Multiple Chemotherapy Treatments Research Articles

Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013–2017: A Population-Based Cohort Study

Introduction: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013–December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. Methods: A retrospective, descriptive study of consecutive cases was conducted at Qatar’s NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. Results: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36–95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. Conclusions: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar’s immigration patterns.

Efficacy of Cobimetinib in Rosai-Dorfman Disease

▪INTRODUCTIONRosai-Dorfman disease (RDD) is a rare histiocytic disorder associated with histiocytes expressing high level of macrophage colony stimulating factor receptor (c-fms). Mutations in mitogen-activated protein kinase (MAPK) pathway have been reported in RDD, indicating an underlying clonal process in some patients. Aberrant activation of MAPK pathway can occur due to mutations or high c-fms expression. Data on the use of MAPK/extracellular-signal-related kinase (ERK)-inhibitor therapy in RDD are very limited. Cobimetinib is a MEK inhibitor, which is listed in the National Comprehensive Cancer Network Compendium ® for the treatment of RDD. We present our retrospective experience of cobimetinib treatment in a large series of patients with RDD.METHODSFollowing approval of the institutional reviewed board, patients (pts) with RDD who were consecutively seen at Mayo Clinic and treated with cobimetinib between 2013-2021 were included. Response was assessed as described by Goyal et al (Haematologica 2020;105:2). Cobimetinib was given 20-60 mg once a day by mouth for 21 days in a 28-day cycle. Adverse events (AEs) were graded using the National Cancer Institute Common Toxicity Criteria v5.0. Time-to-event analyses were calculated from the time of treatment initiation, while duration of response was calculated from the time of 1 st response. Tumor genomic profile was analyzed using Tempus-xT ® assay (Chicago, IL), which includes targeted DNA sequencing (648 oncogenes) and whole transcriptome sequencing.RESULTSOf the 54 pts with RDD, ten were treated with cobimetinib and included in this study. The median follow-up was 16 months (m) [95% confidence interval (CI): 13-not reached (NR)] and most (n=8; 80%) were females. The median age at the time of treatment was 63 years (range: 36-74). Cobimetinib was used as first line therapy in four pts.Overall response rate was 70%, with 30% and 40% achieving complete (CR) and partial (PR) responses, respectively. One had stable disease (SD) and two had progressive disease (PD) (Table 1). The median progression-free-survival was 6.4 m (95%CI: 4.9-NR) and at 6 and 12 m, 67% and 50% of pts remained free from disease progression or death, respectively (Figure 1). The median duration of response was 7.6 m (95%CI: 3.1-NR). At the time of last follow-up, nine (90%) pts were alive. One pt died due to myelodysplastic syndrome with excessive blasts. She had multiple chemotherapy treatments before initiation of cobimetinib. Cobimetinib was discontinued in this pt due to grade 3 anemia and skin toxicity after 6 m of therapy and had SD as the best response.Median duration of treatment for the entire cohort was 6 m (range: 2-14). In the seven pts who responded, the median duration of treatment was 7 m (range: 2-14). Cobimetinib was discontinued in seven pts: disease progression (n=3; one disease progression after achieving PR and two PD while on therapy), grade 3 left ventricular systolic dysfunction (n=1), grade 3 diarrhea (n=1), grade 3 anemia (n=1), and grade 2 creatinine elevation (n=1). Five (50%) pts were started at a reduced dose of cobimetinib at the discretion of treating physician [20 mg (n=4) and 40mg, (n=1)]. Two pts were started at 60 mg and dose reduced to 20 mg after one cycle of treatment due to grade 2 skin toxicity in one and grade 2 skin toxicity and diarrhea in the other. Both pts achieved a PR but progressed after four and six cycles, respectively. One pt started at 40 mg and reduced to 20 mg due to grade 2 skin toxicity after two cycles achieving a PR. The response was sustained in this pt for at least 9 months, until the time of last follow-up (Table 1).Tissue molecular testing showed five pts with MAPK pathway alterations and all of them responded to therapy (CR=3 and PR=2). Of the other five pts who either did not have a MAPK pathway alteration (n=4) or had test failure (n=1), responses were observed in two (40%) pts, both PR (Table 1).CONCLUSIONOur study suggests that cobimetinib is an effective treatment in RDD, with responses observed in all pts having MAPK pathway alterations. Less than half of pts without a MAPK pathway alteration achieved a response. However, treatment discontinuations due to AEs were common despite dose reductions. Patients who were treated at low doses of cobimetinib also had remarkable clinical response. Further studies are needed in evaluating other MAPK pathway inhibitors with better toxicity profile to improve adherence and outcomes. [Display omitted] DisclosuresTobin: National Institutes of Health: Research Funding; Mayo Clinic Center for MS and Autoimmune Neurology: Research Funding; Mallinckrodt Pharmaceuticals: Research Funding. Bennani: Vividion: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Verastem: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Kymera: Other: Advisory Board. Vassallo: Pfizer: Research Funding; Bristol-Myers-Squibb: Research Funding; Sun Pharma.: Research Funding.

