Validation of the Combined Clinical Cell-Cycle Risk Score to Prognosticate Early Prostate Cancer Metastasis From Biopsy Specimens and Comparison With Other Routinely Used Risk Classifiers.

PURPOSE: We aim to independently validate the prognostic utility of the combined cell-cycle risk (CCR) multimodality threshold to estimate risk of early metastasis after definitive treatment of prostate cancer and compare this prognostic ability with other validated biomarkers. METHODS: Patients diagnosed with localized prostate cancer were enrolled into a single-institutional registry for the prospective observational cohort study. The primary end point was risk of metastasis within 3 years of diagnostic biopsy. Secondary end points included time to definitive treatment, time to subsequent therapy, and metastasis after completion of initial definitive treatment. Multivariable cause-specific Cox proportional hazards regression models were produced accounting for competing risk of death and stratified on the basis of the CCR active surveillance and multimodality (MM) thresholds. Time-dependent areas under the receiver operating characteristic curve were calculated. RESULTS: The cohort consisted of 554 men with prostate cancer and available CCR score from biopsy. The CCR score was prognostic for metastasis (hazard ratio [HR], 2.32 [95% CI, 1.17 to 4.59]; P = .02), with scores above the MM threshold having a higher risk than those below the threshold (HR, 5.44 [95% CI, 2.72 to 10.91]; P < .001). The AUC for 3-year risk of metastasis on the basis of CCR was 0.736. When men with CCR above the MM threshold received MM therapy, their 3-year risk of metastasis was significantly lower than those receiving single-modality therapy (3% v 14%). Similarly, a CCR score above the active surveillance threshold portended a faster time to first definitive treatment. CONCLUSION: CCR outperforms other commonly used biomarkers for prediction of early metastasis. We illustrate the clinical utility of the CCR active surveillance and multimodality thresholds. Molecular genomic tests can inform patient selection and personalization of treatment for localized prostate cancer.

Evaluating patterns of care for early-stage low-grade follicular lymphoma in the rituximab era.

Radiotherapy (RT) utilization for early-stage, low-grade follicular lymphoma (FL) is low despite treatment guideline recommendations. We compare treatment trends for early-stage FL in the era of involved-site RT and rituximab. We identified 11,645 patients in the National Cancer Database (NCDB) with stage I-II, grade 1-2 nodal or extranodal FL diagnosed 2011-2017, with median follow-up of 44 months. From 2011 to 2017, RT utilization rates decreased from 33.4% to 22.4%, observation decreased from 65.3% to 49.7%, chemoimmunotherapy increased from 0.5% to 15.0%, immuno-monotherapy increased from 0.6% to 10.2%, and RT + systemic therapy increased from 0.6% to 2.5%. RT utilization remains low in the involved-site RT and rituximab era.

Survival outcomes for patients with T3N0M0 squamous cell carcinoma of the glottis treated with definitive radiation alone versus chemoradiation.

BACKGROUND: Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis. METHODS: We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation. RESULTS: A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25-0.37] and 0.48 [0.31-0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%-37.2%] vs. 58.0% [55.8%-60.0%]). In patients <70 with no comorbidities this difference persisted (51.0% [44.5%-57.0%] versus 66.7% [64.0%-69.3%]). CONCLUSION: Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.

Multi-Institutional Analysis of Cancer Patient Exposure, Perceptions, and Trust in Information Sources Regarding Complementary and Alternative Medicine.

PURPOSE: Complementary and alternative medicine (CAM) use during cancer treatment is controversial. We aim to evaluate contemporary CAM use, patient perceptions and attitudes, and trust in various sources of information regarding CAM. METHODS: A multi-institutional questionnaire was distributed to patients receiving cancer treatment. Collected information included respondents' clinical and demographic characteristics, rates of CAM exposure/use, information sources regarding CAM, and trust in each information source. Comparisons between CAM users and nonusers were performed with chi-squared tests and one-way analysis of variance. Multivariable logistic regression models for trust in physician and nonphysician sources of information regarding CAM were evaluated. RESULTS: Among 749 respondents, the most common goals of CAM use were management of symptoms (42.2%) and treatment of cancer (30.4%). Most CAM users learned of CAM from nonphysician sources. Of CAM users, 27% reported not discussing CAM with their treating oncologists. Overall trust in physicians was high in both CAM users and nonusers. The only predictor of trust in physician sources of information was income >$100,000 in US dollars per year. Likelihood of trust in nonphysician sources of information was higher in females and lower in those with graduate degrees. CONCLUSION: A large proportion of patients with cancer are using CAM, some with the goal of treating their cancer. Although patients are primarily exposed to CAM through nonphysician sources of information, trust in physicians remains high. More research is needed to improve patient-clinician communication regarding CAM use.

Feasibility and Clinical Utility of a Workflow Interfacing Radiation Oncology Lung Stereotactic Body Radiation Therapy Treatment Planning and Diagnostic Radiology.

Stereotactic body radiation therapy (SBRT) is commonly used to treat early-stage non-small cell lung cancer. Beam arrangements for SBRT include multiple entry and exit pathways resulting in irregular low-dose distributions within normal lung parenchyma. An improved understanding of posttreatment radiographic changes may improve the ability to predict clinical complications including radiation pneumonitis as well as assist in early detection of local failures. Radiation treatment planning is conducted using software systems separate from diagnostic radiology, often not accessible to the diagnostic radiologist. We developed a workflow for interfacing radiation dose information from lung SBRT treatments with a diagnostic radiology picture archiving and communication system (PACS). In an anonymized PACS study folder, SBRT dose maps depicting high-dose, low-dose, and nonirradiated lung volumes were viewable side by side with pretreatment and follow-up diagnostic computed tomography scans. Clinical utility was evaluated by 2 thoracic diagnostic radiologists reviewing posttreatment diagnostic follow-up scans in the PACS both with and without radiation dose maps available. The addition of the biologically effective dose map did not significantly change identification rates of radiation induced lung injury) (92% vs 95%; P = .32) but did significantly decrease radiologic suspicion for local recurrence (22% vs 8%; P = .003). The addition of biologically effective dose maps significantly increased confidence in identifying radiation induced lung injury (7.75 vs 8.82; P = .004) and local recurrence (5.5 vs 6.6; P = .005). The recommendation for additional workup was not significantly different (10% vs 7%; P = .41). We demonstrated the feasibility and clinical utility of a workflow generating simplified radiation dose maps that are viewable within a PACS for diagnostic radiology review.

Worsening Racial Disparities in Utilization of Intensity Modulated Radiation Therapy.

Purpose: The benefits of intensity modulated radiation therapy (IMRT) compared with standard 3-dimensional conformal radiation therapy have been demonstrated in many cancer sites and include decreased acute and late toxicity, improved quality of life, and opportunities for dose escalation. Limited literature suggests non-white patients may have lower utilization of IMRT. We hypothesized that as the use of IMRT has increased in recent years, racial inequities have persisted and disproportionately affect non-Hispanic Black (NHB) patients. We aim to evaluate temporal trends in IMRT utilization focusing on disparities among minoritized populations. Methods and Materials: The National Cancer Database was queried to identify the 10 disease sites with the highest total number of cancer patients treated with definitive intent IMRT in 2017, the most recent year for which data are available. Exclusions included stage IV, age <18 years, unknown insurance status, unknown race, and palliative intent radiation. Race and ethnicity variables were combined and classified as non-Hispanic White, Hispanic, NHB, Asian, Native American/Eskimo, and Hawaiian/Pacific Islander. Multivariable logistic regression for IMRT utilization was performed for each disease site for both early (2004-2010) and contemporary (2011-2017) cohorts, adjusting for clinical and demographic covariates. Results: Among the 10 selected disease sites, 1,010,292 patients received radiation therapy as part of definitive treatment between 2004 and 2017. Overall IMRT utilization rates increased from 22.0% in 2004 to 57.8% in 2017. After adjustment and compared with non-Hispanic White patients, NHB patients were significantly less likely to receive IMRT in 1 of 10 disease sites in the 2004 to 2010 cohort, and 5 of 10 disease sites in the 2011 to 2017 cohort. Conclusions: Despite greater awareness of racial disparities in cancer care and outcomes, this study demonstrates worsening disparities in the use of IMRT, particularly for NHB patients. These differences may exacerbate racial disparities in cancer outcomes; therefore, identification of underlying drivers of differential IMRT utilization is warranted.

The Effect of Maximum Tumor Diameter by MRI on Disease Control in Intermediate and High-risk Prostate Cancer Patients Treated With Brachytherapy Boost.

BACKGROUND: Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer (PCa) outcomes. However, the impact of MTD in PCa treated with external beam radiotherapy and brachytherapy boost (EBRT+BB) remains unknown. MATERIALS AND METHODS: Patients with PCa treated with EBRT+BB were identified from an institutional database. Clinical data including MTD, age, androgen deprivation therapy (ADT) use, prostate specific antigen (PSA), International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging were retrospectively collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced with MTD grouped by receiver operating characteristic (ROC) cut-point. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group. RESULTS: Of 191 patients treated with EBRT+BB, 113 had MTD measurements available. Larger MTD was associated with increased ADT use and seminal vesicle involvement. ROC optimization identified MTD of 24 mm as the optimal cut-point for both BF and DM. MTD was independently associated with both BF (HR 8.61, P = .048, 95% CI 1.02-72.97) and DM (HR 8.55, P = .05, 95% CI 1.00-73.19). In patients with ISUP group 4 to 5 disease, MTD > 24 mm was independently associated with increased risk of DM (HR 10.13, P = .04, 95% CI 1.13-91.12). CONCLUSIONS: This is the first study to evaluate MTD in the setting of EBRT+BB. These results demonstrate that MTD is independently associated with BF and metastasis. This suggests a possible role for MTD in risk assessment models and clinical decision-making for men receiving EBRT+BB.

Comparing adjuvant radiation to adjuvant chemoradiation in postsurgical p16+ oropharyngeal carcinoma patients with extranodal extension or positive margins.

BACKGROUND: Adjuvant guidelines in surgically resected p16+ oropharyngeal carcinoma (OPC) with positive surgical margins (PSM) or extranodal extension (ENE) are based on randomized controlled trials predating p16 status. It remains unclear if adjuvant chemotherapy is necessary in p16+ patients with these features. METHODS: The National Cancer Database was used to identify cases of nonmetastatic p16+ OPC diagnosed from 2010 to 2017. Patients treated with surgical resection followed by adjuvant radiation (aRT) or adjuvant chemoradiation (aCRT) were eligible for analysis. RESULTS: A total of 14 071 patients were eligible for analysis. Overall survival (OS) was not statistically different between aRT and aCRT in patients with PSM (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.56-1.28), ENE (HR 0.93, 95% CI 0.69-1.27) or both (HR 0.73, 95% CI 0.41-1.31). CONCLUSIONS: In patients with p16+ OPC with ENE, PSM, or both, adding chemotherapy to aRT was not associated with improved OS.

Patterns of care and outcomes of early stage I-II Hodgkin lymphoma treated with or without radiation therapy.

Omission of radiotherapy in the upfront management of early-stage classic Hodgkin lymphoma (cHL) has become more common with time. We report patterns of care and outcomes of stage I-II cHL treated with chemotherapy (CT) only versus CT and radiotherapy (combined modality therapy, CMT). From the National Cancer Database, we identified 28,327 early-stage cHL patients treated with CT (n = 15,798) or CMT (n = 12,529) from 2004 to 2018. CMT utilization declined over the period from 58% to 34%. With median follow-up of 6.2 years, the 5- and 10-year overall survival for CT versus CMT was 93.3% versus 96.9% (p < 0.001) and 88.7% versus 93.5% (p < 0.001), respectively. On multivariable analysis, uninsured (OR 0.75, p < 0.001) and Black patients (OR 0.86, p = 0.02) were less likely to receive CMT, and treatment with CT was predictive of death (OR 2.0, p < 0.001). This report highlights real-world outcomes in early-stage cHL, with worse survival with CT and notable disparities in CMT utilization.

Racial and Ethnic Health Disparities in Delay to Initiation of Intensity-Modulated Radiotherapy.

PURPOSE: Delays in initiation of radiotherapy may contribute to inferior oncologic outcomes that are more commonly observed in minoritized populations in the United States. We aimed to examine inequities associated with delayed initiation of intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: The National Cancer Database was queried to identify the 10 cancer sites most commonly treated with IMRT. Interval to initiation of treatment (IIT) was broken into quartiles for each disease site, with the 4th quartile classified as delayed. Multivariable logistic regression for delayed IIT was performed for each disease site using clinical and demographic covariates. Differences in magnitude of delay between subsets of patients stratified by race and insurance status were evaluated using two-sample t-tests. RESULTS: Among patients (n = 350,425) treated with IMRT between 2004 and 2017, non-Hispanic Black (NHB), Hispanic, and Asian patients were significantly more likely to have delayed IIT with IMRT for nearly all disease sites compared with non-Hispanic White (NHW) patients. NHB, Hispanic, and Asian patients had significantly longer median IIT than NHW patients (NHB 87 days, P < .01; Hispanic 76 days, P < .01; Asian 74 days, P < .01; and NHW 67 days). NHW, Hispanic, and Asian patients with private insurance had shorter median IIT than those with Medicare (P < .01); however, NHB patients with private insurance had longer IIT than those with Medicare (P < .01). CONCLUSION: Delays in initiation of IMRT in NHB, Hispanic, and Asian patients may contribute to the known differences in cancer outcomes and warrant further investigation, particularly to further clarify the role of different insurance policies in delays in advanced modality radiotherapy.

Radical trachelectomy and adjuvant vaginal brachytherapy to preserve fertility in pediatric cervical adenocarcinoma.

PURPOSE: This case report describes the use of a trachelectomy and adjuvant vaginal brachytherapy for pediatric clear cell adenocarcinoma as definitive fertility-sparing treatment. METHODS AND MATERIALS: A previously healthy 8-year-old female presented with abdominal cramping and heavy vaginal bleeding. Diagnostic imaging revealed a 3.5 cm circumscribed cervical mass, with subsequent biopsy revealing clear cell adenocarcinoma. Fertility preserving treatment was requested. RESULTS: The patient underwent a radical trachelectomy, with final pathology demonstrating a close radial margin. Due to close margin, adjuvant radiotherapy with a vaginal cylinder was delivered to a total dose of 18 Gray in three fractions prescribed to a depth of 5 mm from the vaginal surface using iridium-192. With 2 years of follow-up, the patient continues to do well with no evidence of recurrence or late toxicity from treatment. CONCLUSIONS: Pediatric clear cell adenocarcinoma of the cervix is a rare occurrence that lacks clinical trials to guide effective treatment. Adjuvant vaginal brachytherapy following trachelectomy in a pediatric patient with clear cell adenocarcinoma of the cervix is feasible and well-tolerated.

Second Primary Malignancies in Diffuse Large B-cell Lymphoma Survivors with 40 Years of Follow Up: Influence of Chemotherapy and Radiation Therapy.

Purpose: Previous studies have shown an increased risk of second primary malignancies (SPMs) in survivors of diffuse large B-cell lymphoma (DLBCL). Survivors live longer due to the intensification of and improvements in therapy; thus, we aimed to characterize SPM patterns in patients with DLBCL by treatment modality. Methods and Materials: Standardized incidence ratio and absolute excess risk of SPMs were assessed in patients with primary DLBCL from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A subgroup analyses based on, sex, race, age at the time of diagnosis, latency, and treatment modality were performed. Propensity score-adjusted cumulative incidence curves were generated, stratified by treatment and accounting for death as a competing risk. Results: In total, 45,946 patients with DLBCL were identified with a mean follow up of 70 months. Overall, 9.2% of patients developed an SPM with a standardized incidence ratio of 1.23 (95% confidence interval, 1.20-1.27). There was no difference in SPM risk between men and women or Black and White patients. Patients age <25 years were particularly susceptible to the development of SPMs, with a risk 2.5 times greater than patients aged 50 to 74 years. Temporal patterns showed increasing risk of solid malignancies and decreasing risk of hematologic malignancies over time, with bladder cancer posing the greatest absolute excess risk of any cancer type after 15 years. Patients treated with radiation therapy (RT), chemotherapy (CT), and chemoradiation therapy (CRT) all had an increased risk of SPM development compared with the general population. The cumulative incidence of SPMs was the lowest in patients treated with RT and the highest when treated with CRT. In the modern treatment era, the cumulative incidence of SPM for patients treated with CT versus CRT was not significantly different. Conclusions: In this large population-based study, we demonstrate unique SPM risk patterns based on age, latency, and treatment modality that have important implications for the treatment and screening of patients diagnosed with DLBCL.

Patterns of Care and Treatment Outcomes in Locoregional Squamous Cell Carcinoma of the Prostate.

Primary squamous cell carcinoma is a rare, aggressive disease with historically poor outcomes and no established treatment guidelines. Case reports are limited but describe multiple treatment approaches. Seeking to identify practice patterns and treatment outcomes, we used the US National Cancer Data Base to identify 66 males with locoregional primary squamous cell carcinoma of the prostate treated with surgery, chemotherapy, and/or radiotherapy between 2004 and 2015. Patients were stratified into treatment groups consisting of local therapy alone (n = 40; 61%), local therapy and chemotherapy (n = 13; 20%), chemotherapy alone (n = 7; 11%), and observation (n = 6; 9%). Patients with clinical stage T3-T4 disease were significantly more likely to receive combined chemotherapy and local therapy on multivariable analysis. Median survival was 20 mo for patients treated with local therapy alone, 37 mo with local therapy and chemotherapy, and 11 mo with chemotherapy alone. Overall survival was not significantly different between treatment groups. Despite limitations in sample size, these data suggest that addition of chemotherapy to local therapy is a reasonable treatment approach for select patients. PATIENT SUMMARY: Squamous cell carcinoma of the prostate is an extremely rare disease. Our review of patterns of care using data from the National Cancer Data Base shows inconsistent use of combined local and systemic therapy. The small sample size for this rare disease limits any conclusions regarding survival differences, but the data suggest that a combination approach using chemotherapy in addition to surgery or radiation is a reasonable treatment option for disease confined to the prostate.

Temporal Trends and Predictors in Diagnosing Pathologic Node-Positive Prostate Cancer in Clinically Node-Negative Patients.

INTRODUCTION: Managing pathologically node positive (pN+) prostate cancer (PCa) is controversial. We describe temporal patterns and predictors of pN+ PCa in men with initially surgically managed clinically node negative (cN-) PCa. MATERIALS AND METHODS: This observational retrospective analysis of nonmetastatic, cN- PCa uses the National Cancer Database. Multivariable logistic regression was used to identify covariates associated with pN+ disease. Cox proportional hazards modeling and Kaplan-Meier analysis were used to evaluate survival patients undergoing radical prostatectomy with or without pelvic lymph node dissection (PLND). RESULTS: The rates of radical prostatectomy in men with grade group (GG) 4 and GG5 increased from 47.6% to 53.1% and from 42.5% to 49.5%, respectively. The annual rate increased from 2.02% in 2010 to 5.12% in 2017 (P < .001). The annual rates of PLND increased from 54.3% to 71.7%. The most significant predictor of pN+ PCa was ISUP GG4 (odds ratio [OR] 12.5, P< .001) and GG 5 (OR 26.2, P < .001). Rates of pN+ identification increased from 5.5% to 9.4% in men with GG4 and from 13.4% to 19.5% in men with GG5 (P< .001). In GG4 and GG5, patients undergoing PLND had superior survival to those managed without PLND (P < .01). CONCLUSION: Among patients with cN- PCa, the diagnosis of pN+ PCa has become more common over time. GG4 and GG5 are the strongest independent predictors of pN+ disease. Because incidental pN+ results in upstaging these data are useful for informing discussions before radical prostatectomy.