Treatment at Twilight: An Analysis of Therapy Patterns and Outcomes in Adults 80 Years and Older With Advanced or Metastatic NSCLC.

Introduction: The aim of this study is to evaluate treatment patterns, survival outcomes, and factors influencing systemic treatment decisions in adults 80 years and older with NSCLC. Methods: This was a retrospective National Cancer Database study evaluating outcomes in adults aged 80 years and older with advanced NSCLC. Patients were analyzed on the basis of systemic therapy, including none, chemotherapy or immunotherapy (IO) alone, and chemotherapy plus IO (chemotherapy + IO). Median overall survival (OS) was compared using Kaplan-Meier methodology. Hazard ratio with 95% confidence interval (CI) was used to assess differences in outcomes, and OR with 95% CI was used to assess factors contributing to systemic therapy provision. Results: Patients 80 years and older (OR = 1.135 [95% CI: 1.127-1.142], p = 0.000), females (OR = 1.129 [95% CI: 1.085-1.175], p < 0.001), blacks (OR = 1.272 [95% CI: 1.179-1.372], p < 0.001), non-Hispanic whites (OR = 1.210 [95% CI: 1.075-1.362], p = 0.002), and those with increasing Charlson-Deyo Comorbidity Index score (p < 0.001) were less likely to receive systemic therapy. Median OS for no therapy, IO alone, chemotherapy alone, and chemotherapy plus IO was 2.63 (95% CI: 2.57-2.69), 10.68 (95% CI: 9.96-11.39), 12.35 (95% CI: 11.98-12.72), and 14.03 (95% CI: 13.87-14.88) months, respectively. In chemotherapy alone, mean OS was 1.12 months (95% CI: 0.55-1.70) (p < 0.001) longer with multiagent versus single agent. There was no difference between IO plus single agent versus IO plus multiagent chemotherapy (0.67 mo [95% CI -1.18 to 2.54], p = 1.00). Conclusions: Age, comorbidities, patient race, and sex affected systemic therapy provision. Multiagent chemotherapy and chemotherapy plus IO significantly improved survival; with the latter, survival was similar with IO plus single or multiagent chemotherapy.

Long-term outcomes in patients with Burkitt lymphoma older than 65 years: an analysis of the Texas Cancer Registry.

Burkitt lymphoma (BL) is an extremely aggressive but curable subtype of non-Hodgkin lymphoma. While younger patients have excellent outcomes in response to aggressive chemoimmunotherapy, the rarity of this disease in older patients and limitations caused by age, comorbidities, and performance status may negate survival advantages. This analysis assessed outcomes of older adults with BL through data provided by the Texas Cancer Registry (TCR). Patients ≥65 years with BL were assessed. Patients were dichotomized into 1997-2007 and 2008-2018. Median overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan-Meier methodology, and covariates including age, race, sex, stage, primary site, and poverty index were analyzed using Pearson Chi-squared analysis. Odds ratio (OR) with 95% confidence intervals (CI) was used to assess factors contributing to patients not offered systemic therapy. P value <0.05 was considered statistically significant. Non-BL mortality events were also categorized. There were 325 adults, 167 in 1997-2007 and 158 in 2008-2018; 106 (63.5%) and 121 (76.6%) received systemic therapy, a trend that increased with time (p = 0.010). Median OS for 1997-2007 and 2008-2018 was 5 months (95% CI 2.469, 7.531) and 9 months (95% CI 0.000, 19.154) (p = 0.013), and DSS was 72 months (95% CI 56.397, 87.603) (p = 0.604) and not reached, respectively. For patients that received systemic therapy, median OS was 8 months (95% CI 1.278, 14.722) and 26 months (95% CI 5.824, 46.176) (p = 0.072), respectively, and DSS was 79 months (95% CI: 56.416, 101.584) and not reached, respectively (p = 0.607). Age ≥75 years (HR 1.39 [95% CI 1.078, 1.791], p = 0.011) and non-Hispanic whites (HR 1.407 [95% CI 1.024, 1.935], p = 0.035) had poorer outcomes, and patients at the 20-100% poverty index (OR 0.387 [95% CI 0.163, 0.921], p = 0.032) and increasing age at diagnosis (OR 0.947 [95% CI 0.913, 0.983], p = 0.004) were less likely to receive systemic therapy. Of 259 (79.7%) deaths, 62 (23.9%) were non-BL deaths, and 6 (9.6%) of these were from a second cancer. This two-decade analysis of older Texas patients with BL indicates a significant improvement in OS over time. Although patients were more likely to receive systemic therapy over time, treatment disparities existed in patients residing in poverty-stricken regions of Texas and in advancing age. These statewide findings reflect an unmet national need to find a systemic therapeutic strategy that can be tolerated by and augment outcomes in the growing elderly population.

Long term outcomes in older patients with primary central nervous system lymphoma: an analysis of the Texas Cancer Registry.

Primary central nervous system lymphoma (PCNSL) is an aggressive subtype of non-Hodgkin lymphoma that carries a poor prognosis in the elderly. The aim of this study is to investigate treatment patterns and survival trends in patients ≥ 65 years with PCNSL through data provided by the Texas Cancer Registry. Adults ≥ 65 years diagnosed with PCNSL and followed between 1995-2017 were identified and separated into three eras: 1995-2003, 2004-2012, and 2013-2017. Baseline covariates compared included patient demographics and treatments administered. Pearson's chi-squared test and Cox proportional hazard models compared covariates; overall survival (OS) and disease-specific survival (DSS) were assessed via Kaplan-Meier methodology. There were 375 patients; 104 (27.7%) in 1995-2003, 146 (38.9%) in 2004-2012, and 125 (33.3%) in 2013-2017. There were 50 (48.1%), 55 (37.7%), and 31 (24.8%) in 1995-2003, 2004-2012, and 2013-2017, respectively, that did not receive treatment. At last follow up, 101 (97.1%), 130 (89.0%), and 94 (75.2%) in each era died, of which 89 (85.6%), 112 (76.7%), and 70 (56.0%) were attributed to PCNSL. Median OS per era was eight (95% confidence interval [CI] 5.06-10.93), six (95% CI, 2.30-9.69), and five months (95% CI, 2.26-7.73) (p = 0.638). DSS per era was nine (95% CI: 0.00, 26.53), 10 (95% CI: 5.14, 14.86), and 19 (95% CI, 0.00-45.49) (p = 0.931) months. Spinal cord as primary disease site (HR: 0.668 [95% CI, 0.45-0.99], p = 0.049), and chemotherapy (HR 0.532 [95% CI, 0.42-0.673], p = < 0.001) or chemotherapy + radiation (HR, 0.233 [95% CI, 0.11-0.48] p < 0.001) had better outcomes compared to no therapy or radiation therapy alone. Survival in older patients ≥ 65 with PCNSL has not improved per our analysis of the TCR from 1995-2017 despite increasing trends of treatment utilization. Strategies to augment recruitment of older individuals in trials are needed in order to determine who would derive treatment benefit and minimize treatment toxicities.

Cardiovascular Risks with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors and Monoclonal Antibody Therapy.

PURPOSE OF REVIEW: Tyrosine kinase inhibitors (TKI) and monoclonal antibodies (mAbs) that target the epidermal growth factor receptor (EGFR) have changed the therapeutic landscape across a range of solid malignancies. However, there is little data regarding the cardiovascular (CV) impact of these agents. The purpose of this review is to discuss reported CV effects, pathophysiology, pre-treatment screening, diagnostic workup, and treatment recommendations in this patient population. RECENT FINDINGS: It is apparent that CV events are not class dependent, and while infrequently reported in clinical trials, unique CV toxicity may occur with EGFR inhibitors, including structural, electrical, and vascular events. There remains an unmet need to fully elucidate the spectrum of CV events associated with EGFR inhibitors. Early CV screening, close clinical monitoring, coupled with a multidisciplinary approach between medical and cardio-oncology is needed to minimize the potentially detrimental impact of cardiotoxicity in this patient population.

Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan−Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4−16.7] vs. 21.03 [95% CI: 14.7−24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26−8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72−19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

Outcomes and prognostic contributors in patients with KRAS mutated non-small cell pulmonary adenocarcinomas: a single institution experience.

