ABSTRACT
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.
Subject(s)
Brachytherapy , Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Female , Humans , Breast Neoplasms/pathology , Brachytherapy/adverse effects , Carcinoma, Intraductal, Noninfiltrating/pathology , Mastectomy, Segmental/adverse effects , Treatment Outcome , Neoplasm Recurrence, Local/surgeryABSTRACT
INTRODUCTION: Clipping and selective removal of axillary lymph nodes in breast cancer patients presenting with initially node-positive disease and achieving a nodal downstaging after primary systemic therapy is a less invasive method for axillary staging. An imaging guided localization and successful extirpation of these clipped lymph nodes is not possible in all patients. To date no follow-up data regarding patients with lost clips are available. MATERIAL AND METHODS: The oncological outcome of all participants of the CLIP-study and the results of postoperative axillary imaging in those patients with unproven clip resection are presented. RESULTS: A total of thirty patients were included into the pilot study. In ten of these patients (33%) the removal of the clipped axillary lymph node could not be verified by intraoperative radiograph. Postoperative imaging did not find lost clips in eight of these ten patients (80%). The lost clip was detected in two patients after surgery (20%), by mammography in one patient during routine follow-up and by computed tomography scan in one patient before radiotherapy. After a median follow-up of 40 months, 26 (87%) patients were still alive. Seven patients (23%) developed distant recurrent disease. No local or axillary recurrences were observed. CONCLUSION: Lost clips were detected by postoperative imaging only in a minority of patients. The impact of lost clips on axillary recurrences in breast cancer patients is still unclear and should be further clarified in larger, multicentric trials.
Subject(s)
Breast Neoplasms/surgery , Lymph Node Excision/methods , Lymph Nodes/surgery , Neoadjuvant Therapy , Neoplasm Recurrence, Local/epidemiology , Surgical Instruments , Adult , Aged , Axilla , Breast Neoplasms/pathology , Female , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis , Mammography , Middle Aged , Neoplasm Staging , Radiography , Tomography, X-Ray Computed , Young AdultABSTRACT
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.
Subject(s)
Brachytherapy/methods , Breast Neoplasms/therapy , Carcinoma/therapy , Mastectomy, Segmental , Quality of Life , Adult , Aged , Brachytherapy/adverse effects , Breast Neoplasms/pathology , Carcinoma/pathology , Europe , Female , Health Status , Humans , Mastectomy, Segmental/adverse effects , Middle Aged , Neoplasm Grading , Neoplasm Staging , Radiotherapy, Adjuvant , Surveys and Questionnaires , Time Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Brachytherapy/adverse effects , Breast Neoplasms/radiotherapy , Cosmetics , Fat Necrosis/etiology , Mastectomy, Segmental/adverse effects , Mastectomy/adverse effects , Radiodermatitis/etiology , Aged , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/radiotherapy , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/radiotherapy , Carcinoma, Lobular/surgery , Combined Modality Therapy , Fat Necrosis/diagnosis , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Radiodermatitis/diagnosis , Radiotherapy Dosage , Time FactorsABSTRACT
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.
Subject(s)
Brachytherapy/methods , Breast Neoplasms/radiotherapy , Breast/radiation effects , Patient Compliance , Adult , Aged , Aged, 80 and over , Brachytherapy/adverse effects , Female , Humans , Middle AgedABSTRACT
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.
Subject(s)
Brachytherapy/methods , Breast Neoplasms/radiotherapy , Carcinoma in Situ/radiotherapy , Carcinoma, Ductal, Breast/radiotherapy , Adult , Aged , Breast Neoplasms/surgery , Breast Neoplasms/therapy , Carcinoma in Situ/surgery , Carcinoma in Situ/therapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Ductal, Breast/therapy , Catheters, Indwelling , Combined Modality Therapy , Female , Humans , Mastectomy, Segmental/methods , Middle Aged , Radiotherapy Dosage , Treatment OutcomeABSTRACT
PURPOSE: In a retrospective analysis of radiotherapy of plasmacytomas, the effectiveness and the prognostic factors in regard to pain reduction and recalcification were evaluated. PATIENTS AND METHODS: 138 patients (70 women, 68 men; 15-86 years, median 61 years) were irradiated at 272 target volumes (TVs) from January 1970 to December 2003. RESULTS: In 192/225 TVs (85.3%), there was a pain reduction. The recalcification rate was 44.7% (51/114 TVs). Significant parameters for pain relief in the multivariate analysis were completeness of therapy (odds ratio [OR] 87.8; p < 0.001 vs. interruption), patients < 60 years (OR 23.0; p < 0.001 vs. >/= 70 years), and a single dose of 2 Gy (OR 11.0; p = 0.027 vs. 4-15.0 Gy). Significant parameters for recalcification in the multivariate analysis were concurrent chemotherapy (OR 12.3; p < 0.001 vs. no chemotherapy), no fractures in the TV (OR 5.9; p < 0.004 vs. fracture), and a dose of 40-< 50 Gy (OR 21.9; p = 0.035 vs. < 30 Gy) or >/= 50 Gy (OR 26.4; p = 0.033 vs. < 30 Gy) CONCLUSION: Radiotherapy is a very effective palliative treatment. Patients with a reduced general condition, with multiple bone lesions and a poor prognosis profit from short-term schemes (e.g., 1 x 8 Gy to 10 x 3 Gy). Patients in good general condition with a life expectancy of > 1 year and an osteolysis at risk of fracture, should be treated with doses up to 40-50 Gy (20-25 x 2 Gy), in order to achieve the best possible recalcification and pain relief.
Subject(s)
Multiple Myeloma/radiotherapy , Palliative Care , Plasmacytoma/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Calcinosis/pathology , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Humans , Male , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Multivariate Analysis , Neoplasm Staging , Pain Measurement , Plasmacytoma/drug therapy , Plasmacytoma/mortality , Plasmacytoma/pathology , Prognosis , Radiotherapy Dosage , Retrospective Studies , Survival Rate , Treatment Outcome , Young AdultABSTRACT
PURPOSE: To obtain long-term data on local tumor control after treatment of invasive breast cancer by breast-conserving surgery and adjuvant radiotherapy (RT), in consideration of the interstitial high-dose-rate boost technique. PATIENTS AND METHODS: A total of 263 women with 268 mammary carcinomas (International Union Against Cancer Stage I-IIB) who had undergone breast-conserving surgery and adjuvant RT between 1990 and 1994 were included. The potential risk factors for local recurrence-free survival were investigated. RESULTS: During a median follow-up period of 94 months, 27 locoregional recurrences, 25 of which were in breast, were diagnosed. The cumulative rate of in-breast recurrence was 4.1% +/- 1.4% at 5 years of follow-up and 9.9% +/- 2.4% at 10 years. The multivariate analysis identified medial tumor location and delayed RT (defined as an interval of >2 months between surgery and the start of RT) as significant risk factors for in-breast recurrence in the overall study population. Medial tumor location vs. lateral/central location (hazard ratio, 2.48; 95% confidence interval, 1.06-5.84) resulted in a cumulative in-breast recurrence rate of 22.5% +/- 8.3% vs. 6.9% +/- 2.3% at 10 years. Delayed RT (hazard ratio, 2.84; 95% confidence interval, 1.13-7.13) resulted in a cumulative in-breast recurrence rate of 18.5% +/- 6.2% vs. 6.8% +/- 2.4% at 10 years. The multivariate analysis also showed that the risk of in-breast recurrence was lower after high-dose-rate boost therapy than after external beam boost therapy in patients with laterally/centrally located tumors (hazard ratio, 3.25; 95% confidence interval, 0.91-11.65). CONCLUSION: Tumor location, interval between surgery and RT, and boost technique might influence local control of breast cancer treated by breast-conserving surgery and RT.