Exploring the landscape of AI-assisted decision-making in head and neck cancer treatment: a comparative analysis of NCCN guidelines and ChatGPT responses.

PURPOSE: Recent breakthroughs in natural language processing and machine learning, exemplified by ChatGPT, have spurred a paradigm shift in healthcare. Released by OpenAI in November 2022, ChatGPT rapidly gained global attention. Trained on massive text datasets, this large language model holds immense potential to revolutionize healthcare. However, existing literature often overlooks the need for rigorous validation and real-world applicability. METHODS: This head-to-head comparative study assesses ChatGPT's capabilities in providing therapeutic recommendations for head and neck cancers. Simulating every NCCN Guidelines scenarios. ChatGPT is queried on primary treatments, adjuvant treatment, and follow-up, with responses compared to the NCCN Guidelines. Performance metrics, including sensitivity, specificity, and F1 score, are employed for assessment. RESULTS: The study includes 68 hypothetical cases and 204 clinical scenarios. ChatGPT exhibits promising capabilities in addressing NCCN-related queries, achieving high sensitivity and overall accuracy across primary treatment, adjuvant treatment, and follow-up. The study's metrics showcase robustness in providing relevant suggestions. However, a few inaccuracies are noted, especially in primary treatment scenarios. CONCLUSION: Our study highlights the proficiency of ChatGPT in providing treatment suggestions. The model's alignment with the NCCN Guidelines sets the stage for a nuanced exploration of AI's evolving role in oncological decision support. However, challenges related to the interpretability of AI in clinical decision-making and the importance of clinicians understanding the underlying principles of AI models remain unexplored. As AI continues to advance, collaborative efforts between models and medical experts are deemed essential for unlocking new frontiers in personalized cancer care.

Overview of glottic laryngeal cancer treatment recommendation changes in the NCCN guidelines from 2011 to 2022.

BACKGROUND: The treatment of glottic cancer remains challenging, especially with regard to morbidity reduction and larynx preservation rates. The National Comprehensive Cancer Network (NCCN) has published guidelines to aid decision-making about this treatment according to the tumor site, clinical stage, and patient medical status. AIM: The present review was conducted to identify changes in the NCCN guidelines for glottic cancer treatment made between 2011 and 2022 and to describe the published evidence concerning glottic cancer treatment and oncological outcomes in the same time period. METHODS AND RESULTS: Clinical practice guidelines for head and neck cancer published from 2011 up to 2022 were obtained from the NCCN website (www.NCCN.org). Data on glottic cancer treatment recommendations were extracted, and descriptive analysis was performed. In addition, a review of literature registered in the PubMed database was performed to obtain data on glottic cancer management protocols and treatment outcomes from randomized controlled trials, systematic reviews, and meta-analyses published from 2011 to 2022. In total, 24 NCCN guidelines and updates and 68 relevant studies included in the PubMed database were identified. The main guideline changes made pertained to surgical and systemic therapies, the consideration of adverse features, and new options for the treatment of metastatic disease at initial presentation. Early-stage glottic cancer received the most research attention, with transoral endoscopic laser surgery and radiotherapy assessed and compared as the main treatment modalities. Reported associations between treatment types and survival rates for this stage of glottic cancer appear to be similar, but functional outcomes can be highly compromised. CONCLUSION: NCCN panel members provide updated recommendations based on currently accepted treatment approaches for glottic cancer, constantly reviewing new surgical and non-surgical techniques. The guidelines support decision-making about glottic cancer treatment that should be individualized and prioritize patients' quality of life, functionality, and preferences.

Capacity of ChatGPT to Identify Guideline-Based Treatments for Advanced Solid Tumors.

