Patterns of Failure in Patients With Borderline Resectable/Locally Advanced Pancreatic Cancer After Preoperative Chemotherapy and Stereotactic Body Radiation Therapy.

Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection. Methods and Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC. Patients who underwent preoperative chemotherapy and SBRT followed by surgical resection were reviewed. SBRT was delivered to a dose of 33 Gy in 5 fractions. Kaplan-Meier overall survival and progression-free survival estimates were calculated. Results: In total, 18 patients (12 BRPC, 6 LAPC) were included. Median age was 69 years (range 41-84 years). Median follow-up was 30 months (range 13-59 months). Seventeen patients (94%) had a R0 resection and 13 (72%) underwent vascular reconstruction. Median overall survival and progression-free survival was 42 months (range 13-59 months) and 23 months (range 1-45 months), respectively. In total, 61% (11/18) patients experienced progression at any point during follow-up. Of the patients who experienced recurrence, 27% (3/11) experienced local progression as component of their first recurrence, whereas 100% (11/11) experienced distant progression as a component of their first recurrence. When examining all recurrences that occurred at any point in follow-up, 28% (5/18) of patients experienced local or locoregional recurrence and 61% (11/18) experienced distant progression. Conclusions: Local control and margin negative resection rates were excellent with preoperative chemotherapy and nondose-escalated SBRT in surgically resected patients with BR/LAPC. Distant recurrence was the predominant site of failure with lower incidences of isolated locoregional recurrences. Additional research is needed to determine the ideal treatment volume and patients who may benefit from dose escalation.

Global epidemiologic patterns of oropharyngeal cancer incidence trends.

BACKGROUND: The emergence of human papillomavirus (HPV)-positive oropharyngeal cancer and evolving tobacco use patterns have changed the landscape of head and neck cancer epidemiology internationally. We investigated updated trends in oropharyngeal cancer incidence worldwide. METHODS: We analyzed cancer incidence data between 1993 and 2012 from 42 countries using the Cancer Incidence in Five Continents database volumes V through XI. Trends in oropharyngeal cancer incidence were compared with oral cavity cancers and lung squamous cell carcinomas using log-linear regression and age period-cohort modeling. RESULTS: In total, 156 567 oropharyngeal cancer, 146 693 oral cavity cancer, and 621 947 lung squamous cell carcinoma patients were included. Oropharyngeal cancer incidence increased (P < .05) in 19 and 23 countries in men and women, respectively. In countries with increasing male oropharyngeal cancer incidence, all but 1 had statistically significant decreases in lung squamous cell carcinoma incidence, and all but 2 had decreasing or nonsignificant net drifts for oral cavity cancer. Increased oropharyngeal cancer incidence was observed both in middle-aged (40-59 years) and older (≥60 years) male cohorts, with strong nonlinear birth cohort effects. In 20 countries where oropharyngeal cancer incidence increased for women and age period-cohort analysis was possible, 13 had negative or nonsignificant lung squamous cell carcinoma net drifts, including 4 countries with higher oropharyngeal cancer net drifts vs both lung squamous cell carcinoma and oral cavity cancer (P < .05 for all comparisons). CONCLUSIONS: Increasing oropharyngeal cancer incidence is seen among an expanding array of countries worldwide. In men, increased oropharyngeal cancer is extending to older age groups, likely driven by human papillomavirus-related birth cohort effects. In women, more diverse patterns were observed, suggesting a complex interplay of risks factors varying by country, including several countries where female oropharyngeal cancer increases may be driven by HPV.

Predicting Pathologic Lymph Node Positivity in cN0 Pharynx and Larynx Cancers.

BACKGROUND: Elective neck dissection is a standard of care for pharynx and most larynx cancer patients undergoing surgery, based largely on historical series. It is unclear if this is necessary for all patients in the modern era. METHODS: Patients with cN0 oropharynx, larynx, and hypopharynx cancers diagnosed from 2010-2015 undergoing primary surgery were identified in the National Cancer Data Base. RESULTS: Inclusion criteria were met by 4117 cN0 patients. The presence of lymphovascular invasion (LVI) was the strongest independent predictor of pN+ (odds ratio [OR] = 4.19, 95% confidence interval [CI] 3.56-4.93, p < 0.001). Histologic grade strongly predicted pN+ (OR 2.58, 95% CI 1.88-3.59, p < 0.001). A nomogram predicted less than 10% of cN0 patients had pN+ risk <15%. CONCLUSION: LVI and grade are the strongest predictors of pN+ among patients with cN0 pharynx and larynx cancer. Even in the modern era, pN+ rates warrant neck dissection for cN0 patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1660-1666, 2023.

