Gabriele Beckmann

The delineation of target volumes for radiotherapy of lung cancer patients.

PURPOSE Differences in the delineation of the gross target volume (GTV) and planning target volume (PTV) in patients with non-small-cell lung cancer are considerable. The focus of this work is on the analysis of observer-related reasons while controlling for other variables. METHODS In three consecutive patients, eighteen physicians from fourteen different departments delineated the GTV and PTV in CT-slices using a detailed instruction for target delineation. Differences in the volumes, the delineated anatomic lymph node compartments and differences in every delineated pixel of the contoured volumes in the CT-slices (pixel-by-pixel-analysis) were evaluated for different groups: ten radiation oncologists from ten departments (ROs), four haematologic oncologists and chest physicians from four departments (HOs) and five radiation oncologists from one department (RO1D). RESULTS Agreement (overlap > or = 70% of the contoured pixels) for the GTV and PTV delineation was found in 16.3% and 23.7% (ROs), 30.4% and 38.6% (HOs) and 32.8% and 35.9% (RO1D), respectively. CONCLUSION A large interobserver variability in the PTV and much more in the GTV delineation were observed in spite of a detailed instruction for delineation. The variability was smallest for group ROID where due to repeated discussions and uniform teaching a better agreement was achieved.

Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer

The purpose of this study was to determine the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HFRCB) combined with simultaneous chemotherapy with weekly cisplatin (CDDP) in locally advanced inoperable head and neck cancer.

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract

PURPOSE To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.

3-D conformal treatment of prostate cancer to 74 Gy vs. high-dose-rate brachytherapy boost: A cross-sectional quality-of-life survey

The effects of two modalities of dose-escalated radiotherapy on health-related quality of life (HRQOL) were compared. Forty-one consecutive patients were treated with a 3-D conformal (3-DC) boost to 74 Gy, and 43 with high-dose rate (HDR) brachytherapy boost (2×9 Gy), following 3-D conformal treatment to 46 Gy. Median age was 70 years in both groups, median initial PSA was 7.9 µg/l in 3-DC boost patients and 8.1 µg/l in HDR boost patients. Stage was ≤T2 in 66% and 67% and Gleason score was ≥7 in 52% and 47%, respectively. HRQOL was assessed cross-sectionally using EORTC QLQ-C30 and organ-specific PR25 modules 3 – 32 (median 19) and 4 – 25 (median 14) months after treatment, respectively. Questionnaires were completed by 93% and 97% of patients, respectively. Diarrhea and insomnia scores were significantly increased in both groups. In the PR25 module, scores of 3-DC boost and HDR boost patients for urinary, bowel and treatment-related symptoms were similar. Among responders, 34% of 3-DC boost patients and 86% of HDR boost patients had severe erectile problems. Dose escalation in prostate cancer by either 3-DC boost to 74 Gy or HDR brachytherapy boost appears to result in similar HRQOL profiles.

Palliative radiotherapy--new approaches.

Most cancer patients will require radiation therapy some time during their disease. Thirty percent to 50% of all radiation treatments are palliative, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life from local progressive disease. Radiotherapy is a locally effective tool. It typically causes no systemic and mostly mild acute side effects. We will provide an overview of principles, decision-making, and new developments in palliative radiation therapy.

Prospective evaluation of quality of life after permanent prostate brachytherapy with I-125: Importance of baseline symptoms and of prostate-V150

BACKGROUND AND PURPOSE Detailed knowledge of quality of life (QoL) after permanent I-125 brachytherapy may aid in counselling patients with early-stage prostate cancer. MATERIALS AND METHODS Seventy-four consecutive patients with low-risk prostate cancer were asked to complete the EORTC QLQ-C30 questionnaire with the prostate-specific PR25 module before implant, four weeks and one year after implant (response rates 97%, 88% and 89%, respectively). Implant characteristics were correlated with QoL scores. RESULTS Global QoL was stable from pre-treatment to one year after implant and similar to age-adjusted scores of healthy controls. Significant changes versus baseline in QLQ-C30 domains were worsened social function at four weeks, increased constipation at four weeks and at one year and improved emotional function at one year. PR25 urinary symptoms were significantly increased at four weeks and, despite some improvement, at one year; bowel symptoms were slightly increased. Both types of symptoms were most strongly related with pre-treatment symptom scores. Prostate-V150 was the only implant parameter significantly associated with both urinary and bowel symptoms at four weeks and one year. CONCLUSIONS Limiting the high-dose subvolume in the prostate may be beneficial to reduce urinary and bowel symptoms but the major determinant of symptoms after I-125 implant is the baseline symptom level.

Oral Vinorelbine and Cisplatin with Concomitant Radiotherapy in Stage III Non-Small Cell Lung Cancer (NSCLC): A Feasibility Study

Background: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. Patients and Methods: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m2). This was to be followed by 2 cycles of cisplatin/ vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. Results: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. Conclusion: Oral vinorelbine 50 mg/m2 (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy.