BACKGROUND: KRAS is the most frequently encountered driver mutation in advanced non-small cell lung cancer (NSCLC). With targeted therapy for the most common KRAS mutation p.G12C on the horizon, the aim of this study is to retrospectively report outcomes in patients with KRAS mutated NSCLC. METHODS: This was a retrospective chart review of 7 hospitals in Texas with reflex biomarker testing in all lung adenocarcinomas. Patients were included if they had pathologically diagnosed adenocarcinoma of any stage originating in the lung with molecularly confirmed KRAS driver mutation of any genotypic subtype. Twelve-month survival was assessed and compared between KRAS p.G12C and all other detected KRAS mutations. Other outcomes including impact of age, sex, smoking status, and pack years smoked were assessed to determine if they had prognostic significance on mortality in KRAS mutated patients. RESULTS: There were 58 patients diagnosed with KRAS mutated NSCLC, 63.8% were at an advanced stage at diagnosis, 55.8% of patients were female, and 82.8% were white. The median age was 72 [52-88] years, and 93.1% were either current or prior smokers. KRAS p.G12C was the most common KRAS mutation (44.8%). At diagnosis, patients with KRAS p.G12C had poorer performance statuses compared to other KRAS mutations. A total of 32 (55.2%) patients died, 26 with advanced disease. In this study, current smoking status (P=0.1652), pack years smoked (P=0.6597), age (P=0.5092), sex (P=0.4309), and underlying KRAS codon mutation controlling for stage (P=0.2287) did not impact survival. However, KRAS p.G12C had a numerically lower 12 months overall survival (OS) compared to all other KRAS mutations in both early stage (56.3% vs. 90.9%) and advanced stage (25.0% vs. 47.6%) disease. Of note, 16 (27.6%) patients had prior, concurrent, or second malignancies, but these did not significantly impact OS (P=0.7696). CONCLUSIONS: This study did not find a prognostic difference with sex, smoking history, age, or p.G12C mutation. The patients in this cohort with KRAS p.G12C had a numerically lower 12-month overall survival in both early and advanced stage disease compared to other mutations, and over one-quarter had a notable history of previous and second primary malignancies.

Post-Marketing Analysis of Peripheral Neuropathy Burden with New-Generation Proteasome Inhibitors Using the FDA Adverse Event Reporting System

Proteasome inhibitors (PIs) are an integral component of multiple myeloma therapies. Peripheral neuropathy (PN) is a well-knownconsequence of PIs, most frequently reported with earlier generations such as bortezomib (BTZ). There is a paucity of data highlighting the risk of developing PN with the new-generation PIs carfilzomib (CFZ) and ixazomib (IZB). This study evaluated reports of PN encountered with all three PIs using the Food and Drug Administration Adverse Event (AE) Reporting System (FAERS). Signal disproportionality analysis was reported using the reporting odds ratio (ROR) with 95% confidence interval (CI). PN was reported in a total of 2.1%, 5.0%, and 10.9% of AEs with CFZ, IZB, and BTZ, respectively. The ROR (95% CI) for PN secondary to BTZ, CFZ, and IZB was 34.10 (32.76-35.49), 6.37 (5.50-7.37), and 14.97 (13.63-16.44), respectively. Compared to BTZ, CFZ and IZB have lower rates of reported PN, with RORs of 0.19 (0.16-0.22) and 0.48 (0.43-0.54), respectively.

Cardiotoxicity Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Recognition, Risk Factors, and Management.

Chimeric antigen receptor T-cells (CAR-T) are improving outcomes in pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemias and subtypes of non-Hodgkin Lymphoma. As this treatment is being increasingly utilized, a better understanding of the unique toxicities associated with this therapy is warranted. While there is growing knowledge on the diagnosis and treatment of cytokine release syndrome (CRS), relatively little is known about the associated cardiac events that occur with CRS that may result in prolonged length of hospital stay, admission to the intensive care unit for pressor support, or cardiac death. This review focuses on the various manifestations of cardiotoxicity, potential risk factors, real world and clinical trial data on prevalence of reported cardiotoxicity events, and treatment recommendations.

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors.

There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration's (FDA) Adverse Events Reporting System (FAERS) queried reported cases of "Hepatitis B reactivation" reported with the PD-1/PD-L1 inhibitors "Pembrolizumab," "Atezolizumab," "Nivolumab," "Durvalumab," "Avelumab," and "Ipilimumab" from initial FDA approval to June 30, 2020. Disproportionality signal analysis was determined by calculating a reporting odds ratio (ROR) and 95% confidence intervals (CI). The ROR was considered significant when the lower and upper limits of the 95% CI were >1 and confirmed by the Fisher exact test (P<0.05). Pembrolizumab had a strong signal associated with HBVr, with a ROR of 2.32 (95% CI: 1.11-4.28) (P=0.013) and was the only statistically significant finding. There were no reports of HBVr with Ipilimumab or Avelumab. Additional prospective studies should be conducted to validate the findings of this retrospective pharmacovigilance analysis to determine the risk of HBVr in patients receiving immune checkpoint inhibitors.

The development of T-cell malignancies in patients with pre-existing myeloproliferative neoplasms: a report of three cases.

Secondary acute myeloid leukaemia complicating the natural disease course of pre-existing Philadelphia chromosome-negative myeloproliferative neoplasms (PN-MPN) is well documented and associated with treatment challenges and significant morbidity. The incidence of a T-cell malignancy developing in patients with pre-existing PN-MPN is uncommon, with one case documented in the literature. We present two cases of angioimmunoblastic T-cell lymphoma (AITL) and one case of T-cell acute lymphoblastic leukaemia (T-ALL) that developed in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively. All malignancies were advanced at diagnosis and exhibited disease progression, regardless of the mutational status of the underlying ET/PMF, presence of cytogenetic abnormalities, type of T-cell neoplasm or systemic chemotherapy utilised. The median time to diagnosis of AITL or T-ALL from the onset of MPN was 4.5 years (range: 6 months-10 years). This single institutional case series demonstrates the possibility of an association between T-cell neoplasms and PN-MPNs.

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review.

BACKGROUND: Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS). MATERIALS AND METHODS: This is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1. RESULTS: There were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died. CONCLUSION: Patients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib.

A Case of Histiocytic Sarcoma Arising from Mycosis Fungoides.

Histiocytic sarcoma (HS) is an uncommon malignant neoplasm arising from mature histiocytes and most commonly characterized by the immunophenotypic expression of CD68, CD163, or lysozyme. Although rare, HS arising as a second primary malignancy following hematolymphoid neoplasms has been reported. To our knowledge, this is the first reported case of HS occurring as a second primary malignancy in a patient with mycosis fungoides (MF), with the retained immunophenotype markers CD30 and CD4.

Primary cardiac angiosarcoma diagnosed in the first trimester of pregnancy.

Primary cardiac angiosarcoma (PCAS) is a malignancy seldom seen in pregnancy. A 23-year-old G1P0 Chinese female was found to have PCAS during her first trimester when she presented with tamponade physiology. The transthoracic echocardiography (TTE) results did not indicate the presence of an intracardiac lesion, and pericardial fluid cytology analysis showed no evidence of malignancy. Cardiac magnetic resonance imaging (CMRI) exhibited a right atrial mass, and tissue biopsy indicated a high-grade angiosarcoma. MRI of the abdomen was suggestive of liver metastasis. She underwent an abortion and was started on combination chemotherapy, with a reduction in both the cardiac and liver masses. In cardiac angiosarcomas, advanced imaging modalities such as MRI should be utilised when there is high clinical suspicion or in the case of pregnancy when trying to minimise foetal harm. Prognosis is poor, and a standardised treatment protocol regardless of pregnancy continues to elude the medical community.

Trends in the Body Mass Index of Pediatric and Adult Patients Undergoing Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The body mass index (BMI) in the United States (US) is rising and may be contributing to increased anterior cruciate ligament reconstruction (ACLR) rates. It is currently unknown whether the BMI is increasing in patients who undergo ACLR. PURPOSE: To determine whether (1) the BMI changed in pediatric and adult patients who previously underwent ACLR or revision ACLR over a 10-year eligibility period, (2) the BMI changed at a greater rate in pediatric or adult patients, and (3) the percentage of overweight and obese patients in the ACLR population was different than that of the general overweight population. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective investigation of patients who underwent ACLR by 6 surgeons from June 3, 2005, to June 3, 2015, was conducted. Patients were divided into pediatric (<18 years) and adult (≥18 years) categories. BMI at the time of surgery was defined as underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Patients with an indeterminate BMI were excluded. Comparisons of overweight and obese patients were made with general population trends determined by the Centers for Disease Control and Prevention (CDC) in a single US state. Pearson (R) and Spearman (Rs) correlations were used to determine correlations, Student t tests were used for 2-variable comparisons, analyses of variance were used for multivariable comparisons, and analyses of covariance were used for comparing linear relationships. RESULTS: There were 1305 patients (733 male, 572 female; 409 pediatric, 896 adult) included. Adults requiring surgical revision demonstrated a strong positive correlation with respect to BMI over time (Rs = 0.906, P < .01). No other statistically significant trends in the BMI over time were found. The proportion of overweight pediatric patients undergoing ACLR was significantly greater than that of the general overweight pediatric population (P < .05), and the proportion of obese pediatric and adult patients in the general population was greater than that of the obese patients in the study cohort (P < .05). CONCLUSION: Between 2005 and 2015, the BMI for pediatric and adult patients who underwent ACLR did not demonstrate a significant change over time. However, there was a statistically significant strong positive correlation for increasing BMI in adult patients requiring revision, although the mean BMI in patients who underwent revision was less than that of the general population. In addition, the percentage of overweight pediatric patients undergoing ACLR was significantly greater than that of the general population of overweight patients in a single US state reported by the CDC.