Biological Effective Radiation Dose for Multiple Myeloma Palliation.

Purpose: Various radiation therapy (RT) dose/fractionation schedules are acceptable for palliation in multiple myeloma. Nine years of single-institution RT experience were reviewed to determine the influence of dose/fractionation and other factors pertinent to individualizing therapy. Methods and Materials: In total, 152 items were identified from Current Procedural Terminology codes for multiple myeloma treatment from 2012 through June 30, 2021. After exclusions, 205 sites of radiation in 94 patients were reviewed. Data were captured from treatment planning and clinical records. To statistically assess the association between biological effective dose (BED10) and variables of interest, BED was first dichotomized to <24 Gy versus ≥24 Gy. Multivariate analysis used SAS software and a generalized estimating equation approach to account for multiple observations per patient. Results: Fractions of 1.8 to 8 Gy were used in 1 to 25 fractions. Most patients had no significant toxicity. Grade 1 toxicity was more likely with greater BED radiation courses, as expected (20% vs 12% for BED <24 Gy). Pain relief was complete or very good for most sites, with <3% reporting no pain relief. Eleven sites in 9 patients required retreatment. All retreatment sites had palliation that was lasting, with a median of 22 months to last follow-up or death after repeat course (range, 0.5-106 months). There was a trend for better pain control and less risk of fracture retreatment with BED ≥24 Gy. Conclusions: Most patients had good palliation without toxicity. BED ≥24 Gy caused 8% greater risk of grade 1 toxicity and trended toward better pain control plus reduced risk of fracture retreatment.

A focused review of statistical practices for relating radiation dose-volume exposure and toxicity.

PURPOSE: Relating dose-volume histogram (DVH) information to patient outcomes is critical for outcomes research in radiation oncology, but this is statistically challenging. We performed this focused review of DVH toxicity studies to characterize current statistical approaches and determine the need for updated reporting recommendations. METHODS AND MATERIALS: We performed a focused MEDLINE search to identify studies published in 5 radiation oncology specialty journals that associated dosimetry with toxicity outcomes in humans receiving radiotherapy between 2015 and 2021. Elements abstracted from each manuscript included the study outcome, organs-at-risk (OARs) considered, DVH parameters analyzed, summary of the analytic approach, use of multivariable statistics, goodness-of-fit reporting, completeness of model reporting, assessment of multicollinearity, adjustment for multiple comparisons, and methods for dichotomizing variables. Each study was also assessed for sufficient reporting to allow for replication of results. RESULTS: The MEDLINE search returned 2,300 studies for review and 325 met the inclusion criteria for the analysis. DVH variables were dichotomized using cut points in 154 (47.4%) studies. Logistic regression (55.4% of studies) was the most common statistical method used to relate DVH to toxicity outcomes, followed by Cox regression (20.6%) and linear regression (12.0%). Multivariable statistical tests were performed in 226 (69.5%) studies; of these, the possibility of multicollinearity was addressed in 47.8% and model goodness-of-fit were reported in 32.6%. The threshold for statistical significance was adjusted to account for multiple comparisons in 41 of 196 (17.1%) studies that included multiple statistical comparisons. Twenty-eight (8.6%) studies were classified as missing details necessary to reproduce the study results. CONCLUSIONS: Current practices of statistical reporting in DVH outcomes suggest that studies may be vulnerable to threats against internal and external validity. Recommendations for reporting are provided herein to guard against such threats and to promote cohesiveness among radiation oncology outcomes researchers.

Prediction of Distant Metastases After Stereotactic Body Radiation Therapy for Early Stage NSCLC: Development and External Validation of a Multi-Institutional Model.

