P-186 Neoadjuvant immune checkpoint inhibition in stage III/IV oral cancer patients: the NeoNivo trial

SummaryBackground. The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Method and patients. Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local–regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). Results. All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7–34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p < 0.001) and 3.6 months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65 years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263–22.942, p = 0.023)). Conclusion. In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

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Exceptional antitumor responses beyond immune checkpoint inhibition in non-small cell lung cancer patients: insights into optimal therapy sequencing

Journal of Thoracic Disease ◽

10.21037/jtd.2019.02.38 ◽

2019 ◽

Vol 11 (3) ◽

pp. E25-E31

Author(s):

Andriani Charpidou ◽

Ioannis Vathiotis ◽

Ioannis Gkiozos ◽

Konstantinos Syrigos

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Small Cell ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition ◽

Small Cell Lung ◽

Lung Cancer Patients

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PO-1195 Residual MTV after chemoradiotherapy ± immune checkpoint inhibition for inoperable stage III NSCLC

Radiotherapy and Oncology ◽

10.1016/s0167-8140(21)07646-5 ◽

2021 ◽

Vol 161 ◽

pp. S991

Author(s):

J. Taugner ◽

M. Unterrainer ◽

L. Käsmann ◽

C. Eze ◽

W. Kunz ◽

...

Keyword(s):

Immune Checkpoint ◽

Stage Iii ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition ◽

Stage Iii Nsclc

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Unveiling a Critical Role of Thrombin in Enhanced CD8+ T Cell Response to Cancer

Blood ◽

10.1182/blood-2019-128739 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4918-4918

Author(s):

Rachel Cantrell ◽

Leah A. Rosenfeldt ◽

Duaa Mureb ◽

Balkrishan Sharma ◽

Alexey Revenko ◽

...

Keyword(s):

T Cell ◽

Tumor Microenvironment ◽

Cancer Patients ◽

Immune Checkpoint ◽

Thrombin Generation ◽

Critical Role ◽

Cd8 T Cell ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition

A serious and life-threatening cancer-associated sequelae is venous thromboembolism (VTE). Indeed, VTE is the second leading cause of death in cancer patients, second only to the malignancy itself. Cancer patients with VTE or at high risk for VTE are generally treated with anticoagulants, which limit thrombin generation. While it's been widely accepted that thrombin plays a role in cancer progression, the effects thrombin has on other cell types within the tumor microenvironment (TME) have not been thoroughly studied. An understudied role of thrombin may be found in its ability to drive T cell functions. Recently, we have identified thrombin as a potential enhancer of CD8+ T cell effector functions by signaling through the protease activated receptor 1 (PAR-1). Our preliminary data shows that thrombin increases CD8+ T cell survival in a PAR-1 dependent fashion. CD8+ tumor infiltrating lymphocytes (TILs) play a critical role in tumor clearance through their cytolytic and anti-tumor cytokine producing capacity. However, the hostile tumor microenvironment (TME) promotes a gradual reduction in CD8+ TIL capacity to produce cytokines and kill targets. Specific components of the TME, including PDL1 expression, are associated with loss of T cell functionality. A promising strategy to block the interaction of CD8+ TILs and the inhibitory TME components is immune checkpoint inhibition (ICI) therapy, as shown by effective blockade of PD1 signaling by anti-PD1 antibodies. However, these ICI therapies leave many patients unresponsive, highlighting the necessity to uncover additional underlying mechanisms involved in modulating CD8+ T cell responses against cancer. Our preliminary findings lead us to hypothesize that thrombin, in conjunction with PD1 blockade, may work in synergy to promote CD8+ T cell killing of tumors. Consistent with our hypothesis, preliminary results suggest that thrombin is necessary for a robust anti-tumor immune response following ICI in vivo. Here, cohorts of C57BL/6 mice with low or normal circulating prothrombin levels bearing B16 tumors were treated with an anti-PD1 antibody or control IgG. Anti-PD1 therapy significantly limited tumor growth in mice with normal prothrombin levels, but had no impact on tumor growth in mice with low prothrombin levels. A major implication of our findings is that limiting thrombin generation with anticoagulants may be detrimental in the context of immune checkpoint inhibition treatment. Better defining the potential risk of reducing ICI efficacy by concurrent treatment with anticoagulants will require a detailed understanding of the role thrombin plays in cancer immunobiology. Disclosures Revenko: Ionis Pharmaceuticals: Employment. Monia:Ionis Pharmaceuticals: Employment. Palumbo:Ionis Pharmaceuticals: Research Funding.

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The Role of Socioeconomic Status and Literacy in the treatment delay in Oral Cancer patients Visiting Mayo Hospital

10.53350/pjmhs211581785 ◽

2021 ◽

Vol 15 (8) ◽

pp. 1785-1787

Author(s):

Ahmad Liaquat ◽

Rabia Naseer ◽

Muhammad Rashid ◽

Saqib Mehmood Khan ◽

Ehsan Ul Haq ◽

...

Keyword(s):

Socioeconomic Status ◽

Oral Cancer ◽

Cancer Patients ◽

Treatment Delay ◽

Stage Iii ◽

Care Hospital ◽

Low Socioeconomic ◽

Oral Cancer Patients ◽

Late Stages

Background: One of the most important prognostic factors of oral cancer is the stage at the time of diagnosis. Unfortunately, most of the patients present in the late stages (stage III and IV). Aim: To assess the role of socioeconomic status and literacy in the treatment delay in patients of oral cancer. By identifying their role, we can educate the general public and healthcare doctors to detect and treat oral cancer. Method: This was a prospective study conducted in the Mayo hospital, a tertiary care hospital of Pakistan, from June 2018 to June 2020. Results: Out of 120 patients, 84 (70%) were males and 36 (30%) were females. The age range was 14 to 85 years. One hundred and eight patients (90%) presented with the late stages (stage III and IV). These late-stage presenter patients belonged to the low socioeconomic status (88.88%) and 83.33% of them were illiterate (<high school education). Only twelve patients (10%) presented with the early stage at the time of diagnosis. Conclusion: Low socioeconomic and lack of education have a significant association with the late presentation of oral cancer patients in the Pakistani population. Keywords: squamous cell carcinoma, treatment delay, socioeconomic status

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