BACKGROUND:  ChatGPT, created by OpenAI, is a large language model which has become the fastest growing consumer application in history, recognized for its expansive knowledge of varied subjects. The field of oncology is highly specialized and requires nuanced understanding of medications and conditions. Herein, we sought to better qualify the ability of ChatGPT to name applicable treatments for patients with advanced solid cancers. METHODS:  This observational study was conducted utilizing ChatGPT. The capacity of ChatGPT to tabulate appropriate systemic therapies for new diagnoses of advanced solid malignancies was ascertained through standardized prompts. A ratio of those medications listed by ChatGPT to those suggested in the National Comprehensive Cancer Network (NCCN) guidelines was produced and called the valid therapy quotient (VTQ). Additional descriptive analyses of the VTQ and its association with incidence and type of treatment were performed. RESULTS:  Some 51 distinct diagnoses were utilized within this experiment. ChatGPT was able to identify 91 distinct medications in response to prompts related to advanced solid tumors. The overall VTQ is 0.77. In all cases, ChatGPT was able to provide at least one example of systemic therapy suggested by the NCCN. There was a weak association between incidence of each malignancy and the VTQ. CONCLUSION:  The capacity of ChatGPT to identify medications used to treat advanced solid tumors indicates a level of concordance with the NCCN guidelines. As it stands, the role of ChatGPT to assist oncologists and patients in treatment decision making remains unknown. Nonetheless, in future iterations, it may be anticipated that accuracy and consistency in this domain will improve, and further studies will be needed to better quantify its capabilities.

Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases. Herein, we summarized the relevant evidence and provided an algorithm for decision-making in MCC management based on the latest 2021 National Comprehensive Cancer Network guidelines. Additionally, we report current active MCC clinical trials in the United States. The initial management of MCC is dependent upon the pathology of the primary tumor and presence of metastatic disease. Patients with no clinical evidence of regional lymph node involvement generally require sentinel node biopsy (SLNB) while clinically node-positive patients should undergo fine needle aspiration (FNA) or core biopsy and full imaging workup. If SLNB or FNA/core biopsy are positive, a multidisciplinary team should be assembled to discuss if additional node dissection or adjuvant therapy is necessary. Wide local excision is optimal for primary tumor management and SLNB remains the preferred staging and predictive tool in MCC. The management of MCC has progressively improved in the last decade, particularly due to the establishment of immunotherapy as a new treatment option in advanced MCC. Ongoing trials and prospective studies are needed to further establish the best practices for MCC management.

Compliance with the Current NCCN Guidelines and Its Critical Role in Pancreatic Adenocarcinoma.

OBJECTIVES: Since 2019, the National Comprehensive Cancer Network (NCCN) has recommended genetic testing for patients diagnosed with pancreatic adenocarcinoma that includes universal germline testing and tumor gene profiling for metastatic, locally advanced, or recurrent disease. However, testing compliance with this guideline has not yet been published in the English literature. METHODS: A quality assurance/quality improvement retrospective review was done to identify patients diagnosed with pancreatic adenocarcinoma from January 2019 to February 2021 to include the patient's clinical status and genetic test results. RESULTS: There were 20 patient cases identified with pancreatic adenocarcinoma. A total of 11 cases had molecular tumor gene profiling and microsatellite instability/mismatch repair (MSI/MMR) testing performed and 1 case had only MSI/MMR testing by immunohistochemistry performed. Only 3 patients of the 20 in total received germline testing. CONCLUSION: There was a significant number of patients for whom tumor gene profiling or germline testing had never been attempted as per recommended NCCN guidelines.

Interpretation of NCCN guidelines version 1. 2023 thymomas and thymic carcinomas / 中国胸心血管外科临床杂志

@#National Comprehensive Cancer Network (NCCN) has updated and released the latest content of NCCN guidelines version 1. 2023 thymomas and thymic carcinomas (known as "guidelines"). The guideline sets standards for the diagnosis and treatment of thymoma and thymic carcinoma based on high quality clinical evidence and the latest advances in research. There have been some updates and revisions in the latest two versions of the guidelines, mainly focusing on the principles of radiotherapy, the principles of systematic therapy, multidisciplinary participation and the improvement of some footnotes, compared with the first version of the guidelines in 2022. In this paper, the contents of the new guideline will be interpreted in order to provide reference for the work of thymoma and thymic carcinoma in our country at the present stage.

