Success of Endoscopic Pharyngoesophageal Dilation after Head and Neck Cancer Treatment

To assess clinical success and safety of endoscopic pharyngoesophageal dilation after chemoradiation or radiation for head and neck cancer and to identify variables associated with dilation failure

Everolimus in Anaplastic Thyroid Cancer: A Case Series

Background: Anaplastic thyroid cancer (ATC) is a very aggressive disease and accounts for over 50% of thyroid-cancer related deaths. mTOR inhibition has shown anti-tumor activity in ATC. We report our experience treating patients with ATC with everolimus off-protocol.Methods: Patients with confirmed ATC and treated with everolimus at DFCI were identified and reviewed retrospectively. NexGen sequencing was performed, and radiologic responses were correlated with mutational profile.Results: Five patients were treated from 2013 to 2016. Three patients had a response, which included one patient who achieved a partial response for 27.9 months, and two patients who had stable disease for 3.7 and 5.9 months, respectively. Genomic analysis was available in two patients and revealed that the partial responder had mutations involving the PI3K/mTOR pathway.Conclusion: Everolimus has anti-tumor activity in ATC, and responses may correlate with mutations involving the PI3K/mTOR pathway. Further studies are warranted

Experimental evaluation of the accuracy of skin dose calculation for a

commercial treatment planning syste

Clinical experience of the importance of daily portal imaging for head

and neck IMRT treatment

Short‐term mortality risks among patients with oropharynx cancer by human papillomavirus status

Background There is substantial variation in head and neck cancer (HNC) mortality and competing mortality among patients with HNC. In this study, the authors characterize the causes and risks of short‐term mortality among patients with oropharynx cancer (OPC) and how these risks differ by human papillomavirus (HPV) status. Methods A custom Surveillance, Epidemiology, and End Results (SEER) data set with HPV status was used to identify 4930 patients with OPC who were diagnosed with nonmetastatic (M0) disease from 2013 to 2014, including 3560 (72.2%) HPV‐positive patients and 1370 HPV‐negative patients. Causes of death and cumulative incidence estimates for HNC‐specific mortality, competing mortality, second‐cancer mortality, and noncancer mortality were analyzed by HPV status. Risk factors for mortality events were determined using multivariable competing risk regression models. Results Compared with HPV‐negative patients, HPV‐positive patients had a lower risk of 2‐year cumulative incidence of all‐cause mortality (10.4% vs 33.3%; P < .0001) and a lower risk of both HNC‐specific mortality (4.8% vs 16.2%; P < .0001) and competing‐cause mortality (5.6% vs 16.8%; P < .0001). Second‐cancer mortality was the most common cause of non‐HNC mortality among HPV‐negative patients. Both second‐cancer mortality and noncancer mortality were significantly higher among patients who had HPV‐negative OPC (10.8% and 6.1%, respectively) compared with those who had HPV‐positive OPC (2.4% and 3.2%, respectively; both P < .0001). The median follow‐up was 11 months (range 1‐23 months) in this cohort with known HPV‐status. Conclusions Patients with HPV‐positive and HPV‐negative OPC have significantly different rates of both HNC mortality and competing mortality. HPV‐negative patients are at substantial risk of competing mortality, even within 2 years of cancer diagnosis. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings. Patients with human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal cancer have significantly different risks of both head and neck cancer–specific and competing mortality, and HPV‐negative patients are at a substantial risk of short‐term competing risks of mortality after diagnosis and treatment of head and neck cancer. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings

Effect of dental restorations and prostheses on radiotherapy dose distribution: a Monte Carlo study

Dental restorations, fixed prosthodontics, and implants affect dose distribution in head and neck radiation therapy due to the high atomic number of the materials utilized. The backscatter of electrons from metallic materials due to the impinging treatment x‐ray results in localized dose enhancements. These dose enhancements cause localized mucositis in patients who have dental work, a significant clinical complication. We investigated the backscatter effect of 23 configurations of dental work using the EGS4nrc Monte Carlo (MC) simulation system. We found that all‐metal fixed partial dentures caused the highest amount of dose enhancement – up to 33% – while amalgam restorations did not cause a significant amount. Restorations with a ceramic veneer caused up to 8% enhancement. Between 3 mm and 5 mm of water‐equivalent material almost completely absorbed the backscatter. MC simulations provide an accurate estimate of backscatter dose, and may provide patient‐specific estimates in future

Short‐term mortality risks among patients with oropharynx cancer by human papillomavirus status

