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Purpose: European data suggest that 8-fraction stereotactic body radiation therapy (SBRT) regimens may be similar in efficacy with less toxicity than ≤5-fraction SBRT for central lung lesions. However, under current Centers for Medicare and Medicaid Services guidelines, SBRT in the United States (US) is reimbursed for only ≤5 fractions, whereas there are no such restrictions for reimbursement in Canada. We hypothesize that US-specific SBRT reimbursement policies influence the use of ≥5-fraction SBRT in US academic centers in comparison with comparable Canadian centers.Methods and Materials: A 15-question electronic survey was distributed to radiation oncologists at National Cancer Institute-designated cancer centers in the US and the 10 highest research-funded cancer centers in Canada. Fisher exact test or exact logistic regression if applicable was used, where P<.05 was considered statistically different from neutral.Results: Of the 143 radiation oncologists from 60 US cancer centers and 6 Canadian cancer centers who completed the survey (17.6% response rate), 125 routinely prescribe SBRT. Fifty percent of US physicians versus 0% of Canadian physicians indicated that there are instances when they would like to prescribe >5-fraction SBRT but prescribe ≤5 fractions because of insurance reimbursement (P=.076 and P=.001, respectively). Seventy percent (P=.006) of US radiation oncologists versus 0% (P=.001) of Canadian radiation oncologists report that SBRT clinical investigation is constrained by the insurance reimbursement. The most common reported deterrent to prescribing >5-fraction SBRT in the US was insurance reimbursement (49.5%).Conclusions: US radiation oncologists are more likely than those in Canada to report that SBRT clinical investigation and >5-fraction SBRT use may be negatively influenced by health insurance reimbursement; this perception was not held by physicians in Canada. Health care environment may significantly affect radiation therapy decision making and practice patterns. [ABSTRACT FROM AUTHOR]

Context: A significant proportion of cancer patients at end of life (EOL) undergo radiotherapy, but this evidence is not from nationwide population-based studies.Objectives: The aims of this population-based study were to investigate the trend in undergoing radiotherapy among Taiwanese cancer patients' last month of life (EOL radiotherapy) in 2001-2010 and to identify factors associated with EOL radiotherapy.Methods: This was a population-based retrospective cohort study analyzing data from Taiwan's national death registry, cancer registry, and National Health Insurance claims for EOL radiotherapy using multilevel generalized linear mixed modeling. Participants were Taiwanese cancer patients (N = 339,546) who died in 2001-2010.Results: Overall, 8.59% (7.97%-9.85%) of patients underwent EOL radiotherapy with a decreasing trend over time. Correlates of EOL radiotherapy included male gender, younger age, residing in less urbanized areas, diagnosis of lung cancer, metastatic disease, death within two years of diagnosis, and without comorbidities. Cancer patients were more likely to undergo EOL radiotherapy if they received primary care from medical oncologists and pediatricians, in a nonprofit, teaching hospital with a larger case volume of terminally ill cancer patients, and greater EOL care intensity.Conclusion: Approximately one-tenth of Taiwanese cancer patients underwent EOL radiotherapy with a decreasing trend over time. Undergoing EOL radiotherapy was associated with demographics, disease characteristics, physician specialty, and primary hospital's characteristics and EOL care practice patterns. Clinical and financial interventions should target hospitals/physicians that tend to aggressively treat at-risk cancer patients at EOL to carefully evaluate the appropriateness and effectiveness of using EOL radiotherapy. [ABSTRACT FROM AUTHOR]

Background Trans-oral surgical and non-surgical management options for oropharyngeal squamous cell carcinoma ( OPSCC) appear to offer similar survival outcomes. Functional outcomes, in particular swallowing, have become of increasing interest in the debate regarding treatment options. Contemporary reviews on function following treatment frequently include surrogate markers and limit the value of comparative analysis. Objectives of review A systematic review was performed to establish whether direct comparisons of swallowing outcomes could be made between trans-oral surgical approaches (trans-oral laser microsurgery ( TLM)/trans-oral robotic surgery ( TORS)) and (chemo)radiotherapy ((C) RT). Type of review Systematic review. Search strategy MEDLINE, Embase and Cochrane databases were interrogated using the following Me SH terms: antineoplastic protocols, chemotherapy, radiotherapy, deglutition disorders, swallowing, lasers, and trans-oral surgery. Evaluation method Two authors performed independent systematic reviews and consensus was sought if opinions differed. The WHO ICF classification was applied to generate analysis based around body functions and structure, activity limitations and participation restriction. Results Thirty-seven citations were included in the analysis. Twenty-six papers reported the outcomes for OPSCC treatment following primary (C) RT in 1377 patients, and 15 papers following contemporary trans-oral approaches in 768 patients. Meta-analysis was not feasible due to varying methodology and heterogeneity of outcome measures. Instrumental swallowing assessments were presented in 13/26 (C) RT versus 2/15 TLM/ TORS papers. However, reporting methods of these studies were not standardised. This variety of outcome measures and the wide-ranging intentions of authors applying the measures in individual studies limit any practical direct comparisons of the effects of treatment on swallowing outcomes between interventions. Conclusions From the current evidence, no direct comparisons could be made of swallowing outcomes between the surgical and non-surgical modalities. Swallowing is a multidimensional construct, and the range of assessments utilised by authors reflects the variety of available reporting methods. The MD Anderson Dysphagia Inventory is a subjective measure that allows limited comparison between the currently available heterogeneous data, and is explored in detail. The findings highlight that further research may identify the most appropriate tools for measuring swallowing in patients with OPSCC. Consensus should allow their standardised integration into future studies and randomised control trials. [ABSTRACT FROM AUTHOR]

The article discusses a study on a manual therapy programme for patients undergoing during radiation therapy for head and neck cancer. The patents have baseline swallow evaluations with speech-language pathology and attended weekly manual therapy sessions during radiation. The results demonstrated the programme's potential to reduce pain, inflammation and contracture. The patients also experienced improvement in mobility.

Background: Hepatopulmonary shunts (HPS) lead to radiation exposure of the lungs in patients undergoing radioembolization (RE) of malignant liver tumors. Purpose: To retrospectively analyze how HPS is affected by prior systemic or local therapy of the liver. Material and Methods: The percentage HPS was calculated from SPECT/CT scans obtained after technetium-99 m macroaggregated albumin administration into hepatic arteries in 316 patients evaluated for RE. Results: Patients with partial liver resection (n = 80) did not differ in HPS from the remaining patient population (n = 236) (HPS (median [range]) = 10.2 [2.1-48.3]resection% vs. 8.9 [2.3-32.9]no resection%; P = 0.527). In patients undergoing sequential RE, HPS was significantly higher in the liver lobe treated second (n = 10; HPS = 6.4 [2.1-10.2]firstlobe/session% vs. 12.0 [2.0-24.6]second lobe/session%; P = 0.019). (Chemo-)embolization (n = 19; HPS = 11.0 [2.8-48.3]%) or transcutaneous ablation (n = 63; HPS = 8.8 [3.0-32.9]%) had no effect on HPS compared to patients without prior interventions (no (chemo-)embolization: n = 297; HPS = 9.3 [2.1-47.3]%; P = 0.489; no ablation: n = 253; HPS = 9.5 [2.1-48.3]%; P = 0.382). Pretreatment with sorafenib (HPS = 9.5 [2.3-35.9]yes% vs. 10.2 [2.8-42.0]no%; P = 0.777) orbevacizumab (HPS = 10.7 [2.1-30.6]yes% vs. 9.0 [3.9-23.3]no%; P = 0.870) had no effect on HPS. Conclusion: Sequential RE results in an increase in the HPS in the contralateral liver lobe at the time of the second RE session. Other investigated therapy do not affect HPS. [ABSTRACT FROM AUTHOR]

