Unmet Needs, Quality of Life, and Financial Toxicity Among Survivors of Lung Cancer.

Importance: Despite a growing population of survivors of lung cancer, there is limited understanding of the survivorship journey. Survivors of lung cancer experience unmet physical, social, emotional, and medical needs regardless of stage at diagnosis or treatment modalities. Objective: To investigate the association of unmet needs with quality of life (QOL) and financial toxicity (FT) among survivors of lung cancer. Design, Setting, and Participants: This survey study was conducted at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center thoracic oncology clinics between December 1, 2020, and September 30, 2021, to assess needs (physical, social, emotional, and medical), QOL, and FT among survivors of lung cancer. Patients had non-small cell lung cancer of any stage and were alive longer than 1 year from diagnosis. A cross-sectional survey was administered, which consisted of an adapted needs survey developed by the Mayo Survey Research Center, the Comprehensive Score for Financial Toxicity measure, and the European Organization for Research and Treatment of Cancer QLQ-C30 QOL scale. Demographic and clinical information was obtained through retrospective medical record review. Data analysis was performed between May 9 and December 8, 2022. Main Outcomes and Measures: Separate multiple linear regression models, treating QOL and FT as dependent variables, were performed to assess the adjusted association of total number of unmet needs and type of unmet need (physical, emotional, social, or medical) with QOL and FT. Results: Of the 360 survivors of lung cancer approached, 232 completed the survey and were included in this study. These 232 respondents had a median age of 69 (IQR, 60.5-75.0) years. Most respondents were women (144 [62.1%]), were married (165 [71.1%]), and had stage III or IV lung cancer (140 [60.3%]). Race and ethnicity was reported as Black (33 [14.2%]), White (172 [74.1%]), or other race or ethnicity (27 [11.6%]). A higher number of total unmet needs was associated with lower QOL (ß [SE], -1.37 [0.18]; P < .001) and higher FT (ß [SE], -0.33 [0.45]; P < .001). In the context of needs domains, greater unmet physical needs (ß [SE], -1.24 [0.54]; P = .02), social needs (ß [SE], -3.60 [1.34]; P = .01), and medical needs (ß [SE], -2.66 [0.98]; P = .01) were associated with lower QOL, whereas only greater social needs was associated with higher FT (ß [SE], -3.40 [0.53]; P < .001). Conclusions and Relevance: The findings of this survey study suggest that among survivors of lung cancer, unmet needs were associated with lower QOL and higher FT. Future studies evaluating targeted interventions to address these unmet needs may improve QOL and FT among survivors of lung cancer.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

BACKGROUND: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied. METHODS: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients. RESULTS: Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408). CONCLUSIONS: Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation.

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057.

BACKGROUND: Nivolumab, a programmed death-1 inhibitor, prolonged overall survival and had a favourable safety profile versus docetaxel in previously treated patients with advanced non-squamous non-small cell lung cancer (NSCLC) in the phase III CheckMate 057 trial. AIM: To evaluate health-related quality of life (HRQoL) using patient-reported outcomes. METHODS: Disease-related symptoms and general health status were assessed using two validated patient-reported instruments, the Lung Cancer Symptom Scale (LCSS) and the European Quality of Life Five Dimensions (EQ-5D), respectively. The proportion of patients with disease-related symptom improvement at 12 weeks on the LCSS average symptom burden index (ASBI) was a secondary end-point. LCSS 3-item global index (3-IGI), EQ-5D utility index and EQ-5D visual analogue scale (VAS) scores were also determined. Mixed-effects model repeated measures (MMRM) and time to first deterioration analyses assessed longitudinal changes. RESULTS: Mean baseline LCSS ASBI scores were similar in both arms. By week 12, rates of disease-related improvement (95% confidence interval) were similar between nivolumab (17.8% [13.6-22.7]) and docetaxel (19.7% [15.2-24.7]); however, numerical differences in LCSS ASBI mean change from baseline favoured nivolumab. Subsequently, LCSS ASBI scores improved with nivolumab and worsened with docetaxel, with statistically significant between-arm differences at weeks 12, 24, 30 and 42. HRQoL improvements with nivolumab versus docetaxel were also supported by the LCSS 3-IGI, EQ-5D VAS and MMRM analysis. Time to first HRQoL deterioration was longer with nivolumab than with docetaxel. CONCLUSION: Nivolumab improved disease-related symptoms and overall health status versus docetaxel for second-line treatment of advanced non-squamous NSCLC. CLINICAL TRIAL REGISTRATION: NCT01673867.

