Protocol-based CT-guided brachytherapy for patients with prostate cancer and previous rectal extirpation-a curative approach.

OBJECTIVE: There are numerous curative treatment possibilities for prostate cancer. In patients who have undergone rectal extirpation for rectal cancer treatment, curative options are limited due to anatomic changes and previous irradiation of the pelvis. In this analysis, we validate the feasibility of CT-guided transperineal interstitial brachytherapy for this specific scenario. PATIENTS AND METHODS: We analyzed the treatment procedures and outcomes of 5 patients with metachronic nonmetastatic prostate cancer. Ultrasound-guided brachytherapy was not possible in any of the patients. Of these 5 patients, 3 were treated for prostate cancer using temporary brachytherapy with Ir-192 only, and 2 were treated with external-beam radiation therapy and temporary brachytherapy as a boost. CT-guided brachytherapy was performed in all patients. We analyzed the feasibility, efficacy, treatment-related toxicity, and quality of life (EORTC-30, IEFF, IPSS, and ICIQ questionnaires) of the treatments. RESULTS: Median follow-up was 35 months. Two out of five patients received boost irradiation (HDR 2â€¯× 9 Gy, PDR 30 Gy). Three out of five patients were treated with PDR brachytherapy in two sessions up to a total dose of 60 Gy. Dosimetric parameters were documented as median values as follows: V100 94.7% (94.5-98.4%), D2bladder 64.3% (50.9-78.3%), D10urethra 131.05% (123.2%-141.2%), and D30urethra 122.45% (116.2%-129.5%). At the time of analysis, no biochemical recurrence had been documented. Furthermore, neither early nor late side effects exceeding CTCAE grade 2 were documented. CONCLUSION: CT-guided transperineal brachytherapy of the prostate in patients with previous rectal surgery and radiation therapy is safe and represents a possible curative treatment option. Brachytherapy can be considered for patients with metachronic prostate cancer in this specific scenario, albeit preferably in experienced high-volume centers.

The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).

BACKGROUND: Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. METHODS: ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. DISCUSSION: ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. TRIAL REGISTRATION: NCT05230251 (ClinicalTrials.gov).

Clinical characteristics of secondary bladder cancer developing after low-/high-dose-rate brachytherapy to treat localized prostate cancer.

BACKGROUND: To explore correlations between the clinical attributes of secondary bladder cancer and brachytherapy, we retrospectively reviewed our institutional database on patients with localized prostate cancer who underwent low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy (HDR-BT) with or without external beam radiation therapy (EBRT) or radical prostatectomy (RP). METHODS: From October 2003 to December 2014, 2551 patients with localized prostate cancer were treated at our institution. Of these, data on 2163 were available (LDR-BT alone: n = 953; LDR-TB with EBRT: n = 181; HDR-BT with EBRT: n = 283; RP without EBRT: n = 746). The times of secondary bladder cancer development subsequent to radical treatment, and their clinical characteristics, were studied. RESULTS: Age-adjusted Cox's regression analyses indicated that brachytherapy did not significantly impact the incidence of secondary bladder cancer. However, the pathological characteristics of such cancer differed between patients treated via brachytherapy and RP without EBRT; invasive bladder cancer was more common in such patients. CONCLUSION: The risk for secondary bladder cancer was not significantly increased after brachytherapy compared to non-irradiation therapy. However, brachytherapy patients exhibited a higher incidence of invasive bladder cancer. Therefore, meticulous follow-up is crucial for early detection and treatment of bladder cancer in such patients.

The prognostic significance of the clinical T stage and Grade Group in patients with locally advanced prostate cancer treated via high-dose-rate brachytherapy and external beam radiation.

BACKGROUND: Although the optimal management of locally advanced prostate cancer (PCa) remains unclear, local definitive therapy, thus combined radiotherapy and androgen deprivation, is one option. We evaluated the long-term outcomes of patients with locally advanced PCa who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT). METHODS: We retrospectively analyzed 173 patients with locally advanced PCa (cT3a-4N0-1M0) who underwent HDR-BT and EBRT. We employed Cox's proportional hazards models to identify pre-treatment predictors of oncological outcomes. Treatment outcomes (biochemical recurrence-free survival [BCRFS], clinical progression-free survival [CPFS], and castration-resistant prostate cancer-free survival [CRPCFS] were compared according to the combination of the pre-treatment predictors. RESULTS: The 5-year BCRFS, CPFS, and CRPCFS rates were 78.5, 91.7, and 94.4% respectively; there were two PCa deaths. Multivariate analysis revealed that the clinical T stage (cT3b and cT4) and Grade Group (GG) 5 status were independent risk factors for poor BCRFS, CPFS, and CRPCFS. In the GG ≤ 4 group, the Kaplan-Meier curves for BCRFS, CPFS, and CRPCFS revealed excellent outcomes. However, in the GG5 group, patients with cT3b and cT4 PCa evidenced significantly poorer oncological outcomes than those with cT3a PCa. CONCLUSION: The clinical T stage and GG status were significantly prognostic of oncological outcomes in patients with locally advanced PCa. In patients of GG ≤ 4 PCa, HDR-BT was effective even in patients with cT3b or cT4 PCa. However, in patients with GG5 PCa, careful monitoring is essential, particularly of patients with cT3b or cT4 PCa.

Comparison of outcomes in high-risk prostate cancer patients treated with low-/high-dose-rate brachytherapy plus external beam radiotherapy.

BACKGROUND: Although brachytherapy is a standard treatment option for patients with high-risk prostate cancer, only a few studies have compared low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT). We applied propensity score-based inverse probability treatment weighting (IPTW) to compare oncological outcomes for LDR-BT and HDR-BT. METHODS: We retrospectively assessed prognosis in 392 patients with high-risk localized prostate cancer who had undergone brachytherapy plus external beam radiation. IPTW was applied to adjust the Kaplan-Meier survival analyses and Cox proportional hazards regression analyses, with the goal of minimizing bias from patient background. RESULTS: The IPTW-adjusted Kaplan-Meier survival analyses showed no statistically significant differences for time to biochemical recurrence, clinical progression, castration-resistant prostate cancer, or death from any cause. The IPTW-adjusted Cox regression analyses also showed that the modality of brachytherapy was not an independent factor in these oncological outcomes. Notably, the two groups differed regarding complications; LDR-BT was associated with a higher rate of acute grade ≥ 2 GU toxicity, and late grade 3 toxicity was noted only in HDR-BT. CONCLUSION: Our analysis of long-term outcomes in patients with high-risk localized prostate cancer shows no significant differences in oncological outcomes between LDR-BT and HDR-BT, but some differences in toxicity, and offers patients and clinicians useful information in deciding management strategies for high-risk localized prostate cancer.

Patients with PSA below 0.2 ng/mL at 8 years post high-dose-rate brachytherapy have an extremely low risk of subsequent recurrence.

OBJECTIVES: We have analyzed the long-term follow-up data of patients with prostate cancer (PCa) who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT). The objective was to determine the optimal time for cessation of PSA monitoring after HDR-BT. METHODS: We included 309 patients with clinical stage T1c-T4 N0-1 M0 PCa who received HDR-BT and EBRT combined with long-term ADT between 2005 and 2018. We stratified the patients based on their prostate-specific antigen (PSA) levels and identified the factors associated with biochemical recurrence (BCR) and clinical progression (CP). RESULTS: The median follow-up duration was 98 months (range: 31-207 months). Among the 306 patients, 76 developed BCR and 47 developed CP subsequently. We found that the PSA levels at 3, 5, and 8 years significantly correlated with the oncological outcomes of brachytherapy. No patient with a PSA level ≤ 0.2 ng/mL at 8 years later developed BCR or CP. CONCLUSION: Our long-term data suggest that in the presence of a PSA level ≤ 0.2 ng/mL at 8 years later, PSA monitoring may be safely discontinued due to the extremely low risk of subsequent oncological events. The data presented in this study will assist clinicians in determining the optimal management strategy for patients with PCa following HDR-BT and EBRT combined with long-term ADT.

Self-configuring nnU-Net for automatic delineation of the organs at risk and target in high-dose rate cervical brachytherapy, a low/middle-income country's experience.

BACKGROUND: The high-dose rate (HDR) brachytherapy treatment planning workflow for cervical cancer is a labor-intensive, time-consuming, and expertise-driven process. These issues are amplified in low/middle-income countries with large deficits in experienced healthcare professionals. Automation has the ability to substantially reduce bottlenecks in the planning process but often require a high level of expertise to develop. PURPOSE: To implement the out of the box self-configuring nnU-Net package for the auto-segmentation of the organs at risk (OARs) and high-risk CTV (HR CTV) for Ring-Tandem (R-T) HDR cervical brachytherapy treatment planning. METHODS: The computed tomography (CT) scans of 100 previously treated patients were used to train and test three different nnU-Net configurations (2D, 3DFR, and 3DCasc). The performance of the models was evaluated by calculating the Sørensen-dice similarity coefficient, Hausdorff distance (HD), 95th percentile Hausdorff distance, mean surface distance (MSD), and precision score for 20 test patients. The dosimetric accuracy between the manual and predicted contours was assessed by looking at the various dose volume histogram (DVH) parameters and volume differences. Three different radiation oncologists (ROs) scored the predicted bladder, rectum, and HR CTV contours generated by the best performing model. The manual contouring, prediction, and editing times were recorded. RESULTS: The mean DSC, HD, HD95, MSD and precision scores for our best performing model (3DFR) were 0.92/7.5 mm/3.0 mm/ 0.8 mm/0.91 for the bladder, 0.84/13.8 mm/5.3 mm/1.4 mm/0.84 for the rectum, and 0.81/8.5 mm/6.0 mm/2.2 mm/0.80 for the HR CTV. Mean dose differences (D2cc/90% ) and volume differences were 0.08 Gy/1.3 cm3 for the bladder, 0.02 Gy/0.7 cm3 for the rectum, and 0.33 Gy/1.5 cm3 for the HR CTV. On average, 65% of the generated contours were clinically acceptable, 33% requiring minor edits, 2% required major edits, and no contours were rejected. Average manual contouring time was 14.0 min, while the average prediction and editing times were 1.6 and 2.1 min, respectively. CONCLUSION: Our best performing model (3DFR) provided fast accurate auto generated OARs and HR CTV contours with a large clinical acceptance rate.

Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer.

PURPOSE: Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. METHODS: From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (DMean). Combined treatment was delivered as 46 Gy (DMean) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D90%). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). RESULTS: The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5­year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5­year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5­year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. CONCLUSION: Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.

Comparing Iridium-192 with Cobalt-60 sources in high-dose-rate brachytherapy boost for localized prostate cancer.

BACKGROUND: Dosimetric and clinical comparison of two cohorts of Iridium-192 (Ir-192) and Cobalt-60 (Co-60) high-dose-rate brachytherapy (DR-BT) boost for localized prostate cancer. MATERIAL AND METHODS: Patients with localized prostate cancer receiving either Ir-192 or Co-60 high-dose-rate brachytherapy (HDR-BT) boost in combination with external beam radiotherapy (EBRT) in the period of 2002-2019 were evaluated for dosimetric differences, side effects, biochemical relapse-free survival (bRFS), metastasis-free survival (MFS), and overall survival (OS). EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) 2 and 4 weeks after EBRT. Genitourinary (GU)/gastrointestinal (GI) toxicity were evaluated utilizing the Common Toxicity Criteria for Adverse Events version 5.0 and biochemical failure was defined according to the Phoenix definition. RESULTS: A total of 338 patients with a median follow-up of 101.8 (IQR 65.7-143.0) months were evaluated. At 10 years the estimated bRFS, MFS, and OS in our patient sample were 81.1%/71.2% (p=.073), 87.0%/85.7% (p=.862), and 70.1%/69.7% (p=.998) for Ir-192/Co-60, respectively. Cumulative 5-year late grade ≥2 GU toxicity was 20% for Ir-192 and 18.3% for Co-60 (p=.771). Cumulative 5-year late grade ≥2 GI toxicity was 5.8% for Ir-192 and 4.6% for Co-60 (p=.610). Grade 3 late GU side effects were pronounced in the Ir-192 cohort with 8.1% versus 1.4% in the Co-60 cohort (p=.01), which was associated with significantly lower dose to the organs at risk in the Co-60 cohort. PTV D90% was 9.3 ± 0.8 Gy versus 9.0 ± 1.1 Gy (p=.027) for Ir-192 versus Co-60. PTV V100% and PTV V150% were not significantly different between both cohorts. CONCLUSION: Co-60 brachytherapy sources are an effective alternative to Ir-192 in combined prostate HDR-BT boost + EBRT.

Syndrome of inappropriate secretion of antidiuretic hormone following high dose rate brachytherapy for prostate cancer: a case report.

BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone is a disorder characterized by the excess release of antidiuretic hormone and can result in hyponatremia. If managed inappropriately, severe hyponatremia can cause seizures, cerebral edema, and even death. There are various known causes of this inappropriate release of antidiuretic hormone, including malignancy, CNS disorders, and disturbances in the hypothalamic-pituitary-renal axis. However, reports of syndrome of inappropriate secretion of antidiuretic hormone after brachytherapy for prostate cancer are exceedingly rare. CASE PRESENTATION: We report a case of symptomatic hyponatremia secondary to the inappropriate secretion of antidiuretic hormone after prostate high-dose rate brachytherapy under general anesthesia in a patient with adenocarcinoma of the prostate. CONCLUSIONS: In rare instances, inappropriate secretion of antidiuretic hormone can occur after high-dose rate brachytherapy for prostate cancer. The cause is likely multifactorial, involving pain or discomfort ensuing from the surgical procedure, the general anesthesia or intraoperative drugs administered. However, due to the potential severity of the side effects, timely diagnosis is crucial to ensure prompt, and effective management.

Simultaneous ThermoBrachytherapy: Electromagnetic Simulation Methods for Fast and Accurate Adaptive Treatment Planning.

The combination of interstitial hyperthermia treatment (IHT) with high dose rate brachytherapy (HDR-BT) can improve clinical outcomes since it highly enhances the efficiency of cell kill, especially when applied simultaneously. Therefore, we have developed the ThermoBrachy applicators. To effectively apply optimal targeted IHT, treatment planning is considered essential. However, treatment planning in IHT is rarely applied as it is regarded as difficult to accurately calculate the deposited energy in the tissue in a short enough time for clinical practice. In this study, we investigated various time-efficient methods for fast computation of the electromagnetic (EM) energy deposition resulting from the ThermoBrachy applicators. Initially, we investigated the use of an electro-quasistatic solver. Next, we extended our investigation to the application of geometric simplifications. Furthermore, we investigated the validity of the superpositioning principle, which can enable adaptive treatment plan optimization without the need for continuous recomputation of the EM field. Finally, we evaluated the accuracy of the methods by comparing them to the golden standard Finite-Difference Time-Domain calculation method using gamma-index analysis. The simplifications considerably reduced the computation time needed, improving from >12 h to a few seconds. All investigated methods showed excellent agreement with the golden standard by showing a >99% passing rate with 1%/0.5 mm Dose Difference and Distance-to-Agreement criteria. These results allow the proposed electromagnetic simulation method to be used for fast and accurate adaptive treatment planning.

Design of the novel ThermoBrachy applicators enabling simultaneous interstitial hyperthermia and high dose rate brachytherapy.

OBJECTIVE: In High Dose Rate Brachytherapy for prostate cancer there is a need for a new way of increasing cancer cell kill in combination with a stable dose to the organs at risk. In this study, we propose a novel ThermoBrachy applicator that offers the unique ability to apply interstitial hyperthermia while simultaneously serving as an afterloading catheter for high dose rate brachytherapy for prostate cancer. This approach achieves a higher thermal enhancement ratio than in sequential application of radiation and hyperthermia and has the potential to decrease the overall treatment time. METHODS: The new applicator uses the principle of capacitively coupled electrodes. We performed a proof of concept experiment to demostrate the feasibility of the proposed applicator. Moreover, we used electromagnetic and thermal simulations to evaluate the power needs and temperature homogeneity in different tissues. Furthermore we investigated whether dynamic phase and amplitude adaptation can be used to improve longitudinal temperature control. RESULTS: Simulations demonstrate that the electrodes achieve good temperature homogeneity in a homogenous phantom when following current applicator spacing guidelines. Furthermore, we demonstrate that by dynamic phase and amplitude adaptation provides a great advancement for further adaptability of the heating pattern. CONCLUSIONS: This newly designed ThermoBrachy applicator has the potential to revise the interest in interstitial thermobrachytherapy, since the simultaneous application of radiation and hyperthermia enables maximum thermal enhancement and at maximum efficiency for patient and organization.

The effectiveness of high-dose-rate brachytherapy with external beam radiotherapy for clinically locally advanced and node-positive prostate cancer: long-term results of a retrospective study.

BACKGROUND: No standard treatment exists for locally advanced prostate cancer (PC). This study evaluated the long-term treatment outcomes and toxicity in patients with clinically locally advanced and/or lymph node (LN)-positive PC who underwent high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT). METHODS: The treatment outcomes and toxicities of 152 patients with PC who underwent HDR-BT with EBRT and had at least 2 years of observation were examined. The treatment dose was 19- and 13-Gy HDR-BT in two and single fractions, respectively, both combined with external irradiation of 46 Gy in 23 fractions. Long-term androgen deprivation therapy (ADT) for patients harboring very high-risk tumors was used in combination. RESULTS: The median observation period was 59.7 (24.4-182.1) months. The 5-year prostate cancer-specific and recurrence-free (RFS) survival rates were 99.0% and 91.8%, respectively, with only two PC mortalities. When 5-year RFS was examined for each parameter, RFS was significantly lower in pre-radiotherapy (pre-RT) prostate-specific antigen (PSA) > 0.5 ng/mL (77.1%; p = 0.008), and presence of LN metastasis (68.1%; p = 0.017). Multivariable analysis demonstrated that pre-RT PSA (HR, 4.68; 95% CI, 1.39-15.67; p = 0.012) and presence of LN metastasis (HR, 4.70; 95% CI, 1.24-17.74; p = 0.022) were independent recurrence predictors. The 5-year cumulative incidence rate of grade ≥ 2 toxicities in genitourinary and gastrointestinal tracts were 15.4% and 1.3%, respectively. CONCLUSIONS: HDR-BT combined with EBRT and long-term ADT shows promising disease control and tolerant toxicities for clinically locally advanced and LN-positive PC.

Inverse planning in high-dose rate brachytherapy improves quality of life of prostate cancer patients compared with forward planning.

OBJECTIVES: To understand differences in quality of life outcomes between cases with forward planning and cases with inverse planning, we examine patients undergoing high-dose rate brachytherapy combined with external beam radiotherapy for localized prostate cancer. METHODS: We prospectively identified 283 patients with localized prostate cancer and divided them into forward planning and inverse planning groups. We extracted data on doses to the prostate, rectum and urethra that could potentially affect quality of life. We also evaluated quality of life using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey and Expanded Prostate Cancer Index Composite at pre-treatment and at 3, 6, 12 and 24 months after treatment. Wilcoxon signed rank test and Bonferroni correction were used to analyze the irradiation dose and any change in quality of life. RESULTS: Doses to the prostate and rectum were not significantly different between the two groups. Notably, however, doses to the urethra were significantly lower in the inverse planning group than in the forward planning group. Patients in the forward planning group had significantly poorer physical component summary scores at 3 months according to survey results. In Expanded Prostate Cancer Index Composite, patients in the forward planning group had statistically significant poorer urinary, bowel and sexual scores than those in the inverse planning group. Quality of life related to decline in sexual function was significantly reduced in the inverse planning group. CONCLUSIONS: Inverse planning in high-dose rate brachytherapy could significantly improve quality of life of patients with prostate cancer.

Comparative dosimetrical analysis of intensity-modulated arc therapy, CyberKnife therapy and image-guided interstitial HDR and LDR brachytherapy of low risk prostate cancer.

BACKGROUND: The objective of the study was to dosimetrically compare the intensity-modulated-arc-therapy (IMAT), Cyber-Knife therapy (CK), single fraction interstitial high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy (BT) in low-risk prostate cancer. MATERIALS AND METHODS: Treatment plans of ten patients treated with CK were selected and additional plans using IMAT, HDR and LDR BT were created on the same CT images. The prescribed dose was 2.5/70 Gy in IMAT, 8/40 Gy in CK, 21 Gy in HDR and 145 Gy in LDR BT to the prostate gland. EQD2 dose-volume parameters were calculated for each technique and compared. RESULTS: EQD2 total dose of the prostate was significantly lower with IMAT and CK than with HDR and LDR BT, D90 was 79.5 Gy, 116.4 Gy, 169.2 Gy and 157.9 Gy (p < 0.001). However, teletherapy plans were more conformal than BT, COIN was 0.84, 0.82, 0.76 and 0.76 (p < 0.001), respectively. The D2 to the rectum and bladder were lower with HDR BT than with IMAT, CK and LDR BT, it was 66.7 Gy, 68.1 Gy, 36.0 Gy and 68.0 Gy (p = 0.0427), and 68.4 Gy, 78.9 Gy, 51.4 Gy and 70.3 Gy (p = 0.0091) in IMAT, CK, HDR and LDR BT plans, while D0.1 to the urethra was lower with both IMAT and CK than with BTs: 79.9 Gy, 88.0 Gy, 132.7 Gy and 170.6 Gy (p < 0.001). D2 to the hips was higher with IMAT and CK, than with BTs: 13.4 Gy, 20.7 Gy, 0.4 Gy and 1.5 Gy (p < 0.001), while D2 to the sigmoid, bowel bag, testicles and penile bulb was higher with CK than with the other techniques. CONCLUSIONS: HDR monotherapy yields the most advantageous dosimetrical plans, except for the dose to the urethra, where IMAT seems to be the optimal modality in the radiotherapy of low-risk prostate cancer.

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term androgen deprivation therapy for very high-risk prostate cancer.

OBJECTIVE: To estimate the outcomes of high-dose-rate brachytherapy combined with hypofractionated external beam radiotherapy in prostate cancer patients classified as very high risk by the National Comprehensive Cancer Network. METHODS: Between June 2009 and September 2015, 66 patients meeting the criteria for very high-risk disease received high-dose-rate brachytherapy (2 fractions of 9 Gy) as a boost of external beam radiotherapy (13 fractions of 3 Gy). Androgen deprivation therapy was administered for approximately 3 years. Biochemical failure was assessed using the Phoenix definition. RESULTS: The median follow-up period was 53 months from the completion of radiotherapy. The 5-year biochemical failure-free, distant metastasis-free, prostate cancer-specific and overall survival rates were 88.7, 89.2, 98.5 and 97.0%, respectively. The independent contribution of each component of the very high-risk criteria was assessed in multivariable models. Primary Gleason pattern 5 was associated with increased risks of biochemical failure (P = 0.017) and distant metastasis (P = 0.049), whereas clinical stage ≥T3b or >4 biopsy cores with Gleason score 8-10 had no significant impact on the two outcomes. Grade 3 genitourinary toxicities were observed in two (3.0%) patients, whereas no grade ≥3 gastrointestinal toxicities occurred. CONCLUSIONS: The present study shows that this multimodal approach provides potentially excellent cancer control and acceptable associated morbidity for very high-risk disease. Patients with primary Gleason pattern 5 are at a higher risk of poor outcomes, indicating the need for more aggressive approaches in these cases.

Extended-field intensity-modulated radiation therapy combined with concurrent chemotherapy for cervical cancer with para-aortic lymph nodes metastasis.

OBJECTIVE: This study was conducted to evaluate the efficacy and toxicity of extended-field intensity-modulated radiation therapy combined with concurrent chemotherapy in patients with cervical cancer with positive para-aortic lymph nodes (PALN). METHODS: From September 2007 to December 2014, a total of 59 patients who had cervical cancer with para-aortic lymph node metastasis were treated with concurrent chemoradiotherapy at our institution. A dose of 45-50.4 Gy in 25-28 fractions with extended-field intensity-modulated radiation therapy was prescribed to planning target volume, and a dose of 30-36 Gy in 5-6 fractions was prescribed to Point A with high-dose-rate brachytherapy. A concurrent first-line cisplatin-based chemotherapy regimen was used. RESULTS: The median duration of follow-up was 32.1 months (range, 3.2-103.7 months). The 2- and 3-year overall survival, disease-free survival and local control rates were 69.0 and 52.8%, 45.0 and 41.3% and 83.4 and 81.0%, respectively. Distant metastasis was the major pattern of treatment failure, which occurred in 26 patients (44.1%). The incidence of Grade 3 or greater acute hematologic, gastrointestinal and genitourinary toxicity was 50.9, 1.7 and 3.4%, respectively. Only one patient had both Grade 3 late gastrointestinal and genitourinary toxicity. CONCLUSIONS: The study found that extended-field intensity-modulated radiation therapy combined with concurrent chemotherapy was safe and effective in patients who had cervical cancer with positive PALN.

Evaluation of Antitumor Efficiency of High Intensity Radiation 169Yb Source on Experimental Sarcoma M-1.

Rats with sarcoma M-1 were exposed to high dose rate irradiation with 169Yb source. In 25 days after introduction of a trocar with sealed capsule with 169Yb source into the tumor, complete tumor regression was observed in 70% animals. The results suggest feasibility of using 169Yb source for high-dose rate brachytherapy and development of the personalized medicine approaches.

A modified technique for fabrication of custom-made afterload brachytherapy appliance.

Radiotherapy for carcinomas that involve the mouth and its related structures has been improved by the usage of different prostheses known as radiation carriers. These prostheses can accurately position radionuclide such as radium, iridium, cesium, and cobalt to allow adequate transfer of a concentrated radiation dose to a tumor region. At the same time, they minimize the exposure to radiation of nearby tissues due to rapid fall-off the radioactivity and thus minimizing the side effects of radiation. This study emphasizes the usage of a modified technique for the development of afterload mold brachytherapy appliance for squamous cell carcinoma patients of hard palate/soft palate.

Preliminary report of a single-channel applicator in high dose rate afterloading brachytherapy for cervical cancer.

The aim of this study was to evaluate whether a patented single-channel applicator, which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in high dose rate (HDR) brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (2009) stage Ib2-IVa cervical cancer were recruited to the trial and finished the allocated intervention. Of the first 151 patients, 71 were allocated to the Fletcher group and 80 to the single-channel group, satisfying the criteria for a preliminary analysis. All but 3 patients were treated with concurrent cisplatin chemotherapy and external beam radiotherapy followed by HDR brachytherapy. The 2-year overall survival, progression-free survival, and locoregional failure-free survival was 80.3%, 77.5%, and 78.9%, respectively, for the Fletcher group, and 86.3%, 82.5%, and 83.8%, respectively, for the single-channel group. The seriousness of acute treatment-related toxicities was similar in the 2 groups. The cumulative rate of late rectal complications of grade 3-4 in the Fletcher group and the single-channel group was 2.8% and 2.5%, respectively. The cumulative rate of grade 3 bladder complications was 2.8% for the Fletcher group and 1.3% for the single-channel group. The preliminary results of our study show that the patented single-channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher-type 3-channel applicator in HDR brachytherapy for carcinoma of the cervix. This trial was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR-TRC-12002321).