János Fodor

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

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

; 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.

Incidence and time of occurrence of regional recurrence in stage i-ii breast cancer: value of adjuvant irradiation

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.

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

PURPOSE The value of adjuvant radiation therapy (RT) of the axilla and supraclavicular fossa is controversial in early-stage breast cancer. This retrospective study was undertaken to identify pathological risk factors that would predict which subsets of patients would benefit from regional nodal irradiation (RNI). METHODS AND MATERIALS A total of 1309 women with Stage I/II breast cancer underwent full axillary dissection and either mastectomy (n = 894) or breast-conserving surgery (n = 415). Of these, 712 patients received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. RESULTS The 10-year actuarial rate of axillary failure (AXF) was 0. 5% in N0 and 2.8% in N1 patients (p 5, also correlated with AXF; the respective rate was 4.3% vs. 1.2% (p = 0.0142). Neither the incidence of AXF nor the time to AXF was affected significantly by the use of RNI, but in N1 patients with retrieved nodes < or = 5, the rate of AXF was 8.3% without RNI vs. 0% with RNI (p = 0.2340). The 10-year actuarial rate of supraclavicular failure (SCF) was 1.2% in N0 and 6.3% in N1 patients (p = 0.0000). SCF was also associated with the extent of nodal involvement (p = 0.0031). The incidence of SCF was not significantly affected by the use of RNI. However, when the results of N1bii and N1biv patients were evaluated as a single group, the effect of RNI was significant (p = 0.0358). The rates of SCF without RNI were high in patients with N1bii or N1biv stage: 10% and 37.5% and, with RNI, 3.2% and 18.2%, respectively. These findings were reinforced by the various combinations of T- and N1-stage. The mean time to SCF was 53.6 months in the irradiated and 24.9 months in the nonirradiated patients (p = 0.0007). CONCLUSIONS After a complete axillary dissection, only N1 patients with retrieved nodes < or = 5 may be considered for axillary RT. Elective supraclavicular RT is suggested for patients with N1bii or N1biv stage. Supraclavicular irradiation decreases the incidence and delays the appearance of SCF.

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

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.

Moderate dose escalation with single-fraction high-dose-rate brachytherapy boost for clinically localized intermediate- and high-risk prostate cancer: 5-year outcome of the first 100 consecutively treated patients

BACKGROUND AND PURPOSE The use of high dose rate stepping source in interstitial brachytherapy provides more possibility to conform the dose distribution to the target volume compared to the classical systems. The purpose of this study was to evaluate implants made according to the Paris, the stepping source and the conformal dosimetry system with respect to dose homogeneity and conformality, and to compare these systems using volumetric parameters. MATERIALS AND METHODS Single-plane and double-plane implants with catheters arranged in square and triangle pattern were used in the analysis. Twenty-seven idealized planning target volumes (PTV) were generated. They formed slabs with rectangular or trapezoidal cross-section. The lengths were 3, 5 and 7 cm, the widths and heights were determined according to the Paris system for catheter separation of 1, 1.5 and 2 cm. The dose specification was selected such that the coverage index was 0.95 for each implant. Optimal active lengths were determined according to the best conformality at the optimized implants. From the dose-volume histogram (DVH) the following indices were calculated for every implant: conformal (COIN), external volume (EI), relative dose homogeneity (HI) and overdose volume (OI). Furthermore, the mean central dose (MCD) and minimum target dose (MTD) was also determined. The dosimetry systems were compared through the mean values of these parameters and the volumetric indices were analyzed according to the geometry of the PTV. RESULTS For the optimized systems the optimal active length was 0.5-1.0 cm shorter than the target volume length, depending on the catheter separation and geometry of the PTV. For the Paris, the stepping source and the conformal dosimetry system, the mean COIN was 0.66, 0.82 and 0.82; the mean HI was 0.71, 0.68 and 0.68; the mean EI was 0.44, 0.17 and 0.17; the mean OI was 0.11, 0.13 and 0.12, respectively. The statistical analysis showed that the Paris system differed from the optimized systems significantly. For the Paris, the stepping source and the conformal dosimetry system, the mean reference isodose was 85, 90 and 95%, the MCD was 100, 100 and 109%, the MTD was 67, 71 and 73%, respectively. Regarding geometry of the PTV, the most conformal and homogeneous dose distributions occurred when the catheter separation was small, the target volume was long and its shape was a thick rectangular slab. CONCLUSIONS Positioning the catheters according to the rules of the Paris system, but applying optimization on dose points placed either between the catheters in the whole target volume or on the surface of the target volume, and selecting the reference isodose by DVH, can provide highly conformal dose distribution to the target volume, with only a slightly worsened dose homogeneity compared to the Paris system.

Evaluation of HDR interstitial breast implants planned by conventional and optimized CT-based dosimetry systems with respect to dose homogeneity and conformality

PURPOSE To analyze the clinical outcome and toxicity data of the first 100 consecutive patients treated with a single-fraction high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT). METHODS AND MATERIALS Two-hundred eighty patients have been treated with HDR-BT boost for localized intermediate- to high-risk prostate cancer. Among these, the outcome and toxicity of the first 100 patients treated with a single HDR-BT fraction were assessed. A median dose of 60Gy EBRT was given to the prostate and vesicles. Interstitial HDR-BT of 10Gy was performed during the course of EBRT. RESULTS Median followup time was 61.5 months. The 5-year actuarial rates of overall survival, cause-specific survival, disease-free survival, and biochemical no evidence of disease (bNED) for the entire cohort were 93.3%, 99.0%, 89.3%, and 85.5%, respectively. The 7-year actuarial rate of bNED was 84.2% for the intermediate-risk group and 81.6% for the high-risk group (p=0.8464). The 7-year actuarial rates of bNED for Grade 1, 2, and 3 tumors were 97.5%, 80.0%, and 67.1%, respectively. The 5-year probability for developing late Grade 3 gastrointestinal and genitourinary (GU) toxicity was 2.1% and 14.4%, respectively. Grade 3 GU complications occurred significantly more frequently in patients with a history of preirradiation transurethral resection (29.1% vs. 8.8%; p=0.0047). CONCLUSIONS Five-year outcome after 60Gy EBRT plus a single fraction of 10Gy HDR-BT boost is encouraging. Preradiation transurethral resection significantly increases the risk of late severe GU complications.