Intensity modulated radiation therapy and oral mucosa sparing in Head and neck cancer patients: A systematic review on behalf of Italian Association of Radiation Oncology - Head and neck working group.

Oral mucositis is a common dose-limiting toxicity during radiotherapy with or without chemotherapy in head and neck cancer patients. This potentially severe complication globally worsens quality of life and negatively impacts local control and survival's outcomes. Several studies have been published on feasibility and/or clinical benefit of intensity modulated radiotherapy (IMRT) mucosa-sparing technique. In 2017, the Italian Association of Radiation Oncology Head and Neck Cancer Working Group organized a study group to perform a systematic review. The aim was to verify if practical indications, including dose-constraints and demonstrated clinical benefit, could be proposed for oral mucosa (OM)-sparing IMRT in order to reduce the incidence of severe acute mucositis. Although dose to OM should be reduced as much as possible without compromising target volumes coverage, it is still tricky to firmly state that OM-sparing procedure should be considered the standard of care, especially due to high subjective variability in OM contour.

Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

BACKGROUND: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. MATERIALS AND METHODS: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). RESULTS: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. CONCLUSIONS: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. CLINICAL TRIAL NUMBER: NCT01086826, www.clinicaltrials.gov.

Nasopharyngeal carcinoma in a low incidence European area : A prospective observational analysis from the Head and Neck Study Group of the Italian Society of Radiation Oncology (AIRO).

PURPOSE: To evaluate the outcomes with respect to long-term survival and toxicity in patients with nasopharyngeal carcinoma (NPC) treated in a European country with low incidence. MATERIALS AND METHODS: A prospective observational study carried out by the AIRO Head and Neck group in 12 Italian institutions included 136 consecutive patients treated with radiotherapy (RT) ± chemotherapy (CHT) for NPC (without distant metastasis) between January 1, 2008 and December 31, 2010. RESULTS: The disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) at 5 years were 92 (±2), 91 (±3), and 69 % (±5 %), respectively. Distant failure was the most frequent modality of relapse. The local, regional, and locoregional control at 5 years were 89 (±3), 93 (±3), and 84 % (±4 %), respectively. The incidence of acute and late toxicity and the correlations with different clinical/technical variables were analyzed. Neoadjuvant CHT prolongs radiotherapy overall treatment time (OTT) and decreases treatment adherence during concomitant chemoradiotherapy. An adequate minimum dose coverage to PTV(T) is a predictive variable well related to outcome. CONCLUSION: Our data do not substantially differ in terms of survival and toxicity outcomes from those reported in larger series of patients treated in countries with higher incidences of NPC. The T stage (TNM 2002 UICC classification) is predictive of DSS and OS. The GTV volume (T ± N) and an adequate minimum PTV(T) coverage dose (D95 %) were also identified as potential predictive variables. Sophisticated technologies of dose delivery (IMRT) with image-guided radiotherapy could help to obtain better minimum PTV(T) coverage dose with increased DFS; distant metastasis after treatment still remains an unresolved issue.

A machine learning tool for re-planning and adaptive RT: A multicenter cohort investigation.

PURPOSE: To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset. MATERIALS AND METHODS: 90 patients (pts) treated for head-neck cancer (H&N) formed a multicenter data-set. 41 H&N pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG). Using deformable image registration (DIR) and GPU, patients' conditions were analyzed automatically. Support Vector Machines (SVM) was used for time-series evaluation. "Inadequate" class identified patients that might benefit from replanning. Double-blind evaluation by two radiation oncologists (ROs) was carried out to validate day/week selected for re-planning by the classifier. RESULTS: The cohort was affected by PG mean reduction of 23.7±8.8%. During the first 3weeks, 86.7% cases show PG deformation aligned with predefined tolerance, thus not requiring re-planning. From 4th week, an increased number of pts would potentially benefit from re-planning: a mean of 58% of cases, with an inter-center variability of 8.3%, showed "inadequate" conditions. 11% of cases showed "bias" due to DIR and script failure; 6% showed "warning" output due to potential positioning issues. Comparing re-planning suggested by tool with recommended by ROs, the 4th week seems the most favorable time in 70% cases. CONCLUSIONS: SVM and decision-making tool was applied to overcome ART challenges. Pts would benefit from ART and ideal time for re-planning intervention was identified in this retrospective analysis.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

Randomised clinical trial: preventive treatment with topical rectal beclomethasone dipropionate reduces post-radiation risk of bleeding in patients irradiated for prostate cancer.

BACKGROUND: Radiotherapy is an established treatment modality for prostate cancer; however, up to a third of patients develops a radiation-induced proctopathy. AIM: To assess the effect of topical beclomethasone dipropionate (BDP) in the prevention of radiation-induced proctopathy in patients undergoing radiotherapy for prostate cancer through a double-blind, placebo-controlled, randomised trial. METHODS: Patients were randomised either to BDP or to placebo (PL). Patients received daily a 3mg BDP enema or identical-looking PL during radiotherapy and, subsequently, two 3mg BDP suppositories or PL for 4 more weeks. Clinical and endoscopic evaluations before, 3 and 12months after the end of radiotherapy were assessed with the RTOG/EORTC toxicity scales, the modified Simple Clinical Colitis Activity Index (SCCAI), the modified Inflammatory Bowel disease Quality of Life Index (IBDQ) and the Vienna Rectoscopy Score (VRS). RESULTS: From June 2007 to October 2008, 120 patients were randomised to the BDP (n=60) and PL (n=60) arms and were followed up for 12months. The overall assessment of rectal side effects did not show significant differences between the two groups of treatment. However, when only rectal bleeding was considered, a significantly reduced risk was observed in patients on BDP (OR 0.38; 95% CI 0.17-0.86; P=0.02; NNT=5). Patients on BDP had also significantly lower VRS scores (P=0.028) and significantly higher IBDQ scores (P=0.034). CONCLUSIONS: Preventive treatment with topical rectal BDP during radiotherapy for prostate cancer significantly reduces the risk of rectal bleeding and radiation-induced mucosal changes and improves patient's quality of life, but does not influence other radiation-induced symptoms.

[Radiotherapy of stage T1 carcinoma of the glottis. Analysis of prognostic factors in 154 patients]. / La radioterapia dei carcinomi della glottide nello stadio T1. Analisi dei fattori prognostici in 154 pazienti.

A retrospective study was carried out on a series of 154 patients affected with vocal cord cancer in stage T1 treated with definitive radiotherapy April, 1979, to November, 1991. According to the 1992 TNM classification (UICC), 121 patients were classified as stage T1a and 33 patients as stage T1b. All patients were treated using parallel opposed fields of a 60 cobalt unit. Field size ranged from 16 to 30 square centimeters and the dose from 4400 to 7000 cGy, but only 15 patients received less than 6400 cGy. All patients were treated with once-daily fractionation (200 cGy/day). Follow-up ranges from 25 to 123 months; the median is 63 months. We observed 14 local recurrences (9.0%), all but one within 36 months from the end of treatment. Ten of 14 patients (71.4%) were rescued by surgery (8 patients underwent total laryngectomy and 2 conservative surgery); 13 patients were lost for intercurrent deaths. The incidence of recurrences is 7.4% for T1a patients (9/121) and 15.1% for T1b patients (5/33). The total dose does not seem to be related to relapse rate since recurrences were found in 6.6% of patients after a dose < 6400 cGy and in 9.3% of patients who had received higher doses. In our experience, field size did not affect, treatment results (< 25 cm2: 7.5% recurrences, > 25 cm2: 10.7%). Besides lesion volume, the main prognostic factor was overall treatment time. The incidence of failure was 3 times lower (5.8%) in the patients who completed the treatment within 7 weeks than in the patients whose treatment lasted more than 8 weeks (16.6%).