Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy.

Introduction: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance. Methods: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes. Results: The levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage. Conclusions: Our study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome.

[PRIMARY GASTRIC PLASMACYTOMA IN A BREAST CANCER MALE PATIENT].

INTRODUCTION: Plasmacytoma is a malignant tumor of the plasma cells. Extra-medullary plasmacytoma is rare and with an even lower incidence appears as a primary tumor of the stomach. Initial onset of the disease in the upper gastrointestinal tract is reported in the literature as just second to primary plasmacytomas of the head and neck system. The presenting symptoms are related to the organ involved and systemic symptoms can be weight loss, pain, bleeding and even fever. As this is a rare disease, there is no standard treatment and patients undergo endoscopic resection or chemotherapy with or without additional radiation. The prognosis of the disease depends on the possible future diagnosis of multiple myeloma which can be up to 50% within only a few years. We hereby report a case of a male patient with a past locally advanced breast cancer who was on prolonged adjuvant hormonal treatment. He developed a new symptom of melena and underwent a thorough evaluation including imaging and repeated biopsies from a large gastric lesion. The results were inconclusive mainly because of the differential diagnosis between breast cancer metastases and a new second primary malignancy. In view of a clinical deterioration and lack of diagnosis, an operation of radical gastrectomy was eventually performed only to surprisingly diagnose a rare hematologic disease of the stomach - gastric plasmacytoma. This diagnosis is rare in itself, especially having his previous male breast cancer and maternal multiple myeloma. The diagnostic procedure in this case had also provided the full treatment for his illness.

Significance of lower uterine segment involvement in women with stage I endometrial adenocarcinoma.

OBJECTIVE: To determine whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma who do not receive postoperative radiotherapy on the basis of this histologic criterion. STUDY DESIGN: Eighty patients with endometrial adenocarcinoma stage I who underwent surgery between 1989 and 2002 were divided into 2 groups according to the presence of LUSI. Group 1 consisted of 25 patients with LUSI; group 2 consisted of 55 patients without LUSI. The 2 groups were compared with regard to prognostic factors and outcome measures. RESULTS: There were no statistically significant differences between the 2 groups with regard to the following parameters: age and proportion of patients who underwent complete surgical staging and postoperative adjuvant radiotherapy. Pathologic parameters of the 2 groups, such as histologic type, grade and deep myometrial invasion, were comparable. A greater proportion of patients with LUSI had capillary space-like involvement. The patients were followed for a median of 48 months (range, 11-168) from the date of surgery. The overall 5-year recurrence-free survival, disease-specific survival and overall survival rates were 91% (SE .04), 94% (SE .03) and 77% (SE .06), respectively. There was no significant difference between the two groups with regards to these measures (P < .05). CONCLUSION: In patients with state I endometrial cancer, the presence of lower uterine segment involvement does not correlate with their outcome.