A comparison of FLT to FDG PET/CT in the early assessment of chemotherapy response in stages IB-IIIA resectable NSCLC.

BACKGROUND: The aim of this study was to compare the percentage change in 18F-fluorothymidine (FLT) standard uptake value (SUV) between baseline and after one cycle of chemotherapy in patients categorized by RECIST 1.1 computed tomography (CT) as responders or non-responders after two cycles of therapy. Change in 18F-fluorodeoxyglucose (FDG) uptake was also compared between these time points. Nine patients with newly diagnosed, operable, non-small cell lung cancer (NSCLC) were imaged with FDG positron emission tomography/CT (PET), FLT PET/CT, and CT at baseline, following one cycle of neoadjuvant therapy (75 mg/m2 docetaxel + 75 mg/m2 cisplatin), and again after the second cycle of therapy. All patients had a biopsy prior to enrollment and underwent surgical resection within 4 weeks of post-cycle 2 imaging. RESULTS: Between baseline and post-cycle 1, non-responders had mean SULmax (maximum standard uptake value adjusted for lean body mass) increases of 7.0 and 3.4% for FDG and FLT, respectively. Responders had mean decreases of 44.8 and 32.0% in FDG and FLT SULmax, respectively, between baseline and post-cycle 1 imaging. On post-cycle 1 imaging, primary tumor FDG SUL values were significantly lower in responders than in non-responders (P = 0.016). Primary tumor FLT SUL values did not differ significantly between these groups. Using the change from baseline to post-cycle 1, receiver-operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.94 for FDG and 0.78 for FLT in predicting anatomic tumor response after the second cycle of therapy. CONCLUSIONS: Fractional decrease in FDG SULmax from baseline to post-cycle 1 imaging was significantly different between anatomic responders and non-responders, while percentage changes in FLT SULmax were not significantly different between these groups over the same period of time.

Needs assessments can identify scores on HRQOL questionnaires that represent problems for patients: an illustration with the Supportive Care Needs Survey and the QLQ-C30.

PURPOSE: A barrier to using HRQOL questionnaires for individual patient management is knowing what score represents a problem deserving attention. We explored using needs assessments to identify HRQOL scores associated with patient-reported unmet needs. METHODS: This cross-sectional study included 117 cancer patients (mean age 61 years; 51% men; 77% white) who completed the Supportive Care Needs Survey (SCNS) and EORTC QLQ-C30. SCNS scores were dichotomized as "no unmet need" versus "some unmet need" and served as an external criterion for identifying problem scores. We evaluated the discriminative ability of QLQ-C30 scores using receiver operating characteristic (ROC) analysis. Domains with an area under the ROC curve (AUC) >or= .70 were examined further to determine how well QLQ-C30 scores predicted presence/absence of unmet need. RESULTS: We found AUCs >or= .70 for 6 of 14 EORTC domains: physical, emotional, role, global QOL, pain, fatigue. All 6 domains had sensitivity >or= .85 and specificity >or= .50. EORTC domains that closely matched the content of SCNS item(s) were more likely to have AUCs >or= .70. The appropriate cut-off depends on the relative importance of false positives and false negatives. CONCLUSIONS: Needs assessments can identify HRQOL scores requiring clinicians' attention. Future research should confirm these findings using other HRQOL questionnaires and needs assessments.

Concordance of cancer patients' function, symptoms, and supportive care needs.

PURPOSE: Although patients' function, symptoms, and supportive care needs are obviously related, a better understanding of these relationships could improve patient management. METHODS: In this cross-sectional, observational study, 117 cancer patients completed the Supportive Care Needs Survey-34 and EORTC-QLQ-C30. Each symptom and function domain from the EORTC-QLQ-C30 was dichotomized (high vs. low) using a cut-off of reference sample mean scores. Each need domain was dichotomized using a cut-off of an average score representing an unmet need. We explored within-patient patterns of function, symptom, and need domains using latent class analysis. Based on these patterns, patients were categorized as high versus low function; high versus low symptom; and high versus low need. We examined the concordance between categorizations of patients' function, symptoms, and needs. RESULTS: The categorizations of function, symptoms, and needs were concordant for 66 patients (56%). Among patients with deficits in at least one area (n = 68), categorizations for 51 patients (75%) were discordant. CONCLUSIONS: About 50% of patients have similar classifications of their level of function, symptoms, and needs, but discordance was common among patients with deficits in at least one area, emphasizing the importance of assessing all of these outcomes as part of patient evaluations.

