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Background and Objective The aim of this study was to investigate the potential role of epidermal growth factor receptor (EGFR) protein expression in predicting the modality of treatment failure in glioblastoma (GB). Methods Patients with unifocal GB undergoing surgery and postoperative radiochemotherapy from February 2008 to July 2015 were included into the study. The EGFR protein expression level was assessed by immunohistochemistry in GB tissues and classified into high and low expression. Time to progression (TTP) and pattern of recurrence (PR) were evaluated. PRs were classified as central, in-field, marginal, or distant recurrences. Results After a median follow-up time of 13 months (range, 6–67 months), 102 patients (79.1%) showed recurrences that were detectable on magnetic resonance imaging. Median TTP was 9 months after the completion of radiochemotherapy. EGFR expression was significantly correlated with TTP (log-rank test, P = 0.003) and PR (Fisher exact test, P = 0.01). The low-EGFR group had a median TTP of 13 months and a prevalence of central/in-field recurrences (accounting to a total 81%). The high-EGFR group had a shorter median TTP (6 months) and a higher rate of marginal/distant recurrences (55.6%). Conclusions Different modality of recurrence related to EGFR expression in patients with GB envisages implication for target contouring of radiotherapy volumes and other therapeutic strategies.

Purpose We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020 ) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer. Methods and Materials The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions. Results A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm. Conclusions In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.

Background Immune-checkpoint blockade has shown anti-tumor activity in MSI mCRC patients only, thus, the research of more efficacious immunological strategies for colon cancer treatment is still open. GOLFIG, is a safe and active chemo-immunotherapy regimen designed on the basis of preclinical immune-oncological findings and evaluated in two subsequent Phase II and III trials in mCRC patients (J Clin Oncol, 2005,23:8950; J Immunother, 2014;37:26). This regimen combines gemcitabine + FOLFOX poly-chemotherapy with salgramostim (GM-CSF) and low dose sc. aldesleukin, to improve both cross-priming and T-cell effector anti-tumor response. Here we report a fifteen-year retrospective analysis of all patients undergone this therapeutic approach. Methods This is a multi-institutional real-life study including one hundred-seventy-nine mCRC patients receiving GOLFIG regimen between October 2001 and November 2018 with a median follow up of 120 months. The treatment was administered to 62 patients (GOLFIG-2 trial, EUDRACT: 2005-003458-81) as a first-line and to 117 patients as second/third-line (49 enrolled in the GOLFIG-1 phase II trial and 68 as real life). Kaplan-Meier and Cox-regression were carried-out to relate their PFS and OS with sex, age, sidedness, RAS mutational status, previous treatment lines, baseline clinical parameters and treatment-related irAEs. Results We recorded a PFS and OS of 15.3 (95%CI:10.4-20.2) and 24.6 (95%CI:19.07-30.14) months, respectively, with 10% of the patients surviving more than ten years. Patients’ outcome did not correlate with sex, sidedness and RAS. First line GOLFIG confirmed superiority over FOLFOX in term of PFS (HR = 0.58 p = 0.006) and OS (HR = 0.69, P = 0.06) (updated from GOLFIG-2 trial). Patients in first-line showed a longer PFS (HR = 0.69; p = 0.041) compared with the others, with no difference in OS. On the overall, a longer PFS and OS correlated with baseline neutrophil counts ≤ 4,500 cells/µl (HR:0.32; P = 0.003) and occurrence of irAEs (HR = 0.36; P = 0.0001) recorded in 24% of the cases. Conclusions These results confirm that the GOLFIG regimen is a reliable therapy for pretreated mCRC patients and offer the rationale to design combination trials with immune-checkpoint blockade. Clinical trial identification 1) GOLFIG-2 phase III trial; EudraCT: 2005-003458-81 2) GOLFIG-1 phase II trial; EudraCT no available, start July 2001. Legal entity responsible for the study The authors. Funding Italian Ministry of Education and Research (MIUR) (2009EHW394). Private grant from the “Associazione Culturale Federico II,” and from the “Associazione Riuniti Calabria Oncologia (ARCO)”. Disclosure All authors have declared no conflicts of interest.

