Csaba Polgár

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1.44% (95% CI 0.51-2.38) with APBI and 0.92% (0.12-1.73) with whole-breast irradiation (difference 0.52%, 95% CI -0.72 to 1.75; p=0.42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3.2% with APBI versus 5.7% with whole-breast irradiation (p=0.08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7.6% versus 6.3% (p=0.53). The risk of severe (grade 3) fibrosis at 5 years was 0.2% with whole-breast irradiation and 0% with APBI (p=0.46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study.

BACKGROUND AND PURPOSE To report the 12-year updated results of accelerated partial-breast irradiation (APBI) using multicatheter interstitial high-dose-rate (HDR) brachytherapy (BT). PATIENTS AND METHODS Forty-five prospectively selected patients with T1N0-N1mi, nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI after breast-conserving surgery (BCS) using interstitial HDR BT. A total dose of 30.3 Gy (n=8) and 36.4 Gy (n=37) in seven fractions within 4 days was delivered to the tumour bed plus a 1-2 cm margin. The median follow-up time was 133 months for surviving patients. Local and regional control, disease-free (DFS), cancer-specific (CSS), and overall survival (OS), as well as late side effects, and cosmetic results were assessed. RESULTS Four (8.9%) ipsilateral breast tumour recurrences were observed, for a 5-, 10-, and 12-year actuarial rate of 4.4%, 9.3%, and 9.3%, respectively. A total of two regional nodal failures were observed for a 12-year actuarial rate of 4.4%. The 12-year DFS, CSS, and OS was 75.3%, 91.1%, and 88.9%, respectively. Grade 3 fibrosis was observed in one patient (2.2%). No patient developed grade 3 teleangiectasia. Fat necrosis requiring surgical intervention occurred in one woman (2.2%). Cosmetic results were rated excellent or good in 35 patients (77.8%). CONCLUSIONS Twelve-year results with APBI using HDR multicatheter interstitial implants continue to demonstrate excellent long-term local tumour control, survival, and cosmetic results with a low-rate of late side effects.

Electron and high-dose-rate brachytherapy boost in the conservative treatment of stage I-II breast cancer: First results of the randomized Budapest boost trial

Background and Aims: To evaluate the effect of electron and high-dose-rate brachytherapy (HDR BT) boost on local tumor control (LTC), side effects and cosmesis after breast-conserving surgery (BCS) in a prospective randomized study. Patients and Methods: 207 women with stage I–II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either a boost to the tumor bed (n = 104) or no further radiotherapy (n = 103). Boost treatments consisted of either 16 Gy electron irradiation (n = 52) or 12–14,25 Gy HDR BT (n = 52). Breast cancer-related events, side effects, and cosmetic results were assessed. Results: At a median follow-up of 5.3 years, the crude rate of local recurrences was 6.7% (7/104) with and 15.5% (16/103) without boost. The 5-year probability of LTC, relapse-free survival (RFS), and cancer-specific survival (CSS) was 92.7% vs. 84.9% (p = 0.049), 76.6% vs. 66.2% (p = 0.044), and 90.4% vs. 82.1% (p = 0.053), respectively. There was no significant difference in LTC between patients treated with electron or HDR BT boost (94.2% vs. 91.4%; p = 0.74). On multivariate analysis, patient age < 40 years (RR: 4.53), positive margin status (RR: 4.17), and high mitotic activity index (RR: 3.60) were found to be significant risk factors for local recurrence. The incidence of grade 2–3 side effects was higher in the boost arm (17.3% vs. 7.8%; p = 0.03). However, the rate of excellent/good cosmetic results was similar for the two arms (85.6% vs 91.3%; p = 0.14). Cosmesis was rated as excellent/good in 88.5% of patients treated with HDR BT and 82.7% of patients with electron boost (p = 0.29). Conclusions: Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy. In spite of the higher incidence of late side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. Positive or close margin status, high mitotic activity index, and young patient age should be viewed as absolute indications for tumor bed boost. LTC and cosmesis are excellent and similar to patients boosted with either HDR BT or electrons.Hintergrund und Ziel: In einer prospektiv randomisierten Studie werden die Effekte eines Elektronenboosts und eines High-Dose-Rate-Brachytherapie-(HDR-BT-)Boosts bezüglich lokaler Tumorkontrolle (LTC), Nebenwirkungen und kosmetischer Ergebnisse nach brusterhaltender Operation (BCS) evaluiert. Patienten und Methodik: 207 Patientinnen mit Brustkarzinomen im Stadium I–II wurden einer BCS zugeführt. Postoperativ erfolgte eine perkutane Radiatio der gesamten Brust bis 50 Gy. Daran schloss sich willkürlich entweder eine Boostbestrahlung des Tumorbetts (n = 104) oder keine weitere Radiatio (n = 103) an. Die Boostbestrahlung erfolgte perkutan mit 16 Gy Elektronen (n = 52) oder in Form einer HDR-BT mit 12–14,25 By (n = 52). Untersucht wurden LTC, Nebenwirkungen und kosmetische Ergebnisse. Ergebnisse: Die mediane Nachbeobachtungszeit betrug 5,3 Jahre. Die Lokalrezidivrate lag mit Boostbestrahlung bei 6,7% (7/104), ohne Boost bei 15,5% (16/103). Die 5-Jahres-Überlebensrate für LTC, für die rezidivfreie Überlebenszeit (RFS) und für die krebsspezifische Überlebenszeit (CSS) betrugen 92,7% vs. 84,9% (p = 0,049), 76,6% vs. 66,2% (p = 0,044) und 90,4% vs. 82,1% (p = 0,053). Bezüglich der LTC bestand kein signifikanter Unterschied zwischen Patienten, die mit einem Elektronen- oder HDR-BT-Boost behandelt wurden (94,2% vs. 91,4