Background Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) in Ontario. Methods An activity-based costing model was developed to estimate the costs of IMRT and 3D-CRT in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (VMAT) alongside IMRT. Results From the perspective of the health care system, treating prostate cancer with IMRT and 3D-CRT respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although IMRT was more costly than 3D-CRT, its cost will likely decline over time as programs mature and VMAT is incorporated. Conclusions Our costing model can be modified to estimate the costs of 3D-CRT and IMRT for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of IMRT cost to consider how VMAT affects time consumption. [ABSTRACT FROM AUTHOR]

Background The majority of patients with locally advanced salivary gland carcinoma will die of the disease even after curative surgery. Few studies on adjuvant therapy have been conducted. In this study, we compared adjuvant chemoradiotherapy (CRT) with adjuvant radiotherapy among the older patient population. Methods Surveillance, Epidemiology, and End Results (SEER)-Medicare database (1992-2009) was analyzed. Eligible cases were those receiving curative surgery followed by adjuvant therapy. Outcomes were overall survival and toxicity. Results Analyses included 741 patients: 641 patients (86.5%) received adjuvant radiotherapy and 100 (13.5%) received adjuvant CRT. The median overall survival was 41.0 months with adjuvant radiotherapy and 24 months with CRT. Both multivariable and propensity score-adjusted analyses indicated that adjuvant CRT was associated with an increased mortality (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.07-1.79 and HR: 1.49; 95% CI: 1.14-1.94, respectively). Toxicity rates were significantly higher in the CRT group. Conclusion Treatment with adjuvant CRT was associated with an increased mortality and toxicity when compared to adjuvant radiotherapy alone. © 2015 Wiley Periodicals, Inc. Head Neck 38: 863-870, 2016 [ABSTRACT FROM AUTHOR]

Background Conflicting results are reported regarding the impact of neck dissection on radiation-associated dysphagia. The purpose of this study was to reexamine this question specific to oropharyngeal intensity-modulated radiotherapy (IMRT). Methods Three hundred forty-nine patients with oropharyngeal cancer treated with bilateral IMRT with systemic therapy (induction and/or concurrent) were reviewed. Chronic dysphagia was defined by aspiration, stricture, pneumonia, and/or gastrostomy dependence ≥12 months post-IMRT. Results Selective neck dissection was performed after IMRT in 75 patients (21%). Overall, 41 patients (12%) developed chronic dysphagia. Neck dissection did not increase the rate of chronic dysphagia (9% neck dissection; 12% no neck dissection; p = .464) or gastrostomy duration ( p = .482). On multivariate analysis, age (odds ratio [OR] per 5-year = 1.25; 95% confidence interval [CI] = 1.04-1.51), baseline abnormal diet (OR = 2.78; 95% CI = 1.31-5.88), and IMRT dose (OR per 5-Gy = 5.11; 95% CI = 1.77-14.81) significantly predicted dysphagia. Conclusion In the setting of selective neck dissection for residual adenopathy after IMRT, neck dissection did not impact dysphagia. © 2015 Wiley Periodicals, Inc. Head Neck 38: 886-893, 2016 [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate the potential of PEGylated Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model. Methods: Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and Cu- and Lu-loading efficiency. The tumor imaging potential of Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of Lu-liposomes. Results: High remote loading efficiency (>95 %) was obtained for both Cu and Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the Cu-liposomes estimated an acceptable total effective dose of 3.3·10 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic Lu-liposomes. Conclusion: The overall preclinical profile of PEGylated Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of Lu-liposomes in animals before potential testing in man. [ABSTRACT FROM AUTHOR]

To better guide the development and optimization of radiotherapy planning, to reduce the incidence of radiation reactions, and to improve the quality of life of the patients with pancreatic cancer using radiotherapy, we conducted this study to explore the dosimetric parameters that predict the risk of gastrointestinal (GI) toxicity with hypofractioned radiotherapy for pancreatic cancer. Between January 2014 and January 2015, the medical records of 68 patients with pancreatic cancer who underwent helical tomotherapy at the Air Force General Hospital were analyzed. The doses delivered to the planning target volume, clinical target volume, and gross tumor volume-internal gross tumor volume of the primary pancreatic lesions were 50, 60, and 70-80 Gy in 15-20 fractions, respectively. GI toxicity was scored according to version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. The stomach and duodenum were contoured separately to determine the dose-volume histogram parameters. Univariate and multivariate analyses were adopted to identify clinical and physical risk factors associated with GI toxicity. The median follow-up was 9 months (range: 4-16 months). Eighteen patients had grade II acute GI toxicity, one patient had grade III acute GI toxicity, 17 patients had grade II late GI toxicity, and one patient had grade III late GI toxicity. On univariate analysis, the volume, the average dose Dmean, the maximum dose to 1,3, 5, and 10 cm³ of the stomach and duodenum (D1,D3, D5, and D10), and the relative volumes receiving 5-40 Gy (V5-V40), and the absolute volumes receiving 5-45 Gy (aV5-aV45) of the duodenum were significantly associated with grade II or higher GI toxicity (P,0.05). On multivariate analysis, aV45 of the duodenum was an independent predictor for grade II or higher GI toxicity (P=0.031). The receiver operating characteristic analysis also showed that an aV45 of 0.5 cm³ was the optimal threshold to predict GI toxicity for the entire cohort. Our findings indicate that many dosimetric parameters of the duodenum correlate with grade II or higher GI toxicity. To reduce GI toxicity, the absolute volume of the irradiated duodenum should be reduced. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy (CCRT) using cisplatin-based doublets represents the standard of care for locally advanced non-small cell lung cancer (NSCLC), having shown good efficacy and activity in clinical trials. Locally advanced NSCLC occurs frequently in the elderly population, which is often excluded by platinum-based CCRT administration, due to severe associated toxicities. This limitation has been overcome using new-generation drugs such as gemcitabine, docetaxel, paclitaxel, and vinorelbine, which have shown not only to be efficacious but also to have a favorable toxicity spectrum, both in association with cisplatin and as single agents. Vinorelbine is a vinca alkaloid that binds to tubulin, thus inhibiting mitotic microtubule polymerization. Previous studies have clearly demonstrated that vinorelbine acts as a radio sensitizing agent when administered intravenously or orally. Moreover, oral administration of vinorelbine has shown a good clinical safety profile in both elderly and younger patients. Methods: A comprehensive review of the literature data regarding use of oral vinorelbine concurrently with radiotherapy in NSCLC was done. Conclusion: Single-agent oral vinorelbine may represent an effective therapy option for elderly patients with locally advanced lung cancer. This review has described the use of oral vinorelbine both as a monochemotherapy and in combination with cisplatin in the context of CCRT. [ABSTRACT FROM AUTHOR]

Objective: This Phase I study aimed to assess the safety and efficacy of concurrent selective lymph node (SLN) late-course accelerated hyperfractionated (LCAF) intensity-modulated radiotherapy (IMRT) and S-1 plus cisplatin (CDDP) for the locally advanced oesophageal squamous-cell carcinoma (ESCC). Methods: The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy (CCRT) was administered as follows: CDDP 25 mg m-2 on Days 1-3 and Days 22-24; S-1 was applied in a deescalating dosage with a decrement of 10 mg m-2 per day, from its full dose level of 80 mg m-2, orally twice daily on Days 1-14 and Days 22-35. We inferred the maximumtolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended dose, according to adverse reaction during CCRT. Results: Totally, 15 patients with ESCC with T2-4NO-1MO-1a were enrolled in Dose Level 1 (80 mg m-2). In the initial five patients, two patients developed DLTs, As MTD was not reached, five additional patients were treated with the same dose level, and DLTs occurred in only one patient. Similar results were found in the last five patients. After CCRT, the objective response rates were 100% for primary tumours and 86.2% for metastatic lymph nodes, respectively. Totally, the observed Grade 3 toxicities during CCRT were leukopenia (20%), neutropenia (20%) and dermatitis (13.3%), and no Grade 4 toxicity occurred. The Kaplan-Meier-estimated overall and progression survival rates were 86.7% and 66.7% (1 year), 73.3% and 60% (2 years) and 73.3% and 60% (3 years). Conclusion: The concurrent SLN LCAF IMRT and chemotherapy with S-1 and CDDP was well tolerated and showed promising efficacy. The dose of S-1 in this regimen was recommended with 80 mg m-2 orally twice daily on Days 1-14 and Days 22-35. Advances in knowledge: CCRT with S-1 plus CDDP exhibited encouraging results with milder toxicities, high objective response rates and ideal overall survival time. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the potential benefit of a split-parotid delineation approach on the parotid gland in the treatment planning of patients with nasopharyn-geal carcinoma (NPC). Methods: 50 patients with NPC with parapharyngeal space (PPS) and/or level lla cervical node involvements were divided into three groups: PPS only, level lla cervical node only and both. Two volumetric-modulated arc therapy plans were computed. The first plan (control) was generated based on the routine treatment-planning protocol, while the second plan (test) was computed with the split-parotid delineation approach, in which a line through the anterolateral margin of the retromandibular vein was created that divided the parotid gland into anterolateral and posteromedial subsegments. For the test plan, the anterolateral subsegment was prescribed, with a dose constraint of 25 Gy in the plan optimization. Dosimetric data of the parotid gland, target volumes and selected organs at risk (OARs) were compared between the control and test plans. Results: The mean dose to the anterolateral subsegment of the parotid gland in all three groups was kept below 25 Gy. The test plan demonstrated significantly lower mean parotid dose than the control plan in the entire gland and the anterolateral subsegment in all three groups. The difference was the greatest in Group 3. Conclusion: The split-parotid delineation approach significantly lowered the mean dose to the anterolateral subsegment and overall gland without greatly compromising the doses to target volumes and other OARs. The effect was more obvious for both PPS and level lla cervical node involvements than for either of them alone. Advances in knowledge: It is the first article based on the assumption that parotid gland stem cells are situated at the anterolateral segment of the gland, and applied the split-parotid delineation approach to the parotid gland in the treatment planning of patients with NPC with PPS and level lla cervical node involvements, so that the function of the post-radiotherapy parotid gland might be better preserved. [ABSTRACT FROM AUTHOR]

MRI has superior soft-tissue definition compared with existing imaging modalities in radiation oncology; this has the added benefit of functional as well as anatomical imaging. This review aimed to evaluate the current use of MRI for lung cancer and identify the potential of a MRI protocol for lung radiotherapy (RT). 30 relevant studies were identified. Improvements in MRI technology have overcome some of the initial limitations of utilizing MRI for lung imaging. A number of commercially available and novel sequences have shown image quality to be adequate for the detection of pulmonary nodules with the potential for tumour delineation. Quantifying tumour motion is also feasible and may be more representative than that seen on four-dimensional CT. Functional MRI sequences have shown correlation with flu-deoxy-glucose positron emission tomography (FDG-PET) in identifying malignant involvement and treatment response. MRI can also be used as a measure of pulmonary function. While there are some limitations for the adoption of MRI in RT-planning process for lung cancer, MRI has shown the potential to compete with both CT and PET for tumour delineation and motion definition, with the added benefit of functional information. MRI is well placed to become a significant imaging modality in RT for lung cancer. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to present our evaluation of the clinical and functional outcomes after salvage total laryngectomy (STL). Methods We conducted a retrospective review of 218 patients who underwent STL between 1994 and 2014. Results Seventy percent of patients originally had T1 or T2, N0 tumors and 73% had definitive external-beam radiotherapy (EBRT) alone. A majority utilized tracheoesophageal prosthesis (77%) and were gastrostomy free (80%) at last follow-up. The 5-year disease control and overall survival (OS) rates were 65% and 57%, respectively. Patients with a disease-free interval after initial treatment <2 years were more likely to develop a recurrence ( p = .001) and die of disease ( p = .032) after STL. The disease-free interval after EBRT impacted disease control ( p < .001), with 5-year disease control of 92% for >5-year disease-free interval and 60% for <2-year disease-free interval. Conclusion Most patients remain disease-free after STL, achieve intelligible tracheoesophageal speech, and maintain an oral diet. Delayed recurrence after initial treatment portends better survival and may indicate a distinct biological profile. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1962-E1968, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to compare the hearing outcomes after surgery with reconstruction of the external auditory canal in combination with tympanoplasty, radiotherapy (RT) alone, and surgery followed by postoperative RT for T1 to 2N0M0 external auditory canal cancer. Methods We performed a retrospective, single-institution review of consecutive patients with early-stage external auditory canal cancer treated with surgery and/or RT between April 1997 and August 2013. Audiological data included the pretreatment hearing thresholds and those obtained at 12 months after the completion of therapy. Results When we compared the functional gains for air-conduction pure-tone average thresholds and mean air-bone gaps, those in the surgery group ( n = 10) were significantly higher than those in the RT ( n = 13) and surgery + RT ( n = 5) groups. Conclusion Adequate techniques for reconstruction of the external auditory canal in combination with tympanoplasty after complete surgical resection is useful for hearing preservation in addition to good survival outcomes. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1110-E1116, 2016 [ABSTRACT FROM AUTHOR]

