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Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129.Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection.Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection.Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors. [ABSTRACT FROM AUTHOR]

BACKGROUND The objective of this study was to identify trends and predictors of the time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). METHODS The National Cancer Database (NCDB) was reviewed for the following head and neck cancer sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was defined as the number of days from diagnosis to the initiation of definitive treatment and was measured according to covariates. Significant differences in the median TTI across each covariate were measured using the Kruskal-Wallis test, and the Spearman test was used to measure trends within covariates. For multivariate analysis, a zero-inflated, negative, binomial regression model was used to estimate the expected TTI, which was expressed in the predicted number of days; and the Vuong test was used to identify the predictors of TTI. RESULTS In total, 274,630 patients were included. Between 1998 and 2011, the median TTI for all patients was 26 days, and it increased from 19 days to 30 days ( P < .0001). Treatment with chemoradiation (CRT) ( P < .0001), treatment at academic facilities ( P < .0001), and stage IV disease ( P < .0001) were associated with increased TTI. TTI significantly increased for each disease stage ( P < .0001), treatment modality ( P < .0001), and facility type ( P < .0001) over time. In addition, patients became more likely to transition care between facilities after diagnosis for treatment initiation ( P < .0001) over time. On multivariate analysis, treatment at academic facilities (33 days), transitioning care (37 days), and receipt of CRT (39 days) predicted for a longer TTI. CONCLUSIONS TTI is rising for patients with HNSCC. Those who have advanced-stage disease, receive treatment with CRT, are treated at academic facilities, and who have a transition in care realized the greatest increases in TTI. Cancer 2015;121:1204-1213. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Head/neck sarcomas are rare, accounting for about 1% of head/neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group, due to anatomic constraints leading to difficulty in completely excising tumors, with high rates of local recurrence. We retrospectively analyzed cases of head/neck soft tissue sarcomas (STS) and osteogenic sarcomas managed in a multi-disciplinary setting at Fox Chase Cancer Center from 1999-2009 to describe clinicopathologic characteristics, treatment, outcomes, and prognostic factors for disease control and survival. Thirty patients with STS and seven patients with osteogenic sarcoma were identified. Most STS were high grade (23) and almost all were localized at presentation (28). Common histologies were synovial cell (6), rhabdomyosarcoma (5), angiosarcoma (4), liposarcoma (4) and leiomyosarcoma (3). The type of primary therapy and disease outcomes were analyzed. Cox proportional hazards regression analysis was performed to identify predictors of disease-free survival (DFS) and overall survival (OS). The HR and 95% CI for Cox model and median DFS/OS analyzed by Kaplan-Meier curves were calculated. [ABSTRACT FROM AUTHOR]

Purpose: Second tumors are an uncommon complication of multimodality treatment of childhood cancer. The present analysis attempted to correlate the dose received as a component of primary treatment and the site of the eventual development of a second tumor. Methods and Materials: We retrospectively identified 16 patients who had received radiotherapy to sites in the craniospinal axis and subsequently developed a second tumor. We compared the historical fields and port films of the primary treatment with the modern imaging of the second tumor locations. We classified the location of the second tumors as follows: in the boost field; marginal to the boost field, but in a whole-brain field; in a whole-brain field; marginal to the whole brain/primary treatment field; and distant to the field. We divided the dose received into 3 broad categories: high dose (>45 Gy), moderate dose (20–36 Gy), and low dose (<20 Gy). Results: The most common location of the second tumor was in the whole brain field (57%) and in the moderate-dose range (81%). Conclusions: Our data contradict previous publications that suggested that most second tumors develop in tissues that receive a low radiation dose. Almost all the second tumors in our series occurred in tissue within a target volume in the cranium that had received a moderate dose (20–36 Gy). These findings suggest that a major decrease in the brain volume that receives a moderate radiation dose is the only way to substantially decrease the second tumor rate after central nervous system radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To report the outcome of patients treated at the University of Florida who developed meningiomas after radiation to the central nervous system (CNS) for childhood cancer. Methods and Materials: We retrospectively identified 10 patients aged ≤19 years who received radiotherapy to sites in the craniospinal axis and subsequently developed a meningioma. We report the histology of the radiation-induced meningioma, treatment received, and ultimate outcome among this cohort of patients. Results: Meningioma was diagnosed at a median of 23.5 years after completion of the primary radiation. Fifty percent of second meningiomas were World Health Organization Grade 2 (atypical) or higher. All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). The actuarial event-free survival and overall survival rate at 5 years after treatment for a radiation-induced meningioma was 89%. Three patients who underwent resection for retreatment experienced a Grade 3 toxicity. Conclusions: Radiation-induced meningiomas after treatment of pediatric CNS tumors are effectively managed with single-modality therapy. Such late-effect data inform the overall therapeutic ratio and support the continued role of selective irradiation in managing pediatric CNS malignancies. [ABSTRACT FROM AUTHOR]

