Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.

PURPOSE: Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. RESULTS: 92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7-100] compared with those with no stage change (58%; 95% CI, 46.2-69.8) or upstage (40%; 95% CI, 9.6-70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078). CONCLUSIONS: Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.

Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504.

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown. METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms. RESULTS: Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol. CONCLUSIONS: Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593).

A phase â ¡ prospective trial of photobiomodulation therapy in limiting oral mucositis in the treatment of locally advanced head and neck cancer patients.

Objective: This study aimed to compare the historical incidence rate of severe oral mucositis (OM) in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy (CRT) versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with prophylactic photobiomodulation therapy (PBMT). Methods: This US-based, institutional, single-arm, phase Ⅱ prospective clinical trial was initiated in 50 patients (age ≥ 18 years, Karnofsky Performance Scale Index > 60, with locally advanced HNSCC (excluding oral cavity) receiving definitive or adjuvant radiation therapy (RT) with concurrent platinum-based chemotherapy (CT). PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system. Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria, version 4.0 (NCI-CTCAE) Grade ≥3 and the World Health Organization Mucositis Grading Scale (WHO) Grade ≥3 versus historical controls; secondary outcome measures included time to onset of severe OM following therapy initiation. Results: At baseline, all patients included in final analysis (N = 47) had OM Grade 0. Average RT and CT dose was (66.3 ± 5.1) Gy and (486.1 ± 106.8) mg/m2, respectively. Severe OM was observed in 11 of 47 patients (23%, confidence interval: 12, 38). OM toxicity grade trended upward during treatment, reaching a maximum at 7 weeks (WHO: 1.8 vs. NCI-CTCAE: 1.7). Subsequently, OM grade returned to baseline 3 months following completion of RT. The mean time to onset of severe OM was (35 ± 12) days. The mean time to resolution of severe OM was (37 ± 37) days. Conclusions: Compared to historical outcomes, PBMT aides in decreasing severe OM in patients with locally advanced HNSCC. PBMT represents a minimally invasive, prophylactic intervention to decrease OM as a major treatment-related side effect.

A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer.

PURPOSE: Aberrant mTOR pathway and somatostatin receptor signaling are implicated in thyroid cancer and offer potential therapeutic targets. We assessed the clinical efficacy of everolimus and Pasireotide long-acting release (LAR) in radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC). PATIENTS AND METHODS: Adults with progressive MTC and DTC untreated or treated with no more than one systemic agent were eligible. The trial was designed to establish the most promising regimen and the optimal combination sequence. Patients were randomized to start treatment with single agent everolimus (10 mg QD; Arm A), pasireotide-LAR (60 mg intramuscular injection, Q4 weeks; Arm B), or the combination (Arm C). At initial progression (PFS1), patients on Arm A or B switched to the combination and continued until progression (PFS2). Efficacy was measured by RECIST criteria. RESULTS: Study enrolled 42 patients: median age 65 years; female 17 (40.5%); White 31 (73.8%), African American 6 (14.3%), others 5 (11.9); DTC 32 (76.2%); MTC 10 (23.8%). There was no objective response by RECIST criteria across the three arms. Median and 1-year PFS1 rates were 8.3, 1.8, 8.1 months and 49.9%, 36.4%, 25.0% for Arms A, B, C, respectively. Median and 1-year PFS2 rates were 26.3, 17.5, 8.1 months and 78.4%, 70.0%, 25% for Arms A, B, C, respectively. The most frequent adverse events were anemia, stomatitis, fatigue, hyperglycemia, and hypercholesterolemia. CONCLUSIONS: The combination of everolimus and pasireotide-LAR showed promising efficacy over single agent. The delayed combination of everolimus and pasireotide-LAR following progression on single agent everolimus appeared intriguing as a combination strategy.

A Pancreatic Cancer Multidisciplinary Clinic Eliminates Socioeconomic Disparities in Treatment and Improves Survival.

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.

Dose-response model for severe late laryngeal toxicity after stereotactic body radiation therapy for previously-irradiated head and neck cancer.

