Electron and High-Dose-Rate Brachytherapy Boost in the Conservative Treatment of Stage I–II Breast Cancer

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.     

Remineralisation und Schmerzlinderung von Knochenmetastasen nach unterschiedlich fraktionierter Strahlentherapie (10mal 3 Gy vs. 1mal 8 Gy) Eine prospektive Studie

BACKGROUND: In a prospective randomized trial we examined pain relief and recalcification following radiotherapy for bone metastases. PATIENTS AND METHOD: One hundred and seven patients with histologically proven breast, lung, prostate or kidney cancer and radiologically confirmed bone metastases were included in this trial. They were stratified to primary tumor sites and randomized in 2 different fractionation schedules: 1 x 8 Gy vs 10 x 3 Gy. Pain relief was registered using of pain score, analgesic usage and subjective perception of pain. The recalcification was measured at the computertomograph. Pain status and recalcification were assessed before, day after, 6 weeks, 3 and 6 months after radiotherapy. RESULTS: There was no significant difference in overall (81% vs 78%) and complete (33% vs 31%) pain response. In the single dose group (1 x 8 Gy) the pain response was measured a little rarer. The recalcification showed a significant difference between patients in the fractionated group (173%) and the single dose group (120%, p < 0.0001). In the fractionated group there was a significant difference between patients with breast and lung cancer (p = 0.015). There was a slight trend favoring 10 x 3 Gy in recalcification for all primary tumor sites but only a significant difference in breast cancer (p < 0.001). CONCLUSION: The basis of pain response and recalcification is different. In mere consideration of pain a short-course fractionation is recommendable. This fractionation schedule is effective, well tolerable and short. In consideration of recalcification a more fractionated schedule is recommendable because the biological efficacy is higher and this leads to better stabilisation.     

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

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

Long-term outcome of breast-conserving therapy for breast cancer

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.     

Second breast-conserving surgery and interstitial brachytherapy vs. salvage mastectomy for the treatment of local recurrences: 5-year results

PurposeThe purpose of this study was to report the clinical outcomes of a second breast-conserving therapy (2nd BCT) with perioperative interstitial brachytherapy (iBT) vs. those of salvage mastectomy (sMT) in the treatment of ipsilateral breast tumor recurrences (IBTRs).Methods and MaterialsBetween 1999 and 2015, 195 patients with IBTR after a previous breast-conserving treatment were salvaged either with reexcision and perioperative high-dose-rate iBT (n = 39), or with sMT (n = 156). In the 2nd BCT group, a total dose of 22 Gy in five fractions of 4.4 Gy was delivered to the tumor bed with intraoperatively implanted catheters for 3 consecutive days.ResultsThe median followup time was 59 months (1–189) in the 2nd BCT, and 56 months (3–189) in the sMT group. The mean size of IBTR was 16 mm (2–70) vs. 24 mm (2–90), respectively (p = 0.0005), but there were no other significant differences in patient- or IBTR-related parameters between the two groups. During the followup period, 4 of 39 (10.2%) and 28 of 156 (17.9%) second local recurrences (2nd LR) occurred in the 2nd BCT and the sMT group, respectively. The 5-year actuarial rate of 2nd LR was 6% vs. 18% (p = 0.22), the 5-year probability of disease-free, cancer-specific and overall survival was 69% vs. 65% (p = 0.13), 85% vs. 78% (p = 0.32), and 81% vs. 66% (p = 0.15), respectively. In the 2nd BCT group, the rate of good to excellent cosmesis was 70%.Conclusions2nd BCT with perioperative high-dose-rate iBT is a safe and feasible option for the management of IBTR, resulting in similar 5-year oncological outcomes and better cosmetic results compared with sMT.     

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$; 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.     

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

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

Late Effects of Post-High-Dose-Rate Brachytherapy for Oropharyngeal Carcinoma: Are They Severer than Post-Low-Dose-Rate?

BACKGROUND:. Late effects by high-dose-rate (HDR) brachytherapy have been believed severer than low-dose-rate (LDR) provided tumor control was constant. Local control of oropharyngeal carcinoma with HDR at Osaka Medical Center was comparable to LDR series from Centre Alexis Vautrin (82%, 79.5%, respectively). To assess the feasibility of HDR brachytherapy, the late effects were compared. PATIENTS AND METHODS:. The data of 29 HDR and 24 LDR patients (median follow-up of 27 and 29.5 months, respectively; p = 0.89) were collected. The HDR schedule was 21 Gy/3.5 fractions/2 days following 46 Gy/23 fractions external beam, while 25 Gy/3 days following 50 Gy/25 fractions external beam was for LDR. Late changes were evaluated using RTOG/EORTC late morbidity scoring scheme. For subclinical late changes, mucosa chapter of Dische score was modified for brachytherapy. Scores were discussed through photos and were agreed on by authors. Late sequelae were estimated, by reviewing charts, concerning frequency, severity, and duration of mucosal damages (erosion and ulcer). RESULTS:. Late changes were of no difference (p = 0.12 for EORTC/RTOG, and p = 0.45, 0.47, 1.00, 0.12, 0.16, 0.95, 0.27, 0.21 for erythema, ulceration, edema, thinning, pallor, telangiectasia, mobility impairment of tongue/faucial pillars, respectively, of the modified Dische score). Late sequelae showed no differences (p = 0.90, 0.12, 0.40 for frequency, severity, duration, respectively, of mucosal damages). CONCLUSION:. The late effects by HDR were not severer than by LDR. HDR oropharyngeal brachytherapy is as safe as LDR.     

Spättoxizität nach präoperativer Kurzzeitvorbestrahlung und risikoadaptierter postoperativer Nachbestrahlung bei operablem Rektumkarzinom Resultate einer randomisierten prospektiven Studie

AIM: Analysis of a randomized study of preoperative radiation therapy for operable carcinoma of the rectum with regard to late sequelae. Results of tumor control and survival, which have already been published in detail are summarized for comparison and for confirmation of the conclusions. PATIENTS AND METHODS: Between January 1988 and October 1993 94 patients with operable carcinoma of the rectum were included in a randomized trial. Fourty-seven patients were treated with 5 x 3.3 Gy (field size 16 x 16 cm, 9 MeV photons) 24 to 48 hours prior to surgery; 46 patients did not receive preoperative irradiation. If risk factors (T4-stage, R1/R2 resection, intraoperative tumor perforation) were present, postoperative irradiation was performed after CT-planning. Total postoperative doses of 41.4 Gy (preoperative irradiation) or 59.8 Gy (surgery only) were applied with doses per fraction of 1.8 to 2.0 Gy. Local control, survival, and pattern of side effects were analyzed at 5 years after conclusion of the trial. RESULTS: The frequency of local recurrence was markedly reduced by preoperative irradiation of R0-resected patients (24% vs 13%, p = 0.08). The time to recurrence was delayed (1.9 vs 3 years). The 5-year actuarial survival rate was significantly higher in the preoperatively irradiated group compared to the not pre-irradiated group (40% vs 28%, p = 0.027). Multivariate analysis revealed UICC-grading as the only independent parameter for local control (p = 0.0003), while preoperative irradiation (p = 0.07) and T-stage (p = 0.08) only displayed a trend. For patient survival, age (p = 0.0003). R-status (p = 0.01) and UICC-score (p = 0.001) were significant prognostic factors. Preoperative irradiation had a non-significant effect only (p = 0.078). Radiation-induced side effects with a LENT-SOMA score > 2 were observed neither during frequent follow-up nor at an additional examination of those patients still alive in 1998 (n = 25). Of 4 pre- and postoperatively irradiated patients with risk factors, 3 had side effects grade 1 or 2, predominantly rectal changes, at 5 to 11 years after treatment. CONCLUSIONS: A positive effect on tumor control and survival is achieved with preoperative irradiation with the doses used in this study, with moderate side effects.     

Remineralisation und Schmerzlinderung von Knochenmetastasen nach unterschiedlich fraktionierter Strahlentherapie (10mal 3 Gy vs. 1mal 8 Gy) Eine prospektive Studie

Hintergrund: Es wurde eine prospektive randomisierte Studie zur Bestrahlung von Knochenmetastasen durchgeführt, die sowohl die Schmerzansprechrate als auch die Remineralisation als Kriterien des Therapieerfolgs berücksichtigte. Patienten und Methode: 107 Patienten mit histologisch gesichertem Mamma-, Bronchial-, Prostata- und Nierenzellkarzinom, die eine schmerzhafte und röntgenologisch sichtbare Osteolyse hatten, wurden in die Studie aufgenommen. Es erfolgten eine Stratifizierung nach den Entitäten und eine Randomisation in zwei unterschiedliche Therapiearme (10mal 3 Gy vs 1mal 8 Gy). Die Erfassung der Schmerzansprechrate erfolgte mit Hilfe eines Schmerz- und Schmerzmittel-Scores und der subjektiven Einschätzung der Patienten. Die Remineralisation wurde am Computertomographen gemessen. Sowohl die Schmerzreduktion als auch die Remineralisation wurden vor, unmittelbar nach der Therapie sowie sechs Wochen, drei und sechs Monate nach Bestrahlungsabschluß erfaßt. Ergebnisse: Bei der Schmerzreduktion ergab sich im Vergleich beider Therapiearme sowohl hinsichtlich der Gesamtansprechrate (81% vs. 78%) als auch der kompletten Schmerzreduktion (33% vs. 31%) kein Unterschied. Im 1mal-8-Gy-Arm wurde ein etwas rascheres Ansprechen auf die Therapie beobachtet. Bei der Remineralisation ergab sich ein hochsignifikanter Unterschied (p < 0,0001) im Vergleich aller Patienten zugunsten des fraktionierten Therapiearms (173% vs. 120%). Im fraktionierten Arm zeigte sich ein signifikanter Unterschied zwischen Mamma- und Bronchialkarzinomen (p = 0,015). Dieser Unterschied wurde im Vergleichsarm (1mal 8 Gy) nicht gesehen. Beim Vergleich der unterschiedlichen Therapiearme hinsichtlich der einzelnen Tumorentitäten zeigte sich zwar bei allen eine Tendenz zugunsten des fraktionierten Therapiearmes, ein signifkanter Unterschied wurde nur beim Mammakarzinom gemessen (p < 0,001). Schlußfolgerung: Schmerzreduktion und Remineralisation liegen unterschiedliche Wirkungsmechanismen zugrunde. Bei alleiniger Berücksichtigung der Schmerzen ist ein Kurzzeitschema zu empfehlen, da es effektiv und wenig belastend für den Patienten ist. Unter Berücksichtigung der Remineralisation ist einem fraktionierten Schema der Vorzug zu geben, da hiermit eine größere biologische Wirksamkeit erzielt wird und damit die Grundlage für eine bessere Stabilisierung gegeben ist. Background: In a prospective randomized trial we examined pain relief and recalcification following radiotherapy for bone metastases. Patients and Methods: One hundred and seven patients with histologically proven breast, lung, prostate or kidney cancer and radiologically confirmed bone metastases were included in this trial. They were stratified to primary tumor sites and randomized in 2 different fractionation schedules: 1 2 8 Gy vs 10 2 3 Gy. Pain relief was registered using of pain score, analgesic usage and subjective perception of pain. The recalcification was measured at the computertomograph. Pain status and recalcification were assessed before, day after, 6 weeks, 3 and 6 months after radiotherapy. Results: There was no significant difference in overall (81% vs 78%) and complete (33% vs 31%) pain response. In the single dose group (1 2 8 Gy) the pain response was measured a little rarer. The recalcification showed a significant difference between patients in the fractionated group (173%) and the single dose group (120%, p < 0.0001). In the fractionated group there was a significant difference between patients with breast and lung cancer (p = 0.015). There was a slight trend favoring 10 2 3 Gy in recalcification for all primary tumor sites but only a significant difference in breast cancer (p < 0.001). Conclusion: The basis of pain response and recalcification is different. In mere consideration of pain a short-course fractionation is recommendable. This fractionation schedule is effective, well tolerable and short. In consideration of recalcification a more fractionated schedule is recommendable because the biological efficacy is higher and this leads to better stabilisation.     

Interstitial brachytherapy alone after breast conserving surgery: interim results of a German-Austrian multicenter phase II trial

PURPOSE: To evaluate the value of interstitial brachytherapy (iBT) alone in the treatment of low-risk breast cancer patients with regard to local control, side effects, and cosmesis. METHODS AND MATERIALS: From November 2000 to January 2004, 176 patients with low-risk breast cancer were treated with iBT only. Patients were eligible for entering the study if: the tumor size was <3 cm; resection margins were clear by at least 2 mm; there were no lymph node metastases or only one micrometastasis (pNo, pNmi); age was >35 years; steroid hormone receptor was positive; and histologic grade was 1 or 2. Seventy-five percent of patients received pulsed-dose-rate brachytherapy (D(ref) = 50 Gy); 25% of patients received high-dose-rate brachytherapy (D(ref) = 32.0 Gy). An interim analysis is presented for all patients after an interim follow-up of 12 months, and for half the patient population with an interim follow-up of 21 months. RESULTS: All patients remained disease-free on the date of analysis. A perioperative complication breast infection was recorded for 1/176 (0.6%) patients. Late toxicity i.e., hypersensation, hyperpigmentation, fibrosis, or teleangiectasia was observed in 1-12% of all patients. Grade I Fibrosis was registered in 7.6% (13/172) and grade II in 7.0% (12/172) of evaluable patients. Similarly, grade I teleangiectasia was observed in 4.7% (8/172), grade II in 0.6% (1/172), and grade III also in 0.6% (1/172) of evaluable patients. Excellent or good cosmetic results have been observed in 92-95% of patients. CONCLUSIONS: Brachytherapy as monotherapy in low-risk breast cancer patients after breast-conserving surgery is an effective, precise treatment modality without perioperative morbidity, low acute, mild late toxicity, and yields good to excellent cosmetic results.     

Accelerated Partial-Breast Irradiation with Interstitial Implants

PURPOSE: To describe relative skin dose estimations and their impact on cosmetic outcome in interstitial multicatheter accelerated partial-breast irradiation (APBI). PATIENTS AND METHODS: Between April 2001 and January 2005, 105 consecutive patients with early breast cancer were recruited in Erlangen, Germany, for this substudy of the German-Austrian APBI phase II trial. 51% (54/105) received pulsed-dose-rate (PDR), and 49% (51/105) high-dose-rate (HDR) brachytherapy. Prescribed reference dose for HDR brachytherapy was 32 Gy in eight fractions of 4 Gy, twice daily. Prescribed reference dose in PDR brachytherapy was 49.8 Gy in 83 consecutive fractions of 0.6 Gy every hour. Total treatment time was 3-4 days. With a wire cross on the skin surface during the brachytherapy-planning procedure the minimal, mean and maximal relative skin doses (SD(min%), SD(max%), SD(mean%)) were recorded. Endpoint of this evaluation was the cosmetic outcome in relation to the relative skin doses. RESULTS: Median follow-up time was 38 months (range, 19-65 months). Cosmetic results for all patients were excellent in 57% (60/105), good in 36% (38/105), and fair in 7% (7/105). The SD(min%) (27.0% vs. 31.7%; p = 0.032), SD(mean%) (34.2% vs. 38.1%; p = 0.008), and SD(max%) (38.2% vs. 46.4%; p = 0.003) were significantly lower for patients with excellent cosmetic outcome compared to patients with a suboptimal outcome. SD(mean%) (37.6% vs. 34.2%; p = 0.026) and SD(max%) (45.4% vs. 38.2%; p = 0.008) were significantly higher for patients with good cosmetic outcome compared with the patients with excellent results. CONCLUSION: The appraisal of skin doses has been shown to be relevant to the achievement of excellent cosmetic outcome. Further investigations are necessary, especially on the basis of CT-based brachytherapy planning, to further improve the treatment results of multicatheter APBI.     

Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission

Aim

In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT.

Patients and Methods

Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n=182) and acute lymphoblastic leukemia (ALL, n=144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 ± 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (≤0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and ≤ 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 ± 29, range: 24 to 130 months).

Results

Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03: MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%: p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age ≤ 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008).

Conclusion

The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.     

Brachytherapy-based partial breast irradiation is associated with low rates of complications and excellent cosmesis

BackgroundRecent retrospective, claims-based analyses have suggested a potential increased rate of toxicities associated with brachytherapy-based accelerated partial breast irradiation (APBI). The purpose of this analysis was to examine cosmesis and toxicity data from the prospective American Society of Breast Surgeons (ASBS) breast brachytherapy registry trial to compare to the findings from the claims analyses.MethodsThe ASBS breast brachytherapy registry is a prospective nonblinded multi-institutional registry trial. Patients with Stage 0–II breast cancer undergoing breast conserving therapy were eligible. A total of 1665 patients were enrolled and 1449 treated between 2002 and 2004 with a median followup of 63 months. All patients were treated with the MammoSite (Hologic, Inc.) single-lumen device to deliver adjuvant APBI (34 Gy in 3.4 Gy fractions).ResultsThe rate of excellent/good cosmesis was 90.6% at 84 months. The rate of a complication (symptomatic seroma, infection, fat necrosis, telangiectasias) at 1 year/any time point was 24.2%/38.5%, whereas the rate of noninfectious complications at 1 year/any time point was 14.8%/28.9%. The rate of symptomatic seroma, fat necrosis, infection, and telangiectasia at any time was 13.4%, 2.5%, 9.6%, and 13.0%, respectively.ConclusionsThe final toxicity analysis from ASBS breast brachytherapy registry trial confirms the previously noted excellent cosmesis and toxicity profiles and fails to confirm retrospective claims analyses that have suggested higher rates of toxicity for brachytherapy-based APBI.     

The fitness training unit in U.S. Army basic combat training: physical fitness, training outcomes, and injuries

This study involved a retrospective examination of physical fitness, training outcomes, and injury rates among personnel in the Fitness Training Unit (FTU). Personnel were assigned to the FTU based on low performance on push-ups, sit-ups, and/or a 1-mile run (N = 44 men, 95 women) and received an augmented physical fitness program before basic combat training (BCT). They were compared with 712 men and 379 women who took the same test but were not assigned to the FTU and went directly to BCT. FTU and non-FTU personnel trained in the same battalions. Army Physical Fitness Test scores and BCT outcomes (discharged or completed BCT in 8 weeks) were obtained from unit training records. Injuries during BCT were documented from a review of the medical records. On entry to BCT, FTU women had similar 2-mile run times compared with non-FTU women (21.6 vs. 21.5 minutes, respectively; p = 0.86); FTU men were considerably slower on the 2-mile run than non-FTU men (20.3 vs. 17.3 minutes; p < 0.01). FTU women and non-FTU women had similar graduation success (60% vs. 68%, respectively; p = 0.14) and time-loss injury rates (1.3 vs. 1.4 people injured/100 person-days, respectively; p = 0.90). FTU men were less likely to graduate than non-FTU men (55% vs. 82%; p < 0.01) and more likely to suffer a time-loss injury (1.2 vs. 0.7 people injured/100 person-days; p < 0.01). Efforts should be directed toward providing a sufficient training stimulus to improve the aerobic fitness level of men (as well as women) in the FTU.     

Radiotherapy of glioblastoma: is shortening of the treatment time justifiable?]

Survival of glioblastoma patients can be double by postoperative radiation but nevertheless rarely exceeds one year. It is therefore desirable to minimize treatment time and hospitalisation. Aim of our study is to investigate the feasibility of a reduction of treatment time by accelerated fractionation. Out of 110 patients treated for glioblastoma from 1975 to 1988 in our institution postoperative radiation was performed in 79 patients using three different fractionation schedules: 60 Gy in six weeks, single fractions 2 Gy (n = 38), 35 Gy in two weeks, single fractions 3.5 Gy (n = 27), 45.5 Gy in 2.5 weeks, single fractions 3.5 Gy (n = 14). No statistically significant differences in both the mean overall and disease free survival were evaluated between the three groups. The larger fraction size was well tolerated and no relevant increase of early or late adverse reactions occurred. As the duration of treatment can be reduced from six to two weeks, this accelerated fractionation schedule seems to be a reasonable alternative to conventional fractionation.     

Postmastectomy Electron-Beam-Rotation Irradiation in Locally Advanced Breast Cancer

BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.     

Results of accelerated hyperfractionated radiotherapy in breast conserving therapy: a pilot study

We performed a pilot study to evaluate the safety, tolerability and clinical usefulness of accelerated hyperfractionated radiotherapy in patients treated with breast conserving therapy (BCT). The radiotherapy was consisted of 1.5 Gy per fraction twice daily to a total dose of 51 Gy to the whole breast with or without 9 Gy boost to the tumor bed in case of positive surgical margin. Thirty-seven patients were treated with accelerated hyperfractionated radiotherapy and 178 patients with conventional radiotherapy between September 1993 and December 1997. Acute or late skin toxicity of Grade 3 or more was not observed. One case of radiation pneumonitis requiring steroid therapy occurred in the conventional group. 8-year local-relapse-free survivals were 100% in accelerated group and 97.0% in conventional group (not significant: p = 0.59). The scores in quality of life at one year after the completion of radiation therapy were not different between the conventional and the accelerated group; symptomatic scores, global QOL scores, and scores by self-estimation for therapy. Admission charges in conventional and in accelerated group were not different, either. These data suggested that accelerated hyperfractionated radiotherapy in BCT was feasible and phase III study to compare conventional with the accelerated hyperfractionated radiotherapy should be planned to evaluate its clinical usefulness in BCT.     

Effektivität und Toxizität einer Re-Bestrahlung (Re-RT) bei metastatisch bedingter Rückenmarkkompression (MBRK)

BACKGROUND AND PURPOSE: Radiation myelopathy is a serious late toxicity after radiotherapy (RT) of metastatic spinal cord compression (MSCC). The risk of myelopathy depends on the equivalent dose in 2-Gy fractions (EQD2). Many radiation oncologists are concerned about spinal Re-RT, because it may result in a high cumulative EQD2. This study investigates effectiveness and feasibility of Re-RT for in-field recurrence of MSCC. PATIENTS AND METHODS: 74 patients, irradiated between 01/1995 and 12/2003 for MSCC, were reirradiated for in-field recurrence of MSCC (Table 1). Primary RT was performed with 1 x 8 Gy (n = 34), 5 x 4 Gy (n = 28), 10 x 3 Gy (n = 4), 15 x 2.5 Gy (n = 4), or 20 x 2 Gy (n = 4). Recurrence occurred after median 6 months (2-40 months). Re-RT was performed with 1 x 8 Gy (n = 35), 5 x 3 Gy (n = 16), 5 x 4 Gy (n = 13), 10 x 2 Gy (n = 4), 12 x 2 Gy (n = 3), or 17 x 1.8 Gy (n = 3). Cumulative EQD2 (alpha/beta = 2 Gy) was 39-40 Gy (n = 21), 49-50 Gy (n = 41), 56-60 Gy (n = 6), or > 60 Gy (n = 6). Follow-up after Re-RT was median 9 months (2-52 months). RESULTS: Re-RT led to an improvement of motor function in 29/74 patients (39%; Figures 1 to 3). On multivariate analysis, outcome was significantly influenced by type of primary tumor (p = 0.013) and by the time of developing motor deficits before Re-RT (p = 0.037), but not by radiation schedule (p = 0.560), by ambulatory status before Re-RT (p = 0.471), by cumulative EQD2 (p = 0.795), nor by the interval between primary RT and Re-RT (p = 0.420; Table 2). Radiation myelopathy was not observed in the whole series. CONCLUSION: Re-RT is an effective treatment for an in-field recurrence of MSCC. After a cumulative EQD2 < or = 50 Gy, radiation myelopathy appears unlikely.     

Radiation Induced Lung Reactions in Breast Cancer Therapy

BACKGROUND AND PURPOSE: Radiologic reactions in lung, usually subclinical, are a frequent side effect of radiotherapy for breast cancer. This study was initiated to identify effects of age and tamoxifen on radiation pneumonitis and consequent fibrosis. PATIENTS AND METHODS: Retrospectively, 451 patients irradiated postoperatively between 1992 and 1995 at the Department of Radiotherapy of Carl-Thiem-Klinikum (Cottbus, Germany) were analyzed. The median age was 58 years. After mastectomy (n = 296), 25 x 2.0 Gy were applied; breast-conserving surgery (n = 155) was followed by 30 x 2.0 Gy. In 221 patients, adjuvant tamoxifen was given. Follow-up included thorax radiography after 15 weeks and 1 year. In patients with reversible observations in standard chest radiography from 15 weeks to 1 year, CT or high-resolution (HR-)CT scans were analyzed after 4-7 years. RESULTS: Clinical symptoms of pneumonitis were seen in 25 patients (5.5%), all with radiologic changes. Early radiologic changes were detected in 134 patients (29.7%). Age (> 58 years; p = 0.0127) and tamoxifen (p = 0.0001) were found as significant parameters of early pneumopathy. Late radiologic changes were seen in 94/425 patients (22.1%), all after a positive early reaction (p = 0.001). CONCLUSION: A low incidence of clinically symptomatic pneumonitis was observed, while the vast majority of patients presented with early radiologic changes. Higher age and tamoxifen treatment significantly increased the incidence of early pneumopathy. Local fibrotic responses must be expected in all patients with early reactions, indicating a strong consequential component of the late reaction.