Background: Positive margins are known to impact survival in oral cavity squamous cell carcinoma (OCSCC). We aimed to determine the impact of positive margins on survival and whether radiation improves survival following positive margins.Methods: Data was obtained from the National Cancer Database and included patients with cT1T2N0 OCSCC. Survival outcomes were assessed via log-rank test. Cox-regression analysis was performed to determine if positive margins or radiation, when applicable, correlated with survival after accounting for covariates.Results: Positive margin patients had worse overall survival compared to negative margin control (HR = 1.76, p < 0.001) and reduced survival by 13%. On multivariate analysis, positive margins correlated with survival (HR = 1.60, p < 0.001). Radiation did not improve survival in positive margin patients (HR = 0.99, p = 0.55).Conclusions: Patients with positive margins have an 11-15% worse overall survival. Radiation does not appear to impact survival in patients with a positive margin. [ABSTRACT FROM AUTHOR]

Background: Palliative care improves symptoms and coping in patients with advanced cancers, but has not been evaluated for patients with curable solid malignancies. Because of the tremendous symptom burden and high rates of psychological distress in head and neck cancer (HNC), we evaluated feasibility and acceptability of a palliative care intervention in patients with HNC receiving curative-intent chemoradiation therapy (CRT). Methods: This was a prospective single-arm study in HNC patients receiving CRT at a single center in the United States. The intervention entailed weekly palliative care visits integrated with oncology care with a focus on symptoms and coping. The primary outcome was feasibility, defined as a >50% enrollment rate with >70% of patients attending at least half of the visits. To assess acceptability, we collected satisfaction ratings post-intervention. We also explored symptom burden, mood, and quality of life (QOL). Results: We enrolled 91% (20/22) of eligible patients. Patients attended 133 of 138 palliative care visits (96%); all 20 attended >85% of visits. Eighteen of 19 (95%) found the intervention "very helpful" and would "definitely recommend" it. QOL and symptom burden worsened from baseline to week 5, but subsequently improved at one-month post-CRT. Overall, patients valued the one-on-one format of the intervention and receipt of additional care. Conclusions: Our palliative care intervention during highly morbid CRT was feasible and acceptable with high enrollment, excellent intervention compliance, and high patient satisfaction. Future randomized studies will further explore the impact on patient-reported outcomes and health care utilization. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the recognized but poorly understood long-term toxicities of radiation therapy (RT) for head and neck cancer (HNC).Materials and Methods: We retrospectively evaluated patients treated with curative-intent RT for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥10years. Long-term toxicities of the upper aerodigestive tract were recorded and assigned to two broad categories: pharyngeal-laryngeal and oral cavity toxicity. Kaplan-Meier estimates and Chi-square tests were used for univariable analysis (UVA). Cox model and logistic regression were used for multivariable analysis (MVA).Results: We identified 112 patients with follow-up ≥10years (median 12.2). The primary tumor sites were pharynx (42%), oral cavity (34%), larynx (13%), and other (11%). Forty-four percent received postoperative RT, 24% had post-RT neck dissection, and 47% received chemotherapy. Twenty-eight (25%) patients developed pharyngeal-laryngeal toxicity, including 23 (21%) requiring permanent G-tube placed at median of 5.6years (0-20.3) post-RT. Fifty-three (47%) developed oral cavity toxicity, including osteoradionecrosis in 25 (22%) at a median of 7.2years (0.5-15.3) post-RT. On MVA, pharyngeal-laryngeal toxicity was significantly associated with chemotherapy (HR 3.24, CI 1.10-9.49) and age (HR 1.04, CI 1.00-1.08); oral cavity toxicity was significantly associated with chemotherapy (OR 4.40, CI 1.51-12.9), oral cavity primary (OR 5.03, CI 1.57-16.1), and age (OR 0.96, CI 0.92-1.00).Conclusion: Among irradiated HNC patients, pharyngeal-laryngeal and oral cavity toxicity commonly occur years after radiation, especially in those treated with chemotherapy. Follow-up for more than five years is essential because these significant problems afflict patients who have been cured. [ABSTRACT FROM AUTHOR]

