Prognostic Significance of Local Recurrence in Breast Cancer after Postmastectomy Radiotherapy

PURPOSE: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. PATIENTS AND METHODS: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4 tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pN0-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. RESULTS: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence 2-96 months after treatment (median 26 months). The local control rate was 92.7% after 5 and 86.4% after 10 years. Axillary lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p = 0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs 15.4%, p = 0.002 and 62.1% vs 34.8%, p = 0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pN0 status vs 27% in with positive axillary nodes (p = 0.025). CONCLUSIONS: Local recurrence after treatment of breast cancer with mastectomy + radiotherapy +/- systemic therapy is associated with a significantly higher risk of distant metastases and death. In this analysis, local recurrence was a strong and, besides lymph node status and T category, an independent risk factor for survival. Minimizing the risk of local recurrence is therefore an essential goal of a curative treatment concept.     

Plesiobrachytherapy for chest wall recurrences of breast cancer after mastectomy and radiotherapy for breast cancer

PurposeThe purpose of the study was to evaluate the results of high-dose-rate plesiobrachytherapy for local relapse after mastectomy and radiotherapy in terms of both local control and survival.MethodsWe reviewed retrospectively 43 patients who experienced a chest wall relapse of breast cancer after local excision (22 patients) or not (21 patients). Patients were treated with an individually designed mold with four to six fractions of 3–6 Gy high-dose-rate brachytherapy, two fractions per week. Mean total dose was 24 Gy.ResultsAfter surgical resection, the 3- and 5-year local control rates were 80% and 73%, respectively. For nonresectable patients, the overall response rate was 86%, and the 3-year infield local control and chest wall local control were 51% and 26%, respectively. The 5-year survival rate was 50.5% for the whole population, 62% after surgery, and 45.4% for irresectable patients. Acute Grade 2 or 3 toxicity occurred in 43% of the patients, resolving in a few days. Two patients had a local necrosis lasting 3 to 7 months. Late toxicity was observed in 5 patients.ConclusionsHigh-dose-rate plesiobrachytherapy is a simple outpatient technique to treat chest wall local relapse of breast cancer. As a reirradiation technique, its tolerance is acceptable. This technique may obtain long-term local control after incomplete surgery; in case of nonresectable disease, a high response rate was observed, which might improve the quality of life of these patients.     

Postmastectomy Electron-Beam-Rotation Irradiation in Locally Advanced Breast Cancer

BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.     

Current status of radiotherapy following ablative and breast-sparing treatment of breast cancer

After a total mastectomy in cases of a high risk of loco-regional recurrence the postoperative irradiation of the chest wall is indicated in the following situations: Inflammatory type of carcinoma, tumor stage T3-T4, extended multifocal and multicentric primary tumor. After radical axillary surgery even in patients with positive nodes irradiation is not necessary except in cases where all axillary nodes are involved or with invasion of the axillary tissue. The supra- and infraclavicular lymph drainage regions caudal to the operated area (clip) should be irradiated with 50 Gy providing both an enlarged or subtotal involvement can be diagnosed. The irradiation of the retrosternal lymph-drainage system with 45-50 Gy is indicated as follows: Medial or central tumor site, extensive involvement of the axillary nodes and advanced stages of the primary tumor (T2-T4). Axillary irradiation alone cannot serve as a substitute for surgery. After segmental mastectomy without postoperative radiotherapy a local failure rate of 30% is to be expected during a 5 year period. After surgery with adjuvant postoperative irradiation the local failure rate can be reduced to about 5%: 50-60 Gy should be applied. In case of an unfavourable histology an additional boost dose is recommended. The objective of breast cancer irradiation is to achieve freedom of loco-regional recurrence. The survival can be improved occasionally after local irradiation, theoretically improvement of survival can be achieved in 7-10% at the most.     

Postmastectomy Radiotherapy of the Chest Wall

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for postmastectomy irradiation. A retrospective analysis of patterns of locoregional failure (LRF) after modified radical mastectomy and axillary lymph node dissection followed by locoregional radiotherapy with or without systemic treatment was performed. Main emphasis was focused on the comparison of two postmastectomy radiotherapy techniques. PATIENTS AND METHODS: 287 evaluable patients with locally advanced disease and/or adverse pathologic features (pT3 17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%) with or without adjuvant chemo-hormonal treatment were included between 1989 and 2000. Median age was 61 years (range 24-88 years). All patients had modified radical mastectomy and axillary lymphonodectomy level I-II(III) for primary breast cancer. Median total dose of conventionally fractionated radiotherapy to the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10 Gy was applied in 72 patients. 80% of the patients received supraclavicular and 60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27% chemotherapy. The median follow-up of patients at risk was 43 months (average 54 months). RESULTS: The 5-year locoregional tumor control (LRC), LRC first event, disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier analysis), respectively. Cox regression analysis showed that stage III (relative risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional failure, while positive estrogen receptor status (RR 0.3) was associated with a reduced risk. No statistically significant differences in LRC were observed for patients treated either with the electron-rotation technique (LRC 92%) or with the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors resected with "close margins" showed a higher LRF rate of 25% after electronbeam-rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed 6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm developed LRF in 29% of patients treated with electron-beam-rotation irradiation and in 17% of patients with photon-based irradiation (p = 0.1). CONCLUSION: In locally advanced breast cancer, the LRC after postmastectomy irradiation with both techniques is comparable with published data from randomized studies. The tangential opposed photon field technique seems to be beneficial after marginal resection (histopathologic "close margins") of the primary tumor.     

Radiotherapy as adjunct to surgery for malignant carotid body paragangliomas presenting with lymph node metastases.

PURPOSE: Three cases of malignant carotid body paragangliomas with nodal metastases are reported. PATIENTS AND METHODS: Between 1985 and 1994, 3 female patients (51 to 65 years of age) were referred for postoperative radiotherapy after complete (2) or incomplete (1) surgical excision of a malignant carotid paraganglioma (Shamblin III). Preoperative angiographic embolization of the tumor-supplying arteries was performed in all cases. In 2 patients resection of the internal carotid artery and reconstruction by saphenous vein graft was necessary. Continuous course radiotherapy of the tumor bed (50 to 56 Gy/2 Gy) and regional lymph nodes (50 Gy) using photon beams was delivered in 2 patients. The third patient having had incomplete resection cancelled radiotherapy after 4 Gy. RESULTS: Within an observation time of 110 and 119 months no evidence of recurrence was obtained in both patients irradiated postoperatively. The third patient died of progressive disease. Twelve months after the withdrawn irradiation she presented with a tumor progression into the brain and an ulcerated mass on the right side of the neck and was irradiated consecutively for palliation (Figures 1a to 1f). In none of the patients severe acute or late radiation-induced complications were observed. CONCLUSION: In patients with malignant paraganglioma moderate dose postoperative radiotherapy of the tumor bed and regional lymph nodes is well tolerated. It seems to be effective to prolong local control after surgery, to eradicate microscopic lymphatic disease and eventually to postpone further spreading.     

The feasibility of a second lumpectomy and breast brachytherapy for localized cancer in a breast previously treated with lumpectomy and radiation therapy for breast cancer

PURPOSE: With accumulating evidence supporting partial-breast irradiation, we conducted a Phase I/II study to evaluate the role of a second conservative surgery and brachytherapy for patients presenting with a local recurrence/new primary in a breast who has previously undergone a lumpectomy and external radiation therapy for breast cancer. METHODS AND MATERIALS: Fifteen patients with a localized lesion in the breast have undergone a second lumpectomy and received low-dose-rate brachytherapy on protocol. The first 6 patients received a dose of 30Gy. With no unacceptable acute toxicity observed, the brachytherapy dose was increased to 45Gy. Three patients received adjuvant chemotherapy and 8 patients are on antiestrogen therapy. RESULTS: The median time interval between the primary breast cancer diagnosis and the second cancer event in the ipsilateral breast is 94 months (range, 28-211). With a median followup of 36 months after brachytherapy, the 3-year Kaplan-Meier overall survival, local disease-free survival and mastectomy-free survival are 100% and 89%, respectively. There was no Grade 3/4 fibrosis or necrosis observed. All patients had baseline asymmetry due to the breast volume deficit from the second lumpectomy. With breast asymmetry as a given, the cosmetic result observed in all patients has been good to excellent. CONCLUSIONS: Early results suggest low-complication rates, high rate of local control and freedom from mastectomy. Additional studies are needed to establish whether a second lumpectomy and breast brachytherapy are an acceptable alternative to mastectomy for patients presenting with a localized cancer in a previously irradiated breast.     

