Financial Toxicity in Patients with Brain and Spine Metastases.

OBJECTIVE: Financial toxicity associated with cancer treatment has a deleterious impact on patient outcomes but has not been well characterized among patients with metastatic cancers. We characterize the extent of financial toxicity among this population and identify factors associated with financial toxicity. METHODS: We prospectively surveyed adult patients with brain and spine metastases who received radiosurgery at a large academic medical center between January 2018 and December 2019. Financial toxicity was measured with the Personal Financial Wellness (PFW) scale. RESULTS: In total, 93 patients were included, with a median survival of 17.7 months. Most patients had private insurance (47%) or Medicare with supplementary insurance (42%), whereas 11% of patients were uninsured or insured by Medicaid/Medicare/Veterans Affairs. Of patients, 60% were primary income earners, of whom 52% had dependents. The median PFW score was 7.0 (interquartile range, 5.1-9.1), with financial toxicity reported in 23 patients (25%). After adjusting for age and education level, private insurance (odds ratio [OR], 0.28; P = 0.080) was associated with a lower likelihood of financial toxicity. Having ≥1 emergency department visit (OR, 3.87; P = 0.024) and a cancer-related change in employment status (OR, 3.63; P = 0.036) were associated with greater likelihood of reporting financial toxicity. CONCLUSIONS: Most patients with cancer with brain and spine metastases with a poor prognosis treated at a tertiary center are primary income earners and experience financial toxicity. Further studies are warranted to assess the longitudinal impact of financial toxicity in patients with metastatic cancer, particularly those with ≥1 emergency department visit and a cancer-related change in employment status.

Proton radiotherapy and treatment delay in head and neck squamous cell carcinoma.

OBJECTIVE: For patients with head and neck squamous cell carcinoma (HNSCC), delays in the initiation of radiotherapy (RT) have been closely associated with worse outcomes. We sought to investigate whether RT modality (proton vs. photon) is associated with differences in the time to initiation of RT. METHODS: The National Cancer Database was queried for patients diagnosed with nonmetastatic HNSCC between 2004 and 2015 who received either proton or photon RT as part of their initial treatment. Wilcoxon rank-sum and chi-square tests were used to compare continuous and categorical variables, respectively. Multivariable logistic regression was used to determine the association between use of proton RT and delayed RT initiation. RESULTS: A total of 175,088 patients with HNSCC receiving either photon or proton RT were identified. Patients receiving proton RT were more likely to be white, reside in higher income areas, and have private insurance. Proton RT was associated with delayed RT initiation compared to photon RT (median 59 days vs. 45, P < 0.001). Receipt of proton therapy was independently associated with RT initiation beyond 6 weeks after diagnosis (adjusted OR [aOR, definitive RT] = 1.69; 95% confidence interval [CI] 1.26-2.30) or surgery (aOR [adjuvant RT] = 4.08; 95% CI 2.64-6.62). In the context of adjuvant proton RT, increases in treatment delay were associated with worse overall survival (weeks, adjusted hazard ratio = 1.099, 95% CI 1.011-1.194). CONCLUSION: Use of proton therapy is associated with delayed RT in both the definitive and adjuvant settings for patients with HNSCC and could be associated with poorer outcomes. LEVEL OF EVIDENCE: 2b Laryngoscope, 122:0000-0000, 2019 Laryngoscope, 130:E598-E604, 2020.

Use of Preoperative Radiation Therapy in Early-stage and Locally Advanced Breast Cancer.

