Sheetal Mehta Kircher

Multicenter Analysis of 80 Solid Organ Transplantation Recipients With Post-Transplantation Lymphoproliferative Disease: Outcomes and Prognostic Factors in the Modern Era

PURPOSE Adult post-transplantation lymphoproliferative disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. METHODS We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, > or = 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001). CONCLUSION This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.

Cardiovascular Risk and Statin Use in the United States

PURPOSE Statins reduce the risk of mortality and coronary artery disease in individuals at high cardiovascular risk. Using nationally representative data, we examined the relationships between statin use and cardiovascular risk, diagnosis of hyperlipidemia, and other risk factors. METHODS We analyzed data from the 2010 Medical Expenditure Panel Survey, a nationally representative survey of the US civilian noninstitutionalized population. The study sample had a total of 16,712 individuals aged 30 to 79 years. Those who reported filling at least 2 statin prescriptions were classified as statin users. We created multiple logistic regression models for statin use as the dependent variable, with cardiovascular risk factors and sociodemographic factors as independent variables. RESULTS Overall, 58.2% (95% CI, 54.6%–61.7%) of individuals with coronary artery disease and 52.0% (95% CI, 49.4%–54.6%) of individuals with diabetes aged older than 40 years were statin users. After adjusting for cardiovascular risk factors and sociodemographic factors, the probability of being on a statin was significantly higher among individuals with both hyperlipidemia and coronary artery disease, at 0.44 (95% CI, 0.40–0.48), or hyperlipidemia only, at 0.32 (95% CI, 0.30–0.33), than among those with coronary artery disease only, at 0.11 (95% CI, 0.07–0.15). A similar pattern was seen in people with diabetes. CONCLUSIONS In this nationally representative sample, many people at high risk for cardiovascular events, including those with coronary artery disease, diabetes, or both, were not receiving statins despite evidence that these agents reduce adverse events. This undertreatment appears to be related to placing too much emphasis on hyperlipidemia and not enough on cardiovascular risk. Recently released guidelines from the American College of Cardiology and the American Heart Association offer an opportunity to improve statin use by focusing on cardiovascular risk instead of lipid levels.

Chemoradiation of hepatic malignancies: Prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization

PURPOSE Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ((90)Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of (90)Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. METHODS AND MATERIALS Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver (90)Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after (90)Y infusion. If a DLT was not observed, the (90)Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of (90)Y with full-dose capecitabine. RESULTS Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing (90)Y MTD were not met, indicating an MTD of >170 Gy. CONCLUSION The MTD of (90)Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest (90)Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.

90Y Radioembolization of Colorectal Hepatic Metastases Using Glass Microspheres: Safety and Survival Outcomes from a 531-Patient Multicenter Study

Hepatic metastases of colorectal carcinoma are a leading cause of cancer-related mortality. Most colorectal liver metastases become refractory to chemotherapy and biologic agents, at which point the median overall survival declines to 4–5 mo. Radioembolization with 90Y has been used in the salvage setting with favorable outcomes. This study reports the survival and safety outcomes of 531 patients treated with glass-based 90Y microspheres at 8 institutions, making it the largest 90Y study for patients with colorectal liver metastases. Methods: Data were retrospectively compiled from 8 institutions for all 90Y glass microsphere treatments for colorectal liver metastases. Exposure to chemotherapeutic or biologic agents, prior liver therapies, biochemical parameters before and after treatment, radiation dosimetry, and complications were recorded. Uni- and multivariate analyses for predictors of survival were performed. Survival outcomes and clinical or biochemical adverse events were recorded. Results: In total, 531 patients received 90Y radioembolization for colorectal liver metastases. The most common clinical adverse events were fatigue (55%), abdominal pain (34%), and nausea (19%). Grade 3 or 4 hyperbilirubinemia occurred in 13% of patients at any time. The median overall survival from the first 90Y treatment was 10.6 mo (95% confidence interval, 8.8–12.4). Performance status, no more than 25% tumor burden, no extrahepatic metastases, albumin greater than 3 g/dL, and receipt of no more than 2 chemotherapeutic agents independently predicted better survival outcomes. Conclusion: This multiinstitutional review of a large cohort of patients with colorectal liver metastases treated with 90Y radioembolization using glass microspheres has demonstrated promising survival outcomes with low toxicity and low side effects. The outcomes were reproducible and consistent with prior reports of radioembolization.

Understanding and Treating Opioid Addiction in a Patient With Cancer Pain

r. D. is a 25-year-old male who has struggled with heroin addiction since his late teens. He had initially completed a 30-day rehabilitation program but relapsed immediately and entered another 2-week program. It was during this hospitalization that laboratory abnormalities were noted, and he was subsequently diagnosed with acute myeloid leukemia. He received high-dose induction chemotherapy with cytarabine and daunorubicin but did not achieve remission. He was reinduced, achieved remission, and subsequently underwent stem cell transplantation with his younger sister as a donor. Throughout this prolonged 8-week hospitalization and treatment, he suffered from severe mucositis as well as abdominal pain of unclear etiology requiring patient controlled analgesia (PCA), delivering, at 1 point, over 600 mg of hydromorphone in a 24-hour period. By the time of discharge, the mucositis had resolved, the opioid gradually titrated downward, and he was transitioned to a 100-mcg fentanyl patch, which was weaned down as an outpatient over a 2-week period. Two weeks after titration off of fentanyl, the patient reported agitation, sweats, and nausea that continued. Mr. D’s parents accompanied him to each appointment; the patient continued to live with his parents so they could closely monitor him and they dispensed his medications due to the history of drug abuse. Less than 6 months from his transplant, his parents discovered evidence of an attempted transaction to purchase heroin, and the patient subsequently admitted to continued heroin use throughout his treatment including during his hospitalization. He continues to struggle with addiction; more than 300 days past transplant, he is currently at an inpatient drug rehab facility.

Effect of the Accountable Care Act of 2010 on Clinical Trial Insurance Coverage

PURPOSE The Affordable Care Act (ACA) of 2010 implemented dramatic changes in our health care system. The new law requires that insurers and health plans provide coverage for individuals participating in clinical trials. Currently, there are states that already have laws or agreements requiring clinical trial coverage, but there remain deficiencies that will need to be addressed to achieve compliance with the new law. METHODS State mandates were reviewed to determine current laws and agreements. The ACA was reviewed to outline its provisions, and these were compared with current mandates to identify deficiencies. RESULTS Eighteen states meet the requirements set forth by the ACA either through a state law or agreement; 33 states do not meet the requirements. Of these 33 states, 15 do not have any existing laws or agreements in place regarding clinical trials. In states that have deficient policies in place, the most common deficiency is the lack of phase I coverage. The second most common deficiency in policy is coverage of only therapeutic studies. CONCLUSION Most states currently do not meet the requirements of the ACA and will be required to make changes by 2014. The implications of the ACA with regard to insurance coverage of clinical trials remain unclear as implementation of the legislation unfolds. State governments can take steps to ensure insurance coverage by creating and expanding agreements with insurance companies.

The Parity Paradigm: Can Legislation Help Reduce the Cost Burden of Oral Anticancer Medications?

Over the last decade, there has been increased development and use of oral anticancer medications, which sometimes leads to high cost sharing for patients. Drug parity laws require insurance plans to cover oral anticancer medications with the same cost sharing as intravenous/injected chemotherapy or have a capped limit on out-of-pocket costs. There are currently 36 enacted state laws (plus the District of Columbia) addressing drug parity, but no federal laws. In this policy perspective piece, we discuss the history, opportunities, and limitations of drug parity laws in oncology. We also discuss the implications of provisions of the Affordable Care Act and other proposed policy reforms on financing oral chemotherapy.

Financial toxicity in cancer care

The cost of cancer care is increasing, with important implications for the delivery of high-quality, patent-centered care. In the clinical setting, patents and physicians express a desire to discuss out-of-pocket costs. Nevertheless, both groups feel inadequately prepared to participate in these discussions, and perhaps not surprisingly, the integration of these discussions into clinical practice seems to be the exception rather than the rule. The resulting neglect of financial issues has the potential to cause unnecessary suffering for oncology patents. In this paper, we review the most relevant literature on financial toxicity in cancer care. In addition, we discuss potential predictors of financial toxicity, and the recent development of instruments to help clinicians and researchers quantify financial burden.

Targeting angiogenesis in colorectal cancer tyrosine kinase inhibitors

Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options.

Reexamining the Ecology of Medical Care

In this analysis of data from the U.S. Medical Expenditure Panel Survey, the overall frequency of outpatient physician visits, emergency department visits, and inpatient hospitalizations did not change significantly between 1996 and 2012.