Psychological Distress, Emergency Room Utilization, and Mortality Risk Among US Adults With History of Prostate Cancer.

PURPOSE: Adults with a history of prostate cancer experience several physical and mental stressors. However, limited information is available about the prevalence of psychological distress in this population and its association with clinical outcomes in a nationally representative sample. METHODS: We identified adults with history of prostate cancer from a nationally representative cohort (2000-2018 US National Health Interview Survey) and its linked mortality files through December 31, 2019. The six-item Kessler Psychological Distress Scale (K6) was used to assess psychological distress. The associations between psychological distress severity, emergency room (ER) usage, and mortality risk were estimated using multivariable logistic and Cox proportional hazards models, which were both adjusted for age, survey year, race/ethnicity, region, education, health insurance, comorbidities, functional limitations, and time since cancer diagnosis. RESULTS: Among the 3,451 adults with history of prostate cancer surveyed, 96 (2.4%), 434 (11.3%), and 2,921 (86.3%) reported severe, moderate, or low/no mental distress, respectively. During the 12 months preceding the survey, 812 (22.8%) adults with history of prostate cancer visited the ER. After a median follow-up of 81 months, 937 (25.5%) deaths occurred. Compared with participants with low/no mental distress, those with severe mental distress reported the highest utilization of the ER (adjusted odds ratio [aOR], 2.57 [95% CI, 1.51 to 4.37]) and exhibited the highest all-cause mortality (adjusted hazard ratio [aHR], 1.83 [95% CI, 1.29 to 2.60]), followed by those with moderate mental distress (ER use aOR, 1.76 [95% CI, 1.29 to 2.42]; all-cause mortality aHR, 1.22 [95% CI, 0.92 to 1.62]). CONCLUSION: Among US adults with history of prostate cancer, psychological distress was associated with increased ER use and mortality risk. Notably, severe psychological distress was correlated with the highest rates of ER visits and mortality risk. However, given the retrospective nature of this study, uncontrolled confounding variables need to be considered when interpreting the findings.

Medicaid expansion and racial disparity in timely multidisciplinary treatment in muscle invasive bladder cancer.

BACKGROUND: Multidisciplinary cancer care (neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy) is crucial for outcome of muscle-invasive bladder cancer (MIBC), a potentially curable illness. Medicaid expansion through Affordable Care Act (ACA) increased insurance coverage especially among patients of racial minorities. This study aims to investigate the association between Medicaid expansion and racial disparity in timely treatment in MIBC. METHODS: This quasi-experimental study analyzed Black and White individuals aged 18-64 years with stage II and III bladder cancer treated with neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy from National Cancer Database 2008-2018. Primary outcome was timely treatment started within 45 days following cancer diagnosis. Racial disparity is the percentage-point difference between Black and White patients. Patients in expansion and nonexpansion states were compared using difference-in-differences and difference-in-difference-in-differences analyses, controlling for age, sex, area-level income, clinical stage, comorbidity, metropolitan status, treatment type, and year of diagnosis. RESULTS: The study included 4991 (92.3% White, n = 4605; 7.7% Black, n = 386) patients. Percentage of Black patients who received timely care increased following the ACA in Medicaid expansion states (54.5% pre-ACA vs 57.4% post-ACA) but decreased in nonexpansion states (69.9% pre-ACA vs 53.7% post-ACA). After adjusting covariates, Medicaid expansion was associated with a net 13.7 percentage-point reduction of Black-White patient disparity in timely receipt of MIBC treatment (95% confidence interval = 0.5% to 26.8%; P < .01). CONCLUSIONS: Medicaid expansion was associated with statically significant reduction in racial disparity between Black and White patients in timely multidisciplinary treatment for MIBC.

