Parag Sanghvi

Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases

The treatment of metastatic brain lesions remains a central challenge in oncology. Because most chemotherapeutic agents do not effectively cross the blood–brain barrier, it is widely accepted that radiation remains the primary modality of treatment. The mode by which radiation should be delivered has, however, become a source of intense controversy in recent years. The controversy involves whether patients with a limited number of brain metastases should undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) delivered only to the radiographically visible tumours. Survival is comparable for patients treated with either modality. Instead, the controversy involves the neurocognitive function (NCF) of radiating cerebrum that appeared radiographically normal relative to effects of the growth from micro-metastatic foci. A fundamental question in this debate involves quantifying the effect of WBRT in patients with cerebral metastasis. To disentangle the effects of WBRT on neurocognition from the effects inherent to the underlying disease, we analysed the results from randomised controlled studies of prophylactic cranial irradiation in oncology patients as well as studies where patients with limited cerebral metastasis were randomised to SRS versus SRS+WBRT. In aggregate, these results suggest deleterious effects of WBRT in select neurocognitive domains. However, there are insufficient data to resolve the controversy of upfront WBRT versus SRS in the management of patients with limited cerebral metastases.

Aspiration pneumonia after concurrent chemoradiotherapy for head and neck cancer

Aspiration pneumonia represents an under‐reported complication of chemoradiotherapy in patient with head and neck cancer. The objective of the current study was to evaluate the incidence, risk factors, and mortality of aspiration pneumonia in a large cohort of patients with head and neck cancer who received concurrent chemoradiotherapy.

Clinical and cosmetic outcomes in patients treated with high-dose-rate electronic brachytherapy for nonmelanoma skin cancer

PURPOSE To retrospectively analyze clinical and cosmetic outcomes in patients treated for nonmelanoma skin cancer (NMSC) with high-dose-rate (HDR) electronic brachytherapy (EBT) using surface applicators. METHODS AND MATERIALS We identified 127 patients who had 154 NMSC lesions, 149 of which were basal cell carcinoma, treated with HDR EBT at our institution between July 2012 and March 2014. Lesions were treated to 40 Gy in 8 fractions. Local control, acute toxicity, late toxicity, and cosmetic outcomes were analyzed retrospectively. Acute and late toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Cosmetic outcomes were graded using a standard scale based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. RESULTS Median (range) follow-up from completion of treatment was 16.1 (3.4-34.8 months). The overall crude recurrence rate was 1.3% (n = 2). Grade 0 to 1 acute radiation dermatitis was observed in 52.6% of treated lesions (n = 81), grade 2 in 34.4% (n = 53), and grade 3 in 13.0% (n = 20). No acute toxicity greater than grade 3 was observed and all acute toxic events resolved after treatment. Grade 0 to 1 late toxicity was observed in 94.2% of cases (n = 145), and grade 2 in 5.8% (n = 9). No late toxicity greater than grade 2 was observed. Across the 152 controlled lesions, cosmetic results were excellent in 94.2% of treated lesions (n = 145), good in 3.3% (n = 5), fair in 0.7% (n = 1), and poor in 0.7% (n = 1). CONCLUSIONS HDR EBT confers promising local control, minimal toxicity, and excellent cosmesis in our institutional experience. It should be considered ideal for NMSC of the head and neck, particularly for basal cell carcinoma involving central facial locations where surgical cosmesis may be inferior.

Single-Isocenter Frameless Volumetric Modulated Arc Radiosurgery for Multiple Intracranial Metastases.

BACKGROUND Stereotactic radiosurgery (SRS) is a well-accepted treatment for patients with intracranial metastases, but outcomes with volumetric modulated arc radiosurgery (VMAR) are poorly described. OBJECTIVE To report our initial clinical experience applying a novel single-isocenter technique to frameless VMAR for simultaneous treatment of multiple intracranial metastases. METHODS We performed a retrospective analysis of 15 patients undergoing frameless VMAR for multiple intracranial metastases using a single, centrally located isocenter in the period 2009 and 2011. Of these, 3 patients were treated for progressive or recurrent intracranial disease. A total of 62 metastases (median, 3 per patient; range, 2-13) were treated to a median dose of 20 Gy (range, 15-30 Gy). Three patients were treated with fractionated SRS. Follow-up including clinical examination and magnetic resonance imaging (MRI) occurred every 3 months. RESULTS The median follow-up for all patients was 7.1 months (range, 1.1-24.3), with 11 patients (73.3%) followed until death. For the remaining 4 patients alive at the time of analysis, the median follow-up was 19.6 months (range, 9.2-24.3). Local control at 6 and 12 months was 91.7% (95% confidence interval [CI], 84.6%-100.0%) and 81.5% (95% CI, 67.9%-100.0%), respectively. Regional failure was observed in 9 patients (60.0%), and 7 patients (46.7%) received salvage therapy. Overall survival at 6 months was 60.0% (95% CI, 40.3%-88.2%). Grade 3 or higher treatment-related toxicity was not observed. The median total treatment time was 7.2 minutes (range, 2.8-13.2 minutes). CONCLUSION Single-isocenter, frameless VMAR for multiple intracranial metastases is a promising technique that may provide similar clinical outcomes compared with conventional radiosurgery.

PHASE I TRIAL OF INTRAVENOUS ONCOLYTIC VACCINIA VIRUS (GL-ONC1) WITH CISPLATIN AND RADIOTHERAPY IN PATIENTS WITH LOCOREGIONALLY ADVANCED HEAD AND NECK CARCINOMA.

