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1.
Cell ; 183(2): 363-376.e13, 2020 10 15.
Article in English | MEDLINE | ID: mdl-33007267

ABSTRACT

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.


Subject(s)
Biomarkers, Pharmacological/blood , Circulating Tumor DNA/analysis , Immune Checkpoint Inhibitors/therapeutic use , Adult , Antineoplastic Agents, Immunological/pharmacology , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , Biomarkers, Tumor/genetics , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Circulating Tumor DNA/genetics , Female , Humans , Immune Checkpoint Inhibitors/immunology , Immune Checkpoint Inhibitors/metabolism , Immunotherapy/methods , Lung Neoplasms/pathology , Male , Middle Aged , Programmed Cell Death 1 Receptor/metabolism
2.
Cancer Invest ; 41(1): 43-47, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36197034

ABSTRACT

There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006 to 2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.


Subject(s)
Drug Approval , Thoracic Neoplasms , United States/epidemiology , Humans , United States Food and Drug Administration , Research Report , Thoracic Neoplasms/drug therapy
3.
J Natl Compr Canc Netw ; 20(13)2022 01 18.
Article in English | MEDLINE | ID: mdl-35042190

ABSTRACT

BACKGROUND: Collecting, monitoring, and responding to patient-generated health data (PGHD) are associated with improved quality of life and patient satisfaction, and possibly with improved patient survival in oncology. However, the current state of adoption, types of PGHD collected, and degree of integration into electronic health records (EHRs) is unknown. METHODS: The NCCN EHR Oncology Advisory Group formed a Patient-Reported Outcomes (PRO) Workgroup to perform an assessment and provide recommendations for cancer centers, researchers, and EHR vendors to advance the collection and use of PGHD in oncology. The issues were evaluated via a survey of NCCN Member Institutions. Questions were designed to assess the current state of PGHD collection, including how, what, and where PGHD are collected. Additionally, detailed questions about governance and data integration into EHRs were asked. RESULTS: Of 28 Member Institutions surveyed, 23 responded. The collection and use of PGHD is widespread among NCCN Members Institutions (96%). Most centers (90%) embed at least some PGHD into the EHR, although challenges remain, as evidenced by 88% of respondents reporting the use of instruments not integrated. Forty-seven percent of respondents are leveraging PGHD for process automation and adherence to best evidence. Content type and integration touchpoints vary among the members, as well as governance maturity. CONCLUSIONS: The reported variability regarding PGHD suggests that it may not yet have reached its full potential for oncology care delivery. As the adoption of PGHD in oncology continues to expand, opportunities exist to enhance their utility. Among the recommendations for cancer centers is establishment of a governance process that includes patients. Researchers should consider determining which PGHD instruments confer the highest value. It is recommended that EHR vendors collaborate with cancer centers to develop solutions for the collection, interpretation, visualization, and use of PGHD.


Subject(s)
Medical Oncology , Quality of Life , Humans , Delivery of Health Care , Electronic Health Records , Surveys and Questionnaires
4.
J Neurooncol ; 160(1): 233-240, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36227422

ABSTRACT

PURPOSE: Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone. METHODS: We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB. RESULTS: We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9-17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87-7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49-3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99-31.81; p = 0.003) were associated with LRiB. CONCLUSIONS: Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.


Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Protein Kinase Inhibitors , Humans , Aniline Compounds/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies
5.
J Natl Compr Canc Netw ; 19(7): 780-788, 2021 07 28.
Article in English | MEDLINE | ID: mdl-34340208

ABSTRACT

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.


