Prognostic impact of clinical tumor size on overall survival for subclassifying stages I and II vaginal cancer: A SEER analysis.

PURPOSE: This study accessed the Surveillance, Epidemiology and End Results (SEER) database to determine if tumor size is an independent predictor of overall survival (OS) for patients with stages I and II vaginal cancer (VC). MATERIALS AND METHODS: We identified in the SEER database, patients with available tumor size having stage I or II squamous cell histology from January 2004 through December 2012 with minimum follow-up of six months. Univariate analyses (UA) and multivariable analyses (MVA) evaluated the effect of several prognostic factors, including tumor size, regarding OS. RESULTS: 529 SEER patients were found with recorded tumor sizes, of which 293 (55.4%) were stage I and 236 (44.6%) stage II. UA found the following significant prognostic factors of worse OS: tumor size >2cm (HR=1.80, p=0.02) and older age at diagnosis (p<0.001) in stage I; and tumor size >2cm (HR=2.13, p=0.04) and older age at diagnosis (p<0.001) in stage II. Estimates of 5-year OS in patients with tumor size ≤2cm vs. >2cm were 79.2% vs. 66.1% in stage I (p=0.0187) and 80.9% vs. 51.2% in stage II (p=0.0369). MVA confirmed about double risk of death for patients with tumor size >2cm (HRs: 1.88 in stage I and 2.06 in stage II). CONCLUSIONS: Tumor size seems to predict OS outcome in patients with stages I/II VC. Further confirmatory investigations are recommended to firmly establish its incorporation into currently accepted staging criteria for these patients.

Disparities in outcomes and access to therapy options in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) disproportionately impacts racial and ethnic minorities and patients with lower socioeconomic status. These social determinants of health (SDH) lead to disparities in access to care and outcomes. We aim to understand the relationship between SDH and survival and locoregional treatment options in HCC. METHODS: Using the National Cancer Database, we evaluated survival and access locoregional treatments including non-transplant surgery, liver transplant (LT), and liver-directed radiation therapy (LDRT) in patients with HCC diagnosed between 2004 and 2017. Variables including clinical stage, age, sex, race, income, rurality, year of diagnosis, facility type (FT), Charlson-Deyo score (CD), and insurance were evaluated. Cox proportional hazards multivariable regression and dominance analyses were used for analyses. RESULTS: In total, 140 340 patients were included. Worse survival was seen with advanced stage, older age, Black race, rurality, public insurance, treatment at a nonacademic center, and lower income. The top predictors for survival included stage, age, and income. Completion of non-transplant surgery was best predicted by stage, FT, and insurance type, whereas LT was predicted by age, year of diagnosis, and CD score. LDRT utilization was most associated with year of diagnosis, FT, and CD score. CONCLUSION: For patients with HCC, survival was predicted primarily by stage, age, and income. The primary sociodemographic factors associated with access to surgical treatments, in addition to FT, were insurance and income, highlighting the financial burdens of health care. Work is needed to address disparities in access to care, including improved insurance access, addressing financial inequities and financial toxicities of treatments, and equalizing care opportunities in community centers.

Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists.

OBJECTIVES: For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. METHODS: From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. RESULTS: A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. CONCLUSIONS: HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for palliative external beam radiation therapy (RT) in symptomatic bone metastases. METHODS: The ASTRO convened a task force to address 5 key questions regarding palliative RT in symptomatic bone metastases. Based on a systematic review by the Agency for Health Research and Quality, recommendations using predefined consensus-building methodology were established; evidence quality and recommendation strength were also assessed. RESULTS: For palliative RT for symptomatic bone metastases, RT is recommended for managing pain from bone metastases and spine metastases with or without spinal cord or cauda equina compression. Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone. Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression. Patients with nonspine bone metastases requiring surgery are recommended postoperative RT. Symptomatic bone metastases treated with conventional RT are recommended 800 cGy in 1 fraction (800 cGy/1 fx), 2000 cGy/5 fx, 2400 cGy/6 fx, or 3000 cGy/10 fx. Spinal cord or cauda equina compression in patients who are ineligible for surgery and receiving conventional RT are recommended 800 cGy/1 fx, 1600 cGy/2 fx, 2000 cGy/5 fx, or 3000 cGy/10 fx. Symptomatic bone metastases in selected patients with good performance status without surgery or neurologic symptoms/signs are conditionally recommended stereotactic body RT over conventional palliative RT. Spine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, 2400 cGy/6 fx, or 2000 cGy/8 fx; nonspine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, or 2400 cGy/6 fx. Determination of an optimal RT approach/regimen requires whole person assessment, including prognosis, previous RT dose if applicable, risks to normal tissues, quality of life, cost implications, and patient goals and values. Relatedly, for patient-centered optimization of treatment-related toxicities and quality of life, shared decision making is recommended. CONCLUSIONS: Based on published data, the ASTRO task force's recommendations inform best clinical practices on palliative RT for symptomatic bone metastases.

