Thoracic Oncology Research Articles

Matched tissue and liquid biopsies for advanced non-small cell lung cancer patients A potentially indispensable complementary approach

The introduction of liquid biopsies (LB) has brought forth a number of therapeutic opportunities into the domain of thoracic oncology. Many of which have been adopted for care of patients presenting with advanced non-squamous non-small cell lung cancer (aNS-NSCLC). For example, one of the most frequent indications to perform a LB in these patients, at least in Europe, is for patients treated with tyrosine kinase inhibitors (TKIs) targeting EGFR and ALK genomic alterations when the tumor progresses. A tissue biopsy (TB) must then be taken, ideally from a site of a tumor that progresses, in particular if the LB does not permit detection of a mechanism of resistance to TKI. A LB from a patient with aNS-NSCLC is recommended before first-line therapy if no tissue and/or cytological material is accessible or if the extracted nucleic acid is insufficient in amount and/or of poor quality. At present a LB and a TB are rarely performed simultaneously before treatment and/or on tumor progression. This complementary/matched testing approach is still controversial but needs to be better evaluated to determine the true benefit to care of patients. This review provides an update on the complementarity of the LB and TB method for care of patients presenting with aNS-NSCLC.

Quantitative multiplexed imaging technologies for single-cell analysis to assess predictive markers for immunotherapy in thoracic immuno-oncology: promises and challenges.

The past decade has witnessed a revolution in cancer treatment by the shift from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular the immune-checkpoint inhibitors (ICIs). These immunotherapies selectively release the host immune system against the tumour and have shown unprecedented durable remission for patients with cancers that were thought incurable such as advanced non-small cell lung cancer (aNSCLC). The prediction of therapy response is based since the first anti-PD-1/PD-L1 molecules FDA and EMA approvals on the level of PD-L1 tumour cells expression evaluated by immunohistochemistry, and recently more or less on tumour mutation burden in the USA. However, not all aNSCLC patients benefit from immunotherapy equally, since only around 30% of them received ICIs and among them 30% have an initial response to these treatments. Conversely, a few aNSCLC patients could have an efficacy ICIs response despite low PD-L1 tumour cells expression. In this context, there is an urgent need to look for additional robust predictive markers for ICIs efficacy in thoracic oncology. Understanding of the mechanisms that enable cancer cells to adapt to and eventually overcome therapy and identifying such mechanisms can help circumvent resistance and improve treatment. However, more than a unique universal marker, the evaluation of several molecules in the tumour at the same time, particularly by using multiplex immunostaining is a promising open room to optimise the selection of patients who benefit from ICIs. Therefore, urgent further efforts are needed to optimise to individualise immunotherapy based on both patient-specific and tumour-specific characteristics. This review aims to rethink the role of multiplex immunostaining in immuno-thoracic oncology, with the current advantages and limitations in the near-daily practice use.

European Epidemiology of Pleural Mesothelioma—Real-Life Data From a Joint Analysis of the Mesoscape Database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma Database

IntroductionPleural mesothelioma (PM) is an aggressive malignancy with increasing prevalence and poor prognosis. Real-life data are a unique approach to reflect the reality of PM epidemiology, treatment, and prognosis in Europe. MethodsA joint analysis of the European Thoracic Oncology Platform Mesoscape and the European Society of Thoracic Surgeons (ESTS) databases was performed to better understand the characteristics and epidemiology of PM, including histologic subtype, staging, and treatment. Overall survival (OS) was assessed, adjusting for parameters of clinical interest. ResultsThe analysis included 2766 patients (Mesoscape: 497/10 centers/ESTS: 2269/77 centers). The primary histologic subtype was epithelioid (71%), with 57% patients on stages III to IV. Within Mesoscape, the patients received either multimodality (59%) or palliative intention treatment (41%). The median follow-up was 47.2 months, on the basis of 1103 patients (Mesoscape: 491/ESTS: 612), with 823 deaths, and median OS was 17.4 months. In multivariable analysis, female sex, epithelioid subtype, and lower stage were associated with longer OS, when stratifying by cohort, age, and Eastern Cooperative Oncology Group Performance Status. Within Mesoscape, multimodality treatment including surgery was predictive of longer OS (hazard ratio = 0.56, 95% confidence interval: 0.45–0.69), adjusting for sex, histologic subtype, and Eastern Cooperative Oncology Group Performance Status. Overall, surgical candidates with a macroscopic complete resection had a significantly longer median OS compared with patients with R2 (25.2 m versus 16.4 m; log-rank p < 0.001). ConclusionsThis combined European Thoracic Oncology Platform/ESTS database analysis offers one of the largest databases with detailed clinical and pathologic outcome. Our finding reflects a benefit for selected patients that undergo multimodality treatment, including macroscopic complete resection, and represents a valuable resource to inform the epidemiology and treatment options for individual patients.