Subject(s)
Neoplasms , Palliative Care , Humans , Medical Oncology , Neoplasms/therapy , Quality of Life
6.
J Neurooncol ; 152(1): 125-134, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33415659

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described. METHODS: We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed. RESULTS: A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF. CONCLUSIONS: In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug-Related Side Effects and Adverse Reactions , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/metabolism , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/secondary , Disease Progression , Female , Humans , Immune System Diseases/chemically induced , Immunotherapy/adverse effects , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Male , Middle Aged , Retrospective Studies
7.
Curr Opin Obstet Gynecol ; 32(1): 65-75, 2020 02.
Article in English | MEDLINE | ID: mdl-31851044

ABSTRACT

PURPOSE OF REVIEW: Patients with gynecologic malignancies experience varied and often difficult-to-manage symptoms through their disease course, along with decisions surrounding preferences for advance care planning. This review focuses on evidence-based symptom management for these patients and offers a framework for conversations regarding goals of therapy. RECENT FINDINGS: There is increasing literature on palliative care specifically in gynecologic oncology, including barriers and possible solutions for early palliative care use, along with updated guidelines on postoperative pain management and tools for communication. SUMMARY: Integration of early palliative care and focus on symptom management is an important and multidisciplinary approach to help patients with gynecologic malignancies.


Subject(s)
Genital Neoplasms, Female/therapy , Medical Oncology/methods , Palliative Care/methods , Advance Care Planning , Female , Humans , Physician-Patient Relations , Quality of Life
9.
Value Health ; 21(8): 931-937, 2018 08.
Article in English | MEDLINE | ID: mdl-30098670

ABSTRACT

OBJECTIVES: Cancer costs have increased substantially in the past decades, prompting specialty societies to urge oncologists to consider value in clinical decision making. Despite oncologists' crucial role in guiding cancer care, current literature is sparse with respect to the oncologists' views on value. Here, we evaluated oncologists perceptions of the use and measurement of value in cancer care. METHODS: We conducted in-depth, open-ended interviews with 31 US oncologists practicing nationwide in various environments. Oncologists discussed the definition, measurement, and implementation of value. Transcripts were analyzed using matrix and thematic analysis. RESULTS: Oncologists' definitions of value varied greatly. Some described versions of the standard health economic definition of value, that is, cost relative to health outcomes. Many others did not include cost in their definition of value. Oncologists considered patient goals and quality of life as important components of value that they perceived were missing from current value measurement. Oncologists prioritized a patient-centric view of value over societal or other perspectives. Oncologists were inclined to consider the value of a treatment only if they perceived treatment would pose a financial burden to patients. Oncologists had differing opinions regarding who should be responsible for determining whether care is low value but generally felt this should remain within the purview of the oncology community. CONCLUSIONS: Oncologists agreed that cost was an important issue, but disagreed about whether cost was involved in value as well as the role of value in guiding treatment. Better clarity and alignment on the definition of and appropriate way to measure value is critical to the success of efforts to improve value in cancer care.


Subject(s)
Neoplasms/economics , Neoplasms/therapy , Oncologists/psychology , Adult , Aged , Attitude of Health Personnel , Clinical Decision-Making/methods , Decision Making , Female , Humans , Interviews as Topic/methods , Male , Middle Aged , Physician-Patient Relations , Qualitative Research , United States
10.
J Natl Compr Canc Netw ; 14(7): 859-66, 2016 07.
Article in English | MEDLINE | ID: mdl-27407126

ABSTRACT

BACKGROUND: ASCO and IOM recommend palliative care (PC) across health care settings for patients with serious illnesses, including cancer. This study provides an overview of the current availability, structure, and basic quality of PC services within NCCN Member Institutions. METHODS: A PC survey was developed by NCCN staff and a working group of PC experts from 11 NCCN Member Institutions under the auspices of the NCCN Best Practices Committee. The survey was piloted and refined by 3 working group members and sent electronically to all 26 NCCN Member Institutions. NCCN staff and working group leaders analyzed the survey data. RESULTS: A total of 22 of 26 institutions responded (85%). All respondents (100%) reported an inpatient PC consult service (staffed by an average of 6.8 full-time equivalents [FTEs], seeing 1,031 consults/year with an average length of stay [LOS] of 10 days). A total of 91% of respondents had clinic-based PC (with an average of 469 consults/year, staffed by an average of 6.8 FTEs, and a 17-day wait time). For clinics, a comanagement care delivery model was more common than strict consultation. Home-based PC (23%) and inpatient PC units (32%) were less prevalent. Notably, 80% of institutions reported insufficient PC capacity compared with demand. Across PC settings, referrals for patients with solid tumors were more common than for hematologic malignancies. Automatic or "triggered" referrals were rare. The most common services provided were symptom management (100%) and advance care planning (96%). Most programs were funded through fee-for-service billing and institutional support. Partnerships with accountable care organizations and bundled payment arrangements were infrequent. PC program data collection and institutional funding for PC research were variable across institutions. CONCLUSIONS: Despite the prevalence of PC inpatient and clinic services among participating NCCN Member Institutions, PC demand still exceeds capacity. Opportunities exist for expansion of home-based PC and inpatient PC units, optimizing referrals, research, and payer collaborations.