Interpretations of the NCCN guidelines for breast cancer risk reduction (version 2023) / 中国胸心血管外科临床杂志

@#Breast cancer, the most common malignancy in the world, also causes the most death cases of women among malignancies. Breast cancer risk reduction guidelines (version 2023) was updated by National Comprehensive Cancer Network (NCCN). Based on high-level evidences from evidence-based medicine and the latest research progress, the guidelines provided standardized guidance for breast cancer risk assessment and risk reduction strategies for individuals without a history of invasive breast cancer or ductal carcinoma in situ, which has attracted widespread attention from clinicians worldwide. Breast cancer is also the most common malignancy in Chinese women, and the number of newly diagnosed breast cancer cases each year in China ranks first in the world due to the large population, so the breast cancer prevention has become a major public health challenge in China. Aimed to provide reference for breast cancer prevention in China, this article interpreted the guidelines (the new version) based on the characteristics of breast structure in Asian women and the epidemiological characteristics of breast cancer in China.

Treatment heterogeneity and overall survival in patients with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma in the United States.

Background: Gastric or gastroesophageal junction (GEJ) adenocarcinoma is the most common form of gastric cancer diagnosed in the United States (US) each year. Diagnosis typically is in later stages of disease when it has advanced. Patients have been treated with a variety of regimens. Methods: The goal of this retrospective study was to understand if treatment patterns were becoming more homogeneous or remaining heterogeneous using the Herfindahl-Hirschman index (HHI) and if treatments were becoming more concordant to treatment guidelines published by the National Comprehensive Cancer Network (NCCN). HHI scores were calculated for each site by 2-year increments. Trend analyses were conducted for HHI scores over time using a linear regression model. Concordance to Category 1 and any category NCCN guidelines was determined based on the date treatment was initiated with the version of the NCCN guidelines at that time. Time trend analyses were conducted using linear regression models. This study utilized data from the Flatiron Advanced Gastric/Esophageal cohort. This study also examined overall survival (OS) rates estimated by the Kaplan-Meier method by line of therapy. Results: There were no statistically significant differences in HHI scores in the first-line setting over time, suggesting heterogeneity has not improved. Concordance to NCCN treatment guidelines for any category significantly increased over time, however Category 1 regimen concordance remained low in the first-line setting. Concordance over time improved in second-line treatment. Median OS from the start of first-line therapy was 13.57 months. There was no relationship between OS time from initiation of first-line therapy and HHI score, concordance with NCCN guidelines, or concordance with NCCN Category 1 guidelines in the first-line setting. Conclusions: Treatment heterogeneity persists in gastric cancer care, though there is a significant association between heterogeneity and concordance with both Category 1 and any category in the NCCN treatment guidelines, and that concordance has increased over time.

Guideline discordant care in patients with metastatic germ cell tumors.

INTRODUCTION: Despite high curability, patients with metastatic germ cell tumors (GCT) in the United States general population persistently face inferior outcomes compared with those treated in specialty referral centers. We characterized guideline discordant management in patients with metastatic GCT who experienced relapse after first-line chemotherapy and compared those who were initially treated in community practices vs. academic referral centers. PATIENTS/METHODS: Retrospective analysis of 53 patients with relapsed GCT between 2005 and 2018. First-line GCT management was assessed against the National Comprehensive Cancer Network guidelines. Guideline discordant management, predictors of discordance, and associations with outcomes were assessed. RESULTS: Of 53 patients with relapsed GCT, 34% received guideline discordant care in the first-line setting. Guideline discordant care was more prevalent in patients initially treated in community practices (12/30, 40%) vs. those initially treated in academic centers (3/22, 14%), though in multivariate logistic regression, this difference was not statistically significant (odds ratio: 4.07, P = 0.08). Most patients in community settings who received guideline discordant care were undertreated (10/12, 83%). There were 3 major reasons for guideline discordant care: (1) failure to resect residual masses after chemotherapy (27%, 4/15), (2) mismanagement of chemotherapy-related adverse events (27%, 4/15), and (3) under staging at diagnosis, resulting either insufficient chemotherapy regimen intensity (13%, 2/15) and/or inappropriately receiving primary surgical resection for metastatic disease (20%, 3/15). CONCLUSION: Under treatment was identified in nearly half of patients initially treated in a community setting who later developed relapsed GCT. Referral to specialized centers for a second opinion should be considered for all metastatic GCT patients in the first-line setting and all patients with post-chemotherapy residual disease. More effective methods should be developed to facilitate second opinions from expert centers in the United States.

