Abstract BACKGROUND This trial aimed to investigate whether re-irradiation based on (O-(2-Fluoroethyl)-L-tyrosine, FET)-positron emission tomography (PET) leads to an improvement in progression-free survival (PFS) in patients with recurrent glioblastoma (rGBM), compared to a target volume delineation based on contrast-enhanced T1-weighted MRI (T1Gd-MRI). MATERIAL AND METHODS GLIAA was a prospective, multicenter, randomized clinical trial (NOA 10/ARO 2013-1, DKTK-a., NCT01252459). Patients with rGBM of 1-6 cm were randomized 1:1 at 14 centers in Germany between a FET-PET- and a T1Gd-MRI-based target volume delineation. The RT was performed with 3 Gy/d, 5x/week, to a total dose of 39 Gy. All patients had been previously irradiated with 59.4-60Gy at least 6 months before study treatment and had a histologically confirmed rGBM with a diameter of 1 - 6 cm on both FET-PET and T1Gd-MRI. The primary end point was PFS. Secondary end points included overall survival (OS), locally controlled survival, assessment of delineated volumes, topography of progression, rate of radiation necrosis after re-irradiation, and safety of FET-application in PET imaging. RESULTS Between November 2013 and September 2021, 200 patients were randomized between FET-PET-based (n=100) and GdT1-MRI-based (n=100) target volume delineation. A total of n=98 and n=97 patients, respectively, were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39;). Median OS was 9.4 months (95% CI 7.8-11.1) in the FET-PET arm and 9.0 months (95% CI 7.6-10.5) in the GdT1-MRI arm (HR 1.01 [95% CI 0.75-1.37], p=0.92). Median LCS was 6.3 months (95% CI 5.1-7.2) in the FET-PET arm and 6.8 months (95% CI 6.2-7.3) in the GdT1-MRI arm (HR 1.20 [95% CI 0.88-1.62], p=0.25). At 12 months, the local control rate was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). In the PET arm, 45.0% of recurrences were in field, 28.3% out of field, and 21.7% marginal. In the MRI arm, 47.4% relapsed in field, 31.6% out of field, and 14.0% marginal. 25.5% of patients in the FET-PET arm and 21.6% in the GdT1-MRI arm had a documented radiation necrosis. There were no adverse events related to the application of the FET tracer. CONCLUSION This is the first randomized trial to investigate the relevance of FET-PET in the irradiation treatment planning of rGBM. There was no survival benefit identified for patients treated with FET-PET- versus GdT1-MRI-based re-irradiation. Both imaging modalities led to similar outcomes and can be therefore used for radiation treatment planning for rGBM. The FET-PET investigation and the re-irradiation were well-tolerated, supporting the safety of this treatment.

PURPOSE:The outcome of treatment of testicular seminoma in 230 patients with stage I and II disease was retrospectively evaluated in regard of survival, pattern of failure, radiation dose, treatment volume, acute and chronic side effects.PATIENTS AND METHODS:From 1978 to 1992, 230 male patients with the diagnosis of pure seminoma of the testis were treated by postoperative radiotherapy at the University of Essen. According to the Royal Marsden Staging System, 188 patients were presenting with stage I disease, 24 with stage IIA, 13 with stage IIB and 5 with stage IIC disease. All patients received irradiation to the paraaortic lymph nodes (median dose: 36 Gy). In 154 patients the ipsilateral iliac lymph nodes were additionally irradiated with or without inguinal lymph nodes and in 66 patients the contralateral pelvic nodes were included. Since 1987, the total dose was reduced to 26 Gy for microscopic disease. A mediastinal irradiation (median dose: 30 Gy) was performed in 22 patients. Eight patients with stage IIB and IIC disease were additionally treated with chemotherapy.RESULTS:Overall actuarial survival (Kaplan-Meier method) for all patients was 97.8% at 5 years and 96.5% at 10 years. Ten-year survival corrected for intercurrent mortality (n = 8) was 100%. In 5 patients recurrent disease (n = 5) was observed, in 6 patients seminoma occurred in the contralateral testis. For stage I seminoma the disease-free survival was 96.8%. For the whole group of stage II seminoma the DFS was 88.1%, for stage IIA 91.7% and for stage IIB 76.9%. In stage IIC no recurrences occurred. In general, the radiation therapy was well tolerated with minor side effects only.CONCLUSIONS:Postoperative radiotherapy for seminoma stage I, IIA and IIB alone offers excellent control and survival rates with tolerable side effects.

PURPOSE:Evaluation of prognostic variables, results and toxicity after chemo-radiation (CRT) of anal canal carcinoma (ACC).MATERIAL AND METHODS:Between 1982 and 1992, 139 patients with epidermoid carcinoma of the anal canal were treated by radiation and chemotherapy with 5-fluorouracil (5-Fu) and mitomycin C (MMC). 99 patients belonged to a prospectively designed trial (50 Gy, 2 courses of chemotherapy) and 40 to a historical control group (40 Gy, 1 course of chemotherapy). The female/male ratio was 116/23. Median age was 62 years. Staging (UICC 1987): T1: 16.5%; T2: 49%; T3: 23%; T4: 9.4%; unknown: 2.1%. Abnormal regional nodes were present in 15% of the patients.HISTOLOGY:Squamous cell carcinoma: 68%; cloacogenic carcinoma: 31%; unknown: 1%. External beam radiation (ERT) was given to the primary tumour including perirectal, inguinal and iliac nodes by a 3 to 4 field box technique (50 patients) or parallel opposed fields (89 patients). Median single fraction and total dose were 1.8 Gy and 50 Gy. An additional boost to the involved sites was delivered by ERT (32 cases; median dose 16 Gy) or interstitial brachytherapy (BT) in 28 cases with a median dose 14 Gy. 84 patients (60%) received 2 or more cycles, 50 patients (36%) 1 cycle, 5 patients (4%) no chemotherapy.RESULTS:The survival rate, NED-survival rate and local tumour control rate were 78%, 64% and 69% at 5 years. Anorectal function was retained in 94 of 139 patients (68%). Multivariate analysis indicated that T-stage (p = 0.037) and belonging to the historical control group (p = 0.003) were significant variables for local tumour control. T-stage was a marginally significant factor (p = 0.09) for NED-survival. Acute toxicity of grade 3 and 4 (WHO) was observed in 36%, severe late toxicity (grade 3 Eschwege) in 3% of the patients.CONCLUSIONS:CRT with 2 courses 5-FU, MMC and ERT to a total dose of 45 to 50 Gy is a safe and effective treatment for ACC. Intensification of treatment is recommended in advanced stages T3/4.

In this retrospective study the records of 157 patients with the diagnosis of multiple myeloma were evaluated with regard to subjective pain relief after a series of radiation therapy at 389 local sites. The most frequently treated region was the spine (50.2 %), followed by the thoracic wall (17.9 %) and the upper and lower extremities (17.8 %). The median survival after diagnosis of all patients was 36 months. 88.4 % of all treated sites showed good to moderate response in terms of pain remission after irradiation. It is shown that pain relief is significantly dependent on the total dose but independent of the dose per fraction. A total dose of 30 Gy in two weeks (5 x 3 Gy/week) is recommended as a well tolerated and reasonable treatment option to achieve maximum palliation and minimum hospitalization time for patients in whom multiple myeloma is diagnosed.