Long-term Clinical Outcomes of Yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma: A 5-Year Institutional Experience.

RATIONALE AND OBJECTIVES: To examine the clinical outcomes of yttrium-90 (Y90) transarterial radioembolization (TARE) for primary hepatocellular carcinoma (HCC) through the evaluation of a 5-year institutional experience. MATERIALS AND METHODS: This retrospective study evaluated 88 consecutive patients with primary HCC receiving Y90 TARE treatment at an academic medical center from 2017 to 2021. Disease distribution was bilobar in 60.2% of patients with an average lesion diameter of 5.0 ± 3.4 cm and Barcelona Clinic Liver Cancer stage B or C in 77% of the participants. Clinical outcomes were elucidated by examination of complications, liver function tests, biochemical response, and radiographic response. Objective response ratio (ORR) and progression-free survival (PFS) were also calculated. RESULTS: The mean administered Y90 radiation dose was 127.8 ± 20.2 Gy. No significant complications or LFT elevations occurred post-therapy. Of the 73.9% of patients with α-fetoprotein-producing tumors, 67.8% experienced a complete or partial biochemical response 1 month post-treatment. The ORR was 83.3% on 6-month imaging and PFS was 9.6 ± 8.5 months. Functional outcomes (Eastern Cooperative Oncology Group) were maintained or improved in 79.6% and 76.1% of patients by 6 months and 1 year post-treatment, respectively. The mean survival was 14.7 ± 12.1 months. At 6 months post-treatment, 77.3% of patients were downstaged to or maintained Milan criteria, which was sustained for 74.4% and 70.0% of patients 1 year and 2 years after treatment, respectively. CONCLUSION: Y90-TARE is a safe and effective therapy for primary HCC. Enduring outcomes further act as a realistic bridge to liver transplantation, with a majority of patients maintaining Milan criteria and preserving their functional status long term.

Treatment Patterns and Outcomes for Patients with Ampullary Carcinoma Who Do Not Undergo Surgery.

Surgical resection is the standard of care for ampullary adenocarcinoma (AC). Many patients are ineligible due to comorbidities/advanced disease. Evidence for the optimal non-operative management of localized AC is lacking. We hypothesize that patients treated with chemotherapy (CT) and definitive radiation (DRT) will have superior survival (OS) compared to those treated with CT alone. We performed a retrospective review of the National Cancer Database from 2004 to 2017 to identify patients with non-metastatic AC and no surgical intervention. Patients were categorized as having received no treatment, palliative radiotherapy (PRT) alone, CT alone, CT + PRT, DRT alone, or CT + DRT. We utilized Kaplan-Meier analysis to determine OS and the log-rank test to compare survival curves. Among 2176 patients, treatment groups were: No treatment (71.2%), PRT alone (1.9%), CT alone (13.1%), CT + PRT (1.6%), DRT alone (2.4%), and CT + DRT (9.7%). One-year OS varied by treatment group, ranging from 35.1% (PRT alone) to 59.4% (CT + DRT). The one-year OS in a matched cohort was not significantly different between CT alone and CT + DRT (HR 0.87, 95% CI 0.69-1.10, p = 0.87). Most patients with non-metastatic AC not treated with surgery do not receive any treatment. There is no difference in one-year OS between those undergoing CT alone and CT + DRT.

Prostate brachytherapy utilization in the COVID-19 era: A cross-sectional study of radiation oncologists in the United States.

