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Primary malignant melanoma of the parotid gland (PGMM) is extremely rare, with a poor prognosis. Surgery is the main treatment option followed by adjuvant treatments such as radiotherapy, but which adjuvant treatment to be optimal is still controversial. In this case, a 63-year-old male PGMM patient was first misdiagnosed as a “myoepithelial tumor” and then treated with surgery, postoperative immunotherapy (sintilimab), chemotherapy, and radiotherapy successfully. The progression free survival was more than 19 months without signs of metastasis or recurrence to date. To our best knowledge, this is the first report of postoperative immunotherapy combined with chemotherapy and radiotherapy for PGMM. Our case indicated that combination therapy including surgery, adjuvant immunotherapy (sintilimab) combined with chemotherapy and radiotherapy may be a potential treatment option for PGMM, which needs further research.

Although the incidence of multiple primary malignancies (MPMs) is increasing, synchronous triple primary malignant tumours with prostate, bladder and lung is rarely reported. Gene mutation is thought to be a reason for MPMs, and severe cardiovascular diseases may interrupt the cancer treatment. Here we reported a 64-year-old male patient with synchronous triple primary malignant tumours of the bladder urothelial carcinoma, prostate adenocarcinoma, and non-small cell lung cancer (NSCLC) with mutations in TP53 and MEK1, all the three malignancies were diagnosed within 10 days. Although being interrupted by severe cardiovascular diseases (including myocardial infarction, venous thrombosis, and aneurism of the aortic root), he was successfully treated with radical cystoprostatectomy, chemotherapy plus pembrolizumab (a PD-1 antibody), and radiotherapy of the lung lesion, followed by maintenance monotherapy of pembrolizumab, overall survival was more than 26 months. In conclusion, a patient of synchronous triple primary malignant tumours with prostate, bladder, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases was treated successfully, which may suggest that comprehensive treatment, especially radical treatment such as operation and radiation, is very important for MPMs.

Background: The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. Methods: Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post‐recurrence survival (PRS) and prognostic factors were evaluated by Kaplan–Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. Results: A total of 170 patients were enrolled, with a median age of 60 years (range 43–77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs. Conclusions: Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs. [ABSTRACT FROM AUTHOR]

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4+ T cells expressed CD39. Most GC‐infiltrating CD39+CD4+ T cells exhibited CD45RA−CCR7− effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39−CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC‐infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients. [ABSTRACT FROM AUTHOR]

CD8+CD103+ tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8+CD103+ TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8+CD103+ TRMs are CD45RA−CCR7− effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8+CD103+ TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8+CD103+ TRMs, and such anti-PD-1-mediated reinvigoration of CD8+CD103+ TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8+CD103+ TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8+CD103+ TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC. [ABSTRACT FROM AUTHOR]

Background: To compare the survival outcomes and neurocognitive dysfunction in non‐small cell lung cancer (NSCLC) patients with brain metastases (BM ≤10) treated by whole‐brain radiotherapy (WBRT) with sequential integrated boost (SEB) or simultaneous integrated boost (SIB). Materials: Fifty‐two NSCLC patients with a limited number of BMs were retrospectively analyzed. Twenty cases received WBRT+SEB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*3 fractions; SEB group), and 32 cases received WBRT+SIB (WBRT: 3 Gy*10 fractions and BMs: 4 Gy*10 fractions; SIB group). The survival and mini‐mental state examination (MMSE) scores were compared between the groups. Results: The cumulative 1‐, 2‐, and 3‐year survival rates in the SEB vs SIB groups were 60.0% vs 47.8%, 41.1% vs 19.1%, and 27.4% vs 0%, respectively. The median survival times in the SEB and SIB groups were 15 and 10 months, respectively. The difference in survival rate was significant (P =.046). Subgroup analysis revealed that 1‐, 2‐, and 3‐year survival rates and median survival time in the SEB group were significantly superior to those of the SIB group, especially for male patients (age <60 years) with 1‐2 BMs (P <.05). The MMSE score of the SEB group at 3 months after radiation was higher than that of the SIB group (P <.05). Nevertheless, WBRT+SEB required a longer treatment time and greater cost (P <.005). Conclusions: WBRT + SEB results in better survival outcomes than WBRT+SIB, especially for male patients (age <60 years) with 1‐2 BMs. WBRT+SEB also appeared to induce less neurocognitive impairment than WBRT+SIB. [ABSTRACT FROM AUTHOR]

Background The purpose of the current study is to analyze the existing data comparing neoadjuvant chemotherapy with primary debulking surgery (PDS) in patients with advanced ovarian carcinoma. Methods Patients with stage IIIC and IV ovarian cancer were identified from articles in Medline, PubMed, Cochrane Library, and EMBASE database (1989 to February 2013). Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used. Meta-analysis on literatures was conducted by using RevMan 5.2 software. Results Two high-quality randomized controlled trials (RCTs) met the inclusion criteria. These multicenter trials randomized 1,220 women with stage IIIc/IV ovarian cancer to NACT or PDS followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (1,120 women; HR 0.98; 95% CI 0.85 to 1.14) or progression-free survival (PFS) (1,120 women; HR 1.03; 95% CI 0.91 to 1.16). Conclusion There was no statistical difference in median OS and PFS between the two treatment groups. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account respectability, age, histology, stage, and performance status. [ABSTRACT FROM AUTHOR]

Objectives: CD4 + T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4 + T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown., Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4 + T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4 + T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity., Results: In comparison with CD4 + T cells from the non-tumor tissues, significantly more GC-infiltrating CD4 + T cells expressed CD39. Most GC-infiltrating CD39 + CD4 + T cells exhibited CD45RA - CCR7 - effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39 - CD4 + counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39 + CD4 + T cells were positively associated with disease progression and patients' poorer overall survival., Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4 + T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)