Patient choice for high-volume center radiation impacts head and neck cancer outcome.

BACKGROUND: Studies suggest treatment outcomes may vary between high (HVC)- and low-volume centers (LVC). Radiation therapy (RT) for head and neck cancer (HNC) requires weeks of treatment, the inconvenience of which may influence a patient's choice for treatment location. We hypothesized that receipt of RT for HNC at a HVC would influence outcomes compared to patients evaluated at a HVC, but who chose to receive RT at a LVC. METHODS: From 1998 to 2011, 1930 HNC patients were evaluated at a HVC and then treated with RT at either a HVC or LVC. Time-to-event outcomes and treatment factors were compared. RESULTS: Median follow-up was 34 months. RT was delivered at a HVC for 1368 (71%) patients and at a LVC in 562 (29%). Patients were more likely to choose HVC-RT if they resided in the HVC's county or required definitive RT (all P < 0.001). HVC-RT was associated with a significant improvement in 3-year LRC (84% vs 68%), DFS (68% vs 48%), and OS (72% vs 57%) (all P < 0.001). On multivariate analysis (MVA), HVC-RT independently predicted for improved LRC, DFS, and OS (all P < 0.05). CONCLUSIONS: In patients evaluated at a HVC, the choice of RT location was primarily influenced by their residing distance from the HVC. HVC-RT was associated with improvements in LRC, DFS, and OS in HNC. As treatment planning and delivery are technically demanding in HNC, the choice to undergo treatment at a HVC may result in more optimal delivered dose, RT duration, and outcome.

Interferon is associated with improved survival for node-positive cutaneous melanoma: a single-institution experience.

AIM: We assessed the role of adjuvant interferon on relapse-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) in node-positive melanoma patients. METHODS: We retrospectively reviewed 385 node-positive patients without distant metastatic disease treated from 1998 to 2015. The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph node biopsy ± completion LND (n = 270). 128 patients (33.2%) received adjuvant interferon. RESULTS: After a median follow-up of 70 months, interferon was associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR: 0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal stage, node size, sex, primary site, adjuvant therapy and extracapsular extension. In an exploratory age-matched comparison of patients treated with (n = 67) and without (n = 233) adjuvant immunotherapy, interferon still showed improved RFS, DMFS and OS. CONCLUSION: Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.

Adjuvant radiation provides survival benefit for resected pancreatic adenocarcinomas of the tail.

BACKGROUND: The appropriate adjuvant treatment for resected pancreatic cancer remains a controversy. We sought to determine the effect of adjuvant treatment on overall survival (OS) in patients with pancreatic tail adenocarcinoma. METHODS: Retrospective review of patients with upfront surgically resected pancreatic tail cancer treated at our institution between 2000-2012 was performed to determine outcomes of patients treated with and without adjuvant radiation therapy (RT). Survival curves were calculated according to the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the Cox proportional hazards model. RESULTS: Thirty-four patients met inclusion criteria. 79% received adjuvant chemotherapy, either concurrent with RT or alone. The groups were well matched, with the only significant difference being patient sex. On both UVA and MVA there was significantly worse survival in patients with a post-op CA19-9 >90 [hazard ratio (HR) 5.55; 95% confidence interval (CI): 1.20-25.7, P=0.03] and improved survival in patients treated with adjuvant RT (HR 0.15; 95% CI: 0.04-0.58, P=0.006). The median and 2-year OS were 21.6 months and 47% for patients treated with adjuvant RT compared with 11.3 months and 21% for those treated without RT. CONCLUSIONS: Although few in patient numbers, this data suggests integration of adjuvant RT in resected pancreatic tail adenocarcinoma may improve OS.

Three-dimensional printer-aided casting of soft, custom silicone boluses (SCSBs) for head and neck radiation therapy.

