Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis‐free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor‐specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under‐addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.

Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.

Significant weight loss is common in patients with head and neck squamous cell carcinoma (HNSCC).^1,2 In these patients, weight loss is complicated by tumor location and the subsequent local toxic effects of radiotherapy (RT) and chemoradiotherapy (CRT). Because these factors make food intake challenging, patients receiving RT or CRT are offered dietary counseling, nutritional supplementation, and often feeding tubes. However, multiple trials evaluating nutritional interventions have failed to show an improvement in survival.³ Weight loss is commonly used to screen the risk for poor outcomes in the clinical setting, but contradictory studies leave the relationship between treatment-associated weight loss and survival unclear.^4-6

Skeletal muscle catabolism is a co-morbidity of many chronic diseases and is the result of systemic inflammation. Although direct inflammatory cytokine action on muscle promotes atrophy, nonmuscle sites of action for inflammatory mediators are less well described. We demonstrate that central nervous system (CNS)–delimited interleukin 1β (IL-1β) signaling alone can evoke a catabolic program in muscle, rapidly inducing atrophy. This effect is dependent on hypothalamic–pituitary–adrenal (HPA) axis activation, as CNS IL-1β–induced atrophy is abrogated by adrenalectomy. Furthermore, we identified a glucocorticoid-responsive gene expression pattern conserved in models of acute and chronic inflammatory muscle atrophy. In contrast with studies suggesting that the direct action of inflammatory cytokines on muscle is sufficient to induce catabolism, adrenalectomy also blocks the atrophy program in response to systemic inflammation, demonstrating that glucocorticoids are requisite for this process. Additionally, circulating levels of glucocorticoids equivalent to those produced under inflammatory conditions are sufficient to cause profound muscle wasting. Together, these data suggest that a significant component of inflammation-induced muscle catabolism occurs indirectly via a relay in the CNS.

Cross sectional imaging is essential for the patient-specific planning and delivery of radiotherapy, a primary determinant of head and neck cancer outcomes. Due to challenges ensuring data quality and patient de-identification, publicly available datasets including diagnostic and radiation treatment planning imaging are scarce. In this data descriptor, we detail the collection and processing of computed tomography based imaging in 215 patients with head and neck squamous cell carcinoma that were treated with radiotherapy. Using cross sectional imaging, we calculated total body skeletal muscle and adipose content before and after treatment. We detail techniques for validating the high quality of these data and describe the processes of data de-identification and transfer. All imaging data are subject- and date-matched to clinical data from each patient, including demographics, risk factors, grade, stage, recurrence, and survival. These data are a valuable resource for studying the association between patient-specific anatomic and metabolic features, treatment planning, and oncologic outcomes, and the first that allows for the integration of body composition as a risk factor or study outcome.