INTRODUCTION: Distant metastases (DMs) are the primary driver of mortality for patients with early stage NSCLC receiving stereotactic body radiation therapy (SBRT), yet patient-level risk is difficult to predict. We developed and validated a model to predict individualized risk of DM in this population. METHODS: We used a multi-institutional database of 1280 patients with cT1-3N0M0 NSCLC treated with SBRT from 2006 to 2015 for model development and internal validation. A Fine and Gray (FG) regression model was built to predict 1-year DM risk and compared with a random survival forests model. The higher performing model was evaluated on an external data set of 130 patients from a separate institution. Discriminatory performance was evaluated using the time-dependent area under the curve (AUC). Calibration was assessed graphically and with Brier scores. RESULTS: The FG model yielded an AUC of 0.71 (95% confidence interval [CI]: 0.57-0.86) compared with the AUC of random survival forest at 0.69 (95% CI: 0.63-0.85) in the internal test set and was selected for further testing. On external validation, the FG model yielded an AUC of 0.70 (95% CI: 0.57-0.83) with good calibration (Brier score: 0.08). The model identified a high-risk patient subgroup with greater 1-year DM rates in the internal test (20.0% [3 of 15] versus 2.9% [7 of 241], p = 0.001) and external validation (21.4% [3 of 15] versus 7.8% [9 of 116], p = 0.095). A model nomogram and online application was made available. CONCLUSIONS: We developed and externally validated a practical model that predicts DM risk in patients with NSCLC receiving SBRT which may help select patients for systemic therapy.

Patterns of Failure and Optimal Treatment Paradigm for Large, Inoperable, Node-Negative Non-small Cell Lung Cancer.

OBJECTIVES: The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt. MATERIALS AND METHODS: Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression. RESULTS AND CONCLUSION: We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.

Why an Increasing Number of Unmatched Residency Positions in Radiation Oncology? A Survey of Fourth-Year Medical Students.

PURPOSE: The number of US fourth-year medical students applying to radiation oncology has decreased during the past few years. We conducted a survey of fourth-year medical students to examine factors that may be influencing the decision to pursue radiation oncology. METHODS AND MATERIALS: An anonymous online survey was sent to medical students at 9 participating US medical schools. RESULTS: A total of 232 medical students completed the survey. Of the 153 students who stated they were never interested in radiation oncology, 77 (50%) reported never having been exposed to the specialty as their reason for not pursuing radiation oncology. The job market was the most commonly cited factor among students who said they were once interested in but ultimately chose not to pursue radiation oncology. Conversely, the recent low pass rates for board examinations and a perception of a lack of diversity within radiation oncology had the least influence. CONCLUSIONS: Despite discussion of potential measures to address this disquieting trend, there have been minimal formal attempts to characterize and address potential causes of a decreasing interest in radiation oncology. This study's data are consistent with previous research regarding the trend of decreased medical student interest in radiation oncology and may be used as part of ongoing introspective assessment to inform future change within radiation oncology.

Nonoperative Treatment of Large (5-7 cm), Node-Negative Non-Small Cell Lung Cancer Commonly Deviates From NCCN Guidelines.

BACKGROUND: Optimal treatment of nonoperative patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. Current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend definitive radiotherapy (RT) with or without sequential chemotherapy and do not include concurrent chemoradiotherapy (chemoRT) as a treatment option. In this study, we identified factors that predict nonadherence to NCCN Guidelines. PATIENTS AND METHODS: Patients who received definitive RT for nonmetastatic, node-negative NSCLC with tumor size of 5 to 7 cm were identified in the National Cancer Database from 2004 through 2016. Patients were evaluated by RT type (stereotactic body RT [SBRT], hypofractionated RT [HFRT], or conventionally fractionated RT [CFRT]) and chemotherapy use (none, sequential, or concurrent with RT). Patients were classified as receiving NCCN-adherent (RT with or without sequential chemotherapy) or NCCN-nonadherent (concurrent chemoRT) treatment. Demographic and clinical factors were assessed with logistic regression modeling. Overall survival was evaluated with Kaplan-Meier, log-rank, and univariable/multivariable Cox proportional hazards regression analyses. RESULTS: Among 2,020 patients in our cohort, 32% received NCCN-nonadherent concurrent chemoRT, whereas others received NCCN-adherent RT alone (51%) or sequential RT and chemotherapy (17%). CFRT was most widely used (64% CFRT vs 22% SBRT vs 14% HFRT). Multivariable analysis revealed multiple factors to be associated with NCCN-nonadherent chemoRT: age ≤70 versus >70 years (odds ratio [OR] , 2.72; P<.001), treatment at a nonacademic facility (OR, 1.65; P<.001), and tumor size 6 to 7 cm versus 5 to 6 cm (OR, 1.27; P=.026). Survival was similar between the NCCN-nonadherent chemoRT and NCCN-adherent groups (hazard ratio, 1.00; P=.992) in multivariable analysis. CONCLUSIONS: A substantial proportion of inoperable patients with large, node-negative NSCLC are not treated according to NCCN Guidelines and receive concurrent chemoRT. Younger patients with larger tumors receiving treatment at nonacademic medical centers were more likely to receive NCCN-nonadherent therapy, but adherence to NCCN Guidelines was not associated with differences in overall survival.

