Randomized phase-III-trial of concurrent chemoradiation for locally advanced head and neck cancer comparing dose reduced radiotherapy with paclitaxel/cisplatin to standard radiotherapy with fluorouracil/cisplatin: The PacCis-trial.

BACKGROUND AND PURPOSE: This multicenter, phase 3 trial investigates whether the incorporation of concurrent paclitaxel and cisplatin together with a reduced total dose of radiotherapy is superior to standard fluorouracil-cisplatin based CRT. MATERIALS AND METHODS: Patients with SCCHN, stage III-IVB, were randomized to receive paclitaxel/cisplatin (PacCis)-CRT (arm A; paclitaxel 20 mg/m2 on days 2, 5, 8, 11 and 25, 30, 33, 36; cisplatin 20 mg/m2, days 1-4 and 29-32; RT to a total dose of 63.6 Gy) or fluorouracil/cisplatin (CisFU)-CRT (arm B; fluorouracil 600 mg/m2; cisplatin 20 mg/m2, days 1-5 and 29-33; RT: 70.6 Gy). Endpoint was 3-year-disease free survival (3y-DFS). RESULTS: A total of 221 patients were enrolled between 2010 and 2015. With a median follow-up of 3.7 years, 3y-DFS in the CisFU arm and PacCis arm was 58.2% and 48.4%, respectively (HR 0.82, 95% CI 0.56-1.21, p = 0.52). The 3y-OS amounted to 64.6% in the CisFU arm, and to 59.2% in the PacCis arm (HR 0.82, 95% CI 0.54-1.24, p = 0.43). In the subgroup of p16-positive oropharyngeal carcinomas, 3y-DFS and 3y-OS was 84.6% vs 83.9% (p = 0.653), and 92.3% vs. 83.5% (p = 0.76) in arm A and B, respectively. Grade 3-4 hematological toxicities were significantly reduced in arm A (anemia, p = 0.01; leukocytopenia, p = 0.003), whereas grade 3 infections were reduced in arm B (p = 0.01). CONCLUSION: Paclitaxel/cisplatin-CRT with a reduced RT-dose is not superior to standard fluorouracil/cisplatin-CRT. Subgroup analyses indicate that a reduced radiation dose seems to be sufficient for p16+ oropharyngeal cancer or non-smokers. CLINICAL TRIAL INFORMATION: NCT01126216; EudraCT Number 2005-003484-23.

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.

Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis.

BACKGROUND AND PURPOSE: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. PATIENTS AND METHODS: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. RESULTS: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). CONCLUSION: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration.

Conformal radiotherapy planning of cervix carcinoma: differences in the delineation of the clinical target volume. A comparison between gynaecologic and radiation oncologists.

PURPOSE: To assess uncertainties in the definition of the clinical target volume (CTV) for patients scheduled for primary radiotherapy of cervix carcinoma. METHODS AND MATERIALS: Seven physicians (five radiation oncologists and two gynaecologists) independently contoured the CTVs for three patients. All observers were provided with the same clinical information. CTVs were entered directly in the treatment planning system. Differences were analysed qualitatively and quantitatively. RESULTS: The qualitative analysis revealed a good agreement by all observers on anatomical structures identified to be at risk for tumour spread. Quantitatively, however, a large interobserver variability was found. The ratio between largest and smallest volumes ranged between 3.6 and 4.9 for all observers (3.6-4.9 for the radiation oncologists, 1.3-2.8 for the gynaecologists). The median three-dimensional difference in gravity centres ranged between 10.9 and 26.3mm for the respective patients. The ratio of common volumes to encompassing volumes ranged between 0.11 and 0.13 for the radiation oncologists, and between 0.30 and 0.57 for the gynaecologists. CONCLUSIONS: Although there was a good consistency in outlined anatomical structures, for the radiation therapy of carcinomas of the uterine cervix a large interobserver variability in CTV delineation concerning the magnitude and relative location of volumes was observed. Compared to other factors, e.g. set-up and organ motion, interobserver variability in CTV definition seems to have the highest impact on the geometrical accuracy in the radiotherapy of this tumour entity.