Follow-up for human papillomavirus-related oropharynx cancer concentrated on unequal symptom change (FOCUS): Prospective patient-reported outcome collection.

BACKGROUND: Post-treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow-up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient-reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer. METHODS: A prospective registry was developed in which ePROs and ctDNA were incorporated into routine surveillance among patients with oropharynx cancer. ePROs were emailed monthly for 1 year and blood HPV ctDNA testing was performed every 3-6 months. The primary objective was to assess patient compliance with ePRO-based surveillance with adequate compliance defined as ≥85% of patients completing monthly ePROs. Sensitivity, specificity, and positive/negative predictive values to detect recurrence were calculated for ePROs, HPV ctDNA, or the combination. RESULTS: Of 122 patients who initially expressed interest, 76 completed the electronic consent process and 44/76 (58%) were compliant with monthly surveys over 1 year; thus adequate compliance was not achieved. Technical difficulties associated with ePRO receipt through email largely limited participation. Provider feedback was significantly associated with heightened ePRO compliance. One hundred and six patients had ctDNA testing with a mean number of three tests per patient. Sensitivity to detect recurrence was 75% for the combination of ePROs and ctDNA. CONCLUSION: Despite lower than anticipated compliance with ePROs, our findings show promise for incorporation of HPV ctDNA into surveillance paradigms for HPV-related oropharynx cancer with suggestions of methods to optimize ePRO formats for personalized surveillance.

Investigating potential disparities in clinical trial eligibility and enrollment at an NCI-designated comprehensive cancer center.

BACKGROUND: Although barriers to trial accrual are well-reported, few studies have explored trial eligibility and trial offers as potential drivers of disparities in cancer clinical trial enrollment. METHODS: We identified patients with gastrointestinal (GI) or head/neck (HN) malignancies who were seen as new patients at the University of Michigan Health Rogel Cancer Center in 2016. By exhaustive review of the electronic medical record, we assessed the primary outcomes: (1) eligibility for, (2) documented offer of, and (3) enrollment in a clinical trial. All 41 of the clinical trials available to these patients were considered. Independent variables included clinical and non-clinical patient-related factors. We assessed associations between these variables and the primary outcomes using multivariable regression. RESULTS: Of 1446 patients, 43% were female, 15% were over age 75, 6% were Black. 305 (21%) patients were eligible for a clinical trial. Among eligible patients, 154 (50%) had documentation of a trial offer and 90 (30%) enrolled. Among the GI cohort, bivariate analyses demonstrated that older age was associated with decreased trial eligibility. Bivariate analyses also demonstrated that Black race was associated with increased trial offer. After adjustment, patients 75 or older were less likely to be eligible for a clinical trial in the GI cohort; however, we found no significant associations between race and any of the outcomes after adjustment. Among eligible GI patients, we found no significant associations between non-clinical factors and enrollment. Among the HN cohort, bivariate analyses demonstrated that female sex, older age, Black race, and unpartnered marital status were associated with decreased likelihood of trial offer; however, we found no significant associations between race, age, and marital status and any of the outcomes after adjustment. We found no significant associations between non-clinical factors and eligibility after adjustment; however, women were less likely to be offered and to enroll in a clinical trial in the HN cohort. CONCLUSION: Factors associated with eligibility, documented offer, and enrollment differed between disease site cohorts at our institution. Future work is needed to ensure the equitable inclusion of women and elderly patients in clinical trials.

Radiation for Early Glottic Cancer.

Multidisciplinary evaluation of early-stage glottic cancer facilitates optimal treatment with either surgery or radiation therapy. Standard of care radiation treatment of early-stage glottic cancer continues to be three-dimensional opposed lateral fields to include the whole larynx. Modern radiation treatment techniques are allowing studies to examine the efficacy and toxicity of altered doses and treatment volumes. Advanced techniques, such as stereotactic body radiation therapy or single-vocal cord irradiation, are not yet considered standard of care for early-stage glottic cancer and should be performed at institutions with clinical trials to ensure adequate expertise and quality assurance.

