Lung Cancer Survivors Research Articles

A Qualitative Exploration of Medication Experience and Factors Contributing to Adherence to Oral-Targeted Therapy Among Lung Cancer Survivors

ObjectivesThe introduction of oral-targeted therapy for cancer improves survival while adherence also presents as a challenge to patients. Current studies on oral anticancer agents are primarily limited to patients from developed countries with breast cancer and chronic myeloid leukemia receiving oral chemotherapy and hormonal therapy. This study explored experience of oral-targeted therapy adherence among Chinese patients with nonsmall cell lung cancer and its contributing factors by using a qualitative research. Data SourcesSemi-structured interviews with 16 patients and 7 family caregivers at a tertiary tumor hospital in China were conducted to understand their experience and perceptions of oral-targeted therapy. Thematic analysis was applied to generate the themes and to identify underlying factors associated with the adherence. ConclusionThe lung cancer survivors struggled with ambivalence between survival and relief during taking targeted anticancer medication and showed diverse models of nonadherence, including intentionally or unintentionally intermittent medication and overadherence. Three main themes were identified: (1) cancer-related distresses, (2) inadequate social support, and (3) forgetfulness, together with seven subthemes, representing factors impeding patients’ medication adherence. The themes demonstrate complicated and interrelated factors from personal, interpersonal, sociocultural, and structural forces contributing to patients’ poor adherence. Implications for Nursing PracticeThe findings suggest the imperativeness of reinforcing community- or home-based oral-targeted medication management in which nurses play a principal role to implement strategies of patient education, symptom management, reminder prompts, and monitoring to improve adherence.

Mindfulness-Based Interventions for Survivors of Lung Cancer and Their Partners: A Systematic Review

BackgroundSurvivors of lung cancer and their partners often have complex unresolved physical, psychosocial, and behavioral needs that can negatively affect the survivors’ and partners’ well-being. This systematic review aimed to (1) examine the content and delivery of mindfulness-based interventions (MBIs) and (2) summarize and synthesize the current evidence for effectiveness of MBIs targeting survivors of lung cancer and/or one selected partner (dyads).MethodSix databases were searched for interventional studies published in English between 1980 and June 2020 using three terms (lung neoplasms, mindfulness, caregivers). For outcome measures, the interventions focused on behavioral change (meditation, yoga, stretching, breathing), symptom management (dyspnea, fatigue, sleep disruption, anxiety, depression, stress reduction), and knowledge. Two reviewers independently assessed article eligibility. One reviewer performed and another independently verified data extraction. The Cochrane risk-of-bias tool for randomized trials was used to critically appraise RCTs.ResultsSearching yielded 307 records, of which 64 were assessed for eligibility. Six studies investigated the impact of an MBI on survivors and partners. Four studies were single-arm feasibility studies; two were RCTs. Two feasibility studies and one RCT recruited romantic couples whereas the others recruited asymmetrical dyads. The single-arm studies reported strong feasibility and acceptability. RCTs reported significant outcomes for reduced cancer-related distress and depression, and improved QOL, self-compassion, mindfulness skills, and rumination.ConclusionDyadic intervention research is a growing field. Few interventions target individuals with lung cancer and their partners. No interventions target partners alone. Future research should evaluate rigorous methodologies that enhance the understanding of independent and interdependent health-related effects within dyads and across relationships and settings.

Colorectal cancer screening utilization among breast, cervical, prostate, skin, and lung cancer survivors.

