A case of primary malignant melanoma of the esophagogastric junction with abscopal effect after nivolumab administration

Background The abscopal effect is a rare phenomenon in which local irradiation causes tumor regression outside the irradiated area. There have been no reports of abscopal effect in patients with gastrointestinal melanoma with metastasis. Here, we report a case of primary malignant melanoma of the esophagogastric junction with abscopal effect after long-term treatment with nivolumab. Case presentation A 75-year-old woman was referred to our hospital with a gastroesophageal lesion. Upper gastrointestinal endoscopy revealed a raised lesion on the posterior wall of the greater curvature of the cardia and tenderness in the lower esophagus. Immunostaining of the tumor biopsy showed positive staining for Melan-A, human melanoma black-45 (HMB45), and S-100, indicating malignant melanoma of the esophagogastric junction. Contrast-enhanced computed tomography (CT) of the abdomen showed a mildly stained lesion protruding into the cardiac part of stomach and enlarged surrounding lymph nodes. The patient was diagnosed with malignant melanoma of the esophagogastric junction and proximal gastrectomy with lower esophagus resection was performed. Histological examination showed large, round tumor cells with nuclear atypia. Immunostaining was positive for Melan A, HMB45, S-100 protein, and SRY-box transcription factor 10, and the final diagnosis was malignant melanoma of the esophagogastric junction, with regional lymph node metastases. Three months after surgery, follow-up CT indicated left pleural metastasis; therefore, the patient was administered nivolumab, an immune checkpoint inhibitor (ICI). Following three courses of nivolumab, the patient exhibited grade 3 renal dysfunction (Common Terminology Criteria for Adverse Events version 5.0). After that, we have not administered nivolumab treatment. Five months after the development of renal dysfunction, a CT scan demonstrated an unstained nodule within the pancreatic, and the patient was diagnosed with pancreatic metastasis; intensity-modulated radiotherapy was performed. Six months later, CT revealed pancreatic nodule and pleural metastasis was shrunk; after an additional 2 months, pleural metastasis and effusion had disappeared. The patient is alive with no additional lesions. Conclusions We report a case of primary malignant melanoma of the esophagogastric junction with an abscopal effect following nivolumab treatment. The findings of this case report suggest that ICIs in combination with radiotherapy may be effective for treating metastatic or recurrent malignant melanoma of the gastrointestinal tract.

Prognostic Difference of Pleural versus Distant Metastasis after Surgery for Lung Cancer

Background: Pleural metastasis in lung cancer found at diagnosis has a poor prognosis, with 5–11 months’ survival. We hypothesized that prognosis might be different for patients who have had curative-intent surgery and subsequent pleural recurrence and that survival might differ based on the location of the first metastasis (distant versus pleural). This may clarify if pleural recurrence is a local event or due to systemic disease. Methods: A database of 5089 patients who underwent curative-intent surgery for lung cancer was queried, and 85 patients were found who had biopsy-proven pleural metastasis during surveillance. We examined survival based on pattern of metastasis (pleural first versus distant first/simultaneously). Results: Median survival was 34 months (range: 1–171) from the time of surgery and 13 months (range: 0–153) from the time of recurrence. The shortest median survival after recurrence was in patients with adenocarcinoma and pleural metastasis as the first site (6 months). For patients with pleural metastasis as the first site, those with adenocarcinoma had a significantly shorter post-recurrence survival when compared with squamous cell carcinoma (6 vs. 12 months; HR = 0.34) and a significantly shorter survival from the time of surgery when compared with distant metastases first/simultaneously (25 vs. 52 months; HR = 0.49). Conclusions: Patients who undergo curative-intent surgery for lung adenocarcinoma that have pleural recurrence as the first site have poor survival. This may indicate that pleural recurrence after lung surgery is not likely due to a localized event but rather indicates systemic disease; however, this would require further study.

Clinical Study of Recombinant Human Endostatin Combined with Iressa in Targeted Treatment of Patients with Lung Adenocarcinoma with Pleural Metastasis

Objective: To evaluate and comprehensively analyze the clinical efficacy of recombinant human endostatin combined with Iressa targeted therapy in patients with pleural metastasis of lung adenocarcinoma. Methods: The interval of the selected study period span was from January 2017 to April 2021. The sample source of the study was 42 patients with lung adenocarcinoma admitted to hospital. The random number table method was used for study grouping, and they were further divided into study groups (n = 21, 14 cases with pleural metastasis) and control group (n=21, 13 cases with pleural metastasis), all patients received systemic chemotherapy with pemetrexed and cisplatin. Patients with pleural metastases in the control group were injected with 60 mg cisplatin into the thoracic cavity. Patients in the study group were treated with Iressa (gefitinib) targeted therapy if genetic testing showed epidermal growth factor receptor (EGRF) mutations, and patients with pleural metastases were treated with pleural metastasis with Endo (recombinant human endostatin YH-16) to control pleural effusion. Two sets of related indicators were compared and analyzed. Results: Comparing the short-term disease control rate, treatment effectiveness and long-term survival rate between the two groups shows that the study group has more advantages (P<0.05). In the comparison between the two groups of serum markers and related indicators, the study group has more advantages (P<0.05), whereas in the comparison between the two groups in the incidence of adverse reactions, there is no significant difference (P>0.05). Based on statistics of the recurrence rate of pleural fluid in the two groups, the study group is significantly lower than the control group (P<0.05). Conclusion: Recombinant human endostatin combined with Iressa targeted therapy for patients with lung adenocarcinoma with pleural metastasis has significant short-term and long-term effects without serious adverse reactions. It can be fully promoted in medical institutions at all levels.

Tumor-secreted versican co-opts myeloid IKKβ during metastasis

The mechanisms tumor cells use to hijack the immune system are largely uncharted. Here we used bioluminescent nuclear factor (NF)-κB reporter mice and macrophages to discover that metastatic tumors trigger NF-κB activation in host macrophages, dependent on mutant KRAS signaling and delivered via secretory versican. Versican activates NF-κB in tumor-associated macrophages via inhibitor of NF-κB kinase (IKK) β, resulting in release of interleukin (IL)-1β into the tumor microenvironment. Versican silencing in cancer cells or conditional IKKβ deletion in macrophages prevents myeloid NF-κB activation and metastasis. Versican is overexpressed and/or mutated in human cancers and metastatic effusions with KRAS mutations, predicts poor survival, can aid in the development of diagnostic platforms for pleural metastasis, and is druggable via toll-like receptor (TLR) 1/2 inhibition. The data indicate a cardinal role for tumor-derived versican in establishing cross-talk with macrophage IKKβ during metastasis and may foster the development of new therapies and diagnostic tools.