Recurrences, the surgical and radiological side effects and new developments in the breast-preserving treatment of breast carcinoma]

In the Department for Gynecology and the Department for Gynecologic Radiology, University of Heidelberg, breast conserving therapy was carried out in 1,330 patients with breast cancer between 1975 and 1990. The tumor size was up to 3 cm, 28% showed positive nodes. The medium age was 47.6 years, segmental resection was the standard operation, whole breast irradiation with 50 Gy and an additional boost of 10 Gy was standard irradiation schedule. After five years (n = 307) the following results were observed: local failure 6.8%, regional lymph node recurrence 2.1%, overall survival 88.3%, disease-free survival 81.2%. Five out of 36 of the death-cases died without recurrence. Significant factors for local failure were following: 1. lymphangiosis of more than 1 cm in size around the tumor (p = 0.03); 2. intra-ductal non-invasive cancer of more than 1 cm in size around the primary (p = 0.01); 3. intra-ductal non-invasive cancer reaches the margin of resection (p less than 0.00001). With segmental resection (2 cm margin macroscopically free of tumor) showed in 19% histologically tumor beyond the margins so-called residuals. In the other three quadrants additional second primaries of (multicentric cancers) macroscopical size could be confirmed in an additional study. In case of high risk for local failure more radicality in operation as well as in irradiation is recommended.     

Prognostic factors for local recurrence in patients with limited surgery and irradiation of breast cancer

Between January 1975 and December 1984, 239 patients after breast conserving surgery were referred to the University Clinic for Radiotherapy and Radiobiology of Vienna. Of these patients 214 were available for analysis with regard to loco-regional control and cosmetic outcome. The breast received supervoltage irradiation from two tangential fields, in 82% with a tumor dose of 50 Gy and in 15% 50 to 60 Gy. In addition 70% of the patients received a boost dose with 7.5 to 15 MeV electrons to the tumor bed and the scar. The overall local failure rate was 10.2%. For patients with T1,2 and negative axillary nodes or less than four positive lymph nodes (N = 160) a recurrence rate of 7.1% was observed. Factors correlated to a higher local recurrence rate were in this retrospective study axillary status (greater than 3 positive lymph nodes), histopathologic grade (G III), absence of clear margin after surgery and absence of additional electron boost.     

Perioperative Brachytherapy for Pretreated Chest Wall Recurrence of Breast Cancer

PURPOSE: To demonstrate the technical aspects of high-dose-rate afterloading (HDR-AL) brachytherapy for isolated local chest wall recurrence of breast cancer pretreated with mastectomy and axillary node dissection plus postoperative radiotherapy. CASE REPORT: A 63-year-old female patient with left ductal breast cancer, pT2pN1biM0, was reoperated for an isolated local chest wall recurrence 13 years after primary treatment (mastectomy, axillary dissection, and 50 Gy postoperative irradiation). Radical surgery would have involved extreme mutilation. Reoperative surgical margins of 3 mm width were involved, and four parallel afterloading catheters were placed intraoperatively in this histologically positive margin site. Perioperative HDR-AL (Ir-192 stepping source, 370 GBq activity, dose rate: reference air kerma rate at 1 m 40.84 mGy/h kg) was performed. Dose per fraction: 6 Gy to the reference line, two fractions per week, total dose 30 Gy. Follow-up after secondary treatment: 5 years. RESULTS: Firm local control and 5-year disease-free survival were obtained with perioperative HDR-AL therapy; staging procedures (clinical exam, MRI, abdominal ultrasound, and bone scan) showed no evidence of disease. The development of radiodermatitis did not exceed grade 2 level and healed spontaneously within 6 weeks. CONCLUSIONS: Isolated local chest wall relapse can be effectively controlled by wide surgical excision and perioperative reirradiation with HDR-AL. This technique may represent a treatment alternative to ultraradical surgery, with equal healing probability and a better quality of life. Small-volume irradiation of the postoperative scar can be performed with HDR-AL brachytherapy, and long-term local control can be achieved with a total dose of 30 Gy.     

