Susanne Staar

Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy—results of a multicentric randomized German trial in advanced head-and-neck cancer

PURPOSE To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC). METHODS AND MATERIALS Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors). RESULTS This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072). CONCLUSION With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.

Risk analysis of linear accelerator radiosurgery.

PURPOSE To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Surgical treatment for hypopharynx carcinoma : feasibility, mortality, and results

This study seeks to evaluate treatment modalities, mortality after surgery, survival, and local control rates for a consecutive cohort of patients with cancer of the hypopharynx treated according to a prospective protocol that favors surgery as an initial approach to the disease. The charts of 228 consecutive patients with previously untreated hypopharyngeal squamous cell carcinoma were reviewed. Outcome measures (overall survival, disease specific survival, and local control) were calculated using the Kaplan-Meier estimator. Of 228 consecutive patients, 136 (59.6%) were found suitable for initial surgical treatment. Of the remaining 92 patients, 18 (7.9%) had nonresectable lymph node metastases, 16 (7.0%) had unresectable primary tumors, 13 (5.7%) refused surgery, and 13 (5.7%) presented distant metastases during initial diagnostic evaluation. Of those who had surgery, 46 had larynx-sparing procedures, 54 had total laryngectomy, and 36 had total laryngo-pharyngectomy. None of the patients who had surgery died postoperatively. Actuarial 5-year overall survival was 27.2% for all 228 patients, 39.5% for the 136 patients with surgical treatment, and 61.1% for the 46 patients who were treated with larynx-sparing procedures.

Linear accelerator radiosurgery for recurrent malignant tumors of the skull base

The efficacy of linear accelerator-based radiosurgery for patients who have preirradiated recurrent nasopharyngeal carcinomas and unresectable recurrent sarcomas invading the base of skull was assessed. Thirteen patients were treated: 8 patients had carcinomas arising from the nasopharynx (lymphoepithelioma, 4; squamous cell carcinoma, 2; adenoid-cystic, 2); 5 patients had sarcomas (rhabdomyosarcoma, 1; chordoma, 1; chondrosarcoma, 1; hemangiopericytoma, 2). All patients had had repeated tumor resections or irradiation, hindering any further conventional fractionated radiotherapy or surgery. Convergent-beam irradiation was performed with a modified linear accelerator (8-MeV photons). Because of irregular tumor configuration, multiple (up to seven) isocenters had to be used in 10 of 13 patients to match the target volume with the reference isodose (60%-80%). Each isocenter was irradiated with 6 to 10 arcs. The median planning target volume was 33 mL (4-128 mL) and the median dose was 15 Gy (9-24 Gy). Median survival time was 9 months in 8 patients who had recurrent nasopharyngeal carcinomas. Three patients who had complete or partial tumor remission survived 1.5 to 3.5 years. All of the sarcoma patients responded to radiosurgery. After a follow-up of 28 to 67 months, 4 of 5 patients are alive. This investigation demonstrates that radiosurgery is an effective tool in palliative treatment for patients who have recurrent, extensively pretreated nasopharyngeal cancer. Patients who have recurrent sarcomas of the base of skull may be treated for long-term palliation or even for cure.

Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma

Background: To evaluate the efficacy of multimodality therapy in patients with esthesioneuroblastoma (ENB). Patients and Methods: From 01/1979 through 08/2001, 47 patients with ENB (20 men, 27 women, age 5–81 years), were registered from 18 oncologic centers. There were 14 tumors stage B and 33 stage C according to the Kadish classification. Initial treatment included surgery alone in seven patients, radiotherapy (RT) with or without chemotherapy (CTX) in twelve, surgery plus postoperative RT in 15, and multimodality therapy (surgery plus pre- or postoperative CTX plus postoperative RT) in 13. Results: The 5-year overall survival (OS) for the whole group was 64 ± 8% and the 5-year event-free survival (EFS) 50 ± 8%. Patients with multimodality treatment had a significantly better 5-year EFS (74 ± 13%) compared to the other patients (41 ± 9%; p = 0.05), while the 5-year OS was not significantly different between the treatment groups (p = 0.39). For patients with Kadish stage C, multimodality therapy (n = 11) resulted in superior 5-year EFS (72 ± 14% vs 17 ± 9%; p = 0.01). These patients tended to have an improved OS (69 ± 15% vs 47 ± 12%; p = 0.19) compared to the other treatment groups. None of the patients with multimodality treatment had a metastatic relapse. Conclusion: Multimodality treatment (surgery plus pre- or postoperative CTX plus postoperative RT) appears to be highly efficient in preventing local and systemic relapse in patients with advanced ENB. Timing and optimal agents of CTX need to be further evaluated.Hintergrund: Der Stellenwert multimodaler Therapieansätze in der Behandlung von Ästhesioneuroblastomen (ENB) soll untersucht werden. Patienten und Methodik: Analysiert wurden 47 Patienten (20 Männer, 27 Frauen; Alter: 5–81 Jahre), die im Zeitraum 01/1979–08/2001 aufgrund eines ENB in 18 onkologischen Zentren behandelt worden waren (Tabelle 1). Die Stadieneinteilung nach Kadish entsprach 14 Patienten im Stadium B und 33 Patienten im Stadium C. Im Rahmen der Primärtherapie wurden sieben Patienten nur operiert, zwölf erhielten eine definitive Radiotherapie (RT) ± Chemotherapie (CTX), 15 wurden operiert und postoperativ bestrahlt und 13 erhielten eine multimodale Therapie (Operation plus prä-/postoperative CTX plus postoperative RT). Ergebnisse: Das 5-Jahres-Gesamtüberleben (OS) aller Patienten betrug 64 ± 8% und das ereignisfreie 5-Jahres-Überleben (EFS) 50 ± 8% (Abbildung 1). Patienten mit multimodaler Therapie hatten ein signifikant verbessertes 5-Jahres-EFS (74 ± 13%) im Vergleich zu den anderen Therapiegruppen (41 ± 9%; p = 0,05; Abbildung 2), allerdings zeigte sich kein signifikanter Unterschied im 5-Jahres-OS (p = 0,39). In der Gruppe der Patienten im Stadium C nach Kadish erzielte die multimodale Therapie (n = 11) ein statistisch signifikant verbessertes 5-Jahres-EFS (72 ± 14% vs. 17 ± 9%; p = 0,01; Abbildung 3) und tendenziell auch ein verbessertes OS (69 ± 15% vs. 47 ± 12%; p = 0,19). Keiner der Patienten mit multimodaler Therapie entwickelte Metastasen. Schlussfolgerung: Multimodale Therapieansätze unter Einschluss von Operation plus prä-/postoperativer CTX plus postoperativer RT erscheinen hocheffektiv in der Verhinderung eines lokalen und systemischen Rezidivs bei Patienten mit Kadish-C-ENB. Der Zeitpunkt und die optimale Zusammensetzung einer Polychemotherapie müssen weiter untersucht werden.

The HD12 panel of the German Hodgkin Lymphoma Study Group (GHSG): a quality assurance program based on a multidisciplinary panel reviewing all patients' imaging.

The purpose of this report is to determine the value of a central specialist radiologic review and to determine the image quality of computed tomography (CT) in Hodgkin disease. The HD12 protocol is a multicenter prospective randomized trial of the GHSG for advanced stages of Hodgkin disease. The indication and effectiveness of additional radiotherapy (30 Gy), in the area of initial bulky disease and of residual disease, following intensive chemotherapy using the BEACOPP schema (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone), is to be investigated. A multidisciplinary panel of radiation oncologists, radiologists, and medical oncologists reviews, blinded to treatment arms, the diagnostic imaging with comparison to the documentation forms. For patients with poor response to chemotherapy, the panel recommends radiotherapy independent of the randomization. This procedure guarantees that patients with a poor response to chemotherapy receive additional radiotherapy. Furthermore, the panel evaluates the quality of CT examinations in this multicenter study. Since July 1999, a total of 2607 CT of 371 patients have been evaluated. Helical CT showed significantly higher contrast enhancement and imaging quality than conventional CT (P < 0.001). CT from university hospitals was assessed as superior to that from other institutions (P < 0.001). Compared with the written disease documentation by the study centers, the panel assessed different extensions of disease in 814 of 2607 CT (31%), resulting in a change of stage in 17 of 371 patients (5%). After chemotherapy, 167 of 371 patients (45%) showed residual disease (>1.5 cm), and for 53 of 371 patients (14%) the panel recommended additional radiotherapy independent of the randomization arm. Patients with Hodgkin disease receive high-quality CT imaging. A central independent multidisciplinary panel markedly improves quality assurance for these study patients.

