Prognostic value of total tumor regression after pre-operative chemo-radiotherapy in rectal cancer (RC)

The main objective of this study is to determine the prognostic value of complete tumor regression after pre-operative chemoradiotherapy in RC. Our study confirms that a complete pathological response on T (Dworak 4) after pre-operative treatment is an important prognostic factor. The persistance of microscopic residual disease (Dworak 3) is associated with a favourable local control

Prognostic value of "Dworak" tumor regression grade (TRG) after pre-operative chemo-radiotherapy in rectal cancer (RC)

Our study confirms the prognostic value of pathological stage and Dworak TRG after pre-operative treatment. Moreover in post- operative stage I II-III our analysis has demonstrated a trend in disease free survival improvement for patients with a high Dworak TRG

Prognostic value of "Dworak" tumor regression grade (TRG) after pre-operative chemo-radiotherapy in rectal cancer (RC)

none10noneF. Bertolini; L. Losi; F. Iachetta; P. Giacobazzi; E. Romagnani; C. Dealis; F. Bertoni; G. Luppi; C. Bengala; P. ConteF., Bertolini; L., Losi; F., Iachetta; P., Giacobazzi; E., Romagnani; C., Dealis; F., Bertoni; G., Luppi; C., Bengala; Conte, Pierfranc

Expert system classifier for adaptive radiation therapy in prostate cancer

A classifier-based expert system was developed to compare delivered and planned radiation therapy in prostate cancer patients. Its aim is to automatically identify patients that can benefit from an adaptive treatment strategy. The study predominantly addresses dosimetric uncertainties and critical issues caused by motion of hollow organs. 1200 MVCT images of 38 prostate adenocarcinoma cases were analyzed. An automatic daily re-contouring of structures (i.e. rectum, bladder and femoral heads), rigid/deformable registration and dose warping was carried out to simulate dose and volume variations during therapy. Support vector machine, K-means clustering algorithms and similarity index analysis were used to create an unsupervised predictive tool to detect incorrect setup and/or morphological changes as a consequence of inadequate patient preparation due to stochastic physiological changes, supporting clinical decision-making. After training on a dataset that was considered sufficiently dosimetrically stable, the system identified two equally sized macro clusters with distinctly different volumetric and dosimetric baseline properties and defined thresholds for these two clusters. Application to the test cohort resulted in 25% of the patients located outside the two macro clusters thresholds and which were therefore suspected to be dosimetrically unstable. In these patients, over the treatment course, mean volumetric changes of 30 and 40% for rectum and bladder were detected which possibly represents values justifying adjustment of patient preparation, frequent re-planning or a plan-of-the-day strategy. Based on our research, by combining daily IGRT images with rigid/deformable registration and dose warping, it is possible to apply a machine learning approach to the clinical setting obtaining useful information for a decision regarding an individualized adaptive strategy. Especially for treatments influenced by the movement of hollow organs, this could reduce inadequate treatments and possibly reduce toxicity, thereby increasing overall RT efficacy

Pancreatic metastases from renal cell carcinoma: The state of the art

Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease

Cosmetic Results and Side Effects of Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Low-Risk Invasive Carcinoma of the Breast: The Randomized Phase III IRMA Trial

PURPOSE: The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. METHODS: We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. RESULTS: Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities. CONCLUSION: External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range

SIS epidemiological model for adaptive RT: Forecasting the parotid glands shrinkage during tomotherapy treatment

Purpose: A susceptible-infected-susceptible (SIS) epidemic model was applied to radiation therapy (RT) treatments to predict morphological variations in head and neck (H&amp;N) anatomy. Methods: 360 daily MVCT images of 12 H&amp;N patients treated by tomotherapy were analyzed in this retrospective study. Deformable image registration (DIR) algorithms, mesh grids, and structure recontouring, implemented in the RayStation treatment planning system (TPS), were applied to assess the daily organ warping. The parotid's warping was evaluated using the epidemiological approach considering each vertex as a single subject and its deformed vector field (DVF) as an infection. Dedicated IronPython scripts were developed to export daily coordinates and displacements of the region of interest (ROI) from the TPS. MATLAB tools were implemented to simulate the SIS modeling. Finally, the fully trained model was applied to a new patient. Results: A QUASAR phantom was used to validate the model. The patients' validation was obtained setting 0.4 cm of vertex displacement as threshold and splitting susceptible (S) and infectious (I) cases. The correlation between the epidemiological model and the parotids' trend for further optimization of alpha and beta was carried out by Euclidean and dynamic time warping (DTW) distances. The best fit with experimental conditions across all patients (Euclidean distance of 4.09 +/- 1.12 and DTW distance of 2.39 +/- 0.66) was obtained setting the contact rate at 7.55 +/- 0.69 and the recovery rate at 2.45 +/- 0.26; birth rate was disregarded in this constant population. Conclusions: Combining an epidemiological model with adaptive RT (ART), the authors' novel approach could support image-guided radiation therapy (IGRT) to validate daily setup and to forecast anatomical variations. The SIS-ART model developed could support clinical decisions in order to optimize timing of replanning achieving personalized treatments. (C) 2016 American Association of Physicists in Medicine

Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients

ABSTRACTCancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1β-converting enzyme)-inhibitory protein (c-FLIP), which acts as an important modulator of caspase-8, is required for the development and function of monocytic (M)-MDSCs. Here, we assessed the effect of immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape, including FLIP-expressing MDSCs, in non-small cell lung cancer (NSCLC) patients. Longitudinal changes in peripheral immunological parameters were correlated with patients’ outcome. In detail, 34 NSCLC patients were enrolled and classified as progressors (P) or non-progressors (NP), according to the RECIST evaluation. We demonstrated a reduction in pro-inflammatory cytokines such as IL-8, IL-6, and IL-1β in only NP patients after ICI treatment. Moreover, using t-distributed stochastic neighbor embedding (t-SNE) and cluster analysis, we characterized in NP patients a significant increase in the amount of lymphocytes and a slight contraction of myeloid cells such as neutrophils and monocytes. Despite this moderate ICI-associated alteration in myeloid cells, we identified a distinctive reduction of c-FLIP expression in M-MDSCs from NP patients concurrently with the first clinical evaluation (T1), even though NP and P patients showed the same level of expression at baseline (T0). In agreement with the c-FLIP expression, monocytes isolated from both P and NP patients displayed similar immunosuppressive functions at T0; however, this pro-tumor activity was negatively influenced at T1 in the NP patient cohort exclusively. Hence, ICI therapy can mitigate systemic inflammation and impair MDSC-dependent immunosuppression