Defining the efficacy of accelerated partial breast irradiation: the importance of proper patient selection, optimal quality assurance, and common sense.

; p = 0,74). Die multivariate Analyse zeigte, dass Faktoren wie Patientenalter > 40 Jahre (RR: 4,53), positive Resektionsränder (RR: 4,17) und ein hoher Mitoseaktivitätsindex (RR: 3.60) das Risiko eines lokalen Rezidivs signifikant erhöhen. Die Inzidenz von Nebenwirkungen Grad 2–3 war im Boost-Arm höher (17,3% vs. 7,8%; p = 0,03). Allerdings waren die sehr guten kosmetischen Ergebnisse in beiden Armen gleich (85,6% bs. 91,3%, p = 0,14). Sehr gute kosmetische Ergebnisse wurden bei 88,5% der Patientinnen mit HDR-BT-Boost und 82,7% der Patientinnen mit Elektronenboost erreicht (p = 0,29). Schlussfolgerungen: Die Boost-Dosis verbessert signifikant LTC und RFS bei Patientinnen, die einer BCS und anschließender Radiatio zugeführt wurden. Obwohl eine höhere Inzidenz an Spätnebenwirkungen im Boost-Arm gefunden wurde, wird eine Boost-Dosis für Patientinnen mit hohem Risiko für die Entwicklung eines Lokalrezidivs empfohlen. Unserer Meinung nach ist bei Faktoren wie positive Schnittränder, schmaler Sicherheitssaum, hoher Mitoseaktivitätsindex und niedriges Patientenalter, die absolute Indikation zur Boost-Bestrahlung des Tumorbetts gegeben. LTC und die kosmetischen Ergebnisse sind sehr gut und unterscheiden sich nicht in Bezug auf Elektronenboost oder HDR-BT-Boost.

Radiotherapy confined to the tumor bed following breast conserving surgery: Current status, controversies, and future prospects