PURPOSE: Despite advantages such as abbreviated treatment course, brachytherapy (BT) utilization rates for prostate cancer (PC) in the United States (US) are declining. We surveyed practicing US radiation oncologists (ROs) to determine the proportion who offer BT for PC and whether the COVID-19 pandemic influenced practice patterns. MATERIALS AND METHODS: From July-October 2021, we surveyed practicing US ROs. Provider demographic and practice characteristics were collected. Questions assessing utilization of BT and external beam (EBRT) for patients of varying risk groups and the effect of the pandemic on practice patterns were administered. Descriptive statistics were reported. The bivariate relationships between provider characteristics and likelihood of offering BT were assessed using the Chi-square test (α < 0.05). RESULTS: Six percent of surveyed ROs responded, with 203 meeting inclusion criteria (72% male, 72% white, 53% non-academic, 69% >10 years in practice) and 156 (77%) treating PC. For low-risk, fewer providers offered BT (41% total; 25% low dose rate [LDR], 10% high dose rate [HDR], 6% both) than stereotactic body (SBRT) (54%) and moderately hypofractionated radiation therapy (MHFRT) (83%). For favorable intermediate risk, fewer offered BT (37% total; 21% LDR, 10% HDR, 6% both) than SBRT (48%), MHFRT (87%), and conventionally fractionated EBRT (38%). For high (44%) and very-high (37%) risk, fewer offered EBRT+BT than EBRT alone. For every risk group, academic ROs were significantly more likely to offer BT (all p-values<0.05). <1% of respondents reported increased pandemic-related BT usage. CONCLUSIONS: US ROs, particularly in non-academic settings, do not routinely offer BT monotherapy or boost (<50%). Practice patterns were unaffected by COVID-19. Retraining may be critical to increasing utilization.

Promoting Women and Historically Excluded Minorities in Medicine as Essential Leaders of Research.

Women and historically excluded minorities are underrepresented in clinical research. At the ASTRO 2021 annual meeting, the authors reviewed several strategies to improve on this issue. Implementation of such strategies should not only improve their visibility but also provide increased opportunities for their advancement and work in clinical research.

Social determinants of health, workforce diversity, and financial toxicity: A review of disparities in cancer care.

Disparities in cancer care and outcomes between racial and ethnic groups, urban and rural populations, and socioeconomic classes are well documented and represent one of the greatest forms of injustice throughout the United States. Despite the development of increasingly efficacious treatments, survival disparities have widened over time, with known impacts based on both medical factors and social determinants of health including education, neighborhood, factors, and access to care, among others. In this review, we discuss current state of inequities in access to cancer services, treatment-related financial toxicity, and disparities within the oncology workforce, all of which significantly impact the ability of clinicians to provide high quality, equitable, and guideline-compliant care for all people with cancer.

Radiotherapy in Oligometastatic, Oligorecurrent and Oligoprogressive Prostate Cancer: A Mini-Review.

Globally, prostate cancer is one of the most common malignancies affecting men. With the advent of advanced molecular imaging, an increasing number of men are found to have oligometastatic disease (OD) either at primary diagnosis or at the time of biochemical failure. No strict definition exists for OD, with historical and ongoing studies utilizing diverse criteria. There is mounting evidence from many different malignancies that patients with OD have improved outcomes compared to their widely metastatic counterparts. As such, treatment intensification of those with OD or oligoprogressive disease has become an area of intense interest and study. This article will review the biology, evidence and controversy behind the treatment of de novo oligometastatic, oligorecurrent and oligoprogressive prostate cancer.

Racial and Gender Differences in Patient Satisfaction Scores Among Oncologists.

