Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Death

Breast Neoplasms

Neoplasms, Second Primary

Breast Diseases

Skin Diseases

We will enroll women with a biopsy-proven diagnosis of early-stage breast cancer (T1 N0), not eligible for neo-adjuvant therapy, scheduled to breast surgery (mastectomy or nodulectomy), who have given the informed consent for the study.

We will recruit 20 women who will undergo cryoablation.

The results will be compared with those obtained from a control group of 20 women, who will follow the same therapeutic pathway for the treatment of breast cancer without performing cryoablation.

cryoablation of breast cancer smaller than 2 cm

cryoablation

Federica Pediconi, MD

The aim of our study is to examine the cryoimmunologic response and its mechanisms induced by US-guided cryoablation of small breast tumors (\<2 cm) not eligible to neoadjuvant therapy. We will recruit 30 women who will undergo cryoablation and their results will be compared with a control group of 30 women, who will follow the same therapeutic pathway without performing cryoablation. All recruited patients will undergo an enrollment check, pre-cryoablation breast MRI and blood test to assess immune response, breast cancer US-guided cryoablation, post-cryoablation breast MRI and the same blood test to evaluate immunologic response. Within 21 days all patients will undergo breast surgery, with immuno-histopathological analysis on surgical specimen.

At least 10 days after surgery the patient will undergo clinical breast examination, blood test to assess immune response and patient satisfaction questionnaire.

Cryoablation treatment will be performed using a 14G cryoprobe under us-guidance for visualization of the ice ball surrounding the lesion. The ultrasound guide is used to ensure that the action affects the entire tumor and that therapeutic temperatures are reached in every part of the tumor.

Pre- and post- cryoablation breast MRI will be performed on a 3T magnet to assess cryoablation rate of success. Artificial intelligence algorithms will also be used for this purpose. Cryoablation treatment efficacy will also be evaluated with ultrasound.

The immunological fitness of cancer patients will be studied by flow cytometry, evaluating the presence of cytokines/chemokines relevant during anticancer immune response/tumor progression and for the presence of molecules released by cells during an immunogenic cell death.

The goal of our study will be to demonstrate that cryoablation of breast cancer can induce an antitumor immune response.

Therefore this approach could become an additional tool in the oncological treatment of breast cancer.

We will enroll women with a biopsy-proven diagnosis of early-stage breast cancer (T1 N0), not eligible for neo-adjuvant therapy, scheduled to breast surgery (mastectomy or nodulectomy), who have given informed consent for the study.

We will recruit 30 women who will undergo cryoablation. Their results will be compared with those obtained from a control group of 30 women, who will follow the same therapeutic pathway for the treatment of breast cancer without performing cryoablation.

The primary objective of our study is the characterization of the Immunogenic Cell Death (ICD) induced, the inflammatory response and the modulation of circulating T immune cells induced by tumor cryoablation treatment in the serum of breast cancer patients.

The circulating ICD biomarkers HMGB1, calreticulin and HSