Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Racial and Ethnic Disparities in Prostate Cancer Outcomes in the Veterans Affairs Health Care System.

Importance: Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans. Objective: To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital. Design, Setting, and Participants: This retrospective cohort study included 7 889 984 veterans undergoing routine care in VA hospitals nationwide from 2005 through 2019 (incidence cohort). The age-adjusted incidence of localized and de novo metastatic PCa was estimated. Treatment response was evaluated, and PCa-specific outcomes were compared between African American veterans and White veterans. Residual disparity in PCa outcome, defined as the leftover racial and ethnic disparity in the outcomes despite equal response to treatment, was estimated. Exposures: Self-identified African American (or Black) and White race and ethnicity. Main Outcomes and Measures: Time to distant metastasis following PCa diagnosis was the primary outcome. Descriptive analyses were used to compare baseline demographics and clinic characteristics. Multivariable logistic regression was used to evaluate race and ethnicity association with pretreatment clinical variables. Multivariable Cox regression was used to estimate the risk of metastasis. Results: Data from 7 889 984 veterans from the incidence cohort were used to estimate incidence, whereas data from 92 269 veterans with localized PCa were used to assess treatment response. Among 92 269 veterans, African American men (n = 28 802 [31%]) were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) and had higher prostate-specific antigen levels (>20 ng/mL) at the time of diagnosis compared with White men (n = 63 467; [69%]). Consistent with US population-level data, African American veterans displayed a nearly 2-fold greater incidence of localized and de novo metastatic PCa compared with White men across VA centers nationwide. Among veterans screened for PCa, African American men had a 29% increased risk of PCa detection on a diagnostic prostate biopsy compared with White (hazard ratio, 1.29; 95% CI, 1.27-1.31; P < .001). African American men who received definitive primary treatment of PCa experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; P < .001). However, African American men who received nondefinitive treatment classified as "other" were more likely to develop metastasis (adjusted hazard ratio, 1.29; 95% CI, 1.17-1.42; P < .001). Using the actual rate of metastasis from veterans who received definitive primary treatment, a persistent residual metastatic burden for African American men was observed across all National Comprehensive Cancer Network risk groups (low risk, 4 vs 2 per 100 000; intermediate risk, 13 vs 6 per 100 000; high risk, 19 vs 9 per 100 000). Conclusions and Relevance: This cohort analysis found significant disparities in the incidence of localized and metastatic PCa between African American veterans and White veterans. This increased incidence is a major factor associated with the residual disparity in PCa metastasis observed in African American veterans compared with White veterans despite their nearly equal response to treatment.

Late Feeding Tube Dependency in Head and Neck Cancer Patients Treated with Definitive Radiation Therapy and Concurrent Systemic Therapy.

Objective The study aimed to evaluate the impact of late swallowing dysfunction leading to percutaneous endoscopic gastrostomy (PEG) tube dependence on the overall survival (OS) in a cohort of locally advanced head and neck cancer patients treated and cured with definitive radiotherapy (RT) and concurrent systemic therapy (CST).  Materials and methods A total of 62 patients with locally advanced head and neck cancer were included in the analysis based on the following selection criteria: stage III, IVA, or IVB disease, treated with definitive RT and CST, no major head and neck surgery, no evidence of local or distant recurrent disease, and at least one post-RT modified barium swallow study. Patients were classified as PEG dependent or PEG independent at the time of the last follow-up. Estimates of OS were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to evaluate the impact of various clinical factors on OS. Results The median follow-up was 48 months (range: 7.6-235 months). The five-year OS was 64.3% in the PEG-dependent group and 86.1% in the PEG-independent group (p=0.022). Age over 70 at diagnosis was also associated with poorer OS (p=0.044). On univariate analysis, PEG dependency maintained a significantly worse OS (hazard ratio [HR]: 2.59; 95% confidence interval [CI]: 1.11-5.99, p=0.028). On multivariate analysis, PEG dependency (HR: 4.25; 95% CI: 1.33-13.62; p=0.015), advanced N stage (HR: 4.74; 95% CI: 1.17-19.26, p=0.035), and older age at diagnosis (HR: 4.37; 95% CI: 1.21-15.84; p=0.025) were significantly associated with worse OS. Conclusions Late PEG dependency is associated with poor OS in head and neck cancer patients cured with definitive RT and CST. Interventions designed to help head and neck cancer patients maintain swallowing function may result in improved outcomes.

Predicting the risk of secondary lung malignancies associated with whole-breast radiation therapy.

PURPOSE: The risk of secondary lung malignancy (SLM) is a significant concern for women treated with whole-breast radiation therapy after breast-conserving surgery for early-stage breast cancer. In this study, a biologically based secondary malignancy model was used to quantify the risk of secondary lung malignancies (SLMs) associated with several common methods of delivering whole-breast radiation therapy (RT). METHODS AND MATERIALS: Both supine and prone computed tomography simulations of 15 women with early breast cancer were used to generate standard fractionated and hypofractionated whole-breast RT treatment plans for each patient. Dose-volume histograms (DVHs) of the ipsilateral breast and lung were calculated for each patient on each plan. A model of spontaneous and radiation-induced carcinogenesis was used to determine the relative risks of SLMs for the different treatment techniques. RESULTS: A higher risk of SLMs was predicted for supine breast irradiation when compared with prone breast irradiation for both the standard fractionation and hypofractionation schedules (relative risk [RR] = 2.59, 95% confidence interval (CI) = 2.30-2.88, and RR = 2.68, 95% CI = 2.39-2.98, respectively). No difference in risk of SLMs was noted between standard fractionation and hypofractionation schedules in either the supine position (RR = 1.05, 95% CI = 0.97-1.14) or the prone position (RR = 1.01, 95% CI = 0.88-1.15). CONCLUSIONS: Compared with supine whole-breast irradiation, prone breast irradiation is associated with a significantly lower predicted risk of secondary lung malignancy. In this modeling study, fractionation schedule did not have an impact on the risk of SLMs in women treated with whole-breast RT for early breast cancer.

Predictors of metastatic disease after prostate brachytherapy.

PURPOSE: To identify predictors of metastatic disease after brachytherapy treatment for prostate cancer. METHODS AND MATERIALS: All patients who received either brachytherapy alone (implant) or brachytherapy in combination with external beam radiation therapy for treatment of localized prostate cancer at The Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of 2 years were included. Univariate and multivariable analyses were performed on the following variables: risk group, Gleason score (GS), clinical T stage, pretreatment prostate-specific antigen level, post-treatment prostate-specific antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external beam radiation therapy), treatment era, total biological effective dose, use of androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and greater than 360 days. RESULTS: We included 1,887 patients in this study. Metastases developed in 47 of these patients. The 10-year freedom from distant metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was 6 years (range, 2-15 years). The only two significant predictors of metastatic disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of 8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p < 0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to patients presenting with higher-grade disease in more recent years was observed. CONCLUSIONS: GS and post-treatment PSA-DT are both statistically significant independent predictors of metastatic disease. Patients with a high GS and/or short PSA-DT have a higher likelihood of developing metastatic disease and should be considered for systemic therapy.

Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer.

BACKGROUND: The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. METHOD: Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m²), HU (500 mg twice daily), and cetuximab (250 mg/m²). RESULTS: From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≥4 adverse events. CONCLUSIONS: The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer.

Long-term outcome and toxicity of salvage brachytherapy for local failure after initial radiotherapy for prostate cancer.

PURPOSE: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. METHODS AND MATERIALS: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with (103)Pd or (125)I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. RESULTS: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade > or = 2 toxicity (p = 0.03). CONCLUSION: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

Young men have equivalent biochemical outcomes compared with older men after treatment with brachytherapy for prostate cancer.

PURPOSE: To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer. METHODS AND MATERIALS: From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy +/- hormone therapy (HT) +/- external beam radiotherapy and underwent > or = 2 years of follow-up. Patients were stratified on the basis of age: < or = 60 (n = 378) and >60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF). RESULTS: Median follow-up was 68 months (range, 24-180) for men < or = 60 years and 66 months (range, 24-200) for men >60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Men < or = 60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was not (p = 0.665). CONCLUSION: Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer.

Concurrent chemotherapy and radiotherapy for head and neck cancer.

Head and neck cancer is best managed in a multidisciplinary setting. Surgery, radiation therapy, chemotherapy and, more recently, biologic therapy are often employed in various combinations in an attempt to eradicate both clinically apparent and occult disease. The goals of treatment include maximizing tumor control while maintaining function and quality of life. Most patients present with locally advanced disease, and multimodality organ-conserving therapy is often employed for these patients based on the results of multiple Phase III clinical trials. This article focuses on the rationale and evidence supporting the use of concurrent chemotherapy and radiation therapy in the management of locally advanced head and neck cancers.

Radiation dose predicts for biochemical control in intermediate-risk prostate cancer patients treated with low-dose-rate brachytherapy.

PURPOSE: To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer. METHODS AND MATERIALS: From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of <0.05 was considered significant. RESULTS: Overall, the actuarial FFbF at 10 years was 86%. Dose (BED <150 Gy(2) vs. >or=150 Gy(2)) was the only significant predictor of FFbF (p < 0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF. CONCLUSIONS: Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer.

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.

Correlation of positron emission tomography standard uptake value and pathologic specimen size in cancer of the head and neck.

PURPOSE: To correlate positron emission tomography (PET) standard uptake value (SUV) with pathologic specimen size in patients with head-and-neck cancers. METHODS AND MATERIALS: Eighteen patients with Stage II-IVB head-and-neck cancer with 27 tumors who underwent PET and computed tomography (CT) imaging of the head and neck followed by surgical resection were selected for this study. Various SUV thresholds were examined, including the software default (SUV(def)), narrowing the window by 1 standard deviation (SD) of the maximum (SUV-1SD), and SUV cutoff values of 2.5 or greater (SUV2.5) and 40% or greater maximum (SUV40). Volumetric pathologic data were available for 12 patients. Tumor volumes based on pathologic examination (gold standard), CT, SUV(def), SUV-1SD, SUV2.5, and SUV40 were analyzed. RESULTS: PET identified five tumors not seen on CT. The sensitivity of PET for identifying primary tumors was 94% (17 of 18). The Sensitivity of PET for staging the neck was 90% (9 of 10), whereas the specificity was 78% (7 of 9). The SUV2.5 method was most likely to overestimate tumor volume, whereas SUV(def) and SUV-1SD were most likely to underestimate tumor volume. CONCLUSIONS: The PET scan provides more accurate staging of primary tumors and nodal metastases for patients with advanced head-and-neck cancer than CT alone. Compared with the gold standard, significant variability exists in volumes obtained by using various SUV thresholds. A combination of clinical, CT, and PET data should continue to be used for optimal treatment planning. The SUV40 method appears to offer the best compromise between accuracy and reducing the risk of underestimating tumor extent.

TGFB1 single nucleotide polymorphisms are associated with adverse quality of life in prostate cancer patients treated with radiotherapy.

PURPOSE: To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. METHODS AND MATERIALS: A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: (1) prospective decline in erectile function, (2) urinary quality of life, and (3) rectal bleeding. Median follow-up was 51.3 months (range, 12-138 months; SD, 24.4 months). RESULTS: Those patients who possessed either the T/T genotype at position -509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) (p = 0.02). In addition, patients with the -509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) (p = 0.05). CONCLUSIONS: Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy.

PURPOSE: To examine whether possession of genetic alterations in the ATM (ataxia telangiectasia) gene is associated with rectal bleeding in a dose-dependent and volume-dependent manner. METHODS AND MATERIALS: One hundred eight prostate cancer patients who underwent brachytherapy using either an (125)I implant, a (103)Pd implant, or the combination of external beam radiotherapy with a (103)Pd implant and had a minimum of 1 year follow-up were screened for DNA sequence variations in the 62 coding exons of the ATM gene using denaturing high-performance liquid chromatography. Rectal dose was reported as the volume (in cubic centimeters) of rectum receiving the brachytherapy prescription dose. The two-sided Fisher exact test was used to compare differences in proportions. RESULTS: A significant correlation between the presence of any ATM sequence alteration and Grade 1 to 2 proctitis was obtained when the radiation dose to rectal tissue was quantified. Rectal bleeding occurred in 4 of 13 patients (31%) with a variant versus 1 of 23 (4%) without a genetic alteration for patients who had <0.7 cm(3) of rectal tissue receiving the implant prescription dose (p = 0.05). Of patients in whom 0.7-1.4 cm(3) of the rectum received the implant prescription, 4 of 11 (36%) with an ATM alteration exhibited Grade 1 to 2 proctitis, whereas 1 of 21 (5%) without a variant (p = 0.04) developed this radiation-induced late effect. CONCLUSIONS: The possession of genetic variants in the ATM gene is associated with the development of radiation-induced proctitis after prostate cancer radiotherapy for patients who receive the full prescription dose to either a low or a moderate volume of rectal tissue.

Is seminal vesicle implantation with permanent sources possible? A dose-volume histogram analysis in patients undergoing combined 103Pd implantation and external beam radiation for T3c prostate cancer.

PURPOSE: Combined brachytherapy and external beam radiation therapy (EBRT) of the prostate and seminal vesicles (SVs) is evolving as a successful treatment option for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV was performed in patients with biopsy-positive SV who received implantation of the SV and prostate. METHODS AND MATERIALS: Fifteen consecutive patients with high-risk features (prostate-specific antigen [PSA] > or =10 ng/mL, Gleason score > or = 7, or clinical stage > or = T2b) and a positive SV biopsy were treated with a 103Pd implant of the prostate and SV followed by 45Gy of EBRT. DVHs were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 3-mm-thick volumes identified as SV1, SV2, SV3, SV4, SV5, and SV6 starting from the junction of the prostate and SV and extending distally. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH). RESULTS: The median number of seeds implanted into the prostate and the SVT was 59 (41-94) and 9 (4-21), respectively. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, SV5, and SV6 were 103.2 (87.4-137.1), 46.2 (4.0-69.4), 76.0 (31.2-147), 63.4 (25.1-145.9), 49.7 (15.3-118), 27.4 (9.3-135.1), 14.2 (2.3-100.3), and 3.9 (0-61.5) Gy, respectively. CONCLUSIONS: Implantation of the SV using a real-time intraoperative approach is technically feasible and results in higher doses to the SV than has been reported with implantation of the prostate alone. Although dose distribution in the SV can be variable and unpredictable, these doses, in combination with 45 Gy of EBRT, may be adequate to control disease spread in these organs.