Lung Cancer Screening in People With HIV: A Mixed-Methods Study of Patient and Provider Perspectives.

INTRODUCTION: People with HIV are at higher risk of lung cancer; however, there is limited research on attitudes, barriers, and facilitators to lung cancer screening in people with HIV. The objective of this study was to understand the perspectives on lung cancer screening among people with HIV and their providers. METHODS: Surveys of people with HIV and HIV-care providers were complemented by qualitative focus groups and interviews designed to understand the determinants of lung cancer screening in people with HIV. Participants were recruited through an academic HIV clinic in Seattle, WA. Qualitative guides were developed by integrating the Consolidated Framework for Implementation Research and the Tailored Implementation of Chronic Diseases checklist. Themes that emerged from thematic analyses of qualitative data were compared with surveys in joint displays. All study components were conducted between 2021 and 2022. RESULTS: Sixty-four people with HIV completed surveys, and 43 participated in focus groups. Eleven providers completed surveys, and 10 were interviewed for the study. Themes from joint displays show overall enthusiasm for lung cancer screening among people with HIV and their providers, particularly with a tailored and evidence-based approach. Facilitators in this population may include longstanding engagement with providers and health systems and an emphasis on survivorship through preventive healthcare interventions. People with HIV may also face barriers acknowledged by providers, including a high level of medical comorbidities and competing issues such as substance abuse, mental health concerns, and economic instability. CONCLUSIONS: This study reveals that people with HIV and their providers have overall enthusiasm toward screening. However, tailored interventions may be needed to overcome specific barriers, including complex decision making in the setting of medical comorbidity and patient competing issues.

Predicting recurrence risks in lung cancer patients using multimodal radiomics and random survival forests.

Purpose: We developed a model integrating multimodal quantitative imaging features from tumor and nontumor regions, qualitative features, and clinical data to improve the risk stratification of patients with resectable non-small cell lung cancer (NSCLC). Approach: We retrospectively analyzed 135 patients [mean age, 69 years (43 to 87, range); 100 male patients and 35 female patients] with NSCLC who underwent upfront surgical resection between 2008 and 2012. The tumor and peritumoral regions on both preoperative CT and FDG PET-CT and the vertebral bodies L3 to L5 on FDG PET were segmented to assess the tumor and bone marrow uptake, respectively. Radiomic features were extracted and combined with clinical and CT qualitative features. A random survival forest model was developed using the top-performing features to predict the time to recurrence/progression in the training cohort ( n = 101 ), validated in the testing cohort ( n = 34 ) using the concordance, and compared with a stage-only model. Patients were stratified into high- and low-risks of recurrence/progression using Kaplan-Meier analysis. Results: The model, consisting of stage, three wavelet texture features, and three wavelet first-order features, achieved a concordance of 0.78 and 0.76 in the training and testing cohorts, respectively, significantly outperforming the baseline stage-only model results of 0.67 ( p < 0.005 ) and 0.60 ( p = 0.008 ), respectively. Patients at high- and low-risks of recurrence/progression were significantly stratified in both the training ( p < 0.005 ) and the testing ( p = 0.03 ) cohorts. Conclusions: Our radiomic model, consisting of stage and tumor, peritumoral, and bone marrow features from CT and FDG PET-CT significantly stratified patients into low- and high-risk of recurrence/progression.

Improving the efficacy of immunotherapy in small cell lung cancer: Leveraging recent scientific discoveries and tumor-specific antigens.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine neoplasm with poor survival outcomes and little change to treatment standards over decades. SCLC is associated with heavy tobacco exposure and a high rate of somatic mutations in tumor cells, leading to hope that immune checkpoint inhibitors would dramatically reshape the treatment landscape of SCLC. Instead, immune checkpoint inhibitors have led to real but modest gains in outcomes, with only a small minority of patients deriving more durable benefit. Furthermore, biomarkers of ICI efficacy that have succeeded in other tumor types have not been validated in SCLC. However, recent research advances have suggested that epigenetic heterogeneity and plasticity play especially key roles in SCLC biology. Leveraging this emerging perspective, a new slate of candidate biomarkers of immune checkpoint inhibitor benefit have been described, and the novel treatment strategies combining rational epigenetic perturbation with immune checkpoint inhibitors are being developed. Finally, other immunotherapy strategies targeting SCLC-specific mechanisms are being tested. Together, these developments may lead to a second generation of much more efficacious immunotherapies in SCLC.

