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BACKGROUND: In the US, new malignancies among cancer survivors comprised a substantial proportion of total incident cancers, ranging from 11% in younger adults (aged 20-64 years) to 25% in adults aged 65 years and older. These survivors with multiple primary cancer (MPC) have poorer mental status than those with a single cancer diagnosis. However, limited studies have focused on this unique survivor population. We aimed to compare social and physical limitation as well as financial hardship between cancer survivors with MPC and those with single cancer diagnosis to provide more information about the well-being of cancer survivors with MPC in the US. METHODS: This study is based on the adult samples data from the US population-based 2021 National Health Interview Survey. Individuals with non-melanoma skin cancer or skin cancer of unknown type and those diagnosed before 18 years old are excluded. The MPC group was compared with the single cancer diagnosis group about social limitations (difficulty doing errands alone, difficulty participating in social activities and health-related work limitation), physical limitations (vision, hearing, mobility, communication, cognition and self-care) and medical financial hardship (care access failure due to finance, problems or worries in paying medical bills). Life satisfaction was also evaluated among the two groups. The Mann-Whitney U test and binary logistic regression were used to analyze differences between the two groups. Analyses were performed using SPSS (version 27.0; SPSS Inc., Chicago, Ill). 2-sided at P RESULTS: We identified 2633 adult cancer survivors, including 343 MPC survivors and 2290 survivors with a single cancer diagnosis. Compared to cancer survivors with single cancer diagnoses, cancer survivors with MPC have a significantly increased risk of social limitation, including difficulty doing errands alone (OR 1.80, P < .001) and participating in social activity (OR 1.88, P < .001), although no difference in health-related work limitation. Meanwhile, cancer survivors with MPC are significantly related to physical disabilities, including vision (OR 1.38, P = 0.014), hearing(OR 1.33, P = 0.022), mobility (OR 1.77, P < .001), communication (OR 1.50, P = 0.038), cognition (OR 1.26, P = 0.051) and self-care (OR 1.57, P = 0.017). Cancer survivors with MPC are also found to be associated with life dissatisfaction (OR 1.88, P = 0.001). We observed no significant differences in care access failure due to finance, problems or worries in paying medical bills. CONCLUSIONS: Cancer survivors with MPC are associated with increased risks for social function and physical disabilities and tend to report life dissatisfaction more than cancer survivors with single cancer. Survivors with MPC need more attention and support from the family, community and medical care. Citation Format: Jiazhang Xing. Social/physical limitations and financial hardship among the US adult cancer survivors with multiple primary cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1983.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor prognosis. In resectable PDAC, the recurrence rate is still high even when surgery and adjuvant chemotherapy (CT) are applied. Regional lymph node metastasis and positive margins are associated with higher recurrence risk and worse survival. Adjuvant radiotherapy has been explored, but its efficacy remains controversial. In recent years, some characteristics have been reported to stratify patients who may benefit from adjuvant chemoradiation (CRT), such as lymph node metastasis and margin status. Adjuvant chemotherapy followed by chemoradiation (CT-CRT) was also proposed. A total of 266 patients with resectable PDAC who have lymph node metastasis or R1 resection after surgery were enrolled. In multivariate Cox regression analyses, pancreatic body or tail tumor location (HR 0.433, pvs. 21.4% in the CT and CT-CRT group, respectively). However, no significant differences in disease-free survival among these two groups were observed.