Following NCCN guidelines within one hospital system in the United States: Comparison between cancer centers and genetic counselor utilization.

Genetic testing is an instrumental tool used to determine whether an individual has a predisposition to certain cancers. Knowing of a hereditary cancer predisposition may allow a patient and their family to consider high-risk screening or risk-reducing options. Genetic counselors work with physicians to identify patients at increased risk for genetic testing using available guidelines such as those provided by the National Comprehensive Cancer Network (NCCN). Information within one hospital system's cancer registry was used to identify individuals who qualify for genetic testing. This includes patients with a history of cancer of the breast (diagnosis ≤45, triple negative (TN) ≤60, and male), ovaries, colon (diagnosis ≤50), or uterus (diagnosis ≤50). Within this hospital system's registry, there are six cancer centers. Data were collected from cancer centers that utilized genetic counselors (GCs), and cancer centers that did not (non-GC) to determine whether there was a difference in genetic testing rates between GC and non-GC cancer centers. An analysis of 695 patients demonstrated a significantly higher proportion of eligible patients undergoing genetic testing at the GC cancer centers than at the non-GC cancer centers (91.6% versus 68.7%, p < .001). Further analysis of specific cancers showed a significantly higher uptake of genetic testing for eligible patients with colon cancer (90.8% versus 50%, p < .001), breast cancer ≤45 (99.5% versus 86%, p < .001), and ovarian cancer (91.3% versus 62.8%, p < .001) at the GC cancer centers than at the non-GC cancer centers. There was no significant difference in the proportion of testing of TN breast cancer ≤60 or uterine cancer ≤50 between cancer centers. These data suggest that having a GC working within a cancer center increases the ability to identify and offer testing to patients who meet NCCN genetic testing criteria based on their cancer type.

Interpretation of updated NCCN guidelines for non-small cell lung cancer (version 1, 2022) / 中国胸心血管外科临床杂志

@#The National Comprehensive Cancer Network (NCCN) has updated and released the latest content of the NCCN guidelines for the clinical diagnosis and treatment of non-small cell lung cancer (NSCLC) in the version 1, 2022. Based on high-quality clinical evidence and the latest research progress of the diagnosis and treatment of NSCLC, the guidelines have been widely recognized and welcomed by clinicians around the world. Compared with the version 7, 2021, the new version has been updated and revised in some parts of chapters and sections, mainly focusing on targeted therapies and molecular testing. This article will interpret the updated therapy content of the new version.

Importance of Compliance With Guidelines for the Prevention of Varicella-Zoster Virus Reactivation in Multiple Myeloma.

BACKGROUND/AIM: The importance of compliance with National Comprehensive Cancer Network (NCCN) guidelines for preventing varicella-zoster virus reactivation (VZVr) in multiple myeloma (MM) in a clinical setting has not been well investigated. PATIENTS AND METHODS: We retrospectively studied the clinical characteristics and outcomes of 118 patients with MM treated with proteasome inhibitors. RESULTS: Thirty-nine episodes of VZVr were observed in 37 patients (VZVr group). The proportion of prophylactic antiviral prescriptions and compliance with antiviral prophylaxis based on the NCCN Clinical Practice guidelines was 76% and 30% in the VZVr group, and 88% and 74% in the non-VZVr group, respectively. Multivariate analysis showed that compliance with the NCCN guidelines was the only independent risk factor for VZVr (p=0.0017). CONCLUSION: It is important that prophylactic antivirals are prescribed for an appropriate duration of time to prevent the reactivation of VZV in compliance with existing guidelines.

Compliance with sentinel lymph node biopsy guidelines for invasive melanomas treated with Mohs micrographic surgery.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has not been studied for invasive melanomas treated with Mohs micrographic surgery using frozen-section MART-1 immunohistochemical stains (MMS-IHC). The primary objective of this study was to assess the accuracy and compliance with National Comprehensive Cancer Network (NCCN) guidelines for SLNB in a cohort of patients who had invasive melanoma treated with MMS-IHC. METHODS: This retrospective cohort study included all patients who had primary, invasive, cutaneous melanomas treated with MMS-IHC at a single academic center between March 2006 and April 2018. The primary outcomes were the rates of documenting discussion and performing SLNB in patients who were eligible based on NCCN guidelines. Secondary outcomes were the rate of identifying the sentinel lymph node and the percentage of positive lymph nodes. RESULTS: In total, 667 primary, invasive, cutaneous melanomas (American Joint Committee on Cancer T1a-T4b) were treated with MMS-IHC. The median patient age was 69 years (range, 25-101 years). Ninety-two percent of tumors were located on specialty sites (head and/or neck, hands and/or feet, pretibial leg). Discussion of SLNB was documented for 162 of 176 (92%) SLNB-eligible patients, including 127 of 127 (100%) who had melanomas with a Breslow depth >1 mm. SLNB was performed in 109 of 176 (62%) SLNB-eligible patients, including 102 of 158 melanomas (65%) that met NCCN criteria to discuss and offer SLNB and 7 of 18 melanomas (39%) that met criteria to discuss and consider SLNB. The sentinel lymph node was successfully identified in 98 of 109 patients (90%) and was positive in 6 of those 98 patients (6%). CONCLUSIONS: Combining SLNB and MMS-IHC allows full pathologic staging and confirmation of clear microscopic margins before reconstruction of specialty site invasive melanomas. SLNB can be performed accurately and in compliance with consensus guidelines in patients with melanoma using MMS-IHC.

Adherence to National Comprehensive Cancer Network ALK Testing Guidelines for Patients with Advanced Non-Small Cell Lung Cancer in U.S. Community Medical Centers.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend biomarker testing as the first step in the management of patients with advanced non-small cell lung cancer (aNSCLC). We assessed anaplastic lymphoma kinase (ALK) testing rates and factors related to underuse in community medical systems between 2012 and 2019 to understand guideline adoption. METHODS: A retrospective observational study using a nationwide electronic health record (EHR)-derived deidentified database was conducted. Patients with aNSCLC diagnosed in community medical centers from January 2012 to May 2019 were included to describe the ALK testing trend. This cohort was further restricted to patients diagnosed after 2015 to understand factors associated with testing underuse using mixed-effects multivariable logistic regression models. RESULTS: Trends for increased ALK testing rates by year were observed in both NCCN guideline-eligible patients (59.5% in 2012 to 84.1% in 2019) and -ineligible patients (15.6% to 50.8%) in a cohort of 41,728 patients. Histology type and smoking status had the greatest impact on test use. Compared with patients with nonsquamous histology and no smoking history, patients with squamous histology and no smoking history (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 5.6-10.4), NSCLC histology not otherwise specified (NOS) with smoking history (aOR, 3.4; 95% CI, 2.8-4.2); NSCLC NOS/nonsmoker (aOR, 1.8; 95% CI, 1.1-3.2), and nonsquamous/smoker (aOR, 1.5; 95% CI, 1.3-1.7) were less likely to be tested. Factors related to underuse also included Eastern Cooperative Oncology Group performance status, stage at initial diagnosis, and demographics. CONCLUSION: This analysis of real-world data shows increasing test use by year; however, one fifth of patients eligible for ALK testing still remain untested and potentially missing therapeutic options. IMPLICATIONS FOR PRACTICE: Advancement in treatment of lung cancer is accompanied by an increasing number of tests that should be run to determine potential therapy options for each patient. This study assessed adoption of testing recommendations for anaplastic lymphoma kinase rearrangements in a national database. Although test use increased over the time period studied (2012-2019), there is still room for improvement. Efforts are needed to increase test use in undertested groups, thus enabling eligible patients to benefit from novel lung cancer therapies.

Male Breast Cancer in Australia.

