A prospective observational study evaluating two patient immobilisation methods in lung stereotactic radiotherapy.

PURPOSE: The main objective of this study was to assess inter- and intrafraction errors for two patient immobilisation devices in the context of lung stereotactic body radiation therapy: a vacuum cushion and a simple arm support. MATERIALS AND METHODS: Twenty patients who were treated with lung stereotactic body radiation therapy in supine position with arms above their head were included in the study. Ten patients were setup in a vacuum cushion (Bluebag™, Elekta) and ten other patients with a simple arm support (Posirest™, Civco). A pretreatment four-dimensional cone-beam computed tomography and a post-treatment three-dimensional cone-beam computed tomography were acquired to compare positioning and immobilisation accuracy. Based on a rigid registration with the planning computed tomography on the spine at the target level, translational and rotational errors were reported. RESULTS: The median number of fractions per treatment was 5 (range: 3-10). Mean interfraction errors based on 112 four-dimensional cone-beam computed tomographies were similar for both setups with deviations less than or equal to 1.3mm in lateral and vertical direction and 1.2° in roll and yaw. For longitudinal translational errors, mean interfraction errors were 0.7mm with vacuum cushion and -3.9mm with arm support. Based on 111 three-dimensional cone-beam computed tomographies, mean lateral, longitudinal and vertical intrafraction errors were -0.1mm, -0.2mm and 0.0mm respectively (SD: 1.0, 1.2 and 1.0mm respectively) for the patients setup with vacuum cushion, and mean vertical, longitudinal and lateral intrafraction errors were -0.3mm, -0.7mm and 0.1mm respectively (SD: 2.3, 1.8 and 1.4mm respectively) for the patients setup with arm support. Intrafraction errors means were not statistically different between both positions but standard deviations were statistically larger with arm support. CONCLUSION: The results of our study showed similar inter and intrafraction mean deviations between both positioning but a large variability in intrafraction observed with arm support suggested a more accurate immobilization with vacuum cushion.

Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer.

BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.

Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial.

BACKGROUND: The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). PATIENTS AND METHODS: Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. RESULTS: The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively. CONCLUSION: CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. EUDRA CT NO: 2007-007029-38.

[Best practice guide for radiation therapy of non-small cell bronchial cancers]. / Guide de bonne pratique pour la radiothérapie thoracique exclusive ou postopératoire des carcinomes non à petites cellules.

The objective was the drafting of a practical document intended for radiotherapists and radiophysicists, describing the technique of irradiation of a non small cell bronchial cancer. The good practices concern the care of patients affected by bronchial cancer localized in the thorax and inoperable or patients who must undergo postoperative irradiation. The document has been developed according to a methodology aiming to join the current scientific data from an analysis of the literature on the subject and the assessment of radiotherapists, radiophysicists, lung specialists and methodologists from Rhône-Alpes area. From the stages necessary for the good progress of a radiotherapy, the writers of this document proposed common definitions concerning the centering and the location of the zone to be treated, the calculation of the dose distribution, the preparation of the patient for the treatment, the treatment and the surveillance during the treatment. The recommendations of this guide took into account the peculiarities bound to the nature of the treated region and more particularly the lung heterogeneity, respiratory movements and the radiosensibility of healthy lung tissue. Even if the technical aspect of the radiotherapy was particularly developed, the interest accorded to patient information takes on all its importance for a therapeutic coverage of quality. The authors of the document wished that this Guide of Good Practices, which will be regularly updated, helps the radiotherapists and allows them to harmonize their practices.

Conformal irradiation for pure and mixed oligodendroglioma: the experience of Centre Leon Berard Lyon.

PURPOSE: To assess whether conformal radiotherapy (CRT) after incomplete surgery or biopsy for pure oligodendrogliomas and mixed gliomas results in decreased long-term sequelae without impairing local control and while reducing irradiated volume. MATERIALS AND METHODS: Twenty-six consecutive patients who presented with pure (21) or mixed (5) oligodendrogliomas and who were given incomplete resections were treated according 3 different strategies: CRT alone (12), chemotherapy followed by CRT (4), and chemotherapy and delayed CRT at the time of tumor progression (10). CRT consisted of multiple noncoplanar fields. Median dose was 60 Gy. Quality of CRT was assessed using tumor and normal tissue conformal indexes. The location of recurrences was assessed with MRI and dosimetric data. Late sequelae were assessed by a questionnaire exploring professional outcome, and also by a Mini Mental State Examination test. RESULTS: The mean overall survival was 5.2 years. Fifteen patients experienced a local relapse. All but 1 occurred in the 95% isodose. Among 11 nonevolutive patients, 6 have a full-time or part-time job. CONCLUSIONS: Despite CRT, infield recurrence was a common feature in patients with oligodendrogliomas and mixed tumors. Further research, including molecular biology typing of tumors and type of treatment, is warranted to improve survival and quality of life.

Prospective evaluation of early lung toxicity following three-dimensional conformal radiation therapy in non-small-cell lung cancer: preliminary results.

PURPOSE: Radiation pneumonitis is the restricting complication following lung cancer irradiation. The correlation between dose-volume histograms (DVHs) and pneumonitis, with a clinical, radiological, and respiratory function evaluation was assessed. Special endpoint was the evaluation of respiratory function after three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Fifty-four patients with non metastatic non-small-cell lung cancer (NSCLC) were treated with a curative intent with 3D-CRT (66 Gy). Thirty-one patients were treated postoperatively (pneumonectomy in 9 patients) for residual tumor or massive nodal involvement (N2 or N3); 23 patients were treated with exclusive radiotherapy. Clinical evaluation, CT scan, and pulmonary functional tests were performed before and 6 weeks after irradiation. The DVHs were calculated applying lung density heterogeneity. RESULTS: Twenty patients had radiation pneumonitis. Irradiation significantly decreased total lung capacity. Volume of the PTV2 (more than 200 cm(3)) was a significant prognostic factor for lung complication. CONCLUSION: DVHs combined with initial pulmonary functional tests can predict pulmonary toxicity and could allow us to adjust volume that received total highest dose with acceptable toxicity.

[Innovations in the treatment of medulloblastoma]. / Innovation dans le traitement du médulloblastome.

Prognosis of medulloblastoma remains serious with a disease-free survival rate of 70% at 5 years and severe sequelae in the majority of children. In order to improve this survival rate without unacceptable toxicity, various ways are currently under investigation. Among them, hyperfractionation and conformal therapy seem to be promising. Quality control of radiotherapy treatment could surely also play a major role on outcome.