Marin Feldman Xavier

The incidence of second primary malignancies after gastrointestinal stromal tumor before and after the introduction of imatinib mesylate

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Imatinib mesylate was FDA-approved in 2002 for the treatment of unresectable and metastatic GISTs and has become the standard of care. Its use has resulted in greatly increased survival rates for patients with GIST. The increased survival in patients with GIST raises concerns about long term effects of therapy, particularly the development of second primary malignancies (SPMs), which has been reported with imatinib treatment of chronic myeloid leukemia. In addition, the diagnosis of GIST itself may pose a risk for the development of SPMs. The purpose of this study was to examine the incidence of SPMs after GIST, particularly before (pre-imatinib era: 1992-2001) and after (imatinib era: 2002-2009), and factors related to the occurrence of SPMs. Data from the NCI’s Surveillance Epidemiology and End Results (SEER) 1992-2009 program was utilized. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for these were calculated using SEER*Stat 8.0.1. Observed incidences were then compared between preimatinib and imatinib eras using Fisher’s exact test. The relationship between the presence of SPMs and each of the variables was examined using logistic regression. There were significantly more patients in the imatinib era alive after follow-up (n=533, 63.99%) than in the pre-imatinib era (n=130, 22.41%, P<0.001). Overall, the rate of SPMs after GIST in the imatinib era was 7.07%, compared with the rate of 1.15% that occurred in the pre-imatinib era (P=0.030). This difference was mainly accounted for by a higher incidence of colon adenocarcinoma in the imatinib era (P=0.023). Renal cell carcinoma also accounted for this difference. In contrast, the rate of melanoma of the skin was significantly lower in the imatinib era compared with the pre-imatinib era (P=0.030). In the pre-imatinib era for melanoma, the SIR was 17.64 (95% CI: 3.64-51.57). Patients with SPMs were significantly older at diagnosis (mean =64.18, SD =12.95) than patients without SPMs (mean =60.63, SD =15.27, P=0.024). Marital status was significantly related to the presence of SPMs (78.26% vs. 65.62%, P=0.0154) with those patients with SPMs more likely to be married compared to those without SPMs. This relationship is most likely due to increased survival. Of note, patients with SPMs had greater number of months of survival (mean =70.83, SD =51.54) than those without SPMs (mean =39.33, SD =37.30, P<0.0001). The findings in our study demonstrate that patients after GIST are at increased risk of developing SPMs and that this risk is increased following the introduction of imatinib in 2002. The increased incidence of SPMs in the era of imatinib could be explained by the increased survival of patients with metastatic GIST and therefore more time to develop SPMs, however, further studies are needed to investigate this mechanism.

A pilot trial of quantitative Epstein–Barr virus polymerase chain reaction in patients undergoing treatment for their malignancy: potential use of Epstein–Barr virus polymerase chain reaction in multiple cancer types

Epstein – Barr virus (EBV) is a herpes virus that infects over 90% of the world ’ s population. After primary infection, the virus enters an asymptomatic latent phase that typically lasts the remainder of life. However, under certain circumstances – such as extreme age or in the setting of immunosuppression – the virus may reactivate and express genes that contribute to neoplastic transformation. A variety of malignancies have been associated with EBV reactivation, including Hodgkin lymphoma, several non-Hodgkin lymphoma subtypes (Burkitt lymphoma, post-transplant lymphoproliferative disorder [PTLD] and EBV-associated diff use large B-cell lymphoma [DLBCL] of the elderly) and nasopharyngeal carcinoma [1 – 5]. In patients with EBV-driven malignancy, EBV can be detected within malignant cells as well as in the patient ’ s blood. Quantitative EBV viral load measurement by polymerase chain reaction (EBV PCR) has been used as a marker for disease activity in selected EBV-associated malignancies. In acquired immune defi ciency syndrome (AIDS)-related lymphomas and PTLD, the presence and degree of EBV viremia has been established as a marker of disease activity, facilitating both diagnosis and response assessment [6,7]. In Hodgkin lymphoma, the presence of EBV viremia has been shown to be prognostic at baseline and post-treatment [8]. EBV PCR has shown promise in these diseases as a tool for conveniently and non-invasively monitoring the activity of an EBV-associated tumor. While EBV PCR has been found to be clinically useful in the management of some EBV-associated lymphomas, there are malignancies for which the association with EBV is uncertain, and for which the use of EBV viral load assessment for diagnosis and response monitoring is unknown. To explore the use of EBV PCR for the diagnosis and monitoring of malignancy, we conducted an institutional review board approved prospective clinical trial of quantitative whole blood (WB) and plasma (P) EBV PCR

Updates in immunotherapy for acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common acute leukemia among adults with an overall poor prognosis. For 40 years there has been minimal improvement in treatment beyond induction chemotherapy and consolidation with chemotherapy or allogeneic stem cell transplantation. Increased understanding of immune system involvement in tumor growth and destruction has led to incredible success with multiple malignancies treated with immunotherapy. AML is now being heavily researched with these revolutionary techniques, encountering many challenges in treatment related to myeloid line aplasia, immune evasion, and other on and off target toxicities. This is a review of current methods including vaccinations, monoclonal antibodies (MoAbs), chimeric antigen receptor T cells (CAR T cells) and checkpoint inhibitors.

Social factors, treatment, and survival in patients with advanced-stage non-small cell lung cancer

Background: Lung cancer is the leading cause of cancer death in North America with at least 40% of patients presenting with advanced, incurable non-small cell cancer (NSCLC) at the time of diagnosis. Chemotherapy has been shown to increase median survival in patients with a good performance status [Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2]. Objective: To determine factors associated with treatment in patients presenting with advanced NSCLC in two academic community-based hospital settings. Methods: Data were extracted from the 2009-2010 Scripps Cancer Registry. Advanced NSCLC patients were followed from initial diagnosis until death. The influence of socioeconomic status, performance status and access to care on the decision to pursue treatment and the correlating overall survival was assessed. Results: Chemotherapy was given to 64% of 111 patients from Scripps Mercy Hospital (SMH) and Scripps Green Hospital (SGH) diagnosed with advanced NSCLC. Chemotherapy was given to 58.8% of SMH patients and 78.3% of SGH patients (P=0.03). Patients with an ECOG status between 0-2 were more likely to receive chemotherapy compared with patients whose ECOG status was 3-4 (81% versus 0%, respectively, P<0.001). Those tested for the epidermal growth factor (EGFR) mutation were more likely to receive chemotherapy, compared to those not tested (96% versus 60%, P<0.001). Conclusions: Chemotherapy utilization for advanced NSCLC is increasing over time. Chemotherapy administration is associated with socioeconomic status, performance status, and access to care, relationships that likely reflect evolving clinical practice patterns.

Cancer immunotherapy in review: preface to special edition

As we emerge head first into this new era of immuno-oncology, it seems timely for clinicians and scientists alike to review how far we have come in engineering the immune system to fight cancer. Whether by stem cell transplantation and graft versus tumor effect, monoclonal antibody therapy, vaccines, cellular therapies with CAR-T cells, or checkpoint inhibitors each cancer has had varying levels of success with immune system-related strategies. In this special issue I have guided our authors to consider and review the immune-mediated tools we have recently gained in both solid and hematologic malignancies. Upon review of the treatments available I have also asked each author to catapult us to the next wave of strategies currently in development and in clinical trials. Ultimately each topic chapter touches on a new class of immune toxicities that we have recently discovered as we explore and unleash the power of immunotherapy.

Delirium rate and risk factors in palliative oncology outpatients and associated caregiver coping.

46 Background: Delirium causes suffering and undermines important palliative goals of care at end of life. Prior evaluation of outpatient delirium rate was 14% among demented elders. It is hypothesized that frail, palliative oncology outpatients have high rates of missed delirium. Improved knowledge and screening can improve patient outcomes through treatment in the home. This study examined the prevalence rate and risk factors for delirium among palliative care outpatients, and identified caregiver coping strategies associated with the episode. METHODS This was a descriptive, correlational study using a convenience sample of patient/caregiver dyads at an urban cancer center based on Rigneys Allopathic Load in Delirium Model. Oncology patient participants consented to a chart review for demographic risk factors. Caregivers of patients with a life-limiting illness were asked to complete two surveys at the time of their usual visit. The Family Administered Confusion Assessment Method, FAM-CAM scale reflected upon the patients behavior over the past month using 12 simple yes/no questions. Risk factors such as age, gender, marital status, medications and diagnosis were correlated with delirium. The Folkman Lazarus Ways of Coping compared coping styles. RESULTS The rate of delirium among palliative care outpatients in this sample of 52 patient/caregiver dyads was 27%. The results suggested that opioid use slightly increases the odds for an episode of delirium, and approaches significance (r(50) =.270, p =.052). The majority of caregiver participants reported positive coping styles, however positive reappraisal and emotion-focused coping mechanism were more common in caregivers with a cognitively intact patient. Problem-focused coping was more common if the patient screened positive for delirium (m =.22, SD =.073). CONCLUSIONS Oncology clinicians must screen for delirium in order to improve quality of care, especially among those on palliative chemotherapy.