Initial Feasibility and Acute Toxicity Outcomes From a Phase 2 Trial of 18F-Fluorodeoxyglucose Positron Emission Tomography Response-Based De-escalated Definitive Chemoradiotherapy for p16+ Oropharynx Cancer: A Planned Interim Analysis.

PURPOSE: 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We used FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT), hypothesizing that acute toxicity will be improved with de-escalation. METHODS AND MATERIALS: This is a planned interim initial feasibility and acute toxicity report from a phase 2, prospective, nonrandomized study, which enrolled patients with stage I-II p16+ OPSCC. All patients started definitive CRT to 70 Gy in 35 fractions, and those who met de-escalation criteria on midtreatment FDG-PET at fraction 10 completed treatment at 54 Gy in 27 fractions. We report the acute toxicity and patient-reported outcomes for 59 patients with a minimum follow-up of 3 months. RESULTS: There were no statistically significant differences between baseline patient characteristics in the standard and de-escalated cohorts. There were 28 of 59 (47.5%) patients who met FDG-PET de-escalation criteria and collectively received 20% to 30% less dose to critical organs at risk known to affect toxicity. At 3 months posttreatment, patients who received de-escalated CRT lost significantly less weight (median, 5.8% vs 13.0%; P < .001), had significantly less change from baseline in penetration-aspiration scale score (median, 0 vs 1; P = .018), and had significantly fewer aspiration events on repeat swallow study (8.0% vs 33.3%, P = .037) compared with patients receiving standard CRT. CONCLUSIONS: Approximately half of patients with early-stage p16+ OPSCC are selected for de-escalation of definitive CRT using midtreatment FDG-PET biomarkers, which resulted in significantly improved rates of observed acute toxicity. Further follow-up is ongoing and will be required to determine whether this de-escalation approach preserves the favorable oncologic outcomes for patients with p16+ OPSCC before adoption.

Development and Clinical Implementation of an Automated Virtual Integrative Planner for Radiation Therapy of Head and Neck Cancer.

Purpose: Head and neck (HN) radiation (RT) treatment planning is complex and resource intensive. Deviations and inconsistent plan quality significantly affect clinical outcomes. We sought to develop a novel automated virtual integrative (AVI) knowledge-based planning application to reduce planning time, increase consistency, and improve baseline quality. Methods and Materials: An in-house write-enabled script was developed from a library of 668 previously treated HN RT plans. Prospective hazard analysis was performed, and mitigation strategies were implemented before clinical release. The AVI-planner software was retrospectively validated in a cohort of 52 recent HN cases. A physician panel evaluated planning limitations during initial deployment, and feedback was enacted via software refinements. A final second set of plans was generated and evaluated. Kolmogorov-Smirnov test in addition to generalized evaluation metric and weighted experience score were used to compare normal tissue sparing between final AVI planner versus respective clinically treated and historically accepted plans. A t test was used to compare the interactive time, complexity, and monitor units for AVI planner versus manual optimization. Results: Initially, 86% of plans were acceptable to treat, with 10% minor and 4% major revisions or rejection recommended. Variability was noted in plan quality among HN subsites, with high initial quality for oropharynx and oral cavity plans. Plans needing revisions were comprised of sinonasal, nasopharynx, P-16 negative squamous cell carcinoma unknown primary, or cutaneous primary sites. Normal tissue sparing varied within subsites, but AVI planner significantly lowered mean larynx dose (median, 18.5 vs 19.7 Gy; P < .01) compared with clinical plans. AVI planner significantly reduced interactive optimization time (mean, 2 vs 85 minutes; P < .01). Conclusions: AVI planner reliably generated clinically acceptable RT plans for oral cavity, salivary, oropharynx, larynx, and hypopharynx cancers. Physician-driven iterative learning processes resulted in favorable evolution in HN RT plan quality with significant time savings and improved consistency using AVI planner.

Optimizing Palliative Focal Radiation Therapy Dose in Cutaneous T-Cell Lymphoma: How Low Can You Go?