Radiotherapeutic Options for Symptom Control in Breast Cancer

The majority of breast cancer patients will require radiation therapy at some time during the course of their disease. An estimated 30–50% of all radiation treatments are of palliative nature, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life due to locally progressive disease. Radiotherapy is a locally effective tool, and typically causes no systemic and mostly mild acute side effects. The following article provides an overview of options and decision-making in palliative radiotherapy for symptom control.

Wo stehen wir bei der Behandlung des Nasopharynxkarzinoms

Ziel: Übersicht über die Entwicklung kombinierter Behandlungsstrategien beim Nasopharynxkarzinom. Ergebnisse: Die Strahlentherapie ist akzeptierte Standardtherapie bei der Behandlung des Nasopharynxkarzinoms. Es herrscht jedoch keineswegs Einigkeit über das optimale Therapieregime bezüglich Dosierung, Fraktionierung, Technik oder gar Einsatz von systemischer Chemotherapie. Die vergleichende Beurteilung neuerer Studien wird durch unterschiedliche Stagingsysteme und das Auftreten biologisch differenter Karzinome in der westlichen Hemisphäre und in Ostasien erschwert. Schlussfolgerungen aus älteren Publikationen, die vorwiegend retrospektive Analysen darstellen, sind aufgrund der Weiterentwicklung in Diagnostik und Therapie eingeschränkt bewertbar. Der gültige Standard bei lymphknotenpositiven Tumoren ist eine simultane Radiochemotherapie. Schlussfolgerungen: Um die Bedeutung der beiden Komponenten Strahlentherapie und Chemotherapie in der Behandlung der Nasopharynxkarzinome zu klären, müssen Patienten mit unterschiedlichen histologischen Subtypen nach einheitlichen Schemata behandelt werden. Nur so wird es möglich sein, stadiengerechte Behandlungskonzepte, die zudem die Tumorbiologie berücksichtigen, festzulegen.Aim: Review of the evolution of combined treatment strategies in nasopharyngeal carcinoma. Results: Radiotherapy is accepted standard for treatment of nasopharyngeal cancer. Nevertheless, there is no uniform opinion with regard to doses, fractionation, technique or use of systemic chemotherapy. It is hardly possible to compare the results of recent and historical trials because of different staging systems and because nasopharyngeal cancer occurring in the Oceano-Asian region are biologically different to those in Western countries. Conclusions drawn from former, mostly retrospective analyses are not applicable to newer standards regarding the developments in diagnostics and therapy. Presently simultaneous chemoradiotherapy is standard for lymphnode positive nasopharyngeal cancer. Conclusions: It will be necessary to treat patients with different histologic subtypes with an uniform treatment schedule to define the place of combined modality treatment. This will probably be the only way to develop treatment concepts for distinct stages and biological entities.

Wo stehen wir bei der Behandlung des Nasopharynxkarzinoms?@@@Present Status of Treatment in Nasopharyngeal Carcinoma?

Ziel: Übersicht über die Entwicklung kombinierter Behandlungsstrategien beim Nasopharynxkarzinom. Ergebnisse: Die Strahlentherapie ist akzeptierte Standardtherapie bei der Behandlung des Nasopharynxkarzinoms. Es herrscht jedoch keineswegs Einigkeit über das optimale Therapieregime bezüglich Dosierung, Fraktionierung, Technik oder gar Einsatz von systemischer Chemotherapie. Die vergleichende Beurteilung neuerer Studien wird durch unterschiedliche Stagingsysteme und das Auftreten biologisch differenter Karzinome in der westlichen Hemisphäre und in Ostasien erschwert. Schlussfolgerungen aus älteren Publikationen, die vorwiegend retrospektive Analysen darstellen, sind aufgrund der Weiterentwicklung in Diagnostik und Therapie eingeschränkt bewertbar. Der gültige Standard bei lymphknotenpositiven Tumoren ist eine simultane Radiochemotherapie. Schlussfolgerungen: Um die Bedeutung der beiden Komponenten Strahlentherapie und Chemotherapie in der Behandlung der Nasopharynxkarzinome zu klären, müssen Patienten mit unterschiedlichen histologischen Subtypen nach einheitlichen Schemata behandelt werden. Nur so wird es möglich sein, stadiengerechte Behandlungskonzepte, die zudem die Tumorbiologie berücksichtigen, festzulegen.Aim: Review of the evolution of combined treatment strategies in nasopharyngeal carcinoma. Results: Radiotherapy is accepted standard for treatment of nasopharyngeal cancer. Nevertheless, there is no uniform opinion with regard to doses, fractionation, technique or use of systemic chemotherapy. It is hardly possible to compare the results of recent and historical trials because of different staging systems and because nasopharyngeal cancer occurring in the Oceano-Asian region are biologically different to those in Western countries. Conclusions drawn from former, mostly retrospective analyses are not applicable to newer standards regarding the developments in diagnostics and therapy. Presently simultaneous chemoradiotherapy is standard for lymphnode positive nasopharyngeal cancer. Conclusions: It will be necessary to treat patients with different histologic subtypes with an uniform treatment schedule to define the place of combined modality treatment. This will probably be the only way to develop treatment concepts for distinct stages and biological entities.