Resensitization to Nivolumab after Intratumoral Chemotherapy in Recurrent Head and Neck Squamous Cell Cancer: A Report of 2 Cases.

The survival of patients with head and neck squamous cancer with locoregional recurrence is short if salvage surgery or radiation cannot be performed. Systemic chemotherapy based on platinum salts and cetuximab produces only partial and transient responses. Immune checkpoint inhibitors (i.e., nivolumab) lead to a low complete response rate of only about 10%, but in some cases the effects can be long-lasting. Intratumoral chemotherapy (ITC) has been proposed for patients with local recurrence of head and neck squamous cell carcinoma with an objective response rate of 27-50%. However, it often leads to peritumoral tissue necrosis, and the duration of local control is limited. Here, we present 2 patients with head and neck squamous cell cancer whose local recurrences were refractory to intravenous chemotherapy and nivolumab. ITC using nonnecrotizing molecules, associated with nivolumab, led to complete stable local and distant response. ITC seems to trigger tumor resensitization to previously ineffective immunotherapy. This combination deserves an evaluation in the framework of a prospective trial.

Impact of dosimetric parameters on local control for patients treated with three-dimensional pulsed dose-rate brachytherapy for cervical cancer.

PURPOSE: To investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT). METHODS AND MATERIALS: Within a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center. RESULTS: At 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control. CONCLUSIONS: This multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control.

Merkel cell carcinoma of skin-current controversies and recommendations.

The review covers the current recommendations for Merkel cell carcinoma (MCC), with detailed discussion of many controversies. The 2010 AJCC staging system is more in-line with other skin malignancies although more complicated to use. The changes in staging system over time make comparison of studies difficult. A wide excision with margins of 2.5-3 cm is generally recommended. Even for primary

Whole brain radiotherapy: prognostic factors and results of a radiation boost delivered through a conventional linear accelerator.

PURPOSE: Assess prognostic factors for overall survival and the potential benefit of a boost in patients treated with whole brain radiation therapy (WBRT). METHODS AND MATERIALS: From 2002 to 2006, a retrospective analysis was made from 250 unselected consecutive patients with secondary brain metastases from lung cancer, breast cancer and melanoma. Eighteen patients received surgery and were excluded from analysis. Four potential prognostic factors have been studied: primary tumor type, gender, number of metastases and improvement of neurological symptoms after radiation therapy. A subgroup analysis was performed to determine whether an additional boost could potentially improve outcome in patients who presented with less than three metastases, performance status <2, and no surgical resection of their metastasis. RESULTS: Average follow-up was 10.3 months. Median overall survival was 5.6 months and survival rates at 1 and 2 years were 22.7% and 10%, respectively. Age less than 65 (p<0.01), neurological improvement after WBRT (p<0.01), and presence of less than three metastases were significant factors for overall survival in multivariate analysis. When focusing on the selected subgroup (120 assessable patients), median overall survival was 4.0 months in patients with no radiation boost, versus 8.9 months in patients with radiation boost (p=0.0024). CONCLUSIONS: Survival and prognostic factors were similar to those found in the literature. Boost delivered after WBRT by a conventional particle accelerator could provide a benefit in selected patients, especially for centers that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment.

Management of Merkel cell carcinoma with emphasis on small primary tumors--a case series and review of the current literature.

A case series of Merkel cell carcinoma (MCC) is reported here and illustrates some of the current controversies in clinical management of this disease. From 1988-2007, 145 cases (74 men and 71 women) were analyzed. These were combined with other cases in the literature, hence the total number of patients was 433. Nodal metastases occurred clinically at presentation in 9/105 (9%) patients with primary tumor size <1 cm. The rate of nodal metastases is too high to obviate sentinel node biopsies even for these small tumors. For the 87 patients with intermediate tumor size (>1 - <2 cm), nodal metastases occurred clinically in 11 of 87 patients (13%) at presentation and 23 of 87 patients (26%) during follow-up. Distant metastases occurred in 20 of 87 patients (23%) only at follow-up. The risks of nodal and distant failures for tumors of intermediate sizes were sufficient to be classified as high-risk for clinical study purposes.

Multimodality management for 145 cases of Merkel cell carcinoma.

The results of the multimodality management of 145 cases of cutaneous Merkel cell carcinoma (MCC) are reported herein. Patient information was obtained from medical records of four Canadian institutions and one French institution. These data included ages, pathological stages, disease sites, histological and treatment details. Cause-specific survival (CSS), overall survival (OS) and disease-free survival (DFS) rates were analyzed by the log-rank and Kaplan-Meier methods. From 1988 to 2007, 145 cases were analyzed. There were 74 men and 71 women. Median age was 78 years (range 47-95.2). Median follow-up was 21.5 months (range 0.5-169.1). During the follow-up period, 37 local, 37 regional nodal and 15 distant recurrences were determined to be either solitary or multifocal sites of treatment failure. Relapsing patients were treated with multimodal treatments provided that their general state of health did not preclude this approach. Either initially and/or at relapse, 30 patients were treated with either multiagent (mostly etoposide with cisplatin or carboplatin) or single-agent chemotherapy, including irinotecan, taxotere and topotecan. In conclusion, recurrence should be treated with multimodalities. Our experience of long-term survivors after treatment of recurrence is encouraging.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results.

PURPOSE: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. METHODS AND MATERIALS: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. RESULTS: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). CONCLUSIONS: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.