Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Death

Breast Neoplasms

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Bupivacaine

Anesthetics, Local

all patients will receive general anesthesia and will receive intravenous paracetamol (1 g) before skin closure and then given every 6 hrs in the 1st postoperative day

Patients will receive total volume (20 ml) 0.25% bubivicaine divided equally at each level of T4 and T6 at thoracic paravertebral space then they will recive general anesthesia.

TPVB will be given using high frequency linear U/S transducer, place the U/S ultrasound probe was placed parallel to the vertebral spine at T4, and, T6 level and shifted 2-3 cm laterally to obtain the appropriate visualization. Following the identification of pleura, transverse process and paravertebral space, the needle was inserted in caudocranial direction using in-plane approach. Confirm negative vessel or pleural breach via aspiration then proceed with local anaesthetic 0.25% bupivacaine (20 ml) delivery slowly divided equally at T4and T6; the pleura will be seen to be pushed downward

Thoracic Paravertebral block

shereen M kamal, assocate professor

Hassan I Kotb, professor

Shereen M Kamal, Lecturer

Hassan M Kotb, Professor

Surgery is first-line treatment for solid tumors. However, surgical trauma-induced physiologic stress has been demonstrated to facilitate metastasis and recurrence in different types of cancer. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.

The cellular immune response plays a central part in postoperative clearance of tumor cells. T lymphocytes and natural killer (NK) cells are two predominant cytotoxic effector cells that are the major components of antitumor immunity. In mouse models, proliferation of T lymphocytes in response to surgical trauma is defective . Programmed death-1 (PD-1) belongs to the CD28 receptor superfamily. It is an inhibitory receptor, and its expression is upregulated on activated leukocytes, resulting in an inhibited immune response. PD-1 interacts with two ligands: programmed death ligand-1 (PD-L1, also referred to as B7-H1) and programmed death ligand-2 (PD-L2, also known as B7-DC). PD-L2 is expressed mainly on activated dendritic cells (DCs) and macrophages, whereas PD-L1 is distributed widely. In addition to immune cells, some subsets of tumor cells also express PD-L1 to escape from immunosurveillance. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.

Effect of Anesthesia on Expression of Programmed Death-1 and Programmed Death-1 Ligand in Breast Cancer

Effect of Anesthesia and Surgical Stress on the Expression of Programmed Death-1 and Programmed Death-1 Ligand on T Lymphocyte After Breast Cancer Surgeries

blood sample will be withdrawn and human peripheral blood monocyte cells (PBMCs) will be separated with a Ficoll-Isopaque density gradient. Flow cytometric analyses will be carried out immediately. For ex vivo experiments, PBMCs will be cultured with Iscove's modified Dulbecco's medium (IMDM) containing 10 % human serum albumin.

the total amount of analgesia (paracetamol) will be recorded and calculated

Assiut University

Lecturer of anesthesia, ICU and pain managment

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy.

Patients receive cadonilimab (10mg/kg) every 3 weeks.

Cadonilimab

Patients receive pemetrexed (500mg/m2) every 3 weeks.

Patients receive carboplatin (AUC=5) every 3 weeks for 4 cycles.

Qian Chu

This is a single arm, multi-center clinical trial. Target population is advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell Death Ligand 1 (PD-L1) negative, aiming to evaluate the efficacy and safety of the combination therapy of Cadonilimab and chemotherapy. Cadonilimab is a PD-1/CTLA-4 bi-specific antibody.

This trial enrolled advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell Death Ligand 1 (PD-L1) negative. Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy. The primary endpoint is 12-month progression-free-survival (PFS) rate assessed by investigators. Key secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR), time to response (TTR), progression free survival (PFS), overall survival (OS), and safety.

Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative

Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative：A Multi-center, Single-arm, Phase II Study

Rate of patients with complete/partial response at 12-month from enrollment

objective response rate using RECIST 1.1 criteria

Time from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause

disease control rate using RECIST 1.1 criteria

Time from the date of enrollment to the first documented response (CR or PR) (RECIST 1.1)

Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)

Time from enrollment until death due to any cause

Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Akeso Pharmaceuticals, Inc.

Professor

Breast Diseases

Skin Diseases

The pretherapeutic cores or specimen from patients who meet the following criteria were subjected for analysis

INCLUSION CRITERIA Primary Breast cancer Completed scheduled treatment at SGPGI Adequate quality histopathology material available in Department of Pathology archives With minimum 6 months follow up

EXCLUSION CRITERIA Insufficient data Incomplete treatment Insufficient follow up information Insufficient histological material for review

Assessment of Prognostic and Predictive value of Tumor-Infiltrating Lymphocytes and Programmed cell Death - Ligand 1 in Breast cancer

Observational Study

Vishvak Chanthar

Gaurav Agarwal

Vishvak Chanthar K M M

The morphological evaluation of Tumor-infiltrating Lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. In breast cancer (BC) lesions, TILs are seen in intratumoral and stromal areas. TILs are predictive of response to treatment and this association appears to be strongest in Triple-negative (TNBC) and Her 2 (Human epidermal growth factor receptor) positive breast cancer subtypes. Contrastingly, the association in Estrogen Receptor (ER) positive, HER 2 negative tumors have not been established.

