Volumetric Modulated Arc Therapy Craniospinal Irradiation Utilizing a Vertebral Body Sparing Approach: An Alternative Approach to Improve Access and Minimize Toxicity.

Introduction: Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral body sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. A recent phase II trial has shown efficacy of proton-based CSI to treat non-small cell lung and breast cancer with LMD. We hypothesize that VBS CSI using volumetric modulated arc therapy (VMAT) could also effectively reduce dose to vertebral bodies and surrounding organs at risk, minimizing toxicity for adult patients with LMD and comparing favorably to proton-based CSI. Methods and Materials: Consecutive patients with LMD received VMAT VBS CSI, 30 Gy in 10 fractions, as a part of a prospective registry. Full VMAT arcs for the brain fields matched to 2 spine isocenters for the upper and lower spine were created using limited posterior arcs. To further decrease the vertebral body dose, an avoid entry and exit contour was created. Acute toxicity data were collected using Common Terminology Criteria for Adverse Events v5. Results: Ten adult patients were treated in this cohort. One patient experienced grade 2 neutropenia with the remaining 9 experiencing grade 1 hematologic toxicity. Three patients experienced grade 2 gastrointestinal toxicity with the remaining 7 experiencing grade 1 nausea. No patient experienced grade 3+ toxicities in this cohort. One patient experienced a 5-day delay in systemic therapy initiation due to neutropenia; otherwise, all patients planned for systemic therapy started without delay. Conclusions: In this study, VMAT VBS CSI led to acceptable toxicity compared with patients treated with proton CSI on a phase 2 clinical trial. Given its promising early results, future prospective evaluation of the technique is warranted.

Multimodal intensification regimens for advanced, resectable, previously untreated squamous cell cancer of the oral cavity, oropharynx, or hypopharynx: a 12-year experience.

OBJECTIVE: To determine the feasibility of, compliance with, and long-term survival with intensification treatment regimens for patients with advanced, resectable, previously untreated head and neck squamous cell carcinoma. DESIGN: Prospective phase 2 clinical trial (3 similar, consecutively evolved trials). SETTING: Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University. PATIENTS: One hundred twenty-three patients (median age, 60 years; range, 30-78 years) with previously untreated, resectable, advanced squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx. INTERVENTIONS: Perioperative cisplatin chemoradiotherapy, surgical resection with intraoperative radiotherapy, and postoperative paclitaxel and cisplatin chemoradiotherapy. MAIN OUTCOME MEASURES: The feasibility, compliance, and long-term survival associated with the 3 intensification regimens. RESULTS: Compliance with all 3 intensification regimens averaged 61% (75/123). Patient-directed noncompliance occurred in 16 patients (13%). The average locoregional (112/123, 91%) and systemic (106/123, 86%) disease control rates were excellent. Overall long-term disease-specific survival was 73%. Median time at risk was 62.5 months (range, 1 day to 100.4 months). CONCLUSIONS: The intensification regimens result in excellent disease control rates and long-term survival in this particular patient population. Future evolution of these regimens will include some modifications to further decrease toxic effects followed by phase 2 multi-institutional trials to determine whether the single-institutional experience can be duplicated. The results of these studies will determine whether phase 3 trials can be proposed.

Long-term results of a multimodal intensification regimen for previously untreated advanced resectable squamous cell cancer of the oral cavity, oropharynx, or hypopharynx.

BACKGROUND: Long-term disease control of an intensified treatment regimen for previously untreated stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed. METHODS: Forty-three patients with previously untreated, advanced stage, resectable squamous carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective phase II institutional clinical trial at a tertiary care National Cancer Institute-designated comprehensive cancer center. It includes preoperative accelerated hyperfractionated radiotherapy with concurrent cisplatin followed immediately by surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent once-daily radiotherapy beginning on day 28 after surgery. RESULTS: Forty-three patients enrolled in the study. Protocol compliance was 53%. The range of time at risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and systemic (91%) disease control rates were excellent. Overall long-term survival was 79%. CONCLUSIONS: An intensive treatment regimen that improves compliance and long-term disease control is clearly feasible for this patient population.

Multimodal intensification therapy for previously untreated advanced resectable squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx.

BACKGROUND: An intensified treatment regimen for previously untreated Stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed to assess disease control, patient compliance, and toxicity. METHODS: Forty three patients with previously untreated, advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective Phase II institutional clinical trial at a tertiary care comprehensive cancer center. This regimen was a continuum of multimodal treatment in a contracted time interval. It included preoperative slightly accelerated hyperfractionated radiotherapy with concurrent cisplatin, followed immediately with surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel (beginning on Day 6 after surgery), two additional cisplatin cycles, and concurrent once daily radiotherapy beginning on Day 28 after surgery. RESULTS: The current trial was designed to reduce the toxicity of the systemic therapy while maintaining or improving locoregional/distant disease control and patient compliance. There were 43 patients enrolled, and the range of time at risk was 2.6 to 24.7 months (median, 14.6 months). Of the 43 registered patients, 43 were evaluable. The locoregional (100%) and systemic (93%) disease control rates were excellent, with low rates of patient noncompliance (21%) and reduced levels of toxicity. CONCLUSIONS: An intensive treatment regimen that improves disease control and treatment compliance is clearly feasible for this patient population. Future plans include modifications to continue to reduce toxicity and expansion to a multi-center Phase II trial to determine if the single institutional results can be duplicated.