Influence of Residual Tumor Volume and Radiation Dose Coverage in Outcomes for Clival Chordoma.

PURPOSE: The purpose of this study was to evaluate factors associated with tumor control in clival chordomas. METHODS AND MATERIALS: A retrospective review of 39 patients treated with surgery and proton therapy for clival chordomas between 2004 and 2014 was performed. The median prescribed dose was 77.4 Gy (relative biological effectiveness [RBE]); range was 70.2-79.2 Gy (RBE). Minimum and median doses to gross tumor volume (GTV), radiation dose received by 1 cm(3) of GTV (D1cm(3)), and the equivalent uniform dose were calculated. Receiver operating characteristics curves evaluated the predictive sensitivity and specificity for local failure of potential cutpoint values for GTV and D1cm(3). RESULTS: After a median follow-up of 51 months, the 5-year estimate of local control (LC) was 69.6% (95% confidence interval [CI] 50.0%-89.2%), and overall survival (OS) was 81.4% (95% CI: 65.3%-97.5%). Tumor histology, GTV at the time of radiation, and prescribed radiation dose were significantly associated with local control on multivariate analysis, whereas D1cm(3) was associated with overall survival. Compared to those patients whose conditions remained controlled, patients experiencing tumor failure had statistically significant larger GTVs and lower D1cm(3), and prescribed and median doses to GTV. A subset of 21 patients with GTV of ≤20 cm(3) and D1cm(3) of >67 Gy (RBE) had a median follow-up of 47 months. The 5-year estimate of local control in this subset was 81.1% (95% CI: 61.7%-100%; P=.004, overall comparison by GTV ≤20 cm(3) stratified by D1cm(3)). A D1cm(3) of 74.5 Gy (RBE) had 80% sensitivity for local control and 60% specificity, whereas a GTV of 9.3 cm(3) had 80% sensitivity for local control and 66.7% specificity. CONCLUSIONS: Local control of clival chordomas was associated with both smaller size of residual tumor and more complete high-dose coverage of residual tumor. Multidisciplinary care should seek maximal safe surgical resection, particularly to facilitate delivery of high-dose radiation therapy in proximity to critical structures. A D1cm(3) ≥74.5 Gy (RBE) represents a proposed treatment planning objective.

Proton therapy for head and neck adenoid cystic carcinoma: initial clinical outcomes.

BACKGROUND: The purpose of this study was to report outcomes of proton therapy in head and neck adenoid cystic carcinoma. METHODS: We conducted a retrospective analysis of 26 patients treated between 2004 and 2012. Twenty patients (77%) had base of skull involvement; 19 (73%) were treated for initial disease and 7 (27%) for recurrent disease. Twenty patients were treated postoperatively, 6 after biopsy alone and 24 had positive margins or gross residual disease.Median dose delivered was 72 Gy (relative biological effectiveness[RBE]). RESULTS: Median follow-up was 25 months (range, 7­50 months). The 2-year overall survival was 93% for initial disease course and 57% for recurrent disease (p5.19). The 2-year local control was 95% for initial disease and 86% for recurrent disease (p5.48). The 2-year distant metastatic rate was 25%. Late toxicity of grade 0 or 1 was seen in 17 patients, grade 2 in 5, grade 3 in 2, grade 4 in 1, and grade 5 in 1. CONCLUSION: Initial outcomes of proton therapy are encouraging. Longer follow-up is required.

Dose-volume relationships associated with temporal lobe radiation necrosis after skull base proton beam therapy.

PURPOSE: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. METHODS AND MATERIALS: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose-volume parameters associated with radiation necrosis. RESULTS: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose-volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm(3), or aV70 > 1.7 cm(3). CONCLUSIONS: Dose-volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm(3) or aV70 > 1.7 cm(3). Treatment planning goals should include constraints on the volume of temporal lobes receiving higher dose. The EC50 model provides suggested dose-volume temporal lobe constraints for conventionally fractionated high-dose skull base radiation therapy.

Prognostic significance of basaloid squamous cell carcinoma in head and neck cancer.

IMPORTANCE: Head and neck basaloid squamous cell carcinoma (BSCC) has been considered a more aggressive variant of squamous cell carcinoma (SCC) with a poorer prognosis, although case-control studies have reached conflicting conclusions. OBJECTIVE: To examine the prognostic significance of head and neck BSCC on overall survival in a large population-based registry. DESIGN AND SETTING: Retrospective data review of a population-based registry from the Surveillance, Epidemiology, and End Results database. PARTICIPANTS: Individual case data for 34,196 patients treated between January 2004 and December 2009 with head and neck primary SCC (n = 33,554) and BSCC (n = 642) of the oral cavity, oropharyx, larynx, or hypopharynx. Patients with metastatic disease, incomplete staging information, and those who did not receive surgery or radiation were excluded. INTERVENTIONS: Patients had been treated with surgery, radiation, or both. MAIN OUTCOMES AND MEASURES: Distribution of patient characteristics between patients of each histology. Hazard ratios, 3-year overall survival, subgroup, and multivariate analysis of patient and treatment characteristics were investigated. RESULTS: Across each cohort, patients with BSCC more often had high-grade tumors and treatment with lymph node dissection. Multivariate analysis found that group stage, T stage, N stage, size, lymph node dissection, and age statistically significantly influenced overall survival. In multivariate analysis, the hazard ratio for death for patients with BSCC in the oral cavity and larynx and hypopharynx was not statistically significantly different from that for SCC. In the oropharynx, the hazard ratio for death for BSCC histology compared with SCC histology was 0.73 (P = .03). CONCLUSIONS AND RELEVANCE: Compared with SCC, BSCC is not an independent adverse prognostic factor for patients with head and neck cancer. The Surveillance, Epidemiology, and End Results analysis has limits, including lack of information regarding chemotherapy, but after controlling for disease and treatment variables, including neck dissection and radiotherapy, BSCC histology did not have an independent adverse prognostic effect on overall survival. The reported association between human papillomavirus and BSCC histology may explain the lower hazard ratio for death in patients with oropharynx BSCC.