The use of accelerated partial breast irradiation (APBI) in the treatment of patients with Stage I and II breast cancer with breast-conserving therapy (BCT) has generated a tremendous amount of recent interest owing to an expanding volume of maturing clinical data demonstrating comparable 5-year local control rates and cosmetic results as with conventional whole breast radiotherapy (RT). The advantages of this treatment approach in terms of improving the quality of life of patients and potentially increasing the BCT option have been recognized by patient groups, surgeons, and oncologists alike to such a degree that several Phase III trials comparing this novel treatment approach with whole breast RT have recently been started in Europe and are under development through the National Surgical Breast and Bowel Project and the Radiation Therapy Oncology Group in the United States. In this issue of the Journal, we are presented with the report of a small, pilot study of APBI by Perera et al. ,i n which the authors describe what they believe to be an unusually high rate of failures in remote parts of the breast (“elsewhere” failures) with their treatment technique (1). On the basis of this limited experience (4 of 39 patients experienced an “elsewhere” failure), the authors concluded that elsewhere failures represent the predominant pattern of failure in their study, indirectly suggesting that elective treatment of the whole breast may be necessary for the successful application of BCT. Is this a reasonable interpretation of their data, signaling a potential danger with not electively irradiating the entire breast after lumpectomy? Should this be a warning to proceed cautiously until data from Phase III trials have sufficiently matured before introducing APBI routinely into the clinic? Or, is this simply another example of a suboptimal APBI technique applied to a less than ideal set of patients? We believe the evidence points to the latter. PATIENT SELECTION It cannot be overstated that proper patient selection is critical to the successful application of APBI. Patients who may harbor disease a significant distance from the edge of the excision cavity or potentially have multicentric disease should not be treated with APBI. A careful review of Table 1 clearly points out the significant differences in the clinical and pathologic characteristics of patients treated successfully in APBI trials that mandate strict selection criteria vs. less successful APBI trials that did not. One could even argue that many of the patients treated in the “negative” APBI trials from the Christie Hospital and Guy’s Hospital were not acceptable candidates (or, at best, were borderline acceptable) for BCT in general. As we have stated numerous times, patients who are not good candidates for BCT should not be treated with APBI. The “negative” APBI studies only reinforce this obvious, and yet inconsistently applied, recommendation. Although the selection criteria were reasonable in the study by Perera et al., 3 cases were documented to have an extensive intraductal component, 6 had positive axillary nodes, 2 had unknown nodal status, and 12 had 2-mm negative margins. Interestingly, two of six local failures occurred in these patients (one with an extensive intraductal component and one with 1-mm margins).

Locoregional failure 15 years after mastectomy in women with one to three positive axillary nodes with or without irradiation: The significance of tumor size

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.

