Radiotherapy alone for Merkel cell carcinoma: a comparative and retrospective study of 25 patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin cancer. Cumulative data from retrospective series support the notion that benefits are obtained by both wide excision and adjuvant radiation therapy. However, surgery may be difficult to perform with tumors located in the head and neck region and/or in elderly patients with comorbidities incompatible with general anesthesia. OBJECTIVE: We assessed the benefit of treating MCC exclusively with radiation when conventional treatment (surgery followed by radiotherapy) is not possible. METHODS: A total of 25 patients with primary MCC were treated at our institution exclusively with radiotherapy. Because there is no consensus about this specific approach, we compared the recurrence rate of the 25 patients receiving radiotherapy alone with that of 25 patients who received conventional treatment at our institution. RESULTS: The median follow-up periods were 3 years (range: 5 months-11 years) for the group receiving only radiotherapy (group 1) and 9 years (range: 12 months-16 years) for the conventional therapy group (group 2). No local relapses were observed, but two locoregional relapses were observed in group 1, and 4 in group 2. No statistical differences were found in overall and disease-free survival between the two groups of patients. LIMITATIONS: The limitation of this study is its retrospective nature. CONCLUSIONS: This study confirms the results of our previous research demonstrating that it is possible to treat inoperable MCC exclusively with radiotherapy to obtain an outcome similar to that which is achievable with conventional treatment.

Atypical and malignant meningioma: outcome and prognostic factors in 119 irradiated patients. A multicenter, retrospective study of the Rare Cancer Network.

PURPOSE: To retrospectively analyze and assess the outcomes and prognostic factors in a large number of patients with atypical and malignant meningiomas. METHODS AND MATERIALS: Ten academic medical centers participating in this Rare Cancer Network contributed 119 cases of patients with atypical or malignant meningiomas treated with external beam radiotherapy (EBRT) after surgery or for recurrence. Eligibility criteria were histologically proven atypical or anaplastic (malignant) meningioma (World Health Organization Grade 2 and 3) treated with fractionated EBRT after initial resection or for recurrence, and age >18 years. Sex ratio (male/female) was 1.3, and mean (+/-SD) age was 57.6 +/- 12 years. Surgery was macroscopically complete (Simpson Grades 1-3) in 71% of patients; histology was atypical and malignant in 69% and 31%, respectively. Mean dose of EBRT was 54.6 +/- 5.1 Gy (range, 40-66 Gy). Median follow-up was 4.1 years. RESULTS: The 5- and 10-year actuarial overall survival rates were 65% and 51%, respectively, and were significantly influenced by age >60 years (p = 0.005), Karnofsky performance status (KPS) (p = 0.01), and high mitotic rate (p = 0.047) on univariate analysis. On multivariate analysis age >60 years (p = 0.001) and high mitotic rate (p = 0.02) remained significant adverse prognostic factors. The 5- and 10-year disease-free survival rates were 58% and 48%, respectively, and were significantly influenced by KPS (p = 0.04) and high mitotic rate (p = 0.003) on univariate analysis. On multivariate analysis only high mitotic rate (p = 0.003) remained a significant prognostic factor. CONCLUSIONS: In this multicenter retrospective study, age, KPS, and mitotic rate influenced outcome. Multicenter prospective studies are necessary to clarify the management and prognostic factors of such a rare disease.

External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma.

PURPOSE: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. PATIENTS AND METHODS: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy (+/-4.83) and 8.82 Gy (+/-3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. RESULTS: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). CONCLUSION: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.

Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance.

EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab is a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling pathways and induce EGFR internalization. This study aims to investigate the role of the EGFR signaling pathway and EGFR internalization in a cetuximab-resistant cell line and to propose a new therapeutic strategy to optimize treatment of HNSCC. The HNSCC cell line, CAL33 was sensitive to gefitinib but resistant to cetuximab. Cetuximab induces an unexpected EGFR phosphorylation in CAL33 cells similarly to EGF but this EGFR activation does not trigger EGFR internalization/degradation, the process currently implicated in the response to cetuximab. Cetuximab inhibits ERK and AKT phosphorylation in cetuximab-sensitive A431 cells, whereas the level of AKT phosphorylation is unmodified in cetuximab-resistant cells. Interestingly, CAL33 cells harbor a PIK3CA mutation. The treatment of CAL33 cells with PI3K inhibitor and cetuximab restores the inhibition of AKT phosphorylation and induces growth inhibition. Our results indicate that EGFR internalization is impaired by cetuximab treatment in CAL33 cells and that the AKT pathway is a central element in cetuximab resistance. The combination of cetuximab with a PI3K inhibitor could be a good therapeutic option in PIK3CA-mutated HNSCC.