Impact of Diagnostic Delays on Lung Cancer Survival Outcomes: A Population Study of the US SEER-Medicare Database.

PURPOSE: Time from diagnosis to treatment has been associated with worse survival outcomes in non-small-cell lung cancer (NSCLC). However, little is known about the impact of delay in time to diagnosis. We aimed to evaluate the impact of time from radiographic suspicion to histologic diagnosis on survival outcomes using the US SEER-Medicare population database. METHODS: We identified patients from the SEER-Medicare data set diagnosed with any stage NSCLC between January 1, 2011, and December 31, 2015, who received stage-appropriate treatment and had a computed tomography scan within 1 year of diagnosis. Time to confirmation was determined as the interval between most recent computed tomography imaging and date of histologic diagnosis. Our primary outcome was overall survival (OS). RESULTS: In total, 10,824 eligible patients were identified. The median time to confirmation was 20 (range 0-363) days. Using multivariate Cox regression models, longer time to confirmation was associated with improved OS in all comers driven by stage IV patients after adjustment for age, sex, diagnosis year, histology, and comorbidity index. In a separate landmark analysis excluding patients deceased within 6 months of diagnosis, the association between time to diagnosis and survival was no longer evident. CONCLUSION: Time to confirmation of NSCLC was inversely associated with OS in this US SEER population study. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that retrospective registry-claims databases may not be the optimal data source to study time to diagnosis as a quality metric because of the unaccounted confounding effects of tumor behavior. Prospective evaluations of clinically enriched data sources may better serve this purpose.

Adaptive Fluorodeoxyglucose-Positron Emission Tomography Based Chemotherapy Selection for Metastatic Non-small Cell Lung Cancer.

Objectives The change in tumor fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) scan after one cycle of platinum-based chemotherapy has been shown to predict progression-free and overall survival (PFS and OS) among advanced non-small cell lung cancer (NSCLC) patients. Using early FDG-PET response to determine subsequent chemotherapy, we aim to evaluate the role that adaptive chemotherapy regimens have on later CT response, PFS, and OS in patients with advanced NSCLC. Materials and Methods Chemotherapy-naïve patients with metastatic NSCLC received carboplatin and paclitaxel (CP) on day one and repeated FDG-PET on day 18. PET-responding patients continued CP chemotherapy for a total of four cycles. PET non-responders were switched to alternate docetaxel and gemcitabine (DG) for three additional cycles. The primary outcome was the CT Response Evaluation Criteria in Solid Tumors (RECIST 1.0) response. Secondary endpoints included PFS and OS. Results  Forty-six patients initiated treatment with chemotherapy on trial and were evaluable by PET/CT. Of these, 19 (41%) met the FDG-PET criteria for the response after a single cycle of CP. Only one non-responding patient had a CT response. Despite the lack of CT response in the DG arm, no trend for worse PFS or OS was seen between the two arms. Conclusions This work demonstrates that changing chemotherapy in the event of non-response by PET did not lead to improved CT RECIST response. However, non-responding patients who switched chemotherapy had similar PFS and OS to those who responded by PET and continued the same regimen.

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution.

OBJECTIVES: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. MATERIALS AND METHODS: This is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. RESULTS: 180 eligible patients were identified. The median time to PORT start was 61 (range 8-121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes. CONCLUSION: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT.

18F-fluorodeoxyglucose (FDG) PET or 18F-fluorothymidine (FLT) PET to assess early response to aromatase inhibitors (AI) in women with ER+ operable breast cancer in a window-of-opportunity study.

PURPOSE: This study evaluated the ability of 18F-Fluorodeoxyglucose (FDG) and 18F-Fluorothymidine (FLT) imaging with positron emission tomography (PET) to measure early response to endocrine therapy from baseline to just prior to surgical resection in estrogen receptor positive (ER+) breast tumors. METHODS: In two separate studies, women with early stage ER+ breast cancer underwent either paired FDG-PET (n = 22) or FLT-PET (n = 27) scans prior to endocrine therapy and again in the pre-operative setting. Tissue samples for Ki-67 were taken for all patients both prior to treatment and at the time of surgery. RESULTS: FDG maximum standardized uptake value (SUVmax) declined in 19 of 22 lesions (mean 17% (range -45 to 28%)). FLT SUVmax declined in 24 of 27 lesions (mean 26% (range -77 to 7%)). The Ki-67 index declined in both studies, from pre-therapy (mean 23% (range 1 to 73%)) to surgery [mean 8% (range < 1 to 41%)]. Pre- and post-therapy PET measures showed strong rank-order agreement with Ki-67 percentages for both tracers; however, the percent change in FDG or FLT SUVmax did not demonstrate a strong correlation with Ki-67 index change or Ki-67 at time of surgery. CONCLUSIONS: A window-of-opportunity approach using PET imaging to assess early response of breast cancer therapy is feasible. FDG and FLT-PET imaging following a short course of neoadjuvant endocrine therapy demonstrated measurable changes in SUVmax in early stage ER+ positive breast cancers. The percentage change in FDG and FLT-PET uptake did not correlate with changes in Ki-67; post-therapy SUVmax for both tracers was significantly associated with post-therapy Ki-67, an established predictor of endocrine therapy response.

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome.

BACKGROUND: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. RESULTS: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). CONCLUSIONS: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION: NCT00227539 registered September 28th, 2005.

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

INTRODUCTION: Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. METHODS: A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the ß-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. RESULTS: Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1ß-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1ß-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. CONCLUSIONS: This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.

An Assessment of Primary Care and Pulmonary Provider Perspectives on Lung Cancer Screening.

RATIONALE: Lung cancer screening has a mortality benefit to high-risk smokers, but implementation remains suboptimal. Providers represent the key entry point to screening, and an understanding of provider perspectives on lung cancer screening is necessary to improve referral and overall implementation. OBJECTIVES: The objective of this study was to understand knowledge, beliefs, attitudes, barriers, and facilitators to screening in a diverse group of referring pulmonologists and primary care providers. METHODS: We conducted an electronic survey of primary care and pulmonary providers within a tertiary care medical center across different practice sites. The survey covered the following domains: 1) beliefs and assessment of evidence, 2) knowledge of lung cancer screening and guidelines, 3) current screening practices, 4) barriers and facilitators, and 5) demographic and practice characteristics. RESULTS: The 196 participants included 80% primary care clinicians and 19% pulmonologists (1% others). Forty-one percent practiced at university-based or affiliated clinics, 47% at county hospital-based clinics, and 12% at other or unidentified sites. The majority endorsed lung cancer screening effectiveness (74%); however, performance on knowledge-based assessments of screening eligibility, documentation, and nodule management was suboptimal. Key barriers included inadequate time (36%), inadequate staffing (36%), and patients having too many other illnesses to address screening (38%). Decision aids, which are used at the point of referral, were commonly identified both as important lung cancer screening clinical facilitators (51%) and as provider knowledge facilitators (59%). There were several differences by provider specialty, including primary care providers more frequently reporting time constraints and their patients having too many other illnesses to address screening as significant barriers to lung cancer screening. CONCLUSIONS: Providers endorsed the benefits of lung cancer screening, but there are limitations in provider knowledge of key screening components. The most frequently reported barriers to screening represent a lack of clinical time or resources to address lung cancer screening in clinical practice. Facilitators for nodule management as well as point-of-care referral materials may be helpful in reducing knowledge gaps and the clinical burden of referral. These are all modifiable factors, which could be addressed to increase screening referral. Differences in attitudes and barriers by specialty should also be considered to optimize screening implementation.

Task-Specific Fatigue Among Older Primary Care Patients.

OBJECTIVE: Fatigue is a common condition contributing to disability among older patients. We studied self-reported task-specific fatigue and its relation with mobility task performance among community-dwelling primary care patients. METHOD: Cross-sectional analysis of baseline demographic and health data from a prospective cohort study of 430 primary care patients aged 65 years or older. Fatigue was measured using the Avlund Mobility-Tiredness Scale. Performance tasks included rising from a chair, walking 4 m, and climbing two flights of stairs. RESULTS: Among demographic and health factors, pain was the only attribute consistently predictive of fatigue status. Self-reported chair rise fatigue and walking fatigue were associated with specific task performance. Stair climb fatigue was not associated with stair climb time. DISCUSSION: Pain is strongly associated with fatigue while rising from a chair, walking indoors, and climbing stairs. This study supports the validity of self-reported chair rise fatigue and walking fatigue as individual test items.