Impact of polypharmacy and comorbidity on survival and systemic parenteral treatment administration in a cohort of hospitalized lung-cancer patients

BackgroundAlthough polypharmacy has been described among cancer patients, very few studies have focused on those with lung cancer. We aimed to assess whether polypharmacy and comorbidity have an impact on systemic parenteral treatment administration and survival among lung-cancer patients.MethodsIn this retrospective monocenter cohort study, we included patients hospitalized in thoracic oncology for the first time between 2011 and 2015. The Elixhauser score was used to assess comorbidity and polypharmacy was estimated with a threshold of at least five prescribed medications. The Fine and Gray competitive risk model was used to estimate the impact of polypharmacy and comorbidity on systemic parenteral treatment administration within the first two months of hospitalization. The effect of comorbidity and polypharmacy on overall survival was evaluated by Cox proportional hazards analysis.ResultsIn total, 633 patients were included (71% men), with a median age of 66 years. The median Elixhauser score was 6 and median overall survival was four months. Among the patients, 24.3% were considered to be receiving polypharmacy, with a median number of medications of 3, and 49.9% received systemic parenteral treatment within two months after hospitalization. Severe comorbidity (Elixhauser score > 11), but not polypharmacy, was independently associated with a lower rate of systemic parenteral treatment prescription (SdHR = 0.4 [0.3;0.6], p < 0.01) and polypharmacy, but not a high comorbidity score, was independently associated with poorer four-month survival (HR = 1.4 [1.1;1.9], p < 0.01)ConclusionsThis first study to evaluate the consequences of comorbidity and polypharmacy on the care of lung-cancer patients shows that a high comorbidity burden can delay systemic parenteral treatment administration, whereas polypharmacy has a negative impact on four-month survival.

Cemiplimab + Chemo Shows Clinical Benefit in Advanced NSCLC

Cemiplimab + Chemo Shows Clinical Benefit in Advanced NSCLC

ERS International Congress 2022: highlights from the Thoracic Oncology Assembly.

Thoracic malignancies are associated with a substantial public health burden. Lung cancer is the leading cause of cancer-related mortality worldwide, with significant impact on patients' quality of life. Following 2 years of virtual European Respiratory Society (ERS) Congresses due to the COVID-19 pandemic, the 2022 hybrid ERS Congress in Barcelona, Spain allowed peers from all over the world to meet again and present their work. Thoracic oncology experts presented best practices and latest developments in lung cancer screening, lung cancer diagnosis and management. Early lung cancer diagnosis, subsequent pros and cons of aggressive management, identification and management of systemic treatments' side-effects, and the application of artificial intelligence and biomarkers across all aspects of the thoracic oncology pathway were among the areas that triggered specific interest and will be summarised here.

Improving Access to Early Palliative Care Delivery for Patients With an Advanced Thoracic Malignancy Through an Embedded Oncopalliative Clinic Model.

Early integration of palliative care (PC) with standard oncology care is driving the development of innovative PC delivery models. This was a single-institution retrospective study of outpatient PC before and after the opening of an embedded thoracic oncology-palliative clinic at The Ohio State University. Patients included in the preintervention (October 2017-July 2018) and postintervention (October 2018-July 2019) cohorts had a diagnosis of any non-small-cell lung cancer (stages I-IV) or small-cell lung cancer (limited or extensive stage) and were newly established in the thoracic medical oncology clinic during the study time periods. All patients in the preintervention cohort had access to outpatient PC through a freestanding clinic, while the postintervention cohort had access to both freestanding and embedded clinics. Using time-to-event analyses, we evaluated differences in time intervals from first medical oncology visit to PC referral and first PC visit between cohorts. The majority of patients in both cohorts had metastatic disease at diagnosis. In the postintervention cohort, 20.9% of patients were referred to outpatient PC compared with 9.2% in the preintervention cohort (P < .01). PC referrals for patients outside of Franklin and adjacent counties increased from 4.0% to 14.2% after opening the embedded clinic (P < .01). Completion percentages of PC referrals increased from 57.6% to 76.0% in the preintervention versus postintervention cohorts (P = .048). Median time from palliative referral order to first PC visit decreased from 29 to 20 days (P = .047). Similarly, median time from the first oncology visit to PC referral completion decreased from 103 to 41 days (P = .08). Implementation of an embedded PC model was associated with increased access to early PC among patients with thoracic malignancies.