PURPOSE: Primary cutaneous T-cell lymphomas (CTCLs) are radiosensitive tumors with variable and often relapsing courses. Local disease can be treated with low-dose focal palliative radiation therapy (RT), though little data supports the use of a specific dose. This study assesses clinical outcomes after focal RT to a total dose of 4 Gy, 8 Gy, or 12 Gy. METHODS AND MATERIALS: An International Review Board-approved, retrospective, single-institution study was performed of 225 lesions in 41 patients with primary CTCL treated with low-dose focal RT from 2015 to 2020. Patient, tumor, and treatment characteristics were reviewed. The primary outcome was freedom from treatment failure (FFTF), defined as time to requiring local retreatment, and secondary outcomes included response rates and toxicities. RESULTS: Of the 225 lesions, 90 received 4 Gy, 106 received 8 Gy, and 29 received 12 Gy. Lesions treated with 12 Gy (96%) or 8 Gy (92%) had a significantly higher 1-year FFTF compared with 4 Gy (77%) (P = .034). Overall response rate and complete response rate were not significantly different between different doses (P = .117), though there was a trend toward higher overall response rate at initial assessment with 8 Gy versus 4 Gy (91.5% vs 82.2%, P = .057). Toxicity was low, with 7.1% of lesions having grade 2 or higher radiation dermatitis. CONCLUSIONS: In primary CTCL lesions treated with focal palliative RT, a dose response was noted favoring 8 to 12 Gy, with 1-year FFTF rates over 90%. However, 4 Gy resulted in substantially better outcomes than previously reported, with 77% requiring no further treatment at 1 year and comparable response rates to higher doses. While our data substantiates 8 to 12 Gy as the standard of care, it also suggests that 4 Gy should be considered an acceptable alternative in situations with concern for radiation toxicities, such as with fragile or heavily pretreated skin.

Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma.

OBJECTIVES: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. MATERIALS AND METHODS: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining. CONCLUSION: Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future.

Pilot Study of a Wearable Activity Monitor During Head and Neck Radiotherapy to Predict Clinical Outcomes.

PURPOSE: Given the established associations between performance status and survival in a variety of cancers, there is significant interest in using a biometric wearable device (WD) to predict outcomes in the oncology population. In this pilot study, we investigated the ability of a WD to predict meaningful clinical end points in patients undergoing head and neck radiotherapy. METHODS: Patients receiving head and neck definitive chemoradiotherapy or postoperative radiotherapy/chemoradiotherapy were enrolled in this pilot study, designed to show 90% compliance with using the device. Individuals were asked to wear the WD for 23 hours a day, and hospital admissions, pain medication usage, and FACT-G quality-of-life (QoL) score were prospectively recorded. RESULTS: Fifty-one patients were enrolled and started using the WD, but eight patients stopped wearing it, resulting in a compliance probability of only 84%. There were 15 hospital admissions, 13 of which were planned for feeding tube placement. There was no step count threshold that predicted the need for admission or more pain medications. However, among the 25 patients with a significant reduction in FACT-G score, the average reductions in daily steps during the week and weekend before the decline were 988 (P = .005) and 1,311 (P = .018), respectively, and the odds of a QoL reduction were more than 4-fold higher among patients experiencing a week-to-week reduction of at least 1,000 daily steps. There was no association between heart rate and any end point. CONCLUSION: Although not meeting the compliance goal, the majority of patients did use the WD. The WD signal could not identify patients requiring hospitalization or significantly more pain medication, but the finding of reduced step counts before a significant reduction in QoL is provocative.

Financial Hardship in Patients With Head and Neck Cancer.

PURPOSE: Financial hardship is a growing concern for patients with cancer. Patients with head and neck cancer (HNC) are particularly vulnerable, given that a third leave the workforce following treatment. The goal of our study was to characterize financial hardship in the psychologic response (response to increased expenses) and coping behaviors (behaviors patients adopt to manage their care in the setting of increased expenses) domains in patients with HNC compared with patients with other cancers. METHODS: This was a retrospective cohort study of nationally representative public survey data from 2013 to 2018 in the National Health Interviews Survey, an annual cross-sectional household survey. We included respondents age ≥ 18 years who reported a diagnosis of cancer and identified a subset of patients with HNC. Our main outcomes were financial hardship in the psychologic response and coping behaviors domains. RESULTS: Our sample included a weighted population of 357,052 patients with HNC and 21.4 million patients with other cancers. Compared with patients with other cancers, patients with HNC reported greater levels of coping behaviors hardship (31% v 23%, P = .015), but similar levels of psychologic financial hardship (73% v 72%, P = .787). Medicaid or uninsured patients more often reported coping behaviors hardship. On multivariable analysis, HNC (odds ratio, 1.51; 95% CI, 1.01 to 2.24) was independently associated with coping behaviors hardship. CONCLUSION: To our knowledge, this is the first study to evaluate financial hardship in patients with HNC compared with patients with other cancers that includes Medicaid and uninsured patients, who are more often to have financial hardship. Patients with HNC have greater levels of hardship in the coping behaviors domain compared with patients with other cancers, but similar levels in the psychologic response domain.

CT and FDG-PET radiologic biomarkers in p16+ oropharyngeal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). METHODS: An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). RESULTS: There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). CONCLUSIONS: In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. STATEMENT OF TRANSLATIONAL RELEVANCE: Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.

Prospective Phase 2 Study of Radiation Therapy Dose and Volume De-escalation for Elective Neck Treatment of Oropharyngeal and Laryngeal Cancer.

PURPOSE: The required elective nodal dose and volumes for head and neck intensity modulated radiation therapy have largely been extrapolated from conventional radiation therapy fields. In this prospective, dual-center, phase 2 study, we investigated the efficacy and tolerability of reduced elective nodal volume and dose in oropharyngeal and laryngeal squamous cell carcinoma. METHODS AND MATERIALS: Patients with newly diagnosed squamous cell carcinoma of the oropharynx and larynx were eligible for enrollment. Each lymph node was characterized as involved or suspicious based on imaging criteria. For oropharynx cancer, only involved and immediately adjacent stations were treated to 40 Gy in 20 fractions. In larynx patients, at least bilateral levels II and III were treated to 40 Gy, with level IV treated only if level III was involved. Involved and suspicious nodes were then boosted with 30 Gy and 24 Gy in 15 fractions, respectively. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was solitary elective volume recurrence, with secondary endpoints including patterns of failure and patient-reported outcomes. RESULTS: A total of 72 (51 oropharynx, 21 larynx) patients completed treatment on this trial from January 2017 through November 2018. The stages at presentations were 5, 17, and 50 stage I-II, III, and IV, respectively, with 90% treated with chemoradiation therapy. At a median follow-up of 24.7 months for surviving patients, there have been no solitary elective nodal recurrences. Seven patients developed a nodal recurrence, 5 of which were in-field and 2 were elective with synchronous in-field recurrence. Patient-reported outcomes assessment at 1 year showed superior or equivalent outcomes compared with baseline, except for saliva and taste measures. CONCLUSIONS: The results of this trial suggest that elective dose and volume reduction is oncologically sound for oropharyngeal and laryngeal cancer treated with intensity modulated radiation therapy, with promising quality-of-life outcomes.

A population-based study of invitation to and participation in clinical trials among women with early-stage breast cancer.

PURPOSE: Although many studies clearly demonstrate disparities in cancer clinical trial enrollment, there is a lack of consensus on potential causes. Furthermore, virtually nothing is known about associations between patients' decision-making style and their participation in clinical trials. METHODS: Women with newly diagnosed, stage 0-II breast cancer reported to the Georgia and Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registries in 2013-2014 were surveyed approximately seven months after diagnosis. We investigated two primary outcome variables: (1) invitation to participate in a clinical trial, (2) participation in a clinical trial. We evaluated bivariate associations using Chi-squared tests and used multivariable logistic regression models to investigate associations between patient variables, including decision-making style, and the primary outcomes. RESULTS: 2578 patients responded (71% response rate); 30% were > age 65, 18% were black, 18% were Latina, 29% had ≤ high school education. 10% of patients reported invitation to participate in a clinical trial; 5% reported participation in a clinical trial. After adjustment younger age, receipt of chemotherapy or radiation, disease stage, and a more rational (versus more intuitive) decision-making style were associated with a higher odds of invitation to participate. Being married was associated with a higher odds of participation; having an annual family income ≥ $40,000 was associated with a lower odds of participation. CONCLUSIONS: 10% of patients reported invitation to participate in a clinical trial, and half of these reported participation. Invitation to participate varied by age and decision-making style, and participation varied by marital status and income.

Nodular Leptomeningeal Disease-A Distinct Pattern of Recurrence After Postresection Stereotactic Radiosurgery for Brain Metastases: A Multi-institutional Study of Interobserver Reliability.

PURPOSE: For brain metastases, surgical resection with postoperative stereotactic radiosurgery is an emerging standard of care. Postoperative cavity stereotactic radiosurgery is associated with a specific, underrecognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease. We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve interrater reliability (IRR) and validity in diagnosing LMD. METHODS AND MATERIALS: Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system expertise, completed a 2-phase survey that included magnetic resonance imaging and treatment information for 30 patients. In the "pretraining" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "posttraining" phase and relabeled the 30 cases using the 4 following labels: LR, DR, classical leptomeningeal disease, and nLMD. RESULTS: IRR increased 34% after training (Fleiss' Kappa K = 0.41 to K = 0.55, P < .001). IRR increased most among non-central nervous system specialists (+58%, P < .001). Before training, IRR was lowest for LMD (K = 0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD. CONCLUSIONS: This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training.

Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma.

Glioblastoma is the most common primary brain tumor in adults. Standard therapy depends on patient age and performance status but principally involves surgical resection followed by a 6-wk course of radiation therapy given concurrently with temozolomide chemotherapy. Despite such treatment, prognosis remains poor, with a median survival of 16 mo. Challenges in achieving local control, maintaining quality of life, and limiting toxicity plague treatment strategies for this disease. Radiotherapy dose intensification through hypofractionation and stereotactic radiosurgery is a promising strategy that has been explored to meet these challenges. We review the use of hypofractionated radiotherapy and stereotactic radiosurgery for patients with newly diagnosed and recurrent glioblastoma.

Stereotactic Ablative Radiotherapy for Early-Stage Lung Cancer.

The rising incidence of early-stage lung cancer, particularly in medically inoperable patients, is anticipated because of the implementation of early detection strategies and population aging in the United States and worldwide. This mandates the development of noninvasive curative treatment approaches for this disease. Stereotactic ablative radiotherapy (SABR) has recently emerged as a standard of care for early-stage lung cancer in medically inoperable patients who cannot safely tolerate surgical lobectomy, the established standard for operable patients. Further experience has demonstrated key principles with this highly conformal and dose-intensive radiation technique, including the need for sufficiently high biologically effective dose to achieve optimal local control, dose-fractionation modifications needed to treat centrally located tumors safely, and individualization of treatment based on tumor size, location, and other factors. SABR requires particular technical expertise including a nuanced understanding of dose prescription and calculation and appropriate management of tumor and organ motion. Progress continues as increasing experience with and data on SABR in selected cohorts of medically operable patients suggest comparable oncologic outcomes and a more favorable toxicity profile that challenges the historical standard of care for broader patient populations.

Clinical Outcomes in Elderly Patients Treated for Oral Cavity Squamous Cell Carcinoma.