早期乳腺癌根治术后辅助放疗指征探讨

目的 探讨腋窝淋巴结阳性数为1~3个的早期乳腺癌患者根治术后辅助放疗的指征。 方法 回顾性分析根治术后并经病理证实腋窝淋巴结阳性数为1~3个的早期乳腺癌患者92例,腋窝淋巴结阳性数为1、2、3个的患者数分别为40、30、22例。其中45例接受同侧胸壁、内乳区及锁骨上淋巴引流区放疗。定义预后指数≥4分者为高危患者, < 4分者为低危患者。采用Kaplan-Meier法计算生存率,并用Logrank法进行检验。 结果 放疗患者和未放疗患者的5年生存率分别为93.5%和86.4%(χ2=3.43,P＞0.05),10年生存率分别为73.0%和56.8%(χ2=2.82,P＞0.05),局部复发率为6.7%和19.1%(χ2=4.66,P＜0.05)。低危和高危患者中未放疗患者的10年生存率分别为73.0%和56.8%(χ2=3.45,P＞0.05),局部复发率分别为11.0%和24.0%(χ2=4.64,P＜0.05)。低危和高危患者中接受放疗患者的10年生存率分别为82.0%和72.3%(χ2=4.07,P＜0.05),局部复发率分别为11.0%和5.0%(χ2=5.64,P＜0.05)。 结论 对腋窝淋巴结阳性数为1~3个的早期乳腺癌根治术后且预后指数为高危的患者,建议术后行胸壁和同侧锁骨上淋巴结辅助放疗。     

Regional Nodal Recurrence in the Management of Breast Cancer Patients with One to Three Positive Axillary Lymph Nodes

PURPOSE: To examine the prognosis of breast cancer patients (T1-3, one to three positive axillary lymph nodes) and locoregional failure rate after breast-conserving therapy/modified radical mastectomy and adequate axillary dissection following tangential radiotherapy without irradiation of the regional lymph nodes. PATIENTS AND METHODS: From 1994 to 2002, the medical records of 183 breast cancer patients (T1-3, one to three involved axillary lymph nodes) were examined in order to identify those experiencing regional nodal recurrence, with or without local recurrence. The median age of the patient population was 58 years (range, 28-86 years). All patients underwent surgical treatment, either breast-conserving therapy (n = 146) or modified radical mastectomy (n = 37). The median number of lymph nodes removed was twelve (range, seven to 26 nodes). Irradiation was given to the breast through tangential fields. Chemotherapy was administered to 101 patients (55%), hormonal therapy to 124 (60%), and combined systemic treatment to 47 (26%). RESULTS: The median observation time was 44.4 months (range, 11-102 months). Of the 14 patients (7.7%) with a relapse, six (3.3%) had a local recurrence, five (2.8%) a regional relapse, and three (1.6%) a simultaneous recurrence. Nine out of 14 patients with locoregional relapse developed distant failure subsequently and seven of them (78%) died of the disease. CONCLUSION: Regional recurrence is uncommon among patients with one to three positive axillary lymph nodes treated with surgery, adequate axillary dissection, and tangential field irradiation only. The authors conclude that regional nodal irradiation should not routinely be given following adequate axillary dissection when only one to three lymph nodes are positive.     

Predisposing factors for local recurrence after conservative treatment of breast cancer

The factors predisposing to local relapse after conservative treatment of early stage breast cancer are controversial. To determine these factors, we analysed the results obtained in a series of 512 patients consecutively treated for invasive breast carcinomas by conservative surgery and radiotherapy. All patients were treated by tumorectomy and axillary dissection, radiation therapy of 45 Gy to the whole breast with a boost of 15 Gy to the tumor area, and adjuvant medical treatment for 168 out of 187 patients. The overall 5-year and 10-year survival rates were respectively 92.5% and 79.9%. The actuarial 5-year and 10-year local control rates were respectively 91.2% and 83.6%. Local relapses occurred in 35 patients. Local relapse occurred more frequently in premenopausal patients, in patients less than 50 years-old as compared to older patients, in patients with low body-mass index (BMI), and in patients with small breast size. Local control was not significantly affected by tumor size or node involvement. With multivariate analysis, the only factor influencing local control was the body-mass index: the actuarial risk of local relapse was increased by 5.7 in patients with a BMI less than or equal to 22 as compared to patients with a BMI greater than 22 (p less than 0.02). We concluded that although certain clinical factors such as age, menopausal status, breast size and body-mass index have an influence on local control, these factors are not sufficiently discriminant to question the indication of conservative treatment. There is a need to individualize factors that could allow a better discrimination of patients with a high probability of local relapse.     

Interstitial radiotherapy of breast cancer. Preliminary report of a prospective study of 165 cases subjected to breast-conserving treatment

The results of a prospective study on breast conserving therapy in early stage breast cancer are presented. From January 1983 to June 1987 165 patients were treated by a standardized therapy-protocol. The criteria for entering the trial were stage T1 to T2 and N0 to N1. Surgical breast conservation was achieved by segmental resection in 148 cases and by tumorectomy in 17 cases. 160 patients underwent axillary lymph node dissection. Obligatory 45 to 50 Gy were delivered percutaneously to the operated breast and optional 50 Gy to the regional lymph nodes (axillary lymph node involvement greater than 3 nodes). In addition, the area of the primary breast lesion itself was boosted interstitially by an Iridium 192 implant (LDR-technique: 15 to 20 Gy, HDR-technique: 10 to 12 Gy). Results: Progression of disease in 10% of the patients (16/165), local recurrence rate in the operated breast: 2% (3/165), axillary recurrence: 0.5% (1/165). 5% of the patients (8/165) died from metastatic disease, two patients died free of recurrence for reasons unrelated to cancer, two other patients died on unknown reasons. Because of the low number of local recurrences and the observation period of 32 months, no statistically contribution on high risk factors for local failure could be found.     

Prognostic Significance of Local Recurrence in Breast Cancer after Postmastectomy Radiotherapy

Purpose: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. Patients and Methods: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4-tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pNO-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. Results: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p = 0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs. 15.4%, p = 0.002 and 62.1% vs. 34.8%, p = 0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pNO status vs 27% in with positive axillary nodes (p = 0.025). Conclusions: Local recurrence after treatment of breast cancer with mastectomy + radiotherapy - systemic therapy is associated with a significantly higher risk of distant metastases and death. In this analysis, local recurrence was a strong and, beside lymph node status and T category, an independent risk factor for survival. Minimizing the risk of local recurrence is therefore an essential goal of a curative treatment concept. Hintergrund: Wir haben in einer retrospektiven Analyse unseres Patientenkollektivs den Einfluss eines Lokalrezidivs auf die Prognose bei mastektomierten Mammakarzinompatientinnen untersucht. Patienten und Methode: Von Januar 1985 bis Dezember 1993 erhielten 959 Patientinnen an unserer Klinik eine Bestrahlung nach Mastektomie in kurativer Intention. Das Alter betrug 34-79 Jahre. 368 (38%) waren prämenopausal, 35% hatten T3-4-Tumoren, und 62% wiesen einen axillären Lymphknotenbefall auf. Alle Patientinnen erhielten eine Bestrahlung der Thoraxwand und der regionären Lymphknoten (Axilla inklusive Supraklavikularregion und beidseitig parasternal) mit einer modifizierten Großfeldtechnik. Die Lymphknoten und laterale Thoraxwand wurden durch ein ventrales Stehfeld mit Telekobalt oder 9-MV-Photonen mit 50 Gy in Einzeldosen von täglich 2 Gy bestrahlt (RP in 2,5 cm Gewebetiefe); die Lunge wurde ausgeblendet und die Thoraxwand im Schatten dieses Absorbers mit einem individuell kollimierten Elektronenfeld mit 44 Gy in Einzeldosen von 2 Gy bestrahlt. 66% der Patientinnen erhielten eine zusätzliche Systemtherapie. Die Nachbeobachtungszeit betrug 3 Monate bis 12,2 Jahre (im Median 3,1 Jahre). Ergebnisse: Die Gesamtüberlebensrate betrug 70,5% nach 5 und 59,8% nach 10 Jahren. 53 Patientinnen entwickelten ein Lokalrezidiv. Die rezidivfreie Zeit betrug 2-96 Monate (Median: 26 Monate). Die lokale Kontrollrate betrug 92,7% nach 5 und 86,4% nach 10 Jahren. Axillärer Lymphknotenbefall war (in multivariater Analyse) der einzige Risikofaktor für ein Lokalrezidiv (p = 0,0001). Patientinnen mit lokaler Kontrolle hatten im Vergleich zu Patientinnen mit Lokalrezidiv ein signifikant besseres fernmetastasenfreies Überleben (44,5% vs. 15,4% nach 10 Jahren, p = 0,002) und eine höhere Gesamtüberlebensrate (62,1% vs. 34,8% nach 10 Jahren, p = 0,004). Ein Lokalrezidiv erhöhte das Todesrisiko um den Faktor 1,7. In der Cox-Regression waren axillärer Lymphknotenbefall, T-Kategorie und das Auftreten eines lokalen Rezidivs unabhängige und signifikante Prognosefaktoren für das Gesamtüberleben. Bei Patientinnen mit Lokalrezidiv war der initiale axilläre Lymphknotenstatus der wichtigste Prognosefaktor für die Überlebenszeit nach dem Lokalrezidiv. Die 3-Jahres-Überlebensrate nach Lokalrezidiv betrug 86% für Patientinnen mit initialem pNO-Status vs. 27% für Patientinnen mit pN+, p = 0,025). Schlussfolgerungen: Das Lokalrezidiv nach Mastektomie und postoperativer Radiotherapie - Systemtherapie ist ein wichtiger und unabhängiger Prognosefaktor. Patientinnen mit Lokalrezidiv haben ein erhöhtes Risiko für Fernmetastasen und eine erhöhte Mortalität. Eine optimale lokale Kontrolle ist deshalb Grundlage eines kurativen Behandlungskonzepts.     

Radiotherapy in the treatment of locoregional relapses of breast cancer

Locoregional recurrences of breast cancer are associated with considerable morbidity and frequently present with concurrent metastatic disease. Yet patients without systemic spread can be treated with curative intent. In a retrospective analysis, the results of treatment of these patients have been evaluated at our institution. Between 1987 and 1996, 113 patients with locoregional breast cancer relapse, without systemic manifestation, received irradiation after local tumour excision. 13 patients (11.5%) had already received radiotherapy as part of their primary treatment. In these cases, only the area involved was treated. In all other patients, the chest wall and the ipsilateral lymph nodes were irradiated. Median dose was 50 Gy (range 20-65 Gy). Median follow-up was 4.4 years. 76 patients (67.3%) presented with chest wall recurrence only, 25 patients (22.1%) with nodal relapse only and 12 patients (10.6%) with combined relapses. 93% of patients had local control of disease after treatment. Local control rate after 5 years was 59%. 63 patients (55.8%) died within the follow-up interval, 45 patients (39.8%) owing to metastases, 4 patients (3.5%) owing to local failure and 8 patients (7%) owing to causes unrelated to tumour. Overall survival after 5 years was 43%. In multivariate analysis, positive hormone receptor status, small tumours on relapse and chest wall relapses alone were associated with improved survival. Radical local therapy is necessary in order to achieve and maintain local control and to prevent secondary dissemination in patients with only local recurrence of breast cancer.     

Lokale Tumorkontrolle und kosmetisches Ergebnis nach brusterhaltender Operation und Strahlentherapie bis 56 Gy Gesamtdosis ohne Boost beim Mammakarzinom

PURPOSE: To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation. PATIENTS AND METHODS: In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire. RESULTS: Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size. CONCLUSION: The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good compatibility with tolerable side effects and good cosmetic results.     

Soft tissue sarcomas after radiation treatment for breast cancer. Three case studies and review of literature.

AIMS: By means of 3 cases with infield soft tissue carcinomas after radiotherapy for breast cancer, symptoms and therapy are described. Consequences for treatment planning and patient's information before radiotherapy for breast cancer are discussed. PATIENTS: Three of 1,025 patients with breast cancer irradiated from 1984 to 1997 suffered from infield secondary soft tissue sarcomas. The latency periods were 61, 49 and 59 months. Two patients had been treated with breast-conserving therapy (computerized planning, 50 Gy to reference point, 5 times 2 Gy/week, 5-MV photons), 1 patient received a local boost dose of 15 Gy (10-MeV electrons), patient 3 radiotherapy of the thoracic wall and regional lymph nodes after mastectomy using 12-MeV electrons (thoracic wall) and 5-MV photons (lymph node areas) to 50 Gy, 5 times 2 Gy/week. No adjuvant chemotherapy was given. All sarcomas were very extensive, all patients died from local progression and/or distant failure after 17, 13 and 12 months. RESULTS: The incidence of spontaneous sarcomas of the breast is about 0.06%, after operation and radiotherapy 0.09 to 0.45%. No correlations to radiotherapy technique and no risk factors were found. Radiation dose could play a role, but there are very sparse data about this. CONCLUSIONS: Secondary soft tissue sarcomas are very rare, but familiar complications of radiotherapy. Only early diagnosis leads to a chance for cure. Because of unclear correlations to the treatment parameters and rareness of this event, in our opinion no regular information to the patient receiving radiotherapy for breast cancer is mandatory.     

High-Dose-Rate (HDR) or Pulsed-Dose-Rate (PDR) Perioperative Interstitial Intensity-Modulated Brachytherapy (IMBT) for Local Recurrences of Previously Irradiated Breast or Thoracic Wall Following Breast Cancer

PURPOSE: In patients receiving salvage high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy for a local recurrence on the chest wall or in the previously treated breast, clinical outcome and benefit were investigated. All patients had previously been treated with full-dose adjuvant external-beam irradiation (EBRT). Disease-free interval after salvage treatment, local tumor control and side effects were analyzed retrospectively. PATIENTS AND METHODS: Between 1996 and 2002, a total of 32 consecutive patients were treated. 13 patients initially treated with mastectomy and postoperative irradiation and 19 patients initially treated with breast-conserving surgery and postoperative irradiation developed a local recurrence. The mean dose of previous radiation therapy was 58 Gy (range, 42-64 Gy), applied by conventional fractionation. After implantation +/- surgery of recurrent disease and CT-based 3-D planning, 15 patients were irradiated with HDR-IMBT (intensity-modulated brachytherapy) with a mean dose of 28 Gy (range, 10-30 Gy, 2 x 2.5 Gy/day at 6-h daily interfraction interval) and 17 patients received PDR-IMBT with a mean dose 30 Gy (range, 10-45 Gy, 5 x 1 Gy/day at 2-h pulse intervals). Four patients underwent additional EBRT using a dose of 24-40 Gy electrons. Treatment was performed only on working days. RESULTS: After a mean post-implant follow-up of 19 months (range, 1-83 months), no signs of local recurrence were observed in 20 of the 32 patients. In twelve patients, local recurrence occurred after a mean follow-up of 13 months (range, 1-78 months). 20 of the 32 patients experienced an additional systemic progress. In one patient, an EORTC/RTOG grade 3 side effect (ulceration of the skin) was described, which was followed by a local recurrence 12 months posttherapeutically. CONCLUSION: Perioperative interstitial HDR/PDR-IMBT of localized breast or thoracic wall recurrences following previous full-dose EBRT appears to be a meaningful salvage treatment with acceptable toxicity.     

Spättoxizität nach präoperativer Kurzzeitvorbestrahlung und risikoadaptierter postoperativer Nachbestrahlung bei operablem Rektumkarzinom Resultate einer randomisierten prospektiven Studie

AIM: Analysis of a randomized study of preoperative radiation therapy for operable carcinoma of the rectum with regard to late sequelae. Results of tumor control and survival, which have already been published in detail are summarized for comparison and for confirmation of the conclusions. PATIENTS AND METHODS: Between January 1988 and October 1993 94 patients with operable carcinoma of the rectum were included in a randomized trial. Fourty-seven patients were treated with 5 x 3.3 Gy (field size 16 x 16 cm, 9 MeV photons) 24 to 48 hours prior to surgery; 46 patients did not receive preoperative irradiation. If risk factors (T4-stage, R1/R2 resection, intraoperative tumor perforation) were present, postoperative irradiation was performed after CT-planning. Total postoperative doses of 41.4 Gy (preoperative irradiation) or 59.8 Gy (surgery only) were applied with doses per fraction of 1.8 to 2.0 Gy. Local control, survival, and pattern of side effects were analyzed at 5 years after conclusion of the trial. RESULTS: The frequency of local recurrence was markedly reduced by preoperative irradiation of R0-resected patients (24% vs 13%, p = 0.08). The time to recurrence was delayed (1.9 vs 3 years). The 5-year actuarial survival rate was significantly higher in the preoperatively irradiated group compared to the not pre-irradiated group (40% vs 28%, p = 0.027). Multivariate analysis revealed UICC-grading as the only independent parameter for local control (p = 0.0003), while preoperative irradiation (p = 0.07) and T-stage (p = 0.08) only displayed a trend. For patient survival, age (p = 0.0003). R-status (p = 0.01) and UICC-score (p = 0.001) were significant prognostic factors. Preoperative irradiation had a non-significant effect only (p = 0.078). Radiation-induced side effects with a LENT-SOMA score > 2 were observed neither during frequent follow-up nor at an additional examination of those patients still alive in 1998 (n = 25). Of 4 pre- and postoperatively irradiated patients with risk factors, 3 had side effects grade 1 or 2, predominantly rectal changes, at 5 to 11 years after treatment. CONCLUSIONS: A positive effect on tumor control and survival is achieved with preoperative irradiation with the doses used in this study, with moderate side effects.