Current status and perspectives of brachytherapy for breast cancer

Background: There is insufficient evidence to suggest the routine use of postmastectomy radiotherapy (PMRT) in patients with one to three positive axillary nodes and T1/2 tumors. We have assessed the risk of locoregional recurrence (LRR) with or without RT in this group of patients, and focused on the results in subgroups defined by tumor size. Patients and Methods: 249 women with T1/2 tumors and one to three positive nodes underwent mastectomy and axillary dissection between 1983 and 1987. Locoregional RT of 50 Gy was given to 175 patients. Chemotherapy or hormonal therapy was administered to 41 and 71 women, respectively. The median follow-up time of survivors was 189 months (range, 167–227 months). Results: The rates of isolated LRR without or with RT were 16% (12/74) and 8% (14/175), respectively (p = 0.05), and the total (with or without distant relapse) LRR rates 23% and 12%, respectively (p = 0.03). 15-year overall survival amounted to 41% without RT and to 52% with RT (p = 0.2). The rates of isolated LRR for patients treated with chemotherapy or hormonal therapy only were 25% and 12%, respectively. In the absence of RT, age (> 45 vs = 45 years; p = 0.06), tumor size (T1 vs T2; p = 0.07), and extranodal invasion (ENI; absent vs present; p = 0.09) were related to the risk of developing an isolated LRR. On multivariate analysis, only tumor size (relative risk [RR], 3.92; 95% confidence interval [CI], 1.11–15.14) and age (RR, 3.37; 95% CI, 1.03–11.09) emerged as independent significant predictors, whereas ENI (RR, 1.50; 95% CI, 0.81–2.77) did not. In the T1 subgroup, the estimated 15-year isolated LRR rate was 9% (3/36) without and 9% (8/99) with RT (p = 0.9775). 15-year disease-free survival amounted to 62% and 57%, respectively (p = 0.5153). For patients without RT, according to the age groups (= 45 vs > 45 years), the 15-year rates of isolated LRR were 9% and 9%, respectively (p = 0.9910). In the T2 subgroup, the estimated 15-year isolated LRR rate was 30% (9/38) without and 10% (6/76) with RT (RR, 0.33; 95% CI, 0.12–0.92; p = 0.0244). 15-year disease-free survival amounted to 32% and 50%, respectively (p = 0.1213). For patients without RT, according to the age groups (≤ 45 vs > 45 years), the 15-year rates of isolated LRR were 57% and 16%, respectively (p = 0.0049). Conclusion: Patients with T1 tumor and one to three positive nodes are at low risk of isolated LRR either with or without RT. Patients with T2 tumor and one to three positive nodes are at high risk of isolated LRR without RT. Our findings support the routine use of PMRT in patients with T2 tumor, especially those aged ≤ 45 years.Hintergrund: Es gibt nicht genügend Hinweise darauf, ob eine adjuvante Strahlentherapie nach Mastektomie bei Patientinnen mit kleinen Tumoren (T1/2) und ein bis drei positiven axillären Lymphknoten indiziert ist. Wir haben das Risiko, lokoregionäre Rezidive (LRR) zu entwickeln, bei dieser Gruppe mit oder ohne Radiotherapie (RT) untersucht und insbesondere die Untergruppen analysiert, die aus der Größe des Primärtumors gebildet wurden. Patienten und Methodik: Von 1983 bis 1987 führten wir bei 249 Patientinnen mit T1/2-Karzinomen der Brust und ein bis drei positiven axillären Lymphknoten eine Mastektomie und Dissektion der Axilla durch. Bei 175 Patientinnen folgte eine adjuvante lokoregionale Strahlenbehandlung mit 50 Gy. Die Nachbeobachtungszeit lag zwischen 167 und 227 Monaten, im Median bei 189 Monaten. Ergebnisse: Von 249 Patientinnen entwickelten zwölf (16%) ohne RT (n = 74) und 14 (8%) mit RT (n = 175) ein isoliertes LRR (p = 0,05). Im Gesamtkollektiv entstanden LRR bei 23% ohne RT und bei 12% mit RT (p = 0,03). Folgende Rezidivlokalisationen wurden beobachtet: Brustwand 17 (65%), Achselhöhle fünf (19%), Supraklavikulargrube drei (12%) und parasternale Lymphknoten eine (4%). Die 15-Jahres-Gesamtüberlebensrate betrug 52% für Patientinnen mit vs. 41% ohne Strahlenbehandlung (p = 0,2). In der Subgruppe der pT1-Tumoren lag die Rate an isolierten LRR bei 9% (3/36) ohne RT vs. 9% (8/99) mit RT (p = 0,9775). Die krankheitsfreie 15-Jahres-Überlebensrate betrug 62% für Patientinnen ohne RT vs. 57% mit RT (p = 0,5153). In der Subgruppe der pT2-Tumoren lag die Rate an isolierten LRR bei 30% (9/38) ohne versus 10% (6/76) mit RT (relatives Risiko 0,33; 95%-Vertrauensintervall 0,12–0,92; p = 0,0244). Die krankheitsfreie 15-Jahres-Überlebensrate betrug 32% für Patientinnen ohne vs. 50% mit RT (p = 0,1213). Schlussfolgerung: Patientinnen mit T1-Tumoren und ein bis drei axillären Lymphknotenmetastasen weisen insgesamt ein niedriges Risiko auf, ein isolierte LRR zu entwickeln. Patientinnen mit T2-Tumoren und ein bis drei axillären Lymphknotenmetastasen haben dagegen ein hohes Risiko für die Entwicklung eines LRR mit oder ohne adjuvante Strahlenbehandlung, jedoch signifikant niedriger in der Gruppe mit RT. Aufgrund unserer langjährigen Erfahrungen und der Ergebnisse dieser retrospektiven Auswertung empfehlen wir die adjuvante Strahlenbehandlung für Tumorgrößen ab pT2 mit ein bis drei Lymphknotenmetastasen, nicht jedoch für pT1.

The role of boost irradiation in the conservative treatment of stage I-II breast cancer

Before the era of breast-conserving therapy, brachytherapy implants were used to treat large inoperable breast tumors. In later years, interstitial brachytherapy with rigid needles or multiple flexible catheters has been used to deliver an additional (boost) dose to the tumor bed after breast-conserving surgery and whole-breast irradiation. Reexcision followed by reirradiation using interstitial breast implants has also been implemented as an alternative to mastectomy to treat ipsilateral breast local recurrence after previous breast-conserving therapy. In the past two decades, the new concept of accelerated partial breast irradiation opened a new perspective for breast brachytherapy. The first technique utilized in early accelerated partial breast irradiation studies was multicatheter interstitial brachytherapy. Beyond classical interstitial brachytherapy, recently, new intracavitary applicators have been developed in the United States to decrease the existing barriers against the widespread use of multicatheter brachytherapy. Furthermore, interstitial low-dose-rate seed implants have also been implemented as an alternative for stepping-source multicatheter brachytherapy. In this article, we give an overview of the past achievements, current status, and future perspectives of breast brachytherapy.

Locoregional Failure 15 Years after Mastectomy in Women with One to Three Positive Axillary Nodes with or without Irradiation

In this article, we review the current status, indication, technical aspects, controversies, and future prospects of boost irradiation after breast conserving surgery (BCS). BCS and radiotherapy (RT) of the conserved breast became widely accepted in the last decades for the treatment of early invasive breast cancer. The standard technique of RT after breast conservation is to treat the whole breast up to a total dose of 45 to 50 Gy. However, there is no consensus among radiation oncologists about the necessity of boost dose to the tumor bed. Generally accepted criteria for identification of high risk subgroups, in which boost is recommended, have not been established yet. Further controversy exists regarding the optimal boost technique (electron vs. brachytherapy), and their impact on local tumor control and cosmesis. Based on the results of numerous retrospective and recently published prospective trials, the European brachytherapy society (GEC-ESTRO), as well as the American Brachytherapy Society has issued their guidelines in these topics. These guidelines will help clinicians in their medical decisions. Some aspects of boost irradiation still remain somewhat controversial. The final results of prospective boost trials with longer follow-up, involving analyses based on pathologically defined subgroups, will clarify these controversies. Preliminary results with recently developed boost techniques (intraoperative RT, CT-image based 3D conformal brachytherapy, and 3D virtual brachytherapy) are promising. However, more experience and longer follow-up are required to define whether these methods might improve local tumor control for breast cancer patients treated with conservative surgery and RT.

Conformality and homogeneity of dose distributions in interstitial implants at idealized target volumes: A comparison between the Paris and dose-point optimized systems