PurposeTo examine whether sociodemographic characteristics, access to care, risk behavior factors, and chronic health conditions were associated with colorectal cancer (CRC) screening utilization among breast, cervical, prostate, skin, and lung cancer survivors.MethodsWe analyzed the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data on 9780 eligible cancer survivors. Descriptive statistics and multivariable logistic regression models were applied to assess the association between guideline-concordant CRC screening and the mentioned characteristics.ResultsOverall, 81.9%, 65%, 88%,78.1%, and 80.1% of breast, cervical, prostate, skin, and lung cancer survivors received CRC screening, respectively (p-value < 0.001). In multivariable analysis, breast, cervical, and skin cancer survivors aged 60 years or older were associated with higher odds of receiving CRC screening. Respondents that had their recency of routine checkup two or more years before had lower odds of having CRC screening among cervical (OR = 0.06; 95% CI, 0.02–0.22), prostate (OR = 0.26; 95% CI, 0.14–0.49), and skin cancer (OR = 0.50; 95% CI, 0.36–0.70) survivors. The presence of chronic diseases was also associated with guideline-concordant CRC screening among breast, prostate, and skin cancer survivors.ConclusionsOur findings provide important evidence on potential factors that are associated with guideline-concordant CRC screening utilization across different cancer survivors, which include older age, recency of routine checkup, and multiple chronic diseases. Moreover, variation in CRC screening utilization across cancer survivors may highlight missed opportunities for secondary cancer prevention.Implications for Cancer SurvivorsEstablishing clear CRC screening guidelines and including patient-provider communication on recommendation in cancer survivorship care may increase adherence to CRC screening.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11764-022-01258-0.

Defining the needs of lung cancer survivors: Physical, social, emotional, and medical needs.

225 Background: Lung cancer survivors (LCS) are a rapidly growing population. Cancer survivors benefit from dedicated survivorship care, but the physical, psychosocial, and medical needs of LCS are poorly defined. Methods: Non-small cell LCS (defined as alive ≥1 years from diagnosis) of any stage treated at Johns Hopkins were invited to complete an IRB-approved cross-sectional survey of needs of 4 subscales (physical, social, emotional, and medical needs) rated on a 5-point Likert scale (1 = no need, 5 = highest need). Demographic and clinical information were collected by chart review and patient reported questionnaire. Multiple regression models identified factors that were significantly associated with greater total number of needs on each subscale. Results: 235 surveys were completed. We excluded surveys with &lt; 80% completion. Non-Caucasian race was associated with a significantly lower rate of survey completion (p = 0.002). Median age of LCS who completed the survey was 69, most were female (62%), Caucasian (74%), married (71%), or had stage III/IV cancer (60%). More than half of respondents reported emotional needs of fear of recurrence (79%) and living with uncertainty (74%). Common physical needs included fatigue (70%), sleep disturbance (60%), memory and concentration (57%), and weakness (54%). Multivariate analysis identified factors associated with higher needs in physical, social, and emotional needs (Table). We did not identify any factors associated with differences in medical needs. NS – non-significant value. Conclusions: We identified physical, emotional, social, and medical needs that burden survivors of NSCLC. Emotional needs are prevalent. Clinical and demographic factors are independently associated with higher needs in physical, social, and emotional domains. These results are critical in identifying high-impact gaps in providing survivorship care for lung cancer survivors. Future work to identify interventions to address needs is crucial.[Table: see text]

Second surgery for metachronous primary lung cancer

: As curative surgeries for early-stage non-small cell lung cancer (NSCLC) increase and longer postoperative survival becomes possible, metachronous primary lung cancer (MPLC) have become more common in recent years. Lung cancer survivors have a high risk of MPLC for the rest of their lives, so long-term follow-up and close surveillance are needed. MPLC is often detected relatively early by routine surveillance after the initial surgery, and 64.7% to 85.2% of the cases reported to date have been stage I. Operative mortality after resection of MPLC has been reported to be 0% to 13.0%. Operative morbidity has been reported to be 19.7% to 36.2%. The Five-year overall survival from second surgery was recently reported to be 42% to 78.7%. If the new lesion is solitary and cardiopulmonary function is preserved, complete surgical resection should be considered, regardless of the duration of disease-free survival from initial surgery. Lung-sparing surgery such as segmentectomy or wedge resection and lobectomy have been often reported to have comparable outcomes. Sublobar resection would be acceptable depending on the tumor size and location of the tumor. Because residual pulmonary function is the most important factor for decision-making regarding surgical resection of MPLC, lung preservation should be attempted as much as possible at the time of initial surgery.

