Véronique Favrel

Intensity-modulated radiotherapy in head and neck cancer: Results of the prospective study GORTEC 2004–03

BACKGROUND AND PURPOSE In 2003, the French Authority for Health (HAS) recommended the use of intensity modulated radiotherapy (IMRT) in prospective trial before its routine use. The Oncology and Radiotherapy Group for Head and Neck Cancer (GORTEC) proposed to evaluate prospectively acute and late toxicities, locoregional control and overall survival for patients treated for head and neck cancer (HNC) with IMRT and bilateral neck irradiation. MATERIALS AND METHODS Between 2002 and 2008, 208 patients with HNC were treated with IMRT in 8 centres. There were 38 nasopharynx, 117 oropharynx, 25 pharyngo-larynx, 24 oral cavity and 4 unknown primary (28.5% stage I-II and 71% Stage III-IV). Ninety-three patients (46%) had postoperative IMRT and 78 patients (37.5%) received concurrent chemotherapy. The doses were 70 Gy to the gross tumour, 66 Gy to the high-risk postoperative sites and 50 Gy to the subclinical disease. Toxicities were graded according to the RTOG-EORTC scales. RESULTS The median follow-up was 25.3 months (range: 0.4-72 months). There were 29 local-regional failures: 24 were in-field, three were marginal and one was out-field. The two-year loco-regional control and overall survival were 86% and 86.7%, respectively. At 18 months, grade ≥ 2 xerostomia was 16.1%. A mean dose to the spared parotid below 28 Gy led to significantly less grade ≥ 2 xerostomia (8.5% vs 24%) with a relative risk of 1.2 [95% CI: 1.02-1.41, p = 0.03]. Grade ≥ 2 xerostomia increased by approximately 3% per Gy of mean parotid dose up to 28, Gy then 7% per Gy above 33 Gy. CONCLUSIONS IMRT for HN cancer seems to reduce late toxicities without jeopardising local control and overall survival.

Randomized clinical trial of post-operative radiotherapy versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement

BACKGROUND AND PURPOSE Post-operative radiotherapy is indicated for the treatment of head and neck cancers. In vitro, chemotherapy potentiates the cytotoxic effects of radiation. We report the results of a randomized trial testing post-operative radiotherapy alone versus concomitant carboplatin and radiotherapy for head and neck cancers with lymph node involvement. MATERIALS AND METHODS The study involved patients undergoing curative-intent surgery for head and neck cancers with histological evidence of lymph node involvement. Patients were randomly assigned to receive radiotherapy alone (54-72Gy, 30-40 fractions, 6-8 weeks) or identical treatment plus concomitant Carboplatin (50mg/m(2) administered by IV infusion twice weekly). RESULTS Between February 1994 and June 2002, 144 patients were included. With a median follow-up of 106 months (95% confidence interval (CI) [92-119]), the 2-year rate of loco-regional control was 73% (95% CI: 0.61-0.84) in the combined treatment group and 68% (95% CI: 0.57-0.80) in the radiotherapy group (p=0.26). Overall survival did not differ significantly between groups (hazard ratio for death, 1.05; 95% CI: 0.69-1.60; p=0.81). CONCLUSIONS Twice-weekly administration of carboplatin concomitant to post-operative radiotherapy did not improve local control or overall survival rates in this population of patients with node-positive head and neck cancers.

Prognostic factors of squamous cell carcinoma of the anal margin treated by radiotherapy: the Lyon experience

BackgroundTo report our patient experience with squamous cell carcinoma of the anal margin and to evaluate the prognostic factors influencing outcome.Materials and methodsBetween 1980 and 2001, 26 patients with anal margin squamous cell carcinoma were treated in Lyon-Sud: 7 T1, 14 T2, 4 T3, and 1 T4 with 20 N0, 3 N1, and 3 N2. The anal canal was invaded in five patients. Treatment consisted of definitive external irradiation in 14 patients and adjuvant irradiation (after a local excision) in 12 patients. External irradiation was combined with chemotherapy in seven patients, brachytherapy in four patients, and both brachytherapy and chemotherapy in one patient.ResultsThe local control rate was initially 61.4%, and it was 80.8% after salvage treatment. The 5-year overall and specific survival rates were 71 and 88.3%, respectively. Three factors correlated with specific survival: cell differentiation (P=0.038) and T (P=0.001) and N category (P=0.0005). A salvage abdominoperineal resection was successfully employed in five of seven local recurrences. Four grade 3 and two grade 4 toxicities were observed. Sphincter preservation was possible in 66% of alive patients.ConclusionOur results confirm the dominating place of definitive irradiation and radiochemotherapy in the treatment of anal margin squamous cell carcinoma. The indications for abdominoperineal resection must be limited to local relapse. The prognosis of squamous cell carcinoma is correlated to T and N staging and cell differentiation.

