Hedgehog Inhibitor Induction with Addition of Concurrent Superficial Radiotherapy in Patients with Locally Advanced Basal Cell Carcinoma: A Case Series.

BACKGROUND: Locally advanced basal cell cancer is a rare and challenging clinical problem. Historically, these patients were treated with aggressive surgery or radiotherapy. Most sporadic basal cell carcinomas have somatic mutations in the hedgehog pathway. Oral hedgehog inhibitors induce rapid and often complete clinical responses in locally advanced basal cell tumors. Unfortunately, these responses are usually transient. We hypothesized that treatment failure represents persistence of drug resistant cells that could be eradicated by addition of localized radiotherapy. MATERIALS AND METHODS: We performed a retrospective review of our patients with locally advanced basal cell cancer treated with sonidegib or vismodegib induction therapy who were treated with added superficial radiotherapy at the time of maximal response. RESULTS: Twelve patients met inclusion criteria. All patients achieved a complete response following hedgehog inhibitor therapy with addition of radiotherapy. Progression-free survival at 40 months was 89%, with a median follow-up of 40 months. Relapses occurred in only 2 of 12 patients (16.6%). Nine patients experienced grade I-II toxicity from hedgehog inhibitor induction therapy (taste changes [3], weight loss [3], muscle cramps [3]). Eight patients experienced mild radiotherapy-induced skin toxicity during concurrent therapy. No patients had to discontinue treatment. CONCLUSION: Induction therapy with hedgehog inhibitors followed by addition of concurrent radiation therapy resulted in an extremely high clinical response rate with relatively minor and reversible toxicity. This gave a high rate of progression-free survival and a low disease-specific progression rate. Further prospective evaluation of this treatment approach is needed to confirm the apparent clinical activity. IMPLICATIONS FOR PRACTICE: Locally advanced basal cell cancers are challenging to treat. Previously, aggressive surgical resection or radiotherapy represented the best treatment options. Most basal cell cancers have somatic mutations in the hedgehog pathway. Oral inhibitors of this pathway produce rapid but transient clinical responses. This study reports 12 patients treated with hedgehog inhibitor induction therapy to near-maximal response. Addition of concurrent involved field radiotherapy resulted in a very high complete response rate with minimal toxicity. There was prolonged progression-free survival in 90% of patients. This study identified a novel treatment approach for patients with advanced basal cell carcinoma.

Effectiveness and toxicity of cetuximab with concurrent RT in locally advanced cutaneous squamous cell skin cancer: a case series.

BACKGROUND: Treatment for locally advanced cutaneous squamous cell cancers (laCSCC) remains poorly defined. Most laCSCC tumors express high levels of epidermal growth factor receptors (EGFR). Cetuximab has activity in other EGFR expressing cancers and enhances the effectiveness of radiotherapy. METHODS: A retrospective review of institutional data identified eighteen patients with laCSCC treated with cetuximab induction and concurrent radiotherapy. The loading dose of cetuximab was 400 mg/m² IV. Subsequent weekly doses of 250 mg/m² IV were infused throughout the period of radiation. The treatment doses ranged from 4500-7000 cGy, with a dose fraction of 200-250 cGy. RESULTS: The objective response rate was 83.2% with 55.5% complete responses and 27.7% partial responses. Median progression-free survival was 21.6 months. Progression-free survival was 61% at 1 year and 40% at 2 years. With longer follow-up, some patients developed a local recurrence (16.7%), distant metastases (11.1%) or a second primary cancer (16.3%). Cetuximab was well tolerated, with 68.4% patients experienced only mild acneiform skin rash or fatigue (Grade 1 or 2). Radiotherapy produced expected side effects (skin erythema, moist desquamation, mucositis). DISCUSSION: Cetuximab plus radiotherapy represents an active and tolerable treatment option for laCSCC, including patients with contraindications for checkpoint inhibitor therapy.

Assessment of quality of life and oral function of patients participating in a phase II study of radioprotection of oral and pharyngeal mucosa by the prostaglandin E(1) analog misoprostol (RTOG 96-07).

PURPOSE: The oral complications associated with radiotherapy to the head and neck are a significant dose-limiting factor. The goals of this study were to determine whether oropharyngeal rinsing and ingestion of misoprostol protect mucous membranes from the acute effects of irradiation, and to evaluate the quality-of-life (QOL) outcomes of patients receiving misoprostol. We report the results of the QOL outcomes of patients in this study. METHODS AND MATERIALS: A total of 33 patients with resected or intact cancer of the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were registered to receive postoperative radiotherapy plus misoprostol or primary radiotherapy plus misoprostol. All patients were scheduled to receive 60-70 Gy at 2 Gy/d within 6-7 weeks. QOL and function were evaluated. RESULTS: A decrease in the QOL and function occurred in all areas covered by the questionnaire at the 6-week interval. This decrease was significant for eating, saliva, taste, and mucous. Of these significant factors, taste, saliva, and mucous consistency had not resolved by 12 weeks. CONCLUSION: Increased understanding of the impact of treatment on QOL and symptoms will formulate the rational design of toxicity interventions and enhance the multidisciplinary care of head-and-neck patients.