Causes of death and conditional survival estimates of long-term lung cancer survivors.

IntroductionLung cancer ranks the leading cause of cancer-related death worldwide. This retrospective cohort study was designed to determine time-dependent death hazards of diverse causes and conditional survival of lung cancer.MethodsWe collected 816,436 lung cancer cases during 2000-2015 in the SEER database, after exclusion, 612,100 cases were enrolled for data analyses. Cancer-specific survival, overall survival and dynamic death hazard were assessed in this study. Additionally, based on the FDA approval time of Nivolumab in 2015, we evaluated the effect of immunotherapy on metastatic patients’ survival by comparing cases in 2016-2018 (immunotherapy era, n=7135) and those in 2013-2016 (non-immunotherapy era, n=42061).ResultsOf the 612,100 patients, 285,705 were women, the mean (SD) age was 68.3 (11.0) years old. 252,558 patients were characterized as lung adenocarcinoma, 133,302 cases were lung squamous cell carcinoma, and only 78,700 cases were small cell lung carcinomas. TNM stage was I in 140,518 cases, II in 38,225 cases, III in 159,095 cases, and IV in 274,262 patients. 164,394 cases underwent surgical intervention. The 5-y overall survival and cancer-specific survival were 54.2% and 73.8%, respectively. The 5-y conditional survival rate of cancer-specific survival is improved in a time-dependent pattern, while conditional overall survival tends to be steady after 5-y follow-up. Except from age, hazard disparities of other risk factors (such as stage and surgery) diminished over time according to the conditional survival curves. After 8 years since diagnosis, mortality hazard from other causes became higher than that from lung cancer. This critical time point was earlier in elder patients while was postponed in patients with advanced stages. Moreover, both cancer-specific survival and overall survival of metastatic patients in immunotherapy era were significantly better than those in non-immunotherapy era (P<0.001), indicating that immunotherapeutic intervention indeed bring remarkable benefits to advanced lung cancer patients.ConclusionsOur findings expand on previous studies by demonstrating that non-lung-cancer related death risk becomes more and more predominant over the course of follow-up, and we establish a personalized web-based calculator to determine this critical time point for long-term survivors. We also confirmed the survival benefit of advanced lung cancer patients in immunotherapy era.

Treating with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Accompanying Lower Incidence of Second Primary Cancers.

Lung cancer survivors are at risk of developing second primary cancers (SPCs). Although some risk factors for the development of SPCs have been addressed, their impacts have not been clarified. This study, based on Taiwan’s National Health Insurance Research Database (NHIRD), a nationwide database, was designed to investigate the risk factors for SPCs in patients with initial lung cancer and identify the impacts of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment on the development of SPCs. In this study, 37,954 individuals were included, of whom 2819 had SPCs. These patients were further divided into the second primary lung cancers (SPLC) and second primary extrapulmonary cancer (SPEC) groups. Among the patients with lung cancer without SPCs, those aged <65 years accounted for 53.15%. Patients aged ≥65 years accounted for 40.18% and 53.24% in the SPLC and SPEC groups, respectively. Females accounted for 50.3% of patients without SPC, 54% of the SPLC group, and 44.3% of the SPEC group. Univariate and multivariate Cox proportional hazard models showed increased hazard ratios for smoking, hypertension, and diabetes mellitus, and lower HRs for surgery, chemotherapy, radiotherapy, and TKIs. Patients undergoing surgery, chemotherapy, and radiotherapy were associated with a lower risk of SPCs. Treatment with EGFR TKIs was a significant and independent factor associated with lower incidence of SPCs. This study may encourage researchers to establish predictive models based on our results to assess the risk factors for SPCs, and therefore, early screening and intervention could be applied, and the SPCs-related mortality and relevant medical costs could be reduced.