TP53 mutation is the most frequent genetic event in head and neck squamous cell carcinoma (HNSCC), found in more than 80% of patients with human papillomavirus–negative disease. As mutations in the TP53 gene are associated with worse outcomes in HNSCC, novel therapeutic approaches are needed for patients with TP53 -mutated tumors. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issues of identifying and developing clinical trials for patients with TP53 mutations. Subcommittees, or breakout groups, were tasked with developing clinical studies in both the locally advanced and recurrent and/or metastatic (R/M) disease settings as well as considering signal-seeking trial designs. A fourth breakout group was focused on identifying and standardizing biomarker integration into trial design; this information was provided to the other breakout groups prior to the meeting to aid in study development. A total of 4 concepts were prioritized to move forward for further development and implementation. This article summarizes the proceedings of the Clinical Trials Planning Meeting with the goal of developing clinical trials for patients with TP53- mutant HNSCC that can be conducted within the National Clinical Trials Network. [ABSTRACT FROM AUTHOR]

• Mandibular osteoradionecrosis causes morbidity and increases healthcare costs. • Mandibular dose constraints for definitive radiotherapy are outdated. • V 44Gy < 42% and V 58Gy < 25% are novel mandibular constraints that need validation. • They were easily achieved without increased dose to surrounding tissues. • These intermediate-dose volumetric constraints can improve osteoradionecrosis rate. Mandibular dose constraints are designed to limit high dose to small volumes to avoid osteoradionecrosis (ORN). Based upon a published experience, intermediate-dose constraints were introduced but have not been independently validated. We hypothesize that these constraints lower ORN rate without compromising other organs at risk (OAR). Oropharyngeal cancer patients treated with standard fractionation adjuvant/definitive VMAT from 01/2014–08/2020 were included. In 09/2017, mandibular dose constraint was changed from historical constraint (HC) of D 0.1 cc < 70 Gy to modified constraints (MC) of V 44 Gy < 42%, V 58 Gy < 25%, D 0.5 cc < 70 Gy. OAR dosimetric changes and ORN development were evaluated. Regression modelling predicted long-term ORN cases in MC group. There were 174 patients, 71 in MC group. Seven cases of ORN in HC group at a median follow up (FU) of 39 months and 1 case of ORN in MC group at a median FU of 11 months were observed. More patients in the MC group met V 44 Gy (87% vs 62%, p < 0.01) and V 58 Gy constraints (92% vs 73%, p < 0.01). Mean doses to OARs did not rise. Mandible V 44 Gy and V 58 Gy were significantly associated with ORN (p < 0.01 and p = 0.03, respectively) across all patients. In the HC group, V 44 Gy was independently associated with ORN (p = 0.01). To account for shorter FU in MC group, logistic regression of ORN based on V 44 Gy in HC patients was performed. This predicts 3.2 ORN cases in the MC group (95% CI: 0.00–6.4). Achieving V 44 Gy and V 58 Gy was successful in 87% of cases without sacrificing target coverage or OARs and resulted in non-significant ORN decrease. [ABSTRACT FROM AUTHOR]

Retreatment of recurrent or second primary head and neck cancers occurring in a previously irradiated field is complex. Few guidelines exist to support practice. We performed an updated literature search of peer-reviewed journals in a systematic fashion. Search terms, key questions, and associated clinical case variants were formed by panel consensus. The literature search informed the committee during a blinded vote on the appropriateness of treatment options via the modified Delphi method. The final number of citations retained for review was 274. These informed 5 key questions, which focused on patient selection, adjuvant reirradiation, definitive reirradiation, stereotactic body radiation, and reirradiation to treat nonsquamous cancer. Results of the consensus voting are presented along with discussion of the most current evidence. This provides updated evidence-based recommendations and guidelines for the retreatment of recurrent or second primary cancer of the head and neck. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to compare the cosmesis and recurrence rates of conventional excision (CE), Mohs micrographic surgery (MMS), external-beam radiation therapy (EBRT), or brachytherapy (BT), for basal cell carcinoma and squamous cell carcinoma of the skin.Methods: Population, Intervention, Control, Outcome, Study Design (PICOS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) methods were used to identify studies on PubMed (from 1985 to 2018), including patients with American Joint Committee on Cancer (AJCC) T1-T2N0 basal cell carcinomas and squamous cell carcinomas and ≥10 months follow-up who received CE, MMS, EBRT, or BT. The primary endpoint was cosmesis, classified as "good," "fair," or "poor." The secondary endpoint was 1-year recurrence. Fixed-effects and random-effects meta-analyses were performed to evaluate primary and secondary outcomes with respect to treatment modality.Results: In total, 18,095 studies met initial search criteria. There were 24 CE, 13 MMS, 19 EBRT, and 7 BT studies included with a total of 21,371 patients. The summary effect size for "good" cosmesis was 81% (95% CI, 70.6%-89.6%), 74.6% (95% CI, 63%-84.6%), and 97.6% (95% CI, 91.3%-100%) for CE, EBRT, and BT, respectively. Good cosmesis was 96.0% in the only MMS study that reported cosmesis. BT had improved "good" cosmesis over EBRT (P = .0025) and was similar to CE and MMS. No significant differences were seen for "fair" or "poor" cosmesis. One-year recurrence rates were low throughout at 0.8% (95% CI, 0.3%-1.6%), 0.2% (95% CI, 0%-0.6%), 2% (95% CI, 1.3%-2.7%), and 0% (95% CI, 0%-0.5%) for CE, MMS, EBRT, and BT, respectively.Conclusions: For T1-T2N0 skin cancers, BT and MMS have improved cosmesis over EBRT and CE. It is unclear whether this is because of treatment superiority or selection and reporting bias. Local control is similar among all modalities at 1 year. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment.Materials and Methods: We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation.Results: We identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP.Conclusion: Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation. [ABSTRACT FROM AUTHOR]