Background There is interest in different treatment strategies, including deintensification in good prognosis human papillomavirus-positive (HPV(+)) oropharyngeal squamous cell carcinoma (SCC). We reviewed our experience with weekly cisplatin in low-risk, locoregionally advanced HPV(+) oropharyngeal SCC since late 2009. Methods Data from patients with low-risk HPV(+) oropharyngeal SCC treated with weekly cisplatin (40 mg/m2) and 70 Gy radiotherapy were collected. Low risk was defined as stage III to IV oropharyngeal SCC excluding T1-2N1, T4 or N3 disease, or N2b to N2c disease in patients with >10 pack-year smoking history. Results Of 31 patients, the median age was 56 years (range, 41-69 years). All patients completed 70 Gy radiotherapy within 51 days and 84% completed at least 5 cycles of cisplatin. Grade 3 mucositis occurred in 22 patients (71%) and grade 3 febrile neutropenia in 6 patients (19%). No patients required enteral feeding at 12 months. The median follow-up was 30 months (range, 21-57 months) with no recurrences or deaths. Conclusion Concurrent weekly cisplatin is relatively well-tolerated and associated with excellent disease control in low-risk, locoregionally advanced HPV(+) oropharyngeal SCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1117-E1121, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the efficacy and tolerability of the addition of 2 monoclonal antibodies, bevacizumab and cetuximab, to 2 cycles of high-dose cisplatin administered concurrently with intensity-modulated radiation therapy (IMRT) for head and neck squamous cell carcinoma (HNSCC). Methods Patients with newly diagnosed stage III/IVB (M0) HNSCC received cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2 weekly), bevacizumab (15 mg/kg, days 1 and 22), and cisplatin (50 mg/m2, days 1, 2, 22, and 23) concurrently with IMRT (70 Gy). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety and tolerability. Results Among 30 patients enrolled in this study, the primary tumor site was the oropharynx in 24 patients (p16 immunohistochemistry was positive in 17, negative in 1, and not done in 6 of the oropharyngeal tumors). Median age was 57 years (range, 38-77 years) and 27 patients had clinical stage IVA disease. All patients completed the full planned dose of radiation therapy. The most common ≥ grade 3 adverse events were lymphopenia, mucositis (functional), and dysphagia. With a median follow-up of 33.8 months, 2-year PFS was 88.5% (95% confidence interval [CI] = 68.1-96.1) and 2-year OS was 92.8% (95% CI = 74.2-98.1). Conclusion The addition of bevacizumab and cetuximab to 2 cycles of cisplatin, given concurrently with IMRT, was well-tolerated and was associated with favorable efficacy outcomes in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck 38: E566-E570, 2016 [ABSTRACT FROM AUTHOR]

Background No consensus has been reached on the optimal treatment for patients with nasopharyngeal cancer (NPC) who develop distant metastasis after initial radiation therapy (RT). Methods Two hundred eighty-two patients with NPC received curative RT (+/- chemotherapy). Forty-six patients (16.3%) who developed distant metastasis as first failure formed the study group for the current analysis. Results The median interval from initial RT until distant metastasis was 11.6 months. With a median follow-up of 30 months among survivors, overall survival (OS) rates at 2 and 5 years were 53.7% and 30.5%, respectively. On multivariate analyses, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT for initial staging, RT plus chemotherapy as initial treatment, metastatic lesion number <6, disease-free interval >9 months, distant metastasis only to lungs, and treatment with curative intent after distant metastasis were predictive of significantly better OS. Conclusion Combined with FDG-PET/CT, an aggressive treatment approach using locoregional modalities might be beneficial to patients with NPC with favorable prognostic factors, even after distant metastasis. © 2015 Wiley Periodicals, Inc. Head Neck 38: E293-E299, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT Background The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers. Methods T4 laryngeal cancers treated with curative intent from January 2003 to December 2010 were analyzed. Outcomes were evaluated in both primary radiotherapy (+/− chemotherapy) (RT/CRT) and primary surgery cohorts. Results Among the 65 primary RT/CRT and 42 primary surgery patients included, median follow-up was 4.4 years. There was a trend for improved locoregional control with surgery (74% vs 88%; p = .08). In the RT/CRT group the 3-year laryngectomy-free survival was 67%. The 2-year gastrostomy dependency rate was 23% with RT/CRT versus 6% with primary surgery ( p = .07). Overall survival (OS) at 3 years was significantly lower in the RT/CRT versus primary surgery group (41% vs 70%; p < .01). Conclusion Laryngeal preservation is achieved in over two thirds of patients with primary RT/CRT. Patients with low volume minimal cartilage involvement T4 disease may be best suited to RT/CRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2035-E2040, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this prospective study was to evaluate the swallowing performance of patients with head and neck cancer treated with parotid-sparing intensity-modulated radiotherapy (IMRT). Methods Sixty-two patients were recruited. Data were collected before and up to 12 months after treatment. Measures included the Performance Status Scale for head and neck cancer (PSS-HN Normalcy of Diet and Eating in Public subscales), tube feeding status, and 100 mL water swallow test (WST) volume and capacity scores. Results There was a significant reduction in PSS-HN and WST scores from baseline to 3 months ( p < .001). Significant improvements were observed up to 12 months on the PSS-HN. Swallowing volume and capacity scores recovered but did not reach statistical significance. Tube feeding was not required in 47% of the patients. Conclusion IMRT significantly impacts on swallowing performance, although there is a trend for improvement up to 12 months after treatment. Our data support a case-by-case approach to tube feeding. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1436-E1444, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to examine outcomes, toxicity, and dosimetric characteristics of patients treated with reirradiation for head and neck cancers. Methods Fifty patients underwent ≥2 courses of radiation therapy (RT) postoperatively or definitively with or without chemotherapy. Composite dose volume histograms (DVHs) for selected anatomic structures were correlated with grade ≥3 late toxicity. Results Median initial and retreatment radiation dose was 64 and 60 Gy, respectively. Median overall survival (OS), progression-free survival (PFS), and 1-year PFS rates were 18 months, 11 months, and 45%, respectively, with 13 months median follow-up. Thirty-four percent of patients experienced grade ≥3 late toxicity with 1 death from carotid blowout. The DVH corresponding to the carotid blowout fell above the third quartile compared with other patients. Conclusion Our analysis is the first to systematically evaluate the dose to the carotid artery using composite dosimetry in head and neck reirradiation patients, and demonstrates a promising technique for evaluating the dose to other normal tissue structures. © 2015 Wiley Periodicals, Inc. Head Neck 38: E961-E969, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to examine patterns of failure and the relationship to radiation doses in patients with head and neck carcinoma of unknown primary (HNCUP). Methods We reviewed 85 patients with HNCUP treated with curative-intent radiation therapy (RT) during 1995 to 2012. Results There have been no failures in the pharyngeal axis. Relapse at initial neck sites of disease developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range, 63-70 Gy). Failure at neck sites without initial disease occurred in 4 patients (4.7%). The median dose was 54 Gy (range, 50-58.8 Gy). There were no contralateral failures in a small cohort of patients receiving unilateral treatment ( n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5 patients (5.9%). Conclusion RT for HNCUP produces excellent locoregional control rates with acceptably low levels of late toxicity. Doses prescribed to sites of eventual failure did not vary significantly from those sites that were treated and remain in control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E426-E431, 2016 [ABSTRACT FROM AUTHOR]

