Citations

Abstract Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. Significance: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access. This article is highlighted in the In This Issue feature, p. 1426

AbstractThis article is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The guidelines panel consisted of medical oncologists, pathologists, gastroenterologists, endocrinologists, and radiologists. The panel reviewed a series of questions regarding the medical management of patients with pancreatic neuroendocrine tumors as well as questions regarding surveillance after resection. The available literature was reviewed for each of the question and panel members voted on controversial topics, and the recommendations were included in a document circulated to all panel members for a final approval.

AbstractLutetium-177-dotatate (177Lu-dotatate), a form of peptide receptor radionuclide therapy, was approved by the U.S. Food and Drug Administration for the treatment of advanced somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (NETs) in 2018 based on the promising results of the NETTER-1 trial for grade 1–2 midgut NETs. Here, we present a patient with a grade 3 pancreatic neuroendocrine tumor and BRCA1 germline mutation who had a significant response to 177Lu-dotatate.

e16702 Background: There are only a few reports examining the treatment patterns for poorly differentiated rectal/anal NEC. In this study, we sought to report treatment and survival outcomes for patients with NEC of the anus and rectum seen at Mayo Clinic. Methods: We identified patients with a primary NEC of the anus or rectum using Mayo Clinic databases (Minnesota, Arizona, Florida) from the year 2000 to present. NEC identified within polyps on colonoscopy was excluded from this study. Patients’ demographics were compiled. Kaplan Meier analyses were performed to evaluate overall survival (OS) for all patients, as well as subgroups with locoregional disease (LRD) and metastatic disease at diagnosis. Progression free survival (PFS) was also evaluated for patients with LRD treated with chemoradiation therapy (CRT). Results: 38 patients with NEC of the anus/rectum were identified with a median age of 55.5 years. 23 patients (61%) had metastatic disease at diagnosis and 15 (39%) had LRD. The most common site of metastasis was the liver (n = 20). Patients with metastatic disease at presentation had significantly shorter OS compared to patients with LRD (median OS 10.4 vs. 18.9 months, p = 0.039; HR 2.46, 95% CI [1.001-6.050]). 34 total patients received chemotherapy (ORR 11.8%), with platinum + etoposide (EP) being the most common first-line chemotherapy (n = 26). 10 of 15 patients with LRD received CRT (9 with EP and 1 with 5-FU) with median PFS of 6.3 months (95% CI 2.3-16.5 months), a 1-year PFS rate of 20%, and median OS of 18.6 months (95% CI 13.5-23.7 months). 2/10 received induction chemotherapy prior to CRT with 6/10 undergoing primary tumor resection (1 prior to CRT and 5 after CRT). Only 3 CRT patients were living at time of analysis (all underwent surgical resection), 2 without any active disease, 1 who achieved complete response with CRT then suffered recurrence and is still undergoing treatment. Conclusions: NEC of the anus and rectum is an aggressive malignancy with most patients experiencing metastatic disease at presentation and poor response to chemotherapy at all stages. Even those with LRD experience a very poor prognosis with OS of 18.9 months from diagnosis. For LRD, most patients underwent CRT with only a short-lived response (median PFS 6.3 months). Those achieving sustained response also underwent surgical resection. Overall, prognosis is poor for all stages and further study on a large scale is warranted to better characterize this rare, aggressive malignancy.

Abstract Background: Copper deficiency is an established cause of hematological abnormalities, traditionally described in malnourished infants and persons with malabsorption or short bowel syndromes, particularly those requiring long-term parenteral nutrition. With the recent increase in bariatric (weight reduction) surgery, acquired copper deficiency may be increasing in incidence but the diagnosis is frequently delayed. Methods: To outline the natural history of copper deficiency we searched the Mayo Clinic database and our heavy metals laboratory for patients diagnosed with low serum copper during the years 1974–2005. Copper deficiency was defined as a serum level < 0.75 μg/ml. Results: We identified 123 patients with a low serum copper. 77 patients were excluded as the the hypocupremia was either transient or due to other factors such as Wilson’s disease. The remaining 46 patients were all symptomatic. 25 patients had hematological abnormalities, 20 of these patients also had neurological involvement. 5 had isolated hematological manifestations and 21 patients had isolated neurological findings, most commonly myeloneuropathy. 13 presented with anemia and leukopenia, 5 with pancytopenia, 6 with anemia and 1 with isolated neutropenia. In 10 of the 25 cases, a secondary contributing cause for the hematological findings was identified. These included possible anemia of chronic disease (4), renal insufficiency (2), iron deficiency (1), B12 deficiency (1), GI hemorrhage (1), and splenomegaly (1) while copper deficiency was the only identifiable cause in the remaining 15 patients. Hematological parameters at diagnosis are outlined in the table. 15 of the 25 patients with hematological manifestations had a history of GI surgery, including 6 patients who had bariatric surgery. The median time from surgery to diagnosis was 11.5 years (range 8 months - 45 years) and was shorter for bariatric surgery (10 years, range: 8 months - 25 years) than for non-bariatric surgery (18 years, range: 2–45 years). 1 patient had a history of excessive zinc ingestion, 1 had malabsorption secondary to chronic pancreatitis and 1 patient had celiac disease. In 7 cases, no explanation was found. 24 of 25 patients received treatment with oral or intravenous copper, 5 were lost to follow up. In 16 patients the hematologic parameters either improved significantly or normalized, while in the remaining 3 patients there was no improvement. Factors that may explain the lack of response in these patients included splenomegaly (1), renal insufficiency (1) and multiorgan illness (1). Conclusion: Copper deficiency is an increasingly frequent cause of hematological abnormalities, and can manifest with refractory cytopenias with or without associated neurological symptoms. Thrombocytopenia is relatively rare. Previous GI surgery, especially bariatric surgery, appears to be a major causative factor. Most patients will have an improvement in hematological parameters after copper supplementation. Recognition of copper deficiency is therefore assuming greater importance in view of the increasing frequency of bariatric surgery, ease of treatment and potential for irreversible neurological damage if diagnosis is delayed. Hematologic parameters at diagnosis HgB (g/dL) MCV (fL) WBC (x109/L) ANC(x109/L) Plts(x109/L) Median 10.6 99 3.0 1.25 215 Range 7.9-13.6 83.9-114.1 1-5.6 0.18-4.0 54-554

Abstract Background: Copper deficiency is increasingly being diagnosed in adults with malabsorption syndromes, especially following GI surgery such as gastric and bowel resections and bariatric surgery. The most common hematologic manifestations are refractory anemia and neutropenia and patients have been misdiagnosed as having myelodysplasia. Certain findings on bone marrow examination are felt to be characteristic for copper deficiency such as maturation arrest in the myeloid lineage, vacuolization of the erythroid and myeloid precursors and ringed sideroblasts. Methods: We reviewed all cases of copper deficiency diagnosed at the Mayo Clinic from 1974 – 2005. We also reviewed all cases of low serum copper (< 0.75 μg/ml) identified in our heavy metals laboratory. Results: 123 patients with hypocupremia were identified. 77 patients were excluded as the hypocupremia was either transient or due to other factors such as Wilson’s disease. Twenty-five patients had hematologic manifestations, including anemia and leukopenia (13), isolated anemia (6), pancytopenia (5), and isolated neutropenia (1). Eighteen patients had a bone marrow biopsy. We were able to retrieve and review bone marrow slides in 11 cases. The bone marrow examination findings are shown in the table. The marrow cellularity was decreased in four cases. All cases had granulocytic hypoplasia but preserved megakaryopoiesis. Nine cases had relative erythroid hyperplasia. All but one bone marrow had cytoplasmic vacuoles in pronormoblasts and myelocytes. Increased iron within macrophages was seen in 9 cases and increased iron in plasma cells was noted in 8 cases. This was especially prominent in the cases with low peripheral white blood count. Ringed sideroblasts were seen in 4 cases and were more commonly seen in anemic patients. The initial bone marrow examination commonly suggested toxic effect (drugs or alcohol), myelodysplasia or were non-diagnostic. Conclusion: We have described the bone marrow findings in 11 copper deficient patients with abnormal blood counts. None of these patients was suspected of copper deficiency based on the initial marrow examination. The initial impression was commonly toxic effect due to the presence of cytoplasmic vacuolization. Patients with ringed sideroblasts were suspected of having MDS. Copper deficiency should be considered in patients with cytopenias and the described bone marrow findings, especially if there is evidence of malabsorption or a history of GI surgery such as gastric resection or bariatric surgery. Bone marrow findings Patient Cellularity Ery/gran/meg Vacuoles Iron (mø/PC) RS Hgb/Plt WBC/ANC nl: normal, 0: absent, Ery/gran/meg: erythro-/granulo-/megakaryopoiesis, Iron (mø/PC): Iron in macrophages and plasma cells, RS: Ringed sideroblasts 1 ↓ ↑/↓/nl Yes ↑/↑ No 11.3/203 3.2/1.1 2 Nl ↑/↓/nl Yes 0/0 No 11.4/192 5.6/4.0 3 Nl ↑/↓/nl No ↑/0 No 10.6/95 3.0/2.2 4 ↓ ↑/↓/nl Yes ↑/↑ No 13.6/128 4.2/0.92 5 Nl ↑/↓/nl Yes ↑/↑ 10% 9.8/215 1.4/0.6 6 ↓ ↑/↓/nl Yes ↑/↑ No 7.9/292 1.8/0.18 7 Nl ↑/↓/nl Yes ↑/↑ No 10.6/280 2.7/1.4 8 Nl nl/↓/nl Yes ↑/↑ 20% 8.1/330 1.5/0.24 9 Nl ↑/↓/nl Yes ↑/↑ <1% 9.4/252 1.3/0.25 10 ↓ Nl/↓/nl Yes 0/0 No 10.5/167 2.4/1.67 11 Nl ↑/↓/nl Yes ↑/↑ yes 12.5/224 4.2/3.9