We sought to evaluate the association between larynx dose and risk of severe late laryngeal toxicity in patients undergoing re-irradiation SBRT for recurrent HNC. Fifty-five patients with an intact larynx underwent re-irradiation SBRT to a median dose of 44 Gy in 5 fractions. Five (41.7%) patients treated for a laryngeal/hypopharyngeal recurrence experienced late grade ≥3 laryngeal toxicity, compared to 0.0-7.1% for other sites. Logistic dose-response models were created to predict risk of severe late laryngeal toxicity, including dysphagia and airway compromise. According to the model, the risk of severe laryngeal toxicity with a larynx D5cc of 5 Gy is 5.8% (95% CI 2.9-9.9%) and rises to 11.4% with a D5cc of 20 Gy and 25.3% with a D5cc of 40 Gy. In patients with a laryngeal/hypopharyngeal recurrence, SBRT planning should carefully assess the dose to laryngeal structures given these dose findings, and SBRT should be approached with significant caution in such patients.

Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors.

PURPOSE: Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-in-human study evaluated MEDI0562 in adults with advanced solid tumors. PATIENTS AND METHODS: In this phase I, multicenter, open-label, single-arm, dose-escalation (3+3 design) study, patients received 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg MEDI0562 through intravenous infusion every 2 weeks, until confirmed disease progression or unacceptable toxicity. The primary objective evaluated safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. RESULTS: In total, 55 patients received ≥1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell carcinoma of the head and neck (47%). Median duration of treatment was 10 weeks (range, 2-48 weeks). Treatment-related adverse events (TRAEs) occurred in 67% of patients, most commonly fatigue (31%) and infusion-related reactions (14%). Grade 3 TRAEs occurred in 14% of patients with no apparent dose relationship; no TRAEs resulted in death. Two patients had immune-related partial responses per protocol and 44% had stable disease. MEDI0562 induced increased Ki67+ CD4+ and CD8+ memory T-cell proliferation in the periphery and decreased intratumoral OX40+ FOXP3+ cells. CONCLUSIONS: MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing.

Transition to a virtual multidisciplinary tumor board during the COVID-19 pandemic: University of Pittsburgh experience.

Multidisciplinary conferences (MDC) are an important component of head and neck oncologic care including diagnosis, treatment, and survivorship. Virtual MDC allows for improved collaboration between providers at distant sites and proper allocation of health care resources in a time of crisis. When approached systematically, a virtual MDC is feasible to design and implement in a large academic medical center with multiple satellite hospitals.

Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer.

PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.

Dose-response modeling the risk of carotid bleeding events after stereotactic body radiation therapy for previously irradiated head and neck cancer.

Given the lack of clear dose constraints for the carotid artery, we created dose-response models to better quantify the risk of carotid bleeding events following re-irradiation stereotactic body radiation therapy (SBRT) for head and neck cancer (HNC). We performed a retrospective analysis on 75 patients treated with SBRT for recurrent, previously irradiated HNC. Logistic dose-response models were created to predict the risk of a carotid bleeding event, defined as any mucosal bleeding event or bleeding resulting from rupture of the carotid artery or its major branches in the setting of controlled disease. According to the models, the risk of a carotid bleeding event with a cumulative D0.1cc of 20 Gy from SBRT is 0.8% (95% CI 0.1%-3.9%), and rises to 5.0% with a D0.1cc of 50 Gy. No patient experienced a carotid bleeding event with D0.1cc < 39.4 Gy, and none experienced carotid blowout syndrome with a cumulative D0.1cc < 47.6 Gy.

Cost-effectiveness analysis of salvage therapies in locoregional previously irradiated head and neck cancer.

BACKGROUND: The purpose of this study was to present our evaluation of the cost-effectiveness of salvage therapies for patients with recurrent head and neck cancer. METHODS: A Markov model was developed with 5 salvage treatment strategies: (1) platinum-based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity-modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life years (QALYs), and evaluated with a willingness-to-pay (WTP) threshold of $100 000 per QALY gained. RESULTS: In the base case analysis, no treatment strategy was cost-effective at a WTP threshold. The most cost-effective therapy was SBRT alone with $150 866 per QALY gained. If median survival of SBRT alone was ≥11 months, SBRT was considered to be cost-effective. CONCLUSION: None of the treatment strategies were cost-effective. However, SBRT-based reirradiation has potential to be cost-effective.

Carotid Dosimetry and the Risk of Carotid Blowout Syndrome After Reirradiation With Head and Neck Stereotactic Body Radiation Therapy.