Epidemiologic and Clinical Patterns of Lymphoma in Qatar 2013-2017: A Population-Based Cohort Study

Background:Lymphoma: either most common non-Hodgkin (NHL) or less common Hodgkin (HL), are well-known hematological malignancies. With advancement in treatment modalities, the survival in both lymphomas especially the “poor prognosis” non-Hodgkin lymphoma has evolved in the last decades. Hence, patient's outcome may be diverse and quite complicated; with some need extended time for observation, and others having multiple chemotherapy treatments. In this review, we will focus on the clinic-epidemiological patterns of various malignant lymphoma subtypes in Qatar in recent years (2013-2017)Objective:The primary aim is to investigate and compare the overall survival (OS) for both types of lymphoma; HL and NHL at 1, 3 and 5-years of follow up in adult lymphoma patients in Qatar between January 2013 - December 2017. Other objectives include comparing between the most frequent histological varieties, clinical and epidemiological characteristics of HL and NHL lymphoma in Qatar. The secondary objectives included clinical characteristics, treatments used, treatment response, disease-free survival and overall survival.Methods:A retrospective, descriptive study of consecutive cases was carried out at NCCCR, Qatar between 2013-2017. Inclusion criteria included: ≥ 18 years of age, male or female, any clinical stage at diagnosis, who had received any chemotherapy regimen, with a known outcome. Descriptive statistics was performed for all variables, and survival was assessed using Kaplan-Meier curves. Data was abstracted by Qatar National Cancer Registry and the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors is used as reference for disease staging and pathological classification. We used STATA version 13.0 (StataCorp., College Station, TX) for exploratory data analysis and descriptive statistics.Results:During the period 2013-2017, 414 men and women were diagnosed with lymphoma in the state of Qatar. The median age at diagnosis being 49 years (interquartile range IQR 36-95 years; p<0.001)) for all lymphoma patients combined. Males were more likely to develop both lymphoma types; HL and NHL than females; accounting for 2/3 of cases in each, yet statistically insignificant (74% and 70%, p=0.45). Based on subtypes, mature B-cell neoplasms (61 cases, 60%) were the most common among 13 identifiable NHL-B subtypes. Majority of HL cases belonged to Lymphocyte rich subtype (54 cases, 49%). With a median follow up of 17.3 months, the 1-year, 3-year and 5-year OS for the entire population of lymphoma patients were 99%, 82% and 64% (Figure 12). When stratified by major subtypes; HL and NHL, some trends became evident at 3-years follow-up (94% versus 82%). The 5-year OS were 67% and 60%, respectively. Throughout the study period, the OS in HL group were higher than NHL (p<0.001), yet median OS was not reached.Conclusions:Diffuse large B-cell lymphoma constitutes the most frequent subtype for all lymphomas in Qatar. Overall, the survival was generally better for HL than NHL 67% and 60% respectively. Survival can be slightly deflated than other countries or regions especially HL, this is in part due to higher immigration rate in the country, so changes in survival over time (especially for longer periods) need to be examined alongside trends in incidence rates to interpret improvement in cancer control policies implemented. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

CHEMOTHERAPY-INDUCED PSEUDOCIRRHOSIS RESULTING IN HEPATIC ENCEPHALOPATHY

SESSION TITLE: Critical Care Complications SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Pseudocirrhosis is an uncommon complication seen in breast cancer patients with liver metastasis who are treated with chemotherapy. It resembles both the clinical presentation and radiologic imaging of cirrhosis and can result in portal hypertension and hepatic failure. Pseudocirrhosis develops in response to the chemotherapeutic effects on hepatic masses leading to hepatocellular injury and is associated with a high mortality with most patients dying within weeks to months from liver failure or complications of portal hypertension. Described below is a case of a patient who developed hepatic encephalopathy secondary to pseudocirrhosis following treatment with Paclitaxel, Trastuzumab, and Pertuzumab. CASE PRESENTATION: A 43-year-old female with metastatic breast cancer to the liver treated with bilateral mastectomy, radiation therapy, and multiple chemotherapy treatments as well as thyroid cancer status post thyroidectomy presented to the emergency department with encephalopathy and right lower extremity twitching. On physical exam, she was minimally responsive with jaundice, scleral icterus, and abdominal distension. She was emergently intubated for airway protection. Her labs were significant for a transaminitis, hyperammonemia, hyperbilirubinemia, and prolonged prothrombin time. She had a computed tomography scan of her abdomen and pelvis and when compared with her prior scan two weeks before admission, it revealed interval development of a nodular heterogeneous liver concerning for pseudocirrhosis along with bilateral pleural effusions and ascites. Blood cultures, Hepatitis B and C, and Anti-nuclear, Anti-smooth muscle, and Anti-mitochondrial antibodies were negative. Her family denied that she had any regular alcohol consumption. She was given lactulose, rifaximin, and vitamin K with improvement in her mental status and was successfully extubated. DISCUSSION: The etiology of altered mental status can be difficult to establish with it frequently being attributed to metabolic derangements, stroke, or delirium. Although a rare diagnosis, it is important to recognize pseudocirrhosis may be the cause of encephalopathy in a patient with liver metastases who has received chemotherapy. Checking ammonia levels may be helpful in diagnosis. Treatment is similar to classic hepatic encephalopathy by eliminating nitrogenous waste products with lactulose and/or rifaximin. CONCLUSIONS: Early diagnosis of pseudocirrhosis in patients with metastatic breast cancer who are treated with chemotherapy is essential to begin appropriate treatment to avoid the complications of cirrhosis. Reference #1: Adike A, Karlin N, Menias C, Carey EJ. Pseudocirrhosis: A Case Series and Literature Review. Case Rep Gastroenterol. 2016;10(2):381-391. Published 2016 Jul 29. https://doi.org/10.1159/000448066 DISCLOSURES: No relevant relationships by Nathan Brewster, source=Web Response No relevant relationships by Brian Civic, source=Web Response No relevant relationships by Kareem Godil, source=Web Response No relevant relationships by Brian Holahan, source=Web Response No relevant relationships by Alaynna Kears, source=Web Response

Quantum Optimal Control Dynamics for Delay Intracellular and Multiple Chemotherapy Treatment (MCT) of Dual Delayed HIV - Pathogen Infections

Quantum Optimal Control Dynamics for Delay Intracellular and Multiple Chemotherapy Treatment (MCT) of Dual Delayed HIV - Pathogen Infections

Tumor-secreted PGE2 Inhibits CCL5 Production in Activated Macrophages through cAMP/PKA Signaling Pathway

One of the major characteristics of tumors is their ability to evade immunosurveillance through altering the properties and functions of host stromal and/or immune cells. CCL5 has been shown to play important roles in T cell proliferation, IFN-γ, and IL-2 production, which promotes the differentiation and proliferation of Th1 cells important for immune defense against intracellular infection. In this study we found that tumor-bearing mice were more susceptible to bacterial infection and showed reduced CCL5 levels in serum during endotoxic shock. Our data further demonstrated that the soluble factors secreted by mammary gland tumor cells but not normal mammary gland epithelial cells inhibited CCL5 expression in macrophages in response to LPS, but not to TNF-α stimulation. The inhibitory effect of tumor-secreted molecules on LPS-induced CCL5 expression was regulated at the post-transcriptional level. Blocking PGE(2) synthesis by NS398 or through the use of PGE(2) receptor antagonists AH-6809 (EP2 antagonist) and AH-23848 (EP4 antagonist) completely reversed the inhibitory effect of tumor-conditioned medium (TCM) on LPS-induced CCL5 expression. Moreover, PGE(2) and the cAMP analog forskolin could mimic tumor-mediated CCL5 inhibition, and the inhibitory effects of TCM, PGE(2), and cAMP analog on LPS-induced CCL5 expression could be completely reversed by the PKA inhibitor H89. Furthermore, blocking PGE(2) synthesis in vivo led to partial recovery of CCL5 production during endotoxic shock. Taken together, our data indicate that PGE(2) secreted from breast cancer cells suppresses CCL5 secretion in LPS-activated macrophages through a cAMP/PKA signaling pathway, which may result in suppression of host immune responses against subsequent bacterial infection.

Erlotinib as first-line treatment for untreated advance stage NSCLC with good prognosis

7178 Background: Erlotinib demonstrated improved survival in previously treated NSCLC, but did not affect survival in untreated NSCLC when used with concurrent chemotherapy. A potential hypothesis for this paradox is erlotinib may be more effective for patients with less aggressive tumors (i.e. those still surviving after multiple chemotherapy treatments). The current trial was designed to evaluate erlotinib before initial chemotherapy in a population of patients with less aggressive tumors based on clinical criteria. Methods: Eligibility criteria included stage IIIB/IV or recurrent NSCLC, no prior chemotherapy for systemic disease, PS = 0–1, weight loss less than 10%, and no urgent symptoms. Patients received erlotinib 150 mg po/day until objective or symptomatic progression before they were switched to chemotherapy. The 10 endpoint was time-to-progression after 1st chemotherapy. Results: 40 patients have been accrued. The median age was 65, 35 had PS = 1, 8 were never-smoker, and 23 were former smokers. Histologies were: Adeno 20, BAC 2, Sq 6, NSCLC 11, Other 1. The major toxicity was rash (Gr0 in 4, Gr1in 15, Gr2 in 14, Gr3 in 3, 4 too early. Other toxicity included liver (Gr 1 in 2, Gr2 in 1), mucositis (Gr1 in 1, Gr2 in 1) and diarrhea (liver (Gr1 in 10, Gr2 in 1, Gr3 in 2). 34 have been followed long enough for response evaluation, which identified 4 (12%) with PR (median 37 wks), 8 with stable (median 20 wk) and 22 with progression. At progression only 2 patients were too ill to start chemotherapy due to inadequate performance status. The median time on erlotinib was 8 wks overall: for rash Gr 0–1 8 wks, Gr 2–3=43 wks (p = 0.03). The median and 6-month PFS for chemotherapy are 22 wks and 45% with17 still on treatment. The median and 1-yr survivals are 50 wks and 47% with 24 pts still alive. Conclusions: Mid-term safety analyses exceeded expectations. Rash predicts duration of erlotinib effectiveness. Preliminary results suggest single agent, erlotinib may be as effective (PFS and survival) as initial chemotherapy with less toxicity and merits randomized testing as first treatment for advanced lung cancer. No significant financial relationships to disclose.

EVALUATION AND MANAGEMENT OF GASTRIC ADENOCARCINOMA

This article reviews the epidemiology, cause, and current staging of gastric adenocarcinoma. An in-depth discussion regarding patient assessment and treatment options is presented. Advanced disease management and clinical trials are reviewed.