Chemoimmunotherapy in patients with extensive-stage small cell lung cancer and a poor performance status.

BACKGROUND: Immune checkpoint inhibitor combined with platinum-etoposide is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The phase 3 clinical trials that led to the approval of chemoimmunotherapy in ES-SCLC excluded patients who had an Eastern Cooperative Group (ECOG) performance status (PS) of 2-3. Therefore, data on the efficacy of chemoimmunotherapy in patients with an ECOG PS of 2-3 are limited. METHODS: A retrospective analysis was performed on patients diagnosed with ES-SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. The objective of this study was to compare the overall survival (OS), progression-free survival (PFS), and best clinical response to therapy in patients with an ECOG PS of 0-1 vs. patients with an ECOG PS of 2-3 who received chemoimmunotherapy for newly diagnosed ES-SCLC. RESULTS: In total, 82 patients were included in the study. The mean ± standard deviation age was 68.1 ± 8.3 years. Of these, 56 patients were identified with an ECOG PS of 0-1, and 26 patients were identified with an ECOG PS of 2-3. The median PFS was similar regardless of ECOG PS (5.8 months [95% CI, 4.3-6.0 months] in the ECOG PS 0-1 group vs. 4.1 months [95% CI, 3.8-6.9 months] in the ECOG PS 2-3; p = .2994). The median OS was also similar regardless of ECOG PS (10.6 months [95% CI, 8.4-13.4 months] in the ECOG PS 0-1 group vs. 9.3 months [95% CI, 4.9-12.8 months]; p = .2718) in the ECOG PS 2-3 group. CONCLUSIONS: The study results demonstrated no significant difference in PFS or OS among the ECOG PS 2-3 and ECOG PS 0-1 groups. Therefore, chemoimmunotherapy should be considered for patients who have ES-SCLC with an ECOG PS of 2-3.

Immune-Related Adverse Events in Patients with Lung Cancer.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) have been widely adopted for the treatment of lung cancer since receiving first U.S Food and Drug Administration (FDA) approval in 2015. However, along with their use, the occurrence of immune-related adverse events (irAEs) has presented a challenge for both patients and oncology providers. In this manuscript, we reviewed the clinical trials that led to the approval of ICI by the FDA for the treatment of lung cancer between 2015 and 2023 to establish the frequency of irAEs in this patient population. Among the adverse events associated with ICI, we focused on the most common and relevant ones, including hypothyroidism, pneumonitis, diarrhea/colitis, skin rash, and hepatitis. RECENT FINDINGS: We thoroughly examined the available literature, including society guidelines concerning these complications, to discuss various aspects such as their pathophysiology, epidemiology, diagnostic process, grading system, and clinical management. Additionally, we explored the association between irAEs and disease response. The management of irAEs is a crucial aspect of oncologic care, particularly due to their potential to cause severe and life-threatening clinical manifestations. We present each pertinent aspect in a concise and organized manner to provide guidance and assistance to oncology providers managing these patients in both outpatient and inpatient settings.

Impact of Benzodiazepine Use on Length of Stay and 30-Day ED Visits among Hospitalized Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: This study assesses the impact of benzodiazepine (BNZ) use on length of stay (LOS) and 30-day emergency department (ED) visits after hematopoietic stem cell transplant (HSCT). METHODS: Adult patients (18 years and older) who underwent an allogeneic or an autologous HSCT from 2015 to 2018 at the study site were included. Five multivariable models were used for both allogeneic and autologous HSCT: BNZ-naïve status, diazepam equivalent daily dosage (DEDD; 0 vs any), DEDD (excluding 0), ED visits, and LOS. RESULTS: BNZ-naïve autologous HSCT recipients were less likely to use any BNZs in the hospital (odds ratio [OR] 0.07, P < 0.001). If prescribed BNZs, then they used a lesser amount (incidence rate ratio 0.39, P < 0.001). BNZ-naïve autologous HSCT recipients were less likely to experience a 30-day ED visit (OR 0.17, P = 0.009). BNZ-naïve allogeneic HSCT recipients were also less likely to use any BNZ than previous users (OR 0.11, P = 0.014). Patient characteristics influenced BNZ naïvety, DEDD usage, LOS for autologous patients, and BNZ naïvety and DEDD for allogeneic patients. CONCLUSIONS: BNZ use resulted in increased 30-day ED visits after autologous HSCT. BNZ-naïve recipients were less likely to use BNZs during hospital stays; if they required BNZs, then it was in lower dosages.

Initial treatment of patients with thyroid cancer: Outcomes and factors associated with care at academic versus nonacademic cancer centers.

BACKGROUND: Factors associated with receiving initial care for thyroid cancer (TC) at academic centers (ACs) versus nonacademic centers (NACs) and their impact on patient outcomes have not been reported. METHODS: The National Cancer Database with TC cases from 2004 to 2013 was evaluated for association of type of center for initial care with socioeconomic factors and disease and treatment characteristics, as well as overall survival (OS; all-cause mortality). RESULTS: The patients with TC (n = 200,824) included were predominantly women (74%), non-Hispanic Whites (85%), and from metro areas (84%). Sixty percent received initial care at a NAC. There were no significant differences between treatment groups by age or gender. Among those treated at an AC, a higher proportion belonged to racial/ethnic minorities (16.5%) versus at a NAC (11.6%). Hormone therapy was used more in an AC versus a NAC (60% vs 47%). Patients with all TC pathologies combined had a lower likelihood of death when they received initial care at an AC (hazard ratio [HR], 0.948; P = .0006). Among individual pathologic subtypes, a lower likelihood of death was noted when initial care was received at an AC for follicular (HR, 0.828, P = .0010) and Hurthle cell cancers (HR, 792; P = .0008), as well as stage II papillary thyroid cancer (HR, 0.828; P = .0026), but not for other histopathologic subtypes. CONCLUSIONS: Initial care at an AC was associated with lower likelihood of death for patients with TC, especially for those with follicular or Hurthle cell subtypes. Optimal resource use with consideration of patients' socioeconomic and demographic factors is imperative to ensure the most appropriate management of patients with TC in various treatment settings.

Establishing and Evaluating an ASCO Learning Cohort: a Longitudinal Project Assessing the Learning Needs and Behaviors of Oncology Professionals.

BACKGROUND: In 2013, the American Society of Clinical Oncology (ASCO)'s Continuing Education Committee recommended establishing an interprofessional, longitudinal cohort pilot project. The main goals of the cohort were to gain feedback from oncology providers on how they use resources to address their learning needs and gain insights into the utility of different ASCO educational activities. METHODS: The ASCO Learning Cohort Pilot Project included 49 ASCO members that were representative of the overall Society membership demographics and ran from November 2015 through August 2016. Participants documented monthly learning needs and completed monthly feedback activities focused on specific ASCO educational resources. RESULTS: The Learning Cohort Pilot Project proved a viable and innovative cohort model for analyzing the learning process for oncology healthcare professionals. The development, operations, and compliance required unique infrastructure to accomplish this project. Relationships between participant demographic variables and learning preferences are reported elsewhere. CONCLUSION: The ASCO Learning Cohort Project is a unique educational project that demonstrated feasibility and has met its goals. This paper outlines the processes of establishing a learning cohort, including participant selection, project design, and participant feedback. We evaluate the project model as a means to better understand the learning needs and behaviors of oncology healthcare professionals.

Quantitative Assessment of Learning Behaviors for Oncology Providers.

How health care providers select topics and activities for learning is key to meeting their needs. The goal of this study was to investigate how oncology providers identify knowledge gaps and choose learning activities. An online focus group within a larger longitudinal study was conducted between November 2015 and August 2016. Participants were chosen by convenience and stratified random sampling of diverse types of oncology providers. Providers were asked monthly to identify learning needs, explain how they identified those needs, and describe the learning activity they chose to meet those needs. Thirty-two oncology providers recorded 201 learning needs via online journal entries (mean 6 entries per person). Needs were associated with practice setting and professional role (p < .05). Colleague recommendation predicted learning needs for advanced practice providers (APPs) (p = .003). Patient cases drove > 50% of identified learning needs across groups. Learning activity preferences were associated with practice setting (p < .05). Choice of learning activity was associated with practice setting, professional role, and geographic location. Colleague recommendation was important for APPs (p = .025). Over 75% of learner responses identify convenience and content quality as important factors in choosing an activity. This study represents a quantitative assessment of learning behaviors for oncology providers and shows that identification of learning needs and activity selection differ by provider demographics. Limitations include small size and underrepresentation of some groups. Our findings should be confirmed with larger samples. Future research should focus on assessment of cohort versus individual needs and learning priorities.

Impact of Depression and Anxiety on Opioid Use in Hospitalized Hematopoietic Cell Transplantation Recipients.

BACKGROUND: Hematopoietic cell recipients are reported to have a high prevalence of depression and anxiety. The impact of depression and anxiety on opioid use has not been well characterized. This is of significance as the opioid epidemic continues, and over 60% of deaths secondary to drug overdose involve the use of opioids. OBJECTIVE: In this retrospective, single-center study of 275 patients who underwent hematopoietic cell transplantation (HCT) (allogeneic and autologous) for hematological malignancies, we explore the impact of depression and anxiety on opioid use. RESULTS: Patients who were both anxious and depressed at admission for HCT had increased odds of receiving an opioid (odds ratio of 4.50 [95% confidence interval: 1.75, 11.56]) compared with patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared with those who were neither depressed nor anxious. Autologous HCT recipients had reduced odds of receiving an opioid (odds ratio of 0.17 [95% confidence interval: 0.08, 0.38]) compared with patients undergoing allogeneic HCT. Patients with lower Karnofsky performance status (<90 on a scale of 1-100) had an increased incidence of receiving a higher Morphine milligram equivalent daily dosage (incidence rate ratio of 2.59 [95% confidence interval: 1.18, 5.67]) when modeled by zero truncated negative binomial regression. CONCLUSION: Presence of depression and anxiety impacts opioid use in patients undergoing HCT.

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

BACKGROUND: Immune-related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti-programmed cell death protein 1 (PD-1) therapy. MATERIALS AND METHODS: All patients with metastatic melanoma and non-small cell lung cancer (NSCLC) treated with anti-PD-1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan-Meier method and log-rank test was used for time-to-event analysis. RESULTS: In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression-free-survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs. CONCLUSION: Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations. IMPLICATIONS FOR PRACTICE: The results of this study suggest that women may be at a higher risk for immune-related adverse events (irAEs) compared with men when treated with anti-programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow-up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment-related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.

Targeting CD38 with daratumumab is lethal to Waldenström macroglobulinaemia cells.

CD38 is expressed on Waldenström macroglobulinaemia (WM) cells, but its role as a therapeutic target remains undefined. With recent approval of the anti-CD38 monoclonal antibody, daratumumab (Dara), we hypothesized that blocking CD38 would be lethal to WM cells. In vitro Dara treatment of WM cells (including ibrutinib-resistant lines) elicited antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cell phagocytosis (ADCP) and direct apoptosis. In vivo, Dara treatment was well tolerated and delayed tumour growth in RPCI-WM1-xenografted mice. CD38 is reported to augment B-cell receptor (BCR) signalling; we noted that Dara significantly attenuated phosphorylated SYK, LYN, BTK, PLCγ2, ERK1/2, AKT, mTOR, and S6 levels, and this effect was augmented by cotreatment with ibrutinib. Indeed, WM cells, including ibrutinib-resistant WM cell lines treated with the ibrutinib + Dara combination, showed significantly more cell death through ADCC, CDC, ADCP and apoptosis relative to single-agent Dara or ibrutinib. In summary, we are the first to report the in vitro and in vivo anti-WM activity of Dara. Furthermore, we show a close connection between BCR and CD38 signalling, which can be co-targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.

Launching an International Community of Practice in Hematology/Oncology Medical Education.

A community of practice (CoP) is a group of people who share a concern or a passion for something they do and learn how to do it better as they interact regularly. While the field of hematology/oncology has historically prioritized clinical care and biomedical research, medical education has received increasing attention within hematology/oncology in recent years. In 2018, ASCO launched the Education Scholars Program to train hematology/oncology clinicians in the science of teaching and learning. However, the number of hematology/oncology educators nationally and internationally far exceeds the capacity of the Education Scholars Program to train them. In addition, hematology/oncology educators often lack sufficient mentorship and guidance at their own institutions to pursue their chosen career path effectively. To ensure high-quality clinical care and research for generations to come, attention must be paid to improving support for hematology/oncology educators. Therefore, supported by ASCO, we developed an international medical education (Med Ed) CoP for hematology/oncology educators with the purpose of providing them with support, community, mentorship, resources, and scholarly opportunities in medical education. In this article, we describe the development of the Med Ed CoP using a three-stage framework (Establish-Grow-Sustain) including successes, challenges, and reflections. By supporting the needs of hematology/oncology educators, the Med Ed CoP will serve as a home for all who contribute to the field of hematology/oncology.

The role of immunotherapy sensitizers and novel immunotherapy modalities in the treatment of cancer.

The importance of the immune system in the response against cancer has always been a subject of intense investigation. The advent of immune checkpoint inhibitors has transformed the landscape of oncologic treatments, while expanding the understanding of this disease's pathophysiology. Consequently, many therapies are being investigated, with interventions directed at different steps and pathways of the immune response. Relevantly, immunotherapy sensitizers have arisen as approaches focused on the synergistic effects of immunotherapy combination, or the combination of immunotherapy and other treatment modalities, such as chemotherapy or radiation therapy. Concomitantly, novel immunotherapy modalities are also in development. Approaches focusing from the tumor intrinsic pathways to the tumor microenvironment and ex-vivo interventions, such as CAR-T cell therapies and tumor-infiltrating lymphocytes are important examples. Although many of those interventions were initially envisioned as standalone options, their combination has demonstrated promising results in early-phase in vitro studies and clinical trials. The possibility of coupling different immunotherapy modalities, as well as with other techniques, further strengthen the concept of sensitizers, allowing for deeper and more robust responses in cancer treatment. This review aims to present an overview of the concepts of these sensitizing mechanisms that are the basis for the synergistic effects of immunotherapy combination, or the combination of immunotherapy and a multitude of therapeutic strategies. Novel immunotherapy modalities are also presented, focusing on the potential of combining them with sensitizer interventions. Understanding the complexity underlying these principles may be the key for future breakthroughs and improved patient outcomes.

Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy.

Background: Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy were excluded from these trials. The standard of care second-line therapy for these patients remains to be docetaxel with or without ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in immunotherapy-pretreated patients are unknown. Methods: We conducted a retrospective study of all patients with locally advanced or metastatic NSCLC who were pretreated with immunotherapy at Mayo Clinic Jacksonville and Rochester from 2016 to 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. Results: In this cohort of 165 patients, 12.7% (n=21), 49.1% (n=81), and 38.2% (n=63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. 1-year landmark progression-free survival (PFS) were 23.8%, 6.2%, and 3.2% (p=0.006), and 2-year landmark PFS were 14.3%, 0%, and 0% (p<0.0001), in the Atezo, Doce, and Doce+Ram groups, respectively. About 20% patients with positive PD-L1 had durable response to atezolizumab. The Atezo group showed significantly greater overall survival (OS) improvement over Doce group (median OS 17.7 vs. 7.7 months, HR 0.47, 95% CI 0.29 - 0.76, p=0.008), and over Doce+Ram group (median OS 17.7 vs. 8.9 months, HR 0.55, 95% CI 0.32 - 0.95, p=0.047). 4 of 21 (19%) patients in the Atezo group developed immune-related adverse events (irAE). Conclusion: We observed statistically significant and clinically meaningful overall survival benefits of atezolizumab monotherapy compared with docetaxel +/- ramucirumab in patients with advanced NSCLC who were pretreated with immunotherapy. The survival benefit seems to be mainly from PD-L1 positive patients. Subsequent immunotherapy with Atezolizumab did not increase irAE rate.

Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis.

Introduction: Limited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs). Methods: We conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis. Results: A total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1-2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI. Conclusions: Patients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.

From Boring to Bravo! Using Learning Science to Create Memorable Presentations.

The practice of oncology continues to evolve over time. Educators find themselves in a position where they are no longer able to teach a topic in its entirety. Moreover, the rapid expansion of information available through research and discovery in the field of oncology makes it difficult for learners to process the constant barrage of new content. Lecturers continue to impart knowledge using didactic techniques, often trying to include as much material as possible in the time permitted. The question becomes: In the face of an impossibly large field, how can one assist learners in learning, and retaining, what is most important? The science of learning continues to develop, and we now recognize that there are ways to teach that optimally facilitate the retention and application of knowledge. By using these strategies, educators can make it easier for learners to absorb and retain key information. This article will touch upon several such techniques: cognitive load optimization, analogy, contrasting cases, elaboration, and just-in-time telling. By applying these methods to didactic presentations, educators can ensure that their lessons are heard, understood, and ultimately transformed into something unforgettable.

Trends in participant race and sex reporting in lung cancer phase III clinical trials.

BACKGROUND: Clinical trials are an essential part of advancing care for cancer patients. Historically, however, racial minorities and females have been underrepresented in these trials. Efforts like the National Institute of Health Revitalization Act attempted to mitigate these disparities, but despite these efforts, they continue to exist. These disparities can subsequently lead to minorities and females receiving suboptimal care. AIMS: The purpose of our study was to understand the changing trends in reporting of participant race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years given these consequences of poor representation. METHODS AND RESULTS: A total of 426 articles reporting the results of phase III lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. From these articles, data on participant sex and race were collected from the demographic tables to construct the database for this study. This database was subsequently used to determine the rate of reporting of demographic factors like race and sex and the participation trends over the time of minority and female participation in lung cancer phase III clinical trials. The SciPy Stats package for Python was used to calculate descriptive statistics, 95% confidence intervals, two sample t-test, one-way analysis of variance test, and Pearson's correlation coefficients. The Matplotlib package for Python was used for figure generation. Only 137 (32.2%) of the 426 studies analyzed reported the race of participants. Among those studies, we found that the mean participation rate of White participants was significantly higher (82.65%; p < .001). We found a decrease in African American participants and an increase in Asian participants over time. When looking at sex, we found that although the rate of male participation (69.02%) was significantly higher than that of female participation (30.98%), female participation has improved with time at a rate of 0.65% per year. CONCLUSION: We found that the reporting and participation of minority races continue to lag that of other demographic factors like sex in phase III clinical trials in lung cancer. Based on our analysis, we note a decline in participation of African Americans in lung cancer phase III clinical trials despite the rising incidence of lung cancer.

First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non-Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report.

ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal transformation with SCLC development is an ALK-independent mechanism of resistance that has not been previously reported with sequential ALK I1171T mutation while the patient is on treatment for the SCLC. Here, we report the first case of sequential SCLC transformation followed by ALK I1171T mutation in a patient with ALK-EML4 fusion-positive LUAD. After progression on multiple lines of therapy, we describe our experience of managing ALK-mutant LUAD and transformed SCLC with a novel combination of lorlatinib and temozolomide. We also briefly summarize cases of endothelial to mesenchymal transformation ALK-mutant LUAD from the literature.

Lung Cancer in Patients With Lynch Syndrome: Association or Coincidence?

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC) occurs due to microsatellite instability (MSI) caused by mutations in one of the mismatch repair genes leading to deficient mismatch repair proteins (dMMR). Although lung cancer is very common there is no established association between LS and lung cancer. In this manuscript we describe a case of lung cancer in a LS patient and then summarize available literature on this topic. Sixty seven y/o female patient with history of stage I colon and urothelial cancer, meeting the Amsterdam criteria, was diagnosed with LS on genetic testing. Sixteen years after the diagnosis of colon cancer, she was found to have adenocarcinoma of the lung with Next-generation sequencing (NGS) testing revealing the presence of germline mutation in MSH2 in the tumor cells indicating the possibility of LS driven lung cancer. However, subsequent immunohistochemistry (IHC) on tumor cells indicated proficient mismatch repair genes confirming the sporadic nature of lung cancer. On review of literature, we found that the coincidental presence of lung cancer in patients with LS can sometimes be mistaken for causation and may lead to confusion. Lynch syndrome associated tumors which are microsatellite instable (MSI) can be treated effectively with immunotherapy with durable responses, however, not all tumors in patient with LS are MSI impacting the choice of therapy.

Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year.

Brief report: risk stratification following curative therapy for stage I NSCLC.

Introduction: Surveillance with computed tomography (CT) imaging following curative treatment of stage I non-small cell lung cancer (NSCLC) is important to identify recurrence or second primary lung cancers (SPLC). The pattern and risks of recurrence following curative therapy and optimal duration of surveillance scans remain unknown. The objective of our study is to assess the pattern of recurrence and development of SPLC to risk stratify patients with stage I NSCLC following curative therapy. Methods: We identified 261 patients who received curative therapy for stage I NSCLC at Mayo Clinic Florida. Data was collected on clinical and demographic features including gender, smoking history, stage, treatment, histologic subtype, and tumor grade. Kaplan-Meier method was used to evaluate the disease free survival (DFS). Cox proportional hazard model was used to identify risk factors for recurrence. Results: Negative tobacco history and stage IA tumors were associated with significantly prolonged DFS after adjusting for co-variates (p=0.001 and p=0.005). Univariate Cox proportional hazards model identified tobacco history and stage 1B as risk factors for recurrence with unadjusted hazard ratio (HR) of 2.8 and 2.0, respectively. After adjusting for covariates, only stage IB was statistically significant predictor of recurrence with a hazard ratio of 2.1 (Confidence Interval (CI) 95% 1.2-3.6; p=0.007). Conclusions: An individualized approach that considers risk factors of stage and smoking history may be useful in determining whether to continue annual CT surveillance after five years post curative therapy for stage I NSCLC.