Receipt of financial drug assistance for oral targeted therapy among older adults with advanced non-small cell lung cancer (NSCLC).

e18916 Background: Financial drug assistance programs are a critical resource to mitigate financial toxicity for oral targeted therapy but can be challenging to access and navigate. Older adults with cancer frequently face high copayments for oral targeted therapy, yet they may be less able to navigate assistance programs due to functional and cognitive impairments. To identify potential barriers to receipt of assistance among older adults with advanced NSCLC, we evaluated associations between demographic, clinical, and geriatric assessment characteristics and receipt of financial drug assistance. Methods: We conducted a prospective cohort study at a Comprehensive Cancer Center where thoracic oncology nurses and pharmacists are available to help patients navigate financial drug assistance applications. We enrolled adults age &gt; 65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or oral targeted therapy regimen with non-curative intent. For this analysis, we included only older adults who received oral targeted therapy. Patients completed a pretreatment geriatric assessment to evaluate function, cognition, social support, comorbidities, mood, and nutrition. Receipt of financial drug assistance was abstracted from the medical record. We used Fisher’s exact tests to evaluate for differences in demographic, clinical, and geriatric assessment characteristics between those who did and did not receive financial drug assistance. Results: Of the 168 older adults with advanced NSCLC in the parent cohort study, 45 received oral targeted therapy and were included in this analysis. Median age was 74 (range 65-94); 56% were White, 40% Asian, 2% Black, and 2% Hispanic. The majority had Medicare (76%) followed by private insurance (18%), Medicare and Medicaid (4%), and Medicaid alone (2%). On the geriatric assessment, 60% were dependent in instrumental activities of daily living, 20% were dependent in basic activities of daily living, 51% had an abnormal Montreal Cognitive Assessment, and 42% had poor tangible social support. Overall, 9 older adults (20%) received financial drug assistance for their oral targeted therapy. Older adults with a lower household income were more likely to receive financial drug assistance (p = 0.007). There were no statistically significant differences in receipt of financial drug assistance according to other demographic, clinical, or geriatric assessment characteristics including function, cognition, and social support. Conclusions: Older adults with advanced NSCLC on oral targeted therapy with lower household incomes were appropriately more likely to receive financial drug assistance. The lack of associations between receipt of financial drug assistance and function, cognition, and social support suggests that thoracic oncology staff are successfully helping older adults navigate financial drug assistance programs.

Transitions of care with a community-based palliative care program: Results from a pilot project for advanced solid tumor oncology patients.

e24113 Background: Hospice underutilization among patients with advanced cancer at the end of life can result in patients not receiving the full benefit of hospice and lead to significant distress to patients, families, staff and caregivers. Through multidisciplinary root cause analyses, we identified a gap in services where hospice care, if pursued at all, did not occur until late in the course. A pilot program for community-based palliative services partnering with Calvary Hospital Advanced Healthcare Coordination was introduced for patients with advanced solid tumor cancer in February 2022. Methods: Solid tumor oncologists, social workers and palliative care physicians identified eligible patients with advanced stage cancer who may or may not be undergoing cancer-directed treatment with palliative intent. Patients received home-based support by palliative trained nurse practitioners, licensed social workers and spiritual counsel including symptom management, advanced care planning, care coordination and hospice transition if indicated. The pilot was launched initially in thoracic oncology in February 2022, with expansion to all solid tumor oncology patients in April 2022. Results: From February 1, 2022 to December 31, 2022, a total of 34 patients were referred for community-based palliative care services. Only 15/34 (44%) referrals were taken under care. Of the patients taken under care 7/15 (46.7%) were eventually transitioned to hospice services, and 4/15 (26.7%) patients expired while receiving community-based palliative care services. Of the remaining patients that were not taken under care (n = 19), 6/19 (31.5%) required a higher level of care and were hospitalized, 4/19 (21.1%) went directly to hospice care. Process measures including pain scores, completion of advanced care planning documents, depression scores, treatments given while in pilot, number of hospitalizations, as well as patient-reported outcomes are ongoing. Conclusions: Our pilot demonstrates that while community-based palliative care services can potentially bridge patients from palliative care services to hospice at the end of life, several patients may still have been referred “too late” in their course. Future plan-do-study-act cycles aim to continue to improve the number and timing of referrals to this pilot program and evaluate its impact in hospice utilization for patients with advanced cancer at end of life.