Lifestyle and sociodemographic factors associated with treatment choice of clinically localized prostate cancer in an equal access healthcare system.

Sociodemographic and lifestyle factors may play a role in determining whether patients with clinically localized prostate cancer (PC) are managed with active surveillance (AS), radical prostatectomy (RP), or radiation therapy (RT); however, these relationships have not been well examined. In a cross-sectional study conducted within an equal access healthcare system, multivariable adjusted regression analysis revealed that living with a spouse or partner was associated with a 65% lower chance of being managed by RT (P = 0.001) and 57% lower risk of being managed by AS (P = 0.042) compared with RP. No other sociodemographic or lifestyle factors were independently associated with treatment modality.

Nodal Metastasis Count and Oncologic Outcomes in Head and Neck Cancer: A Secondary Analysis of NRG/RTOG 9501, NRG/RTOG 0234, and EORTC 22931.

PURPOSE: A better understanding of the relationship between the spread of head and neck squamous cell carcinoma (HNSCC) to regional lymph nodes (LNs) and the frequency and manner of treatment failure should help design better treatment intensification strategies. In this study, we evaluated the relationship between recurrence patterns, mortality, and number of pathologically positive (+) LNs in HNSCC in 3 prospective randomized controlled trials. METHODS AND MATERIALS: We performed a secondary analysis of 947 patients with HNSCC enrolled in RTOG 9501 (n = 410), RTOG 0234 (n = 203), and EORTC 22931 (n = 334) undergoing surgery and postoperative radiation ± systemic therapy. Multivariable models were constructed for overall survival (OS), disease-free survival (DFS), locoregional relapse (LRR), and distant metastases (DM). Restricted cubic splines were used to model the nonlinear relationship between +LN number and outcomes. RESULTS: In multivariable analysis, OS and DFS decreased with each +LN without plateau, most pronounced up to 5 +LNs (OS: hazard ratio [HR], 1.21 per +LN; 95% confidence interval [CI], 1.10-1.34; P < .001; DFS: HR per +LN, 1.19; 95% CI, 1.08-1.30; P < .001) and more gradually beyond this (OS: HR per +LN, 1.02; 95% CI, 1.01-1.06; P < .001; DFS: HR per +LN, 1.04; 95% CI, 1.02-1.06; P < .001). In contrast to LRR risk, which increased sharply up to 5 +LNs (HR per +LN, 1.28; 95% CI, 1.10-1.50; P < .001) but plateaued beyond this (HR per +LN, 1.00; 95% CI, 0.96-1.04; P = .98), DM risk increased continuously with increasing +LNs (≤5 +LNs: HR per +LN, 1.10; 95% CI, 1.01-1.20; P = .04; >5 +LNs: HR per +LN, 1.05; 95% CI, 1.02-1.08; P = .003). CONCLUSIONS: In high-risk resected HNSCC, increased mortality was associated with increased +LN count. LRR and DM risk both increased in parallel up to 5 +LNs, but only DM continued to increase for further +LN increases. These differing recurrence patterns can help inform design of future treatments.

Quantitative Nodal Burden and Mortality Across Solid Cancers.

BACKGROUND: Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors. METHODS: We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses. RESULTS: Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites. CONCLUSIONS: Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors.

Pathologic primary tumor factors associated with risk of lymph node involvement in patients with non-endometrioid endometrial cancer.

PURPOSE/OBJECTIVES: Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies. MATERIALS/METHODS: Patients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement. RESULTS: Among 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15-4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06-1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43-5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22-1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48-2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92-1.24, p = 0.42). CONCLUSION: Among patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies.

Ovarian Transposition Before Pelvic Radiation Therapy: Spatial Distribution and Dose Volume Analysis.