Purpose: Preclinical models have shown that the effectiveness of GL-ONC1, a modified oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy to patients with primary, nonmetastatic head and neck cancer. Experimental Design: Patients with locoregionally advanced unresected, nonmetastatic carcinoma of the head/neck, excluding stage III–IVA p16-positive oropharyngeal cancers, were treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and chemotherapy. The primary aims were to define the MTD and dose-limiting toxicities, and to recommend a dose for phase II trials. Results: Between May 2012 and December 2014, 19 patients were enrolled. The most frequent adverse reactions included grade 1–2 rigors, fever, fatigue, and rash. Grade 3 adverse reactions included hypotension, mucositis, nausea, and vomiting. In 2 patients, the rash was confirmed as viral in origin by fluorescence imaging and viral plaque assay. In 4 patients, viral presence in tumor was confirmed on midtreatment biopsy by quantitative PCR. In 1 patient, live virus was confirmed in a tongue tumor 7 days after receiving the first dose of virus. The MTD was not reached. With median follow-up of 30 months, 1-year (2-year) progression-free survival and overall survival were 74.4% (64.1%) and 84.6% (69.2%), respectively. Conclusions: Delivery of GL-ONC1 is safe and feasible in patients with locoregionally advanced head/neck cancer undergoing standard chemoradiotherapy. A phase II study is warranted to further investigate this novel treatment strategy. Clin Cancer Res; 23(19); 5696–702. ©2017 AACR.

Exceptional Response to Nivolumab and Stereotactic Body Radiation Therapy (SBRT) in Neuroendocrine Cervical Carcinoma with High Tumor Mutational Burden: Management Considerations from the Center For Personalized Cancer Therapy at UC San Diego Moores Cancer Center

This article reports a patient with a rare metastatic, chemotherapy‐refractory neuroendocrine carcinoma who was treated with stereotactic body radiation therapy (SBRT) combined with anti‐programmed cell death protein 1 antibody. The novel treatment modality of SBRT combined with a checkpoint inhibitor is discussed, as well as the implications of molecular profiling and tumor mutational burden as potential predictors of response.

Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

PURPOSE Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administrations postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non-radiation oncology devices. METHODS AND MATERIALS MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ2 test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. RESULTS There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). CONCLUSIONS Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance, improved software design, and manufacturer-user training may help mitigate these events.

Five Simultaneous Primary Tumors in a Single Patient: A Case Report and Review of the Literature.

Multiple primary malignancies (MPMs) are present when a patient is diagnosed with more than one primary malignancy and when each tumor is histologically unrelated to the others. MPMs are considered synchronous when they present within 6 months of one another. Here, we report the case of a 57-year-old woman with a past medical history significant for melanoma in 1988, who presented in 2014 with 5 distinct tumors within 4 months: malignant melanoma of the right popliteal fossa, invasive lobular breast carcinoma, diffuse large B cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a giant cell tumor of tendon sheath/pigmented villonodular synovitis. We discuss her treatment and also present a brief review of the literature. The incidence of MPMs appears to be on the rise, which demands an interdisciplinary, multimodal, and personalized approach to care.

Fully automated, comprehensive knowledge-based planning for stereotactic radiosurgery: Preclinical validation through blinded physician review

PURPOSE As knowledge-based planning (KBP) attempts to augment and potentially supplant manual treatment planning, it is imperative to ensure any implementation maintains or improves overall plan quality in any disease site. The purpose of this study was to demonstrate the overall quality of KBP-driven automated stereotactic radiosurgery (SRS) treatment planning using blinded physician comparison and determine systematic factors predictive of physician plan preference to guide future KBP refinement. METHODS AND MATERIALS Automated noncoplanar volume modulated arc therapy KBP routines were developed for 199 plans across 3 clinical SRS scenarios: isolated lesions (isolated), lesions closely abutting (<3 cm) organs at risk (involved), and single-isocenter multiple metastases (multimet). Overall plan quality and preference were assessed via blinded review of the plans by two SRS physicians. Quantitative quality metrics were also compared to determine systematic differences in the treatment plans. Multiple parameters were investigated as predictors of KBP plan selection. RESULTS For the isolated, involved, and multimet scenarios, the KBP plans were considered to be superior or equivalent to clinical plans 86.7% (91/105), 81.1% (43/53), and 78.1% (32/41) of the time, respectively. All investigated quality metrics were equivalent or indicated more sparing for all KBP plans. The only nondosimetric predictor was planning target volume in the isolated (P = .02) and involved (P = .05) groups. The dosimetric predictors for the isolated group were gradient measure and heterogeneity index (both P < .01). In the multimet category, the only significant dosimetric predictor was interlesion dose (P = .01). CONCLUSIONS The fully automated KBP SRS plans were equivalent or superior to previously treated plans in 83.4% (166/199) of cases. In clinical implementation, geometric features found to be predictive of KBP performance can be used to identify plans where KBP results might benefit from further refinement, whereas dosimetric predictive features could be used to further refine KBP optimization priorities.

Nonmelanoma subungual malignancies: A case-based review of radiation therapy.

Subungual squamous cell carcinoma (SCC) is a rare malignant tumor that originates underneath the nail plate. Its etiology remains unknown, though trauma, chronic infections, immunosuppression, and radiation are possible predisposing factors.1 Here we report the first case of subungual SCC in a 69-year-old man associated with chronic Candida parapsilosis infection and review nonmelanoma subungual malignancies. An association between chronic esophageal candidiasis and esophageal SCC has been described.2 This study draws attention to a possible association between the skin microbiome and carcinogenesis. We describe current treatments and propose a promising alternative radiotherapeutic option.