Showing papers by "Aminah Jatoi published in 2018"

Prevalence and survival impact of pretreatment cancer-associated weight loss: A tool for guiding early palliative care

Abstract: Purpose:Cancer-associated weight loss is associated with poor prognosis in advanced malignancy; however, its pretreatment prevalence and survival impact are inadequately described in large cohorts. Such data, stratified by tumor type and stage, may facilitate the optimal and timely allocation of complementary care, leading to improvements in patient survival and quality of life.Methods:We performed a retrospective cohort study of 3,180 consecutively treated adult patients with lung or GI (including colorectal, liver, and pancreatic) cancer. Pretreatment cancer-associated weight loss was based on the international consensus definition of cachexia. Prevalence and survival impact of pretreatment cancer-associated weight loss were evaluated using the Kaplan-Meier method and compared using log-rank test.Results:Cancer-associated weight loss was observed at the time of cancer diagnosis in 34.1% of patients. Pretreatment weight loss was documented in 17.6%, 25.8%, 36.6%, and 43.3% of stage I, II, III, and IV can...

The Role of Systemic Inflammation in Cancer-Associated Muscle Wasting and Rationale for Exercise as a Therapeutic Intervention.

Abstract: Progressive skeletal muscle wasting in cancer cachexia involves a process of dysregulated protein synthesis and breakdown. This catabolism may be the result of mal-nutrition, and an upregulation of both pro-inflammatory cytokines and the ubiquitin proteasome pathway (UPP), which can subsequently increase myostatin and activin A release. The skeletal muscle wasting associated with cancer cachexia is clinically significant, it can contribute to treatment toxicity or the premature discontinuation of treatments resulting in increases in morbidity and mortality. Thus, there is a need for further investigation into the pathophysiology of muscle wasting in cancer cachexia to develop effective prophylactic and therapeutic interventions. Several studies have identified a central role for chronic-systemic inflammation in initiating and perpetuating muscle wasting in patients with cancer. Interestingly, while exercise has shown efficacy in improving muscle quality, only recently have investigators begun to assess the impact that exercise has on chronic-systemic inflammation. To put this new information into context with established paradigms, here we review several biological pathways (e.g. dysfunctional inflammatory response, hypothalamus pituitary adrenal axis, and increased myostatin/activin A activity) that may be responsible for the muscle wasting in patients with cancer. Additionally, we discuss the potential impact that exercise has on these pathways in the treatment of cancer-related muscle wasting. Exercise is an attractive intervention for muscle wasting in this population, partially because it disrupts chronic-systemic inflammation mediated catabolism. Most importantly, exercise is a potent stimulator of muscle synthesis, and therefore this therapy may reverse muscle damage caused by cancer cachexia.

Promoting Accrual of Older Patients with Cancer to Clinical Trials: An Alliance for Clinical Trials in Oncology Member Survey (A171602)

Abstract: BACKGROUND There are multiple known individual- and practice-level barriers to enrollment of older patients with cancer to clinical trials, but little is known about how the clinical research workforce feels about potential higher-level strategy changes aimed to promote increased enrollment of older patients. SUBJECTS, MATERIALS, AND METHODS We invited all 11,351 Alliance for Clinical Trials in Oncology ("Alliance") members to participate in an anonymous, web-based survey to examine awareness of current accrual patterns for older patients to clinical trials, to ascertain consensus on how to tackle enrollment challenges, and to provide the impetus for high-level changes to improve clinical trial accrual of older patients with cancer. RESULTS During the period from February 28, 2017, to June 16, 2017, 1,146 Alliance members participated (response rate = 10%), including a national diverse sample of physicians, nurses, administrative/clinical research staff, and patient advocates with representation from community, academic, and rural sites. Overall, one third felt that >50% of clinical trial enrollees should be age ≥65, and 64.9% felt the Alliance could improve upon enrollment of older patients. The four most commonly ranked strategies to improve enrollment of older patients were creating more dedicated trials for this population (36.3%), minimizing exclusion criteria focused on comorbidity (35.5%), developing independent strategies for those aged ≥65 and for those aged ≥70 (33.2%), and requiring that most/all Alliance trials have a specific expansion cohort of older patients (30.0%). CONCLUSION We anticipate that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials. IMPLICATIONS FOR PRACTICE This survey of the Alliance for Clinical Trials membership sought opinions on potential, large-scale, national strategies to improve accrual of older adults with cancer. Consensus was found around multiple strategies, including creating more dedicated trials for older patients, developing less stringent eligibility criteria, and mandating expansion cohorts of older patients within broader Alliance trials. It is anticipated that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.

Nomogram prediction of overall survival for patients with non-small-cell lung cancer incorporating pretreatment peripheral blood markers.

Abstract: Objectives The objective of this study is to build a novel prognostic nomogram in non-small-cell lung cancer (NSCLC) incorporating pre-treatment peripheral blood markers beyond known pathoclinical predictors. Methods We analysed 7158 patients with NSCLC diagnosed between 1 January 1997 and 31 December 2012 from a single institution with a uniform medical record and routine follow-up information. Besides common clinicopathological factors, we investigated the prognostic value of the neutrophil to lymphocyte ratio, monocytes and haemoglobin level in peripheral blood before treatment. Patients were randomly assigned to training (4772 patients, 66.7%) or validation cohorts (2386 patients, 33.3%). Cox proportional hazards models determined the effects of multiple factors on overall survival (OS). A nomogram was developed to predict median survival and 1-, 3-, 5- and 10-year OS for NSCLC. The performance of the nomogram was assessed by a concordance index and calibration curve. Results In the training cohort, the multivariate Cox model identified the neutrophil to lymphocyte ratio, monocytes and haemoglobin level before treatment as significant prognostic factors for OS independent of patient age, gender, smoking history of intensity and cessation, performance status, disease stage, tumour cell type and differentiation grade and therapies. All the significant prognostic variables were incorporated into a nomogram. In the validation cohort, the nomogram showed notable accuracy in predicting OS, with a concordance index of 0.81, and was well calibrated for predictions of OS. Conclusions The proposed nomogram incorporating peripheral blood markers and known prognostic factors could accurately predict individualized survival probability of patients with NSCLC. It could be used in treatment planning and stratification in clinical trials.

Impact of Socioeconomic Status on Pretreatment Weight Loss and Survival in Non-Small-Cell Lung Cancer.

Abstract: Purpose:Socioeconomic status (SES) influences health care outcomes, but the influence of primary payer on cancer-associated wasting is unknown. We hypothesized that primary payer as an indicator of SES would influence pretreatment cancer-associated weight loss and treatment outcomes.Materials and Methods:Retrospective review of medical records identified 1,366 patients with non–small-cell lung cancer (NSCLC) consecutively treated at a tertiary care health system between January 1, 2006 and December 31, 2013. Insurance status was obtained from an institutional tumor registry. Cancer-associated weight loss was based on the validated international consensus definition of cachexia. Multivariable regression analyses were used to identify prognostic factors of pretreatment cancer-associated weight loss and survival.Results:The cohort included a representative group of patients with a median age at diagnosis of 64 years, 47% females, and 33% patients of nonwhite race. Pretreatment cancer-associated weight loss w...

"Ultimately, mom has the call": Viewing clinical trial decision making among patients with ovarian cancer through the lens of relational autonomy.

Abstract: Objective This study employs the concept of relational autonomy to understand how relational encounters with family members (FMs) and care providers may shape decisions around ovarian cancer patients' clinical trial (CT) participation. The study also offers unique insights into how FMs view patients' decision making. Methods In-depth interviews were conducted with 33 patients with ovarian cancer who had been offered a CT and 39 FMs. Data were inductively analysed using a thematic approach and deductively informed by constructs derived from the theory of relational autonomy (RA). Results Patients' relationships, experiences and social status were significant resources that shaped their decisions. Patients did not give equal weight to all relationships and created boundaries around whom to include in decision making. Doctors' recommendations and perceived enthusiasm were described as influential in CT decisions. Both patients with ovarian cancer and their FMs maintained that patients have the "final say," indicating an individualistic autonomy. However, maintaining the "final say" in the decision-making process is constitutive of patients' relationships, emphasizing a relational approach to autonomy. FMs support patients' autonomy and they do so particularly when they believe the patient is capable of making the right choices. Conclusions Although ethical principles underlying informed consent for CT participation emphasize individual autonomy, greater attention to relational autonomy is warranted for a more comprehensive understanding of CT decision making.

Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients.

Abstract: Background: More than 80% of patients with advanced cancer develop weight loss. Because preclinical data suggest poly (ADP-ribose) polymerase (PARP) inhibitors can treat this weight loss, this study was undertaken to explore the PARP inhibitor veliparib for this indication. Objective: The current study was undertaken to analyze prospectively gathered data on weight in cancer patients on PARP inhibitors. Design/Setting: The current study relied on a previously published, prospectively conducted phase 1 single institution trial that combined veliparib and topotecan (NCT01012817) as antineoplastic therapy for advanced cancer patients. Serial weight data and, when available and clinically relevant, computerized tomography scans were also examined. Measurements: The primary endpoint was 10% or greater weight gain from trial enrollment. Results: Nearly all 60 patients lost weight over time. Only one patient manifested a 10% or greater gain in weight. However, review of computerized tomography L3 images...

Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study.

Abstract: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events. Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.

Nasal vestibulitis: an under-recognized and under-treated side effect of cancer treatment?

Abstract: To evaluate the frequency of nasal symptoms termed nasal vestibulitis, including nasal dryness, crusting, bleeding, and pain, among patients receiving systemic, antineoplastic therapy. Patients undergoing systemic antineoplastic therapy were interviewed regarding the presence of nasal symptoms. In an explorative approach, Fisher’s exact tests were used to identify groups in which frequencies of nasal symptoms were higher than the comparator arm. To account for potential confounding factors, including demographic variables and concurrent therapies, logistic regression analyses were performed, and estimated proportions with their standard errors (SEs) and odds ratios (ORs) were reported. Forty-one percent of the 100 surveyed patients had nasal symptoms, including dryness, pain, bleeding, and scabbing. Higher frequencies were reported among those who had received taxanes (71%) and VEGF-related therapies (78%). For the patients who had received taxanes, after controlling for other factors, the odds of experiencing nasal symptoms were 4.86 times higher than those for patients who did not receive taxanes (90% CI 2.01, 11.76). For patients who received VEGF-related therapies, after controlling for other factors and exposure to taxanes, the odds of experiencing nasal symptoms were 7.38 (90% CI 1.68, 32.51) times higher than those for patients who did not. Sixty-one percent of patients with symptoms said they reported them to their provider, but only 41% of chart notes contained documentation of such; 49% of patients reported treating their symptoms. Nasal vestibulitis is common among patients receiving taxane- and VEGF-related therapies; these symptoms are infrequently recorded or treated by healthcare providers.

Looking Back, Looking Forward: The Ethical Framing of Complementary and Alternative Medicine in Oncology Over the Last 20 Years

Abstract: This commentary takes a look back at views on complementary and alternative medicine and reflects on how those views have evolved, advocating for a conversation around complementary and alternative medicine in cancer care that is more nuanced, patient‐centered, and respectful to best meet the needs of patients in the coming decades.

Is there a role for older-patient-specific cancer clinical trials? A pooled analysis of 2277 older patients in adjuvant breast cancer trials (Alliance A151715).

Abstract: 10034Background: Breast cancer incidence increases with age, but older patients tend to be underrepresented in clinical trials. To address this underrepresentation, this study examined the role of ...

Chemotherapy Acute Infusion Reactions: A Qualitative Report of the Perspectives of Patients With Cancer.

Abstract: Objective:A growing number of cancer antineoplastic agents can cause life-threatening acute infusion reactions. Because previous studies have not studied these reactions from the perspective of pat...