Lucio Sebaste

Symptomatic recurrences of carcinoma of the rectum and sigmoid. The influence of radiotherapy on the quality of life.

One hundred forty-three patients irradiated for locoregional recurrences after curative surgery for cancer of the rectum and sigmoid were studied retrospectively. An analysis was made of the symptomatic response and survival in the total series and in three subgroups treated with different dose levels (40 Gy or lower, between 40 and 50 Gy, 50 Gy or higher). The symptom-free period was calculated as percent of the overall survival. Symptomatic control was obtained in 80.4 percent of the cases, and the crude patient survival rate was 17.5 percent at two years. No significant difference was found in the three subgroups treated with different dose levels. The cumulative time/patient asymptomatic periods in the total series and in the three subgroups were 31.5, 30.2, 31.8, and 31.9 percent respectively, of the survival period.

The combined EGFR protein expression analysis refines the prognostic value of the MGMT promoter methylation status in glioblastoma

BACKGROUND/AIMS To investigate the combined prognostic value of the EGFR expression level and the MGMT promoter methylation status in Glioblastoma (GB). METHODS We assessed the EGFR protein expression level by immune-histochemical (IHC) evaluation and the MGMT promoter methylation status by Polymerase Chain Reaction (PCR) in 169 patients affected by GB. We assessed the prognostic significance of combined MGMT methylation status and EGFR expression level in terms of Overall Survival (OS) with univariate and multivariate analysis, and validated this finding using an external data set of GB patient. RESULTS Clustering survival analysis for the methylation status of MGMT (methMGMT/unmethMGMT) and EGFR expression (High EGFR: H-EGFR; Low EGFR: L-EGFR), identified three different prognostic groups (p=0.001), as follows. Patients with unmethMGMT/H-EGFR had the shortest survival time (median OS: 5 months) and patients co-expressing methMGMT/L-EGFR had the best prognosis (median OS: 35 months), as compared to the other two sub-groups (methMGMT/H-EGFR; unmethMGMT/L-EGFR), which had respectively median OSs of 11 and 12 months. The combined MGMT methylation and EGFR amplification status analysis showed a similar prognostic impact in an independent series, which we used for validation (p=0.001). CONCLUSIONS The EGFR expression evaluation refines the prognostic value of MGMT methylation status in GBs.

3D bone texture analysis as a potential predictor of radiation-induced insufficiency fractures

Background The aim of our work is to assess the potential role of texture analysis (TA), applied to computed tomography (CT) simulation scans, in relation to the development of insufficiency fractures (IFs) in patients undergoing radiation therapy (RT) for pelvic malignancies. Methods We analyzed patients undergoing pelvic RT from Jan-2010 to Dec-2016, 31 of whom had developed IFs of the pelvis. We analyzed CT simulation scans using LifeX Software©, and in particular we selected three regions of interest (ROI): L5 body, the sacrum and both the femoral heads. The ROI were automatically contoured using the treatment planning software Raystation©. TA parameters included parameters from the gray-level histogram, indices from sphericity and from the matrix of GLCM (gray level co-occurrence matrix). The IFs patients were matched (1:1 ratio) with control patients who had not developed IFs, and were matched for age, sex, type of tumor, menopausal status, RT dose and use of chemotherapy. Univariate and multivariate analyses (logistic regression) were used for statistical analysis. Results Significant TA parameters on univariate analysis included both parameters from the histogram distribution, as well from the matrix of GLCM. On logistic regression analysis the significant parameters were L5-energy [P=0.033, odds ratio (OR): 1.997, 95% CI: 1.059-3.767] and FH-Skewness (P=0.014, OR: 2.338, 95% CI: 1.191-4.591), with a R2: 0.268. A ROC curve was generated from the binary logistic regression, and the AUC was 0.741 (95% CI: 0.627-0.855, P=0.001, S.E.: 0.058). Conclusions In our experience, 3D-bone CT TA can be used to stratify the risk of the patients to develop radiation-induced IFs. A prospective study will be conducted to validate these findings.

Patients Affected by Unmethylated O(6)-Methylguanine-DNA Methyltransferase Glioblastoma Undergoing Radiochemotherapy May Benefit from Moderately Dose-Escalated Radiotherapy

Purpose To compare the therapeutic results of two radiotherapy (RT) dose schedules in combined temozolomide- (TMZ-) RT treatment in newly diagnosed glioblastoma (GB), according to the O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status. Material and Method Patients received either standard (60 Gy) or moderately escalated dose (70 Gy) radiotherapy (RT) with concomitant and adjuvant TMZ between June 2006 and October 2013. We retrospectively evaluated the therapeutic effectiveness of RT schedules in terms of Overall Survival (OS) and Progression-Disease Free Survival (PDFS) analyzing the MGMT methylation status. Results One hundred and seventeen patients were selected for the present analysis. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the escalated schedule (HDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in unmethylated-MGMT GB patients, HDRT-TMZ and SDRT-TMZ groups had different median OS (p = 0,01) and PDFS (p = 0,007), that is, 8 months and 5 months for the SDRT-TMZ group and 14 months and 9 months for the HDRT-TMZ group, respectively. No difference in survival outcomes was found in methylated MGMT patients according to the two RT schedules (p = 0,12). Conclusions In our experience, unmethylated-MGMT GB patients benefited from a moderately escalated dose of RT plus TMZ.

PO-0927: Bone texture analysis as predictive of bone radiation damage in patients undergoing pelvic RT

S449 ________________________________________________________________________________ Conclusion: Using a sophisticated approach for PET/histopathology coregistration PSMA-PET/CT yielded high R2-values which can be translated in excellent overlap with PCa. Furthermore, we were able to provide SUV-guidance values for PSMA-PET/CT which opens the opportunity for SUV-based GTV-delineation techniques using PSMA-PET as a base for focal dose escalation on DIL.

Chemo-radiotherapeutic management of advanced head and neck cancer.

Stage III and IV head and neck cancer patients usually achieve poor therapeutic results after radiotherapy. The search for more effective treatment modalities is justified, provided that tolerance is not lower than that of the usual radiation therapy schedules. Chemotherapy has been shown to be effective, and cisplatinum and bleomycin based treatments are reported to result in objective remissions in a substantial proportion of cases. There is also experimental evidence of a radiosensitizing activity of cisplatinum. Thirty-five locally advanced head and neck cancer patients were given combined chemo-radiotherapeutic treatment consisting of a cisplatinum and bleomycin induction followed by a standard radiotherapy course integrated with weekly administrations of cisplatinum. Before radiotherapy, an overall 48.5 % objective remission rate was achieved, that rose to 85.8 % after completion of the entire treatment, with a 31.5 % complete response rate. Incidence and severity of radiation mucositis seem not to be increased, and systemic toxicity is very low, with the adopted drug administration schedule. Overall results do not show any obvious superiority over those of radiotherapy alone.