Purpose The purpose of this retrospective study was to This retrospective study aims to evaluate the potential use of MRI TA to predict the outcome and relapse of locally advanced rectal cancer (LARC) in patients undergoing Chemo-radiotherapy (C-RT) before radical surgery (TME). Methods This study regarded patients affected to glioblastoma and treated with concomitant postoperative radiotherapy with before surgery MRI exams (T1, This study included patients treated with C-RT (45 Gy + 9 Gy 1,8 Gy/day and capecitabine) at our Radiation Oncology Unit between January 2010 and December 2015. Another inclusion criterion was the execution of pelvic MRI (T2 and DWI) examinations (1.5-T system, Signa Excite HD, GE) made at baseline, 30 ± 15 days after the end of C-RT and at 9–12 weeks after TME. The use of Mandard score permits to evaluate the tumour regression grade (TRG). To calculate TA parameters calculation and to perform the necessary statistical analysis is possible with the programs LifeX and SPSS. The research of the correlation of TA parameters and multiple prognostic factors with early progression of disease (ePD) was the primary focus of this study. The omission of the variables with the lowest Pearson correlation coefficient permitted to avoid the model overfitting. With k-fold and ROC analysis was possible to validate our performance model. Results This study included 73 patient38 patients included in this study had characteristic reported in the table. The reliability analysis performed with ICC showed that the TA parameters that resulted significantly reproducible (ICC > 0.70) were 48% for the T2, 56% for the DWI and 84% for the ADC. The figure shows Pearson correlation analysis significant results. Logistic regression also showed a significant association of DWI GLCM Correlation (p:0.006) and T stage (p:0.036), with an overall R2 of 0.641, a ROC AUC of 0.938 (95% CI 0.854–1.00) and a successful k-fold validation. 38 patients included in this study had characteristic reported in the table. The reliability analysis performed with ICC showed that the TA parameters that resulted significantly reproducible (ICC > 0.70) were 48% for the T2, 56% for the DWI and 84% for the ADC. The figure shows Pearson correlation analysis significant results. Logistic regression also showed a significant association of DWI GLCM Correlation (p:0.006) and T stage (p:0.036), with an overall R2 of 0.641, a ROC AUC of 0.938 (95% CI 0.854-1.00) and a successful k-fold validation. Conclusion This study shows that there is a correlation between TA GLCM parameters ex A non-invasive mathematical analysis of MRI imaging such as TA, can be used to predict the outcome of patients with LARC and may help to the selection of patients who need additional treatments over the classical neoadjuvant C-RT.

Objective To explore therapeutic results of different radiotherapy (RT) dose schedules combined to Temozolomide (TMZ)-RT treatment in newly diagnosed glioblastoma (GB), according to the O (6)-methylguanine-DNA methyltransferase (MGMT) methylation status. Patients and methods Patients with newly diagnosed GB received either standard (60-59.4 Gy) or reduced (54-52 Gy) dose radiation therapy (RT) with concurrent and adjuvant TMZ between June 2010 and October 2016. We retrospectively evaluated the therapeutic effectiveness of the RT ranges schedules in terms of overall survival (OS) with univariate and multivariate analysis, after analyzing the MGMT methylation status. Results One hundred and seventeen patients were selected for the present analysis out of 146 total treated patients accrued. Seventy-two out of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the reduced dose schedule (RDRT-TMZ). The analysis according to the MGMT promoter methylation status showed that, in methylated-MGMT GB patients, SDRT-TMZ and RDRT-TMZ groups did not show different median OS (p = ns) according to the two RT schedules, independently by the extent of surgical resection. Instead, a difference in survival outcomes was confirmed in unmethylated-MGMT GB patients with better survival for patients undergoing to SDRT, particularly in sub-total resection. Conclusion In our experience, a reduction of radiation dose schedule does not seem to jeopardize survival in methylated-MGMT patients independently by the extent of resection. A therapeutic approach to a standard reduction of RT dose for the methylated subset of patients may be feasible and could deserve prospective trials for validation.

Purpose This work aims to evaluate the possibility to use volumetric Texture analysis (TA) of T2 images and ADC maps to predict the clinical output in patients affected by advanced rectal cancer (LARC). Methods For this work were considered patients with non-mucinous extraperitoneal rectum adenocarcinoma with different degree of differentiation treated with neoadjuvant chemo-radiotherapy (C-RT) and radical surgery (TME). The Mandard score permitted to establish the tumour regression grade (TRG). Enrolled patients were treated with C-RT (45 Gy + 9 Gy 1,8 Gy/day and oxaliplatin and capecitabine) and subjected to pelvic MRI (T2 and DWI) examinations (1.5-T system, Signa Excite HD, GE) made at baseline and 40 ± 20 days after the end of C-RT. Two blinded readers manually segmented tumour volumes and used a homemade Image macro to evaluate TA parameters. The application of a Laplacian of Gaussian bandpass filter between 0.5 and 2.5 permits to highlight different spatial scales. Using SPSS software Pearson correlation, Cox regression, ROC and Kaplan Meier curve were evaluated considering TA parameters (TAp), TRG and metastasis development. Were correlated with early progression of disease (ePD) omitting the variable with the lowest Pearson correlation coefficient to avoid a model overfitting. With k-fold and ROC analysis was possible to validate our performance model. Results This study included 23 patients (average age 65,9 ± 11,7 years): 9 were TRG1 and 14 TRG2. No statistically significant correlation was found considering TAp calculated from T2 images. From ADC images emerged a significant correlation between tumour stage (p = 0.016) and metastasis development (p = 0.013). Moreover, ROC analysis showed how this parameter is predictive for complete treatment response (specificity 86% and accuracy 83%). Conclusion This work shows how TAp could predict the outcome of patients to implement a personalised treatment.