PURPOSE: Custom tissue compensators provide dosimetric advantages for treating superficial or complex anatomy, but currently available fabrication technology is expensive or impractical for most clinical operations and yields compensators that are difficult for patients to tolerate. We aimed to develop an inexpensive, clinically feasible workflow for generating patient-specific, soft, custom silicone boluses (SCSBs) for head-and-neck (HN) radiation therapy. METHODS AND MATERIALS: We developed a method using 3-dimensional printed parts for generating SCSBs for the treatment of HN cancers. The clinical workflow for generation of SCSBs was characterized inclusive of patient simulation to treatment in terms of resource time and cost. Dosimetric properties such as percentage depth dose and dose profiles were measured for SCSBs using GaF films. Comprehensive measurements were also conducted on an HN phantom. SCSBs were generated and used for electron or photon based radiation treatments of 7 HN patients with lesions at nose, cheek, eye, or ears. In vivo dose measurements with optically simulated luminescence dosimeters were performed. RESULTS: Total design and fabrication time from patient simulation to radiation treatment start required approximately 1 week, with fabrication constituting 1 to 2 working days depending on bolus surface area, volume, and complexity. Computed tomography and dosimetric properties of the soft bolus were similar to water. In vivo dose measurements on 7 treated patients confirmed that the dose deposition conformed to planned doses. Material costs were lower than currently available hard plastic boluses generated with 3-dimensional printing technology. All treated patients tolerated SCSBs for the duration of therapy. CONCLUSIONS: Generation and use of SCSBs for clinical use is feasible and effective for the treatment of HN cancers.

Tumour radiosensitivity is associated with immune activation in solid tumours.

PURPOSE: Our goal was to determine whether tumour radiosensitivity is associated with activation of the immune system across all tumour types as measured by two gene expression signatures (GESs). METHODS: We identified 10,240 genomically profiled distinct solid primary tumours with gene expression analysis available from an institutional de-identified database. Two separate GESs were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity) and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumour samples and, in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterised, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumour radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation. RESULTS: Using an RSI cut-point of ≤0.3745, RSI-low tumours (n = 4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [-0.136, 1.095]) compared with RSI-high tumours (-0.17 [-0.82, 0.42]; p < 0.001) across all tumour samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early-stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p = 0.02), with RSI (hazard ratio [HR] 0.63 [95% confidence interval 0.36, 1.09]) and 12-CK (HR 0.66 [0.41, 1.04]) each providing comparable contributions. CONCLUSIONS: Tumour radiosensitivity is associated with immune activation as measured by the two GESs.

Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.

Background: Regional radiation therapy (RT) has been shown to reduce the risk of regional recurrence with node-positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT. Methods: A single-institution, Institutional Review Board-approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions (range, 5-30). Primary outcomes were regional control and overall survival by RSI GES status. Results: Median follow-up was 69 months (range, 13-180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%; P=.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43; P<.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%; P=.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; P<.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14). Conclusions: Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance.

Staged reconstruction brachytherapy has lower overall cost in recurrent soft-tissue sarcoma.

PURPOSE: Adjuvant brachytherapy (AB) with immediate (IR) and staged reconstruction (SR) are distinct treatment modalities available for patients with recurrent soft tissue sarcoma (STS). Although SR may offer local control and toxicity benefit, it requires additional upfront procedures, and there is no evidence that it improves overall survival. With the importance of value-based care, our goal is to identify which technique is more cost effective. MATERIAL AND METHODS: A retrospective review of 22 patients with recurrent extremity STS treated with resection followed by AB alone. Hospital charges were used to compare the cost between SR and IR at the time of initial treatment, at 6-month intervals following surgery, and cumulative cost comparisons at 18 months. RESULTS: Median follow-up was 31 months. Staged reconstruction (n = 12) was associated with an 18-month local control benefit (85% vs. 42%, p = 0.034), compared to IR (n = 10). Staged reconstruction had a longer hospital stay during initial treatment (10 vs. 3 days, p = 0.002), but at 18 months, the total hospital stay was no longer different (11 vs. 11 days). Initially, there was no difference in the cost of SR and IR. With longer follow-up, cost eventually favored SR, which was attributed primarily to the costs associated with local failure (LF). On multivariate analysis, cost of initial treatment was associated with length of hospital stay (~$4.5K per hospital day, p < 0.001), and at 18 months, the cumulative cost was ~175K lower with SR (p = 0.005) and $58K higher with LF (p = 0.02). CONCLUSIONS: In recurrent STS, SR has a longer initial hospital stay when compared to IR. At 18 months, SR had lower rates of LF, translating to lower total costs for the patient. SR is the more cost-effective brachytherapy approach in the treatment of STS, and should be considered as healthcare transitions into value-based medicine.

