Vratislav Strnad

Phase III Randomized Trial of Amifostine as a Radioprotector in Head and Neck Cancer

PURPOSE Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients. PATIENTS AND METHODS Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade > or =2 acute xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point. RESULTS Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51% (P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.

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.

GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas.

Both primary and recurrent squamous cell carcinoma of the head and neck are classic indications for brachytherapy. A high rate of local tumor control at the cost of limited morbidity can be achieved with brachytherapy through good patient selection, meticulous source implantation and careful treatment planning. However, no randomized trials have been performed, and there is scant evidence in the literature especially regarding practical clinical recommendations for brachytherapy for head and neck subsites. The Head and Neck Working Group of the European Brachytherapy Group (Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) therefore decided to formulate the present consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy. The use of brachytherapy in combination with external beam radiotherapy and/or surgery is also covered as well as the use of brachytherapy in previously irradiated patients. Given the paucity of evidence in the literature, these recommendations are mainly based on clinical experience accumulated by the members of the working group over several decades and the respective publications. The recommendations cover in a general part (1) patient selection, the pre-treatment work up and patient care, (2) treatment strategy, (3) target definition, (4) implant techniques, (5) dose and dose rate prescription, (6) treatment planning and reporting, (7) treatment monitoring (8) catheter removal, and (9) post-treatment patient care and follow-up. The recommendations are then specified for the classical brachytherapy tumor sites following an analogue more focussed structure (patient selection, implant technique, target definition, dose and dose rate prescription, results): lip, oral mucosa, mobile tongue, floor of mouth, oropharynx, nasopharynx, paranasal sinuses.

Accelerated Partial Breast Irradiation: 5-Year Results of the German-Austrian Multicenter Phase II Trial Using Interstitial Multicatheter Brachytherapy Alone After Breast-Conserving Surgery

PURPOSE To evaluate the impact of accelerated partial breast irradiation on local control, side effects, and cosmesis using multicatheter interstitial brachytherapy as the sole method for the adjuvant local treatment of patients with low-risk breast cancer. METHODS AND MATERIALS 274 patients with low-risk breast cancer were treated on protocol. Patients were eligible for the study if the tumor size was < 3 cm, resection margins were clear by at least 2 mm, no lymph node metastases existed, age was >35 years, hormone receptors were positive, and histologic grades were 1 or 2. Of the 274 patients, 175 (64%) received pulse-dose-rate brachytherapy (D(ref) = 50 Gy). and 99 (36%) received high-dose-rate brachytherapy (D(ref) = 32.0 Gy). RESULTS Median follow-up was 63 months (range, 9-103). Only 8 of 274 (2.9%) patients developed an ipsilateral in-breast tumor recurrence at the time of analysis. The 5-year actuarial local recurrence-free survival probability was 98%. The 5- year overall and disease-free survival probabilities of all patients were 97% and 96%, respectively. Contralateral in-breast malignancies were detected in 2 of 274 (0.7%) patients, and distant metastases occurred in 6 of 274 (2.2%). Late side effects ≥ Grade 3 (i.e., breast tissue fibrosis and telangiectasia) occurred in 1 patient (0.4%, 95%CI:0.0-2.0%) and 6 patients (2.2%, 95%CI:0.8-4.7%), respectively. Cosmetic results were good to excellent in 245 of 274 patients (90%). CONCLUSIONS The long-term results of this prospective Phase II trial confirm that the efficacy of accelerated partial breast irradiation using multicatheter brachytherapy is comparable with that of whole breast irradiation and that late side effects are negligible.

Accelerated partial breast irradiation with iridium-192 multicatheter PDR/HDR brachytherapy: Preliminary results of the German-Austrian multicenter trial

Purpose:To evaluate perioperative morbidity, toxicity, and cosmetic outcome in patients treated with interstitial brachytherapy to the tumor bed as the sole irradiation modality after breast-conserving surgery.Patients and Methods:From November 1, 2000 to January 31, 2004, 176 women with early-stage breast cancer became partakers in a protocol of tumor bed irradiation alone using pulsed-dose-rate (PDR) or high-dose-rate (HDR) interstitial multicatheter implants. Patients became eligible, if their tumor was an infiltrating carcinoma ≤ 3 cm in diameter, the surgical margins were clear by at least 2 mm, the axilla was surgically staged node-negative, the tumor was estrogen and/or progesterone receptor-positive, well or moderately differentiated (G1/2), the tumor did not contain an extensive intraductal component (EIC) and the patient’s age was > 35 years. Implants were positioned using a template guide, delivering either 49.8 Gy in 83 consecutive hours (PDR) or 32.0 Gy in two daily fractions over 4 days (HDR). Perioperative morbidity, toxicity, and cosmetic outcome were assessed. Interim findings of the first 69 patients, who were treated in this multicenter trial, after a median follow-up of 24 months (range, 15–39 months) are presented.Results:One of the 69 patients (1.4%) developed a bacterial infection of the implant. No other perioperative complications, for example bleeding or hematoma, were observed. Acute toxicity was low: 2.9% of the patients (2/69) experienced mild radiodermatitis. Late toxicity: hypersensation/mild pain 7.2% (5/69), intermittent but tolerable pain 1.4% (1/69), mild dyspigmentation 10.1% (7/69), mild fibrosis 11.6% (8/69), moderate fibrosis 1.4% (1/69), mild telangiectasia (< 1 cm2) 11.6% (8/69), and moderate teleangiectasia (1–4 cm2) 1.4% (1/69). Good to excellent cosmetic results were observed in 92.4% of the patients evaluated. All patients (n = 176) remained disease-free to the date of evaluation.Conclusion:This analysis indicates that accelerated partial breast irradiation with iridium-192 interstitial multicatheter PDR/HDR implants is feasible with low perioperative morbidity, low acute and mild late toxicity, and does not significantly affect cosmetic results at a median follow-up of 24 months.Ziel:Evaluierung von perioperativer Morbidität, Akut- und Spättoxizität sowie des kosmetischen Ergebnisses nach alleiniger interstitieller Pulsed-Dose-Rate-(PDR-)/High-Dose-Rate-(HDR-)Multikatheter-Brachytherapie des Tumorbetts mit 192-Iridium nach brusterhaltender Operation.Patienten und Methodik:Zwischen 11/2000 und 01/2004 erhielten 176 Frauen nach brusterhaltender Operation eine alleinige PDR-/HDR-Brachytherapie des Tumorbetts. Einschlusskriterien in diesem multizentrischen Protokoll waren u. a. ein maximaler Tumordurchmesser von 3 cm, ein negativer Nodalstatus (pN0), eine R0-Resektion mit mindestens 2 mm Sicherheitssaum, nur gut oder mäßig differenzierte Karzinome (G1/2), östrogen- und/oder progesteronrezeptorpositive Tumoren, kein Nachweis einer EIC („extensive intraductal component“) und ein Patientinnenalter von mindestens 35 Jahren. Die PDR-Brachytherapie wurde mit 49,8 Gy in 83 aufeinander folgenden stündlichen Pulsen, die HDR-Brachytherapie bis 32,0 Gy in zwei täglichen Fraktionen über 4 Tage appliziert. Ergebnisse der ersten 69 Patientinnen bezüglich Morbidität, Toxizität und Kosmetik werden präsentiert. Die mediane Nachbeobachtungszeit betrug in dieser Analyse 24 Monate (Bereich: 15–39 Monate).Ergebnisse:Eine der evaluierten 69 Patientinnen (1,4%) entwickelte eine bakterielle Infektion des Implantats. Weitere perioperative Komplikationen, z. B. Blutungen oder Hämatome, wurden nicht beobachtet. Die Akuttoxizität war gering: 2,9% der Patientinnen (2/69) zeigten die Symptome einer Grad-1-Radiodermatitis. Spättoxizität: Überempfindlichkeit/gelegentliches Stechen im Narbenareal 7,2% (5/69), intermittierende, aber tolerable Schmerzen 1,4% (1/69), milde Dyspigmentation 10,1% (7/69), milde Fibrosierung 11,6% (8/69), moderate Fibrosierung 1,4% (1/69), milde Teleangiektasiebildung (< 1 cm2) 11,6% (8/69) und moderate Teleangiektasiebildung (1–4 cm2) 1,4% (1/69). Ein exzellentes oder gutes kosmetisches Ergebnis wurde bei 92,4% der Patientinnen gefunden. Zum Zeitpunkt der Auswertung waren alle behandelten Patientinnen (n = 176) krankheitsfrei.Schlussfolgerung:Diese Analyse zeigt, dass die alleinige interstitielle PDR-/HDR-Multikatheter-Brachytherapie des Tumorbetts nach brusterhaltender Operation mit niedriger perioperativer Komplikationsrate, geringer Akuttoxizität und milder Spättoxizität bei einer medianen Nachbeobachtungszeit von 24 Monaten durchführbar ist und das kosmetische Ergebnis bislang nicht signifikant beeinflusst.

Protective effect of amifostine on dental health after radiotherapy of the head and neck

PURPOSE The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia. METHODS AND MATERIALS The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine. RESULTS Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0. 015, two-tailed Fisher exact test). CONCLUSION Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.

The role of pulsed-dose-rate brachytherapy in previously irradiated head-and-neck cancer ☆

PURPOSE The purpose of this prospective study was to analyze the value of interstitial pulsed-dose-rate (PDR) brachytherapy (iBT) with regard to local control and the incidence of side effects in patients with head-and-neck cancer in a previously irradiated area. METHODS AND MATERIALS From October 1997 to September 2001, 43 patients with head-and-neck cancer in a previously irradiated area (31 patients with recurrent cancer) were treated with iBT alone or in combination with external beam radiation. Thirty-four of 43 patients received interstitial PDR brachytherapy (DREF=20-60 Gy) as part of their curative treatment regimen alone or in combination with external radiation. Nine patients were implanted for palliative purposes. The pulses were delivered 24 h/day with a time interval of 1 h between two pulses. The dose per pulse (dp) ranged from 0.4-0.7 Gy. Sixteen of 43 (37%) patients also received cisplatin or carboplatin with 5-fluorouracil during the time of the iBT. Additionally 20/43 (47%) patients were treated with interstitial hyperthermia. Thirteen of 43 (30%) patients received external beam radiation in a dose range from 20-67 Gy. A follow-up of all patients was done to analyze local control and survival, and acute and delayed toxicity. This analysis was performed after a median follow-up of 24 months (6-48 months). RESULTS Local tumor control was achieved in 34 of a total of 43 patients (79%) and in 30/34 patients (88%) treated for curative intention. Distant metastases were observed in 5/43 (12%) patients. The 2-year local recurrence-free survival rates, disease-free survival rates, and overall survival rates according to the Kaplan-Meier method for all patients were 68%, 62%, and 49%, respectively, and for patients treated with curative intention they were 80%, 77% and 66%, respectively. There was no statistical difference in the probability of local recurrence in patients subgrouped by recurrent tumor vs. secondary primary, tumor size, grading and lymphangiosis. The application of chemotherapy or hyperthermia did not have significant influence on the therapy results. Soft tissue necrosis was the only serious side effect seen in 2/43 patients (4.7%). No other serious side effects were observed. CONCLUSIONS Interstitial pulsed-dose-rate brachytherapy for patients with previously irradiated head-and-neck cancer is an effective therapy with minimal toxicity. The role of chemotherapy and hyperthermia in these patients remains unclear. Further randomized studies with larger patient numbers are necessary to draw a definite conclusion.

Interstitial Brachytherapy with Ir-192 Low-Dose-Rate in the Treatment of Primary and Recurrent Cancer the Oral Cavity and Oropharynx

Aim: To evaluate the impact of postoperative interstitial brachytherapy with and without external radiotherapy in the treatment of primary and recurrent squamous cell carcinoma of the oral cavity and oropharynx. Patients and Methods: Between 1985 and 1997, a total of 318 patients were treated by interstitial Ir-192 low-dose-rate brachytherapy as part of their primary (n = 236) or recurrent treatment (n = 82). There were 263 male (83%) and 55 (17%) female patients. The distribution of UICC (1997) stages was as follows: I (61 patients, 19%), II (71 patients, 22%), III (58 patients, 18%), IV (128 patients, 40%). The primary tumor site was located in the oral cavity in 201 patients (63%), in the oropharynx in 86 patients (27%), lower lip in 19 patients (6%) and other regions in twelve cases (4%). Treatment concepts did not vary over the time and were dictated by the initial tumor extension: a total of 175 patients (55%) received a combination of surgery, interstitial brachytherapy (23–25 Gy) and external radiotherapy (50–60 Gy), 60 patients (19%) surgery and interstitial brachytherapy (45–55 Gy) alone. Advanced disease not amenable to primary surgery was either treated by radiochemotherapy and interstitial brachytherapy in 39 patients (12%) or a combination of interstitial brachytherapy, external radiotherapy and interstitial hyperthermia in 44 patients (14%). Results: Overall survival rates following primary and recurrent treatment were 50 ± 4% and 29 ± 5%, respectively, at 5 years (p < 0.0001). A significant impact on overall survival rate was noted for UICC stage: patients in stage I/II had survival rates of 64 ± 5% and 57 ± 10%, respectively, while patients in stage III/IV had survival rates of 39 ± 5% and 15 ± 5%, respectively, at 5 years (p < 0.0001). In addition, grading (p = 0.01) and hemoglobin levels (p = 0.05) had a significant influence on overall survival. Local tumor control rates for all patients were 74 ± 3% and 57 ± 7% at 5 years following primary and recurrent treatment (p = 0.01), respectively. The 145 patients treated for primary disease by a uniform concept of surgery, interstitial brachytherapy and external radiotherapy achieved excellent local control rates with 92 ± 4% (stage I/II) and 65 ± 6% (stage III/IV) at 5 years. Late treatment-related toxicity with soft tissue necrosis and/or osteonecrosis requiring mandibular resection was 7.5%. Conclusion: Local tumor excision followed by postoperative interstitial brachytherapy with and without external radiotherapy is associated with excellent locoregional control, a low risk of chronic sequelae and may therefore considered as a new approach avoiding mutilating radical surgery.Zielsetzung: Es sollte der Einfluss der postoperativen interstitiellen Brachytherapie mit und ohne externe Radiotherapie in der Behandlung von primären und rezidivierten Plattenepithelkarzinomen der Mundhöhle und des Oropharynx untersucht werden. Patienten und Methoden: Zwischen 1985 und 1997 wurden insgesamt 318 Patienten mit einer interstitiellen Iridium-192-low-dose-rate-Brachytherapie als Teil der Primärbehandlung (n = 236) oder der Rezidivbehandlung (n = 82) therapiert. Es waren 263 Männer (83%) und 55 Frauen (17%). Die Verteilung der UICC-Stadien (1997) war wie folgt: I (61 Patienten, 19%), II (71 Patienten, 22%), III (58 Patienten, 18%), IV (128 Patienten, 40%). Die primäre Tumorregion betraf die Mundhöhle bei 201 Patienten (63%), den Oropharynx bei weiteren 86 Patienten (27%), die Unterlippe bei 19 Patienten (6%) und andere Regionen in 12 Fällen (4%). Das Behandlungskonzept wurde völlig unverändert über die Jahre beibehalten und richtete sich nach der initialen Tumorausdehnung: Insgesamt 175 Patienten (55%) erhielten eine Kombination aus primär enoraler Chirurgie, interstitieller Brachytherapie (23–25 Gy) und einer externen Bestrahlung (50–60 Gy), 60 Patienten (19%) erhielten nach einer enoralen Resektion ausschließlich eine interstitielle Brachytherapie (45–55 Gy). Fortgeschrittene Karzinome, die für eine primär chirurgische Intervention ungeeignet waren, wurden entweder einer initialen Radiochemotherapie und anschließender Brachytherapie in 39 Fällen (12%) oder einer Kombination aus interstitieller Brachytherapie, externer Radiotherapie und interstitieller Hyperthermie bei 44 Patienten (14%) zugeführt. Ergebnisse: Die Gesamtüberlebensrate nach Primär- und Rezidivtherapie betrug 50 ± 4% und 29 ± 5% nach 5 Jahren (p < 0,0001). Das UICC-Stadium hatte einen signifikanten Einfluss auf die Gesamtüberlebensrate: Patienten in den Stadien I und II wiesen Überlebensraten von 64 ± 5% und 57 ± 10% auf, während Patienten in den fortgeschrittenen Stadien III und IV lediglich Überlebensraten von 39 ± 5% und 15 ± 5% hatten (p < 0,0001). Zusätzlich hatten das Grading (p = 0,01) und der Hb-Wert (p = 0,05) einen signifikanten Einfluss auf das Überleben. Die lokale Tumorkontrollrate fülr alle 318 Patienten betrug 74 ± 3% und 57 ± 7% nach 5 Jahren für die Primär- bzw. die Rezidivbehandlung (p = 0,01). Die 145 Patienten, welche primär durch enorale Chirurgie, interstitielle Brachytherapie und externe Radiotherapie behandelt wurden, erzielten exzellente lokale Tumorkontrollraten on 92 ± 4% in den Stadien I und II und 65 ± 6% in den Stadien III und IV nach 5 Jahren. Die Rate an Spätnebenwirkungen einschließlich Weichteilnekrosen und/oder Osteonekrosen betrug 7,5%. Schlussfolgerung: Die lokale Tumorexzision gefolgt von postoperativer interstitieller Brachytherapie mit oder ohne externe Bestrahlung führte zu ausgezeichneter lokaler Tumorkontrolle mit einem sehr niedrigen Risiko chronischer Spätfolgen und wird daher als sinnvolles Konzept zur Vermeidung einer funktionseinschränkenden radikalen Chirurgie empfohlen.

Accelerated Partial Breast Irradiation with Iridium-192 Multicatheter PDR/HDR Brachytherapy

Purpose:To evaluate perioperative morbidity, toxicity, and cosmetic outcome in patients treated with interstitial brachytherapy to the tumor bed as the sole irradiation modality after breast-conserving surgery.Patients and Methods:From November 1, 2000 to January 31, 2004, 176 women with early-stage breast cancer became partakers in a protocol of tumor bed irradiation alone using pulsed-dose-rate (PDR) or high-dose-rate (HDR) interstitial multicatheter implants. Patients became eligible, if their tumor was an infiltrating carcinoma ≤ 3 cm in diameter, the surgical margins were clear by at least 2 mm, the axilla was surgically staged node-negative, the tumor was estrogen and/or progesterone receptor-positive, well or moderately differentiated (G1/2), the tumor did not contain an extensive intraductal component (EIC) and the patient’s age was > 35 years. Implants were positioned using a template guide, delivering either 49.8 Gy in 83 consecutive hours (PDR) or 32.0 Gy in two daily fractions over 4 days (HDR). Perioperative morbidity, toxicity, and cosmetic outcome were assessed. Interim findings of the first 69 patients, who were treated in this multicenter trial, after a median follow-up of 24 months (range, 15–39 months) are presented.Results:One of the 69 patients (1.4%) developed a bacterial infection of the implant. No other perioperative complications, for example bleeding or hematoma, were observed. Acute toxicity was low: 2.9% of the patients (2/69) experienced mild radiodermatitis. Late toxicity: hypersensation/mild pain 7.2% (5/69), intermittent but tolerable pain 1.4% (1/69), mild dyspigmentation 10.1% (7/69), mild fibrosis 11.6% (8/69), moderate fibrosis 1.4% (1/69), mild telangiectasia (< 1 cm2) 11.6% (8/69), and moderate teleangiectasia (1–4 cm2) 1.4% (1/69). Good to excellent cosmetic results were observed in 92.4% of the patients evaluated. All patients (n = 176) remained disease-free to the date of evaluation.Conclusion:This analysis indicates that accelerated partial breast irradiation with iridium-192 interstitial multicatheter PDR/HDR implants is feasible with low perioperative morbidity, low acute and mild late toxicity, and does not significantly affect cosmetic results at a median follow-up of 24 months.Ziel:Evaluierung von perioperativer Morbidität, Akut- und Spättoxizität sowie des kosmetischen Ergebnisses nach alleiniger interstitieller Pulsed-Dose-Rate-(PDR-)/High-Dose-Rate-(HDR-)Multikatheter-Brachytherapie des Tumorbetts mit 192-Iridium nach brusterhaltender Operation.Patienten und Methodik:Zwischen 11/2000 und 01/2004 erhielten 176 Frauen nach brusterhaltender Operation eine alleinige PDR-/HDR-Brachytherapie des Tumorbetts. Einschlusskriterien in diesem multizentrischen Protokoll waren u. a. ein maximaler Tumordurchmesser von 3 cm, ein negativer Nodalstatus (pN0), eine R0-Resektion mit mindestens 2 mm Sicherheitssaum, nur gut oder mäßig differenzierte Karzinome (G1/2), östrogen- und/oder progesteronrezeptorpositive Tumoren, kein Nachweis einer EIC („extensive intraductal component“) und ein Patientinnenalter von mindestens 35 Jahren. Die PDR-Brachytherapie wurde mit 49,8 Gy in 83 aufeinander folgenden stündlichen Pulsen, die HDR-Brachytherapie bis 32,0 Gy in zwei täglichen Fraktionen über 4 Tage appliziert. Ergebnisse der ersten 69 Patientinnen bezüglich Morbidität, Toxizität und Kosmetik werden präsentiert. Die mediane Nachbeobachtungszeit betrug in dieser Analyse 24 Monate (Bereich: 15–39 Monate).Ergebnisse:Eine der evaluierten 69 Patientinnen (1,4%) entwickelte eine bakterielle Infektion des Implantats. Weitere perioperative Komplikationen, z. B. Blutungen oder Hämatome, wurden nicht beobachtet. Die Akuttoxizität war gering: 2,9% der Patientinnen (2/69) zeigten die Symptome einer Grad-1-Radiodermatitis. Spättoxizität: Überempfindlichkeit/gelegentliches Stechen im Narbenareal 7,2% (5/69), intermittierende, aber tolerable Schmerzen 1,4% (1/69), milde Dyspigmentation 10,1% (7/69), milde Fibrosierung 11,6% (8/69), moderate Fibrosierung 1,4% (1/69), milde Teleangiektasiebildung (< 1 cm2) 11,6% (8/69) und moderate Teleangiektasiebildung (1–4 cm2) 1,4% (1/69). Ein exzellentes oder gutes kosmetisches Ergebnis wurde bei 92,4% der Patientinnen gefunden. Zum Zeitpunkt der Auswertung waren alle behandelten Patientinnen (n = 176) krankheitsfrei.Schlussfolgerung:Diese Analyse zeigt, dass die alleinige interstitielle PDR-/HDR-Multikatheter-Brachytherapie des Tumorbetts nach brusterhaltender Operation mit niedriger perioperativer Komplikationsrate, geringer Akuttoxizität und milder Spättoxizität bei einer medianen Nachbeobachtungszeit von 24 Monaten durchführbar ist und das kosmetische Ergebnis bislang nicht signifikant beeinflusst.

Fat Necrosis after Conserving Surgery and Interstitial Brachytherapy and/or External-Beam Irradiation in Women with Breast Cancer

Purpose:To investigate the incidence of fat necrosis, breast tissue fibrosis and breast pain after conserving surgery and accelerated partial-breast irradiation (APBI, group A), whole-breast external-beam irradiation (EBRT, group B), or EBRT combined with an interstitial boost (EBIB, group C) in women with breast cancer.Patients and Methods:85 patients who received breast-conserving therapy from 02/2000 to 03/2002 were analyzed. 30 patients received EBRT, 33 patients APBI, and 22 patients EBIB. Median follow-up was 35.5, 35.0, and 37.5 months, respectively. Fat necrosis was detected and rated by mammograms, fibrosis and pain were clinically rated with the LENT-SOMA scores.Results:The incidence of fat necrosis was 15.3% for all patients; and 15.2%, 20.0%, and 9.0% for groups A, B, and C, respectively. The 3-year fat necrosis-free survival probability was 83%, 76%, and 95% (difference not significant). The mean time to first diagnosis of fat necrosis was 25.6, 26.2, and 26.0 months. No patient needed surgical intervention because of fat necrosis-related pain. Fibrosis was present in 27.3%, 63.3%, and 77.3% (p < 0.001), breast pain in 9.0%, 33.4%, and 18.1% (p < 0.05).Conclusion:Asymptomatic fat necrosis is a common finding after both percutaneous and interstitial irradiation after breast-conserving surgery. This analysis did not support the hypothesis that APBI with multicatheter implants leads to higher rates of fat necrosis, fibrosis, or pain.Ziel:Untersuchung und Vergleich der Inzidenz und des Schweregrades des Auftretens von Fettnekrosen, Fibrosierung und Brustschmerz nach brusterhaltender Operation und akzelerierter Teilbrustbestrahlung (Gruppe A), externer Ganzbrustbestrahlung (Gruppe B) sowie externer Ganzbrustbestrahlung mit interstitiellem Brachytherapie-Boost (Gruppe C) bei Frauen mit einem Mammakarzinom.Patienten und Methodik:Die Auswertung umfasst 85 Patientinnen, die zwischen 02/2000 und 03/2002 brusterhaltend therapiert wurden. Davon erhielten 30 Patientinnen eine externe Ganzbrustbestrahlung, 33 Patientinnen eine Teilbrustbestrahlung und 22 Patientinnen eine kombinierte externe und interstitielle Bestrahlung. Die mediane Nachbeobachtungszeit betrug 35,5, 35,0 und 37,5 Monate. Der Endpunkt Fettnekrose wurde mittels Mammographien evaluiert, die Endpunkte Fibrosierung und Brustschmerz wurden klinisch mit den LENT-SOMA-Scores klassifiziert.Ergebnisse:Bei 15,3% aller Patientinnen wurden Fettnekrosen gefunden, in den Gruppen A, B und C bei 15,2%, 20,0% and 9,0% der Fälle. Das fettnekrosenfreie 3-Jahres-Überleben betrug 83%, 76% und 95% (Unterschied nicht signifikant). Die mittlere Zeit bis zum Auftreten der Fettnekrosen betrug 25,6, 26,2 und 26,0 Monate. Fibrosierung wurde bei 27,3%, 63,3% und 77,3% der Fälle (p < 0,001) getastet, Brustschmerz wurde von 9,0%, 33,4% und 18,1% (p < 0,05) der Patientinnen angegeben.Schlussfolgerung:Asymptomatische Fettnekrosen wurden nach brusterhaltender Operation nach externer sowie interstitieller adjuvanter Brustbestrahlung gefunden. Die Hypothese, dass eine Teilbrustbestrahlung mit interstitieller Brachytherapie zu höheren Raten von Fettnekrosen, Fibrosierung und Brustschmerz führt, wird durch die Ergebnisse der vorliegenden Studie nicht gestützt.