PURPOSE: There is a paucity of data analyzing the anatomic locations and dose volume metrics achieved for surgically transposed ovaries in patients desiring fertility or hormonal preservation receiving pelvic radiation therapy (RT), which were examined herein. METHODS AND MATERIALS: This is a retrospective study including women who underwent ovarian transposition before pelvic RT between 2010 to 2020. The craniocaudal (CC) distance of the ovary centroid to the (1) plane of the sacral promontory, (2) iliac crest, and (3) the nearest distance between the ovary edge and RT planning target volume (PTV) were measured (cm). The area under the receiver operating characteristic curve and cut-point analysis estimating ovary location outside the PTV was performed. RESULTS: Thirty-one ovaries were analyzed from 18 patients. Thirteen (72.2%) were treated with intensity modulated RT, and 5 (27.8%) were treated with 3-dimensional conformal radiation therapy. Most ovaries were located above the sacral promontory (64.5%, n = 20), below the iliac crest (96.8%, n = 30), and outside the PTV (64.5%, n = 20). The median distance from the ovaries to the sacral promontory, iliac crest, and PTV was 0.8 cm (interquartile range [IQR], -0.83 to 1.59 cm), -3.22 cm (IQR, -5.12 to -1.84 cm), and 0.9 cm (IQR, -1.0 to 1.9 cm), respectively. The area under the receiver operating characteristic curve and cut-point analysis demonstrated that distance from the iliac crest predicted an ovary to be outside the PTV with an optimal cut-point of -3.0 cm (C-index = 0.82). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6-20.2 Gy) and 32.2 Gy (IQR 24.8-46.5 Gy), respectively. CONCLUSIONS: Despite most transposed ovaries being located outside the PTV, nearly all remained below the iliac crest and received RT doses associated with a high risk of ovarian failure. These findings deepen our understanding of the spatial relationship between transposed ovaries and dose to inform surgical and pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted.

Evaluation of sociodemographic and baseline patient characteristic differences in cervical cancer patients treated with either external beam or brachytherapy boost.

PURPOSE: Chemoradiation is considered the standard of care for locally advanced cervical cancer. While brachytherapy (BT) boost is associated with improved survival and less toxicity compared to external beam radiation therapy (EBRT) boost, it is unclear why many patients do not receive a BT boost. In this study, we compared sociodemographic and baseline patient characteristics between patients receiving EBRT boost versus BT boost. METHODS: We analyzed patients in the National Cancer Database diagnosed between 2004 and 2016 with FIGO stage IIB-IVA cervical cancer treated with nonpalliative doses of chemoradiation. Logistic regression analysis was utilized to evaluate BT utilization over time and by other clinicopathological and sociodemographic factors. RESULTS: Overall, 5764 patients were evaluated, of which 4937 (86%) underwent BT boost. Using multivariable logistic regression, higher FIGO stage was a significant predictor for utilization of EBRT versus BT boost, with odds ratio 2.92 (95% confidence interval [CI] 2.04-4.16; p < 0.001), 2.68 (95%CI 2.22-3.24; p < 0.001), and 4.51 (95%CI 3.05-6.67; p < 0.001) for IIIA, IIIB, and IVA, respectively, compared to IIB. Increased utilization of EBRT boost was also associated with community cancer facility types, lower income (based on zip code), earlier year of diagnosis, and higher comorbidity score. CONCLUSIONS: In FIGO stage IIB-IVA cervical cancer patients treated with nonpalliative doses of chemoradiation, overall utilization of BT is 86%. Higher FIGO stage, community cancer facilities, lower income, earlier year of diagnosis, and higher comorbidity score were significant predictors of EBRT boost utilization. Future studies are needed to better understand reasons for this as higher FIGO stage patients are the mostly likely to benefit from a BT boost.

Development and Validation of a Modified Pathologic Nodal Classification System for Cutaneous Melanoma.

Importance: Given the evolving patterns of lymph node evaluation for cutaneous melanoma, it is unclear whether the current nodal classification system will continue to accurately reflect prognosis in the modern era. Existing nodal staging for cutaneous melanoma was developed primarily for patients undergoing completion lymph node dissection (CLND) for node-positive disease and does not produce groups with continuously increasing mortality. Objective: To develop and validate a modified nodal classification system for cutaneous melanoma. Design, Setting, and Participants: This retrospective cohort analysis included 105 785 patients with cutaneous melanoma undergoing surgery and nodal evaluation from January 1, 2004, to December 31, 2015, in the National Cancer Database. Extent of lymph node dissection was available for patients diagnosed in 2012 and onward. Multivariable models were generated with number of positive lymph nodes modeled using restricted cubic splines. A modified nodal classification system was derived using recursive partitioning analysis (RPA). The proposed lymph node classification system was validated in 85 499 patients from the Surveillance, Epidemiology, and End Results (SEER-18) database. Data were analyzed from April 9, 2020, to May 28, 2021. Main Outcomes and Measures: Overall survival. Results: Among the 105 785 patients included in the analysis (62 496 men [59.1%]; mean [SD] age, 59.9 [15.5] years), number of positive lymph nodes (hazard ratio [HR] per lymph node for 0 to 2 positive lymph nodes, 2.48 [95% CI, 2.37-2-61; P < .001]; HR per lymph node for ≥3 positive lymph nodes, 1.10 [95% CI 1.07-1.13; P < .001]), clinically detected metastases (HR, 1.35; 95% CI, 1.27-1.42; P < .001), and in-transit metastases (HR, 1.48; 95% CI, 1.34-1.65; P < .001) were independently associated with mortality. An RPA-derived system using these variables demonstrated continuously increasing mortality for each proposed lymph node classification group, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 2.72 (95% CI, 2.58-2.86) for N1b, 3.79 (95% CI, 3.51-4.08) for N2a, 4.56 (95% CI, 4.22-4.92) for N2b, 6.15 (95% CI, 5.59-6.76) for N3a, and 8.25 (95% CI, 7.64-8.91) for N3b in the proposed system (P < .001). By contrast, the current American Joint Committee on Cancer (AJCC) nodal classification system produced a more haphazard mortality profile, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 3.81 (95% CI, 3.53-4.12) for N1b, 2.59 (95% CI, 2.30-2.93) for N1c, 2.71 (95% CI, 2.56-2.87) for N2a, 4.51 (95% CI, 4.17-4.87) for N2b, 3.44 (95% CI, 2.60-4.55) for N2c, 6.06 (95% CI, 5.51-6.67) for N3a, 8.15 (95% CI, 7.54-8.81) for N3b, and 6.90 (95% CI, 5.60-8.49) for N3c. As a sensitivity analysis, the proposed system continued to accurately stratify patients when excluding those undergoing CLND for microscopic lymph node metastases. This system was validated for overall survival and cause-specific mortality in SEER-18. Last, a new overall staging system for node-positive patients was developed by RPA and demonstrated improved concordance vs the AJCC, 8th edition system (C statistic, 0.690 [95% CI, 0.689-0.691] vs 0.666 [95% CI, 0.666-0.668]). Conclusions and Relevance: The findings of this cohort study suggest that a modified nodal classification system can accurately stratify mortality risk in cutaneous melanoma in an era of increasing use of sentinel lymph node biopsy without CLND and should be considered for future staging systems.

Improved survival in women versus men with merkel cell carcinoma.

BACKGROUND: Studies have observed that women have better outcomes than men in melanoma, but less is known about the influence of sex differences on outcomes for other aggressive cutaneous malignancies. OBJECTIVE: To investigate whether women and men have disparate outcomes in Merkel cell carcinoma (MCC). METHODS: Patients with nonmetastatic MCC undergoing surgery and lymph node evaluation were identified from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analysis and Cox proportional hazards regression models were used for overall survival, and competing-risks analysis and Fine-Gray models were used for cause-specific and other-cause mortality. RESULTS: The NCDB cohort (n = 4178) included 1516 (36%) women. Women had a consistent survival advantage compared with men in propensity score-matched analysis (66.0% vs 56.8% at 5 years, P < .001) and multivariable Cox regression (hazard ratio, 0.68; 95% confidence interval, 0.61-0.75; P < .001). Similarly, women had a survival advantage in the SEER validation cohort (n = 1202) with 457 (38.0%) women, which was entirely due to differences in MCC-specific mortality (5-year cumulative incidence: 16.4% vs 26.7%, P = .002), with no difference in other-cause mortality (16.8% vs 17.8%, P = .43) observed in propensity score-matched patients. LIMITATIONS: Potential selection bias from a retrospective data set. CONCLUSION: In MCC, women have improved survival compared with men, driven by MCC-related mortality.

Evaluation of Mobile Health Applications to Track Patient-Reported Outcomes for Oncology Patients: A Systematic Review.

PURPOSE: In response to the COVID-19 pandemic, there has been a rapid growth in the use of telehealth/telemedicine that will likely be sustained in the postpandemic setting. Mobile health applications (apps) can be used as part of the telehealth encounter to monitor patient-reported outcomes (PROs) and enhance patient-provider communication. METHODS AND MATERIALS: A systematic review was performed of mobile health apps with symptom trackers. We searched the iOS App Store and Android Google Play using the words cancer, oncology, and symptom tracker. Apps were included if they incorporated a symptom tracking function that could allow patients with cancer to record symptoms and PROs. Apps were evaluated using the mobile apps rating scale, which includes engagement, functionality, aesthetics, information, and app subjective quality. RESULTS: The initial search yielded 1189 apps, with 101 apps eligible after title and description screening. A total of 41 apps met eligibility criteria and were included in this study. The majority of apps (73%, n = 30) were general health/pain symptom trackers, and 27% (n = 11) were cancer-specific. The app quality mean scores assessed using the mobile apps rating scale ranged from 2.43 to 4.23 (out of 5.00). Only 1 app has been trialed for usability among patients with cancer. CONCLUSIONS: Although various symptom tracking apps are available, cancer-specific apps remain limited. Future collaboration between oncologists, app developers, and patients to optimize PRO assessment and integration with telehealth/telemedicine encounters to increase symptom recognition and enhance patient-provider communication is urgently needed.

Quantitative metastatic lymph node burden and survival in Merkel cell carcinoma.

BACKGROUND: Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for the number of metastatic LNs, which is a primary driver of survival in multiple cancers. OBJECTIVE: To determine the impact of the number of metastatic LNs on survival in MCC. METHODS: Patients with MCC undergoing surgery were identified from the National Cancer Database (NCDB). The association between metastatic LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived by using recursive partitioning analysis. MCC patients undergoing surgery in the Surveillance, Epidemiology, and End Results (SEER) Program were used as validation cohort. RESULTS: Among 3670 patients in the NCDB, increasing metastatic LN number was associated with decreased survival (P < .001). Mortality risk increased continuously with each additional positive LN when using multivariable, nonlinear modeling. According to a novel staging system derived via recursive partitioning analysis, the hazard ratio for death in multivariable regression compared with patients without LN involvement was 1.24 (P = .049), 2.08 (P < .001), 3.24 (P < .001), and 6.13 (P < .001) for the proposed N1a (1-3 metastatic LNs with microscopic detection), N1b (1-3 metastatic LNs with macroscopic detection), N2 (4-8 metastatic LNs), and N3 (≥9 metastatic LNs), respectively. This system was validated in the SEER cohort and showed improved concordance compared with the American Joint Committee on Cancer, Eighth Edition. LIMITATIONS: Retrospective design. CONCLUSIONS: Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC.

Variations in the association of grade with survival across the head and neck cancer landscape.

BACKGROUND: Although pathologic tumor grade is a well-established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain. METHODS: HNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed. RESULTS: Among 27 041 HNSCC patients, 13 941 had oral cavity cancers (OCC). Intermediate-grade (hazard ratio [HR] 1.16, 95% CI 1.07-1.26, P < .001) and high-grade (HR 1.38, 95% CI 1.26-1.52, P < .001) tumors had worse survival than low-grade tumors. This magnitude was comparable to other well-established prognostic factors, including margin positivity, extranodal extension, and lymphovascular invasion. By contrast, there was no association between grade and survival in larynx/hypopharynx or HPV(-) oropharynx cancer. CONCLUSIONS: The prognostic impact of pathologic grade is highly variable across head and neck subsites and is the strongest among OCC patients.

Comparison of Survival After Transoral Robotic Surgery vs Nonrobotic Surgery in Patients With Early-Stage Oropharyngeal Squamous Cell Carcinoma.

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data. Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer. Design, Setting, and Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020. Main Outcomes and Measures: Overall survival. Results: Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10). Conclusions and Relevance: This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.

The role of concomitant chemoradiotherapy in AJCC 7th edition T1-2N1 oropharyngeal carcinoma in the human papillomavirus era.

BACKGROUND: Radiotherapy (RT) without chemotherapy is considered a standard of care for the management of American Joint Committee on Cancer (AJCC) 7th edition (7E) T1-2N1 oropharyngeal squamous cell carcinoma (OPSCC). Recent data suggests concurrent chemoradiation (CCRT) may benefit these patients but did not include human papillomavirus (HPV) status. Given the radiosensitivity differences between HPV-positive versus HPV-negative OPSCC, the effect of chemotherapy may differ in these patients. METHODS: We analyzed patients in the National Cancer Database diagnosed between 2010 and 2015 with AJCC 7E stage cT1-2N1M0 OPSCC and known HPV status undergoing definitive RT or CCRT. RESULTS: Overall, 1964 patients were included, including 1297 (66%) HPV-positive and 667 (34%) HPV-negative patients. 66% received CCRT and 34% received RT alone. In multivariate analysis, CCRT was associated with improved survival compared with RT alone (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.57-0.87; P = 0.001). In propensity score-matched cohorts, 4-year overall survival was 87.4% vs 78.4% in HPV-positive patients receiving CCRT and RT alone, respectively (P = 0.002), and 65.5% vs 58.9% in HPV-negative patients, respectively (P = 0.2). There was no evidence that HPV-positivity diminished the association between CCRT and longer survival (HR, 0.57; 95% CI, 0.42-0.81) versus what was observed in HPV-negative patients (HR, 0.86; 95% CI, 0.64-1.16) (interaction P = 0.06). CONCLUSIONS: CCRT is associated with improved survival in AJCC 7E T1-2N1 OPSCC. Despite the radiosensitivity of HPV-positive OPSCC, the association of CCRT with improved survival for T1-2N1 HPV-positive OPSCC was at least as strong, if not stronger, than what was observed in HPV-negative patients.