Predictors of In-Hospital Death in Patients with Lung Cancer Admitted for Acute Radiation Pneumonitis: A Healthcare Cost and Utilization Project (HCUP) Analysis.

BACKGROUND: Radiation pneumonitis (RP) is a dose-limiting and potentially fatal toxicity of thoracic radiotherapy most often seen in patients treated for primary lung cancer. The purpose of this study was to identify predictors of in-hospital death among lung cancer patients admitted for acute RP in the Healthcare Cost and Utilization Project (HCUP) database. MATERIALS AND METHODS: The HCUP National Inpatient Sample database was queried from 2012 through 2016 to capture adult lung cancer patients admitted to the hospital with a principal diagnosis of acute RP. Multivariate logistic regression modeling and χ2 tests were used to determine predictors of in-hospital death. RESULTS: Of the 882 patients with lung cancer admitted for RP, 67 patients (7.6%) died during the hospitalization and 90 patients (10.2%) required mechanical ventilation. Of those requiring mechanical ventilation, 38 patients (42.2%) died. The average age at hospitalization was 70.4 years (range, 35-90). Of those factors associated with death on univariate analysis, interstitial lung disease (odds ratio [OR] = 6.14; 95% confidence interval [CI], 1.9-19.4; P = .002), pulmonary hypertension (OR = 3.1; 95% CI, 1.6-6.2; P = .001), diabetes mellitus (OR = 2.0; 95% CI, 1.1-3.3; P = .013), and more affluent Zip Code (OR = 1.9; 95% CI, 1.1-3.2; P = .021) remained statistically significant on multivariate logistic regression. CONCLUSION: In the largest reported cohort of patients with lung cancer hospitalized with a principal diagnosis of acute RP, the presence of interstitial lung disease, pulmonary hypertension, diabetes mellitus, and more affluent Zip Code were associated with in-hospital death. Comorbid diagnoses may be useful for risk-stratified management of inpatients with RP.

Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma.

BACKGROUND: Lymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date. PATIENTS AND METHODS: The National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof. RESULTS: Of 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P < .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P > .05 for both), was associated with OS. CONCLUSION: Detecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.

Does the Incidence of Treatment-Related Toxicity Plateau After Radiation Therapy: The Long-Term Impact of Integral Dose in Hodgkin's Lymphoma Survivors.

BACKGROUND: Conventional radiation therapy (RT) has produced unprecedented cure rates in patients with Hodgkin's lymphoma (HL) but exposed large volumes of nontargeted tissue to radiation (integral dose). OBJECTIVE: Our goal was to report the effects of integral radiation dose on health outcomes in patients with at least 20 years of potential follow-up time. METHODS AND MATERIALS: We reviewed the medical records of 365 patients who were treated with RT for HL between 1965 and 1995. All patients were confirmed to have received primary RT with curative intent at our institution for de novo HL. Serious adverse events were classified as HL progression or death, grade ≥3 treatment- or staging-related acute or late effects, second malignancies, or cardiovascular events. RESULTS: The minimum potential follow-up time was 20 years, and the actual median follow-up time 22 years (range, <1-49 years) for all patients and 27 years (range, 5-49 years) for surviving patients. The overall survival rates at 5, 10, 20, 30, and 40 years were 86%, 76%, 64%, 44%, and 27%, respectively. The observed-to-expected ratio for second malignancy was 3.6 (95% confidence interval, 2.9-4.4). Grade ≥3 cardiovascular events occurred in 31% of all patients (n = 112). At the time of the most recent follow up, serious adverse events occurred in 70% of the entire cohort (n = 256) and 58% (n = 103), 77% (n = 103), and 93% (n = 50) among those with a potential 20, 30, and 40 years of follow up, respectively. CONCLUSIONS: With increased survivorship, the long-term impact of the integral radiation dose may result in clinically significant adverse events, which suggests the importance of surveillance and affirms advances in both chemotherapy and RT that minimize the integral dose in future patients with HL.