LINAC Radiosurgery for Patients with a Limited Number of Brain Metastases

Patients (pts) with brain metastases have a high risk of cancer-related death due to extra- or intracranial tumor manifestations. The present retrospective analysis demonstrates the ability of linear accelerator (LINAC)-based radiosurgery to control intracranial disease and prolong survival in pts with one to three metastases. From 1991 to 1996, 106 pts (42 females, 64 males; median age, 57 years) with cerebral metastases were treated by stereotactic radiosurgery with a LINAC (8 MeV) equipped with tertiary collimators. In 70 pts, a single metastasis was present; 36 pts had two or three metastases. Fifty-nine pts were treated for their first occurrence of brain metastases; 47 pts had been treated prior to radiosurgery by resection and/or whole-brain irradiation. Histology of the primary tumor was non–small cell lung cancer (36 pts), melanoma (20 pts), breast cancer (15 pts), hypernephroma (15 pts), and other (20 pts). All together, 157 metastases (0.04–69.0 ml; median, 2.7 ml) were irradiated with marginal doses of 12–25 Gy (median, 20 Gy) referred to the 65–80% isodose. Seventy-two percent of the lesions were treated with a single isocenter. Adjuvant whole-brain irradiation was applied in six pts. One hundred thirty-five of 157 metastases were evaluated for response: complete response (CR), 24%; partial response, 31%; no change, 30%; and progression of disease, 15%. CR rates were highest (48%) in small metastases (<1-cm diameter), independent of histological type and dose. The overall median survival was 8 months. Multivariate Cox regression analysis revealed a significant impact on survival for Karnofsky performance score, presence of extracranial tumor, and volume of largest metastasis. Freedom from neurological death was determined only by the volume of the largest metastasis. Patients with multiple metastases and/or extracranial disease had a higher risk of developing new outfield brain metastases. Due to salvage therapy (second or third course of stereotactic radiosurgery, whole-brain irradiation, surgery), the overall survival in pts with two or three metastases did not significantly differ from that in pts with single metastases. LINAC-based stereotactic radiosurgery in pts with up to three cerebral metastases results in survival rates approaching those of pts with resected single brain metastases. As pts with both single and multiple metastases can effectively be salvaged after receiving radiosurgery, extracranial tumor activity becomes a major determinator of survival.

External beam radiation in patients suffering from exudative age-related macular degeneration

Abstract · Background: The aim of this prospective study was to ascertain whether external beam irradiation is effective in patients with subretinal neovascularization (SRN) due to age-related macular degeneration (AMD). · Methods: All patients had subfoveal SRN due to AMD as verified by fluoresceinangiography. Two hundred and eighty-seven patient-eyes were treated by external beam irradiation (total dose of 16 Gy in 2-Gy fractions, 5 times a week) from January 1996. The analysis was restricted to those 73 patients with a minimum follow-up of 11 months. Eighteen patients with subfoveal SRN who refused treatment served as control group (CG). 18 patients of the treatment group (TG) were matched for visual acuity, refraction and extent of SRN. The statistical analysis was performed with the unpaired t-test. · Results: The mean age of the CG was 73.9 years (range 66.9–81.3 years) and of the TG 75.6 years (range: 65.7–80.6 years). The median follow-up was 13.5 months (range 11.9–18.4 months) in the CG and 12.9 months (range 11–13.9 months) in the TG. The initial visual acuity (VA) was 20/80 in both groups. After 7 months the follow-up revealed median VA of 20/400 in the CG and 20/160 in the TG (P=0.0335). The final median VA was 20/400 in both groups, with a range from 20/40 to 20/1000 in the CG and from 20/63 to 20/500 in the TG (P=0.2433). The SRN doubled in size during this time in both groups. · Conclusion: These results suggest that external beam irradiation applied in 2-Gy fractions 5 times a week slows down the visual loss in exudative AMD for a short time. Nevertheless, the patients’ reading vision could not be saved in the long term.

Stellenwert der Gallium-Szintigraphie nach Therapie des Morbus Hodgkin

E ine nordamerikanische Arbeitsgruppe der State University des New Yorker Health Science Center [2] untersuchte die klinische Relevanz der Gallium-Szintigraphie nach Therapie des Morbus Hodgkin. (single photon emission computed tomography) erhielten 38 der 60 Patienten mit Restaging-Gallium-Scans. Die mediane verabreichte Aktivit~it betrug 9,2 mCi Gallium-67-Citrat, gescannt wurde 48 bis 72 Stunden nach Injektion.

External Beam Radiotherapy in Age-Related Macular Degeneration — an Ineffective Treatment Approach?

Age-related macular degeneration (ARMD) is the leading cause of progressive and irreversible loss of vision in the elderly population, affecting approximately one in three people over the age of 65. It is currently incurable and is characterized by progressive degeneration of the sensory retina, supporting retinal pigment epithelium (RPE), and choriocapillaris, which constitutes the blood supply to the outer retina (BRESSLER et a11990; CHERASKIN 1992; SOuBRANE et al. 1990; STEVENS et al. 1997; VINGERLING et al. 1995). Historically, ARMD was first reported as “senile” macular degeneration in 1885 by Otto Haab (HAAB 1885). In 1967, Gass clarified the understanding of ARMD, indicating that drusen, senile macular degeneration, and senile disciform macular degeneration represent a single disease entity in different phases (GASS 1967).