Following chemoradiation for head and neck squamous cell carcinoma (HNSCC), a PET/CT scan is often performed at 13 weeks to assess disease response due to its high negative predictive value. By identifying persistent or recurrent disease early patients can increase their chance of cure with prompt salvage therapy. PET/CT scans can be limited in this setting by post-therapy changes to normal tissue that can interfere with detection of persistent disease, contributing to unsatisfactory false positive rates. This retrospective review examines the clinical course of HNSCC patients with persistent post-treatment PET/CT scans to develop better strategies for management. Hypothesis: HNSCC patients with persistent findings on post-treatment PET/CT scan are likely to have positive disease findings and should be biopsied rather than observed. Clinical characteristics of HNSCC patients treated between 2007 and 2017 with definitive radiation or chemoradiation were abstracted from the medical records. PET/CT was performed on all patients at 13 weeks to assess response to treatment. The radiologist report of each PET/CT scan was qualitatively assessed for treatment response as complete, equivocal, persistent, or metastatic. Clinical course of each patient following post-treatment scans was recorded. A total of 350 patients were included in the analysis. Median time to PET/CT scan after completion of treatment was 13 weeks. Assessment of initial post-treatment PET/CT included 171 complete (49%), 132 equivocal (38%), 33 persistent (9%), and 14 metastatic responses (4%). Of the patients with persistent findings, 13 received a repeat PET/CT scan, 8 were biopsied, 5 went to surgery, 3 went to palliative care, and 4 passed away prior to further management. True persistent findings were present in 24 of 33 patients (73%). Of the 13 patients who received a repeat PET/CT scan, 5 had a positive workup for disease and may have benefited from earlier intervention. The 2-year overall survival of patients with persistent findings was 60%. Most HNSCC patients with persistent findings on post-treatment PET/CT were found to have positive disease findings. Biopsy or surgery in these patients should not be delayed to provide the best chance at successful salvage therapy. Implications for practice or research: HNSCC patients with persistent findings on post-treatment PET/CT should promptly go to biopsy or surgery rather than observation.

Routine surveillance is practiced in head and neck squamous cell carcinoma (HNSCC) patients with the objective of identifying early recurrent or persistent disease. After completion of treatment, a PET/CT scan at 13 weeks is often performed to assess disease response due to its high negative predictive value. The timing of a PET/CT scan at 13 weeks after treatment completion is thought to balance the post-treatment changes in normal tissue that may interfere with detection of persistence against the need to identify treatment failure early to increase the chance of cure with salvage therapy. Despite waiting 13 weeks to perform a PET/CT scan, equivocal findings are frequently seen that make assessing treatment response difficult. This retrospective review examines the utility of a repeat PET/CT scan in patients with an equivocal post-treatment scan. Hypothesis: Repeat PET/CT scans in HNSCC patients with an equivocal post-treatment scan will provide diagnostic clarity. Clinical characteristics of HNSCC patients treated between 2007 and 2017 with definitive radiation or chemoradiation were abstracted from the medical records. PET/CT was performed on all patients at 13 weeks to assess response to treatment. The radiologist report of each PET/CT scan was qualitatively assessed for treatment response as complete, equivocal, persistent, or metastatic. If response was equivocal and repeat PET/CT was ordered, it was performed 2 months after the initial post-treatment scan. A total of 350 patients were included in the analysis. Median time to PET/CT scan after completion of treatment was 13 weeks. Assessment of initial post-treatment PET/CT included 171 complete (49%), 132 equivocal (38%), 33 persistent (9%), and 14 metastatic responses (4%). Of the patients with an initial equivocal response, 49 received a repeat PET/CT. Assessment of these scans included 25 complete, 13 equivocal, 7 persistent, and 4 metastatic responses. Repeat PET/CT provided diagnostic clarity in 36 of 49 patients (73%) and lead to a positive biopsy in 12 of 49 patients. Repeat PET/CT in HNSCC patients with an equivocal post-treatment scan provided diagnostic clarity in the majority of patients. Implications for practice or research: Repeat PET/CT scan should be considered in HNSCC patients when their initial post-treatment scan is equivocal. This can reduce the incidence of unnecessary biopsies and surgeries.

The goal of this study was to examine the effects of radiation treatment volume on overall survival and rates of recurrences among a population of head and neck cancer patient with unknown primaries at two different cancer institutes. Clinical characteristics were abstracted from the medical records of 62 patients with unknown primaries of the head and neck treated between 2000 and 2015 at Roswell Park Cancer Institute (Buffalo, NY, n = 33) and Upstate Medical University (Syracuse, NY, n = 29). Patients either received radiation therapy to one side of the head and neck, unilateral radiation (n = 34, RPCI = 28, Syracuse = 6), or radiation therapy to both sides of the head and neck, bilateral radiation (n = 28, RPCI = 5, Syracuse = 23). Mann Whitney U tests for ordinal data and χ2 and Fischer exact tests for categorical data were conducted to compare demographic and outcome factors between patients treated unilaterally and patients treated bilaterally. Overall survival (OS) and disease-free survival (DFS) trends for unilaterally and bilaterally treated patients were estimated using the Kaplan-Meier method. The effect of treatment volume on overall survival and disease-free survival was examined using multivariate Cox proportional hazard regression models. Models were adjusted for age and nodal stage. No significant differences in the frequency of local (P = .32), regional (P = .50), or distant (P = .76) failures were observed between patients treated unilaterally and those treated bilaterally. No significant differences were found in OS (3-year OS bilateral = 71.67%, unilateral = 77.90%, P =.503) or DFS (3-year DFS bilateral = 77.92%, unilateral = 69.43%, P = .626). Results from univariate (HR = 0.74, 95% CI 0.30, 1.80, P = .504) and multivariate analysis (HR = 0.74, 95% CI 0.31, 1.81, P = .511) for the effect of treatment volume on overall survival showed no significant difference in risk of mortality between the two treatment volumes. There was no statistically significant effect of treatment volume on disease free survival in both univariate (HR = 0.77, 95% CI 0.28, 2.18, P = .627) and multivariate (HR: 0.68, 95% CI 0.24, 1.93, P = .465) analyses. Unilateral radiation therapy is as effective in controlling disease as bilateral radiation therapy with similar overall survival in patients with squamous cell carcinomas of the head and neck from unknown primaries. In addition, unilateral radiation therapy may reduce acute and late toxicity effects of treatment as well as lower the risk of toxicity should a contralateral recurrence emerge.

Oral mucositis occurs in the majority of patients (pts) undergoing radiation therapy (RT) for head and neck cancer (HNC). The Oral Mucositis Daily Questionnaire (OMDQ) is a validated survey for HNC patient pain. This analysis was undertaken to report the course of patient-reported pain and associated narcotic use throughout the duration of RT for pts with HNC. Hypothesis: We hypothesized pts with bilateral elective nodal RT (BL-RT) treatment vs. unilateral elective nodal RT (UL-RT), with or without concurrent chemotherapy (CRT), would have significantly worse pain that coincided with increasing narcotic requirement. Pts with Stage I-IV HNC who were treated with either adjuvant or definitive RT at our institution from 2015 to 2017 were included for analysis. At baseline and weekly on-treatment visits, clinical data including narcotic use was recorded and OMDQ was administered. Pain was treated with either our institution’s standard of care (SOC) analgesic regimen using hydrocodone-acetaminophen +/- transdermal fentanyl as needed, or according to an outside provider (OP). Average daily narcotic use was converted to oral morphine milligram equivalents and reported as a cumulative requirement (dMME). Pts were dichotomized by either unilateral or BL-RT and +/- concurrent chemotherapy (RT vs CRT). To evaluate Mouth/Throat Soreness (MTS) OMDQ score response, the difference between baseline and week 3 (W3D) and at end-of-treatment (EoTD) was calculated for each pt. All other elements of the OMDQ were also analyzed. Two way ANOVA was performed and associations over time were quantified with a random coefficient mixed model. A total of 98 patients were eligible for analysis (42% SOC and 59% OP). The median age was 61.2y (IQR: 55.4-70.1y). Median dose to the primary was 70Gy (Range:50-70Gy). Overall, pts were treated: 44% adjuvantly, 56% definitively, 56% BL-RT, 39% UL-RT, 82% CRT, 18% RT alone. SOC vs. OP had no change in weekly MTS and no significant difference in dMME. There was no difference in overall pain scores, W3D or EoTD when comparing elective nodal RT; however, there was increased narcotic requirement for BL-RT (p<0.001). CRT vs. RT-alone had greater weekly MTS (p=0.03) and an increased dMME (p=0.047). There were no significant differences in all other OMDQ questions. We report on the use of narcotics and mucositis-related pain throughout the course of RT. Surprisingly, BL-RT did not increase MTS scores compared to UL-RT. Not surprisingly, CRT did increase weekly MTS scores. Both BL-RT and CRT increased narcotic requirements. Implications for research: This study suggests that narcotic use as measured by dMME, rather than OMDQ, may be a better metric for quantifying mucositis during radiation.

