Role of Chemoradiation in the Adjuvant Treatment of Radically Resected Pancreatic Cancer Patients: A Mono-Institutional Retrospective Analysis.

INTRODUCTION: Pancreatic cancer (PC) represents an unfavorable prognosis condition, even in patients with resectable disease. The aim of this series was to investigate the role of treatment intensification with adjuvant chemoradiation (CRT) in radically resected PC patients. METHODS: Data from PC patients who underwent radical surgery, adjuvant chemotherapy (CT), and CRT throughout a 20-year period were retrospectively collected. Actuarial local control (LC) and the overall survival (OS) were the primary endpoints, with disease-free survival and metastasis-free survival (MFS) representing secondary endpoints. RESULTS: The analysis included 108 PC patients treated with adjuvant CRT and CT from January 2000 to August 2019. Median age was 66 years (range: 40-83), and all patients underwent radical surgical resection with adjuvant CT (88, 81.5%) plus concomitant CRT (101, 93.5%) or radiotherapy alone (7, 6.5%). The median dose delivered to the tumor bed was 50.4 Gy (range: 45-50.6 Gy), while median dose to regional lymphatic drainage stations was 39.6 Gy (range 39.6-45 Gy). Concomitant CT was a gemcitabine-based regimen in the vast majority of patients (87, 80.6%). Median follow-up time was 21 months; the 2- and 5-year LC rates were 75.8% and 59.1%, respectively. Perineural invasion at pathological assessment was found significantly associated with LC (p = 0.028). Median OS was 40 months with 2- and 5-year OS rates of 73.9% and 41.6%, respectively. CONCLUSIONS: The outcomes of this series suggest to investigate the possible impact of adding adjuvant CRT to CT in PC patients. Timing and combination of modern CRT with new systemic therapies need to be further investigated to personalize therapy and optimize clinical advantages.

11 C-PK11195 PET-based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis.

OBJECTIVE: Neuroinflammation is considered a key driver for neurodegeneration in several neurological diseases, including amyotrophic lateral sclerosis (ALS). SOD1 mutations cause about 20% of familial ALS, and related pathology might generate microglial activation triggering neurodegeneration. 11 C-PK11195 is the prototypical and most validated PET radiotracer, targeting the 18-kDa translocator protein which is overexpressed in activated microglia. In this study, we investigated microglia activation in asymptomatic (ASYM) and symptomatic (SYM) SOD1 mutated carriers, by using 11 C-PK11195 and PET imaging. METHODS: We included 20 subjects: 4 ASYM-carriers, neurologically normal, 6 SYM-carriers with probable ALS, and 10 healthy controls. A receptor parametric mapping procedure estimated 11 C-PK11195 binding potentials and voxel-wise statistical comparisons were performed at group and single-subject levels. RESULTS: Both the SYM- and ASYM-carriers showed significant microglia activation in cortical and subcortical structures, with variable patterns at individual level. Clusters of activation were present in occipital and temporal regions, cerebellum, thalamus, and medulla oblongata. Notably, SYM-carriers showed microglia activation also in supplementary and primary motor cortices and in the somatosensory regions. INTERPRETATION: In vivo neuroinflammation occurred in all SOD1 mutated cases since the presymptomatic stages, as shown by a significant cortical and subcortical microglia activation. The involvement of sensorimotor cortex became evident at the symptomatic disease stage. Although our data indicate the role of in vivo PET imaging for assessing resident microglia in the investigation of SOD1-ALS pathophysiology, further studies are needed to clarify the temporal and spatial dynamics of microglia activation and its relationship with neurodegeneration.