Anthony J. Cmelak

PURPOSE: E2399 showed higher response rates and survival for human papillomavirus–associated (HPV+) oropharynx (OP) cancer than for HPV-negative OP cancer. E1308, a follow-up prospective phase II trial in patients with HPV+ OP, hypothesized that reduced radiation (54Gy) may achieve comparable tumor control in patients who achieve a complete clinical response to induction chemotherapy and that toxicities would be ameliorated. METHODS: Acute and late toxicities for both E2399 and E1308 were recorded prospectively using a battery of patient-reported outcomes (PROs). General quality of life (QOL) PROs used on E1308 included KATZ-Index of Independence in Activities of Daily Living (ADL), Brief Fatigue Index, Instrumental Activities of Daily Living, Baecke, and Community Health Activities Model Program for Seniors Physical Activity Questionnaire; head and neck cancer-specific PROs were Functional Assessment of Cancer Therapy – Head & Neck (FACT-HN) and the Vanderbilt Head and Neck Symptom Survey Version 2 (VHNSSv2). E2399 used the FACT-HN. Toxicities were correlated with both intensity-modulated radiation therapy (IMRT) dose (69.3Gy v 54Gy) used on E1308 and with the IMRT technique used on E1308 versus three-dimensional conformal radiation therapy (3DRT) used on E2399. RESULTS: Radiation dose reduction resulted in significantly decreased toxicities as detected with VHNNSv2 and FACT-HN PRO instruments. The VHNSSv2 showed that late symptoms are significantly reduced by lowering IMRT to 54Gy: eating solids ( P = .011), liquids ( P = .004), voice changes ( P = .026), dry mouth ( P = .02), and neck and shoulder movements ( P = .03). FACT-HN showed less difficulty in eating solids at 6 months ( P = .054), as well as voice strength and quality ( P = .038). Comparing IMRT 69.3Gy with 3DRT 70Gy, the FACT-HN showed eating solids at 12 months ( P = .0067) and greater ability to eat foods the patient liked ( P = .0103) favored IMRT. CONCLUSION: Both radiation dose reduction and using IMRT decreased toxicities in a variety of QOL PROs. Head and neck–specific PROs are more sensitive than general PROs. Interinstrument corroboration validates the FACT-HN and VHNSSv2 utility for treatment deintensification evaluation.

Osteoblastoma is a rare benign osteoid-producing tumor, accounting for about 1% of all primary bone neoplasms

Background We conducted a correlative study for E2399, a function preservation trial for resectable locally advanced oropharynx and larynx cancer, to prospectively assess effects of chemoradiation (CCR) on quality of life (QOL), swallowing and voice. We correlated the results of swallow assessments done via questionnaires and objective assessments. Methods The Functional Assessment of Cancer-HN (FACT-HN), the Performance Status Scale – Head and Neck (PSS-HN), swallow assessments (including modified barium swallow studies), and voice assessments (Voice Handicap Index and the Voice Disability Assessment) were conducted at baseline and periodically post-treatment for 2 years. Results Baseline QOL and swallowing function predicted overall survival. Patients experienced a marked decrease in QOL, swallowing, and speech post CCR although the decrease in vocal function was modest. Function and QOL returned towards baseline in the majority of patients by 12 months post treatment. Less than 10% of patients had severe dysphagia and were PEG dependent at 12 months post treatment. There was a high degree of correlation between the FACT-HN and PSS-HN swallow items. Statistically significant correlations were found between subjective and objective measures of swallow function. Conclusions Patients experience marked loss in swallowing function post CCR which returned to baseline in the majority of patients. The correlations between the FCM and self-report swallow items on the PSS and FACT-HN appear to be sufficiently strong to justify their use as a surrogate marker for swallowing disability in large therapeutic trials.

We conducted a correlative study for E2399, a function preservation trial for resectable locally advanced oropharynx and larynx cancer, to prospectively assess effects of chemoradiation (CCR) on quality of life (QOL), swallowing and voice. We correlated the results of swallow assessments done via questionnaires and objective assessments by modified barium swallow (MBS). The Functional Assessment of Cancer-HN (FACT-HN), the Performance Status Scale – Head and Neck (PSS-HN), swallow assessments (including modified barium swallow studies), and voice assessments: Voice Handicap Index (VHI), the Voice Disability Assessment (VDA), and American Speech-Language Hearing Association’s Functional Communication Measure (FCM) were conducted at baseline and periodically post-treatment for 2 years. Baseline QOL and swallowing function predicted overall survival. Patients experienced a marked decrease in QOL, swallowing, and speech post CCR although the decrease in vocal function was modest. Function and QOL returned towards baseline in the majority of patients by 12 months post treatment. Less than 10% of patients had severe dysphagia and were PEG dependent at 12 months post treatment. There was a high degree of correlation between the FACT-HN and PSS-HN swallow items. Statistically significant correlations were found between subjective and objective measures of swallow function. Patients experience marked loss in swallowing function post CCR which returned to baseline in the majority of patients. The correlations between the FCM and self-report swallow items on the PSS and FACT-HN appear to be sufficiently strong to justify their use as a surrogate marker for swallowing disability in large therapeutic trials.

Objective: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: We evaluated 54 patients with vestibular schwannoma before and after SRS. Intervention(s): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist. Main Outcome Measure(s): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland–Altman method evaluated reproducibility. Linear regression evaluated predictors of model error. Results: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS. Conclusions: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.

Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife (R) or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% - 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.

Objective: To analyze local control (LC) and toxicity rates between stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) in relation to reported surgical rates in the treatment of paragangliomas (PG) in the upfront, adjuvant, and salvage settings, and to explore factors affecting tumor size reduction, toxicity rates, and symptom control. Study Design: Retrospective cohort analysis. Setting: Tertiary referral center. Patients and Interventions: Thirty patients treated with either linear accelerator-based SRS or IMRT in the definitive, planned adjuvant, or unplanned salvage postsurgery settings. Main Outcome Measures: Local control, toxicities, symptom control, tumor size reduction, and factors affecting each. Results: Median follow-up was 4.16 years. LC rates were 100%. Acute grade >3 toxicity rate was 6.7%, 86.7% of tumors had a reduction in volume, and 76.7% of patients had improvement in at least one tumor-induced symptom by last follow-up. Larger tumor size at presentation and longer time to last follow-up were significantly associated with greater tumor size reduction on multivariate analysis. Conclusions: SRS and IMRT are safe and effective treatment for PG with high efficacy and low morbidity rates in the upfront, planned adjuvant, and unplanned salvage settings.