EP03.01-013 Improving the Risk Estimation for Second Primary Lung Cancer after Lung Cancer by Taking Histologic Subtype into Account

Previous research has shown that lung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer are unexpectedly low (e.g. 0.83 and 2.06 for males and females in Germany [1]; 1.47 for both sexes in the UK [2]; 1.62 for both sexes in the United States [3]). These SIRs might be underestimated due to the histology-dependent documentation of SPC with the same location as the first cancer and differing definitions of SPC between International Agency for Research on Cancer (IARC) and US Surveillance, Epidemiology, and End Results (SEER) Program.This study aims to improve the estimation of SIR for second primary lung cancer (SPLC) in LC survivors by using histology-specific reference rates for estimating the expected number of SPLC.

MA08.03 Breathe Anew: Designing and Testing the Feasibility of a Novel Intervention for Lung Cancer Survivorship

Lung cancer survivors often suffer from chronic pain, anxiety, depression, fatigue, and dyspnea, and research in survivorship care has been lacking. We designed and tested the feasibility of Breathe Anew (BA), a multidisciplinary survivorship intervention comprising of physical rehabilitation using wearable technology; symptom management through mindfulness-based cognitive therapy (MBCT); and radiological surveillance. The first part of this study had been presented at the 2020 World Conference on Lung Cancer.

EP10.01-005 Australian Lung Cancer Survivors Experiences of Novel Treatments, Healthcare, and Ongoing Physical and Psychological Needs

People living with lung cancer remain underrepresented in survivorship research largely because of poorer survival rates and a focus on acute illness. However, earlier detection and improved treatments, such as immunotherapy (IO) and targeted therapy (TT), have led to higher numbers of individuals living longer. Given the profound impact lung cancer and treatments can have on physical and psychological wellbeing, understanding post-treatment experiences of survivors is crucial. In 2019, our group published a meta-review of the qualitative cancer survivorship literature and found a paucity of evidence about lung cancer survivor’s experiences.

Quality Of Life Changes In Lung Cancer Survivors After A Four Week Exercise Intervention

Quality Of Life Changes In Lung Cancer Survivors After A Four Week Exercise Intervention

A qualitative study of interactions with oncologists among patients with advanced lung cancer.

IntroductionTo support the care of lung cancer patients, oncologists have needed to stay current on treatment advancements and build relationships with a new group of survivors in an era where lung cancer survivorship has been re-defined. The objectives of the study were to (1) understand the perspectives of advanced lung cancer patients whose tumors have oncogenic alterations about their care experiences with their oncologist(s) and (2) describe the perceptions of advanced lung cancer patients about seeking second opinions and navigating care decisions.MethodsIn this qualitative study, patients with advanced lung cancer (n = 25) on targeted therapies were interviewed to discuss their ongoing experience with their oncologists. We used deductive and inductive qualitative approaches in the coding of the data. We organized the data using the self-determination framework.ResultsPatients described both positive and negative aspects of their care as related to autonomy, provider competency, and connectedness. Patients sought second opinions for three primary reasons: expertise, authoritative advice, and access to clinical trial opportunities. When there is disagreement in the treatment plan between the primary oncologist and the specialist, there can be confusion and tension, and patients have to make difficult choices about their path forward.ConclusionsPatients value interactions that support their autonomy, demonstrate the competency of their providers, and foster connectedness. To ensure that patients receive quality and goal-concordant care, developing decision aids and education materials that help patients negotiate recommendations from two providers is an area that deserves further attention.

Disparities in Psychosocial Distress Screening and Management of Lung and Ovarian Cancer Survivors.