To examine the utility of computed tomography (CT) imaging as a routine surveillance tool for the detection of recurrent head and neck squamous cell carcinoma (HNSCC). Clinical characteristics of HNSCC patients treated between 2008-2017 with radiation therapy (RT) or concurrent chemoradiation (CCRT) were abstracted from medical records. In patients who achieved a complete clinical response (CCR) to treatment by positron emission tomography (PET) scan, surveillance CT scans were conducted to the maxillofacial area, neck, and chest every 3 months in year 1, every 6 months in year 2, and every 12 months in years 3 and beyond. Overall survival (OS) curves and multivariate cox proportional hazard ratios (HR) were examined. At this single institution, 588 patients were treated for HNSCC. Median follow up duration for the entire cohort was 30.9 months (range = 6-88 months). Of the 449 (76%) evaluable patients who achieved a CCR, 85 (19%) patients had a recurrence. Among the 85 patients with disease recurrence, 25 (29%) patients remained alive, of which 15 (18%) underwent successful salvage treatment and became free of disease. Lung screening CT scans detected failure in 8 of these successfully salvaged patients. Among the 8 patients successfully salvaged for locoregional recurrence, 3 failures were asymptomatic at onset and detected by laryngoscope or dental exam. The remaining 5 failures were symptomatic and detected upon work up. One patient was successfully salvaged for both local and distant failure. Maxillofacial and neck screening CT imaging failed to detect any successfully salvaged patients. Routine surveillance for HNSCC patients with lung CT imaging had value but head and neck CT scans failed to identify any successfully salvaged patients. Given this finding, routine CT imaging surveillance in HNSCC patients should be restricted to annual lung screenings. Surveillance head and neck CT imaging is not recommended until better salvage treatment is available to treat locoregional recurrence.

The goal of this study was to examine the effects of radiation treatment volume on quality of life in patients with squamous cell carcinoma of the tonsil. Clinical characteristics of patients with tonsillar squamous cell carcinoma (n=30) treated at Roswell Park Cancer institute (2013-2015) were abstracted from the medical records. Patients were either treated with radiation therapy to one side of the head and neck, unilateral radiation (n=15), or treated with radiation therapy to both sides of the head and neck, bilateral radiation (n=15). Quality of life data was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-30) and head and neck 35 (H&N 35). The EORTC survey was administered prior to the start of radiation therapy treatment, at the end of radiation therapy treatment, and at each follow-up appointment up to 1-year posttreatment. Mann Whitney U tests were used to examine differences in QOL scores between patients treated unilaterally and patients treated bilaterally at various time points posttreatment. Patients who received bilateral treatment had significantly more appetite loss six months posttreatment (55.56% vs 15.15%, t=2.92, P=.02), more dysphagia 3 months posttreatment (40.48% vs 13.63%, t=2.85, P=.03), and more xerostomia e month posttreatment (62.5% vs 33.33%, t=2.37, P=.0486) than patients receiving unilateral radiation. Unilateral patients reported more sticky saliva posttreatment (93.33% vs 75.56%, t=-2.12, P=.01) than patients who received bilateral treatment. Results of this small cohort study indicate that unilateral radiation therapy in tonsillar squamous cell carcinoma may be associated with less severe symptoms than bilateral radiation therapy and more studies on a larger scale are needed to further investigate this association.

Oral mucositis occurs in the majority of patients (pts) undergoing chemoradiation therapy (CRT) for head and neck cancer (HNC). The Oral Mucositis Daily Questionnaire (OMDQ) is a validated survey for HNC patient pain. Gabapentin (GABA) has been used concurrently with opioids to improve pain control in pts with HNC. Methadone (MTD) is a low abuse potential opioid that is used for neuropathic pain. This single center prospective randomized study was undertaken to compare analgesia regimens for pts undergoing CRT. Hypothesis: We hypothesized pts treated with GABA would have improved pain control and delay the onset of narcotic requirement, and the addition of MTD would provide improved pain control. Pts with Stage II-IV HNC who were treated with definitive CRT were randomized to one of two pain regimens: 1) High-dose GABA (900mg TID) with hydrocodone-acetaminophen followed by transdermal fentanyl as needed (HD-HAF) or 2) Low-dose GABA (300mg TID) with methadone (5-15mg BID) and oxycodone as needed (LD-MTD). Pts were stratified by bilateral or unilateral radiation. At baseline and weekly on-treatment visits, clinical data including narcotic use was recorded and OMDQ was administered. Average daily narcotic use was converted to oral morphine milligram equivalents. Two sided T and Fischer exact tests were performed. A total of 60 pts were randomized; at the time of analysis not all patients had completed their scheduled evaluations. Median dose to the primary was 70 Gy. There were no attributable grade 3 adverse events. Approximately half of HD-HAF and three quarters of LD-MTD required a narcotic during CRT. The time to first narcotic was approximately 4.5 weeks for both groups. LD-MTD had better Overall Health at week 7 vs. HD-HAF (p<0.05). This study demonstrates that both pain regimens are safe and well tolerated. Methadone is associated with better overall health at the end of treatment for pts undergoing CRT. Our next study will utilize high dose GABA and methadone. Implications for practice or research: Methadone, as a low abuse potential narcotic, combined with prophylactic GABA can improve overall health at the end of CRT for HNC. Further escalating GABA dose may optimize the therapeutic benefit of MTD and will be tested in a future study.

Treatment for head and neck cancer involves a combination of therapies that are highly toxic impacting both quality of life (QOL) and overall recovery period. The purpose of this project is to prospectively monitor QOL in a cohort of head and neck cancer patients while integrating QOL findings into patient care. QOL is currently being tracked in a head and neck radiation medicine clinic using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ)-30 and EORTC head and neck module (H&N)-35 questionnaires which was translated into a digital platform using a Research Electronic Data Capture (REDCap) survey format. Patients complete the survey at the beginning of treatment, end of treatment, and at each follow-up appointment (3 months, 6 months, 1 year). The REDCap survey program build enables automatic computation of scores upon patient completion. Results are therefore available for immediate review by the clinician. A total of 561 QOL surveys have been completed by 200 patients to date. Patients have completed surveys up to a period of 20 months following treatment.Abstract 211; Table 1Date8/19/1310/14/13*11/13/131/29/144/23/14**7/22/1410/15/144/15/15Global Health Status (QOL)5041.6616.6610083.3366.6691.6650Physical Functioning93.3393.3373.3310010073.3393.3386.66Emotional Functioning66.66752510066.665091.6650Cognitive Functioning10050501001005010066.66*Parkinson disease diagnosis suspected and referral made. **Parkinson disease medication adjustment needed and referral made. Open table in a new tab *Parkinson disease diagnosis suspected and referral made. **Parkinson disease medication adjustment needed and referral made. In this example the physician was able to diagnose a worsening of the patient’s Parkinson disease based on the results of the QOL, physical functioning, emotional functioning, and cognitive functioning scores. The physician was then able to refer her for immediate and appropriate therapy. Prospectively tracking QOL before, during, and after treatment provides clinicians with a more comprehensive understanding of factors related to changes in their patients’ QOL scores, allowing them to provide immediate treatment or appropriate referrals. Using a digital platform (REDCap Surveys) is a novel method for tracking and managing QOL factors in real time in a head and neck cancer population.

There is increasing interest in the use of robotic surgery in carcinoma of the oropharynx. The purpose of this study was to examine survival outcomes among 2 oropharyngeal subsites (tonsillar-fossa [TF] and base of tongue [BOT]). We conducted a retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) Program. The SEER cohort included 8073 primary BOT and TF SCC patients without distant metastases treated between 2004 and 2011. Primary outcome measures were subsite-based differences in overall survival (OS) and disease-specific survival (DSS) for TF and BOT patients stratified by overall stage and comparing treatment method for each subsite. Cox proportional hazard ratios were estimated for each group. For all stages combined, both BOT and TF patients who received surgery with radiation had superior OS (P<.01). The same was true when analyses were stratified by stage within each subsite. Multivariate hazard ratios adjusted for age, gender, race, and tumor grade for OS were statistically significantly higher for both BOT and TF patients who did not receive surgery compared to those who did receive surgery for each stage. In this SEER cohort, OS was superior in both BOT and TF patients who received surgery with adjuvant radiation. OPSCC survival may be improved by treating more BOT and TF patients with surgery and adjuvant radiation. As modern, less invasive surgical techniques such as transoral robotic surgery gain wider acceptance, approaches that combine surgery and radiation (with or without chemotherapy) while minimizing morbidity and lack of function should be attempted.

The effect of smoking and human papillomavirus (HPV) status on the survival of oropharyngeal squamous cell carcinoma (OPSCC) undergoing definitive concurrent chemoradiation (CCRT) remains unclear. The purpose of this review was to examine these effects on survival outcomes among a single institute population. This retrospective review of OPSCC patients treated with CCRT between 2008 and 2015 was conducted. All tumors were examined for HPV 16/18 status (+/). Smoking status and other clinical characteristics were abstracted from the electronic medical record. Former smokers are patients who quit within a month of diagnosis or treatment. Descriptive summaries, overall survival (OS), and multivariate cox proportional hazard ratios (HR) were completed. Out of 134 patients, 94 patients (71%) had HPV-positive (HPV+) tumors. Age, gender, and overall stage were not statistically different between patients with HPV+ or HPV-negative (HPV-) tumors. HPV+ patients had higher tumor grade (P<.01). Patients with HPV+ tumors had a higher percentage of never smokers than patients with HPV- tumors (10.3% vs 26.6%). Median pack-years were 18 for the HPV+ group versus 30 for the HPV- group. OS did not differ for HPV+ versus HPV- patients. Within HPV+ patients, current and former smokers had significantly worse OS than never smokers (P<.01). The same was true for HPV- patients, but the log-rank test for this group did not reach statistical significance (P=.06). The 3-year survival rate for former smokers in each group was similar (HPV+: 0.77 (0.60, 0.88) and HPV-: 0.75 (0.52, 0.88). Hazard ratios for OS among current smokers compared to never/former smokers in each patient group were statistically significantly higher. Current smoking is associated with poor prognosis, independent of HPV status in OPSCC patients treated with CCRT. Former smokers have similar outcomes irrespective of HPV tumor status. The amount of tobacco a patient is exposed to before diagnosis cannot be altered, but every effort should be made to get patients to quit smoking as soon as possible before CCRT regardless of HPV status.

Previous studies on treatment outcomes of patients with advanced oropharyngeal squamous cell carcinomas (OPSCC) have rarely analyzed subsite differences in detail in the era of human papillomavirus (HPV). The purpose of this study was to evaluate subsite-specific differences in survival between squamous cell carcinomas (SCC) of the base of tongue (BOT) and the tonsillar fossa (TF) in a cohort likely to have a high incidence of HPV-associated tumors. Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) Program. The SEER cohort included 8073 primary BOT and TF SCC patients without distant metastases treated between 2004 and 2011. Primary outcome measures were subsite-based differences in overall survival (OS) and disease-specific survival (DSS). Cox proportional hazard ratios were estimated. Among the 8073 primary BOT and TF SCC patients, 3705 (46%) were BOT and 4368 (54%) were TF. Median age for BOT and TF patients was 62 and 58 years, respectively. Other clinical characteristics were similar between groups, but more TF patients had poorly differentiated tumors. Overall survival with all stages combined favored TF (P<.01) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio (HR) for OS was superior for TF tumors in comparison to BOT tumors across all disease stages (stage I HR 1.28, 95% confidence interval [CI] 1.01-1.64; stage II HR 1.30, 95% CI 1.08-1.59; stage III HR 1.30, 95% CI 1.14-1.49; stage IV HR 1.14, 95% CI 1.00-1.30). Similar advantages were noted for DSS favoring improved outcomes for TF. In this large, modern cohort, OS and DSS favored outcomes in TF as compared with BOT. Further study is required to evaluate factors that influence subsite-based survival differences in TF and BOT patients in the era of HPV.

BACKGROUND & AIMS Type 1 hepatorenal syndrome (HRS) is a severe complication of cirrhosis associated with a short median survival time (<2 weeks). Although the administration of terlipressin improves renal function, its effect on survival is unknown. This study investigated predictive factors of survival in patients with type 1 HRS treated with terlipressin. METHODS Ninety-nine patients with type 1 HRS treated with terlipressin in 24 centers were retrospectively studied. Terlipressin-induced improved renal function was defined as a decrease in serum creatinine value to <130 micromol/L or a decrease of at least 20% at the end of treatment. RESULTS At inclusion, the Child-Pugh score was 11.8 +/- 1.6 (mean +/- SD). Terlipressin (3.2 +/- 1.3 mg/day) was administered for 11 +/- 12 days. Renal function improved in 58% of patients (serum creatinine decreased by 46% +/- 17% from 272 +/- 114 micromol/L). Median survival time was 21 days. Survival rate was 40% at 1 month. Multivariate analysis showed that improved renal function and Child-Pugh score < or =11 at inclusion were independent predictive factors of survival (P < 0.0001 and 0.02, respectively). Thirteen patients underwent liver transplantation (92 +/- 95 days after HRS onset), 10 of whom had received terlipressin and had had improved renal function. CONCLUSIONS This retrospective uncontrolled study shows that in patients with type 1 HRS, terlipressin-induced improved renal function is associated with an increase in survival. Thus, a randomized trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.