PURPOSE: Oral cavity squamous cell carcinoma (OCSCC) commonly occurs in elderly patients. This study explores the clinical outcomes in elderly patients with OCSCC based on their functional status and clinical comorbidities. METHODS AND MATERIALS: We retrospectively reviewed 180 patients aged ≥70 who were treated with definitive intent with surgery followed by adjuvant therapy if indicated for newly diagnosed OCSCC from 1998 to 2013. Pathology review was conducted, and Eastern Cooperative Oncology Group (ECOG) performance status and the Head and Neck Charlson Comorbidity Index (HN-CCI) were assessed. We performed Kaplan-Meier analyses and cumulative incidence estimates to assess overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LRR). Univariate and multivariate analyses were used to test age, adjuvant therapy, adverse pathologic features, ECOG status, and HN-CCI status as predictors. RESULTS: The median age was 80 years (range, 70-95 years), with a median follow-up time of 23 months. The median OS was 18 months and 46 months for patients aged 70 to 84 and ≥85, respectively (P=.0017). The LRR was 24% at 1 year and 30% at 2 years for all patients. On univariate analysis, ECOG score ≥2 (hazard ratio [HR] = 1.96; confidence interval [CI] 1.19-3.21; P=.008) and HN-CCI score ≥2 (HR=1.97; CI 1.17-3.34; P=.011) were predictors of worse OS. On multivariate analysis, HN-CCI score was a better predictor of OS, PFS, and LRR than was ECOG score. Predictors of worse OS were age ≥85 (HR=1.78; CI 1.07-2.96; P=.026), HN-CCI score of ≥2 (HR=2.21; CI 1.20-4.08; P=.011), and adverse features (HR=2.35; CI 1.34-4.13; P=.003). Adjuvant therapy did not have a significant impact on OS or LRR for patients with adverse features even though 48% of them did not receive it. CONCLUSION: Elderly patients with good health and performance status may live long enough to experience disease progression from OCSCC. ECOG and HN-CCI scores may be useful to evaluate the candidacy of elderly patients for adjuvant therapy. However, the benefit of adjuvant therapy in this population remains elusive and should be investigated prospectively.

Lymph Node Count From Neck Dissection Predicts Mortality in Head and Neck Cancer.

Purpose Multiple smaller studies have demonstrated an association between overall survival and lymph node (LN) count from neck dissection in patients with head and neck cancer. This is a large cohort study to examine these associations by using a national cancer database. Patients and Methods The National Cancer Database was used to identify patients who underwent upfront nodal dissection for mucosal head and neck squamous cell carcinoma between 2004 and 2013. Patients were stratified by LN count into those with < 18 nodes and those with ≥ 18 nodes on the basis of prior work. A multivariable Cox proportional hazards regression model was constructed to predict hazard of mortality. Stratified models predicted hazard of mortality both for patients who were both node negative and node positive. Results There were 45,113 patients with ≥ 18 LNs and 18,865 patients with < 18 LNs examined. The < 18 LN group, compared with the ≥ 18 LN group, had more favorable tumor characteristics, with a lower proportion of T3 and T4 lesions (27.9% v 39.8%), fewer patients with positive nodes (46.6% v 60.5%), and lower rates of extracapsular extension (9.3% v 15.1%). Risk-adjusted Cox models predicting hazard of mortality by LN count showed an 18% increased hazard of death for patients with < 18 nodes examined (hazard ratio [HR] 1.18; 95% CI, 1.13 to 1.22). When stratified by clinical nodal stage, there was an increased hazard of death in both groups (node negative: HR, 1.24; 95% CI, 1.17 to 1.32; node positive: HR, 1.12; 95% CI, 1.05 to 1.19). Conclusion The results of our study demonstrate a significant overall survival advantage in both patients who are clinically node negative and node positive when ≥ 18 LNs are examined after neck dissection, which suggests that LN count is a potential quality metric for neck dissection.

Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells.

Radiation therapy after lymph node dissection increases the risk of developing painful and incurable lymphedema in breast cancer patients. Lymphedema occurs when lymphatic vessels become unable to maintain proper fluid balance. The sensitivity of lymphatic endothelial cells (LECs) to ionizing radiation has not been reported to date. Here, the radiosensitivity of LECs in vitro has been determined using clonogenic survival assays. The ability of various growth factors to alter LEC radiosensitivity was also examined. Vascular endothelial growth factor (VEGF)-C enhanced radiosensitivity when LECs were treated prior to radiation. VEGF-C-treated LECs exhibited higher levels of entry into the cell cycle at the time of radiation, with a greater number of cells in the S and G2/M phases. These LECs showed higher levels of γH2A.X-an indicator of DNA damage-after radiation. VEGF-C did not increase cell death as a result of radiation. Instead, it increased the relative number of quiescent LECs. These data suggest that abundant VEGF-C or lymphangiogenesis may predispose patients to radiation-induced lymphedema by impairing lymphatic vessel repair through induction of LEC quiescence.