POSTN Secretion by Extracellular Matrix Cancer-Associated Fibroblasts (eCAFs) Correlates with Poor ICB Response via Macrophage Chemotaxis Activation of Akt Signaling Pathway in Gastric Cancer.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment, but its clinical benefit is limited in advanced gastric cancer (GC). Cancer-associated fibroblasts (CAFs) have been reported to be associated with ICB resistance, but the underlying mechanism has not been fully elucidated. Our previous single-cell RNA-seq analysis of GC revealed that POSTN+FAP+ extracellular matrix CAFs (eCAFs) communicate with macrophages. Here, we evaluated the correlation between eCAFs and ICB response in TCGA-STAD and real-world cohorts. Immune infiltration analysis and correlation analysis were performed to assess the relationship between eCAFs and macrophages. We first confirmed a negative correlation between the abundance of eCAFs and the overall response rate (ORR) to anti-PD-1 treatment in TCGA-STAD and real-world GC cohorts. Overexpression of POSTN in CAFs enhanced macrophage chemotaxis, while POSTN interference showed the opposite effect in vitro and in vivo. Furthermore, the cell density of POSTN+ CAFs was positively correlated with the infiltration level of CD163+ macrophages in GC patient tissues. The results demonstrated that POSTN secreted by CAFs enhances macrophage chemotaxis by activating the Akt signaling pathway in macrophages. Additionally, we found that POSTN+FAP+ eCAFs may exist in multiple solid tumors and are associated with ICB resistance. eCAFs promote macrophage chemotaxis through the secretion of POSTN, thereby leading to ICB resistance. High expression of POSTN is likely to predict a poor response to ICB. POSTN downregulation may be considered as a candidate therapeutic strategy to improve ICB efficacy.

Expression of p53 and Rb reveal subtypes of gastric neuroendocrine carcinoma with distinct prognosis.

Gastric neuroendocrine carcinoma (NEC) is a rare tumor with a poor prognosis. Due to its rarity and disparity in prevalence across populations, there is limited data on gastric NEC. TP53 and RB1 genetic alterations or expression were reported for predictive value in neuroendocrine neoplasm and classification in pulmonary large cell NEC. This study investigated the genetic alteration and protein expression of TP53 and RB1 in gastric NEC. Thirty-nine patients were categorized as type A and B subtypes by p53 and Rb expression. Patients with concurrent abnormal p53 and Rb expression were defined as the type A group, and the remainder were defined as the type B group. Significant differences in TNM stages, tumor size, and lymph node metastasis were observed between the two subtypes. Type A characteristic is an independent predictor for worse overall survival (HR: 3.27; 95% CI: 1.12-9.58; p = .022). We further evaluated and compared immunotherapy-related markers, including PD-L1 expression, CD8 T cell infiltration, tumor mutation burden, and microsatellite instability in these two subtypes, whereas no significant differences were detected.

Prognostic Factors and Effect of Adjuvant Chemoradiation Following Chemotherapy in Resected Pancreatic Cancer Patients With Lymph Node Metastasis or R1 Resection.

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, p<0.0001, compared with pancreatic head) and adjuvant CT predicted a better survival, while there were no significant differences among the different CT regimens. Higher T stage indicated poor survival (stage I: reference; stage II: HR 2.178, p=0.014; stage III: HR 3.581, p=0.001). Propensity score matching was applied in 122 patients to explore the role of CRT. A cohort of 51 patients (31 and 20 patients in the CT and CT-CRT groups, respectively) was generated by matching. Further analyses revealed adjuvant CT-CRT was associated with prolonged survival compared with CT alone (HR 0.284, p=0.014) and less frequent local recurrences (56.5% vs. 21.4% in the CT and CT-CRT group, respectively). However, no significant differences in disease-free survival among these two groups were observed.

Systemic treatment of a metastatic carotid body tumor: A case report and literature review.

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.

Immune Checkpoint Markers in Neuroendocrine Carcinoma of the Digestive System.

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 elevation as an indication to start salvage treatment in surveillance after pancreatic cancer resection.

BACKGROUND: 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. METHODS: From January 2014 and July 2017, 80 pancreatic cancer patients who underwent R0 surgical resection and received adjuvant chemotherapy were included. RESULTS: 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. CONCLUSIONS: 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.