Purpose There is growing interest in delivering radiation preoperatively (preopRT) rather than postoperatively (postopRT) for breast cancer. Using the National Cancer Database, we evaluated the use and outcomes of preopRT in breast cancer. Methods We identified adult females diagnosed with non-metastatic breast cancer treated with definitive surgery and radiation between 2004 and 2014. Logistic regression models evaluated factors associated with use of preopRT in early-stage (clinical T1-3/N0-1) and locally advanced (clinical T4/N2-3) disease. Rates of breast-conserving surgery, breast reconstruction, positive surgical margins, and 30-day surgical readmissions were compared between patients receiving preopRT and postopRT. Results Of 373,595 patients who met our inclusion criteria, 1,245 (0.3%) patients received preopRT. Patients receiving preopRT were more likely to be of lower socioeconomic status and have tumors with higher T stage. Younger age and N1 (vs N0) disease predicted for use of preopRT in early-stage disease, while older age and N0 disease predicted for use of preopRT in the locally advanced setting. PreopRT patients were less likely to undergo breast-conserving surgery and more likely to have positive surgical margins. Rates of unplanned readmissions within 30 days of surgery were similar among patients treated with preopRT and postopRT. Conclusions PreopRT is a new treatment strategy for patients with breast cancer with different clinical and sociodemographic drivers of its use in the early-stage and locally advanced settings. We await the results of clinical trials studying the efficacy of this approach.

Adjuvant Radiation Improves Recurrence-Free Survival and Overall Survival in Adrenocortical Carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high rates of recurrence and poor prognosis. The role of radiotherapy (RT) in localized ACC has been controversial, and RT is not routinely offered. OBJECTIVE: To evaluate the benefit of adjuvant RT on outcomes in ACC. DESIGN: This is a retrospective propensity-matched analysis. SETTING: All patients were seen through the University of Michigan's Endocrine Oncology program, and all those who underwent RT were treated at the University of Michigan. PARTICIPANTS: Of 424 patients with ACC, 78 were selected; 39 patients underwent adjuvant radiation. INTERVENTION: Adjuvant RT to the tumor bed and adjacent lymph nodes. MAIN OUTCOMES MEASURES: Time to local failure, distant failure, or death. RESULTS: Median follow-up time was 4.21 years (95% CI, 2.79 to 4.94). The median radiation dose was 55 Gy (range, 45 to 60). The 3-year overall survival estimate for patients improved from 48.6% for patients without RT (95% CI, 29.7 to 65.2) to 77.7% (95% CI, 56.3 to 89.5) with RT, with a hazard ratio (HR) of 3.59 (95% CI, 1.60 to 8.09; P = 0.002). RT improved local recurrence-free survival (RFS) from 34.2% (95% CI, 18.8 to 50.3) to 59.5% (95% CI, 39.0 to 75.0), with an HR of 2.67 (95% CI, 1.38 to 5.19; P = 0.0035). RT improved all RFS from 18.3% (95% CI, 6.7 to 34.3) to 46.7% (95% CI, 26.9 to 64.3), with an HR 2.59 (95% CI, 1.40 to 4.79; P = 0.0024). CONCLUSIONS: In the largest single institution study to date, adjuvant RT after gross resection of ACC improved local RFS, all RFS, and overall survival in this propensity-matched analysis. Adjuvant RT should be considered a part of multidisciplinary management for patients with ACC.

False News of a Cannabis Cancer Cure.

Background There is increasing concern among healthcare communities about the misinformation online about using cannabis to cure cancer. We have characterized this online interest in using cannabis as a cancer treatment and the propagation of this information on social media. Materials & methods We compared search activity over time for cannabis and cancer versus standard cancer therapies using Google Trends' relative search volume (RSV) tool and determined the impact of cannabis legalization. We classified news on social media about cannabis use in cancer as false, accurate, or irrelevant. We evaluated the cannabis-related social media activities of cancer organizations. Results The online search volume for cannabis and cancer increased at 10 times the rate of standard therapies (RSV 0.10/month versus 0.01/month, p<0.001), more so in states where medical or recreational cannabis is legal. The use of cannabis as a cancer cure represented the largest category (23.5%) of social media content on alternative cancer treatments. The top false news story claiming cannabis as a cancer cure generated 4.26 million engagements on social media, while the top accurate news story debunking this false news generated 0.036 million engagements. Cancer organizations infrequently addressed cannabis (average 0.7 Tweets; 0.4 Facebook posts), with low influence compared to false news (average 5.6 versus 527 Twitter retweets; 98 versus 452,050 Facebook engagements, p<0.001). Conclusions These findings reveal a growing interest in cannabis use as a cancer cure, and a crucial opportunity for physicians and medical organizations to communicate accurate information about the role of cannabis in cancer to patients, caregivers, and the general public.

