Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial.

BACKGROUND: Several randomised, phase 3 trials have investigated the value of different techniques of accelerated partial breast irradiation (APBI) for patients with early breast cancer after breast-conserving surgery compared with whole-breast irradiation. In a phase 3 randomised trial, we evaluated whether APBI using multicatheter brachytherapy is non-inferior compared with whole-breast irradiation. Here, we present the 10-year follow-up results. METHODS: We did a randomised, phase 3, non-inferiority trial at 16 hospitals and medical centres in Austria, Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland. Patients aged 40 years or older with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery were centrally randomly assigned (1:1) to receive either whole-breast irradiation or APBI using multicatheter brachytherapy. Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumour bed, and APBI was delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was ipsilateral local recurrence, analysed in the as-treated population; the non-inferiority margin for the recurrence rate difference (defined for 5-year results) was 3 percentage points. The trial is registered with ClinicalTrials.gov, NCT00402519; the trial is complete. FINDINGS: Between April 20, 2004, and July 30, 2009, 1328 female patients were randomly assigned to whole breast irradiation (n=673) or APBI (n=655), of whom 551 in the whole-breast irradiation group and 633 in the APBI group were eligible for analysis. At a median follow-up of 10·36 years (IQR 9·12-11·28), the 10-year local recurrence rates were 1·58% (95% CI 0·37 to 2·8) in the whole-breast irradiation group and 3·51% (1·99 to 5·03) in the APBI group. The difference in 10-year rates between the groups was 1·93% (95% CI -0·018 to 3·87; p=0·074). Adverse events were mostly grade 1 and 2, in 234 (60%) of 393 participants in the whole-breast irradiation group and 314 (67%) of 470 participants in the APBI group, at 7·5-year or 10-year follow-up, or both. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side-effects than those in the whole-breast irradiation group (17 [4%] of 393 for whole-breast irradiation vs seven [1%] of 470 for APBI; p=0·021; at 7·5-year or 10-year follow-up, or both). At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis (six [2%] of 313 patients for whole-breast irradiation and three [1%] of 375 patients for APBI, p=0·56). No grade 4 adverse events or treatment-related deaths have been observed. INTERPRETATION: Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side-effects. FUNDING: German Cancer Aid, Germany.

The value of brachytherapy in the age of advanced external beam radiotherapy: a review of the literature in terms of dosimetry.

Brachytherapy (BT) has long been used for successful treatment of various tumour entities, including prostate, breast and gynaecological cancer. However, particularly due to advances in modern external beam techniques such as intensity-modulated radiotherapy (IMRT), volume modulated arc therapy (VMAT) and stereotactic body radiotherapy (SBRT), there are concerns about its future. Based on a comprehensive literature review, this article aims to summarize the role of BT in cancer treatment and highlight its particular dosimetric advantages. The authors conclude that image-guided BT supported by inverse dose planning will successfully compete with high-tech EBRT in the future and continue to serve as a valuable modality for cancer treatment.

Results of sole postoperative interstitial, high-dose-rate brachytherapy of T1-2 tongue tumours.

PURPOSE: To describe the results of treating tongue cancer patients with single postoperative interstitial, high-dose-rate (HDR) brachytherapy (BT) after resection. METHODS: Between January 1998 and April 2019, 45 patients with squamous cell histology, stage T1-2N0-1M0 tongue tumours were treated by surgery followed by a single HDR BT in case of negative prognostic factors (close or positive surgical margin, lymphovascular and/or perineural invasion). The average dose was 29 Gy (range: 10-45 Gy) and rigid metal needles were used in 11 (24%) and flexible plastic catheters in 34 cases (76%). Survival parameters, toxicities and the prognostic factors influencing survival were analysed. RESULTS: During a mean follow-up of 103 months (range: 16-260 months) for surviving patients, the 10-year local and regional control (LC, RC), overall survival (OS), and disease-specific survival (DSS) probabilities were 85, 73, 34 and 63%, respectively. The incidence of local grade 1, 2 and 3 mucositis was 23, 73 and 4%, respectively. As a serious (grade 4), late side effect, soft tissue necrosis developed in 3 cases (7%). In a univariate analysis, there was a significant correlation between lymphovascular invasion and RC (p = 0.0118) as well as cervical recurrence and DSS (p < 0.0001). CONCLUSION: Sole postoperative HDR brachytherapy can be an effective method in case of negative prognostic factors in the treatment of early, resectable tongue tumours. Comparing the results of patients treated with postoperative BT to those who were managed with surgery or BT alone known from the literature, a slightly more favourable LC can be achieved with the combination therapy, demonstrating the potential compensating effect of BT on adverse prognostic factors, while the developing severe, grade 4 toxicity rate remains low.

Radiotherapy instead of axillary lymph node dissection: evaluation of axillary lymph node dose coverage with whole breast radiotherapy.

Background: The purpose of this study was to investigate the dose coverage of sentinel lymph nodes (SLN), level I, II and III axillary volumes from tangent fields for breast cancer patients with positive SLN without axillary dissection. Materials and methods: In 30 patients with cN0 invasive breast cancer treated with breast conserving surgery and SLN biopsy, the SLN area was intraoperatively marked with a titanium clip. Retrospectively, the SLN area and axillary target volumes were contoured, and three plans [standard tangent fields (STgF), high tangent fields (HTgF), and STgF + axillary-supraclavicular field] were generated for each patient. The prescribed dose was standardized to 50 Gy in 2 Gy fractions to the isocenter. Results: The mean dose with STgF or HTgF was 33.1 and 49.1 Gy (p = 0.0001) in the SLN area, 25.7 and 45.1 Gy (p < 0.0001) in the volume of level I, 7.2 and 28.9 Gy (p < 0.0001) in the level II and 3.5 and 12.7 Gy (p = 0.0003) in the level III. Adequate therapeutic doses to the level II or III volumes were delivered only with STgF + axillary-supraclavicular field. The mean dose of ipsilateral lung was the highest with the three-field-technique, 9.9 Gy. SLN area, level I, II or III were completely included in the HTgF with 93.3%, 73.3%, 13.3% and 0%, respectively. Conclusions: SLN area should be marked by surgical clip and axillary target volumes should be contoured to obtain accurate dose estimations. The use of HTgF improve axillary coverage.

CyberKnife versus multicatheter interstitial brachytherapy for accelerated partial breast irradiation: a dosimetrical assessment with focus on organs at risk.

Background: The purpose of the study was to dosimetrically compare multicatheter interstitial brachytherapy (MIBT) and stereotactic radiotherapy with CyberKnife (CK) for accelerated partial breast irradiation with special focus on dose to organs at risk (OARs). Materials and methods: Treatment plans of thirty-one patients treated with MIBT were selected and additional CK plans were created on the same CT images. The OARs included ipsilateral non-target and contralateral breast, ipsilateral and contralateral lung, skin, ribs, and heart for left sided cases. The fractionation was identical (4 × 6.25 Gy). Dose-volume parameters were calculated for both techniques and compared. Results: The D90 of the PTV for MIBT and CK were similar (102.4% vs. 103.6%, p = 0.0654), but in COIN the MIBT achieved lower value (0.75 vs. 0.91, p < 0.001). Regarding the V100 parameter of non-target breast CK performed slightly better than MIBT (V100: 1.1% vs. 1.6%), but for V90, V50 and V25 MIBT resulted in less dose. Every examined parameter of ipsilateral lung, skin, ribs and contralateral lung was significantly smaller for MIBT than for CK. Protection of the heart was slightly better with MIBT, but only the difference of D2cm3 was statistically significant (17.3% vs. 20.4%, p = 0.0311). There were no significant differences among the dose-volume parameters of the contralateral breast. Conclusion: The target volume can be properly irradiated by both techniques with high conformity and similar dose to the OARs. MIBT provides more advantageous plans than CK, except for dose conformity and the dosimetry of the heart and contralateral breast. More studies are needed to analyze whether these dosimetrical findings have clinical significance.

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.

Normal tissue sparing using different techniques for prostate irradiation.

AIM: The aim of this study was to investigate normal tissue sparing through dosimetric parameters of normal tissue volumes using different irradiation techniques for conventional (CFRT) and simultaneously integrated boost (SIB) schedules. BACKGROUND: Several dose-escalation studies for localized prostate cancer (PCa) have shown advanced biochemical relapse-free (bRFS) rates and also better local control for higher total doses using either CFRT or SIB schedules. Besides the most important organs-at-risk, absorbed dose reduction of other surrounding normal tissues are also preferable. In order to analyse the normal tissue sparing, dosimetric parameters of different normal tissue volumes were examined. MATERIALS AND METHODS: Treatment plans for 15 high risk prostate cancer patients were created using RapidArc (RA), Sliding Window (SW) IMRT and 4-field box (3D-CRT) technique. In order to evaluate normal tissue sparing, the volume of pelvic region was divided into six normal tissue cylinders with 1 cm wall thickness, located in each other. RESULTS: All plans met the criteria of target coverage (V95%>95%). All techniques provided the same results for OARs except 3D-CRT for rectum and bilateral femoral heads. The values of V5, V10 and V15 increased in cases which included RapidArc technique and decreased for V20 and V30. CONCLUSIONS: The dosimetric parameters for the cylindrical normal tissue volumes show that using RapidArc technique gives equal or slightly better normal tissue sparing and SIB provided the same normal tissue sparing as CFRT planned with RapidArc.

Dosimetric comparison of inverse optimisation methods versus forward optimisation in HDR brachytherapy of breast, cervical and prostate cancer.

OBJECTIVE: Dosimetric comparison of HIPO (hybrid inverse planning optimisation) and IPSA (inverse planning simulated annealing) inverse and forward optimisation (FO) methods in brachytherapy (BT) of breast, cervical and prostate cancer. METHODS: At our institute 38 breast, 47 cervical and 50 prostate cancer patients treated with image-guided interstitial high-dose-rate BT were selected. Treatment plans were created using HIPO and IPSA inverse optimisation methods as well as FO. The dose-volume parameters of different treatment plans were compared with Friedman ANOVA and the LSD post-hoc test. RESULTS: IPSA creates less dose coverage to the target volume than HIPO or FO: V100 was 91.7%, 91% and 91.9% for HIPO, IPSA and FO plans (p = 0.1784) in breast BT; 90.4%, 89.2% and 91% (p = 0.0045) in cervical BT; and 97.1%, 96.2% and 97.7% (p = 0.0005) in prostate BT, respectively. HIPO results in more conformal plans: COIN was 0.72, 0.71 and 0.69 (p = 0.0306) in breast BT; 0.6, 0.47 and 0.58 (p < 0.001) in cervical BT; and 0.8, 0.7 and 0.7 (p < 0.001) in prostate BT, respectively. In breast BT, dose to the skin and lung was smaller with HIPO and FO than with IPSA. In cervical BT, dose to the rectum, sigmoid and bowel was larger using IPSA than with HIPO or FO. In prostate BT, dose to the urethra was higher and the rectal dose was smaller using FO than with inverse methods. CONCLUSION: In interstitial breast and prostate BT, HIPO results in comparable dose-volume parameters to FO, but HIPO plans are more conformal. In cervical BT, HIPO produces dosimetrically acceptable plans only when more needles are used. The dosimetric quality of IPSA plans is suboptimal and results in unnecessary larger active lengths.

In vivo dosimetry of the rectum in image-guided adaptive interstitial-intracavitary brachytherapy of cervix cancer - A feasibility study.

AIM AND BACKGROUND: To investigate the feasibility of in vivo rectal dosimetry in image-guided adaptive brachytherapy of cervical cancer. MATERIALS AND METHODS: Error of measurement of dose rate in a semiconductor diode probe was investigated depending on the distance and angle in water, and on temperature in a polymethyl methacrylate phantom using an Ir-192 source. Furthermore, the difference between the measured and calculated dose was analysed in the interstitial brachytherapy of 30 cervix cancer patients. The relationship between in vivo measured dose, calculated dose in the point of the diode, calculated maximal dose in the point of the diodes and calculated maximal dose of the rectum were examined. RESULTS: The dosimeter measured with 85% accuracy at more than 5 cm from the source, but within a closer distance the accuracy decreased significantly. At 45-90° angle, the device measured with a 15% error. The error increased with the temperature, 22% at 35 °C. In 8 cases (26.7%) the maximal dose was measured in the correct diode. The device measured 73% of the calculated dose in the point of the diode. The maximum of the calculated doses of diodes was 60% of the calculated maximal dose. The in vivo measured dose was 35% of the calculated maximal dose. CONCLUSIONS: Under treatment conditions, the semiconductor diode does not provide reliable measured data. The probe pushes the rectal wall closer to the high dose areas and underestimates the dose of it. Semiconductor probe is not recommended for in vivo dosimetry of the rectum in image-guided brachytherapy of cervical cancer.

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.

BACKGROUND: Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. METHODS: We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). INTERPRETATION: APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. FUNDING: German Cancer Aid.

[Second breast conserving surgery and interstitial radiotherapy for the treatment of breast tumor local recurrences. Five-year results]. / Második emlomegtartó mutét és szövetközi sugárkezelés az emlodaganat lokális kiújulásának kezelésére. Ötéves eredmények.

INTRODUCTION AND AIM: To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. METHOD: Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4-24) catheters were implanted into the tumor bed intraoperatively. A total dose of 22 Gy in 5 fractions of 4.4 Gy was delivered to the tumor bed with a margin of 1-2 cm, on 3 consecutive days. The adjuvant systemic treatments consisted of hormonal therapy for 24 patients (73%) and chemotherapy for 6 patients (18%). The survival results were estimated by the Kaplan-Meier method. Late side effects and cosmetic results were also registered. RESULTS: The median follow-up time following the second breast conserving therapy was 61 months (range: 26-189 months). During the follow-up, 4 patients (12.1%) developed second local recurrence. The five-year actuarial rates of the second local, regional and distant recurrence were 6.3%, 6.1%, and 14.9%, respectively. The five-year probabilities of disease-free, cancer-specific and overall survival were 76.2%, 92.4%, and 89.2%, respectively. Four (12%), 19 (58%), 4 (12%) and 6 (18%) patients had excellent, good, fair and poor cosmetic results, respectively. Grade 2 and 3 fibrosis developed in 9 (27%) and 1 (3%) patients. Asymptomatic fat necrosis was detected in 7 (21%) women. CONCLUSION: Second breast conserving therapy with perioperative high-dose-rate interstitial brachytherapy is a safe and feasible option for the management of ipsilateral breast tumor recurrences. Interstitial brachytherapy may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects. Hence, in selected cases it can provide a feasible alternative to salvage mastectomy. Orv Hetil. 2018; 159(11): 430-438.

[Dosimetric evaluation of intracavitary-interstitial image-guided adaptive brachytherapy of cervical cancer and comparison with conventional treatment techniques]. / Méhnyakdaganatok képvezérelt adaptív intersticiális-intrakavitális brahiterápiájának dozimetriai elemzése és a hagyományos kezelési technikákkal való összehasonlítása.

Our aim was the dosimetric evaluation of intracavitary-interstitial high-dose-rate image-guided adaptive cervix brachytherapy, implemented in Hungary. Between 2016 and 2018, 21 patients with cervical cancer were treated with overall 72 fractions. Graphical optimized treatment plans were compared to inverse optimized plans, 3D optimized plans (without needles) and conventional intracavitary 2D plans. Significant difference was found in almost all dose-volume parameters. The most advantageous values came from interstitial plans, inverse optimized plans did not differ dosimetrically from the treatment plans, while intracavitary optimized plans disposed of less appropriate dose-volume parameters, the least of all were intracavitary 2D plans. Needle number showed correlation with conformality, but inverse correlation with Dose Nonuniformity Ratio and D2cm3 of rectum. Volume of High Risk CTV correlated with D2cm3 of bladder, rectum and sigmoid. Although 3D optimization improved the quality of conventional 2D plans, interstitial plans resulted in even more homogeneous dose distribution and significantly lower doses to organs at risks.

[Clinical results of combined intracavitary-interstitial image-guided adaptive brachytherapy in locally advanced cervical cancer]. / Elõrehaladott méhnyakdaganatok képvezérelt adaptív kombinált intrakavitális-intersticiális brahiterápiájának bevezetése Magyarországon.

We present the early clinical results achieved with image-guided adaptive brachytherapy (IGABT) with combined intracavitary-interstitial (IC-IS) technique recently implemented in Hungary in the treatment of locally advanced cervical cancer (LACC). Twenty-one patients were treated with radio-chemotherapy (RCT) followed by combined IC-IS BT. At the end of the RCT we assessed the residual tumour with pelvic MRI. On CT images registered with the applicator in place we contoured the organs at risk and the high-risk clinical target volume, which included the whole cervix and the eventual residual tumour in the parametria. No grade 4 toxicity was noticed. At 11 months follow-up the local control rate was 92.3%, the pelvic control rate 86.5%, the distant metastasis free survival and the disease-free survival were 74%. The combined IC-IS treatment was well tolerated. Our clinical results are similar to those reported in the literature.

Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial.

BACKGROUND: We previously confirmed the non-inferiority of accelerated partial breast irradiation (APBI) with interstitial brachytherapy in terms of local control and overall survival compared with whole-breast irradiation for patients with early-stage breast cancer who underwent breast-conserving surgery in a phase 3 randomised trial. Here, we present the 5-year late side-effects and cosmetic results of the trial. METHODS: We did this randomised, controlled, phase 3 trial at 16 centres in seven European countries. Women aged 40 years or older with stage 0-IIA breast cancer who underwent breast-conserving surgery with microscopically clear resection margins of at least 2 mm were randomly assigned 1:1, via an online interface, to receive either whole-breast irradiation of 50 Gy with a tumour-bed boost of 10 Gy or APBI with interstitial brachytherapy. Randomisation was stratified by study centre, menopausal status, and tumour type (invasive carcinoma vs ductal carcinoma in situ), with a block size of ten, according to an automated dynamic algorithm. Patients and investigators were not masked to treatment allocation. The primary endpoint of our initial analysis was ipsilateral local recurrence; here, we report the secondary endpoints of late side-effects and cosmesis. We analysed physician-scored late toxicities and patient-scored and physician-scored cosmetic results from the date of breast-conserving surgery to the date of onset of event. Analysis was done according to treatment received (as-treated population). This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, we randomly assigned 1328 women to receive either whole-breast irradiation (n=673) or APBI with interstitial brachytherapy (n=655); 1184 patients comprised the as-treated population (551 in the whole-breast irradiation group and 633 in the APBI group). At a median follow-up of 6·6 years (IQR 5·8-7·6), no patients had any grade 4 toxities, and three (<1%) of 484 patients in the APBI group and seven (2%) of 393 in the whole-breast irradiation group had grade 3 late skin toxicity (p=0·16). No patients in the APBI group and two (<1%) in the whole-breast irradiation group developed grade 3 late subcutaneous tissue toxicity (p=0·10). The cumulative incidence of any late side-effect of grade 2 or worse at 5 years was 27·0% (95% CI 23·0-30·9) in the whole-breast irradiation group versus 23·3% (19·9-26·8) in the APBI group (p=0·12). The cumulative incidence of grade 2-3 late skin toxicity at 5 years was 10·7% (95% CI 8·0-13·4) in the whole-breast irradiation group versus 6·9% (4·8-9·0) in the APBI group (difference -3·8%, 95% CI -7·2 to 0·4; p=0·020). The cumulative risk of grade 2-3 late subcutaneous tissue side-effects at 5 years was 9·7% (95% CI 7·1-12·3) in the whole-breast irradiation group versus 12·0% (9·4-14·7) in the APBI group (difference 2·4%; 95% CI -1·4 to 6·1; p=0·28). The cumulative incidence of grade 2-3 breast pain was 11·9% (95% CI 9·0-14·7) after whole-breast irradiation versus 8·4% (6·1-10·6) after APBI (difference -3·5%; 95% CI -7·1 to 0·1; p=0·074). At 5 years' follow-up, according to the patients' view, 413 (91%) of 454 patients had excellent to good cosmetic results in the whole-breast irradiation group versus 498 (92%) of 541 patients in the APBI group (p=0·62); when judged by the physicians, 408 (90%) of 454 patients and 503 (93%) of 542 patients, respectively, had excellent to good cosmetic results (p=0·12). No treatment-related deaths occurred, but six (15%) of 41 patients (three in each group) died from breast cancer, and 35 (85%) deaths (21 in the whole-breast irradiation group and 14 in the APBI group) were unrelated. INTERPRETATION: 5-year toxicity profiles and cosmetic results were similar in patients treated with breast-conserving surgery followed by either APBI with interstitial brachytherapy or conventional whole-breast irradiation, with significantly fewer grade 2-3 late skin side-effects after APBI with interstitial brachytherapy. These findings provide further clinical evidence for the routine use of interstitial multicatheter brachytherapy-based APBI in the treatment of patients with low-risk breast cancer who opt for breast conservation. FUNDING: German Cancer Aid.

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND: In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS: We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46). INTERPRETATION: The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING: German Cancer Aid.

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer : A single institution, prospective study.

PURPOSE: To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT) METHODS AND MATERIALS: Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1-10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients' setup during IGRT. RESULTS: Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0-9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question. CONCLUSION: Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

Implementation of image-guided intensity-modulated accelerated partial breast irradiation : Three-year results of a phase II clinical study.

PURPOSE: To report 3­year results of accelerated partial breast irradiation (APBI) using image-guided intensity-modulated radiotherapy (IG-IMRT) following breast conserving surgery (BCS) for low-risk early invasive breast cancer. PATIENTS AND METHODS: Between July 2011 and March 2014, 60 patients with low-risk early invasive breast cancer underwent BCS and were enrolled in this phase II prospective study. The total dose was 36.9 Gy (9 fractions of 4.1 Gy, two fractions/day). Patient setup errors were detected in LAT, LONG and VERT directions. Local tumour control, survival results, early and late side effects and cosmetic outcome were assessed. RESULTS: At a median follow-up of 39 months, all patients were alive and neither locoregional nor distant failure occurred. One contralateral breast cancer and two new primary malignancies outside the breast were observed. No grade (G) 3-4 acute toxicity was detected. G1 and G2 erythema occurred in 21 (35%) and 2 (3.3%) patients, respectively; while G1 oedema was observed in 23 (38.8%) cases. G1 and G2 pain was reported by 6 (10%) and 2 (3.3%) patients, respectively. Among the late radiation side effects, G1 pigmentation or telangiectasia, G1 fibrosis and G1 asymptomatic fat necrosis occurred in 10 (16.7%), 7 (11.7%) and 3 (5%) patients, respectively. No ≥ G2 late toxicity was detected. Cosmetic outcome was excellent in 43 (71.7%) and good in 17 (28.3%) patients. CONCLUSION: IG-IMRT is a reproducible and feasible technique for delivery of external beam APBI following BCS for treatment of low-risk, early-stage invasive breast carcinoma. In order to avoid toxicity, image guidance performed before each radiation fraction is necessary to minimize the PTV. Three-year results are promising, early and late radiation side-effects are minimal, and cosmetic results are excellent to good.

[Image-guided radiotherapy for muscle invasive bladder cancer with intravesical lipiodol injection. A new option for bladder sparing treatment]. / Izominvazív hólyagrák képvezérelt sugárkezelése intravesicalisan befecskendezett lipiodolos jelöléssel. A hólyagmegtartó kezelés új lehetosége.

INTRODUCTION AND AIM: To implement lipiodol as a fiducial marker of the tumor bed for image-guided radiotherapy with simultaneous integrated boost technique as part of radiochemotherapy for muscle invasive bladder tumors. METHOD: Since April 2016, radiochemotherapy was performed in 3 male patients with muscle invasive, transitional cell bladder carcinoma. Prior to radiochemotherapy, tumor bed resection was performed for each patient, at the same time 10 ml of lipiodol solution was injected submucosally into the resection site, thus marking the tumor bed for escalated dose irradiation. During radiochemotherapy 51 Gy (1.7 Gy/die) to the pelvis, 57 Gy (1.9 Gy/die) to the whole bladder, and 63 Gy (2.1 Gy/die) to the lipiodol-labeled tumor bed was delivered with simultaneous integrated boost technique. The accuracy of the irradiation was controlled by daily kilovoltage CT. Early radiogenic urogenital and gastrointestinal side effects were recorded according to Radiation Therapy Oncology Group side-effects grading recommendation. RESULTS: Substantial perioperative side effect or toxicity were not observed during and after the injection of lipiodol. The prescribed dose was successfully delivered in all patients. Radiotherapy duration was 6 weeks. The lipiodol-labeled tumor bed was clearly visible on daily kilovoltage cone beam CT. In one patient grade II cystitis and proctitis was observed, another patient experienced only grade I cystitis. These complaints improved with symptomatic medication. In the third patient no significant side effect occurred. CONCLUSIONS: The injection of lipiodol into the bladder wall is a safe technique, without any perioperative toxicity or complication. The tumor bed demarcated by lipiodol was visible both on treatment planning and kilovoltage CTs. The total treatment time was shortened by 4 days. The treatment was well tolerated, early side effects were moderate, or slight. Orv Hetil. 2017; 158(51): 2041-2047.

[Is suction drainage necessary in elective total hip arthroplasty?]. / Szükség van szívódrénre elektív csípoprotézis-mutétek során?

INTRODUCTION: Several studies have been published which questioned the use of suction drain during elective hip arthroplasty. AIM: In this prospective study the authors examined how the use of suction drainage affected complications related to perioperative blood loss and hemorrhage in patients undergoing elective hip arthroplasty. METHOD: Eighty-six patients undergoing elective hip arthroplasty were divided into two groups. In 54 patients ("drain" group) suction drains were used during operation, whereas in 32 patients no suction drain was applied. Perioperative blood loss, use of tranexamic acid, method of thrombosis prophylaxis, transfusion requirement, incidental postoperative hemorrhage, septic complications, and all other postoperative complications were recorded. RESULTS: Perioperative blood loss was affected with the use of tranexamic acid but not with the use of drainage (p = 0.94). Patients without the use of drain showed a tendency of lower transfusion requirement (p = 0.08). There was no correlation between any complications and the use of drainage. CONCLUSION: In accordance with published results the authors conclude that the routine use of suction drainage during elective hip arthroplasty is not definitely necessary. Orv. Hetil., 2016, 157(29), 1171-1176.

[Dosimetric comparison of different techniques for external beam accelerated partial breast irradiation]. / Modern besugárzási technikák dozimetriai összehasonlítása gyorsított részleges külsõ emlõbesugárzásnál.

The aim of this article is to evaluate and compare four different radiotherapy techniques of accelerated partial breast irradiation (APBI) considering planning quality, dosimetric and practical aspects. The investigated techniques are three dimensional conformal radiotherapy (3D-CRT), "step and shoot" (SS) and "sliding window" (SW) intensity-modulated radiotherapy, intensity-modulated arc therapy (RA). CT scans of 10 patients previously treated with APBI were selected for the study. Surgical clips were placed on the borders of the tumour bed during breast conserving surgery. Target volume (PTV) was defined as enlarged CTV, which was created from the tumour bed through volume expansion using individual margins. Planning objectives were set up according to the international recommendations. Non-coplanar fields were used only for the 3D-CRT plans. For each plan homogeneity, conformity and plan quality indices were calculated from volumetric and dosimetric parameters of target volumes and organs at risk. The total monitor units and feasibility were also investigated. There was no significant difference in the coverage of the target volume by the prescribed dose between the techniques. SW plans were significantly more homogeneous (HI=0.033) than the 3D-CRT (HI=0.057) and the RA (HI=0.073) plans. The homogeneity of the SS technique (HI=0.053) did not differ significantly compared to others. The conformity of the 3D-CRT technique was significantly worse (CN=0.62) than that of SS (CN=0.85), SW (CN=0.85) and RA (CN=0.86) plans. There was a significant difference between RA (29.4%) and 3D-CRT (44.1%) and SW (35.6%) plans in the V50% of the ipsilateral breast. Mean V10% of the ipsilateral lung in 3D-CRT (10.1%) plans was significantly lower than in SS (34.3%), SW (34.3%) and RA (35.3%) plans. 3D-CRT technique provided the best heart protection. The shortest treatment times were achieved with RA technique. Good target volume coverage and tolerable dose to the organs at risk are achievable with all four techniques. Taking into account all the aspects, we recommend the sliding window IMRT technique for accelerated partial breast irradiation.