Subject(s)
Neoplasms/rehabilitation , Palliative Care , Cancer Care Facilities , Female , History, 21st Century , Humans , Male , Surveys and Questionnaires , United States
11.
Curr Treat Options Oncol ; 17(5): 23, 2016 May.
Article in English | MEDLINE | ID: mdl-27032645

ABSTRACT

OPINION STATEMENT: Palliative care integrated into standard medical oncologic care will transform the way we approach and practice oncologic care. Integration of appropriate components of palliative care into oncologic treatment using a pathway-based approach will be described in this review. Care pathways build on disease status (early, locally advanced, advanced) as well as patient and family needs. This allows for an individualized approach to care and is the best means for proactive screening, assessment, and intervention, to ensure that all palliative care needs are met throughout the continuum of care. Components of palliative care that will be discussed include assessment of physical symptoms, psychosocial distress, and spiritual distress. Specific components of these should be integrated based on disease trajectory, as well as clinical assessment. Palliative care should also include family and caregiver education, training, and support, from diagnosis through survivorship and end of life. Effective integration of palliative care interventions have the potential to impact quality of life and longevity for patients, as well as improve caregiver outcomes.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Palliative Care , Cancer Pain/therapy , Caregivers , Humans , Stress, Psychological
12.
Cancer Control ; 22(4): 386-95, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26678965

ABSTRACT

BACKGROUND: Patients with cancer have complex physical, psychosocial, and spiritual needs that evolve throughout their disease trajectory. As patients are living longer with a diagnosis of cancer, the need is growing to address the morbidity due to the underlying illness as well as treatment-related adverse events. Palliative care includes treating physical symptoms as well as addressing psychosocial and spiritual needs. When these needs are addressed, the quality of care improves, costs decrease, and goals are aligned between the medical care provided and the patient and family. However, how best to integrate palliative care into oncology care is still an area of investigation. METHODS: The authors conducted a literature search, including randomized clinical trials and practice reviews, to evaluate the evidence for integrating palliative care into oncology care. Barriers to integration as well as sustainable paths forward are highlighted. The authors also utilize case studies as representative examples of integration. RESULTS: Current studies demonstrate that integrating palliative care into oncology care improves symptom control, rates of patient and family satisfaction, and quality of end-of-life care. However, for systemwide integration to be successful, commitment must be made to quality improvement, an infrastructure must be built to support palliative care screening, assessment, and intervention, and stakeholders must be engaged in the program. In addition, value must be demonstrated using metrics that affect quality, care utilization, and patient satisfaction. CONCLUSIONS: Even though most US cancer centers have a palliative care program, palliative care remains limited in scope. An integrated approach for palliative care with oncology care requires a systems-based approach, with agreement between all parties on shared common metrics for value.


Subject(s)
Medical Oncology/methods , Neoplasms/drug therapy , Neoplasms/therapy , Palliative Care/methods , Humans , Patient Satisfaction , Quality of Life , Randomized Controlled Trials as Topic
13.
Am Soc Clin Oncol Educ Book ; 44(3): e433298, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38768420

ABSTRACT

People with advanced lung cancer represent a distinct group whose needs remain understudied, especially compared with people diagnosed with limited-stage disease. Fortunately, novel treatments such as tyrosine kinase inhibitors and immune checkpoint inhibitors are leading to significant advances in prognosis and survival, even among those with advanced disease at the time of diagnosis. However, there are known gaps in symptom management, psychosocial and nutritional support, complex care coordination, health behavior coaching, and health care delivery efforts among patients living with advanced lung cancer. Many of these patients would benefit from survivorship and palliative care approaches. In particular, survivorship care may include health care maintenance, treatment of immune-related adverse events and late- or long-term effects, frailty assessment and rehabilitation, and care coordination. Palliative care may be best suited to discuss ongoing symptom management, advanced care planning, and end-of-life considerations, as well as psychosocial well-being. To this end, we share a review of the current status of the palliative and survivorship care infrastructure for patients with advanced lung cancer and provide suggestions across the care continuum for this diverse group of patients and families.


Subject(s)
Lung Neoplasms , Palliative Care , Survivorship , Humans , Lung Neoplasms/therapy , Cancer Survivors , Neoplasm Staging , Quality of Life
14.
J Palliat Med ; 27(1): 83-89, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37935036

ABSTRACT

Background: Patients with serious illness benefit from conversations to share prognosis and explore goals and values. To address this, we implemented Ariadne Labs' Serious Illness Care Program (SICP) at Stanford Health Care. Objective: Improve quantity, timing, and quality of serious illness conversations. Methods: Initial implementation followed Ariadne Labs' SICP framework. We later incorporated a team-based approach that included nonphysician care team members. Outcomes included number of patients with documented conversations according to clinician role and practice location. Machine learning algorithms were used in some settings to identify eligible patients. Results: Ambulatory oncology and hospital medicine were our largest implementation sites, engaging 4707 and 642 unique patients in conversations, respectively. Clinicians across eight disciplines engaged in these conversations. Identified barriers that included leadership engagement, complex workflows, and patient identification. Conclusion: Several factors contributed to successful SICP implementation across clinical sites: innovative clinical workflows, machine learning based predictive algorithms, and nonphysician care team member engagement.


Subject(s)
Critical Care , Critical Illness , Humans , Critical Illness/therapy , Communication , Physician-Patient Relations , Academic Medical Centers
15.
Clin Lung Cancer ; 25(2): 186-189, 2024 03.
Article in English | MEDLINE | ID: mdl-38040540

ABSTRACT

INTRODUCTION: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs). METHODS: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint. CONCLUSION: PACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Adolescent , Lung Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Bayes Theorem , Chemoradiotherapy/methods , Lung , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Trials, Phase II as Topic , Clinical Trials, Phase I as Topic
16.
J Natl Cancer Inst ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39348179

ABSTRACT

BACKGROUND: Advance care planning/serious illness conversations can help clinicians understand patients' values and preferences. There are limited data on how to increase these conversations, and their effect on care patterns. We hypothesized that using a machine learning survival model to select patients for serious illness conversations, along with trained care coaches to conduct the conversations, would increase uptake in cancer patients at high risk of short-term mortality. METHODS: We conducted a cluster-randomized stepped wedge study on the physician level. Oncologists entered the intervention condition in a random order over six months. Adult patients with metastatic cancer were included. Patients with <2 year computer-predicted survival and no prognosis documentation were classified as high-priority for serious illness conversations. In the intervention condition, providers received automated weekly emails highlighting high-priority patients and were asked to document prognosis for them. Care coaches reached out to these patients to conduct the remainder of the conversation. The primary endpoint was proportion of visits with prognosis documentation within 14 days. RESULTS: 6,372 visits in 1,825 patients were included in the primary analysis. The proportion of visits with prognosis documentation within 14 days was higher in the intervention condition than control condition: 2.9% vs 1.1% (adjusted odds ratio 4.3, p < .0001). The proportion of visits with advance care planning documentation was also higher in the intervention condition: 7.7% vs 1.8% (adjusted odds ratio 14.2, p < .0001). In high-priority visits, advance care planning documentation rate in intervention/control visits was 24.2% vs 4.0%. CONCLUSION: The intervention increased documented conversations, with contributions by both providers and care coaches.

17.
medRxiv ; 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38343840

ABSTRACT

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

18.
Article in English | MEDLINE | ID: mdl-39357790

ABSTRACT

HYPOTHESIS: For metastatic non-small cell lung cancer (NSCLC), the addition of radiotherapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS). METHODS: In this single arm phase 2 trial, 45 patients with metastatic NSCLC who had received an anti-PD-1/anti-PD-L-1 ICI for 4+ weeks were enrolled from July 2017-May 2021. Patients received high-dose RT to 1-4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing to a historical control rate of 35%. RESULTS: Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1 positive. Median number of treated tumors was two and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI 44-75%), higher than the historical control rate (p<0.001). Median PFS was 6.9 months (95% CI 4.0-13.5 mo) and median OS was 27.4 months (95% CI 20.4-not reached). Several patients with pre-study disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at one, two, and three years. Two dose-limiting toxicities were observed (5%), including one grade 5 pneumonitis. CONCLUSIONS: The strategy improved 24-week PFS compared to historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.

19.
Cancer ; 119(11): 2074-80, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23504709

ABSTRACT

BACKGROUND: This study sought to develop a predictive model for 30-day mortality in hospitalized cancer patients, by using admission information available through the electronic medical record. METHODS: Observational cohort study of 3062 patients admitted to the oncology service from August 1, 2008, to July 31, 2009. Matched numbers of patients were in the derivation and validation cohorts (1531 patients). Data were obtained on day 1 of admission and included demographic information, vital signs, and laboratory data. Survival data were obtained from the Social Security Death Index. RESULTS: The 30-day mortality rate of the derivation and validation samples were 9.5% and 9.7% respectively. Significant predictive variables in the multivariate analysis included age (P < .0001), assistance with activities of daily living (ADLs; P = .022), admission type (elective/emergency) (P = .059), oxygen use (P < .0001), and vital signs abnormalities including pulse oximetry (P = .0004), temperature (P = .017), and heart rate (P = .0002). A logistic regression model was developed to predict death within 30 days: Score = 18.2897 + 0.6013*(admit type) + 0.4518*(ADL) + 0.0325*(admit age) - 0.1458*(temperature) + 0.019*(heart rate) - 0.0983*(pulse oximetry) - 0.0123 (systolic blood pressure) + 0.8615*(O2 use). The largest sum of sensitivity (63%) and specificity (78%) was at -2.09 (area under the curve = -0.789). A total of 25.32% (100 of 395) of patients with a score above -2.09 died, whereas 4.31% (49 of 1136) of patients below -2.09 died. Sensitivity and positive predictive value in the derivation and validation samples compared favorably. CONCLUSIONS: Clinical factors available via the electronic medical record within 24 hours of hospital admission can be used to identify cancer patients at risk for 30-day mortality. These patients would benefit from discussion of preferences for care at the end of life.


Subject(s)
Electronic Health Records/statistics & numerical data , Models, Statistical , Neoplasms/mortality , Patient Admission/statistics & numerical data , Aged , Cohort Studies , Female , Hospital Mortality , Humans , Logistic Models , Male , Prognosis , Risk Assessment/methods , Risk Factors
20.
Oncology (Williston Park) ; 27(1): 13-6, 27-30, 32-4 passim, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23461040

ABSTRACT

Palliative cancer care is the integration into oncologic care of therapies that address the issues that cause physical and psychosocial suffering for the patient and family. Effective provision of palliative cancer care requires an interdisciplinary team that can provide care in all settings (home, inpatient, and outpatient). There is clear evidence for improved outcomes in multiple domains-symptoms, quality of end-of-life care, provider satisfaction, cost of care-with the integration of palliative care into cancer care. As a result, there are now guideline-based recommendations for incorporating palliative care into cancer care. Unfortunately there continue to be barriers to effective integration; these include gaps in education and research, and a cultural stigma that equates palliative care with end-of-life care. These barriers will need to be addressed in order to achieve seamless palliative care integration across the continuum of cancer care for all patients and their families.


Subject(s)
Neoplasms/therapy , Palliative Care , Female , Humans , Male
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