Improved local and regional control with radiotherapy for Merkel cell carcinoma of the head and neck.

BACKGROUND: We hypothesized that radiotherapy (RT) would improve both local and regional control with Merkel cell carcinoma of the head and neck. METHODS: A single-institution institutional review board-approved study was performed including 113 patients with nonmetastatic Merkel cell carcinoma of the head and neck. Postoperative RT was delivered to the primary tumor bed (71.7% cases) ± draining lymphatics (33.3% RT cases). RESULTS: Postoperative local RT was associated with improved local control (3-year actuarial local control 89.4% vs 68.1%; p = .005; Cox hazard ratio [HR] 0.18; 95% confidence interval [CI] = 0.06-0.55; p = .002). Similarly, regional RT was associated with improved regional control (3-year actuarial regional control 95.0% vs 66.7%; p = .008; Cox HR = 0.09; 95% CI = 0.01-0.69; p = .02). Regional RT played an important role for both clinical node-negative patients (3-year regional control 100% vs 44.7%; p = .03) and clinical/pathological node-positive patients (3-year regional control 90.9% vs 55.6%; p = .047). CONCLUSION: Local RT was beneficial for all patients with Merkel cell carcinoma of the head and neck, whereas regional RT was beneficial for clinical node-negative and clinical/pathological node-positive patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 48-55, 2017.

A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study.

BACKGROUND: Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose. METHODS: We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical outcome in five clinical cohorts: Erasmus Breast Cancer Cohort (n=263); Karolinska Breast Cancer Cohort (n=77); Moffitt Lung Cancer Cohort (n=60); Moffitt Pancreas Cancer Cohort (n=40); and The Cancer Genome Atlas Glioblastoma Patient Cohort (n=98). FINDINGS: We calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66-172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13-3·94, p=0·018). INTERPRETATION: A GARD-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology. FUNDING: None.

Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy.

BACKGROUND: Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival. MATERIALS AND METHODS: We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax). RESULTS: Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients. CONCLUSION: Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC.

Increased acute mortality with chemoradiotherapy for locally advanced head and neck cancer in patients ≥70years.

PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard of care for many sites of locally advanced head and neck squamous cell carcinomas (LAHNC). However, on meta-analysis, the addition of chemotherapy did not improve survival for patients >70years. We hypothesized that elderly patients treated with CRT would have increased toxicity without similar improvements in survival. METHODS: A single-institution, IRB-approved retrospective study took place from 2005 to 2012 including 369 patients treated with CRT for LAHNC. Multivariate models for death at 3months and death over time were developed using logistic regression and Cox modeling, respectively. RESULTS: Patients ≥70years were treated less often with concurrent cisplatin dosed every 3weeks (25.5% vs. 71.4%, respectively) and more often with weekly carboplatin (31.9% vs. 3.4%) than patients <70years (n=322; p<0.001). Patients ≥70years experienced increased toxicity during treatment with more frequently hospitalizations (36.2% vs. 21.1%; p=0.02) and a lower rate of PEG removal at last follow-up or death (77.1% vs. 92.9%; p=0.004). A higher proportion of patients ≥70years died within 3months (12.8% vs. 2.8%; p=0.001) following CRT. Patients ≥70 had an increased risk of death at 3months following CRT (odds ratio 5.19, 95% CI 1.64-16.41; p=0.005) and worse survival over time (hazard ratio 2.30, 95% CI 1.34-3.93; p=0.002). CONCLUSIONS: Patients ≥70years were more often treated with less toxic chemotherapy, yet experienced higher rates of hospitalization during treatment and increased rates of acute mortality following CRT. The efficacy of chemoradiotherapy for elderly patients should be evaluated in a prospective setting.

Effect of body mass index on operative outcome after robotic-assisted Ivor-Lewis esophagectomy: retrospective analysis of 129 cases at a single high-volume tertiary care center.

The impact of body weight on outcomes after robotic-assisted esophageal surgery for cancer has not been studied. We examined the short-term operative outcomes in patients according to their body mass index following robotic-assisted Ivor-Lewis esophagectomy at a high-volume tertiary-care referral cancer center and evaluated the safety of robotic surgery in patients with an elevated body mass index. A retrospective review of all patients who underwent robotic-assisted Ivor-Lewis esophagectomy between April 2010 and June 2013 for pathologically confirmed distal esophageal cancer was conducted. Patient demographics, clinicopathologic data, and operative outcomes were collected. We stratified body mass index at admission for surgery according to World Health Organization criteria; normal range is defined as a body mass index range of 18.5-24.9 kg/m2. Overweight is defined as a body mass index range of 25.0-29.9 kg/m2 and obesity is defined as a body mass index of 30 kg/m2 and above. Statistics were calculated using Pearson's Chi-square and Pearson's correlation coefficient tests with a P-value of 0.05 or less for significance. One hundred and twenty-nine patients (103 men, 26 women) with median age of 67 (30-84) years were included. The majority of patients, 76% (N = 98) received neoadjuvant therapy. When stratified by body mass index, 28 (22%) were normal weight, 56 (43%) were overweight, and 45 (35%) were obese. All patients had R0 resection. Median operating room time was 407 (239-694) minutes. When stratified by body mass index, medians of operating room time across the normal weight, overweight and obese groups were 387 (254-660) minutes, 395 (310-645) minutes and 445 (239-694), respectively. Median estimated blood loss (EBL) was 150 (25-600) cc. When stratified by body mass index, medians of EBL across the normal weight, overweight and obese groups were 100 (50-500) cc, 150 (25-600) cc and 150 (25-600), respectively. Obesity significantly correlated with longer operating room time (P = 0.05) but without significant increased EBL (P = 0.348). Among the three body mass index groups there was no difference in postoperative complications including thrombotic events (pulmonary embolism and deep venous thrombosis) (P = 0.266), pneumonia (P = 0.189), anastomotic leak (P = 0.090), wound infection (P = 0.390), any cardiac events (P = 0.793) or 30 days mortality (P = 0.414). Our data study demonstrates that patients with esophageal cancer and an elevated body mass index undergoing robotic-assisted Ivor-Lewis esophagectomy have increased operative times but no significantly increased EBL during the procedure. Other potential morbidities did not differ with the robotic approach.

Treatment delays, race, and outcomes in head and neck cancer.

PURPOSE: Patient race has been shown to predict for differences in outcomes and has been attributed to socioeconomic factors such as social support and access to healthcare. In head and neck cancer (HNC), a disease without recommended screening, we sought to investigate the association between race, treatment delays and outcome. METHODS: Records of 1802 patients with non-metastatic squamous cell HNC treated between 1998 and 2013 were retrospectively assessed from an institutional database. Patient demographics, tumor and treatment characteristics, and patient outcomes were abstracted from the chart. Differences between groups were assessed via logistic regression multivariate analysis (MVA). Outcomes including locoregional control (LRC) and overall survival (OS) were then estimated via Kaplan-Meier and Cox-regression MVA. RESULTS: Median follow up was 34 months. Patient races included white (n=1671, 93%), black (n=80, 4%), Asian (n=18, 1%), and other (n=33, 2%). On logistic regression MVA, Black patients were less likely to be married (39% vs. 63%; OR 0.5 95%CI 0.30-0.83, p=0.007) or be currently employed (43% vs. 61%; OR 0.44 95%CI 0.26-0.74, p=0.002) when compared to non-blacks. Black patients were also younger (54 vs. 59 years, p=0.001), more likely to present with advanced tumor stage (T4: 48% vs. 25%), and more often had >45days elapsed from diagnosis to treatment initiation (DTI) (61% vs. 49%, p=0.028). Delays in treatment, such as delayed diagnosis (advanced disease presentation) and delays in DTI>45days were also associated with marital and employment status. Black patients were associated with a lower 3-year LRC rate (65% vs. 81%, p<0.001) and OS rate (43% vs. 69%, p<0.001), compared to non-black patients. Patients with >45days DTI had a detriment in 3-year LRC (77% vs. 83%, p=0.002) and OS (66% vs. 69%, p=0.009). On Cox MVA, black race was independently prognostic for worse LRC (HR 1.62 95%CI 1.04-2.51, p=0.033) and OS (HR 1.55 95%CI 1.15-2.08, p=0.004) vs. non-blacks. CONCLUSION: Black race is independently prognostic for LRC and OS. Delays in HNC treatment, such as more advanced tumor stage presentation and delays in treatment initiation, may be attributed to socioeconomic factors such as employment status and social support. Efforts to accommodate these factors may expedite treatment, in hopes of improving the race related outcome disparity in HNC.