Background: There is insufficient evidence to suggest the routine use of postmastectomy radiotherapy (PMRT) in patients with one to three positive axillary nodes and T1/2 tumors. We have assessed the risk of locoregional recurrence (LRR) with or without RT in this group of patients, and focused on the results in subgroups defined by tumor size. Patients and Methods: 249 women with T1/2 tumors and one to three positive nodes underwent mastectomy and axillary dissection between 1983 and 1987. Locoregional RT of 50 Gy was given to 175 patients. Chemotherapy or hormonal therapy was administered to 41 and 71 women, respectively. The median follow-up time of survivors was 189 months (range, 167–227 months). Results: The rates of isolated LRR without or with RT were 16% (12/74) and 8% (14/175), respectively (p = 0.05), and the total (with or without distant relapse) LRR rates 23% and 12%, respectively (p = 0.03). 15-year overall survival amounted to 41% without RT and to 52% with RT (p = 0.2). The rates of isolated LRR for patients treated with chemotherapy or hormonal therapy only were 25% and 12%, respectively. In the absence of RT, age (> 45 vs = 45 years; p = 0.06), tumor size (T1 vs T2; p = 0.07), and extranodal invasion (ENI; absent vs present; p = 0.09) were related to the risk of developing an isolated LRR. On multivariate analysis, only tumor size (relative risk [RR], 3.92; 95% confidence interval [CI], 1.11–15.14) and age (RR, 3.37; 95% CI, 1.03–11.09) emerged as independent significant predictors, whereas ENI (RR, 1.50; 95% CI, 0.81–2.77) did not. In the T1 subgroup, the estimated 15-year isolated LRR rate was 9% (3/36) without and 9% (8/99) with RT (p = 0.9775). 15-year disease-free survival amounted to 62% and 57%, respectively (p = 0.5153). For patients without RT, according to the age groups (= 45 vs > 45 years), the 15-year rates of isolated LRR were 9% and 9%, respectively (p = 0.9910). In the T2 subgroup, the estimated 15-year isolated LRR rate was 30% (9/38) without and 10% (6/76) with RT (RR, 0.33; 95% CI, 0.12–0.92; p = 0.0244). 15-year disease-free survival amounted to 32% and 50%, respectively (p = 0.1213). For patients without RT, according to the age groups (≤ 45 vs > 45 years), the 15-year rates of isolated LRR were 57% and 16%, respectively (p = 0.0049). Conclusion: Patients with T1 tumor and one to three positive nodes are at low risk of isolated LRR either with or without RT. Patients with T2 tumor and one to three positive nodes are at high risk of isolated LRR without RT. Our findings support the routine use of PMRT in patients with T2 tumor, especially those aged ≤ 45 years.Hintergrund: Es gibt nicht genügend Hinweise darauf, ob eine adjuvante Strahlentherapie nach Mastektomie bei Patientinnen mit kleinen Tumoren (T1/2) und ein bis drei positiven axillären Lymphknoten indiziert ist. Wir haben das Risiko, lokoregionäre Rezidive (LRR) zu entwickeln, bei dieser Gruppe mit oder ohne Radiotherapie (RT) untersucht und insbesondere die Untergruppen analysiert, die aus der Größe des Primärtumors gebildet wurden. Patienten und Methodik: Von 1983 bis 1987 führten wir bei 249 Patientinnen mit T1/2-Karzinomen der Brust und ein bis drei positiven axillären Lymphknoten eine Mastektomie und Dissektion der Axilla durch. Bei 175 Patientinnen folgte eine adjuvante lokoregionale Strahlenbehandlung mit 50 Gy. Die Nachbeobachtungszeit lag zwischen 167 und 227 Monaten, im Median bei 189 Monaten. Ergebnisse: Von 249 Patientinnen entwickelten zwölf (16%) ohne RT (n = 74) und 14 (8%) mit RT (n = 175) ein isoliertes LRR (p = 0,05). Im Gesamtkollektiv entstanden LRR bei 23% ohne RT und bei 12% mit RT (p = 0,03). Folgende Rezidivlokalisationen wurden beobachtet: Brustwand 17 (65%), Achselhöhle fünf (19%), Supraklavikulargrube drei (12%) und parasternale Lymphknoten eine (4%). Die 15-Jahres-Gesamtüberlebensrate betrug 52% für Patientinnen mit vs. 41% ohne Strahlenbehandlung (p = 0,2). In der Subgruppe der pT1-Tumoren lag die Rate an isolierten LRR bei 9% (3/36) ohne RT vs. 9% (8/99) mit RT (p = 0,9775). Die krankheitsfreie 15-Jahres-Überlebensrate betrug 62% für Patientinnen ohne RT vs. 57% mit RT (p = 0,5153). In der Subgruppe der pT2-Tumoren lag die Rate an isolierten LRR bei 30% (9/38) ohne versus 10% (6/76) mit RT (relatives Risiko 0,33; 95%-Vertrauensintervall 0,12–0,92; p = 0,0244). Die krankheitsfreie 15-Jahres-Überlebensrate betrug 32% für Patientinnen ohne vs. 50% mit RT (p = 0,1213). Schlussfolgerung: Patientinnen mit T1-Tumoren und ein bis drei axillären Lymphknotenmetastasen weisen insgesamt ein niedriges Risiko auf, ein isolierte LRR zu entwickeln. Patientinnen mit T2-Tumoren und ein bis drei axillären Lymphknotenmetastasen haben dagegen ein hohes Risiko für die Entwicklung eines LRR mit oder ohne adjuvante Strahlenbehandlung, jedoch signifikant niedriger in der Gruppe mit RT. Aufgrund unserer langjährigen Erfahrungen und der Ergebnisse dieser retrospektiven Auswertung empfehlen wir die adjuvante Strahlenbehandlung für Tumorgrößen ab pT2 mit ein bis drei Lymphknotenmetastasen, nicht jedoch für pT1.