Till Örebro universitet

PURPOSE: Hypofractionated radiation therapy requires high accuracy in dose delivery to enable reduced treatment margins and minimize the dose to organs-at-risk. The purpose of this study was to evaluate whether accelerated (delivered 5 times per week) hypofractionated external beam radiation therapy (EBRT) can be performed without increased acute toxicity using a real-time tracking system. We also aimed to investigate patterns of intrafractional prostate movements.

METHODS AND MATERIALS: Patients with prostate cancer planned for combined high dose rate brachytherapy (14.5 Gy × 1) and EBRT (3 Gy × 14) were included in this randomized trial to receive the EBRT part of the treatment either 3 or 5 times per week. EBRT was delivered using small margins (3 mm) using the Raypilot system for real-time tracking of intrafractional prostate movements. Movements were continuously monitored in 3 dimensions. Primary endpoint was toxicity that was assessed using patient-reported outcome measures through european organisation for research and treatment of cancer (EORTC) quality of life questionnaires QLQ-C30 and QLQ-PR25.

RESULTS: During June 2018 to January 2020, 34 patients (median age 70 years) were included in the study of which 17 were randomized to each group. No statistically significant differences in toxicity were found between the study groups. Target displacement was <2 mm during 97.0% of the time and <3 mm during 99.9% of the active treatment time.

CONCLUSIONS: We found no evidence of increased acute toxicity in patients who received accelerated treatment schedule. Provided that the target is properly delineated, a 3 mm margin seems to be feasible and safe when using a real-time tracking system.

INTRODUCTION: Treating localized high-risk prostate cancer with a combination of external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) is a common approach. Moderately hypofractionated EBRT and a single HDR-BT boost simplifies the treatment. We aim to present our five-year results.

METHODS: In this study, 355 patients treated with moderately hypofractionated EBRT (42 Gy in 14 fractions) and a single HDR-BT boost (14.5 Gy) at Örebro University Hospital between 2008 and 2018 were included. They were followed with regular PSA tests.

RESULTS: The median age of the cohort was 70 years (range: 51-81) and the median follow-up duration was 56 months (range: 6-150). Among them, 45% were classified as very high-risk, 38% as high-risk and 17% as intermediate-risk. Adjuvant androgen deprivation therapy (ADT) with a median duration of 24 months was given to 75% of the patient cohort. The estimated 5-year failure free survival rates were 79% (whole cohort), 66% (very high-risk), 90% (high-risk) and 85% (intermediate-risk), respectively. Initial PSA > 10 ng/mL, Gleason score 9-10 and tumor stage T3 were significantly associated with biochemical failure (BF). A PSA bounce occurred in 53 (15%) cases and was inversely associated with BF (p = 0.001) for patients receiving ADT.

CONCLUSIONS: Moderately hypofractionated EBRT and a single HDR-BT boost seems to be an effective treatment against intermediate- and high-risk localized prostate cancer. Treatment escalation strategies should be investigated for very high-risk patients where the risk of recurrence remains high.

PURPOSE: The aim of this retrospective, single-center cohort study was to evaluate the effectiveness and safety of two-fraction high-dose-rate brachytherapy (HDR-BT) as monotherapy in a consecutive cohort of prostate cancer patients.

METHODS: We included consecutive patients who received 28 Gy HDR-BT in two fractions (14 Gy × 2) as monotherapy during 2005 to 2021 at our institution. Eligible patients were derived from an institutional database consisting of prospectively collected data. Primary endpoint was biochemical recurrence (BCR) and secondary endpoints included toxicity (assessed through both healthcare provider and patient-reported outcomes) and quality-of-life (QoL) assessment.

RESULTS: In total, 175 patients with prostate cancer (94 % classified as low- or intermediate-risk) were treated with HDR-BT during the study period with a median age of 68 years (range: 51-80), and a median follow-up of 60 months (range: 0-174). The estimated five-year cumulative BCR rate was 3.0 % (95 % Confidence Interval (CI): 0 %-13.3 %) for low-risk patients and 9.6 % (95 % CI: 4.7 %-16.7 %) for intermediate-risk patients. PSA exceeding 10 ng/mL at diagnosis was a significant risk factor for BCR (Odds Ratio (OR) = 3.29, 95 % CI: 1.01-10.67) whereas PSA of ≤0.1 ng/ml as nadir was a significant positive prognostic factor, associated with lower risk of BCR (OR = 0.11, 95 % CI: 0.03-0.33). At 12 months, 22 % of the patients had grade 2 and 3 % grade 3 urinary toxicity whereas 2 % of patients had grade 2 and none grade 3 bowel toxicity. At 12 months, 49 % of the patients with at least some erectile function before the treatment, had an impaired function.

CONCLUSION: We found that two-fraction HDR-BT as monotherapy among patients with mainly low- and intermediate-risk prostate cancer appears to be safe in terms of biochemical recurrence, with a low proportion of severe urinary and bowel toxicity.

PURPOSE: Intraoperative breast cancer radiotherapy (IORT) offers an alternative to external beam radiotherapy (EBRT) after breast-conserving surgery (BCS). The Intraoperative brachytherapy (IOBT) trial applies high dose rate (HDR) brachytherapy with a new applicator prototype as IORT after BCS. In this interim analysis of the IOBT trial, we present the oncological safety and toxicity of the method.

METHODS: Eligible patients were women, ≥ 50 years old with an unifocal nonlobular, estrogen-receptor-positive, HER2-negative breast cancer, cN0, ≤ 3 cm, treated with BCS and sentinel node biopsy (SNB). Toxicity was registered according to the LENT-SOMA scale. Cumulative incidence of local (LR) and regional recurrence (RR) were calculated through cumulative incidence function whereas overall survival (OS) was illustrated through Kaplan-Meier curve.

RESULTS: Until February 2023, 155 women (median age 68 years) were included in the trial. Twenty-nine women (18.7%) received supplemental EBRT, mostly due to positive SNB. Three-year cumulative incidence of LR and RR were 1.0% (CI 95 % 0.1%-2.3%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five- year cumulative incidence of LR and RR were 3.9% (CI 95% 1.8%-6.4%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five-year OS was 96.3% (CI 95% 93.6%-98.4%). Side effects were limited, low grade, and transient.

CONCLUSION: Acknowledging the short median follow-up time at interim analysis, our initial results indicate that delivering IORT through HDR brachytherapy in carefully selected breast cancer patients is feasible and oncological safe so far. A long-term follow-up is essential to confirm the initial results.

BACKGROUND: The benefit of prophylactic whole pelvis radiation therapy (WPRT) in prostate cancer has been debated for decades, with evidence based mainly on conventional fractionation targeting pelvic nodes.

AIM: This retrospective cohort study aimed to explore the impact of adding moderately hypofractionated pelvic radiotherapy to prostate-only irradiation (PORT) on prognosis, toxicity, and quality of life in real-world settings.

MATERIALS AND METHODS: Patients with high-risk and conventionally staged prostate cancer (cT1-3N0M0) treated with moderately hypofractionated WPRT or PORT, using external beam radiotherapy alone or combined with high-dose-rate brachytherapy, at Örebro University Hospital between 2008 and 2021 were identified. Biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier method and Cox proportional hazards. Toxicity and quality of life measures were also analysed.

RESULTS: Among 516 patients (227 PORT, 289 WPRT), 5-year BFFS rates were 77 % (PORT) and 74 % (WPRT), adjusted HR=1.50 (95 % CI=0.88-2.55). No significant differences were found in MFS, PCSS, or OS in main analyses. WPRT was associated with a higher risk of acute grade ≥ 2 and 3 genitourinary toxicities whereas no differences in late toxicities or quality of life between PORT and WPRT were observed.

CONCLUSION: We found no significant differences in oncological outcomes or quality of life when comparing moderately hypofractionated PORT to WPRT. Some differences in toxicity patterns were observed. Despite caveats related to study design, our findings support the need for further research on WPRT's impact on treatment-related and patient-reported outcomes.

Purpose: Treating localized prostate cancer (PC) with combination radiotherapy consisting of external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has been proven to result in better disease outcome than EBRT only. We aimed to evaluate the incidence of toxicities due to combination therapy and identify parameters correlated to acute or late urinary, rectal, and erectile toxicities.

Material and methods: Data on symptoms and tumor/treatment parameters were collected from 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) and HDR-BT (14.5 Gy in one fraction) for localized PC, at the Örebro University Hospital. Urinary, rectal, and erectile symptoms were presented descriptively, and bivariate analyses for correlation between grade ≥ 2 toxicity and potential predictors were performed. To evaluate prognostic models, multivariable analyses were applied.

Results: Urinary toxicity grade ≥ 2 was observed in 154 patients (47% of patients without pre-existing symptoms grade ≥ 2), of which 15 were grade 3. Rectal toxicity grade 2 was observed in 22 (6%) patients. Any grade erectile dysfunction was evident in all patients without pre-existing dysfunction (n = 103), whereas only 7 recovered completely. In bivariate analyses age was correlated with higher risk of acute urinary toxicity, and irradiated volume was associated with both urinary and rectal toxicities. However, we found no multivariable model of clinical and statistical significance to predict the risk of urinary or rectal toxicities.

Conclusions: In our study cohort, the severity of toxicities was in general mild or moderate and temporary, whereas the incidence of severe toxicity was considerably low. Although we found no predictive models for toxicities, our findings are reassuring that this treatment approach as curative therapy for localized PC is well-tolerated.

There is an increasing incidence of Basal cell carcinoma (BCC) and Squamous cell carcinoma (SCC) on the external nose. Surgery is the main treatment but often face problems with respect to cosmetic defects and non-radical resection. Brachytherapy (BT) can be used in the primary treatment to preserve cosmetic appearance and to treat with appropriate margins. Brachytherapy are also indicated in tumor recurrence after surgery and in case of non-radical resection. Long-term local control rate (LCR) in literature is 90-95 %. Treatment time is short 1-2 weeks.

There are different BT techniques available such as -Surface BT (Valencia applicator or Mould BT), -interstitial BT (trans-nasal or along nasal) or a combination of both.

The choice of BT technique is depending on; -thickness of the tumor, -location on the nose (cartilage part vs bony part), -tumor growth (flat part, curvature part, exophytic part), -extension to peri-nasal areas (upper lip, cheek, medial eye corner).

Usually a full dose of BT is prescribed  ike 60 Gy PDR (0.83 Gy/ 2nd hour) or 45, 5 Gy HDR (3.5 Gy 2fx/d) (GEC-ESTRO recommendations for head/neck BT RTO 20016:10 and skin RTO 2018:126). Own experience 1998-2019 in 121 patients confirms published results of 93.4 % long-term LCR.

Side effects are uncommon and include: septum perforation, telangiectasia, atrophy and sclerosis. Multidisciplinary conferences and teaching of plastic surgeons about potential benefits of BT are fundamental to avoid unnecessary mutilation.

Purpose: Until now, most long-term results for brachytherapy only has been published for low-dose-rate (LDR) seeds. Due to radiobiology reasons, high-dose-rate (HDR) mono-brachytherapy is of growing interest. The aim of the study was to report long-term biochemical control rate and toxicities with HDR monotherapy.

Material and methods: This was a retrospective single-institution experience, including 229 men, clinically staged T1c-T2b, Gleason 3 + 3 (prostate specific antigen (PSA) <= 15), or Gleason 3 + 4 (PSA <= 10), consecutively treated between 2004 and 2012 with HDR brachytherapy alone, using three different fractionation schedules of 92-95 Gy (EQD(2), alpha/beta = 3). Group 4F (n = 19) had a single implant of 9.5 Gy in four fractions over 2 days. Group 3F (n = 107) had three separate implants of 11 Gy over 4 weeks. Group 2F (n = 103) had two implants of 14 Gy over 2 weeks. No adjuvant hormonal therapy was allowed.

Results: For 4F, 3F, and 2F study groups, median follow-up was 10.2, 7.1, and 6.1 years, respectively, and biochemical failure rate was 10.5%, 4.7%, and 14.6%, respectively. Early and late side effects were followed with common terminology criteria version 2.0 and patient-reported questionnaires. There were a temporary acute urethral toxicity increase, 1-2 grades over baseline lower urinary tract symptoms (LUTS), which usually recovered. About 1/3 of the patients had a remaining one grade over baseline LUTS. Severe grade 3-4 toxicity were only found in 3.5% of patients. No rectal toxicity was observed. Erectile dysfunction (ED) was depending on age and erectile function before treatment. In patients without ED before the treatment, we found a complete ED in 21% of men at the last follow-up.

Conclusions: In the present study, HDR mono-brachytherapy was found to be an effective treatment, with mild long-term side effects difficult to differentiate from aging effects. There were no significant differences in PSA regression, PSA failure rate, and toxicity between the different fraction schedules.

Purpose: To evaluate feasibility, quality of life, toxicity, and cosmetic outcome for intraoperative breast cancer brachytherapy after breast-conserving surgery using high dose rate brachytherapy.

Methods and materials: Fifty-two consecutive women, > 50 years old, diagnosed with a unifocal non-lobular breast cancer <= 3 cm, N0, underwent breast-conserving surgery and sentinel node biopsy. Twenty-five women received intraoperative brachytherapy pre-pathology at primary surgery and the others post-pathology, during a second procedure. An applicator, connected to a high dose rate afterloader, was used. Two of the women were excluded due to metastases found per-operatively at a frozen section from the sentinel node. Quality of life was evaluated using two validated health questionnaires. Treatment toxicity was documented according to the LENT-SOMA scale by two oncologists. The cosmetic result was evaluated using the validated freely available software BCCT.core 2.0.

Results: The clinical procedure worked out well logistically. Seven women received supplementary external radiotherapy due to insufficient margins and, in one case, poor adaptation of the breast parenchyma to the applicator. No serious adverse effects from irradiation were registered. The results from the health questionnaires showed no major differences compared with reference groups from the Swedish population. Only two women were registered as having a "poor" cosmetic result while a majority of the women had a "good" outcome.

Conclusion: This pilot study shows that intraoperative brachytherapy is a feasible procedure and encourages further trials evaluating its role in treatment of early breast cancer.