Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma, as such it can pose a clinical dilemma based solely on its rarity. Also, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. In our clinical practice, the primary focus has been to get a handle on the aggressive nature of the disease, which will then dictate how urgently one needs to treat the patient. Pathological review with immunohistochemistry and molecular characterization is paramount. Our treatment strategy is watch-and-wait versus active therapy on clinical trial or based on results of prior clinical trials. There is evidence to support the use of chemotherapeutics and targeted therapies specifically focusing on anti-angiogenesis. The current landscape of oncology with the emergence and excitement of immunotherapy could also translate in a role for immunotherapy in this disease. While rare, there is certainly no reason that research and trials for patients with EHE should not remain on utmost importance for those of us who specialize in the treatment of sarcomas.

Treatment of locoregionally advanced head and neck squamous cell carcinoma involves a multidisciplinary approach that combines surgery, radiotherapy, and systemic therapy. These curative strategies are associated with significant acute and long-term toxicities. With the emergence of human papillomavirus (HPV) as an etiologic factor associated primarily with oropharyngeal squamous cell carcinoma, higher cure rates juxtaposed with substantial treatment-related morbidity and mortality has led to interest in de-escalated therapeutic strategies, with the goal of optimizing oncologic outcomes while reducing treatment-related toxicity. Currently explored strategies include replacing, reducing, or omitting cytotoxic chemotherapy; reducing dose or volume of radiotherapy; and incorporation of less-invasive surgical approaches. Potential biomarkers to select patients for treatment de-escalation include clinical risk stratification, adjuvant de-escalation based on pathologic features, response to induction therapy, and molecular markers. The optimal patient selection and deescalation strategy is critically important in the evolving treatment of locoregional head and neck cancer. Recently, two large phase III trials, RTOG 1016 and De-ESCALaTE, failed to de-escalate treatment in HPV-associated head and neck cancer by demonstrating inferior outcomes by replacing cisplatin with cetuximab in combination with radiation. This serves as a cautionary tale in the future design of de-escalation trials in this patient population, which will need to leverage toxicity and efficacy endpoints. Our review summarizes completed and ongoing de-escalation trials in head and neck cancer, with particular emphasis on biomarkers for patient selection and clinical trial design. The Oncologist 2020;25:1-9 Implications for Practice: The toxicity associated with standard multimodality treatment for head and neck cancer underscores the need to seek less-intensive therapies with a reduced long-term symptom burden through de-escalated treatment paradigms that minimize toxicity while maintaining oncologic control in appropriately selected patients. Controversy regarding the optimal de-escalation strategy and criteria for patient selection for de-escalated therapy has led to multiple parallel strategies undergoing clinical investigation. Well-designed trials that optimize multimodal strategies are needed. Given the absence of positive randomized trials testing de-escalated therapy to date, practicing oncologists should exercise caution and administer established standard-of-care therapy outside the context of a clinical trial.

Pancreatic adenocarcinoma (PAC) remains one of the leading causes of cancer-related death. Despite multiple advances in targeted and immune therapies, the 5-year survival in advanced PAC remains poor. In this review, we discuss some of the unique aspects of the tumor microenvironment (TME) in PAC that may contribute to its resistance to immune therapies, as well as opportunities to potentially overcome some of these inherent barriers. Furthermore, we discuss strategies to enable immune therapies in PAC such as cytotoxic chemotherapy and radiation therapy, cancer vaccines, cytokine based therapy, oncolytic viruses, and adoptive T-cell therapy. Finally, we address a variety of targeted therapies as a strategy to further amplify immune responses in PAC.

The treatment of patients with HPV-associated oropharyngeal cancer (HPV-OPC) is rapidly evolving and challenging the standard of care of definitive radiotherapy with concurrent cisplatin. There are numerous promising de-escalation strategies under investigation, including deintensified definitive chemoradiotherapy, transoral surgery followed by de-escalated adjuvant therapy, and induction chemotherapy followed by de-escalated locoregional therapy. Definitive radiotherapy alone or with cetuximab is not recommended for curative-intent treatment of patients with locally advanced HPV-OPC. The results of ongoing phase III studies are awaited to help answer key questions and address ongoing controversies to transform the treatment of patients with HPV-OPC. Strategies for de-escalation under investigation include the incorporation of immunotherapy and the use of novel biomarkers for patient selection for de-escalation.

BackgroundIndoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC.ResultsHigh IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001).ConclusionsEC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC.Materials and MethodsmRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic analysis.