Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort.

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.

Intraoperative Neurovascular Bundle Preservation with Hyaluronic Acid during Radical Brachytherapy for Localized Prostate Cancer: Technique and MicroMosfet In Vivo Dosimetry.

PURPOSE: To evaluate the reduction in the absorbed dose delivered to the neurovascular bundle (NB) in patients with localized prostate cancer treated with only HDR brachytherapy and NB protection with hyaluronic acid (HA) on the side of the prostate to increase the distance from NB to the radioactive sources. METHODS: This is the first published report in the medical literature that studies a new approach to decrease neurovascular bundle toxicity and improve quality of life for patients with prostate cancer treated with radical brachytherapy as monotherapy. Transperineal HA injection on the side of the prostate into the lateral aspect of the prostate fat was used to consistently displace several autonomic fibers and vessels on the lateral wall of the prostate away from radiation sources. RESULTS: When a protection in the form of an HA layer is placed, the reduction effect at the maximum dose is between 46% and 54% (calculated values), which means that the method for protection is highly recommended. The values of the absorbed dose calculated in this project have been compared with the ones given by the treatment planning system. CONCLUSIONS: This newly created space decreases absorbed dose in the NB, calculated with the TPS and measured by microMOSFET due to the thickness of HA.

Hyperbaric Oxygen Therapy Does Not Have a Negative Impact on Bone Signaling Pathways in Humans.

INTRODUCTION: Oxygen is emerging as an important factor in the local regulation of bone remodeling. Some preclinical data suggest that hyperoxia may have deleterious effects on bone cells. However, its clinical relevance is unclear. Hence, we studied the effect of hyperbaric oxygen therapy (HBOT) on serum biomarkers reflecting the status of the Wnt and receptor activator of NF-κB ligand (RANKL) pathways, two core pathways for bone homeostasis. MATERIALS AND METHODS: This was a prospective study of 20 patients undergoing HBOT (mean age 58 yrs., range 35-82 yrs.) because of complications of radiotherapy or chronic anal fissure. Patients were subjected to HBOT (100% oxygen; 2.4 atmospheres absolute for 90 min). The average number of HBOT sessions was 20 ± 5 (range 8-31). Serum hypoxia-inducible factor 1-α (HIF1-α), osteoprotegerin (OPG), RANKL, and the Wnt inhibitors sclerostin and dickkopf-1 (DKK1) were measured at baseline and after HBOT by using specific immunoassays. RESULTS: HIF-1α in eight patients with measurable serum levels increased from 0.084 (0.098) ng/mL at baseline to 0.146 (0.130) ng/mL after HBOT (p = 0.028). However, HBOT did not induce any significant changes in the serum levels of OPG, RANKL, sclerostin or DKK1. This was independent of the patients' diagnosis, either neoplasia or benign. CONCLUSION: Despite the potential concerns about hyperoxia, we found no evidence that HBOT has any detrimental effect on bone homeostasis.

Influence of hyperbaric oxygen therapy on bone metabolism in patients with neoplasm.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is useful in the treatment of complications due to radiotherapy in patients with neoplasm. Its effects on bone metabolism are unclear. In our study, we analyzed the effects of HBOT on bone remodeling in oncological patients with radiotherapy. MATERIALS AND METHODS: Prospective clinical study in 23 patients with neoplasms undergoing treatment with HBOT due to complications of radiotherapy (hemorrhagic cystitis, proctitis or radionecrosis) and 25 patients with chronic anal fissure. The average number of HBOT sessions was 20 ± 5 (100% oxygen, 2.3 atmospheres and 90 min per day). Serum levels of aminoterminal propeptide of type I collagen (P1NP), C terminal telopeptide of type I collagen (CTX), alkaline phosphatase (AP), 25hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), were measured at 3 time points: T0 (before beginning HBOT), T1 (at the end of HBOT) and T2 (6 months after HBOT). RESULTS: At baseline, the patients with neoplasm have higher bone turnover than those with anal fissure. These differences were 41% in CTX (0.238 ± 0.202 ng/mL in neoplasm and 0.141 ± 0.116 ng/mL in fissure; p = 0.04), 30% for PTH (46 ± 36 pg/mL in neoplasm and 32 ± 17 pg/mL in fissure; p = 0.04) and 15% for alkaline phosphatase (80 ± 24 U/L in neoplasm and 68 ± 16 U/L in fissure; p = 0.04). In the group with neoplasm, the values of P1NP decreased 6% after HBOT (T0: 49 ± 31 ng/mL, T2: 46 ± 12 ng/mL; p = 0.03). Also, there were non-significant decreases in PTH (-34%) and CTX (-30%). CONCLUSIONS: Patients with neoplasm and complications with radiotherapy have an increase in bone remodeling that may be diminished after HBOT.

Characterization of microMOSFET detectors for in vivo dosimetry in high-dose-rate brachytherapy with 192 Ir.

PURPOSE: The objective of this study was to characterize the Best Medical Canada microMOSFET detectors for their application in in vivo dosimetry for high-dose-rate brachytherapy (HDRBT) with 192 Ir. We also developed a mathematical model to correct dependencies under the measurement conditions of these detectors. METHODS: We analyzed the linearity, reproducibility, and interdetector variability and studied the microMOSFET response dependence on temperature, source-detector distance, and angular orientation of the receptor with respect to the source. The correction model was applied to 19 measurements corresponding to five simulated treatments in a custom phantom specifically designed for this purpose. RESULTS: The detectors (high bias applied in all measurements) showed excellent linearity up to 160 Gy. The response dependence on source-detector distance varied by (8.65 ± 0.06)% (k = 1) for distances between 1 and 7 cm, and the variation with temperature was (2.24 ± 0.05)% (k = 1) between 294 and 310 K. The response difference due to angular dependence can reach (10.3 ± 1.3)% (k = 1). For the set of measurements analyzed, regarding angular dependences, the mean difference between administered and measured doses was -4.17% (standard deviation of 3.4%); after application of the proposed correction model, the mean difference was -0.1% (standard deviation of 2.2%). For the treatments analyzed, the average difference between calculations and measures was 4.7% when only the calibration coefficient was used, but it is reduced to 0.9% when the correction model is applied. CONCLUSION: Important response dependencies of microMOSFET detectors used for in vivo dosimetry in HDRBT treatments, especially the angular dependence, can be adequately characterized by a correction model that increases the accuracy of this system in clinical applications.

Focal high-dose-rate brachytherapy for localized prostate cancer: toxicity and preliminary biochemical results.

BACKGROUND: This study aimed to evaluate the outcomes and the toxicity of focal high-dose-rate (HDR) brachytherapy in selected localized prostate cancer patients. METHODS: Fifty patients were treated with focal high-dose-rate brachytherapy between March 2013 and November 2017, representing 5% of the cases treated by our group during this period. Only patients with very limited and localized tumors, according to strict criteria, were selected for the procedure. The prescribed dose for the focal volume was 24 Gy. RESULTS: The treated volume corresponded to a mean value of 32% of the total prostatic volume. The mean focal D90 in our series was 23 Gy (range 16-26 Gy). The mean initial IPSS was 8.2 (range 0-26), at 6 months 7.5 (range 0-23), and at 24 months 6.7 (range 0-18). No acute or late urinary retention was seen. When the ICIQ-SF score was 0 at the end of treatment, it remained nil thereafter at 1 and 2 years for all patients. No intraoperative or perioperative complications occurred. No rectal toxicity was reported after treatment. Of the total patients identified as potent, only three patients had a very slight decrease of the mean IIEF5. The mean initial PSA was 6.9 ng/mL (range 1.9-13.4). At the last follow-up visit, the mean PSA was 3 ng/ml (range 0.48-8.11). CONCLUSION: HDR focal brachytherapy in selected patients with low intermediate-risk prostate cancer could achieve the same satisfactory results in terms of relapse-free survival as conventional whole prostate brachytherapy with less toxicity.

High-dose-rate interstitial brachytherapy as monotherapy in one fraction of 20.5 Gy for the treatment of localized prostate cancer: Toxicity and 6-year biochemical results.

PURPOSE: To evaluate acute and late genitourinary toxicity, the gastrointestinal toxicity, and the long-term biochemical control after high-dose-rate (HDR) monotherapy in one fraction (20.5 Gy). MATERIALS AND METHODS: Between May 2011 and October 2014, 60 consecutive patients with low- and intermediate-risk prostate cancer were treated; the median followup was 51 months (range 30-79). All patients received one implant and one fraction of 20.5 Gy HDR real-time U/S planned with transperineal hyaluronic acid injection into the perirectal. Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, Version 4.0 (CTAE v4.03) by the National Cancer Institute. Biochemical failure was defined according to the "Phoenix definition". RESULTS: Our experience in a single fraction of 20.5 Gy HDR brachytherapy is well-tolerated. No intraoperative or perioperative complications occurred. Grade 1 acute genitourinary toxicity occurred in 36% of patients, Grade 2 or more was not observed, only 1 patient requiring the use of a catheter for 7 days in the immediate postoperative period. No gastrointestinal toxicity was observed. No chronic toxicity has been observed after treatment. Morbidity is practically the same as that obtained with 19 Gy in our previously published article but the actuarial biochemical control was better, 82% (±3%) at 6 years. CONCLUSIONS: A single dose of 20.5 Gy resulted in a low genitourinary morbidity and no gastrointestinal toxicity and achieves good levels of biochemical disease control.

Long-term outcomes in patients younger than 60 years of age treated with brachytherapy for prostate cancer.

PURPOSE: The purpose of the study was to report the outcomes and late toxicities in patients younger than 60 years of age with long-term follow-up treated with low dose rate (LDR) brachytherapy for localized prostate cancer. METHODS: Between January 2000 and December 2009, 270 consecutive patients were treated with favourable localized prostate cancer; the median follow-up was 111 months (range 21-206). All patients received one implant of LDR brachytherapy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Events, Version 4.0 (CTAE v4.02) by the National Cancer Institute. RESULTS: The overall survival according to Kaplan-Meier estimates was 99 (±1%) at 17 years. The 17-year rate for failure in tumour-free survival (TFS) was 97% (±1%), whereas for biochemical control it was 95% (±1%) at 17 years, 97% (±1%) of patients being free of local recurrence. No intraoperative or perioperative complications occurred. Acute genitourinary (GU) grade II toxicity was 4% at 12 months. No other chronic toxicity was observed after treatment. At 6 months, 94% of patients reported no change in bowel function. CONCLUSIONS: LDR brachytherapy provides patients younger than 60 years of age with low and intermediate-risk prostate cancer excellent outcomes and has a low risk of significant long-term GU or gastrointestinal morbidity.

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer. Longterm results.

OBJECTIVES: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. METHODS AND MATERIALS: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the "Phoenix consensus". Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. RESULTS: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. CONCLUSIONS: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer.

High-dose-rate interstitial brachytherapy as monotherapy in one fraction for the treatment of favorable stage prostate cancer: Toxicity and long-term biochemical results.

BACKGROUND: To evaluate acute and late genitourinary, the gastrointestinal toxicity and the long-term biochemical control after HDR monotherapy in one fraction (19Gy). PATIENTS AND METHODS: Between April 2008 and October 2010, 60 consecutive patients were treated with favorable clinically localized prostate cancer; the median follow-up was 72months (range 32-91). All patients received one implant and one fraction of HDR. Fraction dose was 19Gy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, Version 4.0 (CTAE v4.02) by the National Cancer Institute. RESULTS: No intraoperative or perioperative complications occurred. Acute toxicity grade 2 or more was not observed in any patients. No chronic toxicity, such as incontinence, late urinary retention, urethral narrowing, rectal bleeding, anal ulcer and/or rectourethral fistula has been observed after treatment. The overall survival and failure in tumor-free survival (TFS) according to Kaplan-Meier estimates was 90% (±5%) and 88% (±5%) respectively at 6years. The actuarial biochemical control was 66% (±6%) at 6years. CONCLUSIONS: This protocol is feasible and very well tolerated with low genitourinary morbidity, no gastrointestinal toxicity but no the same level of LDR biochemical control at 6years.

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer. Long-term results

ABSTRACT We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the "Phoenix consensus". Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function.Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer