Five-year potency preservation after iodine-125 prostate brachytherapy.

BACKGROUND: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with (125)I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0-3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation. RESULTS: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy. CONCLUSIONS: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.

A rare instance of latent systematic error in volumetric-modulated arc therapy with field-extended multi-isocentre irradiation leading to a serious dose-delivery accident.

Volumetric-modulated arc therapy (VMAT) with field-extended multi-isocentre irradiation (VMAT-FEMII) is an effective irradiation technique, particularly for large planning target volumes in the craniocaudal direction. A variety of treatment planning techniques have been reported to reduce the dosimetric impact. However, there is no guarantee that unexpected latent systematic errors would not occur. Herein, we report the experience with a rare case that could have led to a serious VMAT-FEMII-related accident. A patient with uterine cervical carcinoma was scheduled for VMAT-FEMII to the whole pelvis and the para-aortic lymph node region. A combination of the two sets of field groups with different isocentres was planned: one to cover the para-aortic lymph nodes and the other to cover the whole pelvis. Measurements based on the pretreatment dose delivery quality assurance (QA) revealed an unexpected overdose of >20% in the field overlap region. This overdose phenomenon is not reflected in the calculated dose distribution in the radiotherapy treatment planning system. Therefore, the plan was altered; a homogeneous dose distribution inside the dose junction was achieved. Several analyses were performed to elucidate the overdosing phenomenon. However, no conclusive answer was found to why non-reflection at the calculated dose distribution was found. The limitations to VMAT-FEMII are primarily related to systematic errors in the positional setup from patient-derived and/or mechanical sources. However, this report highlights a rare case of overdosing caused by inverse optimization and dose calculation. We recommend checking the aperture status of the jaw and multi-leaf collimator at each control point of the treatment plan and using a high-resolution image measurement system on a VMAT-FEMII QA to confirm the dose junction status.

Comparison of preplanning and intraoperative planning for I-125 prostate brachytherapy.

OBJECTIVE: To compare two widely used permanent prostate brachytherapy techniques, preplanning and intraoperative planning, based on postimplant dosimetry, toxicity and biochemical outcomes. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with permanent interstitial implantation. The first 227 consecutive men were treated with the preplanning technique, followed by 438 men treated with the intraoperative technique. Late toxicity was scored by the Common Terminology Criteria for Adverse Events v.4.0. Biochemical failure was defined as a prostate-specific antigen increase of more than 2 ng/ml above the nadir value excluding a benign bounce. Univariate and multivariate analyses were performed to identify the variables associated with biochemical failure-free survival. RESULTS: Postimplant target coverage was similar in the two groups, with a small difference in risk organ doses. Mean V100 was 96.3 vs. 96.7% (P = 0.205), D90 was 119.6 vs. 119.4% (P = 0.884), urethral D10 was 157.5 vs. 146.1% (P = 0.010), rectal V100 was 0.57 vs. 0.43 cc (P = 0.002) in the preplanning and intraoperative planning groups, respectively. Acute and late Grade 3 genitourinary and gastrointestinal toxicities were <1% for both methods. The 5-year biochemical failure-free survival rate was 95.4% for the preplanning and 94.0% for the intraoperative planning group (P = 0.776). Multivariate analysis revealed Gleason score, biopsy positive rate and V100 to be predictors of biochemical failure-free survival, while the planning technique was not significant. CONCLUSION: This large-scale analysis of high-quality implants revealed similar postimplant dosimetry, toxicity profiles and biochemical failure-free survival for the preplanning and intraoperative planning methods.

Dosimetric comparison of rectal dose-reductive techniques in intra-cavitary brachytherapy for cervical cancer: A retrospective analysis.

Purpose: Rectal complications in radiotherapy for cervical cancer can highly affect quality of life and correlate with rectal dose. Vaginal gauze packing (VP) and rectal retraction (RR) are widely used for rectal dose reduction in high-dose-rate brachytherapy. We aimed to perform a dosimetric comparison of these two methods for three-dimensional image-guided adaptive brachytherapy. Material and methods: We retrospectively examined 50 patients with cervical cancer treated with definitive radiotherapy, including intra-cavitary brachytherapy, performed with VP and RR. We extracted two fractions for each patient: one fraction with VP and the next fraction with RR, and then compared dose-volume parameters. In total, 50 fractions each were analyzed in VP and RR groups. Dose to 90% (D90) of high-risk clinical target volume (HR-CTV), and minimum dose to most exposed 2.0 cm3 of other organs at risk (D2cm3) for the rectum and bladder were determined from planning computed tomography. Results: There were no significant differences between VP and RR in D90 of HR-CTV (mean: 7.479 Gy and 7.652 Gy, respectively, p = 0.172). The D2cm3 values for the rectum (mean: 4.234 Gy vs. 4.627 Gy, p = 0.008) and bladder (mean: 5.959 Gy vs. 6.690 Gy, p < 0.001) were significantly lower with VP compared with RR. Conclusions: VP reduced the dose to the rectum and bladder when compared with RR without impairing the dose to CTV.

Time to achieve a prostate-specific antigen nadir of ≤0.2 ng/mL and related factors after permanent prostate brachytherapy.

PURPOSE: The purpose of this study was to identify the time to achieve a prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL and the related factors to achieve this goal. MATERIALS AND METHODS: We retrospectively reviewed 2218 Japanese prostate cancer patients who received 125I brachytherapy with or without external beam radiotherapy between 2003 and 2013 at one institution. Among them, patients followed up for ≥72 months and without luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist were included (total of 1089 patients). The time to a PSA nadir of ≤0.2 ng/mL (months) was defined as the time between the date of implantation and the first time the lowest PSA value reached ≤0.2 ng/mL. Biochemical recurrence (BCR) was determined using the Phoenix definition. Multivariate linear regression analysis was performed to detect the related factors to achieve this nadir. RESULTS: We assigned 409, 592, and 88 patients to the low-, intermediate-risk, and high-risk groups, respectively. The median followup time was 9.5 years. The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 (95% confidence interval: 42.3-45.7) months. The percentage of patients that achieved the nadir was 89.1%. BCR was noted in 107 (9.8%) patients. In the multivariate analysis of patients without BCR, younger age, larger prostate volume at implantation, higher initial PSA level, and monotherapy were significantly associated with longer time to achieve the PSA nadir. CONCLUSION: The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 months. Some patients, however, may require a lengthy period of time to do so.

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score-matched analysis.

PURPOSE: The purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. METHODS AND MATERIALS: Overall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan-Meier curves, and predictors were identified using Cox proportional hazards regression models. RESULTS: After propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58-4.03) and ADT use (HR: 0.55, 95% CI: 0.34-0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16-0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08-1.16) and comorbidities (HR: 1.56, 95% CI: 1.04-2.34) were associated with all-cause mortality. CONCLUSIONS: A risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

A multidisciplinary approach to soft-tissue sarcoma of the extremities.

INTRODUCTION: Soft-tissue sarcoma (STS) denotes a group of rare and highly heterogeneous malignant tumors of mesenchymal origin. Accurate histological diagnosis is critical for selecting appropriate treatment. Complete tumor resection is the primary treatment for STS, and the efficacies of radiotherapy and chemotherapy have been tested in the adjuvant setting to improve oncological outcomes. Because most STS lesions arise in the extremities, preserving limb function and managing limb impairment after radical local treatment represent significant challenges. AREAS COVERED: This article reviews the current front-line treatments for patients with extremity STS and discusses the multidisciplinary team-based efforts needed to improve oncological outcomes and survivorship. EXPERT OPINION: Given the rarity, variety, and complexity of STS, a multidisciplinary approach involving experts in various disciplines is vital for improving outcomes in patients ranging from diagnosis to survivorship. A major challenge is building a sustainable system in each region permitting all patients with extremity STS to be treated at high-volume centers with multidisciplinary teams dedicated to this rare and complex disease.

Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Development and Validation of a Pretreatment Nomogram.

INTRODUCTION: In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. METHODS AND MATERIALS: A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count nadir during chemoradiation therapy of <0.2 × 103/µL. Multivariable logistic regression analysis was used to create a prediction model for grade 4 lymphopenia in the development set, which was internally validated using bootstrapping and externally validated by applying the model to the validation set. The model was presented as a nomogram yielding 4 risk groups. RESULTS: Among 860 included patients, 322 (37%) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower body mass index, photon- rather than proton-based therapy, and lower baseline absolute lymphocyte count were predictive in the final model (corrected c-statistic, 0.76). External validation in 144 patients, among whom 58 (40%) had grade 4 lymphopenia, yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10%, 24%, 43%, and 70%, respectively. CONCLUSIONS: A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiation therapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.

Lymphocyte-Sparing Effect of Proton Therapy in Patients with Esophageal Cancer Treated with Definitive Chemoradiation.

PURPOSE: To assess whether radiation treatment modality with proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) is associated with lymphopenia in patients treated with definitive chemoradiation for esophageal cancer. METHODS AND MATERIALS: Patients with esophageal cancer treated with bimodality therapy (n = 448) between 2004 and 2016 were retrospectively reviewed. Patients treated with PBT were matched by propensity score with those treated with IMRT, based on key patient and disease factors, and stratified by clinical disease stage. Patients who developed early, distant metastatic disease within 1 month of completing radiation were excluded. Univariable and multivariable logistic regression were used to identify variables associated with increased risk of grade 4 lymphopenia. Multivariable Cox proportional hazards regression was used to assess factors associated with overall survival, disease-free survival, and locoregional relapse-free survival. RESULTS: Patients who had IMRT and PBT matched by propensity score (n = 220) were not different with respect to age, sex, stage, performance status, tumor location, histology, tumor target volume, or induction chemotherapy. Treatment with IMRT, compared with PBT (odds ratio [OR], 2.13; 95% confidence interval [95% CI], 1.19-3.81; P = .01), increased age (OR, 1.039/y increase; 95% CI, 1.003-1.076; P = .03), and greater planning target volume (OR, 3.47 per 1-unit increase in log (planning target volume); 95% CI, 1.67-7.21; P < .001), was associated with increased risk of grade 4 lymphopenia. Radiation modality was associated with lymphocyte reduction in patients with tumors in the lower esophagus (P = .005) but not for those with tumors in the upper or middle esophagus (P = 0.32). CONCLUSIONS: In patients with esophageal cancer treated with definitive chemoradiation, PBT reduces the risk of severe, treatment-related lymphopenia, particularly in tumors of the lower esophagus.

Predictive factors of long-term rectal toxicity following permanent iodine-125 prostate brachytherapy with or without supplemental external beam radiation therapy in 2216 patients.

PURPOSE: We analyzed factors associated with rectal toxicity after iodine-125 prostate brachytherapy (BT) with or without external beam radiation therapy (EBRT). METHODS AND MATERIALS: In total, 2216 prostate cancer patients underwent iodine-125 BT with or without EBRT between 2003 and 2013. The median followup was 6.9 years. Cox proportional hazards modeling was used for univariate and multivariate analyses to assess clinical and dosimetric factors associated with rectal toxicity. Dosimetric parameters from 1 day after implantation (Day 1) and 1 month after implantation (Day 30) were included in the analyses. RESULTS: The 7-year cumulative incidence of Grade 2 or higher rectal toxicity was 5.7% in all patients. The multivariate analysis revealed that antiplatelet or anticoagulant therapy, neoadjuvant androgen deprivation therapy, treatment modality, Day 1 rectal volume receiving 100% of the prescribed dose (RV100), and the Day 30 minimal percent of the prescribed dose delivered to 30% of the rectum (RD30) were associated with rectal toxicity. Day 1 RV100 was a common predictor in both BT-alone and the BT + EBRT groups. The 5-year cumulative incidence of Grade 2 or higher rectal toxicity was 12.6%, 5.9%, and 1.7% for BT + 3-dimensional conformal radiation therapy, BT + intensity-modulated radiation therapy, and the BT-alone groups, respectively (p < 0.001). CONCLUSIONS: Rectal dosimetric parameters in BT were associated with late rectal toxicity. Although the risk of rectal toxicity was higher when EBRT was combined with BT, with proper and achievable rectal dose constraints intensity-modulated radiation therapy yielded less toxicity than 3-dimensional conformal radiation therapy.

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy.

BACKGROUND AND PURPOSE: Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). MATERIAL AND METHODS: EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. RESULTS: Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16-0.52; P < 0.0001). CONCLUSION: PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy.

PURPOSE: To compare heart and cardiac substructure radiation exposure using intensity-modulated radiotherapy (IMRT) vs. proton beam therapy (PBT) for patients with mid- to distal esophageal cancer who received chemoradiation therapy. METHODS AND MATERIALS: We identified 727 esophageal cancer patients who received IMRT (n=477) or PBT (n=250) from March 2004 to December 2015. All patients were treated to 50.4Gy with IMRT or to 50.4 cobalt Gray equivalents with PBT. IMRT and PBT dose-volume histograms (DVHs) of the whole heart, atria, ventricles, and four coronary arteries were compared. For PBT patients, passive scattering proton therapy (PSPT; n=237) and intensity-modulated proton therapy (IMPT; n=13) DVHs were compared. RESULTS: Compared with IMRT, PBT resulted in significantly lower mean heart dose (MHD) and heart V5, V10, V20, V30, and V40as well as lower radiation exposure to the four chambers and four coronary arteries. Compared with PSPT, IMPT resulted in significantly lower heart V20, V30, and V40 but not MHD or heart V5 or V10. IMPT also resulted in significantly lower radiation doses to the left atrium, right atrium, left main coronary artery, and left circumflex artery, but not the left ventricle, right ventricle, left anterior descending artery, or right coronary artery. Factors associated with lower MHD included PBT (P<0.001), smaller planning target volume (PTV; P<0.001), and gastroesophageal junction (GEJ) tumor (P<0.001). Among PBT patients, factors associated with lower MHD included IMPT (P=0.038), beam arrangement other than AP/PA (P<0.001), smaller PTV (P<0.001), and GEJ tumor (P<0.001). CONCLUSIONS: In patients with mid- to distal esophageal cancer, PBT results in significantly lower radiation exposure to the whole heart and cardiac substructures than IMRT. Long-term studies are necessary to determine how this cardiac sparing effect impacts the development of coronary artery disease and other cardiac complications.

Definitive Chemoradiation Therapy for Esophageal Cancer in the Elderly: Clinical Outcomes for Patients Exceeding 80 Years Old.

PURPOSE: The optimal treatment approach for patients ≥80 years ("elderly") with esophageal cancer is not well established. We assessed the clinical outcomes in elderly patients treated with definitive chemoradiation therapy (CCRT) at our institution. METHODS AND MATERIALS: 56 consecutive patients ≥80 years with esophageal cancer treated with conventional CCRT between 2001 and 2016 were propensity score matched 1:2 to generate 2 younger patient cohorts treated with CCRT without surgery: "intermediate" (65-79 years, n=112) and "younger" (<65 years, n=112). Treatment related toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The rates of overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. RESULTS: The median ages of the 3 cohorts were 81 years (elderly, 80-92 years), 71 years (intermediate, 65-79 years), and 58 years (younger, 20-64 years). The elderly cohort was more likely to have cardiac comorbidities. Although the clinical complete response (cCR) rate deviated significantly among the 3 cohorts, (78%, 72%, and 56%; P=.004), the data failed to identify statistically significant differences among RFS, 2-year, and 5-year OS, or in median survival, which was 15.5 months, 23.6 months, and 20.2 months (P=.468), respectively. The overall severe toxicity rates were 38%, 32%, and 30%, respectively (P=.644), including comparable rate of radiation pneumonitis (P>.05). The elderly cohort, however, did show statistically significant evidence of an increased rate of severe radiation pneumonitis (grade ≥3) which was observed to be 11% versus 4% and 0%, respectively (P=.003). CONCLUSIONS: The studied elderly population showed evidence of similar long-term clinical efficacy after definitive CCRT when compared with cohorts of younger patients with similar prognostic status. An increased rate of pulmonary toxicity was identified, without evidence of differences for nonpulmonary severe adverse events. Understanding the prognostic risk factors of pulmonary toxicity after CCRT may effectuate improved long-term outcomes for elderly population.

Predictive factors for urinary toxicity after iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy.

PURPOSE: We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer. METHODS AND MATERIALS: We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms. RESULTS: IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the <180, 180-220, and >220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (<30 cc or ≥30 cc) and NADT use, urinary G2+ toxicity was most commonly observed in those patients with larger prostates who received NADT, and least in the patients with smaller prostates and no NADT. CONCLUSIONS: NADT was associated with urinary G2+ toxicity. Higher dose and supplemental EBRT did not appear to increase moderate to severe urinary toxicities or time to IPSS resolution; however, it influenced urinary symptom flare.

Single-energy metal artifact reduction in postimplant computed tomography for I-125 prostate brachytherapy: Impact on seed identification.

PURPOSE: To evaluate the effectiveness of the single-energy metal artifact reduction (SEMAR) technique for improving the accuracy of I-125 seed identification in postimplant computed tomography (CT) after prostate brachytherapy. METHODS AND MATERIALS: Postimplant CT images of 40 patients treated with I-125 prostate brachytherapy were acquired. For all patients, 2 data sets were reconstructed, 1 with SEMAR algorithms (SEMAR image), and the other without SEMAR algorithms (non-SEMAR image). Seed locations are automatically detected by the automatic seed finder tool, and their locations were compared between the SEMAR and non-SEMAR images. Dosimetric parameters using seed locations as detected were compared. RESULTS: The true-positive fraction of properly detected seeds on the SEMAR image as determined from a reference seed distribution defined by one investigator was significantly higher than the true-positive fraction on the non-SEMAR image (p = 0.011). The variabilities in D90 (p = 0.001), V100 (p = 0.007), and V150 (p = 0.007) were significantly reduced for seed location on the SEMAR image as compared with non-SEMAR image. CONCLUSIONS: Prostate postimplant CT with SEMAR improved the accuracy of seed localization and postimplant dosimetric parameters.

Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan: outcomes of 1300 patients.

PURPOSE: To report outcomes for men treated with iodine-125 ((125)I) prostate brachytherapy (BT) at a single institution in Japan. METHODS AND MATERIALS: Between 2003 and 2009, 1313 patients (median age, 68 years) with clinically localized prostate cancer were treated with (125)I BT. Median prostate-specific antigen level was 7.6 ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%, and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6% of patients, respectively. Neoadjuvant androgen deprivation therapy was used in 40% of patients and combined external beam radiotherapy of 45 Gy in 48% of patients. Postimplant dosimetry was performed after 30 days after implantation, with total doses converted to the biologically effective dose. Survival functions were calculated by the Kaplan-Meier method and Cox hazard model. RESULTS: Median followup was 67 months (range, 6-126). The 7-year biochemical freedom from failure for low-, intermediate-, and selected high-risk prostate cancers were 98%, 93%, and 81%, respectively (p < 0.001). Multivariate analysis identified the Gleason score, initial prostate-specific antigen level, positive biopsy rate, dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent patients with normal baseline potency retained normal erectile function at 5 years. CONCLUSIONS: (125)I prostate BT is a highly effective treatment option for low-, intermediate-, and selected high-risk prostate cancers. Side effects were tolerable. An adequate dose may be required to achieve successful biochemical control.

Comparison of genitourinary and gastrointestinal toxicity among four radiotherapy modalities for prostate cancer: Conventional radiotherapy, intensity-modulated radiotherapy, and permanent iodine-125 implantation with or without external beam radiotherapy.

PURPOSE: To compare late genitourinary (GU) and gastrointestinal (GI) toxicity following different prostate cancer treatment modalities. MATERIALS AND METHODS: This study included 1084 consecutive prostate cancer patients treated with conventional radiotherapy, intensity-modulated radiotherapy (IMRT), permanent iodine-125 implantation (PI) alone, and PI combined with external beam radiotherapy (PI+EBRT). The effects of treatment- and patient-related factors on late grade ⩾ 2 (G2+) GU/GI toxicity risk were assessed. RESULTS: The median follow-up was 43 months (range, 12-97 months). Compared to the PI+EBRT, there was significantly less G2+ GU toxicity in the conventional radiotherapy (hazard ratio [HR] = 0.39; 95% CI, 0.20-0.77) and the IMRT (HR=0.45, 95% CI, 0.27-0.73). Compared to the PI+EBRT, there was significantly more G2+ GI toxicity in the IMRT (HR = 2.38; 95% CI, 1.16-4.87). In PI-related groups, prostate equivalent dose in 2 Gy fractions was a significant predictor of G2+ GU toxicity (p = 0.001), and the rectal volume receiving more than 100% of the prescribed dose was a significant predictor of G2+ GI toxicity (p = 0.001). CONCLUSION: The differences in the late G2+ GU/GI risk cannot be explained by the differences in treatment modalities themselves, but by the total radiation dose to the GU/GI tract, which had a causal role in the development of late G2+ GU/GI toxicity across all treatment modality groups.

A dose-response analysis of biochemical control outcomes after (125)I monotherapy for patients with favorable-risk prostate cancer.

PURPOSE: To define the optimal dose for (125)I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity. METHODS AND MATERIALS: Between 2003 and 2009, 683 patients with prostate cancer were treated with (125)I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dose effects on biochemical control and toxicity. RESULTS: The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant. CONCLUSIONS: Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.