Opinions and usage of cancer-associated thrombosis scoring systems among hematologists and oncologists: An international survey.

e22531 Background: Cancer-associated thrombosis (CAT) occurs in 20% of cancer patients and is currently their second leading cause of death. Several scoring systems (i.e., Khorana Risk Score, COMPASS-CAT, Vienna-CATS, etc) have been developed to allow clinicians to determine CAT risk and prescribe appropriate treatments. There is little data about how hematologists and oncologists use these risk assessment models in daily practice. We conducted a survey of hematologists and oncologists in different institutions about their usage and opinions of CAT scoring systems. Methods: We created a twelve-question survey querying hematologists and oncologists regarding their usage and perspectives on CAT and scoring systems. Survey participation was voluntary, non-incentivized, and anonymous. The survey was advertised on social media and email list groups from January to February 2023. Descriptive statistics were analyzed in R version 4.1.2. Results: Seventy hematologists/oncologists responded with 88.4% from the US and 11.6% international. The plurality of respondents (35.7%) identified as sub-specialty oncologists (e.g., GI oncology, thoracic oncology, etc), 18.6% identified as malignant hematologists, and 15.7% identified as non-malignant hematologists. Overall 71.4% of respondents worked in academic settings. The majority (57.1%) stated they do not use any CAT scoring system and 15.7% stated they do not have familiarity with any CAT scoring system. Zero respondents strongly agreed that they often use scoring systems. Of the CAT systems used, the Khorana score was by far the most common (80.0%). Respondents somewhat agreed (14.3), somewhat disagreed (10%), or were undecided (34.3%) that scoring systems make it easier to determine CAT risk in practice. The majority (54.3%) were also undecided that these systems’ predictions of CAT risk are accurate. There was general agreement in worry of bleeding in anticoagulating cancer patients prophylactically (strongly agree 12.9%, agree 32.9%, somewhat agree 22.9%). Respondents strongly agreed (34.3%) or agreed (40.0%) that decisions about anticoagulation are important part in cancer patients’ supportive care. Similarly, respondents strongly agreed (30.0%), agreed (38.6%), or somewhat agreed (22.9%) that counseling patients on CAT is important. Conclusions: To our knowledge, this is the first survey assessment of hematologists and oncologists regarding their opions on CAT and their usage patterns of scoring systems. Despite the widespread agreement that counseling regarding CAT is important and that decisions about anticoagulation are a vital part of a cancer patient's supportive care, most clinicians do not use CAT scoring systems in practice or are not familiar with them. Hematologists and oncologists worry about the risk of bleeding with anticoagulation and agree there is a need for new and improved CAT scoring systems.

Quality assurance in thoracic oncology: the surgeon’s perspective

Quality assurance in thoracic oncology: the surgeon’s perspective

Reduced symptom burden after implementation of an electronic symptom management program.

12006 Background: The SIMPRO consortium implemented an electronic patient reported outcomes (ePRO) symptom management program as part of routine clinical care for patients (pts) receiving systemic cancer therapy or surgery across six health systems including rural and community cancer centers. To evaluate impact of the Epic-integrated electronic symptom management (eSyM) program on quality of life, pre- and post-implementation surveys were sent to a subset of gastrointestinal, thoracic, and gynecologic medical oncology (MO) and surgical (Surg) patients at all sites. Methods: A survey assessing symptom burden, health literacy, and self-efficacy was administered to separate groups of MO and Surg pts before (Pre-Implementation) and after (Post-Implementation) eSyM deployment. A waiver of documentation of consent was obtained for participation. Questions were derived from validated instruments including PROMIS, a standardized measurement tool for patient-reported symptoms. Surveys were completed 30-90 days after surgery or start of systemic therapy. PROMIS item responses were scored individually then translated into standardized T-scores with a mean of 50 based on an established reference population. Mean T-scores for PROMIS depression, anxiety, fatigue, and pain interference were calculated. Higher T-score correlated with greater symptom burden. Comparison between groups utilized non-parametric Kruskal-Wallis testing. Results: The number of survey responses were 498 MO Pre-Implementation, 518 MO Post-Implementation, 566 Surg Pre-Implementation, and 507 Surg Post-Implementation. MO pts reported significantly lower PROMIS mean T-scores for depression, anxiety, fatigue, and pain interference after eSyM compared to a similar group of MO pts prior to eSyM. Surg pts reported lower T-scores for depression, anxiety, fatigue, and pain interference after eSyM compared to a similar group of Surg pts prior to eSyM, although reduction in pain interference was not statistically significant. Conclusions: eSyM deployment in MO was associated with a significant reduction in patient reported depression, anxiety, fatigue, and pain interference. Surgical pts after eSyM deployment reported significantly lower rates of depression, anxiety, and fatigue. External validation with PROMIS based surveys demonstrated small but meaningful benefits of ePRO symptom monitoring as part of routine clinical care across six diverse health systems. Clinical trial information: NCT03850912 . [Table: see text]

Sexual dysfunction in women with lung cancer: Updates from the SHAWL study.

9071 Background: Despite its direct correlation with quality of life, sexual dysfunction is under-discussed and underreported in patients with lung cancer (LC). Sexual dysfunction is highly prevalent in patients with LC, with issues persisting over time; however, most data precede the approval of targeted therapies and immune checkpoint inhibitors. We report updated data from the SHAWL study, focusing on women’s sex life satisfaction. Methods: This cross-sectional, international survey study was administered via the GO2 Foundation Lung Cancer Registry. We utilized the Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction Measures for data collection. Participants were recruited from June 2020 to June 2021. Eligibility criteria included age &gt; 18 years, self-identification as a woman, and an LC diagnosis within ten years. Participants were asked about sexual health pertaining to 30 days before survey completion, now referred to as “recent.” Results: The survey was administered to 249 women (median age: 61 years). Most (67%) had stage IV LC and 47% were receiving targeted therapy; 66% were undergoing active treatment. Before LC diagnosis, 49% (117) of participants reported having no sexual health issues. Most women (54%, 128) indicated having had recent sexual activity, though 77% (183) reported moderate to severe sexual dysfunction. Indeed, only 7.5% (18) reported being quite or very interested in sexual activity, and only 6.7% (16) felt as if they always or often wanted to be involved in it. Out of the 128 women indicating recent sexual activity, the vast majority (72%, 91) also reported minimal to no satisfaction with their sex life, with 17% (22), 31% (39), and 24% (30) reporting none, a little bit, and some satisfaction, respectively. The most common reasons for lack of recent sexual activity were lack of interest (68%, 76) or vaginal dryness or pain (30%, 33). Most women (69%, 88) also reported rarely becoming sufficiently lubricated during sexual activity, with 54% (68) indicating that it was difficult to impossible to do so. Patients with stage IV diagnosis had a lower interest in and desire for sexual activity than those with non-metastatic LC. Patients not receiving active treatment reported similar rates of lack of interest and desire for sexual activity as those in active cancer therapy. Patients on targeted therapy had similar rates of sexual dysfunction as those receiving other LC treatments. Conclusions: The SHAWL study is the largest study evaluating sexual dysfunction and satisfaction in women with lung cancer in our current clinical environment. Sexual dysfunction, dissatisfaction, and lack of interest in sexual activity were highly prevalent in women with LC regardless of treatment status and type of therapy, suggesting that even after treatment completion, sexual issues persist. Sexual health should be integrated into thoracic oncology care for all patients with lung cancer.

Association of tertiary lymphoid structures with outcomes from PD-1 inhibition in advanced malignant pleural mesothelioma.

e20545 Background: Predictive biomarkers of benefit form immunotherapy in malignant mesothelioma patients remain poorly defined. The 9-15 PROMISE-MESO study (NCT02991482) of the European Thoracic Oncology Platform (ETOP) evaluated second-line pembrolizumab against chemotherapy. Pembrolizumab led to an increased response rate compared to chemotherapy, which did not translate to survival benefits. We evaluated if the presence of tertiary lymphoid structures (TLSs) with different compositions or LRRC15+ immune suppressive fibroblasts could predict the clinical benefit from pembrolizumab. Methods: We performed multiplex immune histochemistry analysis on tumor tissues. 144 patients were included in the clinical trial, from whom, 112 had available tumor tissue for analysis: 55 patients in the chemotherapy arm, and 57 patients in the immune therapy arm. We performed the following panel: calretinin or WT1 (mesothelioma cells), CD20, CD23, CD11c, LRRC15, aSMA, and DAPI. We used the Akoya Vectra Polaris platform for analysis. The IFQuant analytical pipeline developed at the Swiss Institute for Bioinformatics (SIB) was used for analyses. Results: We defined three categories of TLSs: general CD20+ TLSs independent of other markers. CD20/CD23 double-positive as mature TLSs (mTLS), and TLSs with dendritic cells (CD11c+, cTLS). Immune suppressive CAFs were defined as LRRC15+ cells/mm2. CD20+ TLSs were identified in 84% of patients' stroma, with a median of 21 TLSs/tumor tissue and 2 TLSs/mm2. mTLSs were rare, only detected in 10 of the 112 patients (9%). cTLSs with dendritic cells were more frequent and present in 45% of all patients (50/112), and roughly half of the TLS+ patients (53%) had CD11c+ cells detected in TLSs. LRRC15+ cancer-associated fibroblasts (CAFs) were detected in 85% of patients, with a median density of 61 cells/mm2. LRRC15- tumors also contained TLSs but had significantly fewer than LRRC15+ tumors (p = 0.0079). We did not find any significant association between the responses or PFS with TLS, mTLS, and LRRC15+ CAFs. We found inverse association between cTLS levels and response to immune therapy (p = 0.037) but not for PFS. Conclusions: Our data shows that advanced malignant mesotheliomas frequently harbor TLSs, but these TLSs are mostly not activated/mature. The absence of antigen-presenting cells in TLSs, like CD11c dendritic cells, is unexpectedly associated with increased response to pembrolizumab. The high prevalence of immune suppressive LRRC15+ CAFs might explain the low response rate to pembrolizumab and could be linked to the absence of maturation of TLSs. Clinical trial information: EudraCT number: 2016-002062-31 .

Clinical pathways innovation: A lesson on the value of clinician based feedback and collaboration with Flatiron Health.

1578 Background: Clinical pathways have emerged as a strategy to provide value-based care by reducing treatment variation across oncology practice. Despite evidence for cost reduction and improved patient outcomes, adoption of clinical pathways has met resistance in the oncology community given concerns regarding the impact on workflow, and cost. Flatiron Assist, an EMR based pathways tool, is a promising solution to minimizing workflow friction by proving a novel, streamlined user interface. Methods: The Abramson Cancer Center at the University of Pennsylvania and Flatiron Health conducted a pilot study from August 2021-December 2022 to test the use of Flatiron Assist within its thoracic oncology practices. The goal of the pilot was to increase utilization as well as usability of the pathways tool over time through clinician and developer iterative collaboration. Penn’s clinical pathways were incorporated into the tool and integrated into the EMR. An education program trained clinicians on the tool’s functionality. Based on clinician feedback, the Penn team identified two areas of improvement for the tool: speed and organization of the tool keys and prompts. Changes made over time included: 1) increasing the speed of the tool 2) restructuring the organization of keys and prompts, and 3) creation of a “hot button” for three common clinical scenarios in order to increase efficiency. Speed of the application (session length in seconds), utilization of the hot button (number of sessions/overall sessions) and overall physician adoption (treatment ordering with Flatiron Assist/total thoracic orders) were calculated during the pilot. Results: Provider utilization of the pathways tool increased over time with a baseline adoption rate of 29% in August 2021 and a peak of 74% in April 2022. Median session length decreased over time from 106.4 seconds (August 2021) to 39.9 seconds (December 2022). Peak performance for session length was 38.2 seconds (November 2022). Usage of the hot button introduced in August 2022 has increased over time from 27.6% of sessions to 41.8 % in November 2022. Thoracic providers ordered, on average, 1.7 new treatment plans per week, resulting in less than 1.5 extra minutes of work per week with optimal use of the pathways tool. Conclusions: Collaboration between Penn and Flatiron Health effectively reduced specific areas of friction associated with the use of Flatiron Assist. Changes made to the speed, button organization and functionality of the tool contributed to increased clinician utilization over time. Future development of EMR based pathway tools should incorporate clinician engagement and feedback.

Characteristics of long-term survivors with EGFR mutant (EGFRm) metastatic non-small cell lung cancer (mNSCLC).

9116 Background: Although osimertinib has become standard first-line (1L) therapy for patients (pts) with EGFRm mNSCLC, a subset treated with earlier-generation EGFR-targeted TKIs and chemotherapy have had long-term survival. We sought to characterize clinical features of long-term survival in pts with EGFRm mNSCLC treated prior to the osimertinib era. Methods: Data were abstracted from electronic medical records at 12 cancer centers participating in the Academic Thoracic Oncology Medical Investigator’s Consortium (ATOMIC). We included patients with mNSCLC with sensitizing mutations in EGFR who started 1L systemic therapy before 2015. Survival distributions and predictors were assessed using Kaplan-Meier estimates and a multivariable Cox proportional hazards model including time-dependent brain metastasis (met) development, age, 1L therapy (targeted vs. chemotherapy), sex, race, and smoking status. Multivariable logistic regression was used to evaluate baseline predictors associated with 5+ year survival vs. not for those with known survival status at 5 years after start of 1L. Results: We identified 304 patients (69% female, 56% White, 29% Asian, mean age 61.2). First-line targeted therapy was given in 70% of patients. With a median follow-up of 81.5 months, median overall survival was 63.5 months (95% CI 59.4-71.9). 135 (44%) pts survived 5+ years; among those with baseline next-generation sequencing (NGS), presence of a baseline pathogenic ERBB2 variant was higher in 5+ year survivors (4/51 [8%], 2x amplification, y772_A775dup, S310F) v others (1/65 [2%], amplification). Among 161 pts with baseline brain imaging, both baseline and on-treatment development of brain mets were associated with worse survival (HR 1.29, 95% CI 1.21-1.37; HR 1.59, 95% CI 1.47-1.72; both P &lt; 0.001). Excluding 22 patients lost to follow-up before 5 years, a history of smoking (OR 2.99, 95% CI 1.35-6.90, P = 0.008) and baseline brain metastases (OR 3.57, 95% CI 1.64-8.13, P = 0.002) were associated with death before 5 years. Conclusions: Long-term survivors with EGFRm mNSCLC treated before the osimertinib era were more likely to be nonsmokers and have no baseline brain metastases. This highlights a subset of EGFRm patients who had excellent outcomes with older treatment strategies and may not benefit as much from intensification approaches. Additional baseline mutational data will be presented at the conference.

The use of minimal residual disease in thoracic oncology: Gaps between promises and the on-the-ground reality of daily practice.

The assessment of minimal residual disease (MRD) from blood samples of patients with resected non-small cell lung carcinoma (NSCLC) is promising and opens up many opportunities for the optimisation of patient care in daily practice. Notably, this includes the potential for escalation or de-escalation of adjuvant therapies. Thus, the evaluation of MRD status can directly contribute to an increase in the overall survival of early stage NSCLC patients and/or limit therapeutic but also "financial" toxicity. Therefore, several clinical trials recently evaluated MRD in early stage NSCLC by integrating and retrospectively comparing the results of MRD assessments. In this context, there is an urgent need to close the gap between clinical research and the use of the evaluation of MRD in routine daily practice. Further action needs to be taken, particularly in evaluating the pertinence of the detection of MRD in prospective interventional clinical studies. This may be done in part by comparing different parameters, such as the techniques used, the different time points and the cutoffs of MRD assessments. This article investigates the assessment of MRD in non-small cell lung cancers, with a special focus on the issues associated with the various assays and the limitations of using circulating free DNA analyses for MRD assessment in early stage lung cancer. Recommendations and tips for the optimisation of MRD evaluation in non-small cell lung cancers are provided.

Interest of ergospirometry in the management of thoracic oncology surgery

Abstract Funding Acknowledgements Type of funding sources: None. Background A cardiopulmonary exercise testing (CPET) is recommended before a resection of a primary pulmonary nodule by surgical approach for patients at risk (with abnormal spirometry). The maximal oxygen consumption measurement (VO2max) evaluates the morbidity/mortality and allows to orient the surgical choice towards a lobectomy or a cuneiform resection. However, the VO2 max can be influenced by some parameters as patient’s motivation, overweight, …. Purpose The objective of this work is therefore to identify other complementary predictive factors of cardiopulmonary exercise test (CPET) in at-risk patients population with abnormal pulmonary function tests. Methods 211 subjects who underwent thoracic surgery for non-small cell lung cancer (NSCLC) between 2016 and 2020 at Erasmus Hospital and performed a CPET were analyzed and divided into 2 groups (G1 At Risk: n = 159: 10 mL/min/kg &amp;lt; VO2max &amp;lt; 20 mL/min/kg; G2 Control: n = 52: VO2max ≥ 20 mL/min/kg). Anthropological, biometric, clinical, and intraoperative data were collected based on the medical record. Results The risk group (G1) had a reduced VO2max associated with a higher VE/VCO2 slope. However, the 30-day and 1-year mortality as well as the number of minor and major complications were comparable to the control group (G2) because of the screening and the operative choices. All groups combined, VO2max was predictive of major complications (OR = 0.98, p = 0.04) and VE/VCO2 slope emerged as a predictor of total and minor postoperative complications (OR = 1.07, p = 0.0054 and respectively OR = 1.05, p = 0.046). Patients with a slope ≥ 34.5 had a higher incidence of total complications (OR = 3.16, p = 0.0004). In a subgroup with medium operative risk (VO2max between 15 and 20 mL/min/kg), VE/VCO2 slope was predictive of total complications (OR = 1.09, p = 0.02) whereas VO2max was predictive of major complications (OR = 0.97, p = 0.04).

Randomized, Phase II study of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous, non-small cell lung cancer: TORG (thoracic oncology research group) 1321.

Cisplatin plus pemetrexed followed by pemetrexed is an efficacious platinum combination regimen for advanced non-squamous, non-small cell lung cancer (NSCLC). Data regarding the addition of bevacizumab, especially in maintenance treatment, are insufficient. Eligibility criteria included: no prior chemotherapy; advanced, non-squamous, NSCLC; performance status ≤1; and epidermal growth factor receptor mutation-negative. Patients (N = 108) received induction chemotherapy with cisplatin, pemetrexed, and bevacizumab every 3 weeks for four cycles, and tumor response was needed to confirm four-week response duration. Patients with at least stable disease were randomized to pemetrexed/bevacizumab or pemetrexed alone. The primary endpoint was progression-free survival (PFS) after induction chemotherapy. Myeloid-derived suppressor cell (MDSC) counts of peripheral blood samples were also analyzed. Thirty-five patients each were randomized to the pemetrexed/bevacizumab group and the pemetrexed alone group. PFS was significantly better in the pemetrexed/bevacizumab group than in the pemetrexed alone group (7.0 vs. 5.4 months, hazard ratio: 0.56 [0.34-0.93], log-rank p = 0.023). In patients with partial response to induction therapy, median overall survival was 23.3 months in the pemetrexed alone group and 29.6 months in the pemetrexed/bevacizumab group (log-rank p = 0.077). Pretreatment monocytic (M)-MDSC counts tended to be greater in the pemetrexed/bevacizumab group with poor PFS than in those with good PFS (p = 0.0724). Addition of bevacizumab to pemetrexed as maintenance therapy prolonged PFS in patients with untreated, advanced, non-squamous NSCLC. Furthermore, an early response to induction therapy and pretreatment M-MDSC counts may be related to the survival benefit of the addition of bevacizumab to the combination of cisplatin and pemetrexed.

Stereotactic ablative radiotherapy before resection to avoid delay for early-stage lung cancer or oligometastases during the COVID-19 pandemic: Pathologic outcomes from the SABR-BRIDGE protocol.

During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. Seventy-two patients underwent SABR. Most common SABR regimens were 34Gy/1 (29%, n=21), 48Gy/3-4 (26%, n=19), and 50/55Gy/5 (22%, n=16). SABR was well-tolerated, with one grade 5 toxicity (death 10days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5months post-SABR (range, 2-17.5months). Surgery was reported as being more difficult because of SABR in 38% (n=10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3months, 50% if 3-6months, and 33% if ≥6months; p=.069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.