TEAM participation in the irradiation of IROC phantoms for cooperative group clinical trials.

The participation of radiation oncology team members in the irradiation of Imaging and Radiation Oncology Core (IROC) phantom for cooperative group clinical trials is essential to comply with the latest quality management philosophy. Medical dosimetrists are expected to develop treatment plans for the irradiation of IROC phantoms. For advanced treatment techniques, such as three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT), the irradiation of the IROC phantoms serves as quality audit. If successful, the irradiation processes demonstrate that the institution has the knowledge of the protocol, and has the appropriate equipment to comply with the protocol requirements. This article describes three IROC phantoms used for credentialing external beam photon beam therapy, delivered using conventional medical linear accelerators, to the medical dosimetry community. Guidance and strategies for the development of treatment plans are discussed. Our institutional irradiation of the three IROC phantoms, delivered using the Truebeam medical linear accelerator, resulted in consistent dose accuracy to within ±1%. The participation of the team members may reduce the overall published failing rate stated to be about one-third of all participating institutions.

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM). OBJECTIVE: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202). DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated. RESULTS AND LIMITATIONS: With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02). CONCLUSIONS: With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT. PATIENT SUMMARY: In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

Analysis of a Biopsy-Based Genomic Classifier in High-Risk Prostate Cancer: Meta-Analysis of the NRG Oncology/Radiation Therapy Oncology Group 9202, 9413, and 9902 Phase 3 Randomized Trials.

PURPOSE: Decipher is a genomic classifier (GC) prospectively validated postprostatectomy. We validated the performance of the GC in pretreatment biopsy samples within the context of 3 randomized phase 3 high-risk definitive radiation therapy trials. METHODS AND MATERIALS: A prespecified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled in the NRG/Radiation Therapy Oncology Group (RTOG) 9202, 9413, and 9902 phase 3 randomized trials. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays and GC scores were obtained. The primary objective was to validate the independent prognostic ability for the GC for distant metastases (DM), and secondary for prostate cancer-specific mortality (PCSM) and overall survival (OS) with Cox univariable and multivariable analyses. RESULTS: GC scores were obtained on 385 samples, of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9-13). In the pooled cohort, on univariable analysis, the GC was shown to be a prognostic factor for DM (per 0.1 unit; subdistribution hazard ratio [sHR], 1.29; 95% confidence interval [CI], 1.18-1.41; P < .001), PCSM (sHR, 1.28; 95% CI, 1.16-1.41; P < .001), and OS (hazard ratio [HR], 1.16; 95% CI, 1.08-1.22; P < .001). On multivariable analyses, the GC (per 0.1 unit) was independently associated with DM (sHR, 1.22; 95% CI, 1.09-1.36), PCSM (sHR, 1.23; 95% CI, 1.09-1.39), and OS (HR, 1.12; 95% CI, 1.05-1.20) after adjusting for age, Prostate Specific Antigen, Gleason score, cT stage, trial, and randomized treatment arm. GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy, but the absolute improvement in outcome varied by GC risk. CONCLUSIONS: This is the first validation of a gene expression biomarker on pretreatment prostate cancer biopsy samples from prospective randomized trials and demonstrates an independent association of GC score with DM, PCSM, and OS. High-risk prostate cancer is a heterogeneous disease state, and GC can improve risk stratification to help personalize shared decision making.

Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial.

PURPOSE: Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer. PATIENTS AND METHODS: The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT. RESULTS: A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 v 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided P = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.76; 95% CI, 0.58 to 0.99; two-sided P = .043). CONCLUSION: For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.

Risk factors for late bowel and bladder toxicities in NRG Oncology prostate cancer trials of high-risk patients: A meta-analysis of physician-rated toxicities.

PURPOSE: A meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level >20) prostate cancer. METHODS AND MATERIALS: Three NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05. RESULTS: A total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced late grade ≥2 bowel and bladder toxicities, respectively, and 2% and 3% experienced late grade ≥3 bowel and bladder toxicities, respectively. Late grade ≥2 clustered bowel and bladder toxicities were seen in approximately 1% of patients and late grade ≥3 clustered toxicities were seen in 2 patients (<1%). The multivariate analysis showed that patients who received prostate-only RT+HT had a lower risk of experiencing grade ≥2 bowel toxicities than those who received whole-pelvic RT+long-term (LT) HT (hazard ratio: 0.36; 95% confidence interval, 0.18-0.73; P = .0046 and hazard ratio: 0.43; 95% confidence interval, 0.23-0.80; P = .008, respectively). Patients who received whole-pelvic RT had similar chances of having grade ≥2 bowel or bladder toxicities no matter whether they received LT or short-term HT. CONCLUSIONS: Patients with high-risk prostate cancer who receive whole-pelvic RT+LT HT are more likely to have a grade ≥2 bowel toxicity than those who receive prostate-only RT. LT bowel and bladder toxicities were infrequent. Future studies will need to confirm these findings utilizing current radiation technology and patient-reported outcomes.

Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: report of the NRG Oncology RTOG 0517 trial.

BACKGROUND: Skeletal-related events (SREs), common sequelae of metastatic cancer, are reduced by bisphosphonates. In this study, it was postulated that radiopharmaceuticals, added to bisphosphonates, could further decrease the incidence of SREs. METHODS: NRG Oncology RTOG 0517 randomized patients with breast, lung, and prostate cancer and blastic bone metastases to either zoledronic acid (ZA) alone or ZA plus radiopharmaceuticals (Sr-89 or Sm-153). The primary endpoint was time to development of SREs. Secondary objectives included quality of life (QOL), pain control, overall survival (OS), and toxicity. RESULTS: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued between July 2006 and February 2011. The study closed early due to a lower than expected rate of SREs. 52 (42%) patients in the ZA arm and 49 (40%) in the radiopharmaceutical arm experienced an SRE. Median time free of SREs was 29.9 and 27.4 months, respectively (p = 0.84). Median OS in the ZA arm and radiopharmaceutical arms was 32.1 and 26.9 months, respectively (p = 0.37). Cox proportional hazards regression model showed that primary disease site (lung) and number of bone metastases (> 2) had a negative impact on OS (p < 0.0001, p = 0.01, respectively). The addition of radiopharmaceuticals to ZA led to a significant reduction in pain at 1 month based on BPI worst score (p = 0.02). No other group differences were noted for QOL or toxicity. CONCLUSION: The addition of radiopharmaceuticals to bisphosphonates did not alter time to SREs or OS for patients with breast, lung, prostate cancers and blastic bone metastases, although it was associated with significant pain reduction at 1 month. CLINICAL TRIAL REGISTRY: This protocol (RTOG 0517) is registered with ClinicalTrials.gov (NCT00365105), and may be viewed online at http://www.clinicaltrials.gov/ct2/show/NCT00365105?term=RTOG+0517&rank=1 .

External beam planning module of Eclipse for external beam radiation therapy.

Eclipse is a 3-dimensional (3D) treatment planning system for radiation therapy offered by Varian Medical Systems, Inc. The system has the network connectivity for the electronic transfer of image datasets and digital data communication among different equipment. The scope of this project for this special issue of Medical Dosimetry on 3D treatment planning systems is the assessment of planning tools in the external beam planning module of Eclipse to generate optimized treatment plans for patients undergoing external beam radiation therapy. This treatment planning system is relatively mature to be able to generate (1) simple treatment plans, (2) conformal radiation therapy plans, (3) static intensity-modulated radiation therapy (IMRT) plans, (4) volumetric-modulated arc therapy (VMAT) plans, and (5) treatment plans for electron beam therapy. The treatment planning tools are relatively plentiful to assist in the radiation therapy treatment planning. Some new features have been incorporated in the latest version and are helpful for making high-quality treatment plans. However, the location of the tools is not intuitive, and hence, familiarity with the user interface is essential to the efficient use of the treatment planning system. In addition, there are a number of dose algorithms available for the computation of dose distributions. The understanding of each dose computation algorithm is essential for the optimal use of this treatment planning system.

Clinical implementation of radiosurgery using the Helical TomoTherapy unit.

The American Society of Radiation Oncology has recently recommended the use of radiosurgery to manage brain metastases. For such a recommendation to be implemented in a widespread manner, radiosurgery must be accessible at community radiation therapy facilities. The work presented here describes our clinical experience in the implementation of radiosurgery using a Helical TomoTherapy unit. Helical TomoTherapy is a unique dose-delivery system designed to perform intensity-modulated radiation therapy (IMRT). The system built on the ring-based gantry has the tight machine tolerances required for radiosurgery. A frameless system consisting of a thermoplastic mask and a noninvasive "stereotactic radiosurgery (SRS)-stereotactic radiotherapy (SRT)" fixation device is used for patient immobilization. Treatment planning is performed using the TomoHD treatment planning system designed for IMRT. The image-guidance system on the Helical TomoTherapy is used for patient localization. Our clinical experience demonstrated that the radiosurgery procedure can be streamlined as we do for IMRT patients. The treatment time of about 10 minutes is comparable with that for IMRT patients. The same patient-specific quality assurance for IMRT is used for radiosurgery. As demonstrated, SRS using Helical TomoTherapy is not a whole-day event, unlike SRS using other dose-delivery systems or SRS performed in the past.

Effect of Long-Term Hormonal Therapy (vs Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate-Risk Prostate Cancer Patients Treated on NRG Oncology RTOG 9202.

PURPOSE: NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20 ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). METHODS AND MATERIALS: An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10 ng/mL, and Gleason score = 7 or cT2 disease, PSA 10-20 ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. RESULTS: With over 11 years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. CONCLUSION: LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset.

Total Mastectomy or Breast Conservation Therapy? How Radiation Oncologist Accessibility Determines Treatment Choice and Quality: A SEER Data-base Analysis.

Mastectomy and breast conservation therapy (BCT) are equivalent in survival for treatment of early stage breast cancer. This study evaluated the impact of radiation oncologist accessibility on choice of breast conserving surgery (BCS) versus mastectomy, and the appropriate receipt of radiotherapy after BCS. In the National Cancer Institute Survival, Epidemiology, and End Results data base, the authors selected breast cancer cases from 2004 to 2008 with the following criteria: T2N1M0 or less, lobular or ductal histology, and treatment with simple or partial mastectomy. We combined the Health Resources and Services Administration Area Resource File to define average radiation oncologist density (ROD) by county over the same time period. We evaluated tumor characteristics, demographic information, and ROD with respect to BCS rates and receipt of radiation therapy after BCS in univariable and multivariable analyses. In 118,773 cases analyzed, mastectomy was performed 33.2% of the time relative to BCS. After adjustment for demographic and tumor variables, the odds of having BCS versus mastectomy were directly associated with ROD (multiplicative change in odds for a single unit increase in ROD [95% CI] = 1.02 [1.01-1.03]; p < 0.001). Adjuvant radiation therapy was not administered in 28.2% of BCS cases. When adjusting for demographic and tumor variables, the odds of having BCS without adjuvant radiation were inversely associated with ROD (0.95 [0.94-0.97]; p < 0.001). We observed a direct relationship between ROD and BCS rates independent of demographic and tumor variables, and an inverse trend for omission of radiotherapy after BCS. Access to radiation oncologists may represent an important factor in surgical choice and receiving appropriate BCT in early stage breast cancer.

Vitamin D deficiency is widespread in cancer patients and correlates with advanced stage disease: a community oncology experience.

The purpose of this study was to correlate serum vitamin D levels with potential clinical variables and to determine the extent of vitamin D deficiency in a large, outpatient oncology practice. One hundred ninety-five consecutive patients referred for consultation at a community radiation oncology center from October 8, 2008 to March 17, 2010 had vitamin D levels ordered. Patients who were deficient in vitamin D were treated with replacement therapy. Demographic and medical data were collected prospectively and subsequently analyzed. Pretreatment baseline patient and tumor characteristics were evaluated with respect to vitamin D concentrations. One hundred and sixty patients were analyzed. A total of 74% of patients had 25-hydroxyvitamin D concentrations considered either deficient (<20 ng/mL) or suboptimal (20-30 ng/mL). Replacement therapy raised serum vitamin D levels by an average of 15 ng/mL (95% CI = 11-18, P < 0.01). Lower than median serum vitamin D levels were associated with stage III disease in univariate analysis [OR = 2.6 (95% CI = 1.1-6.2), p = 0.04] as well as multivariate analysis adjusted for age, sex, body mass index, and season of draw [OR = 3.3 (95% CI = 1.1-9.7), P = 0.03]. Three-quarters of patients in our series had suboptimal or deficient circulating concentrations of 25-hydroxyvitamin D. Low serum vitamin D levels, independent of age, sex, and body mass index, predicted advanced stage disease.

Serum vitamin D levels among patients in a clinical oncology practice compared to primary care patients in the same community: a case-control study.

Objectives Low serum vitamin D levels have been associated with risk for certain malignancies, but studies have not directly analysed levels between community oncology and primary care practices. The purpose of this study was to compare serum vitamin D levels in patients at a community oncology practice with non-cancer patients at a primary care practice. Design Retrospective case-control study. 25-Hydroxyvitamin D levels were ordered for screening in both cancer and non-cancer patients. Levels were compared in univariate and multivariate analyses adjusted for age, body mass index and season of blood draw. Setting A community-based radiation oncology centre and a community-based primary care practice: both located in Northeastern Pennsylvania, USA. Participants 170 newly diagnosed cancer patients referred for initial consultation at the community oncology centre from 21 November 2008 to 18 May 2010, and 170 non-cancer patients of the primary care practice who underwent screening for hypovitaminosis D for the first time from 1 January 2009 to 31 December 2009. Primary and secondary outcome measures The primary outcome measure was mean serum vitamin D level, and the secondary outcome measures were frequencies of patients with vitamin D levels <20 ng/ml and levels <30 ng/ml. Results The oncology patients had a significantly lower mean serum vitamin D level (24.9 ng/ml) relative to a cohort of non-cancer primary care patients (30.6 ng/ml, p<0.001) from the same geographical region. The relationship retained significance after adjustment for age, body mass index and season of blood draw in multivariate analysis (p=0.001). Levels <20 and <30 ng/ml were more frequent in the oncology patients (OR (95% CI)=2.59 (1.44 to 4.67) and 2.04 (1.20 to 3.46), respectively) in multivariate analysis. Conclusions Cancer patients were found to have low vitamin D levels relative to a similar cohort of non-cancer primary care patients from the same geographical region.

Effect of family history on outcomes in patients treated with definitive brachytherapy for clinically localized prostate cancer.

PURPOSE: To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. METHODS AND MATERIALS: A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). RESULTS: A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. CONCLUSIONS: This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

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.

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.

Low-dose rate prostate brachytherapy is well tolerated in patients with a history of inflammatory bowel disease.

PURPOSE: We report on the follow-up of 24 patients with a prior history of inflammatory bowel disease (IBD) treated with brachytherapy for early-stage prostate cancer. METHODS AND MATERIALS: Twenty-four patients with a history of inflammatory bowel disease (17 with ulcerative colitis (UC), 7 with Crohn's disease [CD]) underwent prostate brachytherapy between 1992 and 2004. Fifteen patients were treated with I-125 implantation and 6 patients were treated with Pd-103 alone or in combination with 45 Gy external beam radiation. Charts were reviewed for all patients, and all living patients were contacted by phone. National Cancer Institute common toxicity scores for proctitis were assigned to all patients. Actuarial risk of late toxicity was calculated by the Kaplan-Meier method. Statistical analysis was performed using SPSS software. Follow-up ranged from 3 to 126 months (median, 48.5 months; mean, 56.8 months). RESULTS: None of the patients experienced Grade 3 or 4 rectal toxicity. Four patients experienced Grade 2 late rectal toxicity. The 5-year actuarial freedom from developing late Grade 2 rectal toxicity was 81%. At a median follow-up of 48.5 months, 23 patients were alive and had no evidence of disease with a median prostate-specific antigen for the sample of 0.1 ng/mL (range, <0.05-0.88 ng/mL). One patient died of other causes unrelated to his prostate cancer. CONCLUSIONS: Prostate brachytherapy is well tolerated in patients with a history of controlled IBD. Therefore, brachytherapy should be considered a viable therapeutic option in this patient population.

Tracheomalacia secondary to obstructive sleep apnea.

Tracheomalacia (TM) is abnormal flaccidity of the trachea caused by inadequate cartilaginous support by the C-shaped tracheal rings. This defect generally results in various degrees of dynamic narrowing of the airway lumen. TM usually presents with expiratory stridor, wheeze, and respiratory obstruction. TM is usually associated with tracheoesophageal fistula and esophageal atresia or with other thoracic lesions of vascular rings and tumors. We report a well-documented case of a 20-month-old boy who presented to our institution with a severe history of obstructive sleep apnea and adenotonsillar hypertrophy. On direct laryngoscopy/bronchoscopy, severe TM was noted. Tonsillectomy and adenoidectomy was performed, and by the 37th postoperative day, the TM had completely resolved. We review the literature, discuss the differential diagnosis and clinical evaluation, and propose a new pathophysiological mechanism by which obstructive sleep apnea causes TM.