Analysis of radiation therapy for the control of Merkel cell carcinoma of the head and neck based on 36 cases and a literature review.

Merkel cell carcinoma (MCC) is a rare and aggressive epidermal cancer. We conducted a retrospective study and literature review to investigate the impact that radiation therapy has on local, regional, and distant control as part of the oncologic management of MCC of the head and neck and to further elucidate the role of radiation therapy with regard to regional control for the clinically uninvolved neck. We reviewed all registered cases of head and neck MCC that had occurred at four institutions from January 1988 through December 2005. Treatment and outcomes data were collected on patients with American Joint Committee on Cancer stage I, II, and III tumors. Local, regional, and distant control rates were calculated by comparing variables with the Fisher exact test; Kaplan-Meier analysis was used to report actuarial control data. Stage I to III head and neck MCC was identified in 36 patients-22 men and 14 women, aged 43 to 97 years (mean: 71.6) at diagnosis. Patients with stage I and II tumors were combined into one group, and their data were compared with those of patients with stage III tumors. Twenty-six patients (72%) had clinical stage I/II disease and 10 patients (28%) had clinical stage III disease. Median follow-up was 41 months for the stage I/II group and 19 months for the stage III group. Based on examination at final follow-up visits, local recurrence was seen in 7 of the 36 patients (19%), for a local control rate of 81%. The 2-year actuarial local control rate for all stages of MCC was 83%; by treatment subgroup, the rates were 95% for those who had undergone radiation therapy to the primary site and 69% for those who had not-a statistically significant difference (p = 0.020). Based on information obtained at final follow-ups, 10 of the 36 patients (28%) experienced a regional recurrence, for a regional control rate of 72%. The 2-year actuarial regional control rate among all patients was 70%; by subgroup, rates were 82% for patients who had undergone regional node radiation therapy and 60% for those who had not-not a statistically significant difference (p = 0.225). Nine patients (25%) overall developed a distant metastasis, for a distant control rate of 75%. Salvage therapies included chemotherapy and/or radiation therapy to the metastatic site, but neither had any significant effect on survival. Regardless of treatment, the Kaplan-Meier survival curves leveled off at 30 months with 82% survival for the stage I/II group and at 19 months with 60% survival for the stage III group. We conclude that radiation therapy to the primary tumor site (either following resection or definitively) results in a local control rate of more than 90% in patients with head and neck MCC. We also found a trend toward improved regional control of the clinically negative neck with the addition of radiation therapy.

Proton beam radiation therapy for skull base adenoid cystic carcinoma.

OBJECTIVE: To determine the treatment outcome and prognostic factors in patients with adenoid cystic carcinoma of the skull base treated with proton beam radiation therapy. DESIGN: Retrospective analysis. SETTING: Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston. PATIENTS: From 1991 to 2002, 23 patients with newly diagnosed adenoid cystic carcinoma with skull base extension were treated with combined proton and photon radiotherapy. There was tumor involvement of the sphenoid sinus in 61% of patients (14), nasopharynx in 61% (14), clivus in 48% (11), and cavernous sinus in 74% (17). The extent of surgery was biopsy alone in 48% (11), partial resection in 39% (9), and gross total resection with positive margins in 13% (3). The median total dose to the primary site was 75.9 cobalt-gray equivalent. The median follow-up of all surviving patients was 64 months. MAIN OUTCOME MEASURES: Locoregional control and disease-free survival and overall survival rates. RESULTS: Tumors recurred locally in 2 patients at 33 and 68 months, respectively. No patients developed neck recurrence. Eight patients had distant metastasis as the first site of recurrence. The local control rate at 5 years was 93%. The rate of freedom from distant metastasis at 5 years was 62%. The disease-free and overall survival rates at 5 years were 56% and 77%, respectively. In multivariate analysis, significant adverse factors predictive for overall survival were change in vision at presentation (P = .02) and involvement of sphenoid sinus and clivus (P = .01). CONCLUSIONS: High-dose conformal proton beam radiation therapy results in a very encouraging local control rate in patients with adenoid cystic carcinoma of the skull base. Changes in vision at presentation and tumor involvement of the sphenoid sinus and clivus are important prognostic factors.

Visual outcome of accelerated fractionated radiation for advanced sinonasal malignancies employing photons/protons.

PURPOSE: To investigate the visual outcomes of patients with advanced sinonasal malignancies treated with proton/photon accelerated fractionated radiation (AFR). PATIENTS AND METHODS: Between 1991 and 2001, AFR was used to treat 36 patients with advanced stage primary (n=33) or recurrent (n=3) nasal or paranasal malignant tumors. Full ophthalmologic follow-up was documented. The median dose to the gross tumor volume (GTV) was 69.6 CGE (range 60.8-77). Visual complications were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) and the late effects of normal tissue (LENT) scoring systems. The median follow-up was 52.4 months (range 17-122.8). RESULTS: Thirteen patients developed late visual/ocular toxicity. Cataracts were LENT grade 1 and 3 in 2 patients and 1 patient, respectively. One LENT grade 1 vascular retinopathy and 1 optic neuropathy were also observed. Three and five patients presented with nasolacrimal duct stenosis (CTC grade 2, 2 patients; CTC grade 3, 1 patient) and dry-eye syndrome (CTC grade 1, 1 patient; CTC grade 2, 4 patients), respectively. The 3- and 5-year probability of LENT/CTC grade > or =2 visual toxicity were 15.8+/-6.7% and 20.7+/-7.8%, respectively. CONCLUSIONS: AFR for locally advanced nasal cavity and paranasal sinus tumors enables delivery of 70 CGE to the tumor with acceptable ophthalmologic complications.

Phase I trial and pharmacokinetics of escalating doses of paclitaxel and concurrent hyperfractionated radiotherapy with or without amifostine in patients with advanced head and neck carcinoma.

BACKGROUND: Amifostine was developed to protect normal tissues from radiation exposure. The current study was undertaken to determine whether amifostine would allow the delivery of greater numbers of weekly paclitaxel treatments with concomitant, hyperfractionated radiotherapy in patients with advanced head and neck carcinoma. METHODS: Patients received radiation therapy twice daily using 1.6-gray (Gy) fractions up to a total of 70.4 Gy over an elapsed time of 6.5 weeks. All patients received paclitaxel 60 mg/m(2) once weekly starting on Day 1. The number of doses of paclitaxel was escalated from three to a maximum of six in groups of three patients. For the patients who received amifostine, a dose of 400 mg/m(2) was given intravenously over 15 minutes on Days 1-5, 8, 29-33, and 36. Patients underwent surgery for persistent tumor after radiotherapy. The plasma pharmacokinetics of paclitaxel were characterized during treatment with the first weekly dose to determine the effect of concurrently administered amifostine. RESULTS: Thirty-six patients were evaluable for this study. In the absence of amifostine, a maximum of four doses of paclitaxel were tolerated in combination with the radiotherapy. With amifostine, up to five doses of paclitaxel could be given. Generally, the treatment resulted in Grade 2 and 3 stomatitis. Overall, 69% of patients had a complete remission, and 29% had a partial remission. Both progression-free survival and overall survival were 66% at 30 months. Amifostine had no effect on the pharmacokinetics of paclitaxel. CONCLUSIONS: The administration of amifostine allowed the authors to give an additional dose of paclitaxel to patients who were undergoing hyperfractionated radiotherapy for head and neck carcinoma. This treatment regimen resulted in a high frequency of complete remissions and an excellent progression-free survival pattern without compromising the plasma kinetics of paclitaxel.

A pilot trial of TAC (paclitaxel, doxorubicin, and carboplatin) chemotherapy with filgastrim (r-metHuG-CSF) support followed by radiotherapy in patients with "high-risk" endometrial cancer.

OBJECTIVES: To determine the toxicity, tolerability, and feasibility of delivering combination chemotherapy with subsequent radiation therapy to women with high-risk endometrial cancer and to evaluate the long-term bowel toxicity of this regimen. METHODS: The trial was approved by the Dana Farber/Partners Cancer Care (DFPCC) Institutional Review Board (IRB). Patients with stage 3 or stage 4 endometrial cancer or patients with high-risk histology and any stage disease were prospectively entered. Complete surgical staging and a normal gated blood pool scan were required prior to entry. Patients were treated with three cycles of paclitaxel (160 mg/m(2) ), doxorubicin (45 mg/m(2)) and carboplatin (AUC 5) (TAC) all on day 1 of a 21-day schedule as an outpatient with G-CSF support. At the conclusion of chemotherapy, patients received radiation therapy (4500 cGy to the whole pelvis) commencing within 35 days of the last cycle of chemotherapy. Paraaortic radiation and/or vaginal brachytherapy were allowed at the discretion of the treating radiation oncologist. RESULTS: Twenty patients were entered onto the trial from November 2000 through February 2003. Eighteen patients successfully completed the trial, and two patients came off trial during chemotherapy (both later completed planned radiation therapy). Patients were initially stage 1 (n = 3), stage 3 (n = 14), and stage 4 (n = 3). Papillary serous was the dominant histology with 13 patients. Chemotherapy was given on average within 32 days of surgery (range 11-63 days) and radiation was initiated on average within 14 weeks of surgery (range 10-18 weeks). Chemotherapy was well tolerated, with 57 total cycles delivered of a planned 60 cycles. Two patients required dose modification in two cycles (two patients in cycle 3 secondary to hematologic toxicity). No grade 3 or grade 4 neurotoxicity was reported. There were six episodes of grade 3 short-term toxicity with radiation therapy reported in a single patient. Late radiotherapy toxicity included bowel obstruction requiring laparotomy in two patients and grade 3 constipation in one patient. Late radiation toxicity data are still being collected as follow-up continues. CONCLUSIONS: The TAC chemotherapy regimen is well tolerated and three cycles were delivered successfully with G-CSF support without evidence of the neurotoxicity or cardiac toxicity reported with the cisplatin containing TAP regimen. Standard radiation was deliverable following TAC therapy without excessive toxicity. Further study of this regimen with subsequent radiation therapy is warranted in patients at risk for systemic and regional recurrence of their malignancy.