Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response.

PURPOSE: Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect. METHODS AND MATERIALS: We performed a systematic PubMed search of prostate SBRT studies published between 2001 and 2018. Those that analyzed factors associated with late urinary, bowel, or sexual toxicity and/or quality of life were included and reviewed. Normal tissue complication probability modelling was performed on studies that contained detailed dose/volume and outcome data. RESULTS: We found 13 studies that examined urinary effects, 6 that examined bowel effects, and 4 that examined sexual effects. Most studies included patients with low-intermediate risk prostate cancer treated to 35-40 Gy. Most patients were treated with 5 fractions, with several centers using 4 fractions. Endpoints were heterogeneous and included both physician-scored toxicity and patient-reported quality of life. Most toxicities were mild-moderate (eg, grade 1-2) with a very low overall incidence of severe toxicity (eg, grade 3 or higher, usually <3%). Side effects were associated with both dosimetric and non-dosimetric factors. CONCLUSIONS: Prostate SBRT appears to be overall well tolerated, with determinants of toxicity that include dosimetric factors and patient factors. Suggested dose constraints include bladder V(Rx Dose)Gy <5-10 cc, urethra Dmax <38-42 Gy, and rectum Dmax <35-38 Gy, though current data do not offer firm guidance on tolerance doses. Several areas for future research are suggested.

Tumor Control Probability Modeling and Systematic Review of the Literature of Stereotactic Body Radiation Therapy for Prostate Cancer.

PURPOSE: Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time. METHODS AND MATERIALS: The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group. RESULTS: Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/ß = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%. CONCLUSIONS: We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.

Quality-adjusted survival with first-line cabozantinib or sunitinib for advanced renal cell carcinoma in the CABOSUN randomized clinical trial (Alliance).

BACKGROUND: Cabozantinib Versus Sunitinib as Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial (CABOSUN) was a randomized, open-label, phase 2 trial evaluating first-line cabozantinib versus sunitinib in patients with advanced renal cell carcinoma (aRCC). This post hoc analysis evaluated quality-adjusted survival using Quality-adjusted Time Without Symptoms of disease or Toxicity of treatment (Q-TWiST). METHODS: Survival plots for cabozantinib and sunitinib (650-day follow-up) were partitioned into 3 health states: time spent before disease progression without toxicity (TWiST; toxicity based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] grade 3/4 adverse events), time spent before disease progression with toxicity (TOX; durations of adverse events based on published literature), and time after disease recurrence (relapse) or progression to death (REL). Q-TWiST was the sum of the mean time spent in each state, with each state weighted to reflect patient preferences (from 0 [worst] to 1 [best]) using utility scores. TWiST was always weighted as 1. Overall survival and time to disease progression were based on all randomized patients (157 patients); TOX was based on all randomized and treated patients (150 patients). RESULTS: Across all utility combinations tested, Q-TWiST was found to be longer with cabozantinib versus sunitinib (range of differences, +24 days to +137 days). Q-TWiST differences that were found to be statistically significant (+92 days [95% confidence interval, 5-178 days] to +137 days [95% confidence interval, 60-214 days]) were of a clinically meaningful effect size (≥80 days), and were based on utility values that included those considered relevant for patients with aRCC (REL utility weight of 0.355, TOX utility weight of 0-1, and TWiST utility weight of 1). CONCLUSIONS: In patients with aRCC, first-line cabozantinib was found to provide longer quality-adjusted survival compared with sunitinib. These findings may help to inform clinical decision making. LAY SUMMARY: Cabozantinib and sunitinib are drugs that are used to treat patients with advanced kidney cancer. Clinical trials have shown that cabozantinib offers benefits over sunitinib, giving patients more time before their cancer progresses. It is important that this additional time before disease progression does not come at the expense of patients' quality of life, which can be affected by treatment side effects and/or ongoing cancer symptoms. Both quantity and quality of life are central to optimal treatment. In the current analysis of patients with advanced kidney cancer who were initiating treatment for the first time, cabozantinib provided more quality time before cancer progression compared with sunitinib.

Radiation Therapy as a Bridging Strategy for CAR T Cell Therapy With Axicabtagene Ciloleucel in Diffuse Large B-Cell Lymphoma.

PURPOSE: Axicabtagene ciloleucel (axi-cel) is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma. Bridging therapy may be required for lymphoma control during the manufacturing interval between collection of autologous T cells and final CAR T product administration. The optimal bridging therapy is not known and patients are often chemorefractory. We present a case series of patients receiving radiation as a bridge to axi-cel. METHODS AND MATERIALS: Between December 2017 and October 2018, 12 patients were intended to receive bridging radiation before axi-cel. The group was characterized by highly aggressive disease including 6 of 12 with "double hit" lymphoma and 6 of 12 with disease ≥10 cm in diameter. All patients received 2 to 4 Gy/fraction to a median dose of 20 Gy (range, 6-36.5 Gy). Half of patients received either 30 Gy in 10 fractions or 20 Gy in 5 fractions. Seven patients received concurrent chemotherapy. Eleven patients underwent axi-cel infusion and one did not. Median follow-up was 3.3 months (range, 1.1-12.0 months). RESULTS: No significant toxicities were identified during bridging radiation, and no patient experienced in-field progression of disease before axi-cel infusion. One patient experienced abdominal pain, which resolved after dose reduction. Two patients had out-of-field progression of disease during the bridging period. After axi-cel infusion, 3 of 11 patients (27%) experienced severe cytokine release syndrome or neurotoxicity. At 30 days, the objective response rate was 81.8% (11 of 12 evaluable; 1 stable disease, 1 out-of-field progression), with complete response in 27% (3 of 11). At last follow-up, the best objective response rate was 81.8%, with a complete response attained in 45% (5 of 11). Lymphocyte counts decreased slightly in 10 of 12 patients during radiation (median, 0.25 k/uL). CONCLUSIONS: Radiation (with or without concurrent chemotherapy) can be safely administered as a bridge to axi-cel in high-risk lymphoma. Caution should be taken if irradiation is started before apheresis, and lymphocyte counts should be monitored closely throughout. Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy.

Total Medicare Costs Associated With Diagnosis and Treatment of Prostate Cancer in Elderly Men.

Importance: Localized prostate cancer diagnosis and treatment among elderly men who are not likely to benefit represents a potential source of low-value health care services. Objective: To quantify the costs to the Medicare program associated with detection and treatment of prostate cancer among elderly men in the United States. Design, Setting, and Participants: This nationwide, population-based, retrospective cohort study uses the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to identify men 70 years or older diagnosed with localized prostate cancer between 2004 and 2007 and to ascertain Medicare costs associated with diagnosis and workup, treatment, follow-up, and morbidity management of the disease. National Medicare costs were estimated using per-person costs, stage-adjusted prostate cancer incidence rates by age from SEER 2007 through 2011, and 2010 Census population estimates by age. Main Outcomes and Measures: Estimated costs to the Medicare program overall, and in each (mutually exclusive) category related to diagnosis and workup, treatment, follow-up, and morbidity management. Results: This nationwide, population-based, retrospective cohort study included 49 692 men with nonmetastatic prostate cancer from the SEER-Medicare database (all participants were 70 years or older; 25 981 [52.3%] were 76 years or older). The median per-patient cost within 3 years after prostate cancer diagnosis was $14 453 (interquartile range [IQR], $4887-$27 899). The majority of this cost was attributable to treatment costs (median, $10 558; IQR, $1990-$23 718). Patients with a Gleason score of 6 or lower who pursued initial conservative management (no treatment within 12 months of diagnosis) had a 3-year median total cost of $1914 per patient. The estimated total 3-year cost to the Medicare program associated with the annual detection of prostate cancer in men 70 years or older is approximately $1.2 billion. Increasing active surveillance use in those with Gleason score of 6 or lower could reduce this cost by $320 million. Conclusions and Relevance: There is substantial cost to the Medicare program associated with the diagnosis and treatment of localized prostate cancer among elderly men in the United States, despite the fact that these men are unlikely to die of prostate cancer. The majority of costs are related to treatment. Reducing provision of low-value health care services among this patient population could result in significant health care savings.

Phase 2 Multicenter Trial of Heterogeneous-dosing Stereotactic Body Radiotherapy for Low- and Intermediate-risk Prostate Cancer: 5-year Outcomes.

BACKGROUND: Stereotactic body radiation therapy is an emerging treatment for prostate cancer (PC), with potential biological and oncologic advantages. A well-established radiation dosing schedule (38Gy in 4 fractions) has shown excellent long-term efficacy in high-dose-rate (HDR) brachytherapy. OBJECTIVE: To report 5-yr efficacy, toxicity, and quality-of-life (QOL) outcomes of a novel 4-d SBRT regimen. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm prospective phase 2 trial involving 259 patients with low- or intermediate-risk PC treated at 18 US centers from December 2007 to February 2012. The median follow-up was 5yr (interquartile range 37-85mo). INTERVENTION: SBRT with 38Gy in four fractions; radiation plans mimicked HDR brachytherapy dosimetry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured freedom from biochemical recurrence (BCR) and assessed toxicities using the Common Terminology Criteria for Adverse Events v3.0 and QOL using the Expanded Prostate Cancer Index Composite. RESULTS AND LIMITATIONS: The 5-yr BCR-free rates were 100% and 88.5% for patients with low- and intermediate-risk PC, respectively. The cumulative 5-yr grade 2, 3, and 4 toxicity rates were 12.4%, 1.9%, and 0.4% for urinary, and 3.4%, 0%, and 0% for gastrointestinal toxicities, respectively. The median baseline prostate-specific antigen (PSA) level of 5.12ng/ml decreased to 0.1ng/ml by ≥42mo. QOL scores decreased at 1mo but returned to baseline by 6mo, with a later decline (≥24mo) in the urinary continence domain (pad use was 2% at baseline and 10% at 5yr), and lower sexual potency over time. Comparative outcomes versus other types of radiotherapy are difficult because the trial was not randomized. CONCLUSIONS: This regimen yields a high rate of BCR-free survival, with a very low median PSA nadir suggesting prostate ablation. For properly selected patients with low- or intermediate-risk PC who choose SBRT, this treatment regimen is effective. PATIENT SUMMARY: This potent four-treatment stereotactic body radiotherapy regimen appears to be effective for patients with early prostate cancer.

Aggressive End-of-Life Care for Metastatic Cancer Patients Younger Than Age 65 Years.

Background: Aggressive medical care at the end of life can be harmful to patients and families, but its prevalence in use among younger cancer patients is unknown. The goal of the study was to report on the use of aggressive care and hospice services for patients younger than age 65 years. Methods: Using the HealthCore Integrated Research Database, we analyzed patients who died between 2007 and 2014 with metastatic lung (n = 12 764), colorectal (n = 5207), breast (n = 5855), pancreatic (n = 3397), or prostate (n = 1508) cancer. Based on published quality measures, we assessed uses of chemotherapy, intensive care, emergency room visits, and hospice care at the end of life. We examined additional items including radiotherapy, invasive procedures, hospitalization, and in-hospital deaths. Multivariable modified Poisson regression models were used to adjust for age, sex, geographic region, rural/urban location, year of death, and regional education and income measures. Results: Across the five cancers, 10.1% to 14.1% of patients received chemotherapy within the last 14 days of life, 15.9% to 20.6% received intensive care in last 30 days, and 1.5% to 2.5% went to the emergency room two or more times in last 30 days. Hospice enrollment at least three days before death was 54.4% to 59.6%. However, 55.3% to 59.3% of patients had a hospital admission in the last 30 days, and one-third died (30.3%-35.4%) in the hospital. Conclusions: There was low use of cancer-directed treatment at the end of life for younger cancer patients, and hospice use was higher than 50%. However, there was a relatively high utilization of hospital-based care. These results demonstrate an opportunity for continued improvements in the provision of high-value, patient-centered care at the end of life.

Evaluation of PET/MRI for Tumor Volume Delineation for Head and Neck Cancer.

INTRODUCTION: Computed tomography (CT), combined positron emitted tomography and CT (PET/CT), and magnetic resonance imaging (MRI) are commonly used in head and neck radiation planning. Hybrid PET/MRI has garnered attention for potential added value in cancer staging and treatment planning. Herein, we compare PET/MRI vs. planning CT for head and neck cancer gross tumor volume (GTV) delineation. MATERIAL AND METHODS: We prospectively enrolled patients with head and neck cancer treated with definitive chemoradiation to 60-70 Gy using IMRT. We performed pretreatment contrast-enhanced planning CT and gadolinium-enhanced PET/MRI. Primary and nodal volumes were delineated on planning CT (GTV-CT) prospectively before treatment and PET/MRI (GTV-PET/MRI) retrospectively after treatment. GTV-PET/MRI was compared to GTV-CT using separate rigid registrations for each tumor volume. The Dice similarity coefficient (DSC) metric evaluating spatial overlap and modified Hausdorff distance (mHD) evaluating mean orthogonal distance difference were calculated. Minimum dose to 95% of GTVs (D95) was compared. RESULTS: Eleven patients were evaluable (10 oropharynx, 1 larynx). Nine patients had evaluable primary tumor GTVs and seven patients had evaluable nodal GTVs. Mean primary GTV-CT and GTV-PET/MRI size were 13.2 and 14.3 cc, with mean intersection 8.7 cc, DSC 0.63, and mHD 1.6 mm. D95 was 65.3 Gy for primary GTV-CT vs. 65.2 Gy for primary GTV-PET/MRI. Mean nodal GTV-CT and GTV-PET/MRI size were 19.0 and 23.0 cc, with mean intersection 14.4 cc, DSC 0.69, and mHD 2.3 mm. D95 was 62.3 Gy for both nodal GTV-CT and GTV-PET/MRI. CONCLUSION: In this series of patients with head and neck (primarily oropharynx) cancer, PET/MRI and CT-GTVs had similar volumes (though there were individual cases with larger differences) with overall small discrepancies in spatial overlap, small mean orthogonal distance differences, and similar radiation doses.

Comparison of Patient- and Practitioner-Reported Toxic Effects Associated With Chemoradiotherapy for Head and Neck Cancer.

IMPORTANCE: Agreement between patient- and practitioner-reported toxic effects during chemoradiotherapy for head and neck cancer is unknown. OBJECTIVE: To compare patient-reported symptom severity and practitioner-reported toxic effects among patients receiving chemoradiotherapy for head and neck cancer. DESIGN, SETTING, AND PARTICIPANTS: Forty-four patients participating in a phase 2 trial of deintensified chemoradiotherapy for oropharyngeal carcinoma were included in the present study (conducted from February 8, 2012, to March 2, 2015). Most treatment (radiotherapy, 60 Gy, with concurrent weekly administration of cisplatin, 30 mg/m2) was administered at academic medical centers. Included patients had no prior head and neck cancers, were 18 years or older, and had a smoking history of 10 pack-years or less or more than 10 pack-years but 30 pack-years or less and abstinent for the past 5 years. Cancer status was untreated human papillomavirus or p16-positive squamous cell carcinoma of the oropharynx or unknown head and neck primary site; and cancer staging was category T0 to T3, category N0 to N2c, M0, and Eastern Cooperative Oncology Group performance status 0 to 1. Baseline, weekly, and posttreatment toxic effects were assessed by physicians or nurse practitioners using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Patient-reported symptom severity was measured using the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE). Descriptive statistics were used to characterize raw agreement between CTCAE grades and PRO-CTCAE severity ratings. INTERVENTIONS: Baseline, weekly, and posttreatment toxic effects assessed using CTCAE, version 4.0, and PRO-CTCAE. MAIN OUTCOMES AND MEASURES: Raw agreement indices between patient-reported toxic effects, including symptom frequency, severity, and interference with daily activities (score range, 0 [none] to 4 [very severe]), and practitioner-measured toxic effects, including swallowing, oral pain, and hoarseness (score range, 1 [mild] to 5 [death]). RESULTS: Of the 44 patients included in the analysis (39 men, 5 women; mean [SD] age, 61 [8.4] years), there were 327 analyzable pairs of CTCAE and PRO-CTCAE symptom surveys and no treatment delays due to toxic effects. Patient-reported and practitioner-reported symptom severity agreement was high at baseline when most symptoms were absent but declined throughout treatment as toxic effects increased. Most disagreement was due to lower severity of toxic effects reported by practitioners (eg, from 45% agreement at baseline to 27% at the final week of treatment for pain). This was particularly noted for domains that are not easily evaluated by physical examination, such as anxiety and fatigue (eg, severity of fatigue decreased from 43% at baseline to 12% in the final week of treatment). CONCLUSIONS AND RELEVANCE: Practitioner-reported toxic effects are lower than patient self-reports during head and neck chemoradiotherapy. The inclusion of patient-reported symptomatic toxic effects provides information that can potentially enhance clinical management and improve data quality in clinical trials.

Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer.

BACKGROUND: Randomized trials have shown that androgen-deprivation therapy (ADT) improves survival for men with intermediate-risk prostate cancer treated with radiotherapy (RT). The benefit of ADT to patients with favorable intermediate-risk prostate cancer treated with modern dose-escalated RT is unknown. This study evaluated the effectiveness of ADT on survival of men with favorable intermediate-risk prostate cancer treated with dose-escalated RT. METHODS: This study was a retrospective cohort analysis of men with favorable intermediate-risk prostate cancer from 2004 to 2007 in the National Cancer Data Base. Favorable intermediate-risk disease was defined as 1 adverse risk factor (prostate-specific antigen level of 10-20 ng/mL or Gleason score of 7) and clinical T1/T2 prostate cancer. All patients were treated with primary dose-escalated RT (≥75.6 Gy or RT with a brachytherapy boost). Overall survival was analyzed with propensity score adjustment and Cox multivariate modeling. RESULTS: The study included 18,598 patients. The use of ADT decreased from 43.5% in 2004 to 39.5% in 2007. The propensity score-adjusted survival analysis demonstrated similar 8-year overall survival for men treated with dose-escalated RT and ADT and men treated with RT alone (77.7% vs 78.4%). ADT was not associated with improved survival in any age or comorbidity subgroup. In a sensitivity analysis using Cox multivariate modeling, the receipt of ADT was not associated with overall survival (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; P = .768). CONCLUSIONS: Adding ADT to modern dose-escalated RT was not associated with improved survival for patients with favorable intermediate-risk prostate cancer. The applicability of the survival benefit seen in older trials to modern patients is unclear. Because of the morbidity associated with ADT, dose-escalated RT alone for patients with favorable intermediate-risk prostate cancer may be a reasonable option. Cancer 2016;122:2341-2349. © 2016 American Cancer Society.

Toward a better understanding of task demands, workload, and performance during physician-computer interactions.

OBJECTIVE: To assess the relationship between (1) task demands and workload, (2) task demands and performance, and (3) workload and performance, all during physician-computer interactions in a simulated environment. METHODS: Two experiments were performed in 2 different electronic medical record (EMR) environments: WebCIS (n = 12) and Epic (n = 17). Each participant was instructed to complete a set of prespecified tasks on 3 routine clinical EMR-based scenarios: urinary tract infection (UTI), pneumonia (PN), and heart failure (HF). Task demands were quantified using behavioral responses (click and time analysis). At the end of each scenario, subjective workload was measured using the NASA-Task-Load Index (NASA-TLX). Physiological workload was measured using pupillary dilation and electroencephalography (EEG) data collected throughout the scenarios. Performance was quantified based on the maximum severity of omission errors. RESULTS: Data analysis indicated that the PN and HF scenarios were significantly more demanding than the UTI scenario for participants using WebCIS (P < .01), and that the PN scenario was significantly more demanding than the UTI and HF scenarios for participants using Epic (P < .01). In both experiments, the regression analysis indicated a significant relationship only between task demands and performance (P < .01). DISCUSSION: Results suggest that task demands as experienced by participants are related to participants' performance. Future work may support the notion that task demands could be used as a quality metric that is likely representative of performance, and perhaps patient outcomes. CONCLUSION: The present study is a reasonable next step in a systematic assessment of how task demands and workload are related to performance in EMR-evolving environments.

Stage at presentation and survival outcomes of patients with Gleason 8-10 prostate cancer and low prostate-specific antigen.

OBJECTIVE: To evaluate outcomes for men with high Gleason score and low prostate-specific antigen (PSA) prostate cancer. Low PSA levels among men with Gleason 8-10 prostate cancer may be owing to cellular dedifferentiation rather than low disease burden. We hypothesized that men with Gleason 8-10 prostate cancer and low PSA levels have increased risk for advanced disease and worse survival. MATERIALS AND METHODS: Men diagnosed from 2004 to 2007 with Gleason 8-10 prostate adenocarcinoma in the National Cancer Data Base were included. Patients were stratified by PSA levels at diagnosis: 0.1 to 3.9, 4.0 to 9.9, 10.0 to 19.9, and≥20.0ng/ml. Outcomes were clinical TNM category, pathologic stage (for prostatectomy patients), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards models were used. RESULTS: A total of 37,283 patients were included. Men with PSA levels of<4.0ng/ml were more likely than those with PSA levels of 4 to 9.9ng/ml to present with clinical T3-4 disease (15% vs. 10%, P<0.001), nodal (4% vs. 2%, P<0.001) and distant (5% vs. 3%, P<0.001) metastasis. However, among patients treated with prostatectomy, lower PSA levels were not associated with increased likelihood of pathologic T3-4 disease or nodal metastasis. Six-year OS was 89.1% (PSA: 0.1-3.9ng/ml) vs. 91.0% (PSA: 4.0-9.9ng/ml) for prostatectomy (log-rank P<0.001), and 75.8% vs. 81.0% for radiotherapy (P<0.001). Multivariable analyses showed OS of patients with PSA levels of 0.1 to 3.9ng/ml to be similar to those with PSA levels of 10 to 19.9ng/ml. CONCLUSIONS: Patients with Gleason 8-10 cancer and PSA levels of<4.0ng/ml have more aggressive disease than those with PSA levels of 4 to 9.9ng/ml; these low PSA cancers behave more like those with PSA levels of 10 to 19.9ng/ml. Further study is needed to evaluate potential biological differences in these patients with low PSA-producing cancers.

Increased risk of salivary gland cancer among women with a previous cancer diagnosis.

BACKGROUND: The purpose of this study was to evaluate salivary gland cancer incidence among patients with a previous cancer diagnosis and explore the potential relationship of salivary gland cancer among women with a previous diagnosis of breast cancer. METHODS: We obtained information from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed between 1973 and 2011. Incidence, annual percent change (APC), and survival were examined. RESULTS: Women were more likely than men to experience subsequent salivary gland cancer, female observed to expected (O/E) = 1.63 (95% confidence interval [CI], 1.49-1.78) versus male O/E = 1.34 (95% CI, 1.25-1.44). Index breast cancer does not confer greater risk of salivary gland cancer. Women demonstrate improved overall survival (OS) and cause-specific survival (CSS) compared with men for subsequent salivary gland cancer. CONCLUSION: Among patients with a previous cancer diagnosis, the risk of subsequent salivary gland cancer is greater among women than men. More research is needed to determine the relationship between index breast cancer and subsequent salivary gland cancer risk. © 2015 Wiley Periodicals, Inc. Head Neck 38: E446-E451, 2016.

Use of mobile device technology to continuously collect patient-reported symptoms during radiation therapy for head and neck cancer: A prospective feasibility study.

PURPOSE: Accurate assessment of toxicity allows for timely delivery of supportive measures during radiation therapy for head and neck cancer. The current paradigm requires weekly evaluation of patients by a provider. The purpose of this study is to evaluate the feasibility of monitoring patient reported symptoms via mobile devices. METHODS AND MATERIALS: We developed a mobile application for patients to report symptoms in 5 domains using validated questions. Patients were asked to report symptoms using a mobile device once daily during treatment or more often as needed. Clinicians reviewed patient-reported symptoms during weekly symptom management visits and patients completed surveys regarding perceptions of the utility of the mobile application. The primary outcome measure was patient compliance with mobile device reporting. Compliance is defined as number of days with a symptom report divided by number of days on study. RESULTS: There were 921 symptom reports collected from 22 patients during treatment. Median reporting compliance was 71% (interquartile range, 45%-80%). Median number of reports submitted per patient was 34 (interquartile range, 21-53). Median number of reports submitted by patients per week was similar throughout radiation therapy and there was significant reporting during nonclinic hours. Patients reported high satisfaction with the use of mobile devices to report symptoms. CONCLUSIONS: A substantial percentage of patients used mobile devices to continuously report symptoms throughout a course of radiation therapy for head and neck cancer. Future studies should evaluate the impact of mobile device symptom reporting on improving patient outcomes.

Effect of race and histology on patterns of failure in women with early stage endometrial cancer treated with high dose rate brachytherapy.

BACKGROUND: Clinical trials have helped refine management of early stage endometrial cancer (EC). For patients with intermediate risk features, adjuvant radiation is considered, primarily vaginal cuff brachytherapy. For higher risk patients, there may be a role for chemotherapy and radiation. The purpose of this study is to examine patterns of failure for early stage EC patients treated with postoperative high dose rate brachytherapy. METHODS: In this single institution retrospective cohort study, 208 women with early stage endometrial cancer who received definitive therapy between January 1, 2000 and January 1, 2013 were identified. RESULTS: Median follow-up was 46.4 (range, 6.2-137.3) months. Thirteen (6.3%) patients developed with locoregional recurrent disease and 15 (7.2%) patients developed distant metastasis. Freedom from recurrence at 5 years was 88.6% for white patients and 60.5% for black patients (p=0.0093). Five year recurrence free survival (RFS) for white vs. black patients was 82.9% vs. 48.9% (p=0.0007). Five year overall survival (OS) was 86.8% for white patients and 59.5% for black patients (p=0.0023). Black patients with unfavorable histology treated with chemotherapy and vaginal brachytherapy had a 15% locoregional recurrence rate, more than double the rate of local recurrence compared to AA patients with endometrioid histology and white patients with any histology (6% locoregional recurrence rate). CONCLUSIONS: Black women with unfavorable histology early stage EC experience increased rates of recurrence and worse survival compared to white patients. Patterns of failure in this group also indicate a high locoregional failure rate for the black patients with unfavorable histology (type II).

Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients.

PURPOSE: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. METHODS AND MATERIALS: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsy Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. RESULTS: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. CONCLUSIONS: This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score upgrading based on clinically available information in modern patients. These data inform the selection of radiation therapy strategies and an understanding of whether prostatectomy alone is likely to be curative for patients with early prostate cancers.

Guideline-discordant use of imaging during work-up of newly diagnosed prostate cancer.

PURPOSE: Overuse of radiographic imaging in patients with prostate cancer (CaP) who are unlikely to have metastatic disease is costly and can lead to patient harm from unnecessary procedures. However, underuse of imaging can lead to undiagnosed metastatic disease, resulting in aggressive treatments in patients with incurable disease. The National Comprehensive Cancer Network (NCCN) recommends bone scans and computed tomography (CT) or magnetic resonance imaging (MRI) during initial work-up of select patients with intermediate- or high-risk CaP. We quantify the proportion of patients who received work-up discordant with NCCN guidelines. METHODS: Patients in the SEER-Medicare database diagnosed from 2004 to 2007 were included. We report bone scan and CT/MRI from date of diagnosis to the earlier of first treatment or 6 months. RESULTS: Sixty-five percent of patients for whom bone scan was recommended received it, and 49% received recommended CT/MRI. Further, 43% of patients for whom bone scan was not recommended received it, and 38% received CT/MRI when not recommended. Age and race were significantly associated with discordance on multivariable models. There was significant regional variation. Underuse of recommended bone and CT/MRI scans decreased in more recent years, but overuse of unnecessary CT/MRI increased. CONCLUSION: There is a high prevalence of both overuse and underuse of guideline-recommended imaging in CaP. Additional research is required to examine contributing factors to guideline nonadherence in the imaging work-up of CaP.