Early mammographic and sonographic findings after intraoperative radiotherapy (IORT) as a boost in patients with breast cancer

The aim of this study was to evaluate mammographic and sonographic changes at the surgical site within the first 2 years after IORT as a boost followed by whole-breast radiotherapy (WBRT), compared with a control group treated with WBRT alone. All patients had breast-conserving surgery for early-stage breast cancer. Group A: n = 27, IORT (20 Gy) followed by WBRT (46 Gy). Group B (control group): n = 27, WBRT alone (56-66 Gy). Mammography: fat necrosis in 14 group A versus four group B patients (P < 0.001); parenchymal scarring classified as unorganized at the last follow-up in 16 vs seven cases, respectively (P = 0.03). Ultrasound: overall number of patients with circumscribed findings 27 vs 18 (P < 0.001); particular hematomas/seromas in 26 vs 13 patients (P < 0.001). Synopsis of mammography and ultrasound: overall postoperative changes were significantly higher classified in group A (P = 0.01), but not judged to have a significantly higher impact on interpretation. Additional diagnostic procedures, due to unclear findings at the surgical site, were performed on four patients of both groups. Within the first 2 years after IORT as a boost, therapy-induced changes at the original tumor site are significantly more pronounced compared with a control group. There is no evidence that the interpretation of findings is complicated after IORT.     

Intraoperative Radiotherapy of Soft Tissue Sarcoma of the Extremity

PURPOSE: Evaluation of treatment outcome after intraoperative radiotherapy (IORT) +/- external-beam irradiation (EBRT) in patients with localized soft tissue sarcoma of the extremity at high risk for local recurrence after limb-sparing surgery. PATIENTS AND METHODS: 28 patients treated between 1989 and 1999 were evaluated retrospectively. Patients presented with locally recurrent (n = 17), T2 (n = 20), high-grade (n = 26), or incompletely resected tumors (n = 11). All patients underwent limbsparing surgery and IORT (median dose of 15 Gy) given either with high-dose-rate brachytherapy or a linear accelerator. 25 patients received additional EBRT with a mean of 50.6 Gy (range: 30.6-60 Gy). The mean follow-up time was 4.3 years (95% confidence interval [CI]: 3.0-5.6 years). RESULTS: The 5-year overall and distant disease-free survival rates were 66% and 54%, respectively. The overall actuarial recurrence rate after 5 years is 16% (95% CI: 1%, 31%). The crude rate after 8 years is 18%. Surgical margin status, primary versus recurrent tumor and tumor stage did not show any statistically significant influence (univariate analysis) on local recurrence rates. Patients with T1 tumors exhibited a borderline significant (p = 0.053) better distant disease-free survival (83%) compared to T2 tumors (43%). Five (24%) grade 3-4 late side effects were observed. CONCLUSION: In patients with high-risk soft tissue sarcomas, IORT +/- EBRT after limb-preserving surgery achieves high local control rates. The risk of normal tissue toxicities is comparable to conventional limb-sparing treatment.     

Partial Breast Irradiation after Breast-Conserving Surgery

BACKGROUND: The standard technique of postoperative radiotherapy after breast-conserving surgery is percutaneous irradiation of the entire breast to a total dose of 45-50 Gy which is usually followed by a tumor bed boost. Since the majority of local recurrences in selected patients occur close to the former tumor bed, the question arises whether a sole tumor bed irradiation might be a therapeutic alternative to total breast irradiation. METHODS: A systematic review of relevant literature concerning partial breast irradiation (PBI) up to November 2004 was undertaken. Studies of any design were included for comparison and discussion. RESULTS: Nine unique brachytherapy studies using the multi-catheter technique, one the balloon technique (MammoSite), and eight particular intraoperative radiotherapy (IORT) trials were located of which only one was a randomized trial. Only minor postoperative complications were reported. Preliminary results are similar in terms of local tumor control, disease-free and overall survival. However, the current evidence base of IORT studies is poor. CONCLUSION: Despite controversies regarding PBI after breast-conserving surgery, results of phase I-II trials suggest that sole tumor bed irradiation might be an appropriate therapeutic alternative for selected breast cancer patients. However, more experience and data from ongoing phase III trials are required to define these new methods to be an appropriate treatment option. Therefore, total breast irradiation still remains the standard irradiation modality even in the treatment of early breast cancer, and PBI should be considered investigational.     

5-Year Results of Pulsed Dose Rate Brachytherapy Applied as a Boost after Breast-Conserving Therapy in Patients at High Risk for Local Recurrence from Breast Cancer

PURPOSE: The aim of this study was to evaluate effect, toxicity, and cosmesis of a prospectively applied pulsed dose rate (PDR) brachytherapy boost schedule in patients with stage I/II/IIIa invasive breast cancer. PATIENTS AND METHODS: A total of 113 patients were treated after breast-conserving surgery (BCS) and external beam radiotherapy (median 50 Gy, range 46-52). The boost dose was graded in accordance to the pathologic tumor characteristics: 20-25 Gy: incomplete resection (n = 34), vascular invasion (n = 27), close margin resection (n = 41); 15 Gy: T2G3 stage (n = 11). PDR brachytherapy (37 GBq, (192)Ir source) was carried out after geometric volume optimization with 1 Gy/pulse/h. The implantation and dose specification were performed similar to the rules of the Paris system. RESULTS: The overall local failure rate after a median follow-up of 61 months was 4.4% (5/113). The actuarial 5- and 8-year local recurrence-free survival rates were 95% and 93%, respectively. Cosmesis was rated by 90% of the patients as excellent or good. 14/113 patients experienced grade III (all caused by planar telangiectasia) and none of the patients grade IV late toxicity of the skin (RTOG/EORTC). A boost dose of 25 Gy resulted in a significantly higher rate of late toxicity (Fisher's exact test, p < 0.01). CONCLUSIONS: PDR brachytherapy is safe, effective, and provides good cosmesis. A CLDR breast boost can be replaced by PDR brachytherapy without significant loss of therapeutic ratio.     

Intraoperative Strahlentherapie (IORT) in der Behandlung des Mammakarzinoms – eine neue therapeutische Alternative im Rahmen der brusterhaltenden Therapie? Stellenwert und Zukunftsperspektiven. Erfahrungsbericht aus dem European Institute of Oncology (EIO), Mailand

BACKGROUND: External beam radiation therapy (EBRT) represents an integral component of breast-conserving treatment. In published series it has been demonstrated that the external boost can be replaced by intraoperative radiotherapy (IORT) where irradiation at a single dose from 10 up to 15 Gy was safely delivered directly to the tumor bed. PATIENTS AND METHODS: At the European Institute of Oncology, Milan, we initiated a dose escalation study to investigate the feasibility of applying single doses of IORT from 10 Gy up to 22 Gy. A portable IORT equipment with different electron energies was used. From July to December 1999, a total of 65 patients with T1-2 (max. 2.5 cm) No-1 breast cancer, median age 58 years (range 33-80 years) was treated. Ten patients received 10 Gy, eight patients were treated with an IORT of 15 Gy, eight received 17 Gy, six had 19 Gy, and 33 were treated with 21-22 Gy. Patients with 10 and 15 Gy received an additional EBRT of 44 and 40 Gy, respectively. In all other patients IORT was the sole radiation treatment. RESULTS: No acute side effects or intermediate untoward effects after a follow-up from three to nine months related to IORT were observed. CONCLUSIONS: Since the applicator can be safely placed under the control of the surgeon and radiotherapist IORT has the potential of accurately treating the tumor bed. Skin and subcutaneous tissue are not irradiated thus decreasing the potential risk of fibrosis and eventually obtaining a better cosmesis. With IORT single doses of 22 Gy being equivalent to a 60 Gy EBRT can safely be delivered. Even so the average time of operation was prolonged by around 20 minutes IORT application ultimately improves the quality of life of the patients in shortening overall treatment. Long-term follow-up is necessary to demonstrate whether large single doses of IORT might have the potential of sufficient local tumor control without major side effects. As a future perspective a randomized trial comparing EBRT with IORT as sole treatment will be performed.     

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.     

Do structural changes in the tumour bed after intraoperative radiotherapy (IORT) of breast cancer complicate the evaluation of mammograms in a long-term follow-up?

The purpose of the study was to assess whether postoperative changes in the tumour bed after intraoperative radiotherapy (IORT) with low-energy X-rays complicate the mammographic evaluation. 54 patients receiving breast-conserving surgery and IORT were compared to a control group of 48 patients with conventional breast-conserving treatment. All patients were included in routine follow-ups (≥3 years) with mammography accompanied by ultrasound. By retrospective consensus reading the mammographic changes in the tumour bed were classified as absent, low or distinct. Using the same grading it was classified whether mammographic evaluation was complicated due to postoperative changes. Focusing the yearly follow-ups within a period of four years, distinct changes were found significantly more often after IORT (52-62% vs. 7-30%). After IORT the evaluation was significantly more often distinctly complicated in each follow-up, except for year 1 (16-21% vs. 0-8%). In the IORT group the distribution of findings was nearly stable over time. In the control group it changed over time and a distinctly complicated evaluation was no longer seen in the follow-ups of years 3 and 4. Overall, further non-routine diagnostic procedures due to unclear findings in the tumour bed became necessary in 7% (IORT) vs. 8% (control group) of the patients (p=0.86). Evaluation of mammograms is complicated after IORT. In contrast to conventionally treated patients postoperative changes and difficulties of evaluation do not decrease over time. Overall, after IORT the diagnostic uncertainty does not seem to be increased in ultrasound supported mammographic follow-ups. The topic needs further evaluation with larger study samples.     

Multimodal treatment of locally advanced carcinoma of the breast. Experience at the Galliera di Genova Hospital

All patients with locally advanced breast cancer receiving definitive irradiation (with or without surgery) at the Radiation Oncology Service, Ospedali Galliera, Genova, Italy, from 1969 through 1986, were retrospectively reviewed. Group A consisted of 187 patients, affected with stage III disease, who received radiation therapy after radical surgery. Irradiation of the chest wall and regional lymph node chains was accomplished with divergent tangential beams of Cobalt: the dose was calculated at the mid-plane of the tangential field separation and was 50Gy (2 Gy/day, 5 fractions/week), followed by additional 10-15 Gy boost to the scar. One hundred and five patients received combined hormonotherapy and/or chemotherapy. After a mean follow-up of 49+ months we observed 21 local recurrences (16 in metastatic patients); 64 patients developed only distant metastases. Actuarial survival at 5 years is 55%. Group B consisted of 36 inoperable patients who received definitive irradiation. Radiation therapy planning was very similar to that in group A, even though after 50 Gy the breast and the tumor area were boosted with restricted fields up to a total dose of 80-90 Gy. Fifteen patients received combined hormonotherapy and/or chemotherapy. At the end of the treatment overall response rate was 89%; actuarial survival at 5 years is 38%. Toxicity was generally mild and no death related to the treatment was observed. Our retrospective analysis confirms the importance of a multimodal approach to locally advanced breast cancer in order to free most patients from disease and to produce excellent local control, even though more randomized studies are necessary to improve the long-term survival of these patients.     

Treatment of Solitary Brain Metastasis

BACKGROUND: Whole brain radiation therapy (WBRT) is reported to improve local control after resection of brain metastases. Improvement of survival was only observed in patients with controlled extracranial disease. The optimum radiation schedule has yet to be defined. The authors' experience with a postoperative approach including WBRT and a radiation boost to the metastatic site is presented. PATIENTS AND METHODS: Criteria for inclusion into this retrospective analysis were solitary brain metastasis, Karnofsky performance status > or = 70%, and controlled extracranial disease. Two therapies were compared for local control and survival: surgery followed by 40 Gy WBRT (group A) versus surgery followed by 40 Gy WBRT and a 10 Gy boost (group B). Statistical analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS: 33 patients were included (17 group A, 16 group B). The results suggested better local control (p = 0.0087) and survival (p = 0.0023) for group B. 17/17 patients (100%) of group A and 13/16 patients (81%) of group B showed progression of brain metastasis, 8/17 and 3/16 patients in the area of metastatic surgery. Median time to progression was 7 (1-22) months in group A and 12 (3-42) months in group B. The number of cancer-related deaths amounted to 17/17 (100%) in group A after a median interval of 9 (3-26) months, and to 9/16 (56%) in group B after 14 (4-46) months. CONCLUSION: After resection of solitary brain metastasis, a radiation boost in addition to WBRT seems to improve local control and survival when compared to postoperative WBRT alone. The results should be confirmed in a larger prospective trial.     

Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy

Introduction

The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT).

Method

In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared.

Results

Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5?year Kaplan–Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5–99.2), EBRT 9 events (81.7%, 95%CI 67.6–90.1), hazard ratio (HR) 0.19 (0.04–0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3–95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5–98.4), EBRT 12 events (69.0%, 49.1–82.4), HR 0.23 (0.06–0.80), log rank p = 0.012.

Conclusion

IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.

     

乳腺癌保乳术后放射治疗的疗效观察

目的观察乳腺癌保乳术后放射治疗的疗效和美观效果。方法109例保乳术后在我科接受全乳外照射和瘤床加量(boost)放疗,79例应用高剂量率插植技术,T1肿瘤用单排插植,针距为1.5cm,T2以上肿瘤用双排或三排插植。针距间单次剂量(DB)10～12Gy,靶区周边剂量为85%DB。30例采用电子线常规外照射15Gy。全乳照射应用6MV直线加速器,采用双切线半野照射技术,靶区剂量为45～52Gy(平均48.6Gy)。采用医生评分与患者问卷方法评价美观效果。结果全组109例应用KaplanMeier方法统计5年实际生存率为93.8%。局部复发率为6.5%。全组无放射性溃疡发生,5例出现位于插植针孔周围急性皮肤炎症。在经临床随访体检的75例中,医生打分和患者自评满意度为优的比例分别为87%和81%,无统计学意义(P>0.05)。48例经组织间插植加量放疗;27例经电子线外照加量放疗。两组满意度医生总评为优的患者比例分别为81.2%和85.2%,差异无统计学意义(P>0.05)。结论乳腺癌保乳术后放疗可降低局部复发率,并发症少。不同的瘤床加量放疗方法不影响美观效果。     

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.     

Breast cancer with extensive intraductal component: treatment with immediate interstitial boost irradiation.

Extensive intraductal component (EIC) has been reported to have a prominent role in local recurrence after treatment of early-stage breast cancer with lumpectomy and irradiation. Pathologic specimens from 250 breasts (245 patients) treated between June 1982 and June 1990 with lumpectomy, immediate (boost) interstitial iridium-192 to 15-20 Gy, and external-beam irradiation to the entire breast to 45-50 Gy were reviewed. EIC was present in 61 breasts. At a median follow-up period of 58 months (range, 14-110 months), there were 10 recurrences in the 250 treated breasts. Of these 10, three were in patients from the group with EIC. The 10-year actuarial recurrence rates in breasts with and without EIC were 9.1% and 5.2%, respectively. The difference between the two rates was not significant. If an immediate boost with interstitial iridium is used in therapy, the influence of EIC on local failure is insignificant.     

Breast cancer metastases in liver: laser-induced interstitial thermotherapy--local tumor control rate and survival data

PURPOSE: To evaluate the local tumor control rate and survival data for magnetic resonance (MR) imaging-guided laser ablation of breast cancer liver metastases by using laser-induced interstitial thermotherapy (LITT). MATERIALS AND METHODS: MR-guided LITT was performed in 232 female patients with 578 liver metastases from breast cancer. Survival rates were calculated with the Kaplan-Meier method. Indications for the procedure were defined for patients with no more than five metastases, none of which were larger than 5 cm in diameter, as follows: recurrent liver metastases after partial liver resection (8.2%), metastases in both liver lobes (45.2%), locally nonresectable tumors (19%), general contraindications for surgery (2.6%), or refusal to undergo surgical resection (25%). RESULTS: Local recurrence rate at 6-month follow-up after LITT was 2.3% (five of 213) for metastases up to 2 cm in diameter, 4.3% (seven of 162) for metastases 2-3 cm in diameter, 3.2% (two of 63) for metastases 3-4 cm in diameter, and 1.9% (one of 52) for metastases larger than 4 cm in diameter. No additional local tumor progression was observed beyond 6 months. The mean survival rate for all treated patients, with calculation started on the date of diagnosis of the metastases treated with LITT, was 4.9 years (95% confidence interval: 4.3, 5.4). The median survival was 4.3 years; 1-year survival, 96%; 2-year survival, 80%; 3-year survival, 63%; and 5-year survival, 41%. The mean survival after the first LITT treatment was 4.2 years (95% confidence interval: 3.6, 4.8). CONCLUSION: MR-guided LITT yields high local tumor control and survival rates in patients with liver metastases from breast cancer.     

Full-Dose Intraoperative Radiotherapy with Electrons in Breast Cancer

PURPOSE: To investigate the feasibility of applying exclusive intraoperative radiation therapy (IORT) after conservative surgery in limited-stage breast carcinoma and to evaluate late effects and cosmetic results after this new conservative treatment. PATIENTS AND METHODS: From October 2000 to November 2002, 47 consecutive patients with unifocal breast carcinoma up to a diameter of 2 cm received conservative surgery followed by IORT with electrons as the sole adjuvant local therapy. Three different dose levels were used: 20 Gy (seven patients), 22 Gy (20 patients), and 24 Gy (20 patients). Patients were evaluated using RTOG/EORTC scale to assess the incidence of late complications. During follow-up, a radiologic assessment with mammography and sonography was periodically performed and any breast-imaging alterations were reported. RESULTS: After a follow-up ranging from 36 to 63 months (median, 48 months), 15 patients developed breast fibrosis (grade 2 in 14 patients, grade 3 in one patient), two patients presented with grade 3 skin changes, one patient developed a clinically relevant fat necrosis, and one patient showed breast edema and pain. Two patients developed contralateral breast cancer and one distant metastases; no local relapses occurred. Asymptomatic findings of fat necrosis were observed at mammography in twelve patients (25.5%), while an hypoechoic area was revealed by sonography in ten patients (21.5%). In four patients (8%), mammographic and sonographic findings suggested malignant lesions and required a rebiopsy to confirm the benign nature of the lesion. CONCLUSION: IORT in breast carcinoma is still an experimental treatment option for select patients with breast cancer and its application should be restricted to prospective trials. Although preliminary data on local control are encouraging, a longer follow-up is needed to confirm the efficacy of IORT in breast cancer and to exclude that severe late complications compromise the cosmetic results or modify the radiologic breast appearance during follow-up increasing the need for additional investigations.     

Perioperative high-dose-rate brachytherapy in locally advanced and recurrent gynecologic cancer: Initial results of a phase II trial

BACKGROUND: This study was undertaken to determine the feasibility of perioperative high-dose-rate brachytherapy (PHDRB) as an adjunct to salvage surgery in primary advanced or recurrent gynecologic cancer. METHODS: Twenty-five patients with either locally advanced (n = 4) or recurrent (n = 21) gynecologic cancer suitable for salvage surgery were included. Unirradiated patients were treated with preoperative chemoradiation followed by salvage surgery and PHDRB (R0 and R1 resections receiving 16 or 24 Gy, respectively). Previously irradiated patients were treated with salvage surgery and PHDRB alone with 32 or 40 Gy for R0 or R1 resections, respectively. RESULTS: Resections were categorized as R0 in 9 patients (36.0%) and R1 in 16 (64.0%). Four previously irradiated patients suffered fatal pelvic bleeding between 8 and 13 months after surgery and PHDRB. After a median follow-up of 20 months (3-55+), the 4-year actuarial local and pelvic controls were 88.1% and 80.8%, respectively. The 4-year distant metastases-free survival was 40.9%. Four-year actuarial overall survival was 34.0%, with a median survival of 27.1 months (95% confidence interval: 17.5-36.8). CONCLUSIONS: Local and pelvic control results are excellent for this very high-risk-disease population. PHDRB dose in previously irradiated patients has been shifted to the closest lower level due to unacceptable vascular toxicity.     

5-Year Results of Pulsed Dose Rate Brachytherapy Applied as a Boost after Breast-Conserving Therapy in Patients at High Risk for Local Recurrence from Breast Cancer

Purpose: The aim of this study was to evaluate effect, toxicity, and cosmesis of a prospectively applied pulsed dose rate (PDR) brachytherapy boost schedule in patients with stage I/II/IIIa invasive breast cancer. Patients and Methods: A total of 113 patients were treated after breast-conserving surgery (BCS) and external beam radiotherapy (median 50 Gy, range 46-52). The boost dose was graded in accordance to the pathologic tumor characteristics: 20-25 Gy: incomplete resection (n = 34), vascular invasion (n = 27), close margin resection (n = 41); 15 Gy: T2G3 stage (n = 11). PDR brachytherapy (37 GBq, ¹⁹²Ir source) was carried out after geometric volume optimization with 1 Gy/pulse/h. The implantation and dose specification were performed similar to the rules of the Paris system. Results: The overall local failure rate after a median follow-up of 61 months was 4.4% (5/113). The actuarial 5- and 8-year local recurrence-free survival rates were 95% and 93%, respectively. Cosmesis was rated by 90% of the patients as excellent or good. 14/113 patients experienced grade III (all caused by planar telangiectasia) and none of the patients grade IV late toxicity of the skin (RTOG/EORTC). A boost dose of 25 Gy resulted in a significantly higher rate of late toxicity (Fisher's exact test, p < 0.01). Conclusions: PDR brachytherapy is safe, effective, and provides good cosmesis. A CLDR breast boost can be replaced by PDR brachytherapy without significant loss of therapeutic ratio. Ziel: Diese Studie diente der Evaluierung von Effektivität, Toxizität und kosmetischen Ergebnissen eines prospektiv applizierten PDR- (pulsed dose-rate-)Brachytherapieboostkonzeptes bei Patienten mit invasivem Mammakarzinom im Stadium I/II/IIIa. Patienten und Methoden: Insgesamt wurden 113 Patienten nach brusterhaltender Therapie (BET) und externer Bestrahlung (Median 50 Gy, Range 46-52) behandelt. Die Boostdosis wurde anhand histopathologischer Tumorcharakteristika graduiert (Tabelle 1): 20-25 Gy: inkomplette Resektion (n = 34), Lymphgefäß- oder Gefäßinvasion (n = 27), "close-margin"-Resektion (n = 41); 15 Gy: T2G3 Stadium (n = 11). Die gepulste Brachytherapie (37 GBq, ¹⁹²Ir-Quelle) wurde nach geometrischer Volumenoptimierung mit 1 Gy/Puls/h durchgeführt. Applikation und Dosisspezifikation erfolgten in Anlehnung an das Pariser System. Ergebnisse: Die Lokalrezidivrate betrug nach einer medianen Nachbeobachtungszeit von 61 Monaten 4,4% (5/113). Das aktuarische lokalrezidivfreie 5- und 8-Jahres-Überleben betrug 95% bzw. 93% (Abbildungen 1 und 2). 90% der Patienten beurteilten ihre kosmetischen Ergebnisse als gut oder exzellent (Tablle 3). Bedingt durch flächige Teleangiektasien im Boostareal entwickelten 14/113 Patienten eine Grad-III-Spättoxizität (0/113 Grad IV) der haut (RTOG/EORTC, Tabelle 2). Eine Boostdosis von 25 Gy resultierte in einer signifikant erhöhten Spättoxizitätsrate (Fishers Exakt-Test, p < 0,01, Abbildung 3). Schlussfolgerung: Die gepulste Brachytherapie ist sicher und effektiv. Die kosmetischen Ergebnisse sind gut. Der interstitielle CLDR-Mammaboost kann durch die PDR-Brachytherapie ohne signifikanten Verlust an therapeutischer Breite ersetzt werden.     

Microscopic Residual Disease Is a Risk Factor in the Primary Treatment of Breast Cancer

OBJECTIVES: In the primary treatment of breast cancer, postoperative radiotherapy is performed in high-risk patients after mastectomy and in patients who received breast conserving surgery. In a retrospective analysis, our mono-institutional results of postoperative irradiation have been evaluated. PATIENTS AND METHODS: Between 1992 and 1996, 500 patients have been irradiated after surgery for primary breast cancer. Of these, 489 patients had no initial metastases. 89 patients with loco-regional disease had a mastectomy, 400 patients were irradiated after breast conserving surgery. Radiotherapy at the chest wall was performed with 50 Gy and 2 Gy fractions. After microscopically incomplete resection, an electron boost of 10 Gy was given. The ipsilateral lymph nodes were irradiated with 50 Gy when there was extensive lymph node involvement or invasion of tumor in the axillary fat tissue. RESULTS: The 5-year local control rate after mastectomy was 97.4% and 91.2% after breast conserving surgery. The only statistically significant risk factor for local failure was microscopically incomplete resection. The corresponding 5-year local control rates for microscopically incomplete and complete resections were 76.4% and 92.7% (p = 0.01). The risk of local relapse was increased with both marginal invasive and marginal DCIS-tissue. 86.6% of local relapses were in the same quadrant. CONCLUSIONS: High-risk patients after mastectomy and patients with breast conserving surgery achieve a high local control rate with postoperative irradiation. After microscopically incomplete resection, there is an increased risk for local relapse.     

Intraoperative Strahlentherapie (IORT) in der Behandlung des Mammakarzinoms - eine neue therapeutische Alternative im Rahmen der brusterhaltenden Therapie? Stellenwert und Zukunftsperspektiven. Erfahrungsbericht aus dem European Institute of Oncology (EIO), Mailand

Hintergrund: Die externe Strahlentherapie (EBRT) ist ein integraler Bestandteil der brusterhaltenden Behandlung des Mammakarzinoms. In zwei publizierten Studien konnte gezeigt werden, dass der externe Boost durch eine intraoperative Applikation einer Einzeldosis von 10-25 Gy direkt auf das Tumorbett ohne Einbuße der lokalen Kontrolle ersetzt werden kann. Patientinnen und Methode: Um die Anwendbarkeit höherer intraoperativer Strahlendosen zu untersuchen, wurde am European Institute of Oncology in Mailand eine Dosiseskalationsstudie initiiert. Mittels einer portablen Elektronenstrahlenquelle mit variablen Strahlenenergien wurden intraoperative Dosen zwischen 10 und 22 Gy appliziert. Von Juli bis Dezember 1999 wurden 65 Patientinnen mit einem Mammakarzinom mit maximalem Tumordurchmesser bis 2,5 cm NO-1 mit einem medianen Alter von 58 Jahren (33-80 Jahren) intraoperativ bestrahlt. Zehn Patientinnen wurden mit 10 Gy, acht mit 15 Gy, acht mit 17 Gy, sechs mit 19 Gy und 33 mit 21-22 Gy behandelt. Patientinnen, bei denen 10 bzw. 15 Gy verabreicht wurden, erhielten zusätzlich eine externe Bestrahlung von 44 bzw. 40 Gy. Bei allen übrigen war die IORT die alleinige strahlentherapeutische Behandlung. Ergebnisse: Es wurden keine akuten bzw. intermediären Nebenwirkungen nach 3-9 Monaten in Zusammenhang mit der intraoperativen Strahlentherapie (IORT) beobachtet. Schlussfolgerungen: Die exakte intraoperative Platzierung des Tubus unter Sichtkontrolle durch Chirurgen und Strahlentherapeuten ermöglicht ein Höchstmaß an Präzision bei der Strahlenapplikation. Durch Vermeidung einer Mitbestrahlung von Haut und Subkutangewebe wird das potentielle Risiko einer Fibrosierung verringert; somit dürfte ein besseres kosmetisches Ergebnis zu erwarten sein. IORT-Dosen bis zu 22 Gy (entsprechend einer Äquivalenzdosis von 60 Gy EBRT) können sicher appliziert werden. Obwohl durch die IORT die Operationsdauer um ca. 20 Minuten verlängert wird, resultiert für die Patientin durch eine deutliche Verkürzung der Gesamtbehandlungszeit eine Verbesserung der Lebensqualität. Langzeitnachbeobachtungen sind erforderlich, um die Sicherheit der IORT hinsichtlich einer suffizienten lokalen Tumorkontrolle beurteilen zu können. Als nächster Schritt ist die Durchführung einer randomisierten Studie zum Vergleich der IORT als alleiniger Strahlentherapie mit der EBRT geplant. Background: External beam radiation therapy (EBRT) represnet an integral component of breast-conserving treatment. In published series it has been demonstrated that the external boost can be replaced by intraoperative radiotherapy (IORT) where irradiation at a single dose from 10 up to 15 Gy was safely delivered directly to the tumor bed. Patients and Methods: At the European Institute of Oncology, Milan, we initiated a dose escalation study to investigate the feasibility of applying single doses of IORT from 10 Gy up to 22 Gy. A portable IORT equipment with different electron energies was used. From July to December 1999, a total of 65 patients with T1-2 (max. 2.5 cm) NO-1 breast cancer, median age 58 years (range 33-80 years) was treated. Ten patients received 10 Gy, eight patients were treated with an IORT of 15 Gy, eight received 17 Gy, six had 19 Gy, and 33 were treated with 21-22 Gy. Patients with 10 and 15 Gy received an additional EBRT of 44 and 40 Gy, respectively. In all other patients IORT was the sole radiation treatment. Results: No acute side effects or intermediate untoward effects after a follow-up from three to nine months related to IORT were observed. Conclusions: Since the applicator can be safely placed under the control of the surgeon and radiotherapist IORT has the potential of accurately treating the tumor bed. Skin and subcutaneous tissue are not irradiated thus decreasing the potential risk of fibrosis and eventually obtaining a better cosmesis. With IORT single doses of 22 Gy being equivalent to a 60 Gy EBRT can sefely be delivered. Even so the average time of operation was prolonged by around 20 minutes IORT application ultimately improves the quality of life of the patients in shortening overall treatment. Long-term follow-up is necessary to demonstrate whether large single doses of IORT might have the potential of sufficient local tumor control without major side effects. As a future perspective a randomized trial comparing EBRT with IORT as sole treatment will be performed.