Common Primary Site Research Articles

Investing Peripheral Monocytes, Targeted Therapy and Treatment Outcomes in Erdheim Chester Disease

Introduction Erdheim Chester Disease (ECD) is a rare, non-Langerhans cell histiocytic disease, characterized as a clonal hematopoietic malignancy in 2016. MAP Kinase and PI3-AKT pathway somatic mutations and/or fusion genes play a significant role in disease pathogenesis, and now shape the landscape of targetable treatment options for this patient population. Additionally, previous research has shown that patients with ECD have a higher frequency of concomitant myeloid neoplasms, with clonal hematopoietic mutations detected in peripheral monocytes in such patients. Methods A retrospective analysis of 19 patients diagnosed with ECD at a single institution over a twenty-year period (2002-2022) was conducted. Inclusion criteria included patients age ≥18, histopathologic diagnosis of ECD, and clinical correlation of disease. The following clinical information was collected for each patient: demographics, molecular diagnostics (if utilized), imaging, treatments rendered and best treatment outcomes. Clinical treatments were divided into ‘conventional’ treatments including chemotherapy, immunotherapy, systemic corticosteroids, surgery or radiation, or targeted therapy including all small molecular inhibitors. Information was translated into binary data for comparison of outcomes by treatment type, time to diagnosis and use of targeted agents. Statistical analysis was performed by unpaired-T tests. Variation in treatment response assessment depended on several factors including the anatomic site(s) of disease, extent of disease burden at diagnosis and imaging modality used to assess disease. Determination of stable, progressive, or complete response was made using RECIST assessments (if CT or MR imaging used) or PERCIST assessments (if PET utilized), in addition to overall clinical response. Results In this analysis, 47% of the patients were females; average age at diagnosis was 51.2 years. 36% of patients were diagnosed within 12 months of symptoms onset. Molecular diagnostics were utilized in 100% of patients, (immunohistochemistry 94%, and sequencing 26%). The most common mutations identified were BRAFV600E (7 of 19) and CD68 (7), followed by CD163 (6), S100+ (5) and specific MAP Kinase pathway mutations (3). Most common primary disease site was extranodal (94% of patients), followed by osseous (63%), dermal (52%) and the central nervous system (36%). 57% of patients were treated with targeted therapy, followed by myelosuppressive therapy and steroids (42%), immunotherapy and radiation (10% each). Partial response or better was observed in 83% of patients. Stable disease was seen more often in patients treated with conventional therapy (33%) as compared to patients treated with targeted molecular therapy (11%) and partial response more often in patients treated with targeted therapy (55%). Complete response was more common with conventional therapy than molecular (66 % versus 33%). Lastly, an evaluation of peripheral blood absolute monocytes in all patients who had progressed on therapy identified a decrease in pre-progression absolute monocytes compared to post-progression monocytes after re-initiation of therapy by a mean value of 0.2 K/µL, although results were imprecise (p = 0.3125, 95% CI -0.2373 to 0.6373) (Figure 1A). A decrease in pre-therapy absolute monocytes compared to post-therapy monocytes was observed as well (averages of.0.49 and 0.33 respectively; p = 0.0988, 95% CI -0.0302 to 0.3408) (Figure 1B). Conclusions Peripheral monocytes have been discovered to play a role in histiocytic disease, but to our knowledge, we are the first to look at progression and activity in ECD, as ECD is not commonly known to have overt blood or marrow disease. We theorize that an increase in circulating monocytes may exist as a direct response to disease progression as monocytes may differentiate into dendritic cells and upregulate major histocompatibility class II expression, although this mechanism remains poorly understood. This observation may further explain the high frequency of concomitant myeloid malignancies seen in patients with ECD who have also been found tp harbor clonal hematopoietic mutations in peripheral blood monocytes. Based on our findings, we advocate for the use of absolute monocyte count as an early marker for disease activity or progression. Further studies to explore this trend are in progress.

Malignant Histiocytic Neoplasms' Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background: Malignant histiocytosis, also known as the M-group per the Histiocyte Society classification, represents a rare, aggressive malignant group of histiocytic neoplasms. It includes histiocytic neoplasms that occur de novo (pMHN) and those that develop in association with other malignant diseases (aMHN). However, little is known about factors that impact MHN clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this rare histiocytic group. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 270 cases of MHN. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 270 patients with confirmed MHN were identified, with 77% pMHN and 23% aMHN. The median age was 45, with bimodal peaks between 13-26 and 52-65. There was a male preponderance with M:F of 1.6. The most common primary sites of involvement were liver (15%), CNS and spleen (13% each), thoracic, GI, and soft tissues (12% each), bones (11%), skin (10%), and H&N (8%). Lymphadenopathy and bone marrow (BM) were involved in 28% and 18%, respectively. Constitutional symptoms occurred in 12% and hemophagocytic syndrome (HPS) in 6%. The median time of MHN onset in aMHN was 12 months. The median OS of the whole group was 12 months. BM involvement had a worse median OS (p = 0.003). Stage 1 disease had better median OS than higher stages (p = 0.01). Furthermore, unifocal had better median OS than multifocal/multicentric disease (p = 0.0005). The presence of inflammatory background positively impacted OS (p = 0.01). The occurrence of HPS adversely affected OS (p < 0.0001). Compared to no treatment, localized therapies such as surgery (S) and/or radiation therapy (RT) and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 3, 24, and 18 months, respectively (p = 0.02). When MHN was not amenable to complete resection, CT and CT+/-S+/-RT were superior to RT+S (p = 0.03). Having CNS or splenic-lymphatic primary involvement tended to have a numerical but non-significant worse median OS than soft tissue or visceral disease. While female sex, size<10cm, and pMHN seemed to have numerically better OS, they did not reach statistical significance. There was no difference in median OS for age. Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with MHN. It identifies BM involvement, stage, extent of the disease, the inflammatory background status, occurrence of HPS, and treatment approach as critical determinants of OS.

Epidemiology and Survival Outcomes in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A US Population-Based Study

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematological malignancy arising from plasmacytoid dendritic cell precursors. BPDCN remains poorly understood due to its rarity, constantly changing nomenclature, and defining criteria. This study using the Surveillance, Epidemiology, and End Results Program (SEER) database is the largest and most recent population-based study in BPDCN. We aimed to determine the incidence, clinical characteristics, overall survival, and prognostic factors in BPDCN. Methods: Patients diagnosed with BPDCN from 2000-2019 were identified from the SEER 17 database using the International Classification of Disease for Oncology, 3 rd edition (ICD-O-3) code 9727. Patient characteristics, treatment, and survival information were obtained. Age-adjusted incidence rate per 100,000 population and incidence rate ratio (IRR) were calculated using SEER stat software with the year 2000 US population as the reference standard. Overall survival and prognostic factors were evaluated based on univariate survival analysis using Kaplan-Meier plot with log-rank test, and Cox proportional hazard regression model for multivariate survival analysis. All statistical analyses were conducted with a two-sided significant p value of <0.05 using SEER stat software and STATA software version 15.1. Results: A total of 844 patients with BPDCN were included in the study. The median age at diagnosis was 40 (IQR: 15-68) with majority < 20 years (32.5%) or > 60 years (34.3%) . Majority were males (68.1%) and Caucasians (83.5%). The lymph node was the most common primary site of involvement (56.6%) followed by the bone marrow (19.1%) and skin (13%). . Eighteen percent of the cohort received radiation therapy and 83.6% received chemotherapy. The overall incidence of BPDCN was found to be 0.05 cases per 100,000 population. Incidence was significantly lower in females than males (IRR 0.62, p < 0.01) and in African Americans compared to Caucasians (IRR 0.70m, p<0.01). There was no significant change in disease incidence from 2005 to 2019. Survival rates at 1 year, 2 years and 5 years were found to be 70%, 56% and 41% respectively. On univariate analysis, age > 60 years (p <0.01) and male gender (p< 0.01) was associated with significantly worse overall survival while survival did not differ by race (p=0.10). On multivariate analysis after adjusting for age, sex, race, marital status, radiation therapy, chemotherapy and disease primary site, age > 60 years (HR 2.70; 95% CI 2.01-3.54, p<0.01) and African American race (HR 1.44; 95% CI 1.01-2.04, p<0.04) was associated with worse overall survival. Conclusion: To our knowledge, this is the largest and most recent population-based study in BPDCN. Our study revealed a population level incidence of 0.05 cases per 100,000 population. Majority are Caucasian males with bimodal age distribution (<20 years and above 60 years). The lymph nodes are the most common site of involvement. Older age and African American ethnicity are negative prognostic factors for overall survival. Racial disparities in OS warrant further prognosis. More prospective studies are needed to determine disease characteristics and optimal treatment approaches for this rare life-threatening hematological malignancy.

GLI1-Altered Mesenchymal Tumors With ACTB or PTCH1 Fusion: A Molecular and Clinicopathologic Analysis

Mesenchymal tumors with GLI1 fusions or amplifications have recently emerged as a distinctive group of neoplasms. The terms GLI1-altered mesenchymal tumor or GLI1-altered soft tissue tumor serve as a nosological category, although the exact boundaries/criteria require further elucidation. We examined 16 tumors affecting predominantly adults (median age: 40 years), without sex predilection. Several patients had tumors of longstanding duration (>10 years). The most common primary site was soft tissue (n = 9); other sites included epidural tissue (n = 1), vertebra (n = 1), tongue (n = 1), hard palate (n = 1), and liver (n = 1). Histologically, the tumors demonstrated multinodular growth of cytologically uniform, ovoid-to-epithelioid, occasionally short spindled cells with delicate intratumoral vasculature and frequent myxoid stroma. Mitotic activity ranged from 0 to 8 mitoses/2 mm2 (mean 2). Lymphovascular invasion/protrusion of tumor cells into endothelial-lined vascular spaces was present or suspected in 6 cases. Necrosis, significant nuclear pleomorphism, or well-developed, fascicular spindle-cell growth were absent. Half demonstrated features of the newly proposed subset, “distinctive nested glomoid neoplasm.” Tumors were consistently positive for CD56 (n = 5/5). A subset was stained with S100 protein (n = 7/13), SMA (n = 6/13), keratin (n = 2/9), EMA (n = 3/7), and CD99 (n = 2/6). Tumors harbored ACTB::GLI1 (n = 15) or PTCH1::GLI1 (n = 1) fusions. The assays used did not capture cases defined by GLI1 amplification. We also identified recurrent cytogenetic gains (1q, 5, 7, 8, 12, 12q13.2-ter, 21, and X). For patients with available clinical follow-up (n = 8), half were disease free. Half demonstrated distant metastases (lungs, bone, or soft tissue). Of cases without follow-up (n = 8), 2 were known recurrences, and 1 was presumed metastasis. Our results imply a more aggressive biological potential than currently reported. Given the possibility for metastasis and disease progression, even in cytologically bland, nested tumors, close clinical surveillance, akin to that for sarcoma management, may be indicated. The term GLI1-altered mesenchymal tumor with malignant potential is proposed.

Minimally Invasive Approach to Access Vessels for Microvascular Anastomosis in Head and Neck Reconstruction.

To describe our technique, review indications, and evaluate the outcomes of the minimal access approach for recipient vessel identification in microvascular tissue transfer. Retrospective chart review of all patients who underwent microvascular reconstruction using the minimal access technique between 2015 and 2021. We report 236 cases, comprising 214 patients with a mean age of 60.2 years (3-88). The most common primary defect sites were the mandible (22.6%), cranium (14%), maxilla (13.2%), skull base (12.8%), and nose/nasal cavity (10.6%). Indications for free flap reconstruction included head and neck cancer extirpation (32.2%), osteoradionecrosis (29.7%), acquired deformity (14.0%), chronic wound (11.9%) and oral motor dysfunction (7.2%). Free flap donor sites used were the anterolateral thigh (84.3%), fibula (7.2%), and radial forearm (6.4%). Vessels utilized include superficial temporal (49.8%), facial (38.3%), angular (11.1%), and transverse cervical (0.4%). The overall complication rate was 14% (n = 33), with surgical complications at the recipient site accounting for 67.6% (n = 25). Flap failure occurred in 3.4% of procedures. Prior head and neck surgery and free flaps were associated with an increased risk of major recipient site complications (n = 20, p = 0.0257 and n = 14, p = 0.0117, respectively). Minimal access techniques allow consistent recipient vessel identification for microvascular-free tissue transfer. These approaches may be utilized in reconstructing a broad range of head and neck defects, are low morbidity, and contribute to an overall shorter length of stay. 2 Laryngoscope, 134:2177-2181, 2024.

Epidemiology and Survival of Patients with Marginal Zone Lymphoma Treated at the National Cancer Institute of Peru. a Retrospective Analysis of 187 Cases

Background Marginal zone lymphoma (MZL) represents a heterogeneous subgroup, classified as extranodal, splenic and nodal lymphoma. Extranodal cases, also termed mucosa-associated lymphoid tissue (MALT), account for 70% of MZLs. Splenic marginal zone B-cell lymphoma (SMZL) accounts for <2% of all NHL. There is no data about marginal zone lymphoma in Latin American patients. Methods We evaluated retrospectively all patients diagnosed with marginal zone lymphoma at the National Cancer Institute from 2010 to 2019. Baseline characteristics, treatments and survival were retrieved from medical records. Kaplan Meier method was used to analyze the overall survival. The estimate of the survival curves was performed by the Kaplan-Meier method, and the differences were computed by the log-rank test. The Cox proportional hazard models were used to identify predictors of survival of MZL. A level of p <0.05 was considered for a statistical significance. Results During the study period 2010-2019, 4437 patients with B-cell non-Hodgkin lymphoma were evaluated at the INEN, 187 of them were marginal zone lymphomas, representing 4.2% of all cases. The most frequent marginal zone lymphoma was MALT, followed by nodal and splenic lymphoma with 89.8%, 5.3% and 4.8% of cases, respectively. The median age for the entire cohort was 59 years (range 17-89). The median age for the MALT, nodal and splenic MZL cohort were 58.5 years (range 17-89), 75 years (range 52-88), 68 years (range 43-87), respectively. 37.4% were male for the entire cohort, and 37%, 40%, 44% for the MALT, nodal and splenic MZL group. Elevated LDH was seen in 13% of the entire cohort and in 11% and 24% of the MALT and splenic MZL group. Transformed lymphoma was reported in 6.4% of the entire cohort, but in the 20% of nodal MZL and no one case of the splenic MZL. More data you can see in the table 1. The most frequent primary site locations for MALT lymphoma were gastric, ocular adnexal, parotid gland, cutaneous, intestinal and CNS with 36%, 30%, 7%, 5%, 5% and 5%, respectively. The median overall survival was 114 months (IQR 76-133) for the entire cohort and 133 months, 59 and 59 months for the MALT, nodal MZL, and splenic MZL, respectively (p=0.0011), see the figure 1. The 5-year OS was 81.4% (95% CI, 71.6-88.1) for the entire cohort and 85.7% (95% CI, 76.5-91.5) for the MALT lymphoma group. No one patients were alive at 5 years in both nodal and splenic lymphoma groups. Conclusion Marginal zone lymphoma is a relatively rare type of B-cell lymphoma. The most frequent type is MALT lymphoma, followed by nodal MZL. The median age for the entire group was 59 years, however patients with nodal MZL were older with a median age of 75 years. Transformed lymphoma was present in 6% of the entire cohort and in the 20% of the nodal MZL. Gastric, ocular adnexal and parotid gland were the most common primary site of MALT lymphoma. MALT lymphoma had long survival, but nodal and splenic MZL had shorter survival with no one surviving 5 years from diagnosis.

Interdigitating Dendritic Cell Sarcoma and Indeterminate Dendritic Cell Tumor: Patient Characteristics, Prognostic Factors, and Survival Outcomes for Rare Dendritic Cell Neoplasms

Background Dendritic cells are nonlymphoid, nonphagocytic, antigen-presenting cells present in lymphoid and nonlymphoid tissue. There are 4 types of dendritic cells: follicular, interdigitating, Langerhans, and fibroblastic cells. The WHO 2022 classification system groups dendritic cell and histiocytic neoplasms into 3 categories: plasmacytoid dendritic cell neoplasms, Langerhans cell and other dendritic cell neoplasms, and histiocytic neoplasms. The 2nd category is subdivided into “Langerhans cells neoplasms” and “other dendritic cell neoplasms”, which contains indeterminate dendritic cell tumor (IDCT) and interdigitating dendritic cell sarcoma (IDCS). The 2022 classification eliminated follicular dendritic cell sarcoma (FDCS) as it is no longer thought to be of hematopoietic origin. A prior Surveillance, Epidemiology, and End Results (SEER) review published in 2013 by Perkins and Shinohara grouped FDCS and IDCS and included 20 cases of IDCS diagnosed between 2001 and 2008. To our knowledge, this is the first update of epidemiologic and survival data for non-Langerhans cell and non-plasmacytoid dendritic cell neoplasms since the WHO reclassification. Methods We used the SEER 22 database, which collects data from cancer registries covering approximately 47.9% of the U.S. population. We selected all patients with cancers falling in the “other dendritic cell neoplasms” category according to the WHO 2022 classification from 2000-2020 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code of 9757/3, which codes for IDCS but also includes IDCT. The Kaplan-Meier method was used to display the survival curves. The Cox proportional hazards model was used to determine p values. Results A total of 72 cases of IDCS/IDCT were identified. Median follow up was 19 months and median OS for the entire cohort was 24 months (95% CI 10-92 months). Of these patients, 61.1% (n=44) were White, 16.7% (n=12) were Hispanic, 13.8% (n=10) were Black, 5.6% (n=4) were Asian or Pacific Islander, and 2 patients were of unknown race. IDCS/IDCT was more common in males than females with a ratio of 1.77. The most common primary sites of involvement were connective tissue in 40.2% (n=29), head and neck in 16.7% (n=12), lymph nodes in 11.1% (n=8), and bone marrow in 8.3% (n=6). Patients with bone marrow involvement had a trend towards worse OS (median OS of 5 months). IDCS/IDCT is more common in adults but does occur in children and adolescents. Only 6 cases were diagnosed in patients under the age of 20 years. Patients who were under the age of 60 years at diagnosis had a median OS of 155 months compared to a median OS of only 10 months for patients who were 60 years or older at diagnosis (Figure 1, p<0.001). Staging was unknown in 12 patients. Of patients with known staging, 56.7% (n=34) had localized disease and 43.3% (n=26) had metastatic disease. Patients with localized disease at diagnosis had a better prognosis with a median OS of 120 months compared to 5 months for patients with metastatic disease at diagnosis (Figure 2, p<0.001). Treatment modality was unknown in 29 of the patients. Of patients with known treatment, 34.9% (n=15) had surgery alone, 20.9% (n=9) had chemo alone, 16.3% (n=7) had radiation alone, and 27.9% (n=12) had combination treatment. Single modality treatment regimens were most popular in patients with localized disease with 48% (n=12) of the patients with known treatment modality getting surgery alone, followed by radiation alone at 24% (n=6).The most common cause of death in this cohort was IDCS/IDCT with 76% of deaths being attributed to the cancer (n=35, there were 46 total deaths). Conclusions Though cases of IDCS and IDCT have more than tripled since 2008, it still remains the rarest type of dendritic cell neoplasm. Connective tissue, head and neck, and lymph nodes were the most common sites involved. Surgical resection was the most common treatment modality followed by chemotherapy. Clinical presentation is rare in patients under the age of 20 years. Age 60 years and older and metastatic disease were associated with poor outcomes with a signal towards worse survival when bone marrow was involved. Our study updates current knowledge of IDCS/IDCT and highlights some of the unknowns in this type of neoplasm, particularly regarding other prognostic factors including treatment effect on survival.

Gastrointestinal stromal tumor in North Africa and the middle east: updates in presentation and management from an 11-year retrospective cohort

ABSTRACT Objectives This study described the epidemiological, clinical, and survival profiles of patients with gastrointestinal stromal tumor (GIST) in North Africa and the Middle East (AfME). Methods This regional, multicenter, observational, retrospective study collected 11-year data on demographics, medical history, disease characteristics, current treatment approaches of GIST, the safety of the most common tyrosine kinase inhibitors (TKIs), second cancers, and survival status. Results Data of 201 eligible patients were analyzed: mean age was 56.9 ± 12.6 years; 111 (55.2%) patients were men, 21 (10.4%) patients had previous personal malignancy. The most common clinical presentation of GIST was dysphagia [92 (45.8%) patients]. The stomach was the most common primary site in 120 (60.7%) patients, 171 (85.1%) patients had localized disease at diagnosis. 198 (98.5%) GIST cases were CD117/CD34-positive. Imatinib was used in the neoadjuvant (18/21 patients), adjuvant (85/89 patients), and first-line metastatic treatment (28/33 patients) settings. The most common non-hematological toxicity associated with TKIs was vomiting in 32/85 (37.6%) patients. Overall, 100 (49.8%) patients (95%CI: 42.8–56.7%) were alive and disease-free while 30 (14.9%) patients were alive with active disease. Conclusion Presentation of GIST in our AfME population is consistent with global reports, being more frequent in patients >50 years old and having the stomach as the most common primary site. Unlike what is usually reported, though, we did have more patients with lymphatic spread of the disease. Despite the global trend and advances in the treatment of GIST according to molecular profile, this is still far to happen in our population given the lack of access to molecular profiles and the high associated cost.

Gender differences in pediatric and adolescent melanoma: A retrospective analysis of 4645 cases

There is paucity of data on how genderimpacts melanoma prognosis in pediatric and adolescent patients. This study explores gender differences in presentation and survival among pediatric and adolescent patients with melanoma. The National Cancer Database 2004-2018 was queried for cases of primary invasive cutaneous melanoma in pediatric and adolescent patients (birth to 21years) for a retrospective cohort study. Of the 4645 cases, 63.4% were female. Median Breslow depth was 1.05mm for males (interquartile range 0.50-2.31) and 0.80mm for females (interquartile range 0.40-1.67; P<.001). Trunk was the most common primary site for females (34.3%) and males (32.9%). More females than males were diagnosed with stage I disease (67.8% vs 53.6%). Males had higher rates of regional lymph node positivity (27.9% vs 18.1%; P<.001) and ulceration (17.1% vs 11.4%; P<.001). Five-year overall survival was 95.9% for females and 92.0% for males (P<.001). After adjusting for confounders, male gender independently increased mortality risk (reference: females; adjusted hazard ratio 1.57; 95% confidence interval 1.32-1.86). Retrospective study. Males exhibited more aggressive pathologic features including greater Breslow thickness and higher ulceration and lymph node positivity rates. Male gender independently increased mortality risk.

Prognosis of children and young adults with newly diagnosed rhabdomyosarcoma metastatic to bone marrow treated on Children's Oncology Group studies.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Metastatic disease occurs in 16% of all RMS cases and has a poor prognosis. There are limited studies examining the outcomes specific to patients with RMS metastatic to bone marrow despite an incidence of 6% at diagnosis. Our study aims to document the outcomes, prognostic factors, and clinical courses of children presenting with RMS metastatic to bone marrow treated on Children's Oncology Group (COG) cooperative trials. We performed a retrospective analysis of the patients diagnosed with RMS metastatic to bone marrow between 1997 and 2013 enrolled on one of four COG RMS clinical trials of D9802, D9803, ARST0431, and ARST08P1. We identified 179 cases with RMS metastatic to bone marrow. Patients had a median age of 14.8years, 58% were male, predominantly alveolar histology (76%), extremity was the most common primary site (32%), and 87% had metastatic disease to additional sites; 83% (n=149) received radiation as a treatment modality. The 3- and 5-year event-free survival was 9.4% and 8.2%, respectively. The 3- and 5-year overall survival was 26.1% and 12.6%, respectively. Age ≥10years, alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation were identified as poor prognostic/predictive characteristics. This study represents the largest analysis of RMS metastatic to bone marrow, defining the poor prognostic outcome for these patients. These patients may be eligible for therapy deintensification or early pursuit of novel treatments/approaches that are desperately needed.

Efficacy of Single-Fraction Postoperative Radiotherapy in Resected, Early-Stage Merkel Cell Carcinoma with High-Risk Features

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high recurrence risk. Postoperative radiotherapy (PORT) improves the local recurrence rate (LRR) in early-stage MCC with risk factors per NCCN guidelines: primary tumor size > 1cm, head/neck (HN) location, immunosuppression, lymphovascular invasion (LVI), and positive/narrow surgical margins. Conventionally fractionated PORT (C-PORT, ∼50 Gy in 25 fractions) is often recommended for localized MCC with these risk factors; however, some institutions elect observation. Prior studies suggest LRR of ∼20% for stage I/II MCC with high-risk features managed with surgery alone. C-PORT significantly decreases LRR but may cause significant morbidity and financial toxicity. We have previously reported that single fraction (SF)-PORT with 8 Gy achieves high rates of in-field control both in the metastatic and adjuvant settings with minimal morbidity. Here, we present updated long-term outcomes of SF-PORT, offered as an alternative to C-PORT with the hypothesis that it improves LRR relative to observation while minimizing toxicity, for resected stage I/II MCC. A retrospective, single-institution analysis was completed for stage I/II MCC patients receiving SF-PORT following surgical management. The primary objective was estimating the LRR, defined as recurrence within 2 cm of the primary tumor. Patients with resected, stage I/II MCC with at least one high-risk feature were offered C-PORT as standard of care or SF-PORT as an alternative. Forty-six patients (median age: 74.5; range 50-96 years) received SF-PORT to the primary tumor site at a median 44 days after wide local excision (85%), shave/excisional biopsy (13%), or Mohs (2%). Fifty-four percent of patients had 1 high-risk feature, 35% had 2, and 11% had 3 or more. HN (74%) was the most common primary site, 26% of tumors were > 1cm, 26% were LVI+, and 15% of patients were immunosuppressed (pathological margin status was often not available). There were no local recurrences (LRR = 0%) at a median follow-up time of 2.3 years. In-field locoregional control was 96% (44/46 patients) with 2 in-field, regional recurrences observed in draining nodal basins of HN primary lesions. There were 2 out-of-field regional nodal recurrences (1 patient with IMS; neither received elective nodal SFRT). Of 9 patients who received elective nodal SF-PORT, 8 did not have a successful sentinel lymph node biopsy. No MCC-specific deaths were observed. The most common side effect was in-field, grade 1 erythema (13%); no side effects > grade 1 (CTCAE v5) were noted. SF-PORT is associated with a very low LRR which has proven durable with long-term follow-up. The LRR for SF-PORT appears lower than historical controls treated with surgery alone for patients with resected, stage I/II MCC with high-risk features.

Stereotactic Ablative Radiotherapy for Oligo-Progressive Cancers: Results of the Randomized Phase II STOP Trial

In the metastatic setting, there is uncertain benefit to localized eradication of one or more lesions that are progressing despite systemic therapy. This randomized phase II trial examined if patients with ≤5 sites of oligoprogression benefited from the addition of stereotactic ablative radiotherapy (SABR) to standard of care (SOC) systemic therapy. Eligibility criteria included age ≥18 years, ECOG performance status 0-2, and oligoprogressive disease, defined as 1-5 lesions actively progressing while on systemic therapy. Patients were required to have at least 3 months of disease stability/response on systemic therapy prior to oligoprogression. After stratifying by type of systemic therapy (cytotoxic vs. non-cytotoxic), patients were randomized 2:1 to SABR to all progressing lesions plus SOC (SABR arm) vs. SOC alone (SOC arm). The trial began exclusive to non-small cell lung cancer but did not meet accrual goals and was expanded in 2019 to include all non-hematologic malignancies. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life (QOL), toxicity, and duration of current systemic agent post-SABR. Between February 2017 and June 2021, 90 patients with 125 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 patients randomized to SABR and 31 to SOC. Median age was 67 years (IQR: 61-73 years) and 39 (43%) were female. The most common primary sites were lung (44% of patients), genitourinary (23%) and breast (13%), with the most common oligo-progressive locations being lung (43%), bone (19%), lymph nodes (14%), and liver (13%). In the SABR arm, the most common fractionations were 35 Gy/5 (38% of lesions) and 50 Gy/5 (18%). Protocol adherence in the SOC arm was suboptimal: 3 patients (10%) withdrew immediately after randomization, and 7 additional patients (23%) received high-dose or ablative therapies. Median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs. 4.3 months in the SOC arm; however, the curves cross and 2-year PFS was 9% vs. 24% respectively, p = 0.91). Median OS was 31.2 months vs. 27.4 months, respectively (p = 0.22). Lesional control with SABR was 71% vs. 39% with SOC (p = 0.002). Median duration of post-randomization first-line systemic therapy was 10.3 months vs. 7.6 months, respectively (p = 0.71). Treatment was well-tolerated with 2 (3.4%) grade 3 treatment-related toxicities in the SABR arm and no grade 4/5 related events in either arm. QOL did not differ between arms. Despite being a well-tolerated treatment providing superior lesional control, SABR for oligoprogression did not improve PFS or OS. Results may have been impacted by withdrawals and desire for ablative treatments on the SOC arm, and this lack of equipoise may make accrual to phase III trials difficult, although larger studies in select sub-populations are desired. (NCT02756793).

Feasibility of a Keratin-Based Topical Cream for Radiation Dermatitis in Patients with Head and Neck Cancer: Results of a Randomized Pilot Study

Acute radiation dermatitis (RD) is a frequent toxicity associated with radiotherapy (RT) for head and neck cancer (HNC). KeraStat Cream (KC), an emulsion-based wound dressing that acts as a protective barrier that promotes the healing of minor skin wounds and partial-thickness burns, has not yet been studied in patients receiving RT for HNC. This randomized, open-label pilot study enrolled patients with HNC planned to receive definitive or postoperative RT to a total dose of at least 60 Gy. The study excluded patients with a history of prior RT, use of topical corticosteroids, scleroderma, lupus, or treatment with anti-EGFR therapy. Eligible patients were randomized to KC or routine skin care (RSC, patient choice of a variety of commercially available topical creams/lotions), applied at least twice daily during and for 1 month after RT. Assessments were performed at baseline, weekly during RT, and 1-month after RT. The primary outcome was adherence to the prescribed skin care regimen (at least 10 applications per week of treatment, starting at week 2). Secondary outcomes were the incidence rates of clinician-rated and patient-reported dermatitis (CTCAE and PRO-CTCAE grades 2+) and the Dermatologic Life Quality Index (DLQI, range 0-30 with a higher number indicating worse skin-related quality of life) at the last assessment before radiotherapy completion (end-RT). Of 29 patients enrolled, 24 (n = 12 in each group) were randomized and completed the study. Most patients had stage III-IV disease (17, 71%), and the most common primary site was the oropharynx (n = 11, 46%), followed by the oral cavity (n = 7), larynx (n = 5), and sinonasal (n = 1). The median RT dose was 68 Gy (range 60-70), median skin V60 was 37.2 cc (range 1.5-107.6), and median skin V70 was 0 cc (range 0-24.9), with no differences between groups. The bilateral neck was treated in most patients (n = 19, 79%), primary site treated in 3 and unilateral neck treated in 2 patients. Most patients received concurrent chemotherapy (n = 18, 75%). Complete adherence to assigned skin care was observed in 7/12 (58%) patients in the RSC group vs. 10/12 (83%) patients in the KC group (p = 0.65). Nearly all patient-weeks were adherent: 64/67 patients in the KC group and 61/68 patients in the RSC group (p = 0.20). Incidence rates of G2+ RD were similar between the KC and RSC groups: CTCAE, 9/12 vs. 7/12 (p = 0.67); PRO-CTCAE, 10/12 vs. 8/12 (p = 0.64). When measured at end-RT, mean RD scores were similar between the KC and RSC groups: CTCAE, 1.4 vs. 1.8 (p = 0.30); PRO-CTCAE, 2.0 vs. 2.0 (p = 1); DLQI (4.8 vs. 4.6, p = 0.92). Repeated measures analysis showed no difference between arms for CTCAE (p = 0.72), PRO-CTCAE (p = 0.96), or DLQI (p = 0.78). A randomized study of KC vs. RSC is feasible with good adherence to assigned skin care, particularly in the KC group. Future randomized trials are warranted to investigate the efficacy of this novel topical approach to RD during radiotherapy for HNC.

Stereotactic Body Radiation Therapy for Large Volume Solid Tumor Spinal Metastases Involving Three or More Contiguous Vertebral Levels

Data for treating 3 or more contiguous vertebral bodies with SBRT is limited. The purpose of this study was to explore oncologic outcomes and toxicity of spine SBRT delivered to large volume solid tumor metastases involving 3 or more contiguous vertebral levels. Patients treated with spine SBRT for vertebral metastases involving 3 or more contiguous levels between 2009 and 2021 were retrospectively reviewed. Data on demographics, dosimetry, toxicity, and outcomes were collected. Radiographic local failure was defined as progressive disease on CT and/or MRI in the treatment volume compared to the pre-SBRT baseline. Local control (LC) and overall survival (OS) were calculated from end of SBRT using the Kaplan-Meier and log-rank test. A total of 141 patients were included with a median follow-up of 9.7 months. The majority of patients had either 3 (74%) or 4 (16%) involved contiguous vertebral levels. Twenty-two percent, 57%, 14%, and 7% of treated lesion began in the cervical, thoracic, lumbar, and sacral vertebral levels, respectively. The most common primary sites were NSCLC (15.6%), kidney (14.9%), and breast (13.5%). Thirty-two percent of patients had prior external beam radiation to the same vertebral level, 63% had prior surgery, and 43% had prior vertebral fracture. Paraspinal extension was identified in 26% at time of SBRT. Median pre-SBRT Bilsky grade was 2 (range 0-3). The median total prescription dose was 27 Gy (range: 12-43 Gy) with the most common dose (Gy)/fractionation schedules of 27/5 (32%), 30/5 (25%), and 25/5 (18%). The median Dmax was 4727 cGy (range 2070-7857) with a median prescription isodose of 58% (range 48-97). The median OS was 12.4 months (95% CI 9.6-15.3). 1- and 2- year OS were 51% and 35%, respectively. Local progression occurred across all histologies, most commonly in colon and NSCLC (16.7%). 1- and 2-year LC were 70% and 57%, respectively. In the radiation-naïve cohort, 1- and 2-year LC were 75% and 63%, respectively and 52% and 34% in the prior radiation group with no statistically significant difference in time to local progression (p = 0.075). There was no statistically significant difference in LC when comparing 3 versus 4 or more contiguous lesions (p = 0.66). Forty percent of patients that progressed underwent salvage treatment (58% surgery, 33% SBRT, 8% systemic therapy). Post-SBRT vertebral compression fracture rate was 11.6%. We present the largest series to date of patients treated with SBRT for large volume spinal metastases involving 3 or more contiguous levels. These data suggest reasonable local control and low toxicity with SBRT; therefore, SBRT should be considered a practical modality to offer this cohort.

Hypofractionated Preoperative Radiotherapy 30Gy in Five Fractions for Soft Tissue Sarcoma of the Extremity

Hypofractionated preoperative radiotherapy (HypoRT) is being used with increasing frequency for soft tissue sarcomas (STS) of the extremities. Besides the social and economic advantages, HypoRT has a theoretical advantage in STS because of their low α/β ratio. The objective of this study is to review our experience using HypoRT to a dose of 30Gy in 5 fractions in STS of the extremities. This study is a retrospective review of patients with extremity STS treated at our center with preoperative HypoRT to a dose of 30Gy in 5 fractions given on alternate days over 2 weeks. Inclusion criteria were age ≥18 years, biopsy-proven primary STS in an extremity, and fitness for surgery. The primary endpoint was major wound complications (MWC) defined as the need for wound management or secondary operation under general or regional anesthesia within 120 days from surgery. Secondary objectives were: early toxicity grade ≥ 2 and clinical outcomes, including local control (LC), and metastasis-free survival (MFS). Descriptive statistics were used to evaluate patient and treatment characteristics. The Kaplan-Meier method was used to estimate survival. A total of 40 patients received preoperative HypoRT at our center between 2016 and 2022. The median age was 70 years (30 - 91). Males accounted for 57.5% of the patients. The most common primary site was the lower extremity (62.5%). The most prevalent histologic type was myxofibrosarcoma (27.5%), followed by pleomorphic spindle cell sarcoma (20%). All patients were treated with image-guided intensity modulated radiotherapy with margins for the CTV as tested in the RTOG 0630 study. Median follow-up was 14.8 months (5 - 86). Acute side effects were seen in 80% of the patients, all grade <3. The most common toxicity was dermatitis (37.5%), the second was fatigue (20%), and the third was pain (15%). Surgery was performed in all cases after a median interval from completion of HypoRT of 34 days (16-59). Amputation was performed in one patient with a fungating tumor, HypoRT having been aborted at only 24Gy because of worsening symptoms. On pathologic examination, positive margins were found in four cases (10%). The percentage of necrosis was ≥ 90% in 7 patients and 50%-90% in 10. MWC occurred in 13 patients (32.5%), including 10 who underwent a procedure with anesthesia. Sixteen patients were treated for a wound infection. Only one patient recurred locally. Two-year LC was 91.7%. MFS was 87.4% at 6 months and 60.8% at 2 years. DFS was 84.9% at 6 months and 64.8% at 2 years. The preoperative HypoRT regimen of 30Gy in 5 fractions given on alternate days for extremity STS is safe. Acute toxicity was not different from our previous experience using the conventional regimen of 50Gy in 25 fractions over 5 weeks and the MWC rate was comparable to that reported for the conventional regimen. Local control was excellent.

Extrapulmonary Small Cell Carcinoma: A Single Institution Review of Brain Metastases, Treatment Paradigms and Patient Outcomes

Extrapulmonary small cell carcinoma (EPSCC) is a rare entity with 1,000 cases reported annually in the U.S. It can originate in a variety of sites outside of the lung, and even with locoregional disease, relapse is common, and survival is poor. Prophylactic cranial irradiation (PCI) can improve survival in small cell lung carcinoma, however in the setting of EPSCC its role has not been clearly defined. We offer a single institution retrospective review of EPSCC, outlining the incidence of brain metastases, treatment paradigms, and patient outcomes. Patients with available records were identified from an institutional database. Demographic, disease-related, and treatment details were abstracted from the electronic medical record. Clinical outcomes were obtained by medical record review and brain metastases were identified through diagnostic imaging. Patients were classified as having brain metastases at diagnosis or in follow-up. Brain metastasis-free survival (BMFS) was defined as the duration of time from diagnosis to the development of brain metastases, and extracranial progression-free survival (ePFS), as the duration of time from diagnosis to progression of disease outside the brain. Time to event outcomes were summarized using the Kaplan-Meier method. Analyses were performed using R version 3.6. In total, 68 patients met eligibility criteria for analysis. The majority were male (66%) and median age was 68. The most common primary sites were genitourinary (32%) and gastrointestinal/hepatobiliary (22%). Thirty-eight patients (56%) had diagnostic brain imaging at time of diagnosis, with brain metastases present in 5 (13%). Treatment was delivered to 53 patients (80%) and treatment modalities included chemotherapy (n = 46), radiotherapy (n = 21), and surgery (n = 18). Median follow-up was 9.3 months for all patients and 10.3 months for surviving patients. Overall, 12 patients were observed to have brain metastases: 5 at diagnosis and 7 in follow-up. The competing risk of death without brain metastases at 1 year was 51.5%. Four of 5 patients with de novo brain metastases received WBRT. Of the 7 patients with subsequent brain metastases, 1 received salvage WBRT and 3 received salvage SRS. In total, 49 patients died and median OS was 10.0 months. Those with brain metastases had no significant difference in OS when compared to those without brain metastases (10.8 months v. 9.4 months). There was no association between primary type and survival. EPSCC is a rare entity that is most commonly diagnosed in the genitourinary system. In contrast to SCLC, the incidence of brain metastases is uncommon. No difference in survival was observed between patients with or without brain metastases. While retrospective studies must be interpreted with caution, our data suggest that the risks of PCI may outweigh the benefits. Further studies investigating the role of brain imaging surveillance, as well as the optimal management of brain metastases, is warranted.

Stratifying Response to Stereotactic Radiosurgery for Spinal Metastases by Primary Site Genomic Mutations

Spine stereotactic radiosurgery (SSRS) is effective in achieving durable local control (LC) and palliation of pain in patients with spinal metastases. Per institutional standards, SSRS prescription dose is tailored by primary site histology, with radioresistant disease receiving escalated doses. While the association between tumor histology and radioresistance is well studied, the association between specific genotypic mutations and radioresistance to SSRS is not well known. We sought to determine if a relationship exists between primary tumor mutations and clinical outcomes following SSRS. We performed a retrospective analysis of 201 patients with available primary site mutation profiles who underwent SSRS to 327 spinal metastases from 2007-2022 at a single institution. Associations with overall survival (OS) and LC were identified using univariate and multivariable Cox proportional hazards modeling adjusted for clinicopathologic and treatment-related factors. The median age was 59 years (range: 11-85) at the time of SSRS. One hundred and five patients were male (52%). The median SSRS dose to the gross tumor volume was 24 Gy (range: 12-50) given in a median of 1 fraction (range: 1-5), corresponding to a biologically effective dose (BED10) of 81.6 Gy. The most common primary tumor sites were head and neck (20%), lung (19%), and genitourinary (15%). The most common spine subsites were thoracic (57%) and lumbar (27%). Twenty-four mutated genes were identified in primary tumors with the most common being TP53 (28%), KIT (15%), PIK3CA (15%), and KRAS (10%). Prior to receipt of SSRS, 19% of patients underwent surgical resection and 23% received conventional radiation therapy (RT) to their treated sites. The median follow-up time and OS following SSRS was 97 months (95% confidence interval [CI] 86-128) and 41 months (95% CI 20-31), respectively. The median LC at 1 and 2 years following SSRS was 88% (95% CI 84-92) and 75% (95% CI 70-82), respectively. On multivariable analysis, receipt of prior RT (hazard ratio [HR] 1.86; 95% CI 1.29-2.67; P = 0.0008) and TP53 mutation (HR 1.68; 95% CI 1.20-2.35; P = 0.0024) were associated with shorter OS, whereas STK11 mutation (HR 2.14; 95% CI 0.47-4.70; P = 0.0589) trended towards shorter OS. LC was more durable with increasing BED10 (HR 0.98; 95% CI 0.96-1.00; P = 0.0166) and less durable with mutations in ATM (HR 2.40; 95% CI 1.06-5.44; P = 0.0362), STK11 (HR 4.89; 95% CI 1.40-15.01; P = 0.0119), and CTNNB1 (HR 4.49; 95% CI 1.90-10.62; P = 0.0006). While favorable outcomes among all patients receiving SSRS were seen, increasing BED10 was associated with more durable LC. Primary site ATM, STK11, and CTNNB1 mutations may be associated with poorer LC following SSRS. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

Uncovering the Armpit of Axillary SBRT

The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to applications in new and unique anatomic locations, highlighting the importance of effective, safe, reproducible treatment delivery. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes, safety and process. In this ethics approved single-institution retrospective review, patients treated with SBRT to AM from 2014-2022 had tumor, treatment planning, and dosimetric variables abstracted. Toxicity was assessed per Common Terminology for Adverse Events V5.0. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60%), Eastern Cooperative Oncology Group performance status 0-1 (62%), and elderly (median age: 72), with a median follow-up of 14.6 months. Common primary sites included breast (n = 16, 43%), skin (n = 7, 19%), and lung (n = 5, 14%). Treatment indication included oligoprogression (n = 18, 46%), oligometastases (n = 14, 36%) and symptomatic progression (n = 7, 18%). A minority had prior overlapping radiation (n = 7, 18%) or regional surgery (n = 4, 11%), while most had prior systemic therapy (n = 26, 70%). Significant heterogeneity in simulation, planning and treatment was identified. Immobilization included 5-point thermoplastic mask (n = 12, 32%), Vacloc (n = 12, 32%) arms-up thorax bag (n = 11, 30%). 4-D CT scans were obtained in 46%, MR simulation in 21%, and intravenous contrast in 10%. Median dose was 40 Gy (interquartile range (IQR): 35-40) in 5 fractions, (BED10 = 72 Gy), over a median of 12 days (IQR: 9-14). Seventeen cases (44%) utilized a low-dose elective volume to cover remaining axilla; 14% used a high dose clinical target volume. Median planning target volume margin was 5mm (range: 3-10mm), and plans were generated with 5 different dose constraint protocols. At first radiographic assessment, 87% had partial or complete response, with a single progression. Of symptomatic patients (n = 14), 57% had complete symptom resolution and 21% had improvement. One and 2-year LF rate were 19% and 31%, respectively. Median OS was 21.0 months (95% [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95% [CI] 4.3-11.3). Acute and late toxicities were uncommon, with two grade 3 events (1 plexopathy in a case with tumor involving brachial plexus, 1 skin ulceration) identified, and no grade 4/5. In this series of AM SBRT, low rates of toxicity, and good rates of LF and symptom improvement were observed. As treatment was delivered with a variety of individual treatment differences, an institutional protocol is under development to standardize technique, optimize efficiency and improve evaluability.

The Inpatient Consultation Experience in Radiation Oncology: A Contemporary Evaluation of a Single Academic Institution

Participating in an inpatient consultation service is an essential aspect of radiation oncology residency training. However, there are no reports in the literature describing the inpatient on-call experience. To better describe the clinical burden and define the learning opportunities associated with inpatient consultation service participation, inpatient on-call data were tracked and assessed. From July 1, 2022, through Dec. 31, 2022, radiation oncology residents covering the on-call pager for the inpatient consultation service spanning two hospitals at a single academic institution prospectively self-reported the total number of pages, new consultations, inpatient treatment starts, and treatment indications. Patient billing records and paging logs were reviewed to confirm self-reported cases and track the number of business days between simulation and the first fraction of treatment. A new inpatient consultation was defined as a novel encounter requiring independent evaluation; as such, patients admitted during an ongoing course of radiotherapy who continued the planned course while inpatient were not included. During the initial six months of tracking, on-call residents received a total of 607 pages with an average of 23.1 pages per week (range: 14-38). Of these pages, 212 were for new inpatient consultations with an average of 8.1 consultations per week (range: 2-15). Out of these 212 new consultations, 75 patients (35%) were treated on an inpatient basis. Nine patients (12%) received their first fraction of treatment on the same day as simulation, 13 (17%) on the next day, 11 (15%) two days after, 22 (29%) three days after, and 20 (27%) four or more days after simulation. The most common indications for urgent treatment were malignant spinal cord compression (27%), brain metastases (24%), tumor-related bleeding (8%), malignant obstruction of the airway or vasculature (8%), painful bone metastases (7%), and heterotopic ossification prophylaxis (7%). The most common primary sites of disease were leukemia/lymphoma (16%), gastrointestinal (13%), breast (11%), lung (9%), gynecologic (9%), sarcoma (9%), and benign (9%). Each individual resident's caseload differed greatly in quantity, indication, treatment site, and primary site over this six-month time period. In this longitudinal analysis at a single academic institution, the radiation oncology inpatient consultation service experience was highly variable and diverse in clinical volume and treatment indication on a week-to-week and resident-to-resident basis. Exposure to radiation oncology emergencies is a vital component of residency training. However, the unpredictable nature of inpatient on-call scenarios can lead to variable educational experiences. Tracking inpatient on-call cases during residency may help identify areas needing improvement to enhance both patient care and residency training.

Correlation between clinicopathological characteristics and the clinical prognosis of patients with gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are one of the most common types of NETs, accounting for 65-75% of all NETs. However, epidemiological characteristics of patients with GEP-NETs in China are still lacking. The present retrospective study aimed to investigate the local epidemiology of GEP-NETs and assess the prognostic factors in China. The data of 267 patients with GEP-NETs who were admitted to the First Affiliated Hospital of Bengbu Medical College (Bengbu, China) and the Affiliated Hospital of West Anhui Health Vocational College (Lu'an, China) were retrospectively reviewed. The clinical and pathological characteristics of the patients, as well as follow-up information, were collected, and the 5-year survival rate was calculated. Kaplan-Meier curves and log-rank analysis were used to analyze the prognostic factors. The stomach (100/267; 37.5%) was the most common site of GEP-NETs and the liver (25/39; 64.1%) was the most common metastatic site. A total of 166 (62.2%) and 219 (82.0%) patients had positive results for chromogranin A (CgA) and synaptophysin (Syn), respectively. The percentage of patients with tumor grade G1, G2 and G3 was 33.3, 21.0 and 45.7%, respectively. The 5-year overall survival rate was 79.7%, and the age, tumor site, distant metastasis and tumor grading upon diagnosis were all prognostic factors. In conclusion, the present case series investigated the epidemiology and prognostic factors of GEP-NETs in China. CgA and Syn could be used as diagnostic markers for NETs and the stomach was the most common primary tumor site. Lymph node metastasis, tumor site, distant metastasis and tumor grading were important prognostic factors.