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Purpose: Second conservative treatment has emerged as an option for patients with a second ipsilateral breast tumor event after conserving surgery and breast irradiation. We aimed to address the lack of evidence regarding second breast event treatment by comparing oncologic outcomes after conservative treatment or mastectomy., Methods and Materials: Oncologic outcomes were analyzed using a propensity score-matched cohort analysis study on patients who received a diagnosis of a second breast event between January 1995 and June 2017. Patient data were collected from 15 hospitals/cancer centers in 7 European countries. Patients were offered mastectomy or lumpectomy plus brachytherapy. Propensity scores were calculated with logistic regression and multiple imputations. Matching (1:1) was achieved using the nearest neighbor method, including 10 clinical/pathologic data related to the second breast event. The primary endpoint was 5-year overall survival from the salvage surgery date. Secondary endpoints were 5-year cumulative incidence of third breast event, regional relapse and distant metastasis, and disease-free and specific survival. Complications and 5-year incidence of mastectomy were investigated in the conservative treatment cohort., Results: Among the 1327 analyzed patients (mastectomy, 945; conservative treatment, 382), 754 were matched by propensity score (mastectomy, 377; conservative treatment, 377). The median follow-up was 75.4 months (95% confidence interval [CI], 65.4-83.3) and 73.8 months (95% CI, 67.5-80.8) for mastectomy and conservative treatment, respectively (P = .9). In the matched analyses, no differences in 5-year overall survival and cumulative incidence of third breast event were noted between mastectomy and conservative treatment (88% [95% CI, 83.0-90.8] vs 87% [95% CI, 82.1-90.2], P = .6 and 2.3% [95% CI, 0.7-3.9] vs 2.8% [95% CI, 0.8-4.7], P = .4, respectively). Similarly, no differences were observed for all secondary endpoints. Five-year cumulative incidence of mastectomy was 3.1% (95% CI, 1.0-5.1)., Conclusions: To our knowledge, this is the largest matched analysis of mastectomy and conservative treatment combining lumpectomy with brachytherapy for second breast events. Compared with mastectomy, conservative treatment does not appear to be associated with any differences in terms of oncologic outcome. Consequently, conservative treatment could be considered a viable option for salvage treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4-6 weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with 'only two techniques-1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)'-in terms of equivalent local control/overall survival to the previous standard 'conventionally fractionated WBIR'. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The purpose of this study was to report our initial clinical results of hyaluronic acid gel injection (HGI) in the rectovaginal septum (RVS) to reduce the incidence of rectal bleeding in vaginal brachytherapy for gynecologic malignancies., Methods and Materials: Since 2008, CT based image-guided adaptive brachytherapy (IGABT) was initiated, and since 2015, HGI in the RVS was introduced in our institution. Vaginal cylinder with or without tandem or additional interstitial needles were applied for patients with gynecologic malignancies. Rectum dosimetric parameters and incidence of late rectum bleeding were compared between patients with and without HGI in the RVS., Results: Between May 2008 and October 2017, 83 patients with gynecologic malignancies were treated with IGABT involving vaginal cylinder. Eleven patients who were treated for palliative intention were excluded, and 72 patients were subjected to the analysis. Of the total 72 patients 46 were with uterine cervical cancer, 19 uterine corpus cancer, five vaginal cancer, one vulvar cancer, and one ovarian cancer. Fifteen and 57 patients were irradiated with and without HGI in the RVS, respectively. With a median follow-up period of 57.7 (4.7-123.1) months, 30 (41.7%) patients suffered from radiation-related rectal bleeding. Patients with HGI in the RVS had a statistically significant lower incidence of rectal bleeding compared with those without it (13.3% vs. 49.1%, p = 0.01)., Conclusions: HGI in the RVS reduced the incidence of late rectal bleeding for patients with gynecologic malignancies treated by vaginal cylinder and was not associated with HGI-procedure-related adverse events., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control., Methods and Materials: Combined pelvis-external beam radiation/HDR-BT boost to EQD2 >100 Gy (α/β = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan-Meier/log-rank tests and Cox-regression models were used to compare the study endpoints., Results: The mean FU was 77 months. A PSA nadir within 18 months (nPSA18) <0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group <0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively)., Conclusions: The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 < 0.5 ng/mL., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: This consensus statement from the Breast Cancer Working Group of Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO) aims at generating practical guidelines for multi-catheter image-guided brachytherapy in the conservative management of breast cancer patients used for either Accelerated Partial Breast Irradiation (APBI) or for a breast boost., Methods: Recent advances in techniques of multi-catheter brachytherapy were summarized and all the relevant literature was reviewed by a panel of experts. Panel members of the GEC-ESTRO experts participated in a series of conferences, supplemented their clinical experience, were surveyed to determine their current practices and patterns, performed a literature review, and formulated recommendations for implementing APBI with multi-catheter brachytherapy, focusing on treatment planning issues, catheter insertion, dosimetry and quality assurance. This document was reviewed and approved by the full panel, the GEC-ESTRO executive board and by the ACROP (Advisory Committee on Radiation Oncology Practice)., Results: Three-dimensional (3D) treatment planning, catheter insertion techniques, dosimetry and methods of quality assurance for APBI and boost with multi-catheter image-guided brachytherapy after breast conserving surgery are described. Detailed recommendations for daily practice including dose constraints are given., Conclusions: Recent standards and guidelines for the use of APBI with different multi-catheter image-guided brachytherapy techniques have been defined. Different techniques are used to insert the catheters. Guidelines are mandatory to assure precise catheter insertion for coverage of the target volume and to guarantee high-quality dosimetry. The same rules apply for brachytherapy based boost irradiation for breast cancer after whole breast irradiation as well as for partial breast re-irradiation., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Efficacy of different schedules of HDR brachytherapy in concurrent chemoradiotherapy was evaluated. The study compared the effectiveness of the two HDR brachytherapy schedules which have the same Biological Effective Dose (BED) in locally advanced cervical carcinoma that was treated with concurrent chemoradiotherapy. Included in the study were 377 randomly selected patients with advanced carcinoma of the cervix uteri who were treated during the period 2004-2006. Patients were divided into Group I: 7.2 Gy × 3 fractions and Group II: 6 Gy × 4 fractions. With a median follow-up time of 35 months, local control, disease-free survival and overall survival rates were 80.8%, 63.4%, 98.8% in group I and 86.7%, 63.8%, 97.3% in group II, respectively. There was no statistical significance in terms of local control, disease-free survival, overall survival and complication rates between the two treatment schedules which could be observed. Seven patients in group I developed acute grade 2-4 GI toxicities and two patients in group II. In GU toxicities, there were three patients in group I and three patients in group II who developed grade 2-4 toxicities. In late toxicity, no patient developed grade 3-4 GU toxicities in group I while two patients developed grade 3-4 GU toxicities in group II. In GI toxicities, there were five and six patients in group I and group II, respectively, who developed grade 3-4 severity. Both HDR schedules seem to be safe and effective for the treatment of locally advanced cervical cancer.

