Radiotherapy Confined to the Tumor Bed Following Breast Conserving Surgery

BACKGROUND: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. MATERIAL AND METHODS: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. RESULTS: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been initiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. CONCLUSIONS: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone.     

Radiotherapy Confined to the Tumor Bed Following Breast Conserving Surgery Current Status, Controversies, and Future Projects

Background: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. Material and Methods: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. Results: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been intiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. Conclusions: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone. Hintergrund: Die derzeitige Technik der Radiotherapie (RT) nach brusterhaltender Therapie (BET) ist die Bestrahlung der gesamten Mamma bis zu einer Gesamtdosis von 45-50 Gy mit oder ohne Boost-Bestrahlung des Tumorbetts. Die meisten lokalen Rezidive treten in unmittelbarer Nähe des Tumorbetts auf. Somit kann die Notwendigkeit einer Radiotherapie der gesamten Mamma in Frage gestellt werden. Die Anwendbarkeit und Wirksamkeit einer alleinigen Radiotherapie des Tumorbetts wurde bereits in mehreren Zentren untersucht. Das Ziel dieser Studie ist, die derzeitigen Behandlungsstrategien, Indikationen, technischen Aspekte sowie kontrovers geführte Debatten vorzustellen und neue Therapieansätze bzgl. einer alleinige Radiotherapie nach brusterhaltender Therapie vorzustellen. Patientengut und Methode: Diese Arbeit gibt einen Überblick über publizierte prospektive Studien, welche die Wirksamkeit und die Anwendbarkeit der alleinigen Strahlentherapie des Tumorbetts nach brusterhaltender Operation untersuchen, und analysiert die Behandlungsergebnisse. Ergebnisse: In drei älteren Studien mit alleiniger Tumorbettbestrahlung bei nicht selektiertem Patientengut wurden die lokalen Rezidivraten mit 15,6-37% beschrieben. Allerdings konnten neun Institute über 95,6-100% lokale Kontrollraten berichten unter Anwendung alleiniger Brachytherapie (BT), verschiedener Dosisraten, strikter Patientenauswahl und minutiöser Qualitätssicherung. In unserem Institut in Budapest wurde mit einem Phase-III-Protokoll, das die Wirksamkeit einer alleinigen Radiotherapie des Tumorbetts mit der konventionellen Radiotherapie der ganzen Mamma vergleicht, begonnen. Definierte Parameter bzgl. des geplanten Zielvolumens (PTV) einer Radiotherapie des Tumorbetts existieren nicht, jedoch umschließt in den meisten Studien das PTV die Resektionshöhle mit einem Sicherheitsabstand von 1-3 cm. Die intraoperative Anwendung von Titanclips zur Darstellung der Resektionshöhle stellt die minimale Voraussetzung zur PTV-Lokalisierung dar. Jedoch ist die Kombination von Clipmarkierung und dreidimensionaler (3-D) Darstellung unter Zuhilfenahme von Schnittbildverfahren die beste Methode, um das PTV zu definieren. Auch bietet die virtuelle 3-D-Brachytherapie (3-D-BT) eine gute Möglichkeit, um Planungsfehler zu vermeiden. Bereits ausgereifte Techniken wie die intraoperative Radiotherapie (IORT) und die akzelerierte perkutane 3-D-konforme Radiotherapie (3-D-KRT) sind geeignet, um eine alleinige Tumorbettstrahlung zu gewährleisten. Schlussfolgerung: Trotz kontroverser Argumente bzgl. einer alleinigen Bestrahlung des Tumorbetts nach Brust erhaltender Therapie weisen Ergebnisse von Phase-I- und -II-Studien darauf hin, dass die alleinige Radiotherapie des Tumorbetts eine entsprechende Behandlungsoption für ein ausgewähltes Patientengut mit Mammakarzinom darstellen kann. Die Bestrahlung der gesamten Brust bleibt aber die Standardbehandlung im postoperativen Management nach brusterhaltender Therapie. Die Brachytherapie als alleinige Behandlungsmethode ist derzeit noch als experimentell zu bezeichnen. Weitere Phase-III-Studien sind erforderlich, umd die Gleichwertigkeit einer alleinigen Radiotherapie des Tumorbetts mit einer Bestrahlung der gesamten Brust zu untersuchen. Derzeitige Ergebnisse mit den bekannten Techniken (CT-gestützte konforme Brachytherapie, virtuelle 3-D-BT, IORT, 3-D-KRT) sind viel versprechend. Mehr klinische Erfahrung wird notwendig sein, um festzustellen, welche der aufgeführten Methoden letztendlich eine Verbesserung der Behandlungsergebnisse bei Brustkrebspatientinnen mit alleiniger Radiotherapie des Tumorbetts erzielt.     