Since 2016, the American College of Surgeons' Commission on Cancer (CoC) has required routine distress screening (DS) of cancer survivors treated in their accredited facilities to facilitate early identification of survivors with psychosocial concerns. Lung and ovarian cancer survivors have relatively low 5-year survival rates and may experience high levels of distress. We examined the extent to which ovarian and lung cancer survivors received CoC-mandated DS and whether DS disparities exist on the basis of diagnosis, sociodemographic factors, or facility geography (urban/rural). This study included a quantitative review of DS documentation and follow-up services provided using existing electronic health records (EHRs). We worked with 21 CoC-accredited facilities across the United States and examined EHRs of 2,258 survivors from these facilities (1,618 lung cancer survivors and 640 ovarian cancer survivors) diagnosed in 2016 or 2017. Documentation of DS was found in half (54.8%) of the EHRs reviewed. Disparities existed across race/ethnicity, cancer type and stage, and facility characteristics. Hispanic/Latino and Asian/Pacific Islander survivors were screened at lower percentages than other survivors. Patients with ovarian cancer, those diagnosed at earlier stages, and survivors in urban facilities had relatively low percentages of DS. Non-Hispanic Black survivors were more likely than non-Hispanic White survivors to decline further psychosocial services. Despite the mandate for routine DS in CoC-accredited oncology programs, gaps remain in how many and which survivors are screened for distress. Improvements in DS processes to enhance access to DS and appropriate psychosocial care could benefit cancer survivors. Collaboration with CoC during this study led to improvement of their processes for collecting DS data for measuring standard adherence.

Ten-year-plus Postoperative Survivors of Primary Lung Cancer with Postoperative Recurrence

Ten-year-plus Postoperative Survivors of Primary Lung Cancer with Postoperative Recurrence

COVID-19 perceptions, impacts, and experiences: a cross-sectional analysis among New Jersey cancer survivors.

BackgroundCancer survivors are particularly vulnerable to adverse COVID-19-related outcomes, but limited data exist on perceptions about the pandemic and related experiences in this group.MethodsIn a cross-sectional analysis of 494 survivors of genitourinary, breast, gynecologic, colorectal, lung, melanoma, or thyroid cancer, from a larger study of cancer survivors in New Jersey, we assessed perceptions about COVID-19 threat, impacts, and experiences using three validated instruments. Responses were coded on a 7-point Likert scale, and subscales were averaged across included items, with higher scores indicating greater perceptions of COVID-19 threat and greater impacts and experiences because of the pandemic. Multivariable linear regression models were used to determine factors associated with higher scores, with Bonferroni correction for multiple comparisons.ResultsIn general, cancer survivors reported moderate perceived COVID-19 threat (3 items, mean score = 3.71 ± 1.97), minimal COVID-19-related impacts (6 items, mean score = 2.23 ± 1.34), and COVID-19-related experiences (7 items, mean score = 2.17 ± 1.00). COVID-19 impact subscale scores varied little (mean subscale score range = 2.09 to 2.29), while COVID-19 experiences subscale scores were quite variable (mean subscale score range = 1.52 to 3.39). Asian American/Pacific Islander race, Black race, female sex, and having more cardiovascular and metabolic and other comorbidities were associated with higher scores on the perceived coronavirus threat questionnaire. Having completed the COVID-19 questionnaires earlier in the pandemic, younger age, American/Pacific Islander race, Hispanic ethnicity, and having more comorbidities were associated with higher scores on the COVID-19 impact questionnaire. Younger age, racial minority status, and having more cardiovascular and metabolic comorbidities were associated with higher scores on the COVID-19 experience questionnaire.ConclusionAmong cancer survivors in New Jersey—a state that experienced high rates of COVID-19 infection—sociodemographic and health-related factors (e.g., race and ethnicity, sex, and multimorbidity) correlate with greater perceptions of COVID-19 threat, impacts, and experiences.Implications for Cancer SurvivorsStudies are needed to examine the influence of vaccination status on COVID-19 perceptions and identify inequities in clinical outcomes due to pandemic-related disruptions to cancer care.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11764-022-01236-6.