Background Most cases of adenoid cystic carcinoma (ACC) of the tongue base are radioresistant, and are diagnosed in the advanced stage. Therefore, we evaluated the safety and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced ACC of the tongue base. Methods Eighteen patients with ACC of the tongue base were treated with C-ion RT between May 2002 and April 2014. Seventeen patients had T4a disease and 1 patient had T2 disease before C-ion RT. Results The median follow-up period was 57 months (range, 10-132 months). The 5-year local control rate was 92%. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72% and 44%, respectively. Regarding late reactions, 2 patients developed grade 3 mandible osteoradionecrosis, and 1 had grade 3 hemorrhage of the tongue base. Conclusion C-ion RT was effective with acceptable toxicities for locally advanced ACC of the tongue base. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2122-E2126, 2016 [ABSTRACT FROM AUTHOR]

Background This retrospective study evaluates efficacy and tolerability of high-dose hypofractionated radiotherapy (RT) in patients with head and neck cancer. Methods All patients with head and neck cancer treated between September 2003 and September 2013 with 12 × 4 Gy RT were included. Two and 3D-RT or intensity-modulated radiotherapy (IMRT) were used. Overall survival (OS), tumor response, and palliative effect were evaluated. Results Palliative effect occurred in 63% of 81 included patients, lasted a median of 4.6 months, and was correlated with tumor response ( p = .006). Median OS was 7.2 months. Confluent mucositis occurred more often in patients treated with 2D/3D-RT than IMRT (26% vs 44%; p = .04) and lasted for a median of 2 weeks. Conclusion High-dose hypofractionated RT resulted in meaningful palliation in 63%, lasting for almost 5 months. IMRT should be the technique of choice, as it results in less high-grade toxicity. The 12 × 4 schedule should be opted for patients with reasonable functional capacities and a life expectancy of >6 months. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1264-E1270, 2016 [ABSTRACT FROM AUTHOR]

Background Squamous cell carcinoma (SCC) of the nasal cavity is a rare malignancy and often analyzed in heterogeneous studies with other tumors of the nose or the paranasal sinuses. The purpose of this study was to evaluate distinct risk factors, tumor characteristics, outcome predictors, and the prevalence of human papillomavirus (HPV) in SCC of the nasal cavity. Methods We conducted a retrospective study of 39 patients treated at a single quaternary medical care and cancer center. We analyzed tumor characteristics, HPV status, treatment, and outcome. We present the largest study on SCC of the nasal cavity from a single center. Results The majority of patients (70.2%) presented with an early-stage tumor (T1 or T2). Only 1 patient had a single neck metastasis at the time of diagnosis. Four tumors were HPV-positive. Most patients (61.5%) underwent surgical resection without adjuvant treatment, with 12 patients (30.8%) undergoing additional radiotherapy. Three patients were treated with primary radiotherapy or chemoradiotherapy. No patient treated primarily with total rhinectomy developed local tumor recurrence. Conclusion Local tumor control is crucial, even if it makes radical surgery necessary. Postoperative epithetic treatment enables reliable follow-up examinations. Regional metastases at the time of diagnosis are rare. Neck dissection should therefore be reserved for cases of suspected metastasis. HPV may also play a role in the etiology of SCC of the nasal cavity. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2112-E2117, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this report was to present the results of accelerated radiotherapy (RT) with concomitant weekly cisplatin in head and neck cancer. Methods One hundred six patients received concomitant cisplatin 40 mg/m2 weekly with accelerated RT up to a dose of 68 Gy over 5.5 weeks. Results Ninety-nine percent of the patients received planned RT and 90% received ≥5 cycles of cisplatin. Moist desquamation of skin developed in 45% and confluent mucositis in 82%. Feeding tubes were required in 79% of the patients, and after 12 months in 4%. One patient developed nephrotoxicity. Three-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 72%, 54%, and 61%, respectively. Human papillomavirus (HPV) status was positive on polymerase chain reaction (PCR) and p16 in 11 of 50 patients with oropharyngeal carcinoma. Three-year OS was 81% and 66% in HPV-positive versus HPV-negative patients with oropharyngeal carcinoma. Conclusion Concomitant weekly cisplatin 40 mg/m2 with accelerated RT was well tolerated and treatment compliance was high. © 2015 Wiley Periodicals, Inc. Head Neck 38: E559-E565, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to investigate late toxicities and quality of life (QOL) of patients with nasopharyngeal carcinoma (NPC) with long-term survival after treatment by intensity-modulated radiotherapy (IMRT) versus non-IMRT. Methods An observational, cross-sectional study of QOL and late toxicities was conducted in 242 patients with NPC with survival of >5 years after treatment with IMRT ( n = 100) or non-IMRT ( n = 142) by using physician-assessed toxicities (Common Terminology Criteria for Adverse Events [CTCAE] version 4) and the patient-reported European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC QLQ-C30) and the Head and Neck 35-questions (EORTC QLQ-C30-H&N35) module. Results The IMRT group had both statistically ( p < .05) and clinically (difference of predicted mean scores ≥10 points) better outcome in global QOL, cognitive functioning, social functioning, fatigue, and 11 scales of the head and neck module. Late toxicities, including neuropathy, hearing loss, dysphagia, xerostomia, and neck fibrosis were significantly less severe in the IMRT group. Multivariate analysis revealed that the radiotherapy (RT) technique was statistically significantly associated with late toxicities and QOL outcome after adjusting for other clinical and demographic variables. Conclusion The use of the IMRT technique was associated with the improvement of physician-assessed late toxicities and patient-reported QOL in NPC survivors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1026-E1032, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT Background We attempted to elucidate the mechanism of cell death after radiation by studying how β-catenin silencing controls the radiation sensitivity of radioresistant head and neck cancer cells. Methods The most radioresistant cancer cell line (AMC-HN-9) was selected for study. Targeted silencing of β-catenin was used on siRNAs. Sensitivity to radiation was examined using clonogenic and methylthiazol tetrazolium (MTT) assays. Results A combination of irradiation plus β-catenin silencing led to a significant reduction in the inherent radioresistance of AMC-HN-9 cells. Although expression of Ku70/80 was upregulated in AMC-HN-9 cells after irradiation, Ku70/80 was dramatically decreased in a combination of irradiation and β-catenin silencing. Interestingly, irradiation-induced Ku70/80 was completely prevented by β-catenin silencing-induced LKB1/AMP-activated protein kinase (LKB1/AMPK) signal. Conclusion The LKB1/AMPK pathway might relay the signal between the Wnt/β-catenin pathway and the Ku70/Ku80 DNA repair machinery, and play a decisive role in fine-tuning the responses of cancer cells to irradiation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1909-E1917, 2016 [ABSTRACT FROM AUTHOR]

Background The floor of mouth (FOM) is a common site of oral squamous cell carcinoma (SCC). The purpose of this study was to investigate pathological predictors of survival in FOM SCC. Methods We conducted a retrospective study of 54 consecutive patients undergoing surgery for FOM SCC. Pathological parameters were extracted from histological reports with original pathology slides re-reviewed by 2 pathologists for missing data. Results On univariate analysis, depth of invasion >10 mm ( p = .009), lymphovascular invasion (LVI; p < .001), noncohesive invasive front ( p = .006), perineural invasion (PNI; p = .003), and nodal metastases ( p = .02) were significant predictors of overall survival. On multivariate analysis, LVI ( p = .009) and invasive front ( p < .001) remained significant. Postoperative radiotherapy improved survival in patients with LVI, PNI, and nodal metastases, and was just outside significance for noncohesive invasive front ( p = .06). Conclusion LVI is an adverse prognosticator in FOM SCC and indicates postoperative radiotherapy. Further study is required to investigate the importance of invasive front. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1528-E1534, 2016 [ABSTRACT FROM AUTHOR]

Background This was a retrospective study of patients with human papillomavirus (HPV)-associated oropharyngeal cancer treated with concurrent systemic therapy and radiation. Methods Data were extracted through chart review, and statistical analyses included frequency tabulation, chi-square, and Kaplan-Meier tests. Results Three hundred thirty-nine patients were analyzed; 166 received neoadjuvant chemotherapy. One hundred thirty-six patients were treated with cisplatin, 123 with cetuximab, and 59 with carboplatin. The 2-, 3-, and 5-year actuarial overall survival rates were 92%, 88%, and 78%, respectively. There were no significant differences in survival or disease control when analyzed by systemic agent. Platin-treated patients had greater hematologic toxicity, and required more intravenous hydration. The incidence of confluent mucositis was highest among patients treated with cetuximab. Conclusion Platin and cetuximab seem to have similar efficacy when delivered concurrently with radiation in our retrospective population study. Although platin did cause greater hematologic toxicity, radiation-specific side effects seemed relatively comparable. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1554-E1561, 2016 [ABSTRACT FROM AUTHOR]

Background Dysphagia-related symptoms in patients with head and neck cancer are common before treatment. We hypothesized greater self-reported baseline dysphagia would predict gastrostomy placement during primary radiation. Methods Swallowing-specific/general surveys (SwalQOL/EuroQOL) collected prospectively before definitive radiation were analyzed for associations with gastrostomy placement. Prophylactic gastrostomy was recommended at the discretion of a multidisciplinary team blinded to the surveys. Results Of 84 patients in the cohort, 42 patients (50%) received feeding tubes. Eleven patients (13%) who underwent prophylactic feeding tube placement reported the greatest pretreatment dysphagia, whereas those who avoided gastrostomies reported the least. Prophylactic gastrostomy was more strongly associated with patient-reported measures than other clinical criteria. Controlling for stage IV, T3 to T4 classification, smoking, chemotherapy, and pretreatment weight loss, baseline dysphagia remained an independent predictor of feeding tube placement (odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.05-0.55; p = .01). Patients without gastrostomies during treatment avoided persistent gastrostomy dependence. Conclusion Baseline dysphagia-related symptoms before radiation are independent predictors of gastrostomy placement. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1318-E1324, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to investigate whether the minimum absolute lymphocyte count (ALC) during radiotherapy (RT) could predict clinical outcome in patients with nasopharyngeal cancer (NPC). Methods We analyzed 70 patients with NPC including 63 patients treated with chemoradiotherapy and used multivariate analysis to determine whether minimum ALC affected clinical outcome. Results Patients were grouped by minimum ALC, with a cutoff of 245 cells/μL. Five-year disease-specific survival (DSS) and progression-free survival (PFS) for patients with minimum ALC ≥245 versus minimum ALC <245 were 88.1% versus 60.8% ( p = .004) and 71.2% versus 35.2% ( p = .004). All 10 patients with minimum ALC <120 experienced disease progression. Four of 6 patients (67%) with ALC <120 who died experienced disease progression within 6 months. Conclusion Minimum ALC may predict poor 5-year DSS and should be evaluated by prospective studies. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1061-E1067, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to develop a CMCSCC−1 cell line for head and neck cancer research into new therapies for head and neck squamous cell carcinoma (HNSCC). Methods The CMCSCC-1 cell line was isolated from a primary oral tongue tumor specimen of a female patient. Tumor cells were evaluated for biomarkers expression by Western blots, reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence activated cell sorter, and immunostaining. Cell proliferation in response to radiation was measured by the WST-8 assay. Results The characterization analyses revealed a typical epithelial morphology; a doubling time of approximately 24 hours, high tumorigenicity in immunodeficient mice, and upregulated biomarkers. CMCSCC-1 cells were negative for human papillomavirus (HPV) infection, but more sensitive to radiation compared with those FaDu cell lines. Conclusion CMCSCC-1, a novel oral tongue SCC cell line, was established. It will help in the elucidation of the molecular pathogenesis of HPV-negative radiosensitive tumors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E542-E551, 2015 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to assess predictors of mucositis in oropharyngeal and oral cavity cancer after definitive or adjuvant volumetric modulated arc radiotherapy (VMAT) +/− chemotherapy. Methods Fifty patients were evaluated. Statistical analysis was performed for the following parameters as potential predictors of mucositis ≥ G2: total oral mucosa and oral mucosa minus target high-low radiation dose regions (planning target volumes [PTVs]), mean dose (Dmean), maximum dose (Dmax), chemotherapy, weight loss, and dysphagia. Results Mucositis ≥ G2 was found to be statistically related to chemotherapy, weight loss, dysphagia ≥ G2, total oral mucosa Dmean ≥50 Gy and Dmax ≥65 Gy, V45 Gy >40%, V50 Gy >30%, and V55 Gy >20% of the oral mucosa minus target PTVs. A ratio between total oral mucosa and oral mucosa minus target PTVs >2.5 is related to G3 mucositis ( p = .03). Conclusion New parameters were found as predictors of moderate-severe mucositis. © 2015 Wiley Periodicals, Inc. Head Neck 38: E815-E819, 2016 [ABSTRACT FROM AUTHOR]

Background Salivary duct carcinoma is rare, with distinct morphology and behavior. We reviewed our institutional experience with salivary duct carcinoma, aiming to characterize clinical behavior and treatment outcomes. Methods All salivary duct carcinomas treated curatively between 1999 and 2010 were reviewed. Overall survival (OS), locoregional control, distant control, and patterns of failure were analyzed. Multivariate analysis identified predictors of OS. Results Fifty-four patients with salivary duct carcinoma (parotid gland = 49; submandibular gland = 5) were included in the analysis. Fifty-three patients underwent primary surgery, and 48 (89%) received postoperative radiotherapy (RT; median dose = 60 Gy). Median follow-up was 5.7 years. The 5-year OS, locoregional control, and distant control were 43%, 70%, and 48%, respectively. Nine local (6 involving facial nerve), 10 regional, and 28 distant failures were identified. Multiple pathologic involved lymph nodes (pN2b/N2c) predicted reduced OS (hazard ratio [HR] = 3.6; p = .02). Conclusion Distant recurrence is common. Presence of pN2b/N2c disease is associated with reduced OS. Local recurrence frequently involves the facial nerves. © 2015 Wiley Periodicals, Inc. Head Neck 38: E820-E826, 2016 [ABSTRACT FROM AUTHOR]

Background Current management of nasopharyngeal carcinoma (NPC) uses radiotherapy (RT) as the curative treatment modality. Radiation delivery techniques for NPC can be achieved using 2D conventional RT or intensity-modulated radiotherapy (IMRT). Methods A systematic review and meta-analysis of the literature was undertaken to assess the effectiveness of IMRT versus 2D conventional RT in primary treatment of NPC. Results IMRT showed better results than 2D conventional RT in terms of local control, regional control, and overall survival, but when stratified, only in T4, N2, and stage III were the differences that were seen. Objective saliva measurements and physician-graded xerostomia were better in IMRT. However, patient-reported xerostomia showed minimal improvement only in IMRT. The evidence of superiority of IMRT over 2D conventional RT is not clear. Conclusion In the absence of more clinical data demonstrating the superiority of IMRT in the treatment of nasopharyngeal carcinoma, 2D conventional RT seems to be a reasonable treatment option, especially in limited resource settings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2130-E2142, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to assess the efficacy and safety of induction chemotherapy with docetaxel-S-1, and radiotherapy (RT) with concurrent daily cisplatin in locally advanced head and neck carcinoma. Method Fifty patients received 2 cycles of induction chemotherapy with induction chemotherapy with docetaxel and S-1, followed by 7 cycles of RT with concurrent daily cisplatin. Results The most frequent grade 3 to 4 hematologic toxicity was neutropenia (14%). Forty of 50 patients who completed induction chemotherapy with docetaxel and S-1 subsequently started RT with concurrent daily cisplatin, all within 3 to 4 weeks after the start of the second cycle of induction chemotherapy with docetaxel and S-1. The best response to induction chemotherapy with docetaxel and S-1 and after completion of RT with concurrent daily cisplatin was partial response (PR) in 52.5% and complete response in 47.5%, respectively. With a median follow-up of 61 months, 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 65.7%, respectively. Conclusion Administration of induction chemotherapy with docetaxel and S-1 before RT with concurrent daily cisplatin chemoradiotherapy (CRT) resulted in a high response rate with good tolerability, and did not compromise subsequent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1653-E1659, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the tolerability of concurrent radiotherapy and cetuximab (bioradiotherapy [BRT]) after taxane-based induction chemotherapy in head and neck squamous cell carcinoma (HNSCC). Methods One hundred four patients with HNSCC received BRT with (29%) or without (71%) prior taxane-based induction chemotherapy. Results Radiodermatitis (97%) and skin rash (65%) occurred frequently, but there was no difference of occurrence or the grade of the rash observed in the 2 populations. However, patients receiving taxane-based induction chemotherapy had a less severe rash as compared with patients without induction chemotherapy. Mucositis and dysphagia were frequent and comparable in the 2 groups. The occurrence of a skin rash (at any grade) did not predict an increased overall survival (OS) in the overall population, but it was associated with an improved 3-year OS in patients receiving taxane-based induction chemotherapy. OS was not influenced by the skin rash grade in the overall population of the 2 treatment subgroups. Conclusion Taxane-based induction chemotherapy did not increase the rate of cetuximab-related toxicities. © 2015 Wiley Periodicals, Inc. Head Neck 38: E905-E910, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to prospectively evaluate the scintigraphic results on patients who undergo intensity-modulated radiotherapy (IMRT) to investigate the tolerance doses for the salivary glands. Methods Salivary scintigraphy was performed on 35 patients with head and neck cancer before the beginning of radiotherapy (RT), and then at 6 weeks and again at 3 months after the completion of RT. Xerostomia was recorded according to the Radiation Therapy and Oncology Group (RTOG) grade. Salivary function was evaluated by calculating the excretion rate changes (ΔF) for each salivary gland before and after RT. Results The parotid mean dose was significantly related to parotid ΔF and the submandibular gland mean dose to the submandibular gland ΔF. The parotid mean dose of 23 Gy was best correlated with the RTOG grades. The submandibular gland mean dose significantly related to ΔF ≤-50% and ≤-75% was 42 Gy. Conclusion The parotid mean dose of 23 Gy and the submandibular gland mean dose of 42 Gy is feasible for salivary function preservation in the IMRT era. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1746-E1755, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs. HER3 is a significant factor in HNSCC treatment resistance. Indeed, HER3 is a major mechanism described for cetuximab resistance because of modification of epidermal growth factor receptor (EGFR) internalization and by phosphotidylinositol-3-kinase (PI3K)/AKT signaling pathway activation. HER3 also affects resistance to tyrosine kinase inhibitors (TKIs) and thereby promotes treatment escape and radiotherapy resistance by activation of the survival signaling pathway. To counteract this, pharmacologic inhibitors of HER3 are currently in development and could significantly improve HNSCC treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2412-E2418, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT Background The purpose of this study was to characterize the timing, histology, and behavior of second primary thyroid carcinoma (SPTC) developing after a diagnosis of head and neck squamous cell carcinoma (HNSCC). Methods We conducted a retrospective review of the Surveillance, Epidemiology, and End Results (SEER) 9 database. Results Patients with HNSCC who develop SPTC die 1.6 times sooner than those without SPTC. This effect is only seen if SPTC presents >6 months after diagnosis of HNSCC. Models were adjusted for age, sex, year of diagnosis, and location of HNSCC. There was no effect of prior radiation therapy on either mortality rates or time to development of thyroid cancer in patients with SPTC. The type of thyroid carcinoma that developed was similar between cohorts. Conclusion The development of SPTC in patients with HNSCC results in decreased overall length of survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E890-E894, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT Background The purpose of this study was to present the results of our investigation of malic enzyme (ME) expression and the induction of senescence in head and neck squamous cell carcinoma (HNSCC). Methods P53, ME1, ME2, and aspects of cellular metabolism, such as reactive oxygen species (ROS) were investigated in HNSCC cell lines. Results Both metformin and ionizing radiation inhibited the expression of ME2, but not ME1, in HNSCC. Knockdown of ME1 or ME2 potentiated therapy-induced senescence in HNSCC cells regardless of p53 status, and led to increased p21 and generation of ROS. Therapy-induced senescence in ME-depleted cells was blocked by the antioxidant N-acetyl cysteine. Finally, high expression of ME2 was associated with poorer overall survival (OS) in patients with HNSCC. Conclusion Depletion of ME enhances therapy-induced senescence and seems driven largely by ROS. ME2 expression in HNSCC may be associated with poor outcome, providing a possible link between therapy-induced senescence and patient outcome, and indicating a potential therapeutic benefit of targeting ME2. © 2015 Wiley Periodicals, Inc. Head Neck 38: E934-E940, 2016 [ABSTRACT FROM AUTHOR]

Background The development of a postoperative orocutaneous fistula (OCF) or pharyngocutaneous fistula (PCF) in the irradiated tissues of patients with head and neck cancer represents a high burden of morbidity for the patient. With high postoperative recurrence rates, these fistulae result in a reconstructive challenge for the plastic surgeon. In this study, we propose a new double-layer design to successfully repair these fistulae in a 1-stage reconstruction. Methods Twelve patients with an average age of 56 years (range, 45-67 years) were operated on between January 2006 and December 2012 using this double-layer single-stage technique. All patients had received postoperative radiotherapy after their initial reconstruction. A circumferential turnover flap was designed and raised from the skin surrounding the fistula to recreate inner lining using a tension-free, water-tight repair. No debridement of the fistula itself was performed. The second-layer of the reconstruction, which represents the outer lining, was achieved with either a local or a free flap. Results Fistula size ranged from 0.8 × 0.5 cm to 3 × 3.2 cm with a mean size of 2 cm2. The outer lining was achieved using a free flap in 5 cases and a local flap in 7 cases. All the flaps survived completely with no cases of postoperative infection, however, 1 case was complicated by mandibular plate exposure necessitating its removal. No major complication or recurrence has yet been encountered in any of our patients with a mean follow-up of 28 months (range, 12-78 months). Conclusion This 1-stage double-layer design can provide a reliable and relatively straightforward means of repairing OCF and PCF in the irradiated tissues of patients with head and neck cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E353-E359, 2016 [ABSTRACT FROM AUTHOR]