Patient Experiences and Clinician Views on the Role of Radiation Therapy for Ductal Carcinoma In Situ.

PURPOSE: To evaluate patient experiences with decisions regarding radiation therapy (RT) for ductal carcinoma in situ (DCIS), and to assess clinician views on the role of RT for DCIS with favorable features in the present era. METHODS AND MATERIALS: A sample of women with newly diagnosed breast cancer from the population-based Georgia and Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registries were sent surveys approximately 2 months after undergoing breast-conserving surgery (BCS), with a 70% response rate. The analytic sample was limited to 538 respondents with unilateral DCIS. We also surveyed 761 surgeons and radiation oncologists treating breast cancer in those regions, of whom, 539 responded (71%). RESULTS: After BCS, 23% of patients omitted RT, with twice the rate of omission in Los Angeles County relative to Georgia (31% vs 16%; P < .001). The most common reasons for omitting RT were advice from a clinician that it was not needed (62%) and concern about side effects (24%). Cost and transportation were not reported as influential considerations. After covariate adjustment, low- and intermediate-grade disease (odds ratio [OR] 5.5, 95% confidence interval [CI] 2.5-12; and OR 3.2, 95% CI 1.7-6.1, respectively) and Los Angeles County SEER site (OR 4.3, 95% CI 2.3-8.2) were significantly associated with greater RT omission. Of the responding clinicians, 62% would discuss RT omission for a patient with DCIS with favorable features. Clinicians in Los Angeles County were more likely to discuss RT omission than were those in Georgia (67% vs 56%; P = .01). Approximately one third of clinicians would obtain the Oncotype DX DCIS score. CONCLUSIONS: The heterogeneity in RT omission after BCS for DCIS continues to be substantial, with systematic differences in provider opinions across the 2 regions we studied. Enhanced precision of recurrence estimates, guidance from professional organizations, and better communication are needed to improve the consistency of treatment in this controversial area.

Perspectives of Patients With Cancer on the Ethics of Rapid-Learning Health Systems.

Purpose To inform the evolving implementation of CancerLinQ and other rapid-learning systems for oncology care, we sought to evaluate perspectives of patients with cancer regarding ethical issues. Methods Using the GfK Group online research panel, representative of the US population, we surveyed 875 patients with cancer; 621 (71%) responded. We evaluated perceptions of appropriateness (scored from 1 to 10; 10, very appropriate) using scenarios and compared responses by age, race, and education. We constructed a scaled measure of comfort with secondary use of deidentified medical information and evaluated its correlates in a multivariable model. Results Of the sample, 9% were black and 9% Hispanic; 38% had completed high school or less, and 59% were age ≥ 65 years. Perceptions of appropriateness were highest when consent was obtained and university researchers used data to publish a research study (weighted mean appropriateness, 8.47) and lowest when consent was not obtained and a pharmaceutical company used data for marketing (weighted mean appropriateness, 2.7). Most respondents (72%) thought secondary use of data for research was very important, although those with lower education were less likely to endorse this (62% v 78%; P < .001). Overall, 35% believed it was necessary to obtain consent each time such research was to be performed; this proportion was higher among blacks/Hispanics than others (48% v 33%; P = .02). Comfort with the use of deidentified information from medical records varied by scenario and overall was associated with distrust in the health care system. Conclusion Perceptions of patients with cancer regarding secondary data use depend on the user and the specific use of the data, while also frequently differing by patient sociodemographic factors. Such information is critical to inform ongoing efforts to implement oncology learning systems.