Programmed cell death 1 (PD-1), are receptors expressed on the surface of T, B, and Natural killer cells and in some tumor cells. These attenuate the cellular immune response by inducing T-cell apoptosis. Programmed Cell Death Ligand 1 (PD-L1) overexpression is reported to be associated with large tumor size, lymph node metastasis, and ER-negativity. Importantly, PD-L1 is expressed more frequently in TNBC patients. High PD-L1 expression may be a prognostic indicator for reduced overall survival6. This information may be helpful to screen candidates for anti-PD-1/PD-L1 therapy, especially patients with TNBC The aim of this study is to characterize the cohort of patients with breast cancer based on a semiquantitative assessment of TILs and to correlate the concentration of TILs and PD-L1 in various intrinsic subtypes (based on Immunohistochemistry) with the overall outcome. Also to correlate the TILs and PD-L1 expression with tumor response to Neoadjuvant Chemotherapy (NACT) and to stratify the predictive value of this biomarker in TNBC.

This is a retrospective and prospective study in patients with Primary Breast cancer at Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI). This is a time-bound study, where we include all patients treated between January 2016 and December 2021 who meet the inclusion criteria. We screened out approximately 2000 patients treated over this period, of which about 1000 had met inclusion criteria.

The electronic and physical records of all breast cancer patients maintained in Hospital Information System and Department of Breast and Endocrine Surgery at SGPGI have been screened to identify all appropriate cases and their clinical data were reviewed.

The cohort of patients who met the inclusion criteria was identified from the screened data.

The paraffin blocks of pre-therapeutic core biopsies/ surgical specimens of the study subjects were retrieved and the same from prospective study subjects were included.

Existing data on Immunohistochemistry (IHC) for ER (Estrogen Receptor), PR (Progesterone Receptor), Her 2 neu (Human epidermal growth factor receptor) was tabulated to identify TNBC cohort.

Hematoxylin \& Eosin stained histological slides were reviewed by one set of pathologists for semi quantification of TILs.

TILs have been analyzed both as continuous parameters and in three predefined groups of Low: 0-10%; Intermediate:11 - 59 % and high: ≥ 60 % stromal TILs. In patients with TNBC, the paraffin blocks were retrieved and PD-L1 expression was assessed by IHC.

At this point in time, the recruitment of subjects and semi-quantification of TILs and PDL-1 were over and the analysis/correlation part is yet to be done.

In all study subjects, the concentration of TILs will be correlated with the clinicopathological outcome (treatment response, overall survival, disease-free survival ) and this association will be compared between intrinsic subtypes based on IHC.

In patients treated with Neoadjuvant Chemotherapy (NACT), correlation of TILs with response to NACT (pathologic complete response, partial/static/progression) will be done.

Correlation of PDL-1 expression with outcomes (overall survival, disease-free survival) and with response to Neoadjuvant Chemotherapy (pathologic complete response, partial/static/progression) in patients with Triple Negative Breast Cancer will be done.

The study information obtained will be statistically analyzed to identify the significance of the aforementioned correlations.

Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer

Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer

To Correlate the concentration of TILs and PD-L1 in various intrinsic subtypes (based on Immunohistochemistry) with the overall outcome

To Correlate PDL-1 expression with outcomes in patients with TNBC

To Correlate the TILs with tumor response to Neoadjuvant Chemotherapy and to stratify the predictive value of this biomarker

To Correlate PD-L1 expression with response to Neoadjuvant Chemotherapy in patients with TNBC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Anesthesia on Expression of Programmed Death-1 and Programmed Death-1 Ligand in Breast Cancer	NCT04657237	Programmed Cell...	Thoracic Parave...	18 Years - 65 Years	Assiut University
Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative	NCT06001151	Carcinoma, Non-...	Cadonilimab Pemetrexed Carboplatin	18 Years - 75 Years	Tongji Hospital
Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer	NCT05250336	Breast Cancer Tumor Infiltrat... Programmed Cell...	Observational S...	18 Years - 90 Years	Sanjay Gandhi Postgraduate Institute of Medical Sciences
Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative	NCT06001151	Carcinoma, Non-...	Cadonilimab Pemetrexed Carboplatin	18 Years - 75 Years	Tongji Hospital
Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer	NCT05250336	Breast Cancer Tumor Infiltrat... Programmed Cell...	Observational S...	18 Years - 90 Years	Sanjay Gandhi Postgraduate Institute of Medical Sciences

Spots Global Cancer Trial Database for programmed cell death ligand 1