Intracavitary brachytherapy using tandem and ovoids is an important component of definitive treatment for cervical cancer. In the present study, we analyzed the dose-volume histograms (DVHs) of the tumor volume and organs at risk including the sigmoid colon by CT-based treatment planning for high dose rate (HDR) intracavitary brachytherapy (ICBT) in cervical cancer. Seventeen patients with carcinoma of the cervix uteri were treated with external beam radiotherapy plus concurrent chemotherapy. For brachytherapy, the planning procedure started by performing a conventional plan which prescribed a dose of 6.5-7 Gy per fraction to point A, then optimized the dose based on CT imaging. Volumes and DVHs were calculated for the HR-CTV, bladder, rectum and sigmoid colon. The mean BED(2Gy) total doses of post-optimized plans of HR-CTV, bladder, rectum and sigmoid colon were: 89.6, 94.1, 74.0 and 69.8 Gy, respectively. For conventional plans, the calculated mean BED(2Gy) total doses of HR-CTV, bladder, rectum and sigmoid colon were 92.2, 120.1, 75.7 and 78.3 Gy, respectively. This study showed statistical significant higher BED(2Gy) total doses for bladder and sigmoid colon (p < 0.001) using conventional plans versus post-optimized, CT-based plans, while no difference between HR-CTV and rectum BED(2Gy) total doses could be detected. After a median follow-up of nineteen months, all seventeen patients had a clinical complete response. Two patients developed distant metastasis. Compared with conventional treatment, CT based brachytherapy planning was very effective in reducing doses to OARs, especially bladder and sigmoid colon whilst maintaining a high therapeutic dose for tumor target volumes in the treatment of cervical carcinoma.

Prostate cancer (PCA) is the most frequent onlocological disease in men. Every year there are ca. 202.000 new cases of prostate cancer in Europe. Curative treatment of this carcinoma via brachytherapy is becoming increasingly significant (20-30% of all curative approaches). Initial staging and thus allocation to risk groups prior to the commencement of therapy is esspecially important for successful brachytherapy treatment.Low-dose-rate (LDR) brachytherapy (i.e. SEED implantation) distinguishes itself both with respect to the procedure as well as the indication from high-dose-rate brachytherapy (afterloading procedure). Both treatment procedures are employed as monotherapy as well as in combination with external radiation.LDR monotherapy is reported to achieve biochemically relapse-free outcome of up to 90% in low-risk tumours during 10-year follow-up periods. Combined HDR tele- and brachytherapy is reported to achieve a biochemically relapse-free outcome of 80-90% with intermediate- and high-risk tumours in long-term follow-up.While randomized studies are as yet missing, it is still possible to derive the following application algorithms from monitoring studies and cohort studies: application of LDR monobrachytherapy must be restricted to low-risk tumorus. Combined HDR tele- and brachytherapy can be sucessfully applied in cases of intermediate- and high-risk tumours. The outcome depends significantly on the initial, pre-therapy PSA value and Gleason score. Posttherapeutically, the nadir value is crucial with respect to predicting the biochemically relapse-free outcome.

The role of neoadjuvant androgen deprivation (NAD) in high-risk prostate cancer patients receiving high-dose radiotherapy (RT) remains unstudied. To evaluate the effect of a course of NAD, we reviewed the experiences of three institutions treating these patients with combined RT and high-dose rate brachytherapy (HDR). Of 1260 prostate cancer patients with high-risk features (pretreatment prostate-specific antigen (PSA) > or =10, Gleason Score (GS) > or =7, or T stage > or =T2b), 560 received no NAD (n=308) or NAD for < or =6 months (n=252). Median dose to the prostate from RT and HDR was 42 and 23 Gy, respectively. Average total biologic equivalent prostate dose was >100 Gy (alpha/beta=1.2). Median follow-up was 4.3 years. Pretreatment characteristics were similar on chi(2) tables for all 560 patients treated with or without NAD including pretreatment PSA (P=0.11), GS (P=0.4), and clinical T stage (P=0.2). Outcomes worsened for patients receiving NAD (5-year distant metastasis (DM) 10 vs 5% (P=0.04); cause-specific survival (CSS), 93 vs 98% (P=0.005)). Higher 5-year DM rates and lower CSS occurred in NAD patients with a GS between 8 and 10 (n=112 (P=0.03, P=0.02)), pretreatment PSA> or =15 (n=136 (P=0.03, P=0.008)), and palpable disease > or =T2a (n=434 (P=0.04, P=0.02)). The only two significant risk factors for DM on Cox multivariate analysis were GS (P=0.003, HR 2.8) and NAD (P=0.03, HR 2.7). AD given before definitive high-dose RT did not benefit prostate cancer patients with intermediate- and high-risk features. We favor the use of concurrent/adjuvant AD over prolonged NAD for prostate cancer patients for whom AD is clinically indicated.

Purpose: Feasibility of combined fractionated intensity modulated brachytherapy (IMBT) and external beam radiotherapy (EBRT) as well as the effect of local dose escalation was investigated in a non-randomized retrospective observation trial for histologically-proven macroscopic local recurrences of prostate cancer after radical prostatectomy., Methods and Materials: Thirty-five patients with transrectal ultrasound (TRUS) detectable tumors were treated. Applied dose per IMBT fraction was 15 Gy, prescribed on the target (TRUS visible tumor) surface. For the first 21 patients, two fractions of IMBT were delivered in 2 weeks interval, complementary to 30 Gy EBRT to the small pelvis. Further, as second step of dose escalation, 14 patients were treated with 2 x 15 Gy IMBT combined with 40 Gy EBRT. The total treatment time was 4 and 5 weeks, respectively., Results: PSA was decreased in 34 out of 35 patients post-therapeutically. After a mean follow-up of 27 months, 32 out of 35 patients are alive. However, in 67% of the patients, we observed postimplant PSA elevation with or without detectable local and/or systemic progress. The mean duration of biochemical non-evidence of disease (bNED) after radiation was 12 months for all patients (31% in the 30 Gy group and 42% in the 40 Gy group). No RTOG/EORTC grade III or IV side effects were registered during/after radiotherapy., Conclusion: Combined EBRT and IMBT-boost of TRUS detectable recurrences of prostate cancer after radical prostatectomy seems to be a feasible method of salvage treatment. These early results need to be confirmed by further prospective randomized trials and by longer follow-up in all dose groups.

Purpose: To study the influence of imaging based nodal staging and local dose escalation by a high-dose-rate brachytherapy (HDR-BT) boost in the treatment of locally confined prostate cancer in terms of prostate specific antigen (PSA) recurrence-free survival (biochemical non-evidence of disease (bNED)), treatment toxicity and prognostic variables., Patients and Methods: The prospectively recorded files of 144 men aged in a median of 68 years with a mean follow-up of 8 years (60-171 months) receiving curatively intended, transrectal ultrasound guided high-dose-rate 192-iridium-brachytherapy (HDR-BT) combined with external beam radiation therapy (EBRT) for locally confined prostate cancer were analyzed. T-stages were defined by digital rectal investigation and transrectal sonography (TRUS), nodal staging was performed with computed tomography(CT)/magnetic resonance imaging (MRI) (UICC/AJCR 1992). Twenty-nine patients (20.1%) had T1b-T2a tumors, and 115 patients had T2b-T3 tumors. Median initial PSA (iPSA) was 12.15 ng x mL(-1) (mean 25.61 ng x mL(-1)). The total planned dose applied by external beam radiation was 50 Gy in the pelvis, and 40 Gy in the prostate by in-field-dose modification by individual compensators. The perineal, TRUS guided HDR-BT was delivered in two fractions of 15 Gy each. The target of BT boost was the peripheral zone of the prostate., Results: The overall survival was 71.5% and that of the disease free survival 82.6%. Freedom from distant metastases in T3 stage was 91.3%, whereas for G3 lesions, it was 88.23%. The bNED rate was 72.9%. Regarding treatment related late toxicity according to the EORTC/RTOG score, we observed grade 1, 2, 3 proctitis in 9.72%, 6.94%, 4.10% as well as grade 1, 2, 3 cystitis in 12.5%, 4.16%, 2.08%, respectively. Grade 4 and 5 proctitis or cystitis were not registered., Conclusion: The minimum 5-year and mean 8-year results confirm that local dose escalation by TRUS guided perineal HDR-BT and complementary external beam radiation of the pelvic lymphatics has curative potential in men with locally confined high-risk prostate cancer, although surgical staging results in the literature suggest a high probabilityof microscopic nodal involvements at the level of 25.61 ng x mL(-1) mean PSA. The influence of additional short-term (< 6 months) hormonal ablation on the treatment results could not be stated.

To evaluate a new therapy protocol for local dose escalation by high dose rate (HDR) brachytherapy for survival, morbidity and prognostic variables in men with localized prostate cancer. The prospectively recorded files of 189 men aged in median 69 years with a mean follow-up of 6 years (12-143 months) receiving curatively intended combined high dose rate (HDR) 192-iridium-brachytherapy (BT) and external beam radiation (EBR) for locally confined prostate cancer were analyzed. Mean age was 68.2 (range 44-84 years). Hundred and twenty-seven patients had T1-2 tumors, and 62 patients had T3-tumors. The total planned dose applied by external beam radiation was 50 Gy in the pelvis, and 40 Gy in the prostate by in-field-dose modification. The HDR-brachytherapy was delivered in two fractions. The dose per fraction amounted 15 Gy. Mean survival was 6 years (range 12-143 months), 76.7% of the patients survived and 86.3% were disease-free. The biochemical non-evidence of disease rate (BNED) was 78%. Univariate survival analysis revealed that low stage (T1-2), low grade (G1-2), normal PSA status after radiation therapy, and no adjuvant hormonal treatment were associated with long survival. However, the stratification for adjuvant hormonal treatment was not according to random. In multivariate analyses PSA status was an independent prognostic factor. The six year results confirm that local dose escalation by HDR-brachytherapy and external beam radiation is curative in men with locally confined prostate cancer. The results are especially in high risk patients encouraging.

Purpose: The combined external beam- and high-dose rate brachytherapy (HDR-BT) of localized prostate cancer was introduced at Kiel University in 1986. The aim of this intermediate analysis was to judge the Kiel method of localized prostate cancer radiation treatment after ten years experience., Patients and Methods: In the past ten years 174 patients with histological proven localized prostate cancer were subjected to combined tele-/HDR-brachytherapy. Local staging in all of the cases by transrectal ultrasound, nodal staging in the majority of the cases by CT or MRI. Average age of the patients was 68.2 years (44-84). According to AJCC/UICC staging T1B, T2, T3 was found in 2, 113 and 59 cases, respectively. Highly differentiated tumors (G1) were found in 27, moderately differentiated (G2) in 87, poorly differentiated (G3) in 60 cases. The mean follow-up was 47.1 months with the median of 51.7 months. Total prescribed dose 50 Gy on the small pelvis and 70 Gy on the prostate capsule due to the integration of two, 15 Gy each, HDR-brachytherapy fractions in 6 weeks., Results: Ten patients died of prostate cancer and 18 of intercurrent diseases resulting in a 5 years overall survival rate of 83% and tumor specific survival rate of 94%. Twenty-one patients showed a clinical progression, of these 14 systemic, 5 local and 2 both systemic and local. Additional 16 patients had PSA elevation only. The 5-years biochemical and/or clinical progression-free survival in the cohort was 79% and 73% for the T3 tumors. Side effects were 27 cases of proctitis/colitis and 20 cases of dysuria/cystitis., Conclusion: The integrated HDR-BT combined with external beam radiation treatment is a method with excellent tumor control rates at five years superior to those of external beam treatment alone or external beam combined with iodine-125 implants. This form of radiotherapy would appear to be particularly well-suited to treatment of advanced localized (T3) tumors.

Twenty-eight patients with recurrent (82.1%) and/or noncuratively resected (71.4%) colorectal cancer underwent fractionated interstitial BT (20.1 Gy) by using median 5.6 (3-11) afterloading tubes placed directly on the tumor bed intraoperatively. HDR/PDR BT started 2-3 weeks after multivisceral resection (50%) and was combined with external beam radiation therapy in 96% and with chemotherapy (5-FU/Leucoverin) in 86% of the patients. Though the R0-resection rate before BT was only 28.6% multimodality treatment resulted in a local tumor control rate of 64.3%, a survival rate of 53.6%, and a tumor-free survival rate of 42.9%, in an average of 19.8 months (2-43 months) after BT.

Purpose: The success of an interstitial brachytherapy treatment is based on the correct implantation geometry. Frequently, deviations of top needle vs. template coordinates were observed by transrectal sonography of 358 high-dose-rate (HDR) implantations for prostate cancer., Patients and Methods: In cooperation with the companies BIP GmbH and Isotopen-Technik Dr. Sauerwein GmbH we developed a high-speed implantation machine, which was tested by 22 interstitial prostate applications. We compared the manual needle positioning method to the high-speed machine and observed the sequence of needle deviation as well as the acute postoperative side effects (hematoma, macroscopic hematuria, pain and urin stop)., Results: Using the manual implantation method (n = 12) 43.8% of all implanted needles (42 out of 96, mean 3.5) showed a deviation vs. 3.6% (3 out of 83, mean 0.3) by the use of the high-speed device (n = 10). Acute postoperative side effects according to the implantation were: urin stop (3 vs. 0), macroscopic hematuria (3 vs. 1), and pain (4 vs. 1), respectively., Conclusion: The use of a modified high-speed biopsy device for the interstitial brachytherapy results in a higher accuracy in the needle positioning and in reproducing pretreatment implantation plans. Because of the good clinical experience we introduced the high-speed implantation device into our clinical routine.