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.     

Intraoperative radiation therapy in the management of early stage breast cancer

Adjuvant radiotherapy (RT) following breast conserving surgery (BCS) is associated with an improvement in local control and a reduction in breast cancer mortality. While traditionally delivered with whole breast irradiation (WBI), novel approaches have looked to reduce the duration, target volume, and toxicity of adjuvant RT. One such approach is intraoperative radiation therapy (IORT), which delivers radiation at the time of surgery with 80–90% of patients not requiring additional WBI. The current review presents IORT techniques and outcomes from modern series evaluating IORT as monotherapy or as a tumor bed boost. Based on two randomized trials (TARGIT-A and ELIOT) with recent updates, concern regarding higher rates of local recurrence with IORT exist, whether using electrons or low-energy techniques. In contrast, data is promising regarding IORT used as a boost, with ongoing studies evaluating its role prospectively. With respect to toxicity, the data suggest IORT is associated with comparable to slightly lower rates of toxicity though there may be a higher risk of seroma requiring aspiration and fat necrosis with IORT. Given current data and guidelines, WBI or other partial breast techniques should remain the standard of care in early stage breast cancer patients, while IORT should not be utilized outside of prospective clinical trials at this time.     

Local Recurrence Rates in Breast Cancer Patients Treated with Intraoperative Electron-Boost Radiotherapy Versus Postoperative External-Beam Electron-Boost Irradiation

BACKGROUND AND PURPOSE: The purpose of this sequential intervention study was to determine the rate of local recurrences and the rate of distant metastases in patients with invasive breast cancer who had been treated with breast-conserving surgery and postoperative radiation therapy to the whole breast either with postoperative electron boost in group 1 or with intraoperative electron boost (IORT) in group 2. PATIENTS AND METHODS: After breast-conserving surgery, 378 women with invasive breast cancer of tumor sizes T1 and T2 received 51-56.1 Gy of postoperative radiation therapy to the whole breast in 1.7-Gy fractions. 188 of those patients additionally received a postoperative electron boost of 12 Gy in group 1 from January 1996 to October 1998. Consecutively, from October 1998 to March 2001, 190 patients received intraoperative electron-boost radiotherapy of 9 Gy to the tumor bed in group 2. The groups were comparable with regard to age, menopausal status, tumor size, grading, and nodal status. All statistical tests were two-sided. RESULTS: During a median follow-up period of 55.3 months in group 1 and 25.8 months in group 2, local recurrences were observed in eight of 188 patients (4.3%) in group 1, and no local recurrence was seen in group 2 (p=0.082). Distant metastases occurred in 15 of the 188 patients (7.9%) in group 1 and in two of the 190 patients (1.1%) in group 2 (p=0.09). The 4-year actuarial rates of local recurrence were 4.3% (95% confidence interval, 1.8-8.2%) and 0.0% (95% confidence interval, 0.0-1.9%) and the 4-year actuarial rates of distant metastases were 7.9% (95% confidence interval, 4.5-12.8%) and 1.1% (95% confidence interval, 0.1-3.8%). CONCLUSION: Immediate IORT boost yielded excellent local control figures in this prospective investigation and appears to be superior to conventional postoperative boost in a short-term follow-up.     

DEGRO Practical Guidelines for Radiotherapy of Breast Cancer I

BACKGROUND: The present paper is an update of the practical guidelines for radiotherapy of breast cancer published in 2006 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) [34]. These recommendations have been elaborated on the basis of the S3 guidelines of the German Cancer Society that were revised in March 2007 by an interdisciplinary panel [18]. METHODS: The DEGRO expert panel performed a comprehensive survey of the literature, comprising lately published meta-analyses, data from recent randomized trials and guidelines of international breast cancer societies, referring to the criteria of evidence- based medicine [25]. In addition to the more general statements of the German Cancer Society, this paper emphasizes specific radiotherapeutic aspects. It is focused on radiotherapy after breast-conserving surgery. Technique, targeting, and dose are described in detail. RESULTS: Postoperative radiotherapy significantly reduces rates of local recurrence. The more pronounced the achieved reduction is, the more substantially it translates into improved survival. Four prevented local recurrences result in one avoided breast cancer death. This effect is independent of age. An additional boost provides a further absolute risk reduction for local recurrence irrespective of age. Women > 50 years have a hazard ratio of 0.59 in favor of the boost. For DCIS, local recurrence was 2.4% per patient year even in a subgroup with favorable prognostic factors leading to premature closure of the respective study due to ethical reasons. For partial-breast irradiation as a sole method of radiotherapy, results are not yet mature enough to allow definite conclusions. CONCLUSION: After breast-conserving surgery, whole-breast irradiation remains the gold standard of treatment. The indication for boost irradiation should no longer be restricted to women 相似文献   

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.     

Radiation therapy after breast-conserving surgery

The authors critically reviewed previous articles concerning the significance of breast irradiation following breast-conserving surgery in terms of the following subject items: indications for breast-conserving therapy, the significance and complications of breast irradiation, the timing of the start of breast irradiation, the significance of boost irradiation, the potential improvement of survival with systemic therapy plus breast irradiation, the significance of axillary dissection, indications and the significance of regional nodal irradiation, accelerated hypofractionated radiotherapy, omission of breast irradiation in low-risk patients, and future directions. In addition, our previously reported results of breast irradiation following breast-conserving surgery at the Keio University Hospital are outlined. Our newly developed tangential irradiation technique directed to the axilla and a recently introduced three-dimensional simulation technique for radiotherapy treatment planning are also presented. This work was presented as an educational lecture at the 64^th Japan Radiological Society meeting in April 2005.     

Partial-breast irradiation versus whole-breast radiotherapy for early breast cancer: A systematic review and update meta-analysis

PurposeThe purpose of this study was to compare the treatment outcomes of partial-breast irradiation (PBI) versus whole-breast radiotherapy (WBRT) in early breast cancer.Methods and MaterialsEligible randomized clinical trials were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through December 2019. A meta-analysis for local recurrence (LR), overall mortality (OM), and non-breast cancer mortality (NBCM) was conducted. When possible, the outcomes were calculated for 5, 7, and 10 years of followup. A subgroup analysis by PBI technique (brachytherapy [BT], external beam radiotherapy [EBRT], intraoperative radiotherapy [IORT], and mixed) was performed. A p value < 0.05 was considered significant.ResultsEleven randomized clinical trials with a total of 14,436 patients (7186 PBI vs. 7250 WBRT) were included in the meta-analysis. The odds ratio (OR) for LR in 5 y was 1.46 (95% CI 1.15–2, p = 0.024) for PBI. In the subgroup analysis, no significant difference for LR was observed between PBI and WBRT using BT (p = 0.51), EBRT (p = 0.25), or mixed techniques (p = 0.89). The only subgroup with statistical difference was IORT 3.1 (95% CI 1.2–7.6, p = 0.014). No significant difference in LR was observed with 7 and 10 years among the groups. The OM had no difference at 5, 7, and 10 years of followup for any subgroup. A nonsignificant difference was observed comparing PBI with WBRT for NBCM OR = 1.24 (95% CI 0.98–1.57, p = 0.07). The rates of cardiac death, contralateral breast cancer, and development of second tumor were not significant.ConclusionsThe LR with PBI is low and similar to WBRT in selected early breast cancer with a longer followup. The subgroup analysis detected a significant difference for LR associated with IORT and no significant difference for BT and EBRT. Our results confirm a nonsignificant difference for OM and NBCM between PBI and WBRT.     

Modern radiation techniques in early stage breast cancer for the breast radiologist

Partial breast irradiation (PBI) and ultra-hypofractionated whole breast irradiation (uWBI) are contemporary alternatives to conventional and standard hypofractionated whole breast irradiation (WBI), which shorten treatment from 3 to 6 weeks to 1–2 weeks for select patients. PBI and accelerated PBI (APBI) can be delivered with external beam radiation (3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT)), intraoperative radiation (IORT), or brachytherapy. These new radiation techniques offer the advantage of convenience and lower cost, which ultimately improves access to care. Globally, the COVID 19 pandemic has accelerated APBI/PBI and ultra-hypofractionated regimens into routine practice for carefully selected patients. Recent long-term data from randomized controlled trials (RCTs) have demonstrated these techniques are safe and effective in suitable patients demonstrating equivalent or improved local recurrence, acute/late toxicity, and cosmesis. PBI and APBI should be limited to low risk unifocal invasive ductal carcinoma and ductal carcinoma in situ with tumor size < 2 cm, clear margins (≥2 mm), ER+, and negative nodes. Based on the results from UK Fast-Forward and UK FAST ultra-hypofractionated breast radiation can be safely employed for early stage node negative patients, but is not yet considered an international standard of care. In this review, authors will appraise recent data for these shorter course radiation treatment regimens, as well as, considerations for breast radiologists including surveillance imaging and radiographic findings.     

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 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.     

Radiotherapy of carcinoma of the auditory canal

From 1973 through 1986, twelve patients suffering from carcinomas of the outer auditory canal were irradiated at the Radiologic Hospital of Essen. The five-year survival was 64% after postoperative irradiation and 0% after irradiation alone. Considering the data communicated by other authors, the following therapy recommendations can be deduced: early stages where bones or cartilages are not involved represent an indication for sole operation. These tumors can be successfully treated by sole radiotherapy, too. In case of greater tumors, combined surgery and postoperative radiotherapy is the most favorable method. Besides a high total dose (50 to 60 Gy for microscopic tumor residues, about 70 Gy for macroscopic tumor residues), a sufficiently great target volume has to be chosen which includes the ear, the temporal bone, the preauricular lymph nodes and the angle of mandible. To prevent bone and cartilage necroses, it is recommended to restrict the individual doses to 1.8 to 2 Gy each.     

Einfluß der adjuvanten radiotherapie auf das psychische befinden von patientinnen mit einem brusterhaltend operierten mammakarzinom

BACKGROUND: In literature there are only few informations about the influence of postoperative irradiation on the psychological health of breast cancer patients treated by breast-conserving surgery. However, psychological distress and anxiety related to irradiation are often observed. Purpose of our study was the evaluation of the influence of radiotherapy-induced distress in these patients. PATIENTS AND METHODS: Between October 1995 and June 1996 in 48 breast cancer patients (31 to 76 years old) treated by breast-conserving surgery adjuvant irradiation with or without systemic therapy was applied. On the first and the last day of radiotherapy they were given a questionnaire (Table 1) which was designed together with psychologists. Covering different situations related to radiotherapy the construction of items are determined by factors with possible influence on psychological distress and perception with regard to irradiation. RESULTS: Most of the women (92%) stated to be well informed about the irradiation and tried to obtain further information about this treatment (83%). 56% tried not to think about radiotherapy and/or to distract themselves (81%). 40% were anxious about the fact to undergo irradiation. In the end of treatment 77% reported to have been anxious only initially or never; only 19% were anxious almost or most of the time. 35% were worried about the expected cosmetic alterations of their breast; only 30% observed acute cosmetic changes. With regard to situation-related distress all patients (100%) stated that the communication with the medical staff made it easier to stand the irradiation treatment. CONCLUSIONS: In spite of theoretical considerations our results are explorative in character. However, following statements seem to be important: 1. A large requirement exists to get information about radiotherapy. 2. The patients experience irradiation treatment more positive than initially expected by themselves. 3. With regard to radiotherapy anxiety is reduced during the course of treatment. Here the psychosocial care of the medical staff is an important support for reduction of anxiety.     

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.     

Radiotherapy for intracranial and spinal ependymomas

BACKGROUND: The low incidence of ependymomas results in limited treatment experience. While standard therapy consists of surgery and postoperative radiotherapy, irradiation techniques are still subject to discussion. We report the experience from Münster over the last 35 years. PATIENTS AND METHODS: Since 1961, 25 evaluable patients with ependymoma were irradiated in Münster: 17 intracranial and 8 spinal tumors. Fourteen of 25 patients underwent subtotal resection. Fifteen of 25 patients were treated by local irradiation, 10 of 25 with large-field techniques (whole-brain/cranio-spinal irradiation) and an additional tumor boost. The median tumor dose amounted to 50 Gy (16 to 65 Gy). Sites of recurrence were analyzed and correlated with the irradiated region. RESULTS: Twelve recurrences were observed. Six of 12 could be exactly related to the irradiation portals and were found well inside the local or boost fields. The remaining 6 tumors also recurred locally; whether they were in-field or field margin recurrences was not to be discerned by the imaging available at the time. No out-field recurrences or spinal seeding were observed. For 8 of 17 locally irradiated patients with intracranial ependymomas, 5 local recurrences were recorded. In 9 of 17 patients receiving whole-brain or cranio-spinal irradiation, 6 local recurrences were found. Two of 8 spinal tumors recurred locally. CONCLUSIONS: All tumors recurred within the former tumor bed. In the remaining cranio-spinal axis no recurrences or metastases were found. Similar results are reported from current literature. The value of large-field techniques (whole brain/spinal irradiation) is to be questioned. Modern methods like IORT or stereotactic radiotherapy might be able to deliver a higher tumor dose without increasing toxicity.     

Breast conservation surgery and interstitial brachytherapy in the management of locally recurrent carcinoma of the breast: the Allegheny General Hospital experience

PURPOSE: To evaluate lumpectomy followed by interstitial brachytherapy as an acceptable salvage therapy for women who have developed localized recurrence of breast cancer after conservation surgery and postoperative external radiotherapy. METHODS AND MATERIALS: Between 1/1998 and 10/2006, 21 patients with T0 or T1 in-breast recurrence of carcinoma were offered interstitial low-dose rate brachytherapy after tumor re-excision as an alternative to salvage mastectomy. All patients had failed lumpectomy followed by standard postoperative external beam radiotherapy (range, 5000-6040cGy) as treatment for the initial breast carcinoma. Seven recurred as ductal carcinoma in situ, 2 as infiltrating lobular carcinoma, and 12 as recurrent invasive carcinoma. The recurrent tumors were excised with final margins of resection free of residual disease per National Surgical Adjuvant Breast and Bowel Project definition. Tumor bed implantation was then carried out with an interstitial technique using (192)Ir with the target volume consisting of the tumor bed plus a minimum 1.0-cm clinical margin. The required minimum dose delivered to the target volume was 4500-5000cGy (range, 4500-5530). RESULTS: Twenty of 21 patients were free of local disease with a median observation time of 40 months (range, 3-69). The single patient who developed a second local recurrence was treated successfully with simple mastectomy. Two patients succumbed to systemic disease at 17 and 24 months after salvage implant therapy. One patient developed a contralateral breast cancer. Cosmetic results defined by the National Surgical Adjuvant Breast and Bowel Project cosmesis scale were acceptable. One patient developed a localized seroma requiring multiple needle aspirations before complete resolution. Two patients developed localized skin breakdown in the tumor bed. One healed after 6 months of conservative treatment. The other healed 9 months later with Grade II cosmesis. This patient also developed a concurrent postoperative wound infection. CONCLUSIONS: Repeat lumpectomy followed by brachytherapy is feasible and may be an acceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy; however, longer followup and greater patient numbers may be needed to better define the role of salvage brachytherapy.     

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.

     

Partial breast irradiation: a review of techniques and indications

The addition of whole-breast external beam radiotherapy (EBRT) to breast-conserving surgery results in a significant reduction in the risk of death due to breast cancer, but this may be offset by an increase in deaths from other causes and toxicity to surrounding organs. Because of this, and with a view to patterns of local recurrence, irradiation of the tumour bed has been explored in selected patients with early breast cancer using a variety of radiotherapeutic modalities. This review article explores the treatment options for partial breast irradiation and examines their role within the field of breast cancer treatment.Breast-conserving surgery is a proven alternative to mastectomy in patients with early-stage breast cancer, offering equivalent disease-free and overall survival [1–3]. The addition of whole-breast external beam radiotherapy (EBRT) to breast-conserving surgery results in a significant reduction in the risk of death due to breast cancer, but this is offset by an increase in deaths due to other causes [3]. However, this increase in mortality was seen with a follow-up of over 20 years and as such reflects the use of radiotherapy techniques that have since been replaced with more sophisticated methods that allow more sparing of normal tissue. Therefore, we might not observe similar late toxicities when current EBRT techniques are analysed 20 years from now. When systemic therapy such as tamoxifen is combined with breast-conserving treatment, the risk of ipsilateral breast recurrence and distant metastases is further reduced [4]. Breast-conserving surgery is often preferred by patients, as it provides improved cosmesis and decreased psychological trauma. In some areas, however, eligible patients may not receive breast-conserving therapy for a variety of physician- and patient-based reasons [5]. Whole-breast radiotherapy (WBRT) takes 3–7 weeks with treatment once daily. This can be difficult to achieve, especially in communities where the cancer centre serves a large geographical area.Conventional WBRT has changed very little over the years; it is generally delivered using two tangential beams (Figure 1), typically of 6 MV photons. Traditionally, the dose was defined using one axial contour in the centre of the field; however, more centres are now using CT planning to ensure greater homogeneity across the breast volume, while optimising avoidance of normal tissue. Late toxicities of WBRT can include radiation pneumonitis, osteonecrosis of the ribs and cardiovascular complications. These cardiovascular incidents could contribute to the increased all-cause mortality in radiotherapy patients seen in studies, although, again, these may be decreased with modern radiotherapy techniques [2, 3, 6].Open in a separate windowFigure 1(a) Axial and (b) sagittal CT images demonstrating the isodose curves generated for a parallel opposed pair of 6 MV photon beams with wedges for whole breast radiotherapy of the right breast.In disease sites elsewhere in the body, technological developments have allowed a move towards image-based target definition with sculpting of fields around anatomically defined target volumes. Therefore, the possibility of irradiating the tumour bed rather than the whole breast in patients with early breast cancer has been explored. Some investigators would choose not to treat these patients, but radiation has been shown to decrease local recurrence in this situation [4]. In trials of lumpectomy with or without WBRT, most local recurrences in the non-irradiated arm occurred in the tumour bed with a recurrence rate elsewhere of 1.5–3.5% [1, 2, 7, 8]. Pathological examination of mastectomy specimens from patients with small unifocal invasive carcinomas has shown that invasive tumour foci are generally confined to a narrow margin around the invasive tumour component [9, 10].Therefore, partial breast irradiation (PBI) is being investigated as an alternative treatment for selected patients with early-stage breast cancer. The use of PBI may improve the underutilisation of breast-conserving treatment by decreasing the time, cost and inconvenience of WBRT and improving the quality of life of patients. Case selection is the paramount factor in ensuring the suitability of a patient for PBI, combining pre-operative and surgical tumour staging to exclude patients at a higher risk of locoregional recurrence.A number of methods of PBI exist. Using photons or electrons, a single treatment can be given at the time of surgery [11–13]. EBRT can be used to deliver a partial breast treatment with electrons, conventional beam approaches or intensity-modulated radiotherapy (IMRT) techniques. Brachytherapy can be delivered using low dose rate (LDR), pulsed dose rate (PDR) and high dose rate (HDR) isotopes delivered by way of a single catheter or multiple catheter implants. Many of the data surrounding these different modalities are from Phase I or II trials, but increasing numbers of patients are being enrolled into Phase III randomised trials.     

Mammographically guided noninvasive breast brachytherapy: Preoperative partial breast radiotherapy markedly improves targeting accuracy and decreases irradiated volume

PurposeMammographically based noninvasive image-guided breast brachytherapy (NIBB) partial breast irradiation (PBI) is ideally suited for preoperative treatment. We hypothesize that delivering NIBB PBI to the preoperative tumor volume compared with the postoperative lumpectomy bed would simplify target identification and allow for a reduction in irradiated volume along each orthogonal axis.Methods and MaterialsPatients with invasive breast cancer treated with NIBB PBI at our institution were identified. Preoperative NIBB treatments were modeled along orthogonal craniocaudal and mediolateral axes with an applicator encompassing the gross lesion plus a 1 cm clinical target volume margin. Preoperative treatment volumes were calculated along each axis using the selected applicator surface area multiplied by the preoperative mammogram separation. The actual applicator size and breast separation from the first fraction of postoperative treatment was used to calculate the postoperative treatment volume. Paired -test was used to compare the preoperative and postoperative treatment separation, area, and volume for each patient.ResultsForty-eight patients with Stage I–II breast cancer had imaging and treatment data available for review. Along the axis, the mean preoperative treatment volume was significantly less than the mean postoperative treatment volume (116 cm ³ vs. 204 cm ³, respectively; p < 0.0001). Similarly, along the mediolateral axis, the mean preoperative treatment volume was significantly less than the mean postoperative treatment volume (125 cm ³ vs. 216 cm ³, respectively; p < 0001).ConclusionsBased on our retrospective comparison, PBI delivered using NIBB to the preoperative tumor may reduce the volume of healthy breast tissue receiving radiation as compared with NIBB to the postoperative tumor bed.