A dosimetric evaluation of a single urethral constraint for high-dose-rate prostate brachytherapy.

PURPOSE: The American Brachytherapy Society (ABS) consensus guidelines for high-dose-rate (HDR) prostate brachytherapy suggest 11 different dose constraints for the urethra. The purpose of this study is to evaluate whether a single urethral constraint of D0.1 cm3 < 110% could meet all the proposed ABS urethral constraints and to evaluate the heterogeneity and similarities of other portions of the dose-volume histogram (DVH) when only optimizing to a single constraint. METHODS: This is a retrospective study of 18 consecutively treated HDR prostate brachytherapy patients treated between May 2018 to November 2018. Nine patients underwent HDR brachytherapy combined with external beam radiation therapy, and nine underwent HDR brachytherapy as monotherapy. Additional DVH values were extracted for the whole, proximal, middle, and distal urethra and compared for differences. RESULTS: None of the ABS suggested constraints were violated when optimizing the urethra D0.1 cm3 dose to be less than 110% of the prescription. An evaluation of the DVHs for the whole, proximal, middle, and distal urethra showed a large variation in the shape of the remainder of the DVH for all parts of the urethra. The largest standard deviations in dose to the whole and middle urethra were at the V14 dose level, and that to the proximal and distal urethra were at the V10 dose level. CONCLUSION: A single urethral dose constraint of D0.1 cm3 < 110% can meet all the proposed ABS constraints. There is high variability in other parts of the urethra DVH when only using a single constraint. Additional data is needed to determine ideal constraints for the entirety of the urethra DVH.

Stage I HPV-positive oropharyngeal cancer: Should all patients receive similar treatments?

BACKGROUND: Patients with clinical stage I human papillomavirus (HPV)-positive oropharyngeal squamous cell cancer (OPSCC) according to the American Joint Committee on Cancer (AJCC) eighth edition classification comprise a heterogeneous group formerly classified as stage I to stage IVA according to the seventh edition of the AJCC classification. These patients historically were treated with disparate treatment regimens, particularly with respect to the use of concurrent chemotherapy. METHODS: The National Cancer Data Base was queried for patients with AJCC eighth edition clinical stage I HPV-positive OPSCC (AJCC seventh edition stage T1-2N0-2bM0) who were diagnosed from 2010 to 2014 and underwent definitive radiotherapy. Concurrent chemotherapy with definitive radiotherapy was defined as chemotherapy administered within 7 days of the initiation of radiotherapy. RESULTS: The current analysis included 4473 patients with HPV-positive stage I OPSCC with a median follow-up of 36.3 months. A total of 3127 patients (69.9%) received concurrent chemotherapy. Concurrent chemotherapy was found to be associated with improved overall survival on multivariable analyses (hazard ratio [HR], 0.782; 95% CI, 0.645-0.948 [P = .012]). The effect of chemotherapy on survival varied based on lymph node involvement (P for interaction = .001). Specifically, chemotherapy was associated with improved survival for patients with lymph node-positive stage I disease (stage III-IVA according to the AJCC seventh edition: HR, 0.682; 95% CI, 0.557-0.835 [P < .001]), but not for patients with N0 disease (stage I-II according to the AJCC seventh edition: HR, 1.646; 95% CI, 1.011-2.681 [P = .05]). Similar results were noted among propensity score-matched cohorts. CONCLUSIONS: Treatment with concurrent chemotherapy was associated with improved overall survival for patients with lymph node-positive, but not lymph node-negative, AJCC eighth edition stage I HPV-positive OPSCC undergoing definitive radiotherapy, thereby supporting different treatment paradigms for these patients.