BACKGROUND: Patient satisfaction scores (PSS) have been adopted in health care reimbursement and faculty promotion metrics. Oncology patients face a challenging prognosis, where PSS may be perceived differently. We hypothesized that PSS differed based on gender and racial demographics of oncologists. MATERIALS AND METHODS: This was an institutional review board exempt cross-sectional study utilizing PSS data for outpatient oncologists within a large comprehensive cancer center. Patient demographics included age, gender, race/ethnicity, geographical residence, and disease site. Characteristics of oncologists included gender and race/ethnicity. We used PSS ≥95 to make comparisons. The association between patient and physician characteristics were evaluated using the t test and χ2 test. RESULTS: A total of 15,849 oncology patients were identified between 2011 and 2020. Survey respondents were predominantly female (53.2%), white (93.4%), between 50 and 70 years of age (55.3%), and living in an urban setting (63.6%). There were 303 oncologists with the majority being male (64.4%) and white (58.1%). Compared with white oncologists, Asian and Hispanic oncologists received lower PSS (P=0.001 and 0.0085, respectively). On subset analysis, these differences were significant among patients older than 50 years, living in rural counties, and reporting white or non-Hispanic race/ethnicity, or among patients of either gender (all P<0.05). Patients with genitourinary malignancies provided lower PSS for female oncologists (P=0.005). CONCLUSIONS: Asian and Hispanic oncologists were more likely to receive lower PSS. In addition, female oncologists treating genitourinary malignancies received lower PSS. Appropriate statistical adjustments are needed for PSS among oncologists to account for race, gender, and physician subspecialization to allow for equitable professional opportunities across demographics.

Prospective dual-surrogate validation study of periodic imaging during treatment for accurately monitoring intrafraction motion of prostate cancer patients.

BACKGROUND AND PURPOSE: The goal of this prospective study is to validate the use of periodic imaging during treatment with a fiducial marker detection algorithm using radiofrequency transponders for prostate cancer patients undergoing treatment for radiation therapy. MATERIALS AND METHODS: Ten male patients were enrolled in this study and treated for prostate cancer with implanted electromagnetic monitoring beacons. We evaluated the accuracy and limitations of Intrafraction Motion Review (IMR) by comparing the known locations of the beacons using the electromagnetic monitoring system to the position data reported from IMR images. RESULTS: A total of 4054 images were taken during treatment. The difference in vector magnitude of the two methods is centered around zero (mean: 0.03 cm, SD: 0.16 cm) and Lin's Concordance Correlation Coefficient (CCC) is 0.99 (95% CI: 0.98, 1) overall. The Euclidean distance between the two methods was close to zero (median: 0.09 cm, IQR: 0.06, 0.14 cm). The difference in distance between any two markers was centered around zero (mean: 0.01 cm, SD: 0.12 cm) and Lin's CCC is 0.97 (95% CI: 0.96, 0.98) overall. CONCLUSION: The accuracy of the algorithm for detected markers within the 2D images is comparable to electromagnetic monitoring for fiducial identification when detected. IMR could provide an alternate solution for patients with contraindications of use of an electromagnetic monitoring system and a cost effective alternative to the acquisition of an additional system for patient monitoring, but does not provide data for pre-treatment set-up verification and real-time 3D positioning during treatment.

Smoking Cessation at a Safety-Net Hospital: A Radiation Oncology Resident-Led Quality Improvement Initiative.

PURPOSE: Continued smoking among patients with cancer has been associated with increased toxicities, resistance to treatment, and recurrence. This resident-led quality improvement study attempted to increase smoking cessation by providing free smoking cessation medications in the radiation oncology clinic. METHODS AND MATERIALS: Twenty currently smoking patients with nonmetastatic cancer were prospectively enrolled. First line treatment was protocol-standardized combined nicotine replacement therapy (patches and lozenges). Therapy was initiated before radiation therapy and given for 12 weeks. Patient self-reported tobacco use was assessed at midtreatment, end of 12-week treatment, 3-month follow-up, 6-month follow-up, and 12-month follow-up. RESULTS: Within the initial cohort of 20 patients, average years smoked was 36.3 years (median = 37.5). In addition, 85% had attempted to quit previously. Among patients initially enrolled, 3 did not initiate radiation therapy, and 4 were removed from the study by midtreatment due to noncompliance. Midway through treatment, patients had cut self-reported cigarette use to 31% of baseline. However, 75% or more of patients had smoked within the last week at all timepoints assessed. With further follow-up, the number of cigarettes smoked daily continued to rise, reaching 61% of baseline by the 12-month follow-up. CONCLUSIONS: Patients reduced cigarette consumption, but all patients eventually resumed smoking during the 12-month follow-up. Although it is unfortunate that this study did not result in long-term smoking cessation, the results demonstrate the difficulties faced in helping patients with cancer quit, particularly patients seen at a safety-net hospital. Future efforts could be directed at intensified smoking cessation programs, likely incorporating a more standardized counseling component.

