BACKGROUND:Neuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes across NET subtypes remain poorly characterized, particularly in real-world settings. This study describes baseline health-related quality of life (HRQoL) and care experiences among patients with gastroenteropancreatic and lung NETs, examining differences by tumor site and time since diagnosis. METHODS:The Neuroendocrine Tumors-Patient Reported Outcomes study is a prospective, multi-institutional US cohort of adults (aged 18 years and older) with incident small intestinal, pancreatic, gastroenteropancreatic, or lung NETs diagnosed from January 2018 through September 2024, identified via a validated electronic medical record-based computable phenotype. Baseline surveys assessed HRQoL, symptoms, care experiences, and clinical characteristics using validated instruments. Descriptive statistics and standardized mean differences compared responses by NET site and time since diagnosis. RESULTS:Among 2367 participants (mean age = 57.8 years; 57.3% female), 1974 had gastroenteropancreatic NETs (659 small intestinal NET, 555 pancreatic NET) and 393 had lung NETs. Fatigue (mean = 33.0), insomnia (mean = 32.5), and diarrhea (mean = 25.7) were the most burdensome symptoms. Lung NET patients reported worse dyspnea (standardized mean difference = 0.58, P < .001) and lower physical, role, and global QoL scores than those with gastroenteropancreatic NETs, while pancreatic NET patients reported better functioning. Diarrhea worsened over time, especially in small intestinal NETs. Most rated care highly (75.3%) but cited concerns about treatment side effects (80.4%), costs (60.7%), and travel burden (58.8%). CONCLUSIONS:This large US cohort reveals persistent symptom burden and HRQoL variation by tumor site and disease duration, underscoring the need for longitudinal HRQoL assessment in NET care.

TPS646 Background: SSTR-targeted RPT has transformed the treatment landscape for NETs, significantly improving clinical outcomes in phase 3 studies versus other targeted therapies. Nevertheless, disease progression and renal toxicity after treatment highlight the need for further improvement. Use of the α-emitter 225 Ac as the radioactive component has shown promising results in clinical studies: initial data from ACTION-1 suggest promising efficacy for RYZ101, a first-in-class, highly potent α-emitting RPT, in patients with SSTR+ GEP-NETs progressing after 2–4 cycles of 177 Lu-somatostatin analogs. RYZ401 is a cyclic 6-amino acid SSTR-targeting peptide agonist conjugated to a DOTA chelator bound to 225 Ac. Preclinical data have shown an improved therapeutic window versus DOTATATE. RYZ401 has the potential to deliver higher radiation doses to tumors, with improved renal clearance and lower kidney absorbed dose, potentially eliminating the need for amino acid infusion. Methods: RYZ401-101 is a global, multicenter, phase 1, first-in-human, dose-escalation/-expansion study designed to determine the recommended phase 2 dose (RP2D) and optimal treatment regimen, safety and tolerability, and preliminary efficacy of RYZ401 in patients with NETs and other selected solid tumors expressing SSTRs. Key eligibility criteria: histologically confirmed metastatic or unresectable well-differentiated NETs; WHO grade 1–3 (Ki-67 ≤55%); ≥1 SSTR PET-positive measurable lesion; and disease progression after ≥1 prior treatment line. In dose escalation, 6–18 patients will receive escalating doses of RYZ401 (2.0–11.1 MBq IV Q6W × 2–4 cycles); no amino acid co-infusion is planned. In dose expansion, approximately 80 patients will receive RYZ401 at the RP2D, 40 patients with well-differentiated GEP-NETs (cohort A) and 40 with other SSTR+ tumors including non-GEP-NETs (cohort B). Primary endpoints: dose-limiting toxicities in weeks 1–4 of treatment (dose escalation) and safety (dose expansion). Secondary endpoints: safety, pharmacokinetics, and efficacy outcomes (dose escalation and expansion). RYZ401 dosimetry will be evaluated in a sub-study of 10−16 patients. Enrollment is ongoing in the USA. Clinical trial information: NCT07165132 .

Peptide receptor radionuclide therapy (PRRT) has become an established treatment for patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) that express somatostatin receptors. Among the available agents, lutetium-177 DOTATATE is the most commonly used radiolabeled somatostatin analog and has demonstrated significant clinical benefits, including improved response rates and prolonged progression-free survival, as shown in landmark trials such as NETTER-1 and NETTER-2. As the incidence of GEP-NENs continues to rise, the use of PRRT in clinical practice has grown accordingly. However, this therapy is associated with a range of toxicities that can affect multiple organ systems over different timeframes, including acute, subacute, and long-term periods. This review provides a comprehensive overview of the adverse effects associated with PRRT and presents evidence-based strategies for their monitoring, prevention, and management. This review also discusses the evolving paradigm of screening for clonal hematopoiesis before PRRT treatment, as well as the use of steroids as prophylaxis to prevent carcinoid crisis and bowel obstruction. A multidisciplinary approach is essential to ensure the safe delivery of treatment, early detection of complications, and tailored patient care. As clinical experience with PRRT expands, continued refinement of supportive care strategies will be critical to optimizing outcomes and minimizing toxicity in this complex patient population.

4173 Background: [ 212 Pb]VMT-α-NET is an alpha-particle radiation-delivering agent targeted to somatostatin receptor type 2 (SSTR2)-expressing tumors. Here, we present safety and efficacy results from the dose-finding phase 1/2a clinical trial (NCT05636618). Methods: This phase 1/2a dose-escalation study uses a Bayesian algorithm to identify an optimal dose of [ 212 Pb]VMT-α-NET for participants with advanced, well-differentiated NETs expressing SSTR2. Eligible participants must have unresectable or metastatic disease, documented radiologic progression following at least one prior systemic treatment, and evidence of SSTR2 expression (Krenning Score ³2) in ≥1 lesion confirmed on an FDA-approved somatostatin receptor PET scan. Patients previously treated with systemic peptide receptor radionuclide therapy (PRRT) are excluded from enrollment. During the dose-finding phase, participants may receive up to four administrations of [ 212 Pb]VMT-α-NET at their assigned dose level, and they are monitored for dose-limiting toxicities (DLTs) for 42 days and safety throughout the study. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Dosimetry is included as a supportive analysis. Results: As of the 10-Dec-2025 data cut-off (DCO), 56 participants had been enrolled across Cohorts 1, 2, and 3 and received at least one dose of [ 212 Pb]VMT-α-NET: 2 participants in Cohort 1 (2.5 mCi), 46 in Cohort 2 (5 mCi), and 8 in Cohort 3 (6 mCi). No dose-limiting toxicities, grade 5 adverse events, treatment-related discontinuations, serious renal events, dysphagia, or clinically meaningful treatment-related myelosuppression were observed. The median follow-up for all treated participants was 40 weeks (range 6–97). Efficacy has been summarized in this abstract for 25 participants (2 in Cohort 1 and 23 in Cohort 2). Nineteen of these 25 participants remained progression-free at the time of the DCO, with a median efficacy follow-up of 49 weeks (range 6–97). In Cohort 2, investigators observed RECIST v1.1 objective responses in 9 of 23 participants (39%), including 8 confirmed responses. Both participants in Cohort 1 continued to exhibit stable disease after two years of follow-up. Updated safety for all participants and updated efficacy for participants with sufficient maturity beyond the 25 summarized here will be presented at the congress. Conclusions: Treatment with [ 212 Pb]VMT-α-NET continues to demonstrate a favorable safety profile across all treated participants (n = 56) and shows signs of sustained efficacy at the 2.5 mCi and 5 mCi dose levels. The therapy has been well-tolerated with no observed dose-limiting toxicities or serious treatment-related adverse outcomes. Based on these encouraging safety and efficacy findings, the study is ongoing, and enrollment into Cohort 3 (6 mCi) remains active. Clinical trial information: NCT05636618 .

Abstract Background: [212Pb]VMT-a-NET is a novel, next generation alpha therapy agent for advanced somatostatin receptor 2 positive (SSTR2+) neuroendocrine tumors (NETs). Here, we present safety and efficacy update from the dose-finding phase 1/2a clinical trial (NCT05636618). Methods: Adults with well-differentiated unresectable or metastatic NETs, who were peptide receptor radionuclide therapy-naïve, showed progressive disease after at least one prior line of systemic therapy and demonstrated SSTR2-expression on PET images were treated with up to four cycles of study therapy at the assigned dose level. Participants were followed for dose-limiting toxicity (DLT) observation up to 42 days after the first dose. Efficacy was evaluated by investigators according to RECIST criteria v1.1. Results: As of 10-Dec-2025 (data cut-off [DCO]) a total of 56 participants were enrolled into Cohorts 1, 2 and 3, and received at least 1 dose of [212Pb]VMT-a-NET (n=2 in Cohort 1, n=46 in Cohort 2, and n=8 in Cohort 3 at a dose level of 2.5 mCi, 5 mCi, and 6 mCi, respectively). For data analysis purposes, participants were categorized into two different groups: a safety group and an efficacy group. The safety group included all participants treated by the DCO (n=56), while the efficacy group included only the Cohort 1 participants (n=2) and the first half of participants treated in Cohort 2 (n=23). Among all participants treated with at least 1 dose of [212Pb]VMT-a-NET (n=56), no DLTs, no grade 5 adverse events (AEs), no treatment-related discontinuations, no serious renal complications, no dysphagia and no clinically significant treatment-related myelosuppression were observed. Median follow-up time for all patients treated was 40 weeks (range: 6-97). Among the 25 participants followed for efficacy (n=2 in Cohort 1 and n=23 in Cohort 2), 19 out of 25 were with no progression as of the DCO. Median follow-up time for participants included in the efficacy group was 49 weeks (range: 6-97). Investigator-assessed RECIST v1.1 objective responses were observed in 9 out of 23 participants (39%) enrolled in the first half of Cohort 2 (8 confirmed). The 2 patients enrolled in Cohort 1 at 2.5 mCi still have stable disease after 2 years of follow up. Updated safety outcomes for all participants along with updated efficacy findings for participants in Cohorts 1 and 2 with sufficient maturity will be presented during the congress. Conclusions: Treatment with [212Pb]VMT-α-NET continues to be well-tolerated among all patients treated (n=56), and to show promising efficacy at the dose levels of 2.5 mCi and 5 mCi. The study is ongoing with Cohort 3 (6 mCi) currently open for enrollment. Citation Format: Thorvardur R. Halfdanarson, Richard L. Wahl, Vineeth Sukrithan, Brandon R. Mancini, Seyed A. Mosallaie, Savitha Balaraman, Gregory S. Sibley, Jason Starr, Lowell B. Anthony, Chih Y. Liao, Samuel H. Mehr, Jared Weiss, Robert A. Ramirez, Lucia Baratto, Wenjing Yang, Alaa Hanna, Stephen M. Keefe, Markus Puhlmann, Vikas Prasad. [212Pb]VMT-a-NET in advanced SSTR2+ neuroendocrine tumors: safety and preliminary efficacy results from dose-finding cohorts 1,2 and 3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT088.

We compared demographic and clinical characteristics of patients with gastroenteropancreatic (GEP) and lung neuroendocrine tumors (NETs) enrolled in the NET-PRO study to those in the U.S. Surveillance Epidemiology and End Results (SEER) program to evaluate the comparability of NET-PRO as a resource for real-world evidence generation and patient reported outcomes (PROs). NET-PRO enrolled adults with GEP or lung NETs from 14 health systems between 2018 and 2024. SEER data included patients diagnosed with NETs from 2018 to 2021 across 22 U.S. cancer registries. We compared age, sex, race/ethnicity, tumor site, stage, and surgery between cohorts using standardized mean differences (SMDs), with values ≥ 0.2 interpreted as meaningful. We analyzed 1,974 GEP-NET and 394 lung NET patients in NET-PRO versus 38,942 and 11,265, respectively, in SEER. Most demographic and clinical characteristics were broadly similar between cohorts, with trivial differences by sex (SMDs 0.16–0.22) and moderate differences in mean age (SMD = 0.47 for lung NETs). Race/ethnicity differences were larger, with Non-Hispanic White patients overrepresented in NET-PRO (SMDs 0.53–0.84). Tumor site and stage distributions differed modestly. Surgery rates were comparable for GEP-NETs but higher among NET-PRO lung NET patients (SMD = 0.47). NET-PRO demonstrates broadly comparable demographic characteristics to SEER across factors such as age and sex. While race/ethnicity differences highlight areas for improved inclusion, other areas of variation suggest important future research covariates. These findings support the contextual comparability of NET-PRO with the broader NET population and its value as a resource for real-world evidence generation. NCT05064150 (Start Date: 2022-05-10).

Large cell neuroendocrine carcinomas (LCNECs) of the lung make up only 3.1% of all primary lung cancers, making them highly uncommon when compared to other primary lung cancers. For patients with stage I, II, or III LCNEC of the lung, surgery is the preferred first-line treatment. However, due to high recurrence rates, surgery alone is often insufficient to fully treat patients' disease. Adjuvant therapy utilizing platinum-based chemotherapy has been shown to improve survival in patients with LCNEC. For patients with unresectable or metastatic disease, chemotherapy is generally the first line of treatment, often a combination of either cisplatin or carboplatin with etoposide or irinotecan. However, the low response and survival rates leave room for advancement. There are several other treatments currently being investigated, which will be discussed in this review. Immunotherapy, which is often used to treat small-cell lung cancers, is yet to officially be defined as a treatment for LCNEC of the lung. Additionally, bispecific T-cell engagers (BiTEs) are also being explored in current trials as potential treatments and show promise as a potential treatment. Novel therapies such as chimeric antigen receptor T (CAR-T) cells and oncolytic viruses are being investigated. These studies are critical as patients with large cell neuroendocrine cancers tend to demonstrate poor 5-year survival rates at 35.5%, and even worse rates of 5-year recurrence-free survival at 27.4%. Given the aggressive nature and poor prognosis, further research into this disease is critical. We aim to review and summarize the current literature on systemic treatment in LCNEC.

Background:Pulmonary large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are classified as types of high-grade neuroendocrine carcinoma (HGNEC). The aim of this study was to determine the similarities and differences in clinical features and prognosis between LCNEC and SCLC. Methods:We retrospectively compared the clinical features and prognosis of LCNEC and SCLC, along with well as their two subtypes, including pure LCNEC (P-LCNEC) and combined LCNEC (C-LCNEC) and SCLC combined with LCNEC and SCLC combined with non-LCNEC, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results:We included 341 patients with LCNEC and 580 patients with SCLC who underwent surgical treatment. Significant differences in smoking history, primary site, tumor location, pathological (p) N stage, pTNM stage, and visceral pleural invasion (VPI) were observed between LCNEC and SCLC groups (all P values <0.05). The subgroups of LCNEC (P-LCNEC and C-LCNEC) and SCLC (SCLC/LCNEC and SCLC/non-LCNEC) displayed differences in smoking history, primary site, tumor location, pT stage, pN stage, pTNM stage, VPI, adjuvant chemotherapy, and postoperative adjuvant radiotherapy. LCNEC and its subtypes P-LCNEC and C-LCNEC were associated with superior DFS and OS than were SCLC and its subtypes SCLC/LCNEC and SCLC/non-LCNEC (DFS: P=0.008, P=0.001, P=0.049; OS: P=0.005, P=0.005, P=0.006). Compared to patients who did not receive adjuvant chemotherapy, those with stage I SCLC or LCNEC who underwent adjuvant chemotherapy demonstrated a significantly improved DFS (P=0.005 and P=0.048) and OS (P=0.004 and P=0.03). Conclusions:LCNEC and SCLC, as well as their subtypes, have distinct clinical features and survival outcomes. SCLC exhibited more malignant biological behavior and was associated with a worse prognosis compared to LCNEC. Postoperative chemotherapy is recommended for patients with stage I HGNEC.

824 Background: Timely detection of appendiceal malignant tumors is a clinical priority because of the propensity for this malignancy to metastasize to the peritoneal cavity. Up to one in every 2 patients with this rare tumor type will present with distant metastatic disease, owing to there being no standardized screening tests for early detection of primary appendiceal cancers. Case reports have pointed to broad/non-specific symptoms of patients diagnosed with appendiceal malignant tumors, yet information is needed from large cohorts to support prompt/accurate clinical diagnoses. Methods: We analyzed data from patients with a pathologically-confirmed first primary appendiceal malignant tumor (AC) who prospectively enrolled in the nation-wide Genetics of Appendix Cancer [GAP] clinical cohort study (Clinicaltrials.gov, NCT05734430) between November 2022 and May 2024. The primary outcome was presenting symptoms that led to AC diagnosis. Symptom effects and interactions with diagnosis age/year, sex, body mass index (BMI), and tumor histology, were quantified with negative binomial regression models and presented as incidence rate ratios (IRRs) and 95% confidence intervals. Results: Of the 352 patients included in our analyses (median [IQR] age, 51.0 [42-59] yr), 77.6% were female and 96.6% had an adenocarcinoma histology. Seventy-seven percent of patients (n=270) reported one or more presenting symptoms, of whom 55.2% (n=149) experienced these symptoms for 3+ months prior to diagnosis. On average, patients reported 3 symptoms (mean: 2.9, SD 3.0). The most prevalent symptoms among males and females were abdominal pain (57.1%), bloating/distension (32.1%), pelvic pain (18.5%), and abdominal/pelvic mass (18.2%). Overall, patients with early-onset AC [age<50] more commonly presented with symptoms versus cases with late-onset AC (82.9% vs 71.7%, p =0.01). This finding persisted in adjusted models—the number of symptoms was highest among younger patients, rapidly decreased and plateaued around age 50 (IRR 0.97, 95%CI 0.95-0.99, p =0.002), and slowly increased again with older age (IRR 1.03, 95%CI 1.00-1.05, p =0.037). Patient sex was also significantly associated with symptom number, as males had a lower rate of symptoms versus females (IRR 0.63, 95%CI 0.48-0.83, p =0.001). In contrast, histology (IRR 1.03, 95%CI 0.53-2.02), diagnosis year (IRR 1.01, 95%CI 0.99-1.04, p =0.35) and BMI (IRR 1.01, 95%CI 0.99-1.02) were not associated with symptom number in adjusted models. Conclusions: In a large nation-wide cohort, three of every 4 patients were symptomatic prior to primary AC diagnosis. Compared to the rapid time course of acute appendicitis, over 40% of this population presented with symptoms for 3+ months prior to AC diagnosis. The higher symptom burden among young patients and females supports the need for clinical providers to keep occult appendiceal tumors in the differential diagnosis of patients presenting in this manner.

Background/Objectives: Since 177Lu-DOTATATE was approved for patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (NETs), tumor flare reactions including increased pain and small bowel obstruction (SBO) have been reported. Retrospective reviews report some success in using corticosteroids for treatment and prophylaxis of tumor flare reactions from 177Lu-DOTATATE. Given that corticosteroids are used in practice to help prevent tumor flare reactions based on limited evidence, we aimed to assess if this practice was efficacious in our patient population. Methods: In this retrospective and single-institution study, we identified adult patients with NETs who were treated with 177Lu-DOTATATE between 1 October 2019 and 31 December 2024; these patients received corticosteroids as prophylaxis for flare reactions due to high burden of disease, significant peritoneal or mesenteric disease, or disease involvement of critical structures as determined by the treating provider. Variables including demographics, diagnosis, treatment history, steroid dosing, and outcomes were collected within a RedCAP database. Results: Forty-six patients were identified as having received corticosteroid prophylaxis to prevent a tumor flare reaction due to 177Lu-DOTATATE. Patients had a median age of 66, and 50% were female. The primary disease site was the small intestine (72%) followed by the pancreas (9%). The majority of patients had World Health Organization (WHO) grade 1 (41%) or WHO grade 2 (35%) diseases. Most patients (83%) received corticosteroids prior to the initiation of 177Lu-DOTATATE, while 17% of patients received corticosteroids due to having a previous tumor flare after 177Lu-DOTATATE administration. Despite corticosteroid prophylaxis, 28% of patients still experienced a tumor flare event, with three patients experiencing multiple tumor flare events. Small bowel obstructions occurred in 7% of patients and increased abdominal pain in 22% of patients. Adverse events (AEs) due to corticosteroids occurred in 28% of patients. Conclusions: Short-course corticosteroid prophylaxis to prevent tumor flare reactions in high-risk patients with neuroendocrine tumors treated with 177Lu-DOTATATE did not appear to decrease the incidence of tumor flare reactions compared to previously reported numbers. Randomized, placebo-controlled trials looking at the use of corticosteroids to prevent tumor flare reactions in patients treated with 177Lu-DOTATATE are needed to fully elucidate the safety and efficacy of corticosteroids used in this setting and to determine the impact on treatment outcomes.

Pulmonary neuroendocrine tumors represent a spectrum of disease ranging from typical carcinoid tumors to small cell lung cancers. The incidence of low-grade pulmonary NETs has been increasing, leading to improved awareness and the need for more treatment options for this rare cancer. Somatostatin analogs continue to be the backbone of therapy and may be followed or accompanied by targeted therapy, chemotherapy, and immune therapy. The recent addition of peptide receptor radionuclide therapy (PRRT) to the treatment armamentarium of NETs has led to the development of targeted alpha therapy to overcome PRRT resistance and minimize off-target adverse effects. Herein, we aim to highlight current treatment options for patients with advanced low grade pulmonary NETs along with emerging therapies, sequencing of therapies, upcoming clinical trials, and the importance of a multidisciplinary team to improve patient outcomes.

Background: Stereotactic body radiotherapy (SBRT) is a precise and effective treatment for pulmonary oligometastases, offering high local control (LC) rates. However, the optimal SBRT dose when combined with immunotherapy remains unclear, and there is a lack of comprehensive studies focusing on dose optimization in this setting. This study addresses this knowledge gap by exploring different SBRT dose regimens and their impact on progression-free survival (PFS), overall survival (OS), and LC in patients receiving concurrent immunotherapy, offering novel insights into the synergistic effects of these treatments. Methods: A retrospective cohort study was conducted of 101 patients with 141 pulmonary oligometastases treated from April 2018 to April 2022. Inclusion criteria included patients with a maximum of five lung metastases and an Eastern Cooperative Oncology Group performance status of <= 2. Patients received SBRT with doses ranging from 50-70 Gy in 5-10 fractions. Follow-up was performed quarterly, and the best dose was determined by comparing survival outcomes across different dose groups. The patients received SBRT with doses ranging from 50-70 Gy in 5-10 fractions. Patient demographics, tumor characteristics, treatment details, and outcomes were collected. The Kaplan-Meier method was used for the survival analysis, and Cox regression models were used to identify prognostic factors for LC, PFS, and OS. Results: The median follow-up for the 101 patients was 22.4 months (range, 1-58 months). The cohort comprised 82.2% male patients with a median age of 64 years (range, 36-81 years). The majority of the patients (64.4%) had primary tumors originating from non-lung sites, with adenocarcinoma being the predominant histological subtype (47.5%). The median tumor size was 13.5 mm. Across the entire cohort, the median OS was 39 months, and the median PFS was 11 months. Pre-treatment with immunotherapy significantly improved outcomes: the PFS increased to 13 months compared to 7 months for those who did not receive immunotherapy [P=0.02, hazard ratio (HR) = 0.523, 95% confidence interval (CI): 0.302-0.906], and the OS was also significantly improved (P=0.008, HR =0.411, 95% CI: 0.214-0.792). The SBRT regimen of 60 Gy in 10 fractions provided the best outcomes, with a median OS of 39 months, a median PFS of 10 months, and a LC rate of 92.4%, with relatively low toxicity compared to other regimens. Conclusions: SBRT is a potent, minimally invasive option for managing pulmonary oligometastases, especially when preceded by immunotherapy. The 60 Gy in 10 fractions regimen demonstrated significant efficacy in terms of OS and LC, while maintaining manageable toxicity. Although the retrospective nature of the study introduces some selection bias, this dose regimen appears to offer a promising therapeutic option for pulmonary oligometastases. Further validation through well-designed prospective studies would help confirm the optimal SBRT dose and clarify the role of immunotherapy in this setting.

Background:The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease.Case Description:We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery.Conclusions:This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.