AIMS: Male breast cancer is rare and treatment recommendations are based on female breast cancer guidelines. We analyzed an Australian dataset of patients with early breast cancer (including ductal carcinoma in situ, DCIS) for demographic, pathological and treatment information. The primary objective was to compare treatment delivery for males versus females. METHODS: Australian data from the BreastSurgANZ Quality Audit (BQA) from 1 October 2006 and 30 September 2016 were analyzed. Demographic and pathological information was obtained and compared between males and females. Treatment recommendations were compared to BreastSurgANZ Key Performance Indicators (KPIs) and National Comprehensive Cancer Network (NCCN) guidelines to assess for adherence to national and international guidelines, respectively. RESULTS: A total of 99,768 breast cancer episodes were analyzed, comprising 585 males (544 invasive; 41 DCIS) and 99 183 (99.4%) females (85 596 invasive; 13 525 DCIS; 62 unknown). Compared with females, males were older at diagnosis, more likely to be hormone receptor-positive and lymph node-positive disease, and more likely to have mastectomy. The proportion of males undergoing breast conserving surgery receiving radiotherapy was the only BreastSurgANZ KPI that was not met. Males were less likely to receive adjuvant chemotherapy than females using NCCN guidelines. CONCLUSION: Australian males with breast cancer account for 0.6% of breast cancer incidence and have similar clinico-pathological features as reported internationally. Overall, there is good compliance with the surgical KPIs, and adherence to NCCN guidelines for adjuvant systemic treatment is similar to previous international studies.

Category of evidence and consensus underlying National Comprehensive Cancer Network guidelines: Is there evidence of progress?

National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care, financial reimbursements and quality improvement initiatives in oncology. We studied the distribution of categories of evidence and consensus (EC) in the guidelines for the common cancers in the United States. We evaluated the EC categories in staging, therapy and surveillance recommendations in 2019 guidelines and compared them with the same in 2010. The latest 2019 version of NCCN guidelines were obtained. The definitions for various categories of EC used were, Category 1 (high level evidence, uniform consensus), Category 2A (lower level of evidence [LOE], uniform consensus), Category 2B (lower LOE, no uniform consensus but with no major disagreement) and Category 3 (any LOE, major disagreement). We compared our results with previously published results from 2010 guidelines. Total number of recommendations increased by 77% from 1023 (2010) to 1818 (2019). Of the 1818 recommendations, Category 1, 2A, 2B and 3 EC were 7%, 87%, 6% and 0%, respectively, while in 2010 they were 6%, 83%, 10% and 1%. Breast (30%), lung (10%) and kidney (10%) cancer had the highest proportions of Category 1 therapeutic recommendations in their respective guidelines. No Category 1 recommendations were found in screening or surveillance guidelines or in pancreatic and uterine cancer guidelines. Recommendations in 2019 NCCN guidelines are largely Category 2A (lower levels of evidence, uniform expert opinion), unchanged from the previous study in 2010.

Interpretation of updated NCCN guidelines for small cell lung cancer (version 1. 2022) / 中国胸心血管外科临床杂志

@#The National Comprehensive Cancer Network (NCCN) released the latest version 1, 2022 of "NCCN guidelines for the clinical diagnosis and treatment of small cell lung cancer" (hereinafter referred to as "guideline"). Based on high-quality evidence-based medicine, this guideline provides references of clinical diagnosis and treatment for clinicians around the world. Compared with the version 3, 2021 of the "guideline", updates and revisions mainly focused on the progress of radiotherapy and systemic treatment. This article will interpret the updated therapy content in this new version of the "guideline".

Interpretation of updated NCCN guidelines for non-small cell lung cancer (version 1. 2021) / 中国胸心血管外科临床杂志

@#Based on new clinical evidence, the National Comprehensive Cancer Network (NCCN) annually updates and releases the "NCCN Guidelines for the Clinical Diagnosis and Treatment of Non-Small Cell Lung Cancer" which has become the reference for clinical diagnosis and treatment approved and complied by clinicians worldwide. On November 25, 2020, the latest 2021 V1 version of "NCCN Clinical Diagnosis and Treatment Guidelines for Non-Small Cell Lung Cancer" (hereinafter referred to as "Guidelines") was released. Compared with the 8th edition of the "Guidelines" in 2020, many updates focused on the progress of targeted and immunotherapy. This article will provide the interpretations of the updated therapy content of this edition of the guidelines.

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment.

INTRODUCTION: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)≥180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI ≥ 180 days. MATERIAL AND METHODS: Twenty patients aged ≥18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI ≥ 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. RESULTS: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. CONCLUSION: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI ≥ 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge.