Implementation of a standardized approach to borderline resectable pancreatic cancer in a multisite community oncology program.

BACKGROUND: Treatment paradigms for borderline resectable pancreatic cancer are evolving with increasing use of neoadjuvant chemotherapy and neoadjuvant chemoradiation. Variations in the definition of borderline resectable pancreatic cancer and neoadjuvant approaches have made standardizing care for borderline resectable pancreatic cancer difficult. We report an effort to standardize management of borderline resectable pancreatic cancer throughout Sanford Health, a large community oncology network. METHODS: Starting in October 2013, cases of pancreatic adenocarcinoma without known metastatic disease were categorized as borderline resectable pancreatic cancer if they met ≥ 1 of the following criteria: (1) abutment of superior mesenteric, common hepatic, or celiac arteries with < 180° involvement, (2) venous involvement deemed potentially suitable for reconstruction, and/or (3) biopsy-proven lymph node involvement. Patients with borderline resectable pancreatic cancer were treated with neoadjuvant chemotherapy followed by reimaging and surgery if venous involvement had improved; if disease remained borderline resectable, patients underwent neoadjuvant chemoradiation and surgical exploration as long as reimaging did not reveal evidence of progressive disease. RESULTS: Forty-three patients from October 2013 to April 2017 were diagnosed with borderline resectable pancreatic cancer. Twelve of 42 (29%) patients proceeded to surgical exploration directly after neoadjuvant chemotherapy; 23 (55%) received neoadjuvant chemoradiation. Overall, 28/43 (65%) underwent exploration with 19 (44%) able to undergo resection. Of those, 14/19 (74%) attained R0 resection and 11/19 (58%) were pathologic N0. No pretreatment or treatment variables were associated with resection rates; resection was the only variable associated with survival. CONCLUSION: This report demonstrates the feasibility of implementing a standardized approach to borderline resectable pancreatic cancer across multiple sites over a wide geographic area. Adherence to protocol therapies was good and surgical outcomes are similar to many reported series.

Epstein-Barr Virus Positive Mucocutaneous Ulcer: A Case Report.

Epstein-Barr virus (EBV) is known to be associated with B-cell lymphoproliferative disorders, and EBV-positive mucocutaneous ulcer (EBV-MCU) is a recently described entity observed in immunocompromised individuals. EBV-MCU is an aggressive appearing ulcerated lesion seen in the skin, oral cavity, and gastrointestinal tract. The process has Hodgkin-like features with a self-limited, indolent course, generally responding well to conservative management. We present a case of EBV-MCU recently encountered in a 54-year-old renal transplant recipient. She had persistent rectal pain and bleeding for over a year following hemorroidectomy. A large ulcer in the distal rectum with excoriation and granular margins was noted on examination, and an initial biopsy from the lesion was inconclusive. A repeat biopsy demonstrated ulcerated squamous and colonic mucosa with a polymorphic lymphoid infiltrate in the submucosa that contained large atypical cells. The large atypical cells were positive for PAX-5 and CD30 and demonstrated EBV RNA by in situ hybridization. EBV-MCU is a recently described occurrence in transplant patients, and awareness of this recently described entity is necessary for appropriate diagnosis and treatment.

Scleroderma-like skin changes induced by checkpoint inhibitor therapy.

Checkpoint inhibitors have emerged as beneficial therapies in many different types of malignancy. The most common toxicities of checkpoint inhibitors are immune-related adverse events (irAEs). As clinical experience with these agents increases, more irAEs have been described. We report a case of scleroderma-like skin changes induced by checkpoint inhibitor therapy. A 61-year-old man was treated with nivolumab for oligometastatic renal cell carcinoma. He initially tolerated the therapy well, but after 16 treatments he began experiencing skin thickening and edema of the abdominal wall, which progressed down the trunk and legs. A punch biopsy revealed epidermal attenuation overlying thickened dermal collagen with entrapment and displacement of the eccrine coils and loss of periadnexal adipose tissue. Focally increased plasma cells were present near the junction of the dermis and subcutaneous adipose tissue. Loss of CD34 staining was seen throughout the dermis. These findings were consistent with a diagnosis of scleroderma. After discontinuation of nivolumab and initiation of steroid therapy, the patient's symptoms significantly improved. This case is among the first reports of scleroderma-like changes induced by a checkpoint inhibitor.

EBV-Associated Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis in a Patient with Severe Celiac Disease.

BACKGROUND: Epstein-Barr virus- (EBV-) associated lymphoproliferative disease (LPD) is a rare condition, usually occurring in immunocompromised patients. We report a case of EBV-associated LPD in a patient with severe celiac disease, the first report to describe this syndrome in a patient with this diagnosis. CASE SUMMARY: A 69-year-old Caucasian woman with recent diagnosis of celiac sprue presented to our hospital with persistent diarrhea, abdominal pain, weight loss, and fatigue despite adherence to gluten-free diet for a number of weeks prior to presentation. She underwent evaluation for occult malignancy and was found to have diffuse intra-abdominal mesenteric lymphadenopathy on CT scan. Biopsy of mesenteric nodes revealed an EBV positive, CD20 positive mixed lymphoproliferative process with T-cell predominance, but without a monoclonal cell population felt to be consistent with EBV-associated LPD. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis, complicating her course. She was treated with steroids and rituximab but continued to decline, eventually developing MSSA bacteremia and succumbing to her disease. CONCLUSION: To our knowledge, this is the first report of the constellation of celiac sprue, EBV-associated LPD, and hemophagocytic lymphohistiocytosis. Providers caring for patients with severe, uncontrolled celiac disease and adenopathy should consider EBV-associated LPD.

Delivering Precision Oncology in a Community Cancer Program: Results From a Prospective Observational Study.

INTRODUCTION: Precision oncology (PO) is a growing treatment approach in the era of next-generation sequencing (NGS) and matched therapies. Effective delivery of PO in the community has not been extensively studied. Our program developed a virtual molecular tumor board (MTB) strategy to help guide PO care. MATERIALS AND METHODS: Over 18 months, eligible adult patients with advanced, incurable solid tumor malignancies were enrolled in a molecular profiling (MP) study using the Foundation Medicine NGS panel. Results were reviewed through a weekly, videoconferenced MTB conducted across our largely rural integrated health system. Recommendations from the MTB were used to identify actionable alterations (AAs). Feasibility of PO care delivery was assessed as the primary outcome. Secondary outcomes included the frequency of AAs, genomic matched treatments, genomic matched clinical trial enrollment, and clinical outcomes. RESULTS: A total of 120 participants with a variety of advanced tumor types were enrolled. Of these, 109 (90.8%) had successful MP. Treatment on the basis of an AA was recommended by the MTB in 58% of patients (63 of 109) who had a successful MP result. For those completing MP, treatments included enrollment in a genomic matched clinical trial (n = 16; 14.6%) and genomic matched treatment with a Food and Drug Administration-approved agent (n = 23; 21.1%). Response and survival data were similar regardless of the matched treatment option chosen. CONCLUSION: A video-conferenced MTB-facilitated NGS testing and treatment delivery system was implemented in our integrated community oncology program. Continued use of this model aims to increase understanding of the impact of PO in this setting.

Intratumoral CD14+ Cells and Circulating CD14+HLA-DRlo/neg Monocytes Correlate with Decreased Survival in Patients with Clear Cell Renal Cell Carcinoma.

PURPOSE: Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development. EXPERIMENTAL DESIGN: Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients. RESULTS: We found that CD14(+)HLA-DR(lo/neg) monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14(+)HLA-DR(lo/neg) monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2. CONCLUSIONS: Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome.

Evaluation of pretransplant factors predicting cardiac dysfunction following high-dose melphalan conditioning and autologous peripheral blood stem cell transplantation.

BACKGROUND: Cardiac complications following hematopoietic stem cell transplantation (HSCT) are emerging as a significant concern given the increasing utilization of HSCT for a variety of hematologic malignancies. METHODS: We utilized an existing database to determine the frequency of cardiac dysfunction (CD), namely a decrease in left ventricular ejection fraction, following conditioning with high-dose melphalan (HDM) and autologous HSCT for multiple myeloma (MM) and systemic amyloidosis (AL). We then performed a case-control study to examine variables associated with increased risk of CD in this population. RESULTS: In MM patients undergoing HSCT, the rate of CD was 1.6% (17/1050, 95% CI: [0.9, 2.6]). None of the examined pre-HSCT variables or HDM dose were significantly associated with development of CD in this population. In patients with AL, the rate of CD was 5.6% (24/426, 95% CI: [3.6, 8.3]). On univariate analysis, decision to administer an HDM dose <200 mg/m(2) [odds ratio (OR): 4.59 (1.27-16.57) P = 0.02], pretransplant left ventricular ejection fraction <60% [OR: 17.78 (2.29-138.33) P = 0.006], and documented amyloid involvement of ≥ 3 organs [OR: 4.0 (1.03-15.6) P = 0.046] were associated with the development of CD in the AL population. No other examined peri-transplant factors were associated with development of CD. CONCLUSION: To our knowledge, this is the first series to report a significant rate of CD following HDM conditioning and autologous HSCT in patients with AL.

"Malignant" perivascular epithelioid cell neoplasm: risk stratification and treatment strategies.

Purpose. Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors characterized by a myomelanocytic phenotype, and PEComas occurring in "nonclassic" anatomic distributions are known as perivascular epithelioid cell tumor not otherwise specified (PEComa-NOS). This review aims to compile and analyze cases of PEComa-NOS in an effort to better define their natural history. Design. We evaluated all 234 cases of PEComa-NOS reported in the English literature, extracting information regarding diagnostic features, treatment approaches, and outcomes. Multivariate analysis of a number of variables evaluable on pathologic review was performed to refine preexisting risk stratification criteria. Outcomes for patients receiving nonsurgical treatment are also reported. Results. Primary tumor size ≥5 cm (P = 0.02) and a high (1/50 HPF) mitotic rate (P < 0.0001) were the only factors significantly associated with recurrence following surgical resection. Cytotoxic chemotherapy and radiation therapy have shown little benefit in treating PEComa-NOS; mTOR inhibition is emerging as a treatment option. Conclusion. Progress has been made in understanding the natural history and molecular biology of PEComa-NOS. This review further clarifies risk of recurrence in this disease, allowing clinicians to better risk stratify patients. Further work should focus on applying this knowledge to making treatment decisions for patients with this disease.

Malignant perivascular epithelioid cell tumor of the uterus.

Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors arising in a wide array of anatomic locations and characterized by a myomelanocytic phenotype. PEComas which occur in non-classic anatomic distributions are known as perivascular epithelioid cell tumor-not otherwise specified (PEComa-NOS), and one of the most common primary sites for PEComa-NOS is the uterus. The risk of aggressive behavior of these tumors has been linked to a number of factors evaluable on pathologic review following initial surgical resection. We report a case of PEComa-NOS of the uterus with multiple high-risk features, including frank vascular invasion, with no evidence of recurrent disease 18 months following initial surgical resection.

Thrombocytosis: diagnostic evaluation, thrombotic risk stratification, and risk-based management strategies.

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.