Multi-institutional analysis of stereotactic body radiation therapy for operable early-stage non-small cell lung carcinoma.

PURPOSE: Although stereotactic body radiation therapy (SBRT) is the standard of care for inoperable early-stage non-small cell lung carcinoma (NSCLC), its role for medically operable patients remains controversial. To address this knowledge gap, we conducted a multi-institutional study to assess post-SBRT disease control and survival outcomes in medically operable patients. METHODS: We conducted a retrospective cohort study including patients with biopsy-proven cT1-2N0M0 NSCLC treated with definitive SBRT (2006-2015). Per patient charts, inoperability referred to documentation of poor surgical candidacy with a given rationale for lack of resection. Charts of operable patients contained documentation of patients refusing surgery or choosing SBRT, without a documented rationale for inoperability. Subjects were excluded in cases of ambiguity regarding the aforementioned definitions and/or lack of clearly documented operability status. Endpoints included local failure (LF) and regional-distant failure, both evaluated with Fine and Gray competing risks regression; Kaplan-Meier methodology analyzed overall survival (OS) and progression-free survival (PFS). RESULTS: Of 952 patients, 408 (42.9%) were operable, and 544 (57.1%) were inoperable. Median follow-up was 22 months. Two-year LF was 9.7% in operable patients and 8.2% in inoperable patients (p = 0.36). There was no statistical difference in regional-distant failure (p = 0.55) between cohorts. Operable patients experienced statistically higher OS (p = 0.04), but not PFS (p = 0.11). Respective 1-, 2-, and 3-year OS in operable patients were 85.4%, 66.2%, and 51.2%. CONCLUSIONS: Although patients with operable NSCLC experience higher OS than their inoperable counterparts, disease-related outcomes are similar. These results may better inform shared decision-making between medically operable patients and their multidisciplinary providers.

Stereotactic body radiotherapy with adjuvant systemic therapy for early-stage non-small cell lung carcinoma: A multi-institutional analysis.

PURPOSE: Although adjuvant systemic therapy (ST) is often recommended for the treatment of patients with high-risk, early-stage non-small cell lung carcinoma (NSCLC) after surgery, there is little evidence supporting the use of ST with stereotactic body radiotherapy (SBRT). METHODS: We conducted a retrospective cohort study using a multi-institutional database to identify consecutive patients with T1-3N0M0 NSCLC treated with definitive SBRT from 2006-2015. Treatment groups were defined as those who received SBRT + ST or SBRT alone. Regional-distant failure (RDF) was analyzed with Fine and Gray competing risks regression. Progression-free (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox regression. Additional comparisons were made after 2:1 nearest-neighbor propensity-score matching on clinical risk factors. RESULTS: We identified 54 patients who received SBRT + ST. The most common ST regimen was a platinum doublet (n = 38; 70.4%). Compared with patients receiving SBRT (n = 1269), SBRT + ST patients were younger (median age: 70 v 77 years, p < 0.001), had larger tumors (>3 cm: 38.9% v 21.6%, p = 0.02) and higher T-stage (T2-3: 42.6% v 22.5%, p = 0.002). Compared with SBRT patients, SBRT + ST patients had lower 2-year RDF (3.1% v 16.9%, p = 0.02). On multivariable analysis, SBRT + ST was associated with reduced RDF (HR: 0.15, 95%CI: 0.04-0.62), with a trend toward improved PFS (HR: 0.70, 95%CI: 0.48-1.03), but not OS (HR: 0.74, 95%CI: 0.49-1.11). After propensity-score matching, the SBRT + ST cohort demonstrated improved RDF (HR: 0.17, 95%CI: 0.04-0.76) and PFS (HR: 0.59, 95%CI: 0.38-0.93). CONCLUSION: In this multi-institutional analysis, adjuvant ST was independently associated with reduced RDF in early-stage NSCLC patients treated with SBRT.

Extended duration of dilator use beyond 1 year may reduce vaginal stenosis after intravaginal high-dose-rate brachytherapy.

BACKGROUND: Vaginal dilators (VD) are recommended following vaginal or pelvic radiotherapy for patients with endometrial carcinoma (EC) to prevent vaginal stenosis (VS). The time course of VS is not fully understood and the optimal duration of VD use is unknown. METHODS: We reviewed 243 stage IA-II EC patients who received adjuvant brachytherapy (BT) at an academic tertiary referral center. Patients were instructed to use their VD three times per week for at least 1-year duration. The primary outcome was development of grade ≥ 1 VS using CTCAEv4 criteria during the follow-up period. The log-rank test and multivariable Cox proportional hazards modeling were used to evaluate the effect of VD use (noncompliance vs. standard compliance [up to 1 year] vs. extended compliance [over 1 year]) on VS. RESULTS: The median follow-up was 15.2 months over the 5-year study period. At 15 months, the incidence of VS was 38.8% for noncompliant patients, 33.5% for those with standard compliance, and 21.4% for those with extended compliance (median time to grade ≥ 1 VS was 17.5 months, 26.7 months, and not yet reached for these groups, respectively). On multivariable Cox regression analysis, extended compliance remained a significant predictor of reduced VS risk when compared to both noncompliance (HR 0.38, 95% CI 0.18-0.80, p = 0.012) and standard compliance (HR 0.43, 95% CI 0.20-0.89, p = 0.023). CONCLUSIONS: The risk of VS persists beyond 1 year after BT. Extended VD compliance beyond 1 year may mitigate this risk.

Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma.

Soft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50-50.4 Gy in 25-28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio - 0.16, 95% confidence interval: 0.034-0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.

Cost-effectiveness of adjuvant intravaginal brachytherapy in high-intermediate risk endometrial carcinoma.

PURPOSE: We assessed the cost-effectiveness of adjuvant intravaginal brachytherapy (IVBT) vs. observation after total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO) for high-intermediate risk (HIR) endometrial carcinoma. METHODS AND MATERIALS: A Markov model was used to assess the cost-effectiveness of IVBT by comparing average cumulative costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) between patients allocated to (1) 'observation' or (2) 'IVBT' after TH/BSO. We used a prototype Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-defined HIR patient in the base case analysis. We calibrated the model to match the outcomes reported in the PORTEC-1 and PORTEC-2 trials. Utilities were obtained from published estimates, and costs were calculated based on Medicare reimbursement ($5445 for IVBT). The societal willingness-to-pay threshold was set at $100,000 per QALY. The time horizon was 5 years. RESULTS: IVBT was associated with a net increase of 0.094 QALYs (4.512 vs. 4.418) as well as an increase in mean cost ($17,453 vs. $15,620) relative to observation. The ICER for IVBT was $19,500 per QALY. On one-way sensitivity analysis, IVBT remained cost-effective when its cost was less than $12,937. If the probability of vaginal recurrence in the observation arm was increased or decreased by 25%, the ICER became $1335 per QALY and $87,925 per QALY, respectively. Probabilistic sensitivity analysis revealed that IVBT was the preferred management option in 86% of simulations. CONCLUSIONS: IVBT is cost-effective compared with observation after TH/BSO for HIR endometrial carcinoma by commonly accepted willingness-to-pay thresholds.

Impact of vaginal cylinder diameter on outcomes following brachytherapy for early stage endometrial cancer.