Background Transoral surgery (TOS) for patients with early stage oropharyngeal squamous cell carcinoma (SCC) is increasingly used, however, criticized, because of less optimal access to the tumor than open techniques and thus potentially jeopardizing tumor control in comparison with radiotherapy (RT). Therefore, we compared the currently available data on survival provided by TOS versus RT. Methods Survival data were extracted after a MEDLINE, Web of Science, and Google Scholar search followed by a meta-analysis. Results The analysis was based on 729 patients in the RT group versus 276 in the TOS group with similar quality of studies in both groups. The 5-year disease-specific survival (DSS)/overall survival (OS) was 90.4% (95% confidence interval [CI], 85.6% to 95.2%/58.8%; 95% CI, 52.8% to 64.7%) in the RT group versus 89.6% (95% CI, 81.8% to 97.3%/78.1%; 95% CI, 71.2% to 85.1%) in the TOS group. Conclusion The data suggest equivalent efficacy of both treatments in terms of disease control for early stage oropharyngeal SCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: 2143-2150 [ABSTRACT FROM AUTHOR]

Background Neuromuscular electrical stimulation (NMES) is a highly sought after but poorly studied treatment for dysphagia among patients with head and neck cancer with dysphagia. This study investigated the efficacy of NMES in this patient population. Methods In this double-blinded, randomized controlled trial, 170 patients with head and neck cancer experiencing posttreatment dysphagia were randomized into active NMES + swallow exercise versus sham NMES + swallow exercise groups. Outcomes after a 12-week program included changes in fluoroscopy measures, diet, and quality of life. Results After the 12-week program, the active NMES group had significantly worse Penetration Aspiration Scale scores than the sham group. Both groups reported significantly better diet and quality of life. No other measures were significant. Conclusion NMES did not add benefit to traditional swallow exercises. Unfortunately, swallow exercises were not effective by themselves either. For patients with head and neck cancer with moderate to severe dysphagia caused by radiation therapy, current behavioral therapies are of limited help in reversing long-term dysphagia. © 2015 Wiley Periodicals, Head Neck 38: E1221-E1231, 2016 [ABSTRACT FROM AUTHOR]

Background The primary treatment for head and neck adenoid cystic carcinoma (ACC) is surgery. Infrequently, however, ACC's propensity for perineural and base of skull invasion can preclude definitive surgical management. We present our experience with proton radiation therapy (RT) and concurrent platinum-based chemotherapy. Methods Nine patients with unresectable node-negative, nonmetastatic head and neck ACC received definitive proton RT and concurrent cisplatin. Outcomes and toxicities were recorded. A systematic review of the literature was performed. Results Median follow-up was 27 months (range, 9.2-48.3 months). Four patients achieved complete response at the primary site, and an additional 4 patients achieved stabilization of local disease. Only 1 patient developed local disease progression. Four patients had 5 acute grade 3 (G3) toxicities, and 1 patient developed a chronic G4 optic nerve disorder. Conclusion Our preliminary results suggest proton RT and concurrent chemotherapy is a definitive treatment option for select patients with head and neck ACC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1472-E1480, 2016 [ABSTRACT FROM AUTHOR]

Background Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization. Methods Using the National Cancer Data Base, we identified 3552 patients with ATC. Factors associated with surgery, high-dose radiotherapy (RT; ≥59.4 Gy), and chemotherapy utilization were evaluated using multivariable logistic regression. From this, an inverse probability-weighted propensity score was incorporated into multivariable Cox regression analyses for OS. Results Numerous factors predictive for high-dose RT, total thyroidectomy, and chemotherapy utilization are described. Factors associated with improved survival were absence of clinical or pathologic lymph node involvement, absence of metastasis, tumor size ≤6 cm, negative surgical margins, surgery, RT, and chemotherapy. On conditional landmark analysis, improved survival seen with chemotherapy and surgery other than total thyroidectomy was lost, but persisted for total thyroidectomy and high-dose RT. Conclusion Even after correction for selection and immortal time bias, high-dose RT resulted in improved survival. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2083-E2090, 2016 [ABSTRACT FROM AUTHOR]

Background Grade ≥2 acute xerostomia between 3D conformal radiotherapy (RT) and intensity-modulated radiotherapy (IMRT) was evaluated in patients with head and neck squamous cell carcinomas (HNSCCs) treated radically. Methods Between 2005 and 2007, 59 patients with HNSCC (T1-3, N0-2b) were randomized to IMRT or 3D-RT. On RT, weekly xerostomia, dysphagia, dermatitis, and mucositis were graded by Radiation Therapy Oncology Group (RTOG) acute toxicity criteria. Patients underwent examination under anesthesia, positron emission tomography (PET)-CT, and toxicity assessments per protocol (NCT00652613) thereafter. Results Incidence of grade ≥2 xerostomia at 8 weeks posttreatment was significantly lower with IMRT compared with 3D conformal RT (24% vs 53%; p = .024). At subsequent follow-up, significantly fewer patients receiving IMRT had grade ≥2 xerostomia. Long-term weight loss was higher in patients in the 3D conformal RT arm compared to IMRT (50% vs 21%; p = .038). Disease-related outcomes between arms (median follow-up, 70 months) were similar. Conclusion IMRT significantly reduces incidence of acute and late grade ≥2 xerostomia in patients with HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1481-E1487, 2016 [ABSTRACT FROM AUTHOR]

Background This study assessed outcomes of patients with hypopharyngeal carcinoma treated with organ-preservation therapy utilizing intensity-modulated radiation therapy (IMRT). Methods The medical records of 98 patients treated with definitive IMRT +/- chemotherapy from 2001 to 2013 for nonmetastatic hypopharyngeal cancer were retrospectively reviewed. Results Patients were treated to doses of 66 to 72 Gy. Eighty-three patients (85%) received chemotherapy. With median follow-up of 35 months, 2-year overall survival (OS), locoregional control, progression-free survival (PFS), and laryngectomy-free survival rates were 74%, 77%, 67%, and 65%, respectively. Functional laryngeal preservation rate was 76% at 2 years. N3 disease correlated with worse OS ( p < .01). Concurrent chemotherapy correlated with improved locoregional control ( p = .03) and complete response to induction chemotherapy correlated with improved OS and PFS ( p = .02). Actuarial 2-year and 5-year grade 3 treatment toxicities were 17% and 21%, respectively. Conclusion Favorable disease outcomes and functional laryngeal preservation rates can be achieved with IMRT for patients with hypopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2091-E2099, 2016 [ABSTRACT FROM AUTHOR]