This study tested sleep disturbance as a mediator through which stigma and discrimination predict psychological distress and physical symptom burden in adults with lung cancer.
Lung cancer patients ...on active oncological treatment ( N = 108; 74.1% stage IV) completed questionnaires on lung cancer stigma, sleep, distress, and physical symptoms at study entry and at 6- and 12-week follow-up. Mediation analyses were conducted to investigate whether stigma and discrimination predicted distress and physical symptoms at study entry and across 12 weeks through disrupted sleep.
Higher discrimination ( b = 5.52, 95% confidence interval CI = 2.10-8.94) and constrained disclosure ( b = 0.45, 95% CI = 0.05-0.85) were associated significantly with higher sleep disruption at study entry. Sleep disruption, in turn, was associated with higher distress ( b = 0.19, 95% CI = 0.09-0.29) and physical symptoms ( b = 0.28, 95% CI = 0.17-0.40) at study entry. Sleep disruption significantly mediated relationships between higher discrimination and the outcomes of distress (indirect effect = 1.04, 95% CI = 0.13-1.96) and physical symptoms (indirect effect = 1.58, 95% CI = 0.37-2.79) at study entry. Sleep disruption also mediated relationships between constrained disclosure and the outcomes of distress (indirect effect = 0.85, 95% CI = < 0.01-0.17) and physical symptoms (indirect effect = 0.13, 95% CI = 0.01-0.25).
Lung cancer patients evidenced pronounced sleep disruption, which mediated relationships between indicators of lung cancer stigma and distress and physical symptoms at study entry. Research is needed to test additional mechanisms through which lung cancer stigma predicts these outcomes longitudinally.
The management of malignancy post kidney transplantation includes reduction in immunosuppression and referral to an oncologist management of their malignancy. Recent advances in oncology have ...resulted in the approval of several classes of drugs with immune-modulatory activity. However, activation of the immune system against malignant cells may precipitate allograft rejection in solid organ transplant recipients.
Herein we present a case of acute kidney allograft rejection in a 50 year old man following administration of the novel immune-modulatory agent nivolumab for the treatment of metastatic squamous cell carcinoma.
The management of malignancy in solid organ transplant recipients requires a heightened awareness of the potential for allograft rejection in this new era of cancer therapeutics.
Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in ...melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.
We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8-5.5 years).
PD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited.
In patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.
We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + ...etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.
805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry.
In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype (n = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low CD8A expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of CD4 (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry.
These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T.
ClinicalTrials.gov, NCT03043872.
Internalized lung cancer stigma (i.e., feelings of regret, shame, and self-blame about one’s lung cancer) is related to poorer psychological outcomes. Less is known about how internalized stigma ...relates to physical and functional outcomes or how constrained disclosure (i.e., avoidance of or discomfort about disclosing one’s lung cancer status to others) relates to well-being. Furthermore, no study has examined whether internalized stigma and constrained disclosure predict changes in well-being for lung cancer patients. This longitudinal study characterized relationships of internalized stigma and constrained disclosure with emotional and physical/functional outcomes.
Participants (N = 101, 52.4% male, 63.4% currently/formerly smoked) were lung cancer patients on active medical treatment who completed questionnaires on stigma and well-being at study entry and at 6- and 12-week follow-up. Multivariable linear regressions characterized relationships of internalized stigma and constrained disclosure with emotional and physical/functional well-being at study entry and across time.
Participants who currently or formerly smoked reported higher levels of internalized stigma (but not constrained disclosure), compared to never smokers (p < 0.001). Higher internalized stigma and constrained disclosure were uniquely associated with poorer emotional and physical/functional well-being at study entry (all p < 0.05), beyond sociodemographic characteristics, time elapsed since diagnosis, and smoking status. Higher internalized stigma predicted significant declines in emotional well-being across 6 and 12 weeks (all p < 0.01) and declines in physical/functional well-being across 6 weeks (p < 0.05).
Internalized lung cancer stigma and constrained disclosure relate to emotional and physical/functional maladjustment. Findings carry implications for provider- and patient-focused interventions to reduce internalized stigma and promote well-being.
Objective: The aim of this study was to investigate whether three facets of lung cancer stigma (internalized stigma, constrained disclosure, and perceived subtle discrimination) uniquely predicted ...psychological and physical health-related adjustment to lung cancer across 12 weeks. Additionally, self-compassion was tested as a moderator of the stigma-health relationship. Method: Adults receiving oncologic treatment for lung cancer (N = 108) completed measures of lung cancer stigma, self-compassion, depressive symptoms, cancer-related stress, and physical symptom bother. Multivariable linear regression models were used to investigate cross-sectional and longitudinal relationships (at 6- and 12-week follow-up) between indicators of stigma and health-related outcomes, controlling for covariates. Self-compassion was tested as a moderator of these relationships. Results: At study entry, higher internalized stigma, constrained disclosure, and perceived subtle discrimination were associated significantly and uniquely with higher depressive symptoms (all p < .05). Constrained disclosure and perceived subtle discrimination were also associated significantly with higher cancer-related stress and higher physical symptom bother at study entry (all p < .05). Furthermore, higher internalized stigma predicted significant increases in depressive symptoms across 12 weeks and in cancer-related stress across 6 and 12 weeks (all p < .05). Higher self-compassion significantly moderated relationships between perceived discrimination and psychological health outcomes at study entry as well as between internalized stigma and increasing depressive symptoms across 12 weeks (all p < .05). Conclusions: Results indicated robust relationships between distinct facets of stigma and health-related adjustment to lung cancer. Supportive care programs that bolster self-compassion may be useful for reducing lung cancer stigma.
In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small cell lung cancer (ES-SCLC). We report ...exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB).
Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model.
The PD-L1 and tTMB biomarker-evaluable populations (BEP) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TC), ≥1% immune cells (IC), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with HRs all falling within the 95% confidence interval (CI) for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP vs. EP, P = 0.916; durvalumab plus tremelimumab plus EP vs. EP, P = 0.672).
OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset. See related commentary by Rolfo and Russo, p. 652.
In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful ...disease-free survival benefit in completely resected stage IB-IIIA EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA.
Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB-IIIA; N = 682). Clinically meaningful changes were defined using the SF-36 manual.
Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46-47) and maintained to Week 96, with no clinically meaningful differences between arms; difference in adjusted least squares (LS) mean 95% confidence intervals (CI), -1.18 (-2.02 to -0.34) and -1.34 (-2.40 to -0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS; HR, 1.17 (95% CI, 0.82-1.67) and HR, 0.98 (95% CI, 0.70-1.39), respectively.
HRQoL was maintained with adjuvant osimertinib in patients with stage IB-IIIA EGFRm NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. See related commentary by Patil and Bunn, p. 2204.
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