OBJECTIVE: To examine the outcomes (tolerability, toxicity, and recurrence) of vaginal brachytherapy (VBT) among endometrial cancer (EC) patients treated with small cylinder size. METHODS: Patients with EC who received adjuvant VBT between September 2011 and December 2015 were reviewed. Patients were fitted with the largest vaginal cylinder they could comfortably accommodate, from 2.0-3.0 cm diameter. Small cylinders were defined as size 2.3 cm or less. Patient, tumor, or treatment characteristics were correlated with need for small cylinders. Treatment tolerability, measures of gastrointestinal (GI), genitourinary (GU), and vaginal toxicity, and rates of recurrence were analyzed. RESULTS: Three hundred four patients were included. Small cylinders were used in 51 patients (17%). Normal body mass index (BMI; p<0.001), nulligravidity (p<0.001), and shorter vaginal length (p<0.001) were associated with small cylinder size. There was no acute or late grade 3 toxicity. Rates of acute (grade 1-2) GI, GU, or vaginal symptoms were low (10%, 11%, and 19%, respectively). Small cylinder size was associated with increased likelihood of reporting acute GI (p<0.05) but not GU or vaginal symptoms. Small cylinder size was associated with higher risk of grade 1-2 vaginal stenosis (odds ratio [OR]=4.7; 95% confidence interval [CI]=1.5-14.7; p=0.007). There was no association between cylinder size and recurrence rate (p=0.55). CONCLUSION: VBT is generally very well tolerated, however, patients fitted with smaller cylinders (commonly nulligravid and low BMI) may have increased side effects. Further study to improve the dosimetry of VBT for patients requiring small cylinders may be worthwhile.

Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival.

Background: Radiotherapy alone is often used to treat early-stage glottic cancer (ESGC); however, the optimal radiation treatment schedule remains unknown. The National Comprehensive Cancer Network (NCCN) guidelines recommend both hypofractionated radiotherapy (HFX) and conventionally fractionated radiotherapy (CFX). We compared overall survival (OS) and treatment patterns among patients treated with HFX vs CFX for ESGC using a large national database. Methods: We identified patients diagnosed with stage I-II (cT1-2N0M0) glottic cancer from 2004 to 2013 within the National Cancer Data Base who were treated with either HFX (2.25 Gy/fraction to 63-65.25 Gy) or CFX (2.0 Gy/fraction to 66-70 Gy). The overall survival of patients receiving HFX vs CFX was compared using the log-rank test, multivariable Cox proportional hazards regression, and propensity score matching. All statistical tests were two-sided. Results: Among 10 212 included patients, 4030 patients (39.5%) received HFX and 6182 patients (60.5%) received CFX. Predictors for receipt of HFX included clinical T1 disease, recent year of diagnosis, and treatment at academic and higher-volume centers (all P < .001). Patients treated with HFX increased from 22.1% in 2004 to 58.0% in 2013. HFX was associated with improved OS compared with CFX on univariate (five-year OS = 77.1%, 95% CI = 75.2% to 78.8%, vs 73.5%, 95% CI = 72.1% to 74.8%, respectively, log-rank P < .001) and multivariable analysis (HR = 0.89, 95% CI = 0.81 to 0.98, P = .02), a finding confirmed on propensity score matching. Conclusions: HFX is associated with improved survival compared with CFX among patients treated with definitive radiotherapy for ESGC, particularly among patients with cT2 disease. HFX utilization increased over the study period; however, 40% of patients in our cohort did not receive HFX in the most recent year of our analysis.

Predictors of Nonadherence to NCCN Guideline Recommendations for the Management of Stage I Anal Canal Cancer.

Background: Definitive chemoradiotherapy (CRT) is recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma for all patients with stage I anal canal cancer. Because these patients were not well represented in clinical trials establishing CRT as standard therapy, it is unclear whether NCCN recommendations are being closely followed for stage I disease. This study identified factors that predict for NCCN Guideline-concordant versus NCCN Guideline-discordant care. Methods: Using the National Cancer Data Base, we identified patients diagnosed with anal canal carcinoma from 2004 to 2012 who received concurrent CRT (radiotherapy [RT] 45.0-59.4 Gy with multiagent chemotherapy), RT alone (45.0-59.4 Gy), or surgical procedure alone (local tumor destruction, tumor excision, or abdominoperineal resection). Demographic and clinicopathologic factors were analyzed using the chi-square test and logistic regression modeling. Results: A total of 1,082 patients with histologically confirmed stage I anal cancer were identified, among whom 665 (61.5%) received CRT, 52 (4.8%) received RT alone, and 365 (33.7%) received only a surgical procedure. Primary analyses were restricted to patients receiving CRT or excision alone, as these were most common. Multivariable analysis identified factors independently associated with reduced odds of CRT receipt: low versus intermediate/high tumor grade (adjusted odds ratio [AOR], 0.21; 95% CI, 0.14-0.29; P<.001), tumor size <1 cm vs 1 to 2 cm (AOR, 0.24; 95% CI, 0.17-0.35; P<.001), age ≥70 versus 50 to 69 years (AOR, 0.36; 95% CI, 0.24-0.54; P<.001), male sex (AOR, 0.63; 95% CI, 0.45-0.90; P=.009), and treatment at an academic versus a non-academic facility (AOR, 0.58; 95% CI, 0.41-0.81; P=.002). Conclusions: Despite the NCCN recommendation of CRT for stage I anal cancer, at least one-third of patients appear to be receiving guideline-discordant management. Excision alone is more common for patients who are elderly, are male, have small or low-grade tumors, or were evaluated at academic facilities.

A Long-Term Survivor of Metastatic Pancreatic Adenocarcinoma: Free of Recurrence 12 Years After Treatment of Oligometastatic Disease.

Aggressive local therapy for patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC) has traditionally not been pursued due to high rates of distant progression. We describe a 62-year-old male initially presenting with resectable PDAC who underwent the Whipple procedure but developed multiple liver metastases within two months of starting adjuvant gemcitabine. Oxaliplatin was added to the regimen and complete resolution of the liver lesions resulted. He remained disease-free for five years until re-staging revealed a small lung nodule. This was resected and confirmed to be metastatic PDAC. After additional adjuvant gemcitabine, the patient remained free of recurrence for 12 years after diagnosis of metastatic disease and ultimately passed away from complications of ascending cholangitis associated with stricture at the biliary-enteric anastomosis site. He had no evidence of disease recurrence at the time of death. Next-generation sequencing of the tumor was unrevealing, showing only an activating mutation of KRAS and a deleterious mutation of tumor protein p53 (TP53). Our case suggests that while the prognosis for metastatic PDAC is poor, the population is nonetheless heterogeneous. Prognostic biomarkers are needed for the identification of patients for whom aggressive local treatment of oligometastatic PDAC may be warranted.

The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma.

BACKGROUND: Extranodal (or extracapsular) extension (ENE) is an adverse prognostic factor in patients with head and neck cancers who undergo primary surgery. However, the significance of ENE in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is not well established, and single-institution studies have not established that ENE predicts inferior outcome. The authors investigated the prognostic value of ENE in HPV-positive patients who underwent primary surgery and whether adjuvant chemoradiation improved overall survival (OS) compared with radiation alone in ENE-positive patients. METHODS: Patients who underwent primary surgery for pathologic T1 (pT1) through pT4 tumors, pathologic N1 (pN1) through pN3 lymph node status, HPV-positive OPSCC were identified in the National Cancer Data Base from 2010 through 2012. Features associated with ENE were analyzed. Univariable and multivariable Cox regression analyses identified predictors of OS. The effect of adjuvant treatment on OS in ENE-positive cohort was also evaluated. RESULTS: In total, 1043 patients met inclusion criteria, among whom 43.5% were ENE-positive. Of the ENE-positive patients who had treatment details available, 72% received concurrent chemoradiotherapy, 16% received radiotherapy, and 12% received no adjuvant treatment. After a median follow-up of 28.4 months, ENE was associated with worse 3-year OS (89.3% vs 93.6%; P = .01). On multivariable analysis that included involved lymph nodes, only ENE, lymphovascular invasion, pT3/pT4 tumors, and Charlson-Deyo score were associated with worse OS. Among ENE-positive patients, there was no difference in 3-year OS between those who received adjuvant concurrent chemoradiotherapy versus radiotherapy alone (89.6% vs 89.3%, respectively; P = .55). Propensity score-matched comparison revealed similar results. CONCLUSIONS: ENE is associated with inferior OS in patients with HPV-positive OPSCC. However, OS was not better with adjuvant chemoradiotherapy compared with radiotherapy alone in ENE-positive patients. The current findings support the need for prospective studies of adjuvant chemoradiation in HPV-positive patients with ENE. Cancer 2017;123:2762-72. © 2017 American Cancer Society.