Increasing Radiation Dose to the Thoracic Marrow Is Associated With Acute Hematologic Toxicities in Patients Receiving Chemoradiation for Esophageal Cancer.

Purpose: To test the hypothesis that increasing radiation dose to the thoracic marrow (TM) contributes to the development of hematologic toxicities (HT) in esophageal cancer (EC) patients receiving chemoradiation therapy (CRT). Methods: We identified EC cases treated with curative intent CRT at our institution from 2007 to 2016. The TM was contoured as the union of the vertebral bodies (VB) from T1-L1, the ribs from T1-L1, and the sternum. The TM-mean dose and the TM volume receiving at least 5-50 Gy (V5-V50) were collected. Grade ≥ 3 HT (HT3+) was the primary endpoint. Normal tissue complication probability (NTCP) was evaluated using the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT3+ and dosimetric parameters. Odds ratios (OR) and 95% confidence intervals (CI) are reported with p < 0.05 considered significant. Receiver operating characteristics analysis was used to determine optimal cut points. Results: We identified 137 EC cases, and most received concurrent carboplatin/paclitaxel (N = 83). Median radiation dose was 50.4 Gy (IQR = 50.4-50.4 Gy). The rate of HT3+ was 39.4%. Optimization of the LKB model yielded the results n = 0.70, m = 0.67, and TD50 = 20.1 Gy. The TM-V30 was most strongly associated with HT3+ and on multivariate analysis, patients with TM-V30 ≥ 14% had a 5.7-fold (95% CI 2.42-14.54, p < 0.001) increased odds of HT3+ in the entire cohort and a 4-fold (95% CI 1.54-11.11, p = 0.006) increased odds of HT3+ in the carboplatin/paclitaxel cohort compared to patients with TM-V30 < 14%. Radiation dose to the VB and rib sub-sites of the TM were also associated with HT3+, particularly VB-V40. Conclusion: We found that increasing TM radiation dose was associated with HT3+ in EC patients treated with CRT. Radiation dose to the VB and rib sub-sites were also associated with HT3+. These findings suggest that limiting radiation dose to the TM (or its sub-sites) may be sufficient to decrease HT3+, but further prospective evaluation of these results is needed.

Identifying Clinical Factors Which Predict for Early Failure Patterns Following Resection for Pancreatic Adenocarcinoma in Patients Who Received Adjuvant Chemotherapy Without Chemoradiation.

OBJECTIVES: The role of radiation therapy (RT) in resected pancreatic cancer (PC) remains incompletely defined. We sought to determine clinical variables which predict for local-regional recurrence (LRR) to help select patients for adjuvant RT. MATERIALS AND METHODS: We identified 73 patients with PC who underwent resection and adjuvant gemcitabine-based chemotherapy alone. We performed detailed radiologic analysis of first patterns of failure. LRR was defined as recurrence of PC within standard postoperative radiation volumes. Univariate analyses (UVA) were conducted using the Kaplan-Meier method and multivariate analyses (MVA) utilized the Cox proportional hazard ratio model. Factors significant on UVA were used for MVA. RESULTS: At median follow-up of 20 months, rates of local-regional recurrence only (LRRO) were 24.7%, LRR as a component of any failure 68.5%, metastatic recurrence (MR) as a component of any failure 65.8%, and overall disease recurrence (OR) 90.5%. On UVA, elevated postoperative CA 19-9 (>90 U/mL), pathologic lymph node positive (pLN+) disease, and higher tumor grade were associated with increased LRR, MR, and OR. On MVA, elevated postoperative CA 19-9 and pLN+ were associated with increased MR and OR. In addition, positive resection margin was associated with increased LRRO on both UVA and MVA. CONCLUSIONS: About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation.

Locoregional outcomes in clinical stage IIB breast cancer after neoadjuvant therapy and mastectomy with or without radiation.

Low rates of locoregional recurrence (LRR) in patients with clinical stage IIB breast cancer (cT2N1 or cT3N0) who undergo neoadjuvant therapy (NAT) and mastectomy have been reported. We aimed to quantify the risk of LRR and the relationship between LRR and potential risk factors in this subset of patients. We conducted a retrospective review of 116 patients with clinical IIB breast cancer who underwent NAT followed by mastectomy +/- postmastectomy radiotherapy (PMRT) between 2000 and 2009. We estimated the rate of LRR by cumulative incidence. The effect of prognostic factors was examined by Gray's test and Fine and Gray's test. Median follow-up: 63 months. Median age: 49. 28.4% cT2N1 and 71.6% cT3N0. 62.1% of tumors were ER+, 22.6% HER2+, 19% triple negative (TN). All patients underwent NAT and mastectomy. The majority of patients (87%) received PMRT; 32.3% were treated to chest wall (CW) only, and 67.7% to CW plus supraclavicular (SCV) field. Compared to cT2N1, patients with cT3N0 disease were more likely to be pN0 (60% vs 27%, P = 0.005). There was no significant relationship between risk of LRR and pathologic complete response (pCR), use of PMRT, RT to SCV field, or TN status, but there was higher risk of LRR in cT2N1 than cT3N0 (HR 6.03, P = 0.015). LRR was more common in cT2N1 than in cT3N0 disease, emphasizing the negative prognostic implication of clinically node-positive presentation.

A tissue biomarker-based model that identifies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02.

PURPOSE: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis. EXPERIMENTAL DESIGN: RTOG 92-02 compared external beam radiotherapy (EBRT) to approximately 70 Gy + short-term androgen deprivation therapy (STADT) with EBRT + long-term ADT (LTADT). Immunohistochemical analysis was available for ≥4 biomarkers in 616 of 1,521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of distant metastasis using competing risks hazards regression, adjusting for age, prostate-specific antigen, Gleason score, T stage, and treatment. RESULTS: Modeling identified four biomarkers (Ki-67, MDM2, p16 and Cox-2) that were jointly associated with distant metastasis. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10% (likelihood ratio P < 0.001). Subdivision of the patients into quartiles based on predicted distant metastasis risk identified a high-risk group with 10-year distant metastasis risk of 52.5% after EBRT + STADT and 31% with EBRT + LTADT; associated 10-year prostate cancer-specific mortality (PCSM) risks were 45.9% and 14.5% with STADT and LTADT. CONCLUSION: Four biomarkers were found to contribute significantly to a model that predicted distant metastasis and identified a subgroup of patients at a particularly high risk of both distant metastasis and PCSM when EBRT + STADT was used. LTADT resulted in significant reductions in distant metastasis and improvements in PCSM, and there was a suggestion of greater importance in the very high risk subgroup.

The E2F1/Rb and p53/MDM2 pathways in DNA repair and apoptosis: understanding the crosstalk to develop novel strategies for prostate cancer radiotherapy.

Both the p53- and E2F1-signaling pathways are defective in almost all types of tumors, suggesting very important roles for their signaling networks in regulating the process of tumorigenesis and therapy response. Studies on Radiation Therapy Oncology Group tissue samples have identified aberrant expression of p53, MDM2 (an E3 ubiquitin ligase that targets p53 for proteosomal degradation), and p16 (an upstream regulator of retinoblastoma and hence E2F1 in prostate cancer); abnormal expression of these biomarkers has been associated with clinical outcome after radiotherapy ± androgen deprivation therapy. Although the proapoptotic properties of p53 are well documented, a relatively new aspect of p53 function as an active mediator of prosurvival signaling pathways is now emerging. E2F1 is a transcription factor that possesses both proapoptotic and prosurvival properties. Thus, the role of E2F1 in the process of tumorigenesis versus apoptosis is a contested issue that needs to be resolved. Furthermore, the role of E2F1 in DNA repair is being increasingly recognized. Thus, novel approaches to curb the prosurvival and DNA repair capability of E2F1 while promoting apoptotic function are of interest. In this review, we discuss the challenges involved in targeting the p53/E2F1 pathways and the crosstalk networks, and further propose potential therapeutic strategies for prostate cancer management.