A surrogate urethra for real-time planning of high-dose-rate prostate brachytherapy.

PURPOSE: This study characterizes prostatic urethra cross-section to develop a surrogate urethra for accurate prediction of urethral dose during real-time high-dose-rate prostate brachytherapy. MATERIALS AND METHODS: Archived preoperative transrectal ultrasound images from 100 patients receiving low-dose-rate prostate brachytherapy were used to characterize the prostatic urethra, contoured on ultrasound using aerated gel. Consensus contours, defined using majority vote, described commonalities in cross-sectional shape across patients. Potential simplified surrogates were defined and evaluated against the true urethra. The best performing surrogate, a circle of varying size (CS) was retrospectively contoured on 85 high-dose-rate prostate brachytherapy treatment plans. Dose to this recommended surrogate was compared with urethral doses estimated by the standard 6 mm circle surrogate. RESULTS: Clear variation in urethral cross-sectional shape was observed along its length and between patients. The standard circle surrogate had low predictive sensitivity (61.1%) compared with true urethra because of underrepresentation of the verumontanum midgland. The CS best represented the true urethra across all validation metrics (dice: 0.73, precision: 67.0%, sensitivity: 83.2%, conformity: 0.78). Retrospective evaluation of planned doses using the CS surrogate resulted in significant differences in all reported urethral dose parameters compared with the standard circle, with the exception of D100%. The urethral dose limit (115%) was exceeded in 40% of patients for the CS surrogate. CONCLUSIONS: The proposed CS surrogate, consisting of circles of varying diameter, is simple yet better represents the true urethra compared with the standard 6 mm circle. Higher urethral doses were predicted using CS, and the improved accuracy of CS may offer increased predictive power for urethral toxicity, a subject of future work.

Seroma Visualization and Implant Accuracy in Permanent Breast Seed Implant Brachytherapy.

PURPOSE: This study aimed to evaluate the relationship between seroma visualization and seed placement accuracy in permanent breast seed implant brachytherapy (PBSI). METHODS AND MATERIALS: At the time of planning computed tomography (CT), 10 patients receiving PBSI were imaged with spatially co-registered 3-dimensional ultrasound (US). Seromas were independently contoured by 3 radiation oncologists on CT and US scans. Intra- and interuser conformity indices (CIs) were used as a surrogate for seroma visualization. Intermodality visualization differences were assessed by defining consensus contours, clinical target volume (CTV)CT and CTVUS, and evaluating the CI and the centroid position and volume differences. Seed placement accuracy was represented by the differences between the planned and implanted seed positions (displacements). Correlations among total, systematic, and random seed displacements and seroma visualization metrics were assessed. RESULTS: The median (range) intra-user CI of CT seroma contouring was 0.60 (0.46-0.72), and the median interuser CIs were 0.46 (0.38-0.58) and 0.50 (0.29-0.67) on CT and US, respectively. The CTVUS was a mean 68% ± 12% smaller than CTVCT and differed in centroid position by 8 ± 3 mm. Seeds were placed, on average, 10 ± 5 mm from their planned positions, and intrapatient systematic displacements were observed. The mean seed displacements for the implants were shown to correlate with interuser CI on CT (r = .74; P = .01) and volume differences between CTVCT and CTVUS (r = .65; P = .04), but not with intrauser CI, intermodality CI or centroid differences. Systematic displacements were correlated with interuser CT CI (r = .67; P = .03) and intermodality volume difference (r = .64; P = .04), but random seed displacements were independent of all evaluated metrics. CONCLUSIONS: Consistency in seroma delineation in treatment planning and differences between seroma visualized on CT and US scans are associated with seed placement accuracy in PBSI. Efforts to enhance seroma visualization in treatment planning and implant guidance may have a positive impact on treatment quality and should be pursued to facilitate the widespread implementation of this technique.

Long-Term Prostate Specific Antigen Stability and Predictive Factors of Failure after Permanent Seed Prostate Brachytherapy.

PURPOSE: Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long-term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold. MATERIALS AND METHODS: A total of 2,339 patients with low or intermediate risk prostate cancer received 125iodine brachytherapy from 1998 to 2010 with a minimum 3-year followup. In addition, 49.7% of the patients received 6 months of androgen deprivation. Clinical, dosimetric and prostate specific antigen data were retrieved from a prospective database. Biochemical results were classified as stable or rising prostate specific antigen (0.2 ng/ml or greater and increased 0.1 ng/ml or greater during the preceding 2 years), or biochemical failure (defined as nadir + 2). Multivariate analysis was done to identify predictors of failure used to create logistic regression models. RESULTS: At a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p <0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p <0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p <0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort. CONCLUSIONS: Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous.

Options for Salvage of Radiation Failures for Prostate Cancer.

Biochemical failure after primary external beam radiotherapy for prostate cancer is common, and a significant proportion of these failures are due to local residual or recurrent disease. Early or delayed palliation using androgen deprivation therapy is the most common approach. Although a conservative approach is appropriate for many individuals, selected patients would benefit from retreatment with curative intent. We review the pertinent literature on salvage of locally recurrent prostate cancer after primary radiotherapy, including the modalities of surgery, cryotherapy, high-intensity focused ultrasound, or reirradiation with brachytherapy or stereotactic body radiotherapy. We discuss patient selection, outcomes, and toxicities. Patients with local recurrence and sufficient life expectancy, in the absence of metastatic disease, could be considered for local salvage. Although highly dependent on patient selection, the efficacy of the various salvage options seems comparable, with biochemical-recurrence-free survivals ranging approximately 50% at 5 years. The toxicity profiles differ, but all salvage treatments are more toxic than primary treatment. Management of isolated local failure after radiotherapy remains challenging. However, with the recent progress in salvage techniques, and more sensitive functional imaging for tumor localization and staging, salvage treatments are likely to play an increasingly important role.

Adjuvant Chemotherapy and Vaginal Vault Brachytherapy With or Without Pelvic Radiotherapy for Stage 1 Papillary Serous or Clear Cell Endometrial Cancer.

OBJECTIVE: The aim of this study was to assess and compare adjuvant chemotherapy followed by either high-dose-rate vaginal vault brachytherapy (VBT) alone or combined with pelvic external beam radiotherapy (EBRT) for International Federation of Gynaecology and Obstetrics stage 1 serous or clear cell (CC) endometrial cancer. METHODS: Between 2006 and 2012, 84 women with stage 1 serous or CC endometrial cancer were evaluated postoperatively for adjuvant treatment at our hospital. More than 80% of patients had pelvic lymphadenectomy. Patients declining or not completing adjuvant treatments were excluded. Twenty-five women received 4 to 6 cycles of carboplatin/paclitaxel followed by EBRT and VBT. Thirty-two women received 6 cycles of carboplatin/paclitaxel followed by VBT. Locoregional control and toxicities were assessed during follow-up. RESULTS: The 3-year disease-free survival and overall survival rates for the VBT group compared with the EBRT + VBT group were 88% versus 84%, P = 0.6, and 100% versus 94%, P = 0.6, respectively. Only 1 patient in the EBRT + VBT group developed a distant recurrence. One patient had grade 3 toxicity (chronic gastrointestinal [GI] toxicity) in the EBRT + VBT group. Acute grade 1-to-2 GI and grade 1 genitourinary (GU) toxicities were less frequent in the VBT group compared with the EBRT + VBT group (P = 0.008 and P = 0.019, respectively). Late GI and GU toxicities were comparable. Grade 1 vaginal toxicity was similar in both groups. No acute or late grade 2 GU or vaginal toxicities were reported. CONCLUSIONS: According to this study, VBT alone seems to be as effective as EBRT and VBT for stage 1 serous and CC endometrial cancer treated with surgery and adjuvant chemotherapy. Furthermore, less acute GI and GU toxicities were seen in the VBT group.

Grade 3 Radiation Recall Sigmoiditis after Treatment for Locally Advanced Cervical Cancer: A Case Report.

We report a case of Grade 3 radiation recall sigmoiditis after administration of a combination of carboplatin, paclitaxel, and bevacizumab, following irradiation for a locally advanced cervical cancer. A 50-year-old woman was diagnosed with an FIGO Stage IIIb squamous cell carcinoma of the cervix with bilateral pelvic and para-aortic lymph nodes. She underwent concurrent chemoradiation followed by high dose rate (HDR) intracavitary brachytherapy. She had a complete loco-regional response. A supraclavicular recurrence was diagnosed three months after completing treatment and two cycles of carboplatin, docetaxel, and bevacizumab were given in April 2014. Shortly after the second cycle, she was admitted to the hospital for significant abdominal pain, diarrhea followed by symptoms of bowel subocclusion. The CT scan and endoscopic images revealed thickening of the sigmoid wall with important edema and telangiectasia. The biopsy was consistent with acute radiation-induced colitis. Because of persistent digestive symptoms, a diverting ileostomy was done few months later. The location, timing, pathology, and its association with a high-dose region are analyzed in this case report.

The Quadrella: a novel approach to analyzing optimal outcomes after permanent seed prostate brachytherapy.

BACKGROUND AND PURPOSE: To study a four-point combined analysis (Quadrella) of optimal outcome among patients treated with exclusive permanent seed prostate brachytherapy (PB), as defined by the likelihood of achieving disease control and preserving normal urinary, gastro-intestinal (GI) and sexual function. MATERIALS AND METHODS: 384 patients with localized prostate cancer underwent PB at our institution with (125)I at a dose level of 144Gy. Subjects with erectile dysfunction who did not respond to medication were excluded. 281 patients with minimum 3-year follow-up were evaluated. Patients with concurrent biochemical progression-free survival (bPFS), absent urinary and GI toxicities (grade 0 toxicities according to CTCAE v 3.0) and preserved sexual potency (with our without medication) were classified as the Quadrella group. RESULTS: Among the 281 patients analyzed, the Quadrella was achieved in 49.1%, 48.0%, 50.4%, 41.7% and 65.2% in years 3-7, respectively. bPFS rates were 82.6-96.1%, corresponding potency rates were 63.6-82.3%, and normal urinary and GI function rates were 64.8-82.6% and 95-100%, respectively. By multivariate analysis, significant predictors of Quadrella were age (p=0.015), baseline IPSS (p=0.03) and time since PB (p=0.02). CONCLUSION: Urinary and sexual toxicity remained the most common reasons for excluding patients from a perfect outcome (Quadrella), defined by strict criteria. This analysis can be useful for subsequent comparison between treatment modalities.

Analysis of seed loss and pulmonary seed migration in patients treated with virtual needle guidance and robotic seed delivery.

PURPOSE AND BACKGROUND: To determine whether automated seed delivery system and real-time intraoperative (IO) virtual needle guidance reduce seed loss and pulmonary seed migration. PATIENTS AND METHODS: We analyzed 279 patients with low and intermediate risk prostate cancer treated in our institution with radioactive iodine (I-125) permanent seed implants. Loose seeds were exclusively used. To account for lost seeds, pelvic fluoroscopic imaging from 3 different angles was done 30 days after the implant. Posteroanterior and lateral chest x-rays were done when seed loss was confirmed. Patients were compared using the χ(2) test and Fisher exact test. RESULTS: At least 1 seed was lost in 31.5% of patients with a migration rate of 1.02%; 9.3% of patients had at least 1 seed in the lung with a migration rate of 0.22%. The population was divided into 3 groups according to the order in which they were treated. Seed loss (P=0.02) and pulmonary seed embolization (P=0.008) were significantly lower in the second hundred than in the first hundred patients. No difference was noted between groups 1 and 3 (patient, 201-279). Peri- or extracapsular seed placement was not correlated to seed loss (P=0.780 and P=0.092, respectively). No serious complications from seed migration were reported. Seed loss did not influence dosimetry parameters (V100, V150, and D90). CONCLUSION: Our pulmonary seed migration and total seed loss rates are comparable to the ones reported in the literature. Virtual needle guidance and automated seed delivery system are in our hand as accurate as the manual technique.

Comparison between high and low source activity seeds for I-125 permanent seed prostate brachytherapy.

PURPOSE: To compare low (mean 0.44, SD ± 0.0163 mCi) with high source activity (0.61 ± 0.0178 mCi) in I(125) permanent seed brachytherapy regarding seed loss, dosimetric outcome, and toxicity. METHODS AND MATERIALS: The study included 199 patients with prostate cancer treated by permanent seed brachytherapy alone: the first 105 with seeds of lower activity (first cohort), the following 94 with higher seed activity (second cohort). The V100, V150, V200, and D90 were analyzed on the CT scan 30 days after implantation (CTD30). The V100, V150, and D2 of the rectum were also calculated on CTD30. Seed loss was determined 30 days after implantation. Urinary toxicity was measured with the International Prostate Symptom Score (IPSS) questionnaire. RESULTS: Lower seed activity was associated with lower V150 and V200 (p = 0.01 and p ≤ 0.001, respectively) on CTD30. More patients had a V100 <90% and D90 <140 Gy in the lower activity cohort (p = 0.098 for D90 and p = 0.029 for V100) on CTD30. There was no difference between cohorts in dose to the rectum (p = 0.325-0.516) or difference in patients' IPSS score from baseline (p = 0.0.117-0.618), although there was a trend toward more urinary toxicity at 4 and 8 months for high activity seeds. Seed loss as a percentage of implanted seeds was not different (p = 0.324). CONCLUSIONS: Higher seed activity (I(125) ≥ 0.6 mCi) results in at least equal V100 and D90 on CTD30. However, dose inhomogeneity and a trend toward more urinary toxicity at 4 and 8 months after treatment may lead to a higher long-term urinary complications.