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Introduction: Metastatic involvement of at least one nonregional lymph node currently renders patients with esophageal cancer as having stage IV disease. However, the management and outcomes of patients whose sole determinant of stage IV status is nonregional lymph nodes (abbreviated as “stage IV-nodal” disease) have not been fully characterized. Methods: In this retrospective cohort study, the National Cancer Database was queried to identify patients 18 years of age or older who were diagnosed with stage IV esophageal cancer between 2016 and 2019. Survival was assessed by Kaplan-Meier analysis and Cox models in the overall sample and a propensity-matched sample. Patients with “stage IV-nodal” disease were compared with patients with systemic metastases involving a single organ or multiple organs. Results: Overall, 11,589 patients with clinical stage IV esophageal cancer were identified, including 1331 (11.5%) patients with stage IV-nodal disease. Patients with stage IV-nodal disease were more likely to receive chemotherapy (77%) than those with single systemic organ metastases (64%) and multiorgan metastases (63%) (p < 0.0001); patients with stage IV-nodal disease were also more likely to receive radiation (49%) than those with single systemic organ metastases (40%) and multiorgan metastases (39%) (p < 0.0001). Squamous cell carcinoma (OR = 1.58, 95% confidence interval [CI]: 1.34–1.86, p < 0.0001) and academic facility type (OR = 1.24, 95% CI: 1.09–1.4, p = 0.0009) were associated with higher likelihood of the stage IV-nodal presentation. Patients with stage IV-nodal disease experienced superior survival (hazard ratio = 0.72, 95% CI: 0.66–0.78, p < 0.0001) than those with stage IV-single systemic metastases (reference group) and stage IV-multiorgan disease (hazard ratio = 1.30, 95% CI: 1.24–1.37). Conclusions: Approximately 12% of patients with stage IV esophageal cancer lack systemic metastases at presentation. These patients with stage IV-nodal disease are more likely to receive treatment and experience superior survival. Further study of the stage IV-nodal population and consideration of a potential stage IV subclassification system is justified.

Background: Metastatic gallbladder carcinoma (GBC) is one of the most aggressive malignancies. As GBC is usually diagnosed with distant metastases, only a few patients can receive R0 resection and the relapse rate remains high. Programmed cell death protein 1 (PD-1) blockade therapy has provided encouraging long-term outcomes in a subset of patients in many cancers. However, the data on efficacy of PD-1 blockade in GBC are very limited. Case Presentation: We herein reported a stage IVB GBC patient with localized primary tumor and distant lymph node metastasis. Except for the unresectable multiple metastatic nodes including distant nodes, a complete resection of primary tumor en bloc with partial segment 4B+5 was performed. Tumor tissues of primary tumor and one metastatic lymph node were collected to perform whole-exome sequencing, RNA-seq, and immunohistochemistry. Low TMB (5.38 muts/Mb), low MSI (<20%), and negative PD-L1 expression (TC0) were observed in the primary tumor. Likewise, low TMB (5.44 muts/Mb), low MSI (<20%), and low PD-L1 expression (TC2) presented in the metastatic lymph node. Besides, low genetic intratumor heterogeneity exhibited between the primary and metastatic tumors in this patient. In contrast to the primary tumor, higher-level CD8+ T cell infiltration was revealed in the tumor microenvironment of the metastatic lymph node. Then, chemo-immunotherapy using S1 and anti-PD-1 antibody pembrolizumab was administrated as the first-line treatment for the residual metastatic nodes. Complete response was achieved after 7 courses and has lasted for 32 months up to present. Additionally, blood samples during treatment were further analyzed for immune repertoire sequencing, showing that several T cell receptor clones in metastatic lymph node were predominant in blood during the combined anti-PD-1 treatment. Conclusions: Chemo-immunotherapy may provide a potential curative option for the lymph node metastases of gallbladder cancer. The low intratumor heterogeneity and high level of infiltrating CD8+ T-cells in metastatic node might be indispensable to the durable complete response in this patient. [ABSTRACT FROM AUTHOR]

