With increasing use of immunotherapy agents, pretreatment strategies for identifying responders and non-responders is useful for appropriate treatment assignment. We hypothesize that the local immune micro-environment of NSCLC is associated with patient outcomes and that these local immune features exhibit distinct radiologic characteristics discernible by quantitative imaging metrics. We assembled two cohorts of NSCLC patients treated with definitive surgical resection and extracted quantitative parameters from pretreatment CT imaging. The excised primary tumors were then quantified for percent tumor PDL1 expression and density of tumor-infiltrating lymphocyte (via CD3 count) utilizing immunohistochemistry and automated cell counting. Associating these pretreatment radiomics parameters with tumor immune parameters, we developed an immune pathology-informed model (IPIM) that separated patients into 4 clusters (designated A-D) utilizing 4 radiomics features. The IPIM designation was significantly associated with overall survival in both training (5 year OS: 61%, 41%, 50%, and 91%, for clusters A-D, respectively, P = 0.04) and validation (5 year OS: 55%, 72%, 75%, and 86%, for clusters A-D, respectively, P = 0.002) cohorts and immune pathology (all P < 0.05). Specifically, we identified a favorable outcome group characterized by low CT intensity and high heterogeneity that exhibited low PDL1 and high CD3 infiltration, suggestive of a favorable immune activated state. We have developed a NSCLC radiomics signature based on the immune micro-environment and patient outcomes. This manuscript demonstrates model creation and validation in independent cohorts.

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Running title: CT-based subtypes of pancreatic ductal adenocarcinoma. Keywords Statement of translational relevanceThere are currently limited methods to stratify patients with pancreatic ductal adenocarcinoma (PDAC) into prognostic groups based on disease biology. We focused on the morphological features of the disease on computed tomography (CT) scans and correlated these features with genomic, pathological, and clinical data. We found that tumors with a distinct interface in relation to the surrounding parenchyma (called high delta tumors) had more aggressive biological features than tumors without a distinct interface (called low delta tumors). Patients with high delta tumors were more likely to develop early distant metastasis and die faster than those with low delta tumors. Mathematical modeling suggested that stromal elements strongly influenced the morphological patterns seen on CT scans. These findings indicate that a universally available diagnostic test can be used to interrogate the biology of this deadly disease, providing a means to stratify patients at diagnosis and aiding the design of future clinical trials.

PurposeTo review acute and late toxicities after chemoradiation for locally advanced pancreatic ductal adenocarcinoma in patients who were treated with escalated dose radiation (EDR).Methods and materialsMaximum Common Terminology Criteria for Adverse Events Version 4.0 acute toxicities (AT) during radiation and within 60 days after radiation were recorded for both acute gastrointestinal toxicity and overall toxicity (OT). Late toxicities were also recorded. EDR was generally delivered with daily image guidance and breath-hold techniques using intensity modulated radiation therapy (IMRT) planning. These were compared with patients who received standard dose radiation (SDR) delivered as 50.4 Gy in 28 fractions using 3-dimensional chemoradiation therapy planning.ResultsA total of 59 of 154 patients (39%) received EDR with biologically equivalent doses >70 Gy. The most frequent schedules were 63 Gy in 28 fractions (19 of 154 patients), 67.5 Gy in 15 fractions (10 of 154 patients), and 70 Gy in 28 fractions (15 of 154 patients). No grade 4 or grade 5 OT or late toxicities were reported. Rates of grade 3 acute gastrointestinal toxicity were significantly lower in patients who received EDR compared with SDR (1% vs 14%; P < .001). Similarly, rates of grade 3 OT were also lower for EDR compared with SDR (4% vs 16%; P = .004). The proportion of patients who experienced no AT was higher in the EDR group than the SDR group (36% vs 15%; P = .001). For EDR patients treated with IMRT, a lower risk of AT was associated with a later treatment year (P = .007), nonpancreatic head tumor location (P = .01), breath-hold (P = .002), 4-dimensional computed tomography (P = .003), computed tomography on rails (P = .002), and lower stomach V40 (P = .03). With a median time of 12 months (range, 1-79 months) from the start of radiation therapy to the last known follow-up in the EDR group, 51 of 59 patients (86%) had no late toxicity. Six of 59 EDR patients (10%) had either strictures or gastrointestinal bleeding that required intervention. No significant predictors of late toxicity were identified.ConclusionOverall acute and late toxicity rates were low with EDR using an IMRT technique with image guidance and respiratory gating.

Tumors and tumorlike conditions of the anus and perianal region originate from the anal canal and anal margin or result from direct extension of tumors from adjacent organs. The anatomy of the anal canal is complex, and its different histologic characteristics can lead to diverse pathologic conditions. The anal canal extends from the anorectal junction to the anal verge. The World Health Organization classification of anal canal tumors includes (a) anal intraepithelial neoplasia, the precursor of squamous cell carcinoma (SCC), and (b) invasive tumors. Invasive tumors are further classified on the basis of cell type as epithelial tumors (SCC, adenocarcinoma, mucinous adenocarcinoma, small cell carcinoma, and undifferentiated carcinoma), nonepithelial tumors, carcinoid tumors, melanoma, and secondary tumors (direct spread from rectal, cervical, or prostate carcinoma). The anal margin, or perianal skin, lies outside the anal verge and encompasses a radius of 5 cm from the anal verge. Tumors in the anal margin are classified according to the World Health Organization classification of skin tumors. Anal margin tumors include SCC, anal intraepithelial neoplasia, also known as Bowen disease, adenocarcinoma and its precursor Paget disease, basal cell carcinoma, and verrucous carcinoma (Buschke-Löwenstein tumor), which is a rare variant of SCC. Imaging plays an important role in the evaluation, staging, and follow-up of patients with anal and perianal tumors. However, because of the overlap in imaging features among these diverse entities, a definitive diagnosis is best established at histopathologic examination. Nevertheless, familiarity with the pathogenesis, imaging features, and treatment of these tumors can aid radiologic diagnosis and guide appropriate patient treatment. (©)RSNA, 2016.