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.     

DEGRO practical guidelines: radiotherapy of breast cancer II

Purpose

To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery.

Methods

The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were “non invasive breast cancer”, “ductal carcinoma in situ, “dcis”, “borderline breast lesions”, “lobular neoplasia”, “radiotherapy” and “radiation therapy”. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ.

Results

Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose–volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing.

Conclusion

Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets—even in low risk subgroups (LoE 1a).     

Intraoperative radiotherapy in early stage breast cancer: potential indications and evidence to date

Following early results of recent studies of intraoperative radiotherapy (IORT) in the adjuvant treatment of patients with early breast cancer, the clinical utility of IORT is a subject of much recent debate within the breast oncology community. This review describes the intraoperative techniques available, the potential indications and the evidence to date pertaining to local control and toxicity. We also discuss any implications for current practice and future research.Adjuvant radiotherapy (RT) following surgery in the treatment of early stage breast cancer delivered with external beam RT (EBRT) permits breast conservation with low rates of in-breast tumour recurrence (IBTR).¹ When IBTR occurs, however, the recurrence is most commonly located in the same quadrant as the index tumour.² Furthermore, pathological examination of mastectomy specimens demonstrates that malignant and/or pre-malignant cells are rarely found >4 cm from the index lesion.³ Such data have given rise to the hypothesis that irradiating only the part of the breast tissue in proximity to the index tumour will be associated with local control rates comparable with those seen after adjuvant whole-breast EBRT. Such partial breast irradiation would also be expected to be associated with less toxicity given the reduced volume of non-target tissue irradiation.Partial breast RT may be delivered by a number of techniques, including EBRT, interstitial brachytherapy and intraoperative RT (IORT).^4,5 The use of IORT has been reported in a range of tumour sites, including the breast, head and neck, lung, limbs (sarcoma), gastrointestinal and genitourinary tracts, and lung.^6–12 For most tumour sites, the premise of IORT is to deliver RT directly and therefore potentially more accurately to the tumour itself or to the tumour bed whilst delivering minimal dose to the surrounding normal tissues. Although not in routine clinical practice, in previous studies of IORT, the IORT has been delivered in combination with EBRT as a “boost” or as the sole RT modality.^6,13In the context of adjuvant treatment for early breast cancer, IORT has most commonly been delivered to the tumour bed after surgical excision of the tumour, and a number of technical approaches have been described. IORT to the breast has been used both to deliver a tumour-bed boost in conjunction with EBRT and as definitive adjuvant RT treatment instead of whole-breast EBRT.^13,14 Until recently, there has been a lack of randomized Phase III trial evidence comparing IORT with EBRT in either setting. This review describes the different IORT techniques available, the potential clinical utility of IORT, the evidence to date and the implications for standard practice and future research.     

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.     

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.     

Adaptive radiation therapy of breast cancer by repeated imaging during irradiation

Breast cancer is the most frequent cancer among females and also a leading cause of cancer related mortality worldwide. A multimodality treatment approach may be utilized for optimal management of patients with combinations of surgery, radiation therapy (RT) and systemic treatment. RT composes an integral part of breast conserving treatment, and is typically used after breast conserving surgery to improve local control. Recent years have witnessed significant improvements in the discipline of radiation oncology which allow for more focused and precise treatment delivery. Adaptive radiation therapy (ART) is among the most important RT techniques which may be utilized for redesigning of treatment plans to account for dynamic changes in tumor size and anatomy during the course of irradiation. In the context of breast cancer, ART may serve as an excellent tool for patients receiving breast irradiation followed by a sequential boost to the tumor bed. Primary benefits of ART include more precise boost localization and potential for improved normal tissue sparing with adapted boost target volumes particularly in the setting of seroma reduction during the course of irradiation. Herein, we provide a concise review of ART for breast cancer in light of the literature.     

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.     

Mammographic and ultrasonographic comparison between intraoperative radiotherapy (IORT) and conventional external radiotherapy (RT) in limited-stage breast cancer, conservatively treated

OBJECTIVE: Assess mammographic and echographic modifications in mild cases of breast cancer (suitable for conservative surgery) after intraoperatory radio treatment (IORT) as opposed to conventional post-operative radiotherapy (RT). MATERIALS AND METHODS: We report data from 45 patients in each group (IORT and RT). All patients were examined using the same mammographic and ecographic equipment at 6, 12 and 24 months after treatment. We focused on structural alterations, edema and others, and quantified them using pre-established (unbiased) protocols. Both patient examination and subsequent assessment of the results were performed by radiologists with exepertise in breast cancer evaluation. RESULTS: At 6 months, IORT patients showed slightly more pronounced structural distortions and oedema than RT patients; these differences became more apparent at 12 months, with the addition of fat necrosis and/or calcifications. These alterations were evident and consistent under both mammographic and ecographic examination, and became even more pronounced at 24 months. At this stage, RT patients showed minimal alterations of the tissue (apart from normal post-surgical scarring), whereas IORT patients showed virtually no improvement over the preceding 12-month period. CONCLUSION: We show radiological alterations in post-operative breast cancer are significantly more pronounced in patients treated with IORT as opposed to RT.     

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.     

Resection plus whole-brain irradiation versus resection plus whole-brain irradiation plus boost for the treatment of single brain metastasis

Background

The optimal treatment for patients with a single brain metastasis is controversial. This study investigated the value of a radiation boost given in addition to neurosurgerical resection and whole-brain irradiation (WBI).

Patients and methods

In this retrospective study, outcome data of 105?patients with a single brain metastasis receiving metastatic surgery plus WBI (S?+?WBI) were compared to 90?patients receiving the same treatment plus a boost to the metastatic site (S?+?WBI?+?B). The outcomes that were compared included local control of the resected metastasis (LC) and overall survival (OS). In addition to the treatment regimen, eight potential prognostic factors were evaluated including age, gender, performance status, extent of metastatic resection, primary tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from first diagnosis of cancer to metastatic surgery.

Results

The LC rates at 1?year, 2?years, and 3?years were 38%, 20%, and 9%, respectively, after S?+?WBI, and 67%, 51%, and 33%, respectively, after S?+?WBI?+?B (p?=?0.002). The OS rates at 1?year, 2?years, and 3?years were 52%, 25%, and 19%, respectively, after S?+?WBI, and 60%, 40%, and 26%, respectively, after S?+?WBI?+?B (p?=?0.11). On multivariate analyses, improved LC was significantly associated with OP?+?WBI?+?B (p?=?0.006) and total resection of the metastasis (p?=?0.014). Improved OS was significantly associated with age ???60?years (p?=?0.028), Karnofsky Performance Score >?70 (p?=?0.015), breast cancer (p?=?0.041), RPA class 1 (p?=?0.012), and almost with the absence of extracerebral metastases (p?=?0.05).

Conclusion

A boost in addition to WBI significantly improved LC but not OS following resection of a single brain metastasis.     

Survival after partial breast brachytherapy in elderly patients with nonmetastatic breast cancer

BackgroundDespite growing utilization of accelerated partial breast irradiation using brachytherapy (APBI-Brachy) for elderly breast cancer patients, there are limited data from randomized Phase III trials to support its routine use. This study uses population-based data to examine whether APBI-Brachy results in comparable survival rates compared with whole breast irradiation (WBI).MethodsA sample of 29,647 female patients diagnosed with nonmetastatic breast cancer in 2002–2007 treated with breast-conserving surgery and radiotherapy was identified in the Surveillance, Epidemiology, and End Results Program-Medicare data set. Log-rank tests, Cox proportional hazards models, instrumental variable analysis, and subgroup analysis were used to study the comparative effectiveness of APBI-Brachy and WBI.ResultsDuring a median followup of 3.6 and 4.8 years, 123 (7.7%) and 3438 (13.6%) patients died after APBI-Brachy and WBI, respectively. Recurrence-free survival (p = 0.9711) and overall survival rates (p = 0.0551) did not differ significantly between the two radiation modalities. After accounting for tumor characteristics, patient characteristics, community factors, and comorbidities, the recurrence-free survival (hazard ratio, 1.05; 95% confidence interval, 0.90–1.23; p = 0.5125) and overall survival (hazard ratio, 0.87; 95% confidence interval, 0.72–1.04; p = 0.1332) rates were still not significantly different between patients treated with APBI-Brachy and WBI.ConclusionPartial breast brachytherapy and WBI resulted in similar recurrence-free and overall survival rates in this cohort of elderly breast cancer patients, even after adjustment for the more favorable characteristics of patients in the former group. These findings will need to be confirmed by the randomized trials comparing these modalities.     

The American Brachytherapy Society consensus statement on intraoperative radiation therapy

PurposeAlthough radiation therapy has traditionally been delivered with external beam or brachytherapy, intraoperative radiation therapy (IORT) represents an alternative that may shorten the course of therapy, reduce toxicities, and improve patient satisfaction while potentially lowering the cost of care. At this time, there are limited evidence-based guidelines to assist clinicians with patient selection for IORT. As such, the American Brachytherapy Society presents a consensus statement on the use of IORT.MethodsPhysicians and physicists with expertise in intraoperative radiation created a site-directed guideline for appropriate patient selection and utilization of IORT.ResultsSeveral IORT techniques exist including radionuclide-based high-dose-rate, low-dose-rate, electron, and low-energy electronic. In breast cancer, IORT as monotherapy should only be used on prospective studies. IORT can be considered in the treatment of sarcomas with close/positive margins or recurrent sarcomas. IORT can be considered in conjunction with external beam radiotherapy for retroperitoneal sarcomas. IORT can be considered for colorectal malignancies with concern for positive margins and in the setting of recurrent gynecologic cancers. For thoracic, head and neck, and central nervous system malignancies, utilization of IORT should be evaluated on a case-by-case basis.ConclusionsThe present guidelines provide clinicians with a summary of current data regarding IORT by treatment site and guidelines for the appropriate patient selection and safe utilization of the technique. High-dose-rate, low-dose-rate brachytherapy methods are appropriate when IORT is to be delivered as are electron and low-energy based on the clinical scenario.     

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.     

Could helical tomotherapy do whole brain radiotherapy and radiosurgery?

Whole brain radiotherapy (WBRT) remains the standard management of breast cancer patients with brain metastases, allowing for symptomatic improvement and good local control in most patients. However, its results remain suboptimal in terms of both efficacy and toxicity. In highly selected breast cancer patients, stereotaxic radiotherapy demonstrates a very good local control with a low toxicity. With the purpose of improving the efficacy/toxicity ratio, we report the association of integrated boost with WBRT in a breast cancer patient with brain metastases. Two and a half years after completion of helical tomotherapy (HT), the patient experienced clinical and radiological complete remission of her brain disease. No delayed toxicity occurred and the patient kept her hair without need of radiosurgical procedure. The HT provided a high dosimetric homogeneity, delivering integrated radiation boosts, and avoiding critical structures involved in long-term neurological toxicity. Further assessment is required and recruitment of breast cancer patients into clinical trials is encouraged.     

Evaluation of adaptive radiotherapy (ART) by use of replanning the tumor bed boost with repeated computed tomography (CT) simulation after whole breast irradiation (WBI) for breast cancer patients having clinically evident seroma

Purpose

The aim of this study is to evaluate adaptive radiotherapy (ART) by use of replanning the tumor bed boost with repeated computed tomography (CT) simulation after whole breast irradiation (WBI) for breast cancer patients having clinically evident seroma.

Materials and methods

Forty-eight patients with clinically evident seroma at the time of planning CT simulation for WBI were included. Two RT treatment plannings were generated for each patient based on the initial CT simulation and tumor bed boost CT simulation to assess seroma and boost target volume (BTV) changes during WBI. Also, dosimetric impact of ART was analyzed by comparative evaluation of critical organ doses in both RT treatment plannings.

Results

Median time interval between the two CT simulations was 35 days. Statistically significant reduction was detected in seroma volume and BTV during the conventionally fractionated WBI course along with statistically significant reduction in critical organ doses with ART (p?<?0.0001).

Conclusion

Our data suggest significant benefit of ART by use of replanning the tumor bed boost with repeated CT simulation after WBI for patients with clinically evident seroma.

     

DEGRO practical guidelines: radiotherapy of breast cancer I

Background and purpose

The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012.

Methods

A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms “breast cancer”, “radiotherapy”, and “breast conserving therapy”. Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer.

Results

Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48–0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75–0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified.

Conclusion

After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.     

Hypofractionated radiotherapy in the treatment of early breast cancer

Radiotherapy (RT) after tumorectomy in early breast cancer patients is an established treatment modality which conventionally takes 6-7 wk to complete. Shorter RT schedules have been tested in large multicentre randomized trials and have shown equivalent results to that of standard RT (50 Gy in 25 fractions) in terms of local tumor control, patient survival and late post-radiation effects. Some of those trials have now completed 10 years of follow-up with encouraging results for treatments of 3-4 wk and a total RT dose to the breast of 40-42.5 Gy with or without boost. A reduction of 50% in treatment time makes those RT schedules attractive for both patients and health care providers and would have a significant impact on daily RT practice around the world, as it would accelerate patient turnover and save health care resources. However, in hypofractionated RT, a higher (than the conventional 1.8-2 Gy) dose per fraction is given and should be managed with caution as it could result in a higher rate of late post-radiation effects in breast, heart, lungs and the brachial plexus. It is therefore advisable that both possible dose inhomogeneity and normal tissue protection should be taken into account and the appropriate technology such as three-dimensional/intensity modulated radiation therapy employed in clinical practice, when hypofractionation is used.     

Magnetic resonance for radiotherapy management and treatment planning in prostatic carcinoma

MRI has an important role for radiotherapy (RT) treatment planning in prostate cancer (PCa) providing accurate visualization of the dominant intraprostatic lesion (DIL) and locoregional anatomy, assessment of local staging and depiction of implanted devices. MRI enables the radiation oncologist to optimize RT planning by better defining target tumour volumes (thereby increasing local tumour control), as well as decreasing morbidity (by minimizing the dose to adjacent normal structures). Using MRI, radiation oncologists can define the DIL for delivery of boost doses of RT using a variety of techniques including: stereotactic body radiotherapy, intensity-modulated radiotherapy, proton RT or brachytherapy to improve tumour control. Radiologists require a familiarity with the different RT methods used to treat PCa, as well as an understanding of the advantages and disadvantages of the various MR pulse sequences available for RT planning in order to provide an optimal multidisciplinary RT treatment approach to PCa. Understanding the expected post-RT appearance of the prostate and typical characteristics of local tumour recurrence is also important because MRI is rapidly becoming an integral component for diagnosis, image-guided histological sampling and treatment planning in the setting of biochemical failure after RT or surgery.     

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   

Toxicity and cosmetic outcomes after treatment with a novel form of breast IORT

PurposeIntraoperative radiation therapy (IORT), a form of accelerated partial breast irradiation (APBI), is an appealing alternative to postoperative whole breast irradiation for early-stage breast cancer. The purpose of this study was to examine the toxicity and cosmetic outcomes of patients treated with a novel form of breast IORT (precision breast IORT; PB-IORT), that delivers a targeted, higher dose of radiation than conventional IORT.Methods and MaterialsThe first 204 patients treated with PB-IORT in a Phase II clinical trial (NCT02400658) with 12 months of followup were included. Trial inclusion criteria were age ≥45 years, invasive or in situ breast cancer, tumor size ≤3 cm, and node negative. Toxicity and cosmetic scoring were performed at 6 and 12 months.Results98 patients (48%; 95% CI, 41–55%) experienced toxicity. Seven Grade 3 toxicities occurred (3.4%; 95% CI, 1.4–6.9%). Most patients (95%) had excellent or good cosmetic outcomes (95% CI, 91–98%) at 12 months. Most patients (94%) had little or no pigmentation change (95% CI, 90–97%), 88% little to no size change (95% CI, 82–92%), and 87% experienced minimal shape change (95% CI, 82–92%).ConclusionsOverall, Grade 3+ toxicity was rare and cosmetic outcomes were excellent. Severe toxicity with PB-IORT is similar to that reported in the TARGIT trial (3.3% rate of major toxicity) but lower than APBI (NSABP-39, 10.1% Grade 3/4 toxicities). We propose that the toxicity of PB-IORT compared with TARGIT and NSABP-39 is related to the radiation dose and delivery schedule. PB-IORT offers low-toxicity and good cosmetic outcomes when compared with other forms of APBI.