BackgroundMetastatic gallbladder carcinoma (GBC) is one of the most aggressive malignancies. As GBC is usually diagnosed with distant metastases, only a few patients can receive R0 resection and the relapse rate remains high. Programmed cell death protein 1 (PD-1) blockade therapy has provided encouraging long-term outcomes in a subset of patients in many cancers. However, the data on efficacy of PD-1 blockade in GBC are very limited.Case PresentationWe herein reported a stage IVB GBC patient with localized primary tumor and distant lymph node metastasis. Except for the unresectable multiple metastatic nodes including distant nodes, a complete resection of primary tumor en bloc with partial segment 4B+5 was performed. Tumor tissues of primary tumor and one metastatic lymph node were collected to perform whole-exome sequencing, RNA-seq, and immunohistochemistry. Low TMB (5.38 muts/Mb), low MSI (

Background/Aim: This study aimed to evaluate the outcome of radiation therapy for patients with distant lymph node (LN) metastases, without organ metastases from uterine cervical cancer (UCC). Patients and Methods: Twenty-six patients with UCC with distant LN metastases received radiotherapy and were retrospectively analyzed. The sites of distant LN metastasis were as follows; Supraclavicular in 19, inguinal in nine, axillary in four, and others in three. The mean dose prescribed for these was 50 (range=40-60) Gy. Results: The 2-year overall, cause-specific, and progression-free survival, and local control of primary tumor rates were 51.3%, 51.3%, 46.9%, and 67.9%. In multivariate analysis, performance status ≥1 (p=0.007), para-aortic LN metastases (p=0.001), and lack of high-dose-rate intracavitary brachytherapy (p=0.033) were significantly associated with poor overall survival. Performance status ≥1 (p=0.004), and para-aortic LN metastases (p=0.014) were significantly associated with poor cause-specific survival. Conclusion: This study demonstrated favorable local control in patients with UCC with distant LN metastases. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic involvement of at least one nonregional lymph node currently renders patients with esophageal cancer as having stage IV disease. However, the management and outcomes of patients whose sole determinant of stage IV status is nonregional lymph nodes (abbreviated as "stage IV-nodal" disease) have not been fully characterized., Methods: In this retrospective cohort study, the National Cancer Database was queried to identify patients 18 years of age or older who were diagnosed with stage IV esophageal cancer between 2016 and 2019. Survival was assessed by Kaplan-Meier analysis and Cox models in the overall sample and a propensity-matched sample. Patients with "stage IV-nodal" disease were compared with patients with systemic metastases involving a single organ or multiple organs., Results: Overall, 11,589 patients with clinical stage IV esophageal cancer were identified, including 1331 (11.5%) patients with stage IV-nodal disease. Patients with stage IV-nodal disease were more likely to receive chemotherapy (77%) than those with single systemic organ metastases (64%) and multiorgan metastases (63%) ( p < 0.0001); patients with stage IV-nodal disease were also more likely to receive radiation (49%) than those with single systemic organ metastases (40%) and multiorgan metastases (39%) ( p < 0.0001). Squamous cell carcinoma (OR = 1.58, 95% confidence interval [CI]: 1.34-1.86, p < 0.0001) and academic facility type (OR = 1.24, 95% CI: 1.09-1.4, p  = 0.0009) were associated with higher likelihood of the stage IV-nodal presentation. Patients with stage IV-nodal disease experienced superior survival (hazard ratio = 0.72, 95% CI: 0.66-0.78, p < 0.0001) than those with stage IV-single systemic metastases (reference group) and stage IV-multiorgan disease (hazard ratio = 1.30, 95% CI: 1.24-1.37)., Conclusions: Approximately 12% of patients with stage IV esophageal cancer lack systemic metastases at presentation. These patients with stage IV-nodal disease are more likely to receive treatment and experience superior survival. Further study of the stage IV-nodal population and consideration of a potential stage IV subclassification system is justified., (© 2022 The Authors.)

Eradication of micrometastases present in lymph nodes of cancer patients improves their prognosis significantly. Radionuclide therapy possesses the potential to eliminate such metastases. This study was performed to evaluate the efficacy and safety of 32P-nanocolloid therapy in the treatment of distant carcinoma cell metastases in lymph nodes of VX2 tumor-bearing rabbits. To obtain VX2 tumor micrometastases in right armpit lymph nodes of 12 male New Zealand white rabbits, VX2 tumors were implanted by hypodermal inoculation into the right anterior limb. Animals were randomly divided into therapy ( n = 6) and control ( n = 6) groups. 32P-nanocolloid (0.5 mCi), 95% of which was >50 nm in diameter, was administered to the therapy group, and saline was administered to the control group. Injections were given once weekly for 4 weeks. 2-Deoxy-2[18F]-fluoro- d-glucose positron emission tomography revealed that the number of involved lymph nodes and the maximum standardized uptake value decreased in the 32P-nanocolloid therapy group as compared with the baseline or saline control grou0 ( P < 0.05). The expression of the lymphangiogenesis factors vascular endothelial growth factors (VEGF)-C and VEGF-D by VX2 tumor cells present in lymph nodes was significantly lower in the therapy group as compared with the control group. Additionally, apoptotic VX2 tumor cell death was significantly greater in lymph nodes of the therapy as compared with the control group ( P < 0.01). With the exception of a decrease in white blood cells of peripheral blood ( P < 0.05), standard laboratory values were unaffected throughout the course of therapy with 32P-nanocolloid. These findings support treatment with 32P-nanocolloid as a safe and effective approach for eradication of lymph node micrometastases. [ABSTRACT FROM AUTHOR]

We describe a case of a 58-year-old woman with right inguinal lymph node swelling and a Tl tumor in the right breast. She was referred with an 18-month history of the former complaint and a six-month history of the latter. Excisional biopsy of the inguinal lymph node revealed breast cancer metastasis. Radiographical examination showed no metastases to the lungs, liver or bone. Modified radical mastectomy was performed. Histological examination revealed solid tubular carcinoma, PT2, PM (axillary lymph node metastases 4/16), stage IV. Estrogen and progesterone receptors were negative. Three cycles of postoperative cyclophosphamide, adriamycin and 5-fluorouracil (CAF) chemotherapy were given, and the right inguinal area was irradiated with 40 Gy. The patient complained of swelling in both legs three years after surgery. Computed tomography revealed marked lymph node swellings in the pelvic cavity. She died six months later. Inguinal lymph node metastasis from breast cancer is very rare, although distant lymph node metastasis in the cervix occurs frequently. This case should help clarify how breast cancer metastasizes to distant lymph nodes. [ABSTRACT FROM AUTHOR]

Background/aim: This study aimed to evaluate the outcome of radiation therapy for patients with distant lymph node (LN) metastases, without organ metastases from uterine cervical cancer (UCC)., Patients and Methods: Twenty-six patients with UCC with distant LN metastases received radiotherapy and were retrospectively analyzed. The sites of distant LN metastasis were as follows; Supraclavicular in 19, inguinal in nine, axillary in four, and others in three. The mean dose prescribed for these was 50 (range=40-60) Gy., Results: The 2-year overall, cause-specific, and progression-free survival, and local control of primary tumor rates were 51.3%, 51.3%, 46.9%, and 67.9%. In multivariate analysis, performance status ≥1 (p=0.007), para-aortic LN metastases (p=0.001), and lack of high-dose-rate intracavitary brachytherapy (p=0.033) were significantly associated with poor overall survival. Performance status ≥1 (p=0.004), and para-aortic LN metastases (p=0.014) were significantly associated with poor cause-specific survival., Conclusion: This study demonstrated favorable local control in patients with UCC with distant LN metastases., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)