Furha I. Cossor

Diabetes, Metformin Use, and Colorectal Cancer Survival in Postmenopausal Women

BACKGROUND Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformins influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Womens Health Initiative (WHI) clinical trials and observational study. METHODS 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n=84); women with diabetes with no metformin use (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. RESULTS After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40-1.38, p=0.67) and to women without diabetes (HR 1.00; 95% CI 0.61-1.66, p=0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38-1.55, p=0.47) and for overall survival was 0.86 (95% CI 0.49-1.52; p=0.60). CONCLUSIONS In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.

Bortezomib Subcutaneous Injection in Combination Regimens for Myeloma or Systemic Light-Chain Amyloidosis: A Retrospective Chart Review of Response Rates and Toxicity in Newly Diagnosed Patients

BACKGROUND Bortezomib is a first-in-class proteasome inhibitor approved by the US Food and Drug Administration for the treatment of all phases of multiple myeloma (MM) and it is also used for the treatment of [corrected] light-chain amyloidosis (AL). The subcutaneous formulation of bortezomib was approved in 2012 based on data from Phase III studies in patients with relapsed MM. OBJECTIVE This article reports experience with subcutaneous bortezomib in patients with newly diagnosed MM or AL in a tertiary care center. METHODS This retrospective study analyzed data from all patients newly diagnosed with MM or AL and treated at our center between April 1, 2011, when the hospital pharmacy approved and implemented the option of subcutaneous bortezomib, and April 1, 2013. Patients who received subcutaneous bortezomib as a part of the first line of therapy were identified through the pharmacys database. Data were abstracted from electronic medical records, and data on demographic characteristics, disease profiles, toxicities, responses, and survival were collected. RESULTS Data from 29 patients (MM, 16; AL, 13; 62% male; median age, 66 years [range, 46-84]) were analyzed. Ninety percent of patients received cyclophosphamide, bortezomib, and dexamethasone (CyBorD) as the first line of treatment. None of the patients developed grade 3/4 peripheral neuropathy, whereas 1 patient experienced grade 3 diarrhea, and 2 patients developed grade 3 thrombocytopenia requiring dose reductions. The overall response rate was 93%, with 59% of patients achieving very good partial response or complete response. CONCLUSIONS With the use of subcutaneous bortezomib in combination regimens in patients with newly diagnosed MM or AL, there was a high overall response rate and minimal toxicity. These results are consistent with the findings from prior studies and provide a basis for further studies comparing new proteasome inhibitors to subcutaneous bortezomib in combination regimens for patients with newly diagnosed MM or AL.

Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer

Background: Metformin has been associated with improved colorectal cancer survival, but investigations are limited by small numbers of patients and confounding by diabetic severity. We examined the association between metformin use and overall survival (OS) in patients with diabetes and colorectal cancer in a large population of U.S. veterans, while adjusting for measures of diabetic severity. Methods: Patients diagnosed with colorectal cancer from January 2001 to December 2008 were identified from the Veterans Affairs Central Cancer Registry. Multivariable models were used to examine the adjusted association of OS with diabetes and use of antidiabetic medications. Results: There were 21,352 patients diagnosed with colorectal cancer identified (n = 16,355 nondiabetic patients, n = 2,038 diabetic patients on metformin, n = 2,136 diabetic patients on medications other than metformin, n = 823 diabetic patients not on antidiabetic medication). Diabetic patients had a significantly worse OS than nondiabetic patients, but metformin users had only a 10% increase in death (HRadj 1.10; 95% CI, 1.03–1.17, P = 0.004), as compared with 22% for users of other antidiabetic medications (HRadj 1.22; 95% CI, 1.15–1.29, P < 0.0001). Among colorectal cancer patients with diabetes, metformin users had a 13% improved OS versus patients taking other antidiabetic medications (HRadj 0.87; 95% CI, 0.79–0.95, P = 0.003), while diabetic patients not on any antidiabetic medications did not differ with respect to OS (HRadj 1.02; 95% CI, 0.90–1.15, P = 0.76). Conclusions: Among diabetics with colorectal cancer, metformin use is associated with improved survival, despite adjustments for diabetes severity and other risk factors. Impact: These data lend further support to the conduct of randomized studies of possible anticancer effects of metformin among patients with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(10); 1418–25. ©2016 AACR.

Small Lymphocytic Lymphoma Presenting As a Paraneoplastic Syndrome With Acute Central Nervous System Demyelination

Chronic lymphocytic leukemia (CLL)/small lymphocytic lym-phoma (SLL) is a mature B-cell neoplasm characterized by accu-mulation of functionally incompetent clonal lymphocytes with thesame morphologic and immunophenotypic features. CLL and SLLhave the same cellular basis but SLL lacks significant peripheralblood (PB) lymphocytosis. CLL is the most common leukemia inthe United States, accounting for 30% of all leukemias, and SLLaccounts for less than 5% of all non-Hodgkin lymphomas. Themedian age at diagnosis is 65 years, and there is a Caucasian malepredominance.

Incidence and Evaluation of Incidental Abnormal Bone Marrow Signal on Magnetic Resonance Imaging

Purpose. The increased use of magnetic resonance imaging (MRI) has resulted in reports of incidental abnormal bone marrow (BM) signal. Our goal was to determine the evaluation of an incidental abnormal BM signal on MRI and the prevalence of a subsequent oncologic diagnosis. Methods. We conducted a retrospective cohort study of patients over age 18 undergoing MRI between May 2005 and October 2010 at Tufts Medical Center (TMC) with follow-up through November 2013. The electronic medical record was queried to determine imaging site, reason for scan, evaluation following radiology report, and final diagnosis. Results. 49,678 MRIs were done with 110 patients meeting inclusion criteria. Twenty two percent underwent some evaluation, most commonly a complete blood count, serum protein electrophoresis, or bone scan. With median follow-up of 41 months, 6% of patients were diagnosed with malignancies including multiple myeloma, non-Hodgkins lymphoma, metastatic non-small cell lung cancer, and metastatic adenocarcinoma. One patient who had not undergone evaluation developed breast cancer 24 months after the MRI. Conclusions. Incidentally noted abnormal or heterogeneous bone marrow signal on MRI was not inconsequential and should prompt further evaluation.

A Unique Case of Relapsed B-Acute Lymphoblastic Leukemia/Lymphoma as an Isolated Omental Mass

B-acute lymphoblastic leukemia/lymphoma (B-ALL) is a neoplasm of precursor cells committed to the B-cell lineage. Extramedullary involvement is frequent, with particular predilection for the central nervous system, lymph nodes, spleen, liver, and testis. We report an unusual case of B-ALL relapsing as an isolated omental mass along with bone marrow involvement.

Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer—Response

We appreciate the letter of Alam and colleagues, who underscore the point we made in our discussion section when we noted that time-related biases, such as immortal time bias, can threaten pharmacoepidemiologic studies of metformin as a potential chemotherapeutic agent ([1][1]). Vivid illustrations