Rapid Progression of Tracheoesophageal Fistula Caused by Immunotherapy Administered after Tracheal Stent Placement

Development of a tracheoesophageal fistula (TEF) is a serious complication of treatment for esophageal or lung cancer, especially following radiation therapy. However, development of a TEF as a complication of chemotherapy or tracheal stenting after surgical debulking is quite uncommon. We herein report a rare case involving a patient with advanced adenocarcinoma invading the mediastinum who rapidly developed a TEF after placement of a tracheal stent and administration of nivolumab immunotherapy. A 55-year-old heavy ex-smoker was diagnosed with lung adenocarcinoma with mediastinal invasion. Nine months after first-line therapy (chemotherapy and radiation therapy), he underwent treatment with nivolumab (3 mg/kg) as fourth-line therapy. Two weeks after the first dose, he underwent mechanical debulking of the tumor with tracheal stenting because of the rapid development of paraesophageal lymph node swelling and severe tracheal stenosis. He received a second dose of nivolumab 2 weeks later; however, imaging studies 12 days after this second dose revealed a huge fistula between the upper trachea and esophagus through a metastatic lymph node. Neither an additional stent nor replacement of the stent was considered because of the fistula site expansion and suffocation risk. Despite further treatment, the patient died of his primary disease 2 months later. Our findings will be of great interest to the readers, especially those involved in the clinical treatment of patients with advanced lung cancer treated by immunotherapy. The knowledge of potentially devastating TEF formation in the presence of transmural tracheal metastasis/invasion will allow clinicians to provide the best possible care for their patients.

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236 Evaluation of PD-L1 expression in primary lung tumor and metastatic lymph nodes in the presence of immune cells

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0236 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A253-A253

Author(s):

Chris Hansis ◽

Xiaomei Wang ◽

Tao Wang ◽

Gerald Feldman

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Lymph Node ◽

Tumor Cells ◽

Squamous Cell ◽

Immune Cells ◽

Lymph Node Metastases ◽

Metastatic Lymph Node ◽

Metastatic Lymph ◽

Node Metastases

BackgroundImmunotherapies against programmed death ligand-1 (PD-L1) have been established as an effective treatment for a subset of lung cancer patients. Even though it is critical for a successful therapy to know prevalent PD-L1 expression patterns in all affected tissues, information on matching lymph node metastases and immune cells is particularly limited. The purpose of this study was thus to evaluate comparative PD-L1 expression profiles in those tissues.MethodsFDA-approved IHC assays for PD-L1 (Dako 22C3) were performed on a lung tissue array (LC814A, US Biomax) according to manufacturer’s instructions. Histopathological analysis by H-scoring was performed to determine the rate and intensity of positive tumor and immune cell staining for each of the 80 cores. The H score was calculated as follows: A total of up to 300 cells were assessed, per specimen, at 40x high-power magnification (typically over 7–10 fields). A staining level of 0–3 was then assigned to each cell, to designate the intensity of specific positive membranous-to-cytoplasmic staining. The H score was subsequently calculated as% cells staining at level 1 (x1) +% cells staining at level 2 (x2) +% cells staining at level 3 (x3) = total H score per sample. This resulted in a maximum possible H score of 300.ResultsOf the 16 adenocarcinoma tumor samples with a valid staining, 7 (44%) showed positive PD-L1 staining for tumor cells and 10 (63%) for primary immune cells. Importantly, 9 matching metastatic lymph node samples out of the 16 samples (56%) showed an increased PD-L1 H score compared to primary tumors for both tumor cells and immune cells (figure 1). Of the 15 squamous cell carcinoma samples with a valid staining, 11 (73%) showed detectable PD-L1 expression levels in the primary tumor and 12 (80%) in the primary immune cells, while 7 (47%) and 9 (60%) showed lower scores in matching metastatic lymph node tumor cells and their immune cells, respectively (figure 2). Very low or no expression of PD-L1 was detected in small cell lung cancer, as to be expected from previous studies.Abstract 236 Figure 1PD-L1 Staining in adenocarcinomaAbstract 236 Figure 2PD-L1 Staining in squamous cell carcinomaConclusionsSquamous cell carcinomas and adenocarcinomas display significant heterogeneity with regard to PD-L1 expression in associated lymph node metastases. While the reasons for this frequent discordant PD-L1 expression pattern involving both tumor and immune cells need to be investigated further, our findings may help guide the proper interpretation of PD-L1 companion diagnostic test results and subsequent therapeutic decisions.AcknowledgementsThe views in this Abstract have not been formally disseminated by the U.S. Food and Drug Administration and should not be construed to represent any agency determination or policy.

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Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00448-5 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zhenyu Ding ◽

Qing Li ◽

Rui Zhang ◽

Li Xie ◽

Yang Shu ◽

...

Keyword(s):

Lung Cancer ◽

Dendritic Cell ◽

Cancer Treatment ◽

Checkpoint Inhibitors ◽

Rapid Development ◽

Therapeutic Modality ◽

Advanced Lung Cancer ◽

Cell Vaccine ◽

Lung Cancer Treatment ◽

Dc Vaccine

AbstractNeoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3–14 doses/person). In total, 12–30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1–2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.

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