving procedures when compared with postoperative course.1,2 Furthermore, tumor downstaging may lead to complete clinical response (defined as absence of residual primary tumor clinically detectable) or complete pathologic response (defined as absence of viable tumor cells after full pathologic examination of the resected specimen, pT0N0M0). These situations may be observed in 10% to 30% of patients treated by neoadjuvant CRT and may be referred as stage 0 disease.3–8 Surgical resection of the rectum may be associated with significant morbidity and mortality, and in these patients, with significant rates of stoma construction.9 Moreover, surgical resection may not lead to increased overall and disease-free survival in these patients. For this reason, it has been our policy to carefully follow these patients with complete clinical response assessed after 8 weeks of CRT completion by clinical, endoscopic, and radiologic studies without immediate surgery. Patients considered with incomplete clinical response are referred to radical surgery. Surprisingly, up to 7% of these patients may present complete pathologic response (pT0N0M0) without tumor cells during pathologic examination, despite incomplete clinical response characterized by a residual rectal ulcer.8 To determine the benefit of surgical resection in patients with stage 0 rectal cancer treated by preoperative CRT therapy, we compared long-term results of a group of patients with incomplete clinical response followed by radical surgery versus a group of patients with complete clinical response not operated on.