Patient Perspectives on the Ethical Implementation of a Rapid Learning System for Oncology Care.

INTRODUCTION: A rapid learning system (RLS) of health care harnesses data generated from routine patient care to create a virtuous cycle of data collection and analysis for quality improvement and research. The success of such systems depends on understanding patient perspectives regarding the ethical issues that arise from the ongoing implementation of this transformative concept. METHODS: An interview guide was designed to evaluate patient perspectives to inform the ethical implementation of an oncology RLS. A purposively selected, diverse sample of 32 patients with cancer was recruited from two institutions to participate in semistructured, in-depth interviews for formal qualitative analysis. RESULTS: The extent to which respondents expressed discomfort with more permissive system features (less formal notification/consent, broader uses/users, inclusion of sensitive data) reflected their trust, which in turn seemed to vary by sociodemographic features. It was also influenced by their familiarity with technology and their attitudes and beliefs regarding privacy and the use of electronic medical records more generally. Distrust of insurers and the pharmaceutical industry led subjects to desire greater oversight and restriction of these potential users of the system. Subjects were most comfortable when doctors were the primary users, engaged patients directly in the notification and consent discussion, and oversaw the system. CONCLUSION: Those actively developing RLSs should recognize the critical importance of trust and the key role that doctors will need to play in order for such systems to be successful and to ensure that their implementation is ethically palatable to the patients whose data are being included.

Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. METHODS AND MATERIALS: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. RESULTS: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. CONCLUSIONS: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

Adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, often with an unfavorable prognosis. Here we summarize the knowledge about diagnosis, epidemiology, pathophysiology, and therapy of ACC. Over recent years, multidisciplinary clinics have formed and the first international treatment trials have been conducted. This review focuses on evidence gained from recent basic science and clinical research and provides perspectives from the experience of a large multidisciplinary clinic dedicated to the care of patients with ACC.

Adjuvant therapies and patient and tumor characteristics associated with survival of adult patients with adrenocortical carcinoma.

CONTEXT: Adrenocortical carcinoma is a rare malignant endocrine neoplasia. Studies regarding outcome and prognostic factors rely on fairly small studies. Here we summarize the experience with patients with a diagnosis of adrenocortical carcinoma from a large tertiary referral center. OBJECTIVE: The objective of the study was to identify prognostic factors in patients with adrenocortical carcinoma and evaluate adjuvant treatment strategies. DESIGN: Patient data were collected in a retrospective single-center study. Epidemiological, patient, and tumor characteristics were analyzed for prognostic factors regarding overall and recurrence-free survival in Cox regression models (multivariable and univariable). RESULTS: Three hundred ninety-one adult patients with the diagnosis of adrenocortical carcinoma were identified. Median overall survival was 35.2 months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were identified as negative prognostic factors (HR for death, HR for recurrence). Mitotane therapy increases recurrence-free survival, an effect that was significantly further improved by adjuvant radiation therapy but did not impact overall survival. Patients with open adrenalectomy had improved overall survival. CONCLUSIONS: This study increases the evidence for adverse risk factors (cortisol production, high tumor stage, and high tumor grade) and suggests the following therapy approach: adrenocortical carcinoma patients should be treated with open adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction with radiation, should be considered to delay tumor recurrence.

Targeted radiosensitization of ETS fusion-positive prostate cancer through PARP1 inhibition.

ETS gene fusions, which result in overexpression of an ETS transcription factor, are considered driving mutations in approximately half of all prostate cancers. Dysregulation of ETS transcription factors is also known to exist in Ewing's sarcoma, breast cancer, and acute lymphoblastic leukemia. We previously discovered that ERG, the predominant ETS family member in prostate cancer, interacts with the DNA damage response protein poly (ADP-ribose) polymerase 1 (PARP1) in human prostate cancer specimens. Therefore, we hypothesized that the ERG-PARP1 interaction may confer radiation resistance by increasing DNA repair efficiency and that this radio-resistance could be reversed through PARP1 inhibition. Using lentiviral approaches, we established isogenic models of ERG overexpression in PC3 and DU145 prostate cancer cell lines. In both cell lines, ERG overexpression increased clonogenic survival following radiation by 1.25 (±0.07) fold (mean ± SEM) and also resulted in increased PARP1 activity. PARP1 inhibition with olaparib preferentially radiosensitized ERG-positive cells by a factor of 1.52 (±0.03) relative to ERG-negative cells (P < .05). Neutral and alkaline COMET assays and immunofluorescence microscopy assessing γ-H2AX foci showed increased short- and long-term efficiencies of DNA repair, respectively, following radiation that was preferentially reversed by PARP1 inhibition. These findings were verified in an in vivo xenograft model. Our findings demonstrate that ERG overexpression confers radiation resistance through increased efficiency of DNA repair following radiation that can be reversed through inhibition of PARP1. These results motivate the use of PARP1 inhibitors as radiosensitizers in patients with localized ETS fusion-positive cancers.

Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity.

OBJECTIVES: We reviewed our institution's experience in treating soft tissue sarcomas of the extremity to identify factors associated with local recurrence, metastasis, and overall survival, to identify patients who may benefit from intensification of therapy. METHODS: A retrospective analysis was performed for patients who underwent both limb-sparing surgery and external beam radiotherapy for extremity sarcoma. Those who had gross residual disease or who presented with recurrent or metastatic disease were excluded. The Kaplan-Meier product limit and multivariate Cox regression were used to estimate local failure-free probability, distant failure-free probability, and overall survival along with associations with patient, tumor, and treatment characteristics. RESULTS: One hundred eighty-eight patients were included in the analysis. Twenty-five (13%) and 46 (24%) experienced local and distant recurrence, respectively. Patients with high/intermediate-grade tumors [hazard ratio (HR)=5.63, 95% confidence interval (CI): 1.27-24.89, P=0.023] or with multifocally positive margins (HR=4.27, 95% CI: 1.20-15.24, P=0.026) were more likely to fail locally. Those with a preceding local recurrence (HR=8.58, 95% CI: 3.87-19.04, P<0.0001), high/intermediate-grade tumors (HR=5.68, 95% CI: 1.28-25.25, P=0.023), or no secondary reexcision (HR=2.5, 95% CI: 1.09-5.74, P=0.031) were more likely to develop metastasis. Patients with local recurrence (HR=3.6, 95% CI: 1.77-7.29, P<0.001), metastasis (HR=16.0, 95% CI: 7.93-32.31, P<0.0001), or without secondary reexcision (HR=3.2, 95% CI: 1.27-8.09, P=0.014) had decreased overall survival. CONCLUSIONS: Patients whose tumor grade or margin status put them at high risk for local failure should be considered for intensification of therapy. Those with a local recurrence should be considered for increased surveillance or systemic therapy, as local failure is associated with subsequent metastasis and decreased survival.

Dose--effect relationships for femoral fractures after multimodality limb-sparing therapy of soft-tissue sarcomas of the proximal lower extremity.

PURPOSE: We investigated the clinical and dosimetric predictors for radiation-associated femoral fractures in patients with proximal lower extremity soft tissue sarcomas (STS). METHODS AND MATERIALS: We examined 131 patients with proximal lower extremity STS who received limb-sparing surgery and external-beam radiation therapy between 1985 and 2006. Five (4%) patients sustained pathologic femoral fractures. Dosimetric analysis was limited to 4 fracture patients with full three-dimensional dose information, who were compared with 59 nonfracture patients. The mean doses and volumes of bone (V(d)) receiving specified doses (≥30 Gy, 45 Gy, 60 Gy) at the femoral body, femoral neck, intertrochanteric region, and subtrochanteric region were compared. Clinical predictive factors were also evaluated. RESULTS: Of 4 fracture patients in our dosimetric series, there were three femoral neck fractures with a mean dose of 57.6 ± 8.9 Gy, V30 of 14.5 ± 2.3 cc, V45 of 11.8 ± 1.1 cc, and V60 of 7.2 ± 2.2 cc at the femoral neck compared with 22.9 ± 20.8 Gy, 4.8 ± 5.6 cc, 2.5 ± 3.9 cc, and 0.8 ± 2.7 cc, respectively, for nonfracture patients (p < 0.03 for all). The femoral neck fracture rate was higher than at the subtrochanteric region despite lower mean doses at these subregions. All fracture sites received mean doses greater than 40 Gy. Also, with our policy of prophylactic femoral intramedullary nailing for high-risk patients, there was no significant difference in fracture rates between patients with and without periosteal excision. There were no significant differences in age, sex, tumor size, timing of radiation therapy, and use of chemotherapy between fracture and nonfracture patients. CONCLUSIONS: These dose-volume toxicity relationships provide RT optimization goals to guide future efforts for reducing pathologic fracture rates. Prophylactic femoral intramedullary nailing may also reduce fracture risk for susceptible patients.

The Cancer of the Prostate Risk Assessment (CAPRA) in patients treated with external beam radiation therapy: evaluation and optimization in patients at higher risk of relapse.

BACKGROUND: The Cancer of the Prostate Risk Assessment (CAPRA) was developed to predict freedom from biochemical failure (FFBF) following radical prostatectomy (RP). Its utility following external beam radiation therapy (EBRT) has not been externally evaluated. METHODS: A retrospective study of 612 patients treated with dose-escalated EBRT at the University of Michigan Medical Center. RESULTS: Compared to the derivation cohort, EBRT treated patients had higher-risk disease (28% with CAPRA of 6-10 vs. 5%, respectively). A total of 114 patients (19%) had BF with 5-year BF ranging from 7% with CAPRA 0-3 to 35% with CAPRA 7-10. For RT patients the risk of BF at 5-year was similar to 4 surgical cohorts for CAPRA scores 0-2 but lower for all CAPRA scores ≥ 3. The difference favoring RT increased with increasing CAPRA score reaching a 27-50% absolute improved at 5-years for CAPRA scores of 6-10. On multivariate analysis each CAPRA point increased the risk of BF (p<0.0001) while Gleason pattern 5 in the biopsy also increased BF (p=0.01) and long-term androgen deprivation therapy (ADT) significantly reduced the risk of BF (p=0.015). CONCLUSIONS: Compared to surgical series the risk of BF was lower with dose-escalated EBRT with the greatest difference at the highest CAPRA scores.

Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer.

Recurrent fusions of ETS genes are considered driving mutations in a diverse array of cancers, including Ewing's sarcoma, acute myeloid leukemia, and prostate cancer. We investigate the mechanisms by which ETS fusions mediate their effects, and find that the product of the predominant ETS gene fusion, TMPRSS2:ERG, interacts in a DNA-independent manner with the enzyme poly (ADP-ribose) polymerase 1 (PARP1) and the catalytic subunit of DNA protein kinase (DNA-PKcs). ETS gene-mediated transcription and cell invasion require PARP1 and DNA-PKcs expression and activity. Importantly, pharmacological inhibition of PARP1 inhibits ETS-positive, but not ETS-negative, prostate cancer xenograft growth. Finally, overexpression of the TMPRSS2:ERG fusion induces DNA damage, which is potentiated by PARP1 inhibition in a manner similar to that of BRCA1/2 deficiency.

Gleason pattern 5 is the greatest risk factor for clinical failure and death from prostate cancer after dose-escalated radiation therapy and hormonal ablation.

PURPOSE: The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. METHODS AND MATERIALS: Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). RESULTS: At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. CONCLUSION: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.

Adjuvant and definitive radiotherapy for adrenocortical carcinoma.

PURPOSE: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. METHODS AND MATERIALS: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. RESULTS: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). CONCLUSIONS: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.