Symptoms, supportive care needs, and function in cancer patients: how are they related?

AIMS: To explore the associations among symptoms, supportive care needs, and function. METHODS: One hundred and seventeen cancer patients completed the Supportive Care Needs Survey and EORTC-QLQ-C30 in a cross-sectional study. Associations among function (physical, role, emotional, cognitive, social), symptoms (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), and supportive care needs (physical and daily living, psychological, patient care and support, health system and information, sexual) were tested using multivariate item regression (MIR). We tested (1) function as the dependent variable with symptoms and supportive care needs as independent variables and (2) supportive care needs as the dependent variable with symptoms and function as independent variables. RESULTS: Worse fatigue, pain, and appetite loss were associated with worse function. Greater unmet physical and daily living needs were associated with worse physical, role, and cognitive function. Greater unmet psychological needs were associated with worse emotional and cognitive function. Worse sleep problems were associated with greater unmet needs. Better physical function was associated with fewer unmet physical and daily living needs, and better emotional function was associated with fewer unmet psychological, patient care and support, and health system and information needs. CONCLUSIONS: The results obtained with these models suggest several consistent relationships among symptoms, supportive care needs, and function.

Asking the right questions: investigating needs assessments and health-related quality-of-life questionnaires for use in oncology clinical practice.

GOALS OF WORK: Questionnaires used in oncology practice for individual patient management need to address issues patients find important and want help with and issues cancer center health professionals can address. We investigated the item content from two health-related quality-of-life (HRQOL) questionnaires and two needs assessments for this purpose. PATIENTS AND METHODS: In this preliminary study, 61 cancer patients and 19 cancer center health professionals rated the item content from the EORTC-QLQ-C30, FACT-G, Supportive Care Needs Survey-34 (SCNS), and Kingston Needs Assessment--Cancer. Patients rated each item's importance and whether they wanted help with it; health professionals rated each item's importance and whether they felt able to help patients address it. Patients and health professionals also reported their overall questionnaire preference. MAIN RESULTS: Patients rated information about treatments (options, benefits, side effects) and care coordination as the most important issues and those for which they most wanted help from their health professionals. Health professionals rated pain and other symptom/side effect items as most important to patients and those for which they were most able to help. Findings were consistent across tumor type and treatment status. Patients had an overall preference for the SCNS. Health professionals had no clear questionnaire preference. CONCLUSIONS: This preliminary study suggests that the issues patients most want help with may not be the issues that health professionals feel most able to address. If these findings are confirmed in more representative samples, interventions may be needed to assist health professionals in managing cancer patients' HRQOL issues and needs.

C-fos assessment as a marker of anti-epidermal growth factor receptor effect.

Factors predicting sensitivity to epidermal growth factor receptor (EGFR) blockade are largely unknown and new strategies are being sought to individualize cancer therapy. This study evaluated the variation in the expression of the early response gene c-fos as a distal effect of EGFR inhibition and its relationship to antitumor effects. The growth-inhibitory and c-fos-modulating effects of gefitinib and erlotinib in human cancer cell lines (A431, CAL27, HN11, HuCCT1, and Hep2) were determined. Next, these cell lines were xenografted in mice and treated for 14 days with gefitinib (A431 and HuCCT1) or erlotinib (CAL27, HN11, and Hep2). Fine needle aspiration biopsy of tumors was done at baseline and after 14 days of therapy for c-fos assessment. In addition, we tested the feasibility of analyzing this marker in five paired tumor samples from a clinical trial of gefitinib in patients with solid tumors. In culture, gefitinib and erlotinib decreased c-fos mRNA levels in the susceptible cell lines A431, CAL27, and HN11; however, both drugs failed to achieve c-fos inhibition in resistant cells. Gefitinib or erlotinib abrogated the increase in c-fos expression in vivo in EGFR-sensitive A431, CAL27, and HN11 tumors but not in resistant strains. Ex vivo evaluation was feasible and predicted in vivo effects. The feasibility study in paired human tumor biopsies showed that this biomarker can be reliably measured in clinical materials. In summary, variations in c-fos expression reflect the pharmacologic actions of EGFR inhibitors in in vitro and in vivo models.