Having Medicaid insurance negatively impacts outcomes in patients with head and neck malignancies.

BACKGROUND: Patients covered by Medicaid insurance appear to have poorer cancer outcomes. Herein, the authors sought to test whether Medicaid was associated with worse outcomes among patients with head and neck cancer (HNC). METHODS: The records of 1698 patients with squamous cell HNC without distant metastatic disease were retrospectively reviewed from an institutional database between 1998 and 2011. At the time of diagnosis, insurance status was categorized as Medicaid, Medicare/other government insurance, or private insurance. Outcomes including locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan-Meier method and Cox regression multivariate analysis (MVA). RESULTS: The median follow-up for all patients was 35 months. Medicaid patients comprised 11% of the population; the remaining patients were privately insured (56%) or had Medicare/government insurance (34%). On MVA, Medicaid patients were younger, were current smokers, had higher tumor T and N classifications, and experienced a longer time from diagnosis to treatment initiation (all P<.005). Medicaid insurance status was associated with a deficit of 13% in LRC (69% vs 82%) and 26% in OS (46% vs 72%) at 3 years (all with P<.001). A time from diagnosis to treatment initiation of >45 days was found to be associated with worse 3-year LRC (77% vs 83%; P = .009) and OS (68% vs 71%; P = .008). On MVA, Medicaid remained associated with a deficit in LRC (P = .002) and OS (P<.001). CONCLUSIONS: Patients with Medicaid insurance more often present with locally advanced HNC and experience a higher rate of treatment delays compared with non-Medicaid patients. Medicaid insurance status appears to be independently associated with deficits in LRC and OS. Improvements in the health care system, such as expediting treatment initiation, may improve the outcomes of patients with HNC. Cancer 2016;122:3529-3537. © 2016 American Cancer Society.

Favorable perioperative outcomes after resection of borderline resectable pancreatic cancer treated with neoadjuvant stereotactic radiation and chemotherapy compared with upfront pancreatectomy for resectable cancer.

BACKGROUND: Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) are utilized to increase margin negative (R0) resection rates in borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) patients. Concerns persist that these neoadjuvant therapies may worsen perioperative morbidities and mortality. METHODS: Upfront resection patients (n=241) underwent resection without neoadjuvant treatment for resectable disease. They were compared to BRPC or LAPC patients (n=61) who underwent resection after chemotherapy and 5 fraction SBRT. Group comparisons were performed by Mann-Whitney U or Fisher's exact test. Overall Survival (OS) was estimated by Kaplan-Meier and compared by log-rank methods. RESULTS: In the neoadjuvant therapy group, there was significantly higher T classification, N classification, and vascular resection/repair rate. Surgical positive margin rate was lower after neoadjuvant therapy (3.3% vs. 16.2%, P=0.006). Post-operative morbidities (39.3% vs. 31.1%, P=0.226) and 90-day mortality (2% vs. 4%, P=0.693) were similar between the groups. Median OS was 33.5 months in the neoadjuvant therapy group compared to 23.1 months in upfront resection patients who received adjuvant treatment (P=0.057). CONCLUSIONS: Patients with BRPC or LAPC and sufficient response to neoadjuvant multi-agent chemotherapy and SBRT have similar or improved peri-operative and long-term survival outcomes compared to upfront resection patients.

Management of Oropharyngeal Cancer in the HPV Era.

BACKGROUND: Historically, oropharyngeal cancer (OPC) has been attributed to risk factors such as smoking and alcohol use. The increased incidence of OPC has been driven by human papillomavirus (HPV) infection. METHODS: A search of the literature involving HPV infection and OPC was performed, along with a search of ongoing clinical trials regarding HPV-positive OPC. RESULTS: This review summarizes the differences in epidemiology and prognosis of HPV-positive OPC compared with non-HPV-related OPC. It will also discuss use of de-escalating treatment to minimize toxicity while maintaining excellent outcomes. Disease management is also addressed, including prevention and follow-up recommendations for this cohort of patients. CONCLUSIONS: HPV-positive OPC is a distinct disease, and efforts should be made to personalize its management. Preventive measures and vaccinations, along with de-escalation of treatment, may help optimize outcomes in this population.

Management of BCC and SCC of the Head and Neck.

BACKGROUND: For decades radiotherapy (RT) has been shown to treat skin cancers; however, the indications, delivery methods, and techniques for RT continue to evolve. METHODS: Relevant prospective and retrospective reports were reviewed that addressed outcomes with, indications for, and delivery techniques used with RT for the management of cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the head and neck. RESULTS: Rates of local control higher than 90% are typically achievable for early-stage BCC and SCC of the head and neck. RT is often recommended for tumors located in cosmetically or functionally sensitive areas of the face, for patients who cannot tolerate anesthesia, for those taking anticoagulants, or for patients who prefer RT to other treatment options. A wide range of radiation doses, daily fractionation schedules, and radiation techniques have been shown to be effective for management. In general, postoperative local radiation is recommended following excision for patients with high-risk factors, including those whose tumors have close or positive margins, perineural invasion, invasion of the bone or nerves, or those with recurrent disease. CONCLUSIONS: RT plays an integral role in the treatment of primary and postoperative cutaneous BCC and SCC of the head and neck. Prospective trials are in progress to address the roles of concurrent systemic therapy and RT for both cutaneous BCC and SCC.

Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma.

BACKGROUND: Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival. METHODS: We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). RESULTS: Median follow-up was 33 months. Treatment with RT was associated with improved 3-year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07-0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14-0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31-0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively). CONCLUSIONS: RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.

Stereotactic Body Radiotherapy for Recurrent Unresectable Head and Neck Cancers.

BACKGROUND: Treatment of locoregional, recurrent head and neck cancers following definitive radiotherapy has evolved during the past 30 years. Brachytherapy as well as protracted courses of systemic therapy and chemoradiotherapy result in 12-month survival rates of 40% to 50% but have high rates of severe toxicity. Given the advancements in radiotherapy targeting and delivery, stereotactic body radiotherapy (SBRT) has been investigated as an alternative treatment option with the potential advantages of reduced treatment time and rates of toxicity. METHODS: The authors reviewed prospective trials and retrospective reports from the past decade addressing the management of locoregional, recurrent, previously radiated head and neck cancers, focusing on SBRT. RESULTS: The body of evidence is growing in support of reirradiation using SBRT for the treatment of recurrent head and neck cancers. The 1-year survival rates associated with SBRT are promising and similar to those seen with chemotherapy alone and concurrent, conventionally fractionated radiotherapy and chemotherapy. Treatment-related adverse events of reirradiation using SBRT are also similar to other palliative therapies. Late carotid rupture is a relatively rare but concerning late toxicity associated with reirradiation using SBRT. CONCLUSIONS: SBRT is a promising treatment for locoregional recurrent head and neck cancers. It also offers a logistical advantage over other palliative treatments, as it only requires 1 to 2 weeks of treatment.

Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management. METHODS: An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed. RESULTS: The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years. CONCLUSIONS: HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter.