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.

Analysis of dose distribution between contemporary and standard planning in high-dose-rate endobronchial brachytherapy based on three-dimensional imaging.

PURPOSE: The treatment planning (TP) in high-dose-rate (HDR) endobronchial brachytherapy (EB) can be based on various forms of imaging. In the case of lung cancer, one-dimensional or two-dimensional imaging is standard. The dose coverage of the target (planning target volume - PTV) and organs at risk (OAR) is unknown, because the doses are calculated on the basis of the dose points. In modern brachytherapy, TP can be based on three-dimensional (3D) images. A plan created in this way contains information about the dose distribution in the PTV and OAR. Treatment plans based on standard planning (SP) and contemporary planning (CP) may differ in dose distribution in the patient's body. Those differences between SP and CP may have an effect on the dose distribution in PTV, OAR and follow-up. MATERIAL AND METHODS: The study involved a group of 31 patients prospectively treated with advanced, inoperable, non-small cell lung cancer. As many as 76 treatment fractions were analyzed. Firstly, the coverage of the PTV parameter in 2D and 3D for V85, V100 and V115 was analyzed. Secondly, the dosage that OAR would take in was evaluated. In the cases of the heart, spinal cord and esophagus, the examined dosage equaled D0.1cm3 , D1cm3 and D2cm3 for each of the structures. Also, heart D20 was examined as well as D5 for the healthy lung. RESULTS: The median dose to the target volume was on average 43.33% higher for V85 with the contemporary planning method when compared to standard planning, with statistical significance. This came with the cost of an OAR mean dose increase of 1 Gy in D0.1cm3 for the heart. CONCLUSIONS: Contemporary TP in EB allows one to adjust the dose distribution for individual clinical situations and allows one to improve clinical target volume (CTV) coverage, increase doses to the OAR and increase overall survival. The use of new methods of treatment plans in EB has significantly increased the follow-up to 21 months in a treated group of patients.

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.

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.

GEC-ESTRO multicenter phase 3-trial: Accelerated partial breast irradiation with interstitial multicatheter brachytherapy versus external beam whole breast irradiation: Early toxicity and patient compliance.

BACKGROUND AND PURPOSE: To compare early side effects and patient compliance of accelerated partial breast irradiation (APBI) with multicatheter brachytherapy to external beam whole breast irradiation (WBI) in a low-risk group of patients with breast cancer. MATERIAL AND METHODS: Between April 2004 and July 2009, 1328 patients with UICC stage 0-IIA breast cancer were randomized to receive WBI with 50Gy and a boost of 10Gy or APBI with either 32.0Gy/8 fractions, or 30.1Gy/7 fractions (HDR-brachytherapy), or 50Gy/0.60-0.80Gy per pulse (PDR-brachytherapy). This report focuses on early side-effects and patient compliance observed in 1186 analyzable patients. ClinicalTrials.gov identifier: NCT00402519. RESULTS: Patient compliance was excellent in both arms. Both WBI and APBI were well tolerated with moderate early side-effects. No grade 4 toxicity had been observed. Grade 3 side effects were exclusively seen for early skin toxicity (radiation dermatitis) with 7% vs. 0.2% (p<0.0001), and breast infection with 0% vs. 0.2% (p=n.s.) for patients treated with WBI and APBI. The incidence of grades 1-2 early side effects for WBI and APBI was 86% vs. 21% (p<0.0001) for skin toxicity, 2% vs. 20% (p<0.0001) for mild hematoma, and 2% vs. 5% (p=0.01) for mild breast infection rates, respectively. No differences had been found regarding grades 1-2 early breast pain (26% vs. 29%, p=0.23). CONCLUSIONS: APBI with interstitial multicatheter brachytherapy was tolerated very well and dramatically reduced early skin toxicity in comparison to standard WBI.

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.

The evaluation of treatment plans in high-dose-rate endobronchial brachytherapy by utilizing 2D and 3D computed tomography imaging methods.

PURPOSE: To present comparison of treatment plans made by using 2D and 3D methods in the planning system, as well as to assess the quality of treatment plans using the 2D and 3D methods. MATERIAL AND METHODS: The studies involved a group of 31 patients with advanced lung cancer treated in the Brachytherapy Department of the Subcarpathian Cancer Center in Brzozów from 2011 to 2013. In total, 31 patients and 76 treatment plans were analyzed. We compared coverage of PTV planned in 3D and 2D. In the 3D method of treatment, three-dimensional images from computer tomography were used. In treatment plans performed using the 2D method, images from the simulator were used. RESULTS: The comparison of treatment plans made by using 2D and 3D methods is described. This comparison highlighted the significant differences between these two methods assessing reference dose coverage of the PTV by 100% and 85% isodose. CONCLUSIONS: Reference doses with 100% coverage of the PTV in treatment applied with the 3D method are 31% higher than when applied with the 2D method.

Individual applicator for brachytherapy for various sites of superficial malignant lesions.

The aim of this paper is to discuss brachytherapy treatment and individual applicators suitable for unfavorably localized superficial malignant lesions. Techniques for manufacturing an individual applicator and clinical examples of its use for various locations of cancer are presented. This techniques are based on individual size and shape of the tumour. CT-planning make the technique adequate for individual patient history and type of tumour. Featured techniques seems to be very useful and easy to performed.

Comparison of the GTV coverage by PTV and isodose of 90% in 2D and 3D planning during endobronchial brachytherapy in the palliative treatment of patients with advanced lung cancer. Pilot study.

PURPOSE: Endobronchial brachytherapy (EB) is one way of treatment of patients with advanced lung cancer. Technological progress and the introduction of computed tomography for use in 3D planning allows one to define the area being treated very precisely, which gives an opportunity to extend survival, even in groups of patients receiving palliative care. MATERIAL AND METHODS: In 2011, in the Brachytherapy Department of the Subcarpathian Oncological Center, a group of 12 consecutive patients with advanced cancer of the bronchus underwent palliative EB. We compared the coverage of GTV (gross tumor volume), seen in the computed tomography study with intravenous contrast, by the PTV (planning target volume) planned in 3D and 2D. RESULTS: In 2D planning GTV coverage ranged from 15% to 89%. By analyzing the isodose of 90%, it was found that 2D planning covered GTV in 15-35% of the dose. In 3D planning, this coverage changed positively, and ranged from 85% to 100%. The GTV coverage in 3D planning was 100% by definition. In addition, it should be noted that in the 3D planning one can spare critical organs or pacemakers. CONCLUSIONS: Planning for HDR brachytherapy in all locations should be based on dynamic imaging at present, especially in centers that are equipped with CT. Evaluation should be a routine test in treatment planning. The use of CT, even in palliative treatment planning, allows for much better coverage of GTV areas as well, which is very important to reduce radiation doses to critical organs and thereby reduce the toxic effects of treatment.

Surgical resection with adjuvant brachytherapy in soft tissue sarcoma of the extremity - a case report.

PURPOSE: Surgery is the major therapeutic method in soft tissue sarcomas of the extremity (E-STS). Treatment of large high-grade tumours, which resection cannot be performed with a wide safe margin, should include complementary radiation and/or chemo-therapy. Hopefully, the use of adjuvant brachytherapy will improve the prognosis of E-STS. CASE DESCRIPTION: After a long process of diagnosing a tumour in the medial compartment of the thigh, a 65-year-old woman with diagnosed synovial sarcoma underwent a surgery. Compartment resection was performed and the tumour was removed with a 10 mm safety margin of healthy tissue. Adjuvant brachytherapy was delivered with (192)Ir (MicroSelectron, Nucletron Electa Group, Stockholm, Sweden(®)) with 10 Ci of nominal activity to a dose of 55 Gy in 16 days because of large tumour size (99 × 78 × 73 mm) and its proximity to the neurovascular bundle. No complications were reported. The patient was discharged from the hospital on the 28(th) day after the surgery. The wound healed without any complications and the outpatient follow-up is being continued. DISCUSSION: Adjuvant brachytherapy is rarely used after surgical treatment due to its limited accessibility in hospitals with surgical and orthopaedic departments. There are numerous publications proving positive influence of brachytherapy on local control and decreased number of recurrences. The recurrence-free survival time also increased significantly, however no direct impact on the number of distant metastases was found. Treatment is well tolerated and short. The complication rate varies between centres from 5 to 30%. The most common adverse effects include: peripheral neuropathy, skin necrosis and osteonecrosis of the long bones. CONCLUSIONS: Treatment of large soft tissue sarcomas of the extremity (E-STS) should include combination of surgical intervention and external beam radiotherapy or brachytherapy. Adjuvant brachytherapy improves local control rate up to 78%, is well tolerated and rarely causes complications. We couldn't determine which type of adjuvant radiation therapy is more effective.

Penile cancer brachytherapy HDR mould technique used at the Holycross Cancer Center.

The aim of this pictorial essay is to present the mould based HDR brachytherapy technique used at the Holycross Cancer Center for penile cancer patients. We use images to describe this method step by step.

Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009).

PURPOSE: To give recommendations on patient selection criteria for the use of accelerated partial-breast irradiation (APBI) based on available clinical evidence complemented by expert opinion. METHODS AND MATERIALS: Overall, 340 articles were identified by a systematic search of the PubMed database using the keywords "partial-breast irradiation" and "APBI". This search was complemented by searches of reference lists of articles and handsearching of relevant conference abstracts and book chapters. Of these, 3 randomized and 19 prospective non-randomized studies with a minimum median follow-up time of 4 years were identified. The authors reviewed the published clinical evidence on APBI, complemented by relevant clinical and pathological studies of standard breast-conserving therapy and, through a series of personal communications, formulated the recommendations presented in this article. RESULTS: The GEC-ESTRO Breast Cancer Working Group recommends three categories guiding patient selection for APBI: (1) a low-risk group for whom APBI outside the context of a clinical trial is an acceptable treatment option; including patients ageing at least 50 years with unicentric, unifocal, pT1-2 (30 mm) tumours, and/or EIC positive or LVI positive tumours, and/or 4 or more positive lymph nodes or unknown axillary status (pNx), and (3) an intermediate-risk group, for whom APBI is considered acceptable only in the context of prospective clinical trials. CONCLUSIONS: These recommendations will provide a clinical guidance regarding the use of APBI outside the context of a clinical trial before large-scale randomized clinical trial outcome data become available. Furthermore they should promote further clinical research focusing on controversial issues in the treatment of early-stage breast carcinoma.

Surgery combined with brachytherapy in patients with retroperitoneal sarcomas.

PURPOSE: The primary aim of this work was to analyze feasibility of combined treatment of retroperitoneal sarcomas (RS): surgery (S) and intraoperative brachytherapy (IOBRT). The secondary aim was to analyze results and complications after this treatment. MATERIAL AND METHODS: 84 patients with retroperitoneal sarcomas were qualified for combined treatment (S and IOBRT) between June 1998 and September 2006. 65 of the patients (77.4%) had local recurrences. Sarcomas with intermediate and high grade of histological malignancy (G2, G3 - 76.2%) were the most frequent within the all surgically treated patients. Resection ability (R0/R1) in analyzed group of patients was estimated as 85% (74 cases). After intraoperative evaluation, 57 (67.8%) patients were qualified for IOBRT. Since 2000, in 34 patients (60%) an adjuvant postoperative external beam radiation therapy (EBRT) in dose of 50 Gy was applied. Median follow-up of the surviving patients was 40 months. RESULTS: On the basis of the univariate analysis, relevant aspects negatively influencing overall survival rate within the RS group treated with IOBRT were as follows: surgery of sarcoma recurrence (p = 0.002), higher grade of histological malignancy (p = 0.05), histological type different than liposarcoma (p = 0.05) as well as no adjuvant EBRT (p = 0.05). On the basis of multivariate analysis one can ascertain that relevant factors negatively influencing LRFS in RS patients treated with IOBRT were: surgery due to recurrence of sarcoma (p = 0.008) and lack of EBRT (p = 0.01). CONCLUSIONS: Combined treatment (surgery and brachytherapy) was possible to be carried out on 68% of RS patients. The overall number of complications was quite high, however acceptable, taking into consideration the application of extensive, multi-organ treatments in case of sarcoma recurrences in this localization. The results suggest that the method of treatment will improve the final outcome when most of patients will be qualified for treatment of primary sarcomas in experienced centre.

Cosmetic effect in patients with early breast cancer treated with breast conserving therapy (BCT) and with HDR brachytherapy (HDR-BT) "boost".

PURPOSE: The estimation of cosmetic effect in 93 patients with early breast cancer treated with breast conserving surgery (BCS) followed by combined radiotherapy, including HDR brachytherapy (HDR-BT) boost. MATERIAL AND METHODS: After BCS (tumorectomy or quadrantectomy) external beam radiation therapy (EBRT) was used in total dose of 50 Gy for the whole breast. Tumor bed was localized basing on clinical and mammographic preoperative examinations and histopathology evaluation. 10 Gy in one fraction was applied to all patients using HDR-BT. Steel interstitial needles stabilized by plastic templates were used. 192-Ir with 10 Ci nominal activity and HDR-GammaMed 12i unit (Mick Radio-Nuclear Instruments, Inc., Mt. Vernon, NY) and ABACUS software were used. 31 patients received additional chemotherapy. Cosmetic effect was evaluated in 36 month after the end of brachytherapy treatment basing on modified EORTC scale. For statistical analysis the rang of correlation test, contingent test, linear regression test and ProbRough rulet induction test were used. RESULTS AND CONCLUSIONS: HDR-BT tolerance was good in most of the cases. Excellent and very good cosmetic effect was observed in 79 patients (85%). Statistically important correlations between following examined prognostic factors and cosmetics outcome were observed: clinical and mammographic tumor estimation, method of breast conserving surgery, type of skin incision, number of interstitial applicators, irradiated reference volume (PTV) and type of optimization method. No correlations with cosmetics effect were found in factors such as: age of patients, location of tumor or additional therapy.

HDR brachytherapy as a solution in recurrences of locally advanced prostate cancer.

PURPOSE: The object of this study was to analyze the outcome of salvage HDR brachytherapy treatment after local failure, for patients with prostate specific antigen (PSA) failure without distant metastasis, after external beam radiation and HDR brachytherapy treatment, or after radical prostatectomy, with or without hormonal therapy. MATERIAL AND METHODS: The group of 115 patients, without distant metastasis, after local failure and external beam radiation, followed by HDR brachytherapy treatment, or after radical prostatectomy, with hormonal therapy and without, have been enrolled to salvage HDR brachytherapy (SBR). All patients had minimum 3 months androgen deprivation therapy before salvage brachytherapy, which was continued until the next 9 months after SBR. Brachytherapy was administered in three 10 Gy fractions with 3 weeks gap between them. Each session of SBR was supported by trans-rectal USG real time pictures. The treatment planning was done on the base of Abacus system from Sauerwein® or with SWIFT system from Nucletron®. The following data were collected: Gleason score, clinical staging, the volume of the prostate, PSA before and after the initial treatment and periodically during the follow-up period. Also the time during which the PSA stays at the nadir level, patient's age and toxicity of treatments were taken into consideration. RESULTS: Doses from external radiotherapy or from HDR brachytherapy were recalculated to equivalent biological dose (EBD). The independence from biochemical progression in our group of patients after retreatment was 46% for patients with PSA ≤ 6 and 18% for patients with PSA > 6. Overall survival for patients with PSA ≤ 6 was 86% and 48% for patients with PSA > 6, respectively. CONCLUSIONS: Salvage prostate brachytherapy (SBR) can be safely performed with acceptable biochemical control and toxicity.

Combined therapy: surgery and intraoperative HDR brachytherapy for locally advanced and recurrent rectal cancer. Practical experience of Brachytherapy Department in Warsaw.

PURPOSE: Patients with locally advanced and recurrent rectal cancer have a dismal prognosis. The aim of proposed combined therapy - surgery and intraoperative brachytherapy, is to improve results of already applied methods and to define optimal group of patients for this treatment. We introduce practical experience of Brachytherapy Department in Cancer Centre - Institute in Warsaw. MATERIAL AND METHODS: Patients with primary T4NxM0 rectal cancer and isolated local pelvic recurrence were qualified for therapy. Between January 2005 and September 2008, 13 patients were included: 4 with primary cancer and 9 with recurrence, median age of 56. After surgical resection intraoperative radiotherapy was delivered with boost of high dose rate brachytherapy of 20Gy dose to the tumor bed. RESULTS: Primary point of the study is to evaluate impact of applied therapy on local control (LC), overall survival (OS) and disease free survival (DFS). Median follow-up is 16 months. Four of the patients died and 3 survivors are disease-free. There was no case of perioperative mortality. CONCLUSIONS: A multimodality approach, using surgical resection with intra operative brachytherapy improves local control as well as patients survival in comparison with historical treatment group. Combined therapy is related to high morbidity, but low mortality. The preliminary observations seem to correspond with other authors data.

Acute lumen overdilation improves outcome after brachytherapy of in-stent restenosis.

BACKGROUND: The aim of our study was to test the impact of acute lumen overdilation on neointimal hyperplasia and late lumen size after vascular brachytherapy for in-stent restenosis (ISR). METHODS: Forty-seven ISR lesions located in 47 coronary arteries in 44 consecutive patients underwent beta brachytherapy with serial intravascular ultrasound studies. Vessel, lumen, and stent cross-sectional area were measured at 1-mm steps. Based on an interpolated reference cross-sectional area, each cross section was assessed as overdilated (lumen cross-sectional area>interpolated reference cross-sectional area) or not overdilated (lumen cross-sectional area

Optimization of dose prescription protocol and its impact on delivered dose and vascular response after beta-radiation for in-stent restenosis. A randomized trial with serial volumetric intravascular ultrasound and dose volume histograms.

AIM: The incidence of restenosis within stented segment after intravascular brachytherapy with recommended dose prescription protocols is up to 25%. Therefore, we designed a randomized trial comparing recommended dose prescription protocol with dosing adjusted for the source-to-target distance. METHODS: Fifty-one in-stent restenosis (ISR) lesions in 48 patients underwent centered source beta-irradiation with serial intravascular ultrasound. Patients randomly received 20 Gy at 1 mm either beyond lumen surface [n=25, standard group (S)] or external elastic membrane [n=26, dosing-adjusted (DA) group]. Minimum dose absorbed by 90% of adventitia (DV(90%Adv)) was calculated. RESULTS: DV(90%Adv) was higher for the DA group than for the S group (21.63+/-5.67 vs. 12.05+/-4.88 Gy, P<.001). After 8.9+/-4.5 months there was complete lumen preservation in DA vs. lumen decrease subsequent to neointimal hyperplasia (NIH) in S group (0.10+/-1.20 vs. -0.61+/-1.29 mm3/mm, P<.05). Vessel volume increased significantly in the DA group and was unchanged in S group (+1.73, P=.002 vs. 0.14 mm3/mm, P=NS). DV(90%Adv) correlated inversely with NIH volume and positively with vessel volume change (r=-.405, P=.007 and r=.363, P=.017, respectively). CONCLUSION: For beta-irradiation of ISR, dosing adjusted for the source-to-target distance leads to significant increase in target delivered doses, which is associated with complete NIH inhibition and induction of positive vessel remodeling.

Surgery combined with intraoperative brachytherapy in the treatment of retroperitoneal sarcomas.

BACKGROUND: The purpose of this study was to analyze the results of treatment of retroperitoneal soft tissue sarcomas (RSTS) by surgery combined with intraoperative brachytherapy (IOBRT). METHODS: Seventy adult patients with RSTS were considered for combined treatment (surgery plus IOBRT) between June 1998 and February 2004. There were 64 (91%) recurrent tumors, and 93% of tumors exceeded 5 cm. IOBRT was performed with high-dose-rate Gammamed 12 with iridium 192 (IOBRT time range, 20-87 minutes; median, 56 minutes). RESULTS: After intraoperative re-evaluation, 24 patients (34%) were found to be ineligible for IOBRT because of multiple intraperitoneal recurrences, macroscopically nonradical resection, poor general condition, and technical aspects. Thirty-seven patients underwent IOBRT immediately after surgery during the same general anesthesia procedure. Nine patients underwent delayed IOBRT within 1 to 3 days after the primary operation. Ten (21.5%) of 46 patients underwent reoperation because of surgical complications. One patient died in the postoperative period. After IOBRT, 24 patients (52%) underwent adjuvant external beam radiotherapy (EBRT) to a total dose of 50 Gy. Over a median follow-up time of 20 months, the estimated 5-year overall survival and local recurrence-free survival rates in IOBRT patients were 55% and 51%, respectively. Application of adjuvant EBRT showed a favorable local control rate. CONCLUSIONS: The scheduled combined treatment (surgery plus IOBRT) was possible to perform in 66% of RSTS cases that received surgical treatment. The complication rate was high, but we consider it acceptable because of the necessity for extensive aggressive surgical treatment in regionally advanced RSTS. EBRT seems to be an indispensable part of treatment that provides better local control.

Determinants of model of renarrowing after beta radiation for in-stent restenosis.

UNLABELLED: It is unknown whether model of renarrowing after beta-radiation for in-stent restenosis (ISR) is influenced by the type of geographic miss (GM). METHODS: In 166 ISR treated with Galileo, serial quantitative coronary angiographic analysis was done. Minimal lumen diameters and lengths were measured for (1) stent, (2) peri-stent subsegments subjected to angioplasty with/without irradiation, and (3) irradiation margins. GM was defined as: (Type 1) edge injury within the 32P source dose fall-off: 2.0 mm inside and outside the source end marker or (Type 2) overt, nonirradiated injury: beyond the outer 2.0-mm long dose fall-off zone. RESULTS: Restenosis rate was 28.3% at 8.9+/-4.5 months with 60% located exclusively outside the stent. Type 1 GM was present in 24.7% of proximal edges, whereas Type 2 in 18.1%. Respective percentages for distal edges were 23.5% and 15.7%. Regardless of presence and type of GM, significant late lumen loss occurred only outside the stent. However, the biggest late lumen loss at the proximal edge was induced by the Type 1 GM (0.65+/-0.79, p<0.001), while proximal Type 2 GM was not associated with edge renarrowing (-0.04+/-0.48, p=NS). Both reference lumen diameter and proximal Type 1 GM influenced restenosis independently (OR 0.47; 95%CI 0.24-0.90; p=0.023 and OR 2.46; 95%CI 1.12-5.40; p=0.025). CONCLUSIONS: Regardless of presence and type of geographic miss, late lumen loss after beta-radiation occurs only outside the stent. However, injury within the proximal 32P dose fall-off but not overt edge injury is associated with the biggest late lumen loss at the respective edge, triggering recurrent restenosis.