e16210 Background: Due to the rarity, research on gastric neuroendocrine carcinoma (NEC) is limited. The treatment has been extrapolated from small-cell lung cancer (SCLC) data. However, a previous study found gastric NECs had a genetic feature characterized by a lower frequency of RB1 mutations than SCLC. Several studies also showed RB1mutation or loss of Rb expression could predict the efficacy of SCLC treatment in NEC. Our study investigated a subtyping method by p53 and Rb immunohistochemistry (IHC) staining in gastric NEC, which might help identify patients responding to SCLC treatment. Methods: Patients with gastric NEC who underwent radical surgery in Peking Union Medical College Hospital (PUMCH) from 2013 to 2021 were identified. The expression of Rb, p53, PD-L1 and CD8 T cell infiltration were accessed by IHC stain. The mutations of RB1 and TP53, tumor mutation burden (TMB), and microsatellite instability (MSI) were detected by whole-exom sequencing (WES). Fisher’s exact test and Mann–Whitney test were used to detect differences between groups. Spearman's test was used to detect correlations between variables. Kaplan-Meier and Cox hazards methods were applied to the survival analysis. Samples of gastric adenocarcinoma, gastric neuroendocrine tumor (NET), and SCLC were also included. Results: A total of 41 patients with gastric NEC were included. WES was carried out in 28 patients. TP53 mutation was detected in 14 patients. RB1 mutation was detected in 1 patient. A classification method based on gene mutation was not able to be further investigated. In IHC of 41 patients, 46.2% showed Rb expression absence. 68.4% had abnormal p53 expression. 39 patients were classified based on IHC results. Patients with both abnormal expression of p53 and Rb were defined as SCLC-like type, accounting for 38.5%.The remaining patients were defined as non-SCLC-like type. SCLC-like gastric NEC had an increased number of lymph nodes metastasis (P = 0.001) and higher TNM stage (P < 0.001). The SCLC-like group's overall survival (OS) was significantly lower than the non-SCLC-like group (P = 0.023). Classification based on p53 and Rb expression was an independent predictor of OS (P = 0.021), HR = 4.690, 95%CI (1.263, 17.421). The classification results of gastric NEC were significantly different from those in gastric NET(P = 0.001), gastric adenocarcinoma(P = 0.002), but not in SCLC(P = 0.464). In 39 classified patients, the positive rate of PD-L1 expression was 23.1%; CD8 T cells high infiltration (>25 % of the stromal area) was 46.7%; the median TMB was 4.9 Muts/MB, and MSI was not detected. There was no significant difference in the expression of immunotherapy-related markers between the two types. Conclusions: Our study revealed subtypes of gastric NEC based on p53 and Rb expression with different prognoses. Further research on the treatment efficacy predictive role of this subtyping method is warranted.

Digestive system neuroendocrine carcinomas (NECs) are rare neoplasms originating from neuroendocrine cells with a poor prognosis and limited effective treatments. Programmed cell death protein 1/ligand 1 (PD-1/PD-L1) blockade has been used in the management of more than 10 solid tumors and has achieved promising clinical outcomes. PD-L1 expression, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) are all verified biomarkers that can predict the response to anti-PD-1/PD-L1 therapy. Here, we investigated PD-L1 expression and immune cell infiltration density by immunohistochemical (IHC) staining of tumor samples from 33 patients with digestive system NECs. Tumor and paratumor normal samples from 31 of these patients underwent whole-exome sequencing to evaluate TMB and the MSI-high (MSI-H) status. In total, 29.0% of digestive system NECs had positive PD-L1 expression according to the tumor proportion score (TPS). Infiltration of CD3+, CD8+, and CD68+ cells was observed in 69.7, 27.3, and 54.5% of patients, respectively. The TMB value for patients sequenced ranged from 0.57 to 11.75 mutations/Mb, with a median of 5.68 mutations/Mb. mSINGS, MSIsensor, and MSIseq were used to analyze the MSI status according to the sequencing data, and in our evaluation, no MSI-H status was detected. Our data might indicate a limited potential of anti-PD-1/PD-L1 monotherapy in digestive system NECs, although clinical trials are warranted.

CA19-9 is the most commonly used tumor marker in the diagnosis, prognosis and surveillance of pancreatic cancer. We hypothesized that CA19-9 elevation can be taken as an indication to start salvage treatment in surveillance after resection.From January 2014 and July 2017, 80 pancreatic cancer patients who underwent R0 surgical resection and received adjuvant chemotherapy were included.Twenty-six (32.5%) patients started salvage treatment at the time of CA19-9 elevation without radiological evidence of recurrence. Fifty-four (67.5%) patients treated conventionally before recurrence was confirmed by radiological examinations. Sixty (75%) patients had CA19-9 elevation that preceded radiographic recurrence by about 3 months. In the intervention group, the median DFS (23.6 months vs. 12.1 months, P 0.001) and OS (28.1 months vs. 20.7 months, P = 0.049) were significantly longer than those in the control group.CA19-9 elevation could preceded recurrence confirmed by radiographic examinations in most patients. Tumor marker-guided salvage treatment can significantly prolong disease-free survival and overall survival in patients under surveillance after pancreatic cancer resection.

Rationale Carotid body tumors (CBTs) are head and neck paragangliomas (PGLs) with a low incidence of distant metastasis. To date, only a few metastatic cases treated with detailed systemic therapy are reported and effective management is still inconclusive. Herein, we reported a metastatic CBT case with systemic therapy and reviewed the reported systemic treatment. Patient concerns A 56-year-old man noticed multiple painless nodules on the right side of the neck and developed debilitating chest and back pain 7 years after the CBT resection. Diagnoses Widespread bone and lymph nodes CBT metastases. Interventions Biopsies of the enlarged lymph nodes confirmed the diagnosis of metastatic CBT and 18F-FDG PET-CT detected multiple right cervical lymph nodes and bone metastases. 24 cycles of cyclophosphamide, vincristine and dacarbazine (CVD) chemotherapy were given since May 2016 to Jul 2018 and dacarbazine maintenance therapy was given in the next 15 months follow-up period. Outcomes Partial remission was achieved according to the Response Evaluation in Criteria in Solid Tumors 1.1 criteria. A prominent control in the metastatic lesions were also observed in 18F-FDG PET-CT scan. Lessons Evidence for systemic management of metastatic CBTs is mainly based on studies of PGLs and pheochromocytoma. According to our review on metastatic CBT cases treated with systemic therapy from 1981 to 2018, chemotherapy, especially the CVD regimen, was a common reported management. In SDHB mutated patients, sunitinib and temozolomide could also be considered.

Background Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly differentiated grade 3 neuroendocrine neoplasm, of which the overall survival is poor with limited treatment options. Immune checkpoint related therapy such as PD-1 blocking has successfully been used in some solid tumor treatment. In this study, we investigated the infiltration of immune-cells and PD-1/PD-L1 blockade biomarkers to improve understanding of the tumor immune microenvironment in GEP-NEC. Methods Stromal and tumor cells expressing CD3, CD8 and CD68 protein were assessed in 32 cases of GEP-NEC by immunohistochemistry. Their tumor mutational burden (TMB) and microsatellite instability (MSI) were measured by gene sequencing. Software mSINGS MSIsensor and MSIseq were used to evaluate MSI and MSI status was set when more than two software showed the MSI. The Mann-Whitney U test and Kruskal-Wallis test were used to analyze the correlation of markers expression with clinicopathological parameters. Kaplan -Meier curves were applied in survival analyses. Results In the study, 65.6% of the patients were male and the median age was 65. The predominant primary sites were stomach (66%) and pancreas (19%). High infiltration (more than 25% stromal area infiltration) of CD3, CD8 and CD68 immune cells were found in 84%, 47% and 81% of the patients, respectively. High expression of CD3 correlated with high expression of CD8 and CD68 (p Conclusions The study contributes to the understanding of immune microenvironment of GEP-NEC. The association of clinicopathological features with PD-1/PD-L1 blockade biomarkers and immune cells in GEP-NEC were explored. This understanding should help to improve predictions of the impact of the PD-1/PD-L1 pathway in GEP-NEC patients. Legal entity responsible for the study The authors. Funding Chinese Academy of Medical Sciences (CAMS) Initiative for innovative Medicine (CAMS-I2M) 2017-I2M-1-001. Disclosure All authors have declared no conflicts of interest.