PURPOSE: To correlate carotid dose and risk of carotid blowout syndrome (CBOS) after stereotactic body radiation therapy (SBRT), hypothesizing that carotid dose does not correlate with CBOS. METHODS AND MATERIALS: We retrospectively reviewed 186 patients with recurrent, previously irradiated head and neck cancer treated between January 2008 and March 2013. Patients treated early in our experience with incomplete dosimetry were excluded from analysis (n = 111). A total of 75 patients were identified, providing 150 carotid arteries for analysis. Median follow-up was 8 months (range, 1-91 months) for all patients, and 37 months for surviving patients (range, 31-91 months). Patients were treated with linear accelerator-based SBRT to a median dose up to 44 Gy (range, 40-50 Gy) in 5 fractions delivered on a twice-weekly basis. Concurrent cetuximab was used in 63 patients (84%). The bilateral common, internal, and external carotid arteries were delineated 2 cm above and below the planning target volume. The maximum dose to 0.1 cm3 (D0.1cc), 1 cm3 (D1cc), and 2 cm3 (D2cc) of the carotid and the mean carotid dose from SBRT were recorded and analyzed for association with carotid bleeding events, using binary logistic regression. RESULTS: Median reirradiation interval was 20 months (range, 3-423 months), and median prior radiation dose was 70 Gy (range, 52.5-140 Gy). Sixteen patients (21.3%) received more than 1 course of SBRT, and the cumulative carotid doses from fused summary plans were recorded. The overall median D0.1cc, D1cc, D2cc, and mean carotid doses were 40.8 Gy (interquartile range [IQR], 21.6-47.6 Gy), 26.8 Gy (IQR, 14.1-42.1 Gy), 15.4 Gy (IQR, 8.4-32.7 Gy), and 15.0 Gy (IQR, 8.9-23.3 Gy), respectively. There were a total of 4 bleeding events (5.3%): 2 patients (2.7%) had mucosal bleeds that resolved after embolization of carotid branches, and 2 patients (2.7%) died from complications of CBOS. In the 2 patients with CBOS the D0.1cc was 48.4 Gy and 47.6 Gy, respectively. There was no significant association between bleeding events and D1cc (P = .280), D2cc (P = .571), or mean dose (P = .568). There was a trend toward increased risk of bleeding and D0.1cc (P = .080). CONCLUSIONS: These results demonstrate a low risk of bleeding after reirradiation with SBRT when 5 fractions are delivered on nonconsecutive days, even when tumor is completely encasing the carotid artery. Although limited by the low number of events, no significant association was found between dose-volume parameters and the risk of carotid bleeding. No CBOS was noted when D0.1cc was <47.6 Gy.

Concurrent Chemoradiotherapy in the Adjuvant Treatment of High-risk Primary Salivary Gland Malignancies.

OBJECTIVES: Adjuvant radiation therapy (RT) is indicated for patients with salivary gland malignancies with risk factors for recurrence following resection. We analyzed patients treated with adjuvant RT with or without concurrent chemotherapy to determine the impact of prognostic and treatment factors. MATERIALS AND METHODS: Retrospective analysis was performed of 128 patients treated with surgical resection followed by intensity-modulated radiotherapy. In total, 31 (24.2%) patients were treated with concurrent chemoradiotherapy. The Kaplan-Meier method was used to estimate rates of progression-free survival (PFS), local-regional control, distant control, overall survival. Multivariable Cox regression was performed to evaluate factors significant on univariate analysis. RESULTS: The 5-year rates of PFS, local-regional control, freedom-from distant metastasis, and overall survival were 61.2%, 85.8%, 76.5%, and 73.7%, respectively. Predictors of decreased PFS on univariate analyses were age, tumor stage, nodal stage, positive surgical margins, histology, high grade, perineural invasion, lymphovascular space invasion, extranodal extension, and use of chemoradiotherapy. On multivariable analysis, elevated T-stage, positive surgical margins, and presence of extranodal extension were predictive of decreased PFS. The acute toxicity rates were 30.3% grade 1, 51.5% grade 2, 11.4% grade 3, and 0.8% grade 4. There was no difference in rates of grade 3 or higher acute toxicity with use of RT alone versus chemoradiotherapy (P=0.183). CONCLUSIONS: Use of chemoradiotherapy for adjuvant treatment of salivary gland malignancies was well-tolerated, but no improvement in survival was seen with the use of chemoradiotherapy in both the overall study population and a subset with high-risk features. Caution should be used when using this modality until randomized evidence becomes available.

Tumor volume as a predictor of survival in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: Increasing evidence exists that tumor volume may be a superior prognostic model than traditional TNM staging. It has been observed that oropharyngeal squamous cell carcinoma (oropharyngeal SCC) in the setting of human papillomavirus (HPV) positivity have a greater propensity for cystic nodal metastases, and, thus, presumably larger volume with relatively smaller primary tumors. The influence of HPV status on the predictive value of tumor volume is unknown. METHODS: Fifty-three patients with HPV-positive oropharyngeal SCC were treated with definitive chemotherapy and intensity-modulated radiotherapy (IMRT). RESULTS: The estimated 2-year overall survival (OS) and disease-free survival (DFS) was 92.2% and 83.6%, respectively. Nodal classification did not predict OS (p = .096) or DFS (p = .170). Similarly, T classification did not predict OS (p = .057) or DFS (p = .309). Lower nodal volume was associated with greater DFS (p = .001). CONCLUSION: Nodal tumor volume was found to be predictive of DFS. DFS was best predicted by nodal gross tumor volume (GTV) at 24 months. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1613-E1617, 2016.

Incidence of hospitalization in patients with head and neck cancer treated with intensity-modulated radiation therapy.

BACKGROUND: Patients with primary head and neck cancer managed with radiation therapy (RT) +/- chemotherapy may experience significant treatment-related toxicities. We assessed hospitalization as a metric for severe treatment-related toxicities and evaluated patient and treatment factors for possible association. METHODS: A retrospective review was performed on 147 patients with head and neck cancer treated with definitive or adjuvant intensity-modulated radiation therapy (IMRT) +/- chemotherapy. Multiple Poisson regression model was used to analyze relationships between patient or treatment factors and number of hospital stays during RT and within 8 weeks after RT. RESULTS: Multivariate analysis showed preexisting diabetes or pulmonary disease, primary carcinoma of oral cavity, and prescribed radiation dose (p < .05) were associated with increased number of patient hospital stays during or shortly after RT. CONCLUSION: We found that 34.7% of patients experienced a chemoradiation toxicity-related hospitalization during or shortly after treatment. Prior pulmonary disease, diabetes, and increasing prescribed radiation dose were associated with increased hospital stays.

Stereotactic body radiotherapy for recurrent oropharyngeal cancer - influence of HPV status and smoking history.

PURPOSE: HPV status and smoking history stratifies patients into 3 distinct risk groups for survival following definitive chemoradiotherapy. Local-regional recurrences are common patterns of failure across all 3 risk-groups. SBRT±cetuximab has emerged as a promising salvage strategy for unresectable locally-recurrent, previously-irradiated head-and-neck cancer (rHNC) relative to conventional re-irradiation±chemotherapy. However the influence of HPV and smoking remains unknown in the setting of re-irradiation. METHODS/MATERIALS: Patients (n=30) with rHNC of the oropharynx salvaged with SBRT±cetuximab from August 2002 through August 2013 were retrospectively reviewed; HPV status was determined based on p16 staining of primary pathology. RESULTS: At a median follow-up of 10months for surviving patients, the mean overall survival for all patients was 12.6 months. HPV positivity was a significant predictor of overall survival (13.6 vs. 6.88 months, p=0.024), while smoking status did not significantly impact overall survival (p=0.707). CONCLUSION: HPV status remains a significant predictor of overall survival in the re-irradiation setting with HPV positive rHNC demonstrating superior overall survival following salvage SBRT±cetuximab.

Target delineation in stereotactic body radiation therapy for recurrent head and neck cancer: a retrospective analysis of the impact of margins and automated PET-CT segmentation.

BACKGROUND: Few guidelines exist on stereotactic body radiation therapy (SBRT) treatment planning for recurrent head and neck cancer. We assessed the impact of retrospectively adding margins/automated PET volumes to the gross tumor volume (GTV) in patients with post-SBRT recurrences. MATERIALS AND METHODS: We reviewed 89 patients with recurrent head and neck cancer treated with SBRT using no margin around the GTV. GTVs were recontoured with 1-5mm margins. PET-CT planned GTVs were also recontoured by adding PET-standardized uptake value (SUV)(3.5), SUV(4.5), SUV(40% max), and signal/background ratio (SBR) to the original GTV. We deformably registered recontoured GTVs to post-SBRT scans and assessed fraction of recurrence volume (RV) falling within the GTV, the "RV-GTV overlap." RESULTS: With non-PET-CT planning, median RV-GTV overlap increased from 11.7% to 48.2% using 5mm margins, and median GTV size increased by 41.8 cc (156%). With PET-CT planning, RV-GTV overlap increased from 45% to 93.6% using 5mm margins, and GTV size increased by 34.8 cc (140%). Adding SUV(3.5) and SBR increased RV-GTV overlap from 45% to 73.3% and 73.6%, with GTV size increases of 0.8 (3%) and 3.1 cc (11%), respectively. CONCLUSIONS: Recontouring increased recurrence coverage and also GTV size. Margins up to 5mm may reduce failures but could possibly increase toxicities. Automated PET contours may reduce near-miss failures with smaller increases in GTV size.

Oncologic and functional outcomes of partial laryngeal surgery for intermediate-stage laryngeal cancer.

OBJECTIVE: To evaluate the oncologic and functional outcomes of partial laryngeal surgery (PLS) using transoral laser microsurgery (TLM) and supracricoid laryngectomy (SCL) in patients with intermediate-stage laryngeal squamous cell carcinoma (LSCC). STUDY DESIGN: Historical cohort study. SETTING: Single tertiary care center. SUBJECTS AND METHODS: Retrospective review of oncologic and functional outcomes in intermediate-stage (T2-3/N0-1, stage II and III) LSCC patients who underwent TLM or SCL from 1998 to 2010. RESULTS: Sixty patients were included, of whom 28 (47%) underwent TLM and 32 (53%) underwent SCL. For the entire cohort, 2- and 5-year probabilities were 86.2% (95% confidence interval [CI], 73.0%-93.2%) and 72.9% (95% CI, 52.4%-85.6%), respectively, for overall survival (OS) and 79.3% (95% CI, 65.6%-88.0%) and 62.4% (95% CI, 41.9%-77.4%), respectively, for recurrence-free survival (RFS). There was no difference between the TLM and SCL cohorts in OS (P = .542) or RFS (P = .483). More than 75% of patients avoided adjuvant therapy. Communication Scale and Functional Outcome Swallowing Scale scores at median follow-up of 33 months were 2 or better in 97% and 91% of patients, respectively, reflecting functional voice and swallowing postoperatively. Eighty-eight percent of patients retained a functional larynx. CONCLUSION: PLS provides excellent oncologic and functional outcomes for intermediate-stage LSCC and should be considered an alternative to chemoradiation or total laryngectomy in selected patients.

A retrospective, deformable registration analysis of the impact of PET-CT planning on patterns of failure in stereotactic body radiation therapy for recurrent head and neck cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for selected patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). PET-CT may be advantageous for tumor delineation and evaluation of treatment failures in SBRT. We analyzed the patterns of failure following SBRT for rSCCHN and assessed the impact of PET-CT treatment planning on these patterns of failure. METHODS: We retrospectively reviewed 96 patients with rSCCHN treated with SBRT. Seven patients (7%) were treated after surgical resection of rSCCHN and 89 patients (93%) were treated definitively. PET-CT treatment planning was used for 45 patients whereas non-PET-CT planning was used for 51 patients. Categories of failure were assigned by comparing recurrences on post-treatment scans to the planning target volume (PTV) from planning scans using the deformable registration function of VelocityAI™. Failures were defined: In-field (>75% inside PTV), Overlap (20-75% inside PTV), Marginal (<20% inside PTV but closest edge within 1cm of PTV), or Regional/Distant (more than 1cm from PTV). RESULTS: Median follow-up was 7.4 months (range, 2.6-52 months). Of 96 patients, 47 (49%) developed post-SBRT failure. Failure distribution was: In-field-12.3%, Overlap-24.6%, Marginal-36.8%, Regional/Distant-26.3%. There was a significant improvement in overall failure-free survival (log rank p = 0.037) and combined Overlap/Marginal failure-free survival (log rank p = 0.037) for those receiving PET-CT planning vs. non-PET-CT planning in the overall cohort (n = 96). Analysis of the definitive SBRT subgroup (n = 89) increased the significance of these findings (overall failure: p = 0.008, Overlap/Marginal failure: p = 0.009). There were no significant differences in age, gender, time from prior radiation, dose, use of cetuximab with SBRT, tumor differentiation, and tumor volume between the PET-CT and non-PET-CT groups. CONCLUSIONS: Most failures after SBRT treatment for rSCCHN were near misses, i.e. Overlap/Marginal failures (61.4%), suggesting an opportunity to improve outcomes with more sensitive imaging. PET-CT treatment planning showed the lowest rate of overall and near miss failures and is beneficial for SBRT treatment planning.