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The abscopal effect is a systemic immune response mediated by the effects of radiation on the immune system. This effect has been observed in a number of cancer types in addition to lung cancer, including but not limited to renal cell carcinoma, hepatocellular carcinoma, lymphoma, and melanoma. The combination of radiation therapy and immune checkpoint inhibition (ICI) acts at several stages of the antitumor response, suggesting a mechanism of synergy between the two modalities. This review focuses on recent advances in the understanding of the effect of radiation and immunotherapy in the context of the abscopal effect.

Mantle cell lymphoma (MCL) is a heterogenous disease with a variety of morphologic and genetic features, some of which are associated with high risk disease. Here we critically analyze the current state of the understanding of MCL’s biology and its implications in therapy, with a focus on chemotherapy-free and targeted therapy regimens. Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin’s lymphoma, defined by a hallmark chromosomal translocation t(11;14) which leads to constitutive expression of cyclin D1. Recent discoveries in the biology of MCL have identified a number of factors, including TP53 mutations and complex karyotype, that lead to unresponsiveness to traditional chemoimmunotherapy and poor outcomes. Bruton tyrosine kinase inhibitors, BH3-mimetics and other novel agents thwart survival of the neoplastic B-cells in a manner independent of high-risk mutations and have shown promising activity in relapsed/refractory MCL. These therapies are being investigated in the frontline setting, while optimal responses to chemotherapy-free regimens, particularly in high-risk disease, might require combination approaches. High-risk MCL does not respond well to chemoimmunotherapy. Targeted agents are highly active in the relapsed refractory setting and show promise in high-risk disease. Novel approaches may soon replace the current standard of care in both relapsed and frontline settings.

Mantle cell lymphoma (MCL) is a heterogenous disease with a variety of morphologic and genetic features, some of which are associated with high risk disease. Here we critically analyze the current state of the understanding of MCL's biology and its implications in therapy, with a focus on chemotherapy-free and targeted therapy regimens.Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma, defined by a hallmark chromosomal translocation t(11;14) which leads to constitutive expression of cyclin D1. Recent discoveries in the biology of MCL have identified a number of factors, including TP53 mutations and complex karyotype, that lead to unresponsiveness to traditional chemoimmunotherapy and poor outcomes. Bruton tyrosine kinase inhibitors, BH3-mimetics and other novel agents thwart survival of the neoplastic B-cells in a manner independent of high-risk mutations and have shown promising activity in relapsed/refractory MCL. These therapies are being investigated in the frontline setting, while optimal responses to chemotherapy-free regimens, particularly in high-risk disease, might require combination approaches. High-risk MCL does not respond well to chemoimmunotherapy. Targeted agents are highly active in the relapsed refractory setting and show promise in high-risk disease. Novel approaches may soon replace the current standard of care in both relapsed and frontline settings.

Diffuse large B-cell lymphoma (DLBCL) represents around one quarter of non-Hodgkin lymphomas in both the United States and globally. The activated B-cell (ABC) subtype of DLBCL is associated with higher relapse rates and a worse prognosis when treated with standard regimens in comparison to other subtypes of DLBCL. Recent studies have demonstrated a potential benefit with combination of dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-REPOCH) in comparison to standard combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in ABC DLBCL patients. We aimed to see if there was any benefit on progression-free survival (PFS) and overall survival (OS) in a pooled patient population from a community oncology practice with the use of DA-REPOCH in ABC DLBCL. Our study did not reveal a statistically significant advantage in either PFS or OS with DA-REPOCH; however, a smaller percentage or patients progressed or relapsed when treated with DA-REPOCH. While the toxicity profile was similar, a higher percentage of patients receiving R-CHOP experienced grade 3 or higher toxicities. A prospective trial of R-CHOP versus DA-REPOCH in patients with the ABC subtype of DLBCL is warranted to further determine a potential benefit to DA-REPOCH in this patient population.

Intraductal tubulopapillary neoplasm (ITPN) is a distinctive type of pancreatic tumor first discovered more than three decades ago. ITPNs currently account for less than 1% of all pancreatic exocrine tumor cases recognized, and less than 5% of pancreatic intraductal tumors. A patient’s presentation is often nonspecific in comparison to other intraductal pancreatic neoplasms. We discuss a 52-year-old female presenting with abdominal pain and weight loss with ITPN, and go on to define the typical presentation, clinical features, and pathology behind the tumor.

Unresectable hepatocellular carcinoma has several different therapeutic options, including targeted agents as well as locoregional therapy. Yttrium-90 (Y90) radioembolization therapy is an established treatment for unresectable disease and has been compared to other locoregional options as well as different targeted therapies. Newer case series are also reporting a potential benefit to the addition of immunotherapy to Y90 radioembolization. Here we report a case of prolonged survival in a patient whose treatment course included Y90 radioembolization along with sorafenib and nivolumab.

Hypersensitivity pneumonitis (HSP) is an interstitial lung disease caused by exposure to a large range of environmental antigens. Inhaling aerosolized particles leads to a heightened immune response. HSP comes in acute, subacute, or chronic forms, all with their own potential clinical and radiographic findings. Mycobacterium avium complex (MAC) is the most common nontuberculous mycobacteria and is known to cause HSP with certain exposures. However, although certain histologic findings can be seen with HSP, a high ki-67 proliferation index is unusual and more commonly associated with malignancy. In this report, we discuss a case of MAC that had acute HSP associated with a high ki-67 proliferative index.

This review highlights the importance of the Bcl-2 family members in lymphoma cell survival and discusses the approaches to modulate their function, directly or indirectly, to advance lymphoma therapeutics. The balance of cell death versus survival is ultimately leveraged at the mitochondria. Mitochondrial outer membrane permeabilization (MOMP) is the critical event that governs the release of pro-apoptotic molecules from the intermembrane mitochondrial space. MOMP is achieved through the coordinated actions of pro- and anti-apoptotic Bcl-2 family member proteins. Recognition of functional alterations among the Bcl-2 family member proteins led to identification of tractable targets to combat hematologic malignancies. A new class of drugs, termed BH3 mimetics, was introduced in the clinic. Venetoclax, a Bcl-2 inhibitor, received regulatory approvals in therapy of chronic lymphocytic leukemia and acute myeloid leukemia. Alternative pro-survival Bcl-2 family proteins, in particular Mcl-1, have been successfully targeted in preclinical studies using novel-specific BH3 mimetics. Finally, anti-apoptotic Bcl-2 family members may be targeted indirectly, via interference with the pro-survival signaling pathways, e.g., phosphoinotiside-3 kinase, B-cell receptor signaling, and NF-κB.

Over the past decade, mantle cell lymphoma (MCL), a rare subtype of non-Hodgkin lymphoma, has undergone significant transformation in risk stratification and treatment options available to patients. Frontline management now allows for several approaches to optimize patient responses in both younger and elderly patients. In addition to standard chemotherapy options, targeted therapies improve patient outcomes in relapsed and refractory disease. In this paper we examine the landscape of current treatment modalities for patients with MCL.

Adult, Philadelphia chromosome-positive, Acute Lymphoblastic Leukemia (Ph-positive ALL) had a poor prognosis, but with the use of an initial BCR/ABL tyrosine kinase inhibitor such as Dasatinib in conjunction with chemotherapy such as hyper-CVAD, the projected 24 month disease free survival is 64%. More recently Foa et al. on behalf of the GIMEMA investigators published a phase II trial of Dasatinib and Blinatumomab as initial therapy for adults with ALL. The complete remission rate was 98%, and the projected disease-free survival at 24 months is 88%. We wished to analyze the incremental cost-effectiveness ratio (ICER) of the Dasatinib and Blinatumomab therapy as compared to Dasatinib and hyper-CVAD. The comparison is based on retail costs of chemotherapy for Dasatinib, Blinatumomab and hyperCVAD and excluded hospital and outpatient charges. The cost of hyperCVAD is based on treatment of a person with a BSA I.8m2. The retail cost of therapy is shown below. Drug Dose Cost Dasatinib 100 mg $505.67 Blinatumomab 1 mg $126.81 Cyclophosphamide 1,000 mg $231.00 Mesna 1,000 mg $42.89 Vincristine 2 mg $18.52 Dexamethasone 40 mg $4.12 Cytarabine 100 mg $22.88 Leucovorin 25 mg $7.48 The ICER formula is the cost of new therapy minus (-) the cost of standard therapy/quality of adjusted life new therapy - the quality of adjusted life standard (QALY). The yearly cost of Hyper-CVAD and Dasatinib is $147,288.48 per QALY, whereas, the yearly cost of Dasatinib-Blinatumomab is $187,940.46 per QALY. The difference is $42,451.98 which is less than the 50,000-threshold using cost-effective analysis. In conclusion, the combination of Dasatinib-Blinatumomab appears to be cost effective. Disclosures No relevant conflicts of interest to declare.

Betel nut chewing previously has not been common in North America, yet it is the fourth major source of addiction and abuse worldwide. Approximately 700 million individuals, or 10 % of the global population, chew beetle nut on regular basis. It is important for patient safety and improved quality to recognize its use in uncontrolled diabetes. Our case is of a 49 year-old Burmese female with PMH of DM2, HTN, and benign paroxysmal positional vertigo (BPPV) who presented with a complaint of dizziness. Patient denied alcohol or tobacco use, but reported a 20-year history of betel nut chewing (4-5 times/day). Physical exam showed oral mucosa was dry with poor dentition along with eroded enamel and gums. Point-of-care glucose was extremely elevated at 522 mg/dL with HbA1c of 10.8%. Dix-Hallpike maneuver was negative and CTA of the head and neck was unremarkable. Neurology was also consulted regarding her dizziness, and MRI head demonstrated no acute infarct or hemorrhage. Throughout admission, patient’s point of care glucose fluctuated between 91 and 316 (mg/dL), with several daily spikes. Her dizziness improved by day 2 of hospitalization. At the time of discharge, her glucose was controlled on 50 units of glargine at nighttime along with 8 units of insulin at meals. After a negative initial workup for occult causes of dizziness, it was concluded that her 20-year history of betel nut chewing contributed to dizziness and hyperglycemia. Multiple studies show high risk of diabetes, increased likelihood of coronary artery disease and all-cause mortality in betel nut users. Specifically, one study in Taiwan demonstrated increasing incidence ratios of type II diabetes with increasing age. Conclusion: 1.4 million Americans are diagnosed with diabetes every year. It is the seventh leading cause of death in US, and costs $69 billion in reduced productivity. Prevention and tight glycemic control remain the core of diabetes management. With an increasing Indian and South Asian immigrant population, physicians need to be aware of potential harmful effects of betel nut to improve quality of care. Screening for betel nut use should be a routine part of social history in susceptible populations. Counseling should be provided to educate patients about its harmful effects, and cessation should be encouraged.

Acute myeloid leukemia (AML) is primarily a disease of older adults and can arise de novo, in relation to previous treatment or in the setting of underlying hematological disease. While it is known to arise from chemoradiation in the setting of breast cancer, little is known about the association between BRCA carriers and AML. We report a case of a young female BRCA carrier who develops de novo AML without prior chemoradiation treatment, and examine if there is a link between BRCA and developing leukemia.

e20081 Background: Patients with diffuse large B-cell lymphoma of activated B-cell type (DLBCL-ABC) have a worse prognosis than patients with DLBCL of germinal center origin. Recently, a phase III randomized trial of patients with DLBCL showed no improvement in response rates or progression free survival (PFS) with REPOCH compared to RCHOP. However, the PFS reported in this study was significantly better than expected, indicating that high-risk patients, such as those with DLBCL-ABC, may have been underrepresented. The optimal treatment for patients with DLBCL-ABC remains unknown. Methods: We undertook a retrospective analysis of patients with DLBCL treated in our practice from January 1, 2015 to May 31, 2019. We then examined treatment approaches and outcomes of patients treated for DLBCL-ABC. Results: We treated 136 patients with DLBCL and identified 18 of 136 patients with DLBCL-ABC. There were 9 men and 9 women with a median age of 74 years (range 26-92 years) and a median performance status of Eastern Cooperative Oncology Group 1, (0-2). The median international prognostic index score was 3. Nine of 18 patients were treated with REPOCH, 8 with RCHOP, and one with bendamustine and rituximab (BR). The stage distribution was stage I in 2 patients, stage III in 4 patients, and stage IV in 12 patients. Of 9 patients treated with REPOCH, 9 (100%) achieved a complete remission with no relapses to date. Of 8 patients treated with RCHOP, 6 (75%) achieved a complete remission and 2 had no response and died. The one patient treated with BR failed to respond and died. The median PFS for the 8 patients treated with RCHOP was 19.5 months; whereas, the PFS in the REPOCH group had not been reached at a median follow up of 2 years. Grade 3 and 4 toxicities were more common in the RCHOP group and included cardiomyopathy in 1 patient and two episodes of neutropenic fever (one resulting in septic shock and death). There were no grade 3 or 4 toxicities in the REPOCH group. Conclusions: In this retrospective analysis, our patients with DLBCL-ABC treated with REPOCH had better overall outcomes. A prospective trial in this subset of DLBCL patients is warranted.

e19033 Background: Insurance status impacts access to cancer care and outcomes of cancer patients. Patients who are uninsured and those who are insured by Medicaid are less likely to receive cancer screening, more likely to present at later stages of disease, and more likely to die from cancer compared to those who are privately insured. It is unclear whether patients insured by Medicare have different outcomes than patients with private insurance. Methods: We undertook a retrospective analysis of patients treated in our practice from January 1, 2019 to March 31, 2019. Outcomes of solid tumor patients were tracked after treatment in the neoadjuvant or metastatic setting. Patients were stratified by their insurance status and we then compared treatment outcomes of patients with private insurance to those with Medicare. Results: We treated 86 patients from January 1, 2019 to March 31, 2019 including 63 women and 23 men with a median age of 62 years (range 22-88 years). Several types of malignancies were represented including 21 gynecologic cancers, 17 breast cancers, 11 lung cancers, 10 melanomas, 10 gastrointenstinal cancers, 7 lymphomas, 5 genitourinary cancers, and 5 other tumor types. Among our population, 48 patients had private insurance and 38 had Medicare. Thirty-four patients achieved either a complete response (CR) or partial response (PR), 24 with CR and 10 with PR. Of those who achieved a CR, 11 had Medicare and 14 had private insurance. Among those who achieved a PR, 5 had Medicare and 5 had private insurance. Conclusions: In this retrospective analysis, insurance type did not predict likelihood of achieving a complete or partial response to treatment. Other investigators have suggested that patients with Medicare have poorer outcomes than those with private insurance. One potential explanation for the discrepancy between their data and ours is that we have dedicated system designed to accelerate pre-certifications. Additional investigation is warranted to better understand these trends.

This randomized, crossover pilot study explores timolol eyedrops as an abortive migraine treatment in adults.