Background There is substantial variation in head and neck cancer (HNC) mortality and competing mortality among patients with HNC. In this study, the authors characterize the causes and risks of short‐term mortality among patients with oropharynx cancer (OPC) and how these risks differ by human papillomavirus (HPV) status. Methods A custom Surveillance, Epidemiology, and End Results (SEER) data set with HPV status was used to identify 4930 patients with OPC who were diagnosed with nonmetastatic (M0) disease from 2013 to 2014, including 3560 (72.2%) HPV‐positive patients and 1370 HPV‐negative patients. Causes of death and cumulative incidence estimates for HNC‐specific mortality, competing mortality, second‐cancer mortality, and noncancer mortality were analyzed by HPV status. Risk factors for mortality events were determined using multivariable competing risk regression models. Results Compared with HPV‐negative patients, HPV‐positive patients had a lower risk of 2‐year cumulative incidence of all‐cause mortality (10.4% vs 33.3%; P < .0001) and a lower risk of both HNC‐specific mortality (4.8% vs 16.2%; P < .0001) and competing‐cause mortality (5.6% vs 16.8%; P < .0001). Second‐cancer mortality was the most common cause of non‐HNC mortality among HPV‐negative patients. Both second‐cancer mortality and noncancer mortality were significantly higher among patients who had HPV‐negative OPC (10.8% and 6.1%, respectively) compared with those who had HPV‐positive OPC (2.4% and 3.2%, respectively; both P < .0001). The median follow‐up was 11 months (range 1‐23 months) in this cohort with known HPV‐status. Conclusions Patients with HPV‐positive and HPV‐negative OPC have significantly different rates of both HNC mortality and competing mortality. HPV‐negative patients are at substantial risk of competing mortality, even within 2 years of cancer diagnosis. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings. Patients with human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal cancer have significantly different risks of both head and neck cancer–specific and competing mortality, and HPV‐negative patients are at a substantial risk of short‐term competing risks of mortality after diagnosis and treatment of head and neck cancer. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings

Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients

Background: Preclinical studies suggest a synergistic effect between radiation, immunotherapy and anti-angiogenic therapy, although the mechanisms are unclear. Angiogenic cytokines are known to affect the immune system, and their levels may be associated with response to immunotherapy. Here, we assess changes in circulating VEGF, as well as angiogenic cytokines angiopoietin-1 and -2 (Ang1, Ang2), and placental growth factor (PLGF) that occur during definitive chemo-radiotherapy in HNSCC patients. Methods: We prospectively collected blood samples from patients receiving definitive radiation with or without chemotherapy. Serum Ang1, Ang2, VEGF, and PLGF were measured via cytokine assays. Results: The majority of patients had advanced stage, node positive HPV-associated oropharyngeal cancer, and received radiation to a median dose of 70 Gy with concurrent cisplatin. Over the course of treatment, serum VEGF and Ang1 levels decreased in 20/24 (84 %, p < 0.0001) and 21/24 (88 %, p < 0.0001) patients, respectively, and Ang2 and PLGF levels increased in 20/24 (83 %, p < 0.0001) patients. Conclusions: We find significant changes in angiogenic cytokines in the majority of HNSCC patients over the course of chemoradiation. Decreases in VEGF caused by radiation may represent one mechanism of potential synergy with immunotherapy. Increases in Ang2 and PLGF are interesting given their link to tumor associated angiogenesis and poor prognosis. Additional studies are needed to explore synergies between anti-angiogenic treatments, immunotherapy, and chemoradiation in HNSCC. Electronic supplementary material The online version of this article (doi:10.1186/s40425-016-0138-9) contains supplementary material, which is available to authorized users

Incidence and Demographic Burden of HPV-Associated Oropharyngeal Head and Neck Cancers in the United States

Human papillomavirus (HPV)-positive oropharyngeal head and neck squamous cell carcinoma (OPSCC) is increasing in the United States. Current epidemiologic assessments of the national burden of HPV-positive OPSCC are needed. The Surveillance Epidemiology and End Results HPV Status Database included 12,017 patients with head and neck squamous cell carcinoma of pharyngeal subsites, including OPSCC and non-OPSCC head and neck cancer subsites (hypopharynx, nasopharynx, and "other pharynx"), diagnosed from 2013 to 2014. Age-adjusted incidence rates per 100,000 persons by HPV status were calculated. An exploratory Fine-Gray competing-risks regression determined the associations between HPV status and cancer-specific mortality. From 2013 to 2014, the U.S. incidence of HPV-positive OPSCC was 4.62 [95% confidence interval (CI), 4.51-4.73] versus 1.82 (95% CI, 1.75-1.89) per 100,000 persons for HPV-negative OPSCC. The incidence of HPV-positive versus negative non-OPSCC of the head and neck was 0.62 (95% CI, 0.58-0.66) versus 1.38 (95% CI, 1.32-1.44). White race (5.47) and male sex (8.00) had the highest incidences of HPV-positive OPSCC, with a unimodal age incidence distribution peaking at ages 60 to 64 years (27.23). HPV positivity was associated with lower cancer-specific mortality than HPV-negative disease for OPSCC [adjusted HR (aHR), 0.40; < 0.001], but not non-OPSCC (aHR, 1.08; = 0.81), = 0.002. The U.S. incidence of HPV-positive OPSCC was 4.62 per 100,000 persons. Most cases were found in white male patients younger than 65 years, where it represents the sixth most common incident nonskin cancer. The favorable prognosis associated with HPV appears to be limited to the oropharynx. This large population-based epidemiologic assessment of the U.S. population defines the incidence and demographic burden of HPV-positive OPSCC