Association of quality of life with performance status, circadian rhythm, and activity level of lung cancer patients using wearable devices as ambulatory monitoring

Lung cancer survivorship has two critical attributes: survival time or quantity and quality of life (QoL).[1][1] After decades of efforts focusing on reducing lung cancer incidence and mortality, we are now challenged by the lack of understanding of the health conditions and QoL among people who

Lung Cancer Mortality Racial/Ethnic Disparities in Patient Experiences with Care: a SEER-CAHPS Study.

To determine whether there are racial/ethnic disparities in patient experiences with care among lung cancer survivors, whether they are associated with mortality. A retrospective cohort study of lung cancer survivors > 65years old who completed a CAHPS survey > 6months after the date of diagnosis. We used data from the SEER-Consumer Assessment of Healthcare Providers Systems (SEER-CAHPS®) database from 2000 to 2013 to assess racial/ethnic differences in patient experiences with care multivariable Cox proportional hazards models to assess the association between patient experience with care scores mortality in each racial/ethnic group. Within our cohort of 2603 lung cancer patients, Hispanic patients reported lower adjusted mean score with their ability to get needed care compared to white patients (B: - 5.21, 95% CI: - 9.03, - 1.39). Asian patients reported lower adjusted mean scores with their ability to get care quickly (- 4.25 (- 8.19, - 0.31)), get needed care (- 7.06 (- 10.51, - 3.61)), get needed drugs (- 9.06 (- 13.04, - 5.08)). For Hispanic patients, a 1-unit score increase in their ability to get all needed care (HR: 1.02, 1.00-1.03) care coordination (1.06, 1.02-1.09) was associated with higher risk of mortality. Among black patients, a 1-unit score increase in their ability to get needed care (HR: 0.99, 95% CI 0.98-0.99) care coordination (0.97, 0.94-0.99) was associated with lower risk mortality. There are racial/ethnic disparities in lung cancer patient experiences with care that may impact mortality. Patient experiences with care are important risk factors of mortality for certain racial/ethnic groups.

Abstract 689: A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors

Abstract We designed a 6,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of disadvantaged or minority status, we have recruited multiple community hospitals (Jamaica, Flushing, Wyckoff, and Staten Island/Bronx satellites of Northwell hospitals) to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non-small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. These patients may be on maintenance therapy for their prior lung cancer but may not have any other active malignancy at the time of enrollment. Participants will be randomized 1:1 to standard surveillance at the discretion of the treating physician or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or overdiagnosis. The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include incidence of early cancers (locoregional recurrence or new primary cancer of stage I/II), metastasis-free survival, and utilization of liquid biopsy versus standard of care scans. We will stratify our results by minority and socioeconomic status to specifically ascertain the effect of this intervention on populations of need. This is the first randomized controlled trial of liquid biopsy in a survivor population and the first trial utilizing liquid biopsy in a large minority population. We will have preliminary experiences to report in April 2022. Citation Format: Sana Raoof. A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 689.

Abstract 3445: Long term effect of radiotherapy on risk of second primary lung cancer and overall mortality among lung cancer patients

Abstract Introduction: Radiotherapy has long been examined in association with second malignancies, but the impact of radiotherapy for initial primary lung cancer (IPLC) on the risk of second primary lung cancer (SPLC) remains controversial. We evaluated associations between IPLC radiotherapy and the risks of SPLC and overall mortality among lung cancer survivors. Methods: We identified 689,785 patients diagnosed with IPLC in 1988-2013 from SEER. We applied cause-specific Cox (CSC) regression to evaluate association between IPLC radiotherapy and SPLC risk, adjusting for age at IPLC diagnosis, IPLC stage and histology, and prior history of cancer. To allow a latency period of exposure to IPLC radiotherapy on SPLC risk, we performed subgroup analyses restricted to patients who survived ≥5 and ≥10 years after IPLC diagnosis. Using Cox regression, we evaluated association between IPLC radiotherapy and overall mortality, adjusting for the same covariates used in the CSC analysis. Mediation analysis quantified the indirect effect of IPLC radiotherapy on overall mortality mediated through radiotherapy-driven SPLC diagnosis. Validation utilized data from 7,758 IPLC patients (496 SPLCs) at Mayo Clinic. Results: Of 689,785 IPLC patients, 18,818 (2.7%) developed SPLC in SEER. IPLC patients treated with radiotherapy had a reduced SPLC risk versus non-irradiated patients when evaluated at the time of initial diagnosis (cause-specific hazard ratio [csHR]=0.90, P&amp;lt;1x10-6). However, the association between IPLC radiotherapy and SPLC risk was reversed when analyses were restricted to those who survived at least 5 years (csHR=1.08, P=0.01) and 10 years (csHR=1.16, P=0.009), thus long-term survivors treated with IPLC radiotherapy having a significantly increased risk of SPLC. Mayo Clinic data showed consistent results, with the effect of IPLC radiotherapy increasing from csHR of 2.41 (P&amp;lt;1x10-6) to 3.38 (P=0.001) among 5-year and 10-year survivors, respectively. Similarly, compared to non-irradiated patients, those treated with IPLC radiotherapy showed a significantly increased risk of overall mortality among 10-year survivors (hazard ratio [HR]=1.46, P&amp;lt;1x10-6 in SEER and HR=1.54, P=5.1X10-5 in Mayo Clinic). Mediation analysis showed that a substantial proportion of the total effect of IPLC radiotherapy on overall mortality—ranging from 32% to 59%—was due to radiotherapy-driven SPLC among 10-year survivors in SEER and Mayo Clinic. Conclusions: IPLC radiotherapy is associated with increased risks of SPLC and overall mortality, with its effects more pronounced among long-term survivors. Citation Format: Eunji Choi, Vicky T. Lam, Jacqueline A. Aredo, Ashok V. Kumar, Jason Wampfler, Julie T. Wu, David C. Christiani, Iona Cheng, Christopher I. Amos, Rayjean J. Hung, Leah M. Backhus, Joel W. Neal, Heather A. Wakelee, Ping Yang, Summer S. Han. Long term effect of radiotherapy on risk of second primary lung cancer and overall mortality among lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3445.

A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors.

TPS10617 Background: Lung cancer survivors are highly enriched for extensive smoking histories and have an increased risk of subsequent primary cancers, including those of the larynx, mouth and throat, esophagus, pancreas, bladder, thyroid, stomach, small intestine, colon, rectum, and kidney. Guideline-concordant surveillance after definitive treatment for lung cancer consists of periodic chest CT scans, which do not visualize the majority of second malignancies that this population ultimately develops. Disadvantaged and minority patients are diagnosed with recurrence and second primary cancers at later stages due to reduced compliance with survivorship surveillance. To address these issues, we propose utilizing multi-cancer early detection (MCED) liquid biopsies. MCED liquid biopsies are part of a rapidly growing field of research that assesses parallel cancer screening for multiple cancer types with point of care blood, urine, or saliva sampling. We selected a methylation-based screening liquid biopsy for multiple reasons: 1) it has the highest PPV and specificity of any test clinically validated in the multi-cancer detection setting thus far, 2) it produces a tissue of origin, allowing for targeted workup of positive findings, and 3) it requires only a single test, which we believe will minimize attrition among vulnerable populations with decreased access to healthcare. We designed a 9,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of minority status, we have recruited multiple community hospitals to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non- small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. Participants will be randomized 1:1 to standard surveillance or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or over-diagnosis. Methods: The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include cancer-specific mortality, eligibility for definitive interventions once cancer is diagnosed, and utilization of liquid biopsy versus standard of care scans. This is the first randomized controlled trial of screening liquid biopsy in a survivorship population and the first trial utilizing liquid biopsy in a large minority population.