A RETROSPECTIVE, MULTICENTER STUDY OF THE TOLERANCE OF INDUCTION CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL FOLLOWED BY RADIOTHERAPY WITH CONCOMITANT CETUXIMAB IN 46 CASES OF SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

PURPOSE To investigate, in a multicenter study, the tolerance of induction chemotherapy (ICT) and external radiotherapy (ERT) with concomitant cetuximab in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Clinical data from 46 patients with Stage III or IV nonmetastatic SCCHN who received docetaxel, cisplatin, and 5-fluorouracil as ICT, followed by ERT with concomitant cetuximab, were retrospectively analyzed. Clinical safety (weight, allergy, mucositis, and dermatitis) and paraclinical safety (levels of hemoglobin, polynuclear neutrophils, and creatinine clearance) were studied. The primary objective was the proportion of patients who completed the protocol. RESULTS The percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.6%. Induction chemotherapy was better tolerated than that previously reported. The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalization (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment, although Grade 4 dermatitis was not experienced. There were no allergic reactions to cetuximab. CONCLUSION The completed protocol rate for SCCHN patients receiving ICT and ERT with concomitant cetuximab is high and the toxicity acceptable. Future improvements to protocol will be possible through early action and systematic implementation of nutritional support coupled with antibiotic treatment upon the first signs of radiodermatitis. These data could be useful for prospective studies on the safety and efficacy of this protocol.

Curative treatment can be an option for patients with metastatic squamous cell cancer of the head and neck

Background No specific study has focused on patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) at diagnosis. Due to high response rates of induction chemotherapy in chemo-naïve patients with localized disease, their prognosis should be better than patients with recurrent disease. Methods From January 1, 2008 to July 1, 2012, we retrospectively collected all patients’ records with SCCHN diagnosed as metastatic. Patients, disease, treatment and its results were analyzed. Survival was calculated using the Kaplan–Meier method. Results Of the 749 new patients treated for SCCHN in our institution, 16 (2.1%) were metastatic at diagnosis, of whom five had cytological results to prove it. Six patients died before treatment or had palliative care and ten received initial chemotherapy and then surgery and/or radiotherapy according to the primary response. Four patients treated with first-line chemotherapy with docetaxel-5FU-cisplatin (TPF) showed a complete response of metastatic lesions allowing locoregional treatment. The overall survival at 1 year and 3 years was 50% and 24%, respectively. The median survival was 7 months (1–72 months). Seven patients (43.7%) had a higher survival at 12 months, including five (31.5%) who are still alive without recurrence with a mean follow-up of 30 months. There was a significant difference in overall survival (P<0.01) between patients who had chemotherapy with TPF versus other therapeutic protocols. The median survival of patients with lung metastases only was 15 months (1–72 months), significantly higher than that of patients with liver and/or bone localizations, which was 2 months (1–9 months). Conclusion Patients with metastatic SCCHN treated by TPF followed by multimodal treatment could achieve long survival.

Safety and benefit of using a virtual bolus during treatment planning for breast cancer treated with arc therapy

Abstract Purpose This study evaluates the benefit of a virtual bolus method for volumetric modulated arc therapy (VMAT) plan optimization to compensate breast modifications that may occur during breast treatment. Methods Ten files were replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25 fractions. The planning process used a virtual bolus for the first optimization, then the monitors units were reoptimized without bolus, after fixing the segments shapes. Structures and treatment planning were exported on a second scanner (CT) performed during treatment as a consequence to modifications in patients anatomy. The comparative end‐point was clinical target volumes coverage. The first analysis compared the VMAT plans made using the virtual bolus method (VB‐VMAT) to the plans without using it (NoVB‐VMAT) on the first simulation CT. Then, the same analysis was performed on the second CT. Finally, the level of degradation of target volume coverage between the two CT using VB‐VMAT was compared to results using a standard technique of forward‐planned multisegment technique (Tan‐IMRT). Results Using a virtual bolus for VMAT does not degrade dosimetric results on the first CT. No significant result in favor of the NoVB‐VMAT plans was noted. The VB‐VMAT method led to significant better dose distribution on a second CT with modified anatomies compared to NoVB‐VMAT. The clinical target volumes coverage by 95% (V95%) of the prescribed dose was 98.9% [96.1–99.6] on the second CT for VB‐VMAT compared to 92.6% [85.2–97.7] for NoVB‐VMAT (P = 0.0002). The degradation of the target volume coverage for VB‐VMAT is not worse than for Tan‐IMRT: the median differential of V95% between the two CT was 0.9% for VMAT and 0.7% for Tan‐IMRT (P = 1). Conclusion This study confirms the safety and benefit of using a virtual bolus during the VMAT planning process to compensate potential breast shape modifications.