Background: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab-an antibody against the epidermal growth factor receptor-can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity.Methods: RTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1-T2, N2a-N3 M0 or T3-T4, N0-N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1-T2 vs T3-T4), N category (N0-N2a vs N2b-N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5-7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility criteria are included. This study is registered with ClinicalTrials.gov, number NCT01302834.Findings: Between June 9, 2011, and July 31, 2014, 987 patients were enrolled, of whom 849 were randomly assigned to receive radiotherapy plus cetuximab (n=425) or radiotherapy plus cisplatin (n=424). 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible. After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival (hazard ratio [HR] 1·45, one-sided 95% upper CI 1·94; p=0·5056 for non-inferiority; one-sided log-rank p=0·0163). Estimated 5-year overall survival was 77·9% (95% CI 73·4-82·5) in the cetuximab group versus 84·6% (80·6-88·6) in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (HR 1·72, 95% CI 1·29-2·29; p=0·0002; 5-year progression-free survival 67·3%, 95% CI 62·4-72·2 vs 78·4%, 73·8-83·0), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (HR 2·05, 95% CI 1·35-3·10; 5-year proportions 17·3%, 95% CI 13·7-21·4 vs 9·9%, 6·9-13·6). Proportions of acute moderate to severe toxicity (77·4%, 95% CI 73·0-81·5 vs 81·7%, 77·5-85·3; p=0·1586) and late moderate to severe toxicity (16·5%, 95% CI 12·9-20·7 vs 20·4%, 16·4-24·8; p=0·1904) were similar between the cetuximab and cisplatin groups.Interpretation: For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma.Funding: National Cancer Institute USA, Eli Lilly, and The Oral Cancer Foundation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and toxicity of external beam reirradiation using a pulsed low-dose-rate (PLDR) technique.Methods and Materials: We evaluated patients treated with PLDR reirradiation from 2009 to 2016 at a single institution. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0, and local control was assessed using the Response Evaluation Criteria In Solid Tumors, version 1.1. On univariate analysis (UVA), the χ2 and Fisher exact tests were used to assess the toxicity outcomes. Competing risk analysis using cumulative incidence function estimates were used to assess local progression.Results: A total of 39 patients were treated to 41 disease sites with PLDR reirradiation. These patients had a median follow-up time of 8.8 months (range 0.5-64.7). The targets were the thorax, abdomen, and pelvis, including 36 symptomatic sites. The median interval from the first radiation course and reirradiation was 26.2 months; the median dose of the first and second course of radiation was 50.4 Gy and 50 Gy, respectively. Five patients (13%) received concurrent systemic therapy. Of the 39 patients, 9 (23%) developed grade ≥2 acute toxicity, most commonly radiation dermatitis (5 of 9). None developed grade ≥4 acute or subacute toxicity. The only grade ≥2 late toxicity was late skin toxicity in 1 patient. On UVA, toxicity was not significantly associated with the dose of the first course of radiation or reirradiation, the interval to reirradiation, or the reirradiation site. Of the 41 disease sites treated with PLDR reirradiation, 32 had pre- and post-PLDR scans to evaluate for local control. The local progression rate was 16.5% at 6 months and 23.8% at 12 months and was not associated with the dose of reirradiation, the reirradiation site, or concurrent systemic therapy on UVA. Of the 36 symptomatic disease sites, 25 sites (69%) achieved a symptomatic response after PLDR, including 6 (17%) with complete symptomatic relief.Conclusion: Reirradiation with PLDR is effective and well-tolerated. The risk of late toxicity and the durability of local control were limited by the relatively short follow-up duration in the present cohort. [ABSTRACT FROM AUTHOR]

Background and purpose To compare cosmesis and local recurrence (LR) of definitive external beam radiation therapy (EBRT) vs brachytherapy (BT) for indolent basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin. Materials and methods Studies including patients with T1-2 N0 SCCs/BCCs treated with definitive EBRT/BT and ≥10 months follow-up were analyzed. The primary endpoint was post-treatment cosmesis, categorized as “good,” “fair,” or “poor.” The secondary endpoint was LR. Mixed effects regression models were used to estimate weighted linear relationships between biologically equivalent doses with α / β  = 3 (BED 3 ) and cosmetic outcomes. Results A total of 9965 patients received EBRT and 553 received BT across 24 studies. Mean age was 73 years, median follow-up was 36 months, and median dose was 45 Gy/10 fractions at 4.4 Gy/fraction. At BED 3 of 100 Gy, “good” cosmesis was more frequently observed in patients receiving BT, 95% (95% CI: 88–100%) vs 79% (95% CI: 60–82%), p  < 0.05. Similar results were found for “good” cosmesis at BED 3 >100 Gy. No difference in “poor” cosmesis was noted at any BED 3 . LR was <7% for both at one year. Conclusion BT has favorable cosmesis over EBRT for skin SCCs/BCCs at common fractionation regimens. Prospective studies comparing EBRT vs BT are warranted. [ABSTRACT FROM AUTHOR]

Purpose To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs). Methods A PICOS/PRISMA/MOOSE selection protocol was performed to identify 344 articles published between 1985–2016 evaluating patients with T1–2 N0 SCCs/BCCs treated with definitive RT. Biologically equivalent doses with α/β = 3 (BED 3 s) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED 3 and cosmetic outcomes. Results A total of 21 studies were identified detailing the treatment of 9729 skin BCC/SCC patients, across seven countries, with external beam RT (n = 9255) or brachytherapy (n = 474). Median follow-up was 36 months (range: 12–77). Median dose was 45 Gy/11 fractions (interquartile range: 37.5 Gy/6–55 Gy/18) at 4 Gy/fraction (interquartile range: 2.5–6 Gy); most hypofractionated 18.75 Gy/1. There was a trend to decreased “good” cosmesis with higher total dose: −3.4% “good” cosmesis/10 Gy BED 3 , p = 0.01. Similarly, there was a trend to increased “fair” cosmesis with higher dose: +3.8% “fair” cosmesis/10 Gy BED 3, p = 0.006. At a BED 3 of 100 Gy, the expected rate of “good” cosmesis is 79% (95% confidence interval: 70%, 88%). Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED 3 . Fewer than 8% of patients experienced “poor” cosmesis, independent of dose or fractionation regimen. Conclusion Hypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED 3 of ∼100 Gy: 50 Gy/15 fractions, 36.75 Gy/7 fractions, or 35 Gy/5 fractions, as they result in “good” cosmesis in 80% of patients. [ABSTRACT FROM AUTHOR]

Locoregionally advanced nonmelanoma skin cancer (NMSC) has an aggressive clinical course characterized by high rates of treatment failure and poor survival compared with localized skin cancers. Our goal was to investigate multimodal therapy for lymph-node–positive NMSC. Data from patients with lymph-node–positive NMSC who underwent surgery and adjuvant therapy at a single tertiary center from 2002 to 2012 were retrospectively reviewed. Median follow-up was 1.8 years (range: 0.5 to 8.5). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The chi-square test and logistic regression were used to determine the association between locoregional control (LRC) and the following variables: evidence of extracapsular extension, number of lymph nodes positive, largest involved lymph node, presence of a positive margin, and use of concurrent chemoradiation (CRT). Forty-six patients were evaluated, 13 (28%) of whom received adjuvant CRT. CRT patients were younger (p < 0.001) and had a significantly greater number of positive lymph nodes (p = 0.016) than patients who received adjuvant radiation alone. At 5 years, LRC was 76%, PFS was 65%, and OS was 49%. Univariate analysis demonstrated that CRT (p = 0.006), largest lymph node measurement (p = 0.039), and ≥3 involved lymph nodes (p = 0.001) predicted local recurrence. CRT (p = 0.035, odds ratio [OR] 0.20 [95% confidence interval 0.05 to 0.90]) and ≥3 involved lymph nodes (p = 0.017, OR 0.07 [95% confidence interval 0.01 to 0.62]) remained significant on multivariate analysis. CRT was well tolerated. No grade ≥3 toxicities were observed except for 1 asymptomatic grade-4 thrombocytopenia. Patients with lymph-node–positive NMSC do poorly. Patient selection for intensification of adjuvant therapy needs clarification. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation.Methods and Materials: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT was defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ2 tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status.Results: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01).Conclusion: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies. [ABSTRACT FROM AUTHOR]

Purpose: To assess the relationship between tumor-specific growth rate (TSGR) and oropharyngeal cancer (OPC) outcomes in the HPV era.Methods/materials: Primary tumor volume differences between a diagnostic and secondary scan separated ⩾7days without interval treatment were used to estimate TSGR, defined as percent volume growth/day derived from primary tumor volume doubling time for 85 OPC patients with known p16 status and smoking pack-years managed with (chemo)radiation. Variables were analyzed using Kruskal-Wallis or Fisher's exact test as appropriate. Log-rank tests and Cox proportional models analyzed endpoints. Using concordance probability estimates (CPE), TSGR was incorporated into RTOG 0129 risk grouping (0129RG) to assess whether TSGR could improve prognostic accuracy.Results: Median time between scans was 35days (range 8-314). Median follow up was 26months (range 1-76). The 0129RG classification was: 56% low, 25% intermediate, and 19% high risk. Median TSGR was 0.74%/day (range 0.01-4.25) and increased with 0129RG low (0.41%), intermediate (0.57%) and high (1.23%) risk, respectively (p=0.015). TSGR independently predicted for TF (TSGR: HR (95%CI)=2.79, 1.67-4.65, p<0.001) in the Cox model. On CPE, prognostic accuracy for TF, disease-free survival and overall survival was improved when 0129RG was combined with TSGR. Dichotomizing 0129RG by median TSGR yielded no observed recurrences in low risk patients with TSGR<0.74% and demonstrated significant difference for intermediate risk (8% vs. 50% for TSGR<0.74% vs. ⩾0.74%, respectively, p<0.001).Conclusion: Tumor-specific growth rate correlates with increasing 0129RG and predicts treatment failure, potentially improving the prognostic strength and risk stratification of established 0129 risk groups. [ABSTRACT FROM AUTHOR]

Purpose: This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue.Materials and Methods: Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed.Results: 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52 months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p=0.005 and 49% vs 80%, p=0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p=0.02) and the effect of severe dysplasia at the margin was approaching significance (p=0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p=0.006) and DFS (HR: 2.84, p=0.008) associated with severe or moderate dysplasia at the margin.Conclusions: Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity. [ABSTRACT FROM AUTHOR]

Summary: Purpose: This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue. Materials and methods: Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed. Results: 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p =0.005 and 49% vs 80%, p =0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p =0.02) and the effect of severe dysplasia at the margin was approaching significance (p =0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p =0.006) and DFS (HR: 2.84, p =0.008) associated with severe or moderate dysplasia at the margin. Conclusions: Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity. [ABSTRACT FROM AUTHOR]

Summary: Patients with head and neck squamous cell carcinoma (HNSCC) often require assistance from family caregivers during the treatment and post-treatment period. This review article sought to summarize current findings regarding the psychological health of HNSCC caregivers, including factors that may be associated with poorer psychological health. Online databases (PUBMED, MEDLINE and PSYCINFO) were searched for papers published in English through September 2010 reporting on the psychological health of caregivers of HNSCC patients. Eleven papers were identified. Caregivers experience poorer psychological health, including higher levels of anxious symptoms, compared to patients and to the general population. Fear of patient cancer recurrence is evident among caregivers and is associated with poorer psychological health outcomes. The 6-month interval following diagnosis is a significant time of stress for caregivers. Greater perceived social support may yield positive benefits for the psychological health of caregivers. To date, there have been relatively few reports on the psychological health of caregivers of HNSCC patients. Well designed, prospective, longitudinal studies are needed to enhance our understanding of how caregiver psychological health may vary over the cancer trajectory and to identify strategies for improving caregiver outcomes. [ABSTRACT FROM AUTHOR]