Oncogene-driven non small cell lung cancer (NSCLC) is a distinct entity in thoracic oncology. The availability of effective target therapies, like EGFR inhibitors or ALK inhibitors, have revolutionized the prognosis of these patients. However, despite an initial response in the majority of patients, drug resistance ultimately occurs. In some cases, this resistance develops in few clonal cells (oligoprogression), so that a local ablation of these resistant deposits could allow to maintain the same systemic therapy and possibly to prolong patients' survival. For these purposes, stereotactic body radiation therapy (SBRT) is an ideal local ablative treatment, because it is effective, non invasive and with limited side effects. In this review, we aim to analyze available clinical data to verify whether SBRT can allow these patients to continue with existing target therapy longer, delay the switch to other systemic therapies and improve their outcome modifying the natural history of the disease.

Introduction: Despite recent advances in systemic and local treatments, the prognosis of patients with pancreatic cancer still remains poor, with 5-year survival less than 10%. According to recent literature, a limited number of metastases can define an oligometastatic state, still amenable to local approach. The aim of our study was to evaluate the efficacy of stereotactic body radiation therapy (SBRT) in selected oligometastatic pancreatic cancer patients. Methods: In this retrospective analysis, we included patients with a performance status of 0-2, treatment-naïve or previously treated with chemotherapy, with a maximum of 5 metastases in up to 2 sites. Tumor response was graded according to RECIST 1.1 criteria. Endpoints were local control (LC), progression-free survival (PFS) and overall survival (OS). Results: From 2013 to 2017, a total of 41 patients were treated with SBRT on 64 metastases. Seven (17.1%) patients were systemic therapy naive at time of SBRT and 25 (61%) patients were treated on one single lesion. Most common sites of disease were lung (29.3%) and liver (56.1%). Median biologic effective dose (BED) was 105.6 Gy (57.6 – 262.5). Rates of LC at 1 and 2 years were 88.9% and 73.9%. Median LC was 39.9 months. None of the analyzed risk factors were associated with LC. Rates of PFS at 1 and 2 years were 21.9% and 10.9%. Median PFS was 5.4 months. At univariate analysis sex (HR 2.50; p = 0.014), time to metastases (HR 0.96; p = 0.034), extra-target disease (HR 3.60; p = 0.012), BED (HR 1.00; p = 0.033) were impacting. At multivariable analysis sex (HR 4.59; p = 0.001), time to first diagnoses of metastases (HR 0.96; p = 0.031) and extra-target disease (HR 7.36; p = 0.001) were significant for PFS. Rates of OS at 1 and 2 years were 79.9% and 46.7%. Median OS was 23 months. At univariate analysis time to first diagnoses of metastases (HR 0.95; p = 0.036), and BED (HR 1.00; p = 0.017) were significant for OS. No factor was significant for multivariable analysis. Conclusion: Our study shows that SBRT on oligometastases from pancreatic cancer is a feasible and effective approach in terms of local disease control. Prospective trials are warranted to improve patient's selection and to better define the integration of SBRT into a combined-modality treatment.

AIMS: To investigate the role of intensity-modulated proton therapy (IMPT) for regional nodal irradiation in patients with breast carcinoma in comparison with volumetric-modulated arc therapy (VMAT). MATERIALS AND METHODS: A cohort of 20 patients (10 in the breast-conserving surgery group and 10 post-mastectomy patients with tissue expander implants) was investigated. Proton plans were also computed using robust optimisation methods. Plan quality was assessed by means of dose-volume histograms and scored with conventional metrics. Estimates of the risk of secondary cancer induction (excess absolute risk, EAR) were carried out, taking into account fractionation, repopulation and repair. RESULTS: Concerning target coverage, the data proved a substantial equivalence of VMAT and IMPT: for example, coverage for the 50 Gy target, expressed in terms of V98%, was 47.8 ± 0.4, 47.6 ± 0.4, 47.3 ± 0.8, consistent with the objective of 47.5 Gy, for post-mastectomy patients for the three groups of patients. Also, the conformality of the dose distributions was similar for the two techniques, about 1.1, without statistically significant differences. Organ at risk planning aims were achieved for all structures for both techniques. The mean dose to the ipsilateral lung was 10.8 ± 1.1, 6.2 ± 0.8, 7.2 ± 1.0; for the contralateral lung was 3.2 ± 0.7, 0.3 ± 0.2, 0.4 ± 0.2; for the contralateral breast was: 3.1 ± 0.7, 0.3 ± 0.3 and 0.3 ± 0.3, whereas it was 3.9 ± 0.9, 0.4 ± 0.3 and 0.5 ± 0.5, respectively, for the heart for VMAT, IMPT and robust IMPT plans over the whole group of patients. Robust optimisation affected the near-to-maximum dose values for contralateral lung and breast, the mean dose for the heart and ipsilateral lung, with a deterioration ranging from 20 to 40% of the nominal value of IMPT plans (e.g. from 8.1 ± 6.4 to 11.4 ± 8.8 for the heart compared with 16.2 ± 5.2 for the VMAT plans). The numerical values of EAR per 10 000 patient-years were about one order of magnitude higher for VMAT than for IMPT for contralateral structures: 11.66 ± 2.01, 0.89 ± 0.80, 0.98 ± 0.77 for the contralateral breast and the three groups of plans, respectively; 14.31 ± 2.75, 1.42 ± 0.80, 1.78 ± 0.87 for the contralateral lung; and 34.86 ± 2.64, 18.85 ± 2.15, 20.98 ± 2.35 for the ipsilateral lung. CONCLUSION: IMPT with or without robust optimisation seems to be a potentially promising approach for the radiation treatment of breast cancer when nodal volumes should be irradiated. This was measured in terms of dosimetric advantage and predicted clinical benefit. In fact, the significant reduction in estimated EAR could add further clinical value to the dosimetric sparing of the organs at risk achievable with IMPT.

Purpose or ObjectiveThe re-irradiation of locally recurrent rectal cancer presents challenges due to the proximity of critical organs such as bowel.Ion beam therapy, specifically carbon ions radiotherapy (CIRT) have some advantages for the favorable relative biological effectiveness and physical dose distribution providing a highly conformal dose distribution while minimizing normal tissue damage.The aim of this study is to report our experience on feasibility and toxicity of carbon-ion radiotherapy (CIRT) in previously irradiated patients with locally recurrent rectal cancer. Material and MethodsBetween August 2014 and February 2017, a total of 10 patients (M:F= 8:2) were treated with CIRT as reirradiation for locally recurrent rectal cancer at National Centre of Oncological Hadrontherapy (CNAO).Patient ages ranged between 46 to 78 years (median 58.5 years).All patients had a history of surgery and pelvic radiotherapy.Specifically, the dose of previous radiotherapy ranged from 45 to 50.4 Gy in 9 patients one of which received a brachytherapy boost up to a total dose of 20Gy.One patient was irradiated with a total dose of 76 Gy for a prostatic cancer.One patient, at time of the first recurrence, underwent to re-irradiation with stereotactic radiotherapy (30 Gy in 6 fractions).They had 7 presacral, 1 perineal, 1 perianal and 1 pre-coccygeal relapses.Three patients received spacer implantation prior to CIRT to secure adequate distance between bowel and tumor.Toxicity was scored according CTCAE 4.0 scale. ResultsThe median interval between the two courses of radiotherapy was 89.3 months (range: 13.8 -138.2).Median total dose of CIRT was 60 GyRBE (range: 35-76.8)and was administered in a median number of 16 fractions (range: 15-20) over 4 weeks (from 3 to 4.8 Gy RBE/fraction).The GTV ranged from 7.21 to 300.8 cm 3 with a median of 28.42 cm 3 .The PTV ranged from 53.55 to 742.64 cm 3 .All patients completed the scheduled treatment course.Median follow-up was 13 months.Acute toxicity was mild and mainly neuropathic: grade 2 (G2) neuropathic pain in 1 (10%) and G1 in 2 (20%) patients.The major late toxicities were peripheral neuropathy (20%, G2).No G≥3 acute/late reaction nor pelvic infections were observed.Four patients were diagnosed with local progression after carbon ion radiotherapy with a median disease free survival of 11.4 months (range: 2.4-39.7).Three patients experienced systemic progression.The estimated 1-year-local control rate was 80%. ConclusionIn our experience, CIRT for locally recurrent rectal cancer appears to be safe and effective with an acceptable rate of morbidity of normal tissue.More data and longer follow-up are required to investigate the long-term disease control and to determine late effects.

Regional and distant relapse remain a significant issue in the treatment of early stage non small cell lung cancer with Stereotactic Body Radiation Therapy (SBRT). There is a need for predictive biomarkers able to identify patients that are at higher risk of relapse. In this work we present a radiomic approach using features extracted by routine planning CT, to predict the risk of nodal and distant recurrence. A cohort of 102 patients was retrospectively investigated. All patients were affected by early stage (T1-T2) lung cancer and received the same radiation treatment with 48Gy delivered in 4 fractions. For all patients, a set of 45 radiomics textural features was computed for the tumor volumes segmented on the treatment planning CT images. Patients were split into two independent cohorts used for training (70% of cases) and validation (30% of cases). A stepwise backward linear discriminant analysis (LDA) was applied as a classifier to identify patients at risk of lymph-nodal progression. The performance of the model was assessed by means of standard metrics derived from the confusion matrix. Furthermore, all textural features were correlated to survival data to build predictive models: the features/predictors found significant at univariate analysis and to elastic net regularization, were included in a multivariate model to predict disease specific progression free survival (PFS) and disease specific survival (DS OS). Low and high risk groups were identified by maximizing the separation by means of the Youden method. In the total cohort (77 (75.5%) males and 25 (24.5%) females, median age 76.6 years), 15 patients presented nodal progression at the time of analysis (11 in the training and 4 in the validation sets); 19 patients (18.6%) died because of disease specific causes, 25 (24.5%) died for other reasons, 28 (27.5%) were alive without disease and 30 (29.4%) with either local or distant progression. The mean tumor volume was 5.6±6.4cm3. Figure 1 illustrates the actuarial curves for PFS and DS OS over the entire training and test cohorts (in both cases the difference was not significant) and the same data stratified in low and high risk groups identified. In all case highly significant differences were identified. Radiomics features extracted from treatment planning CT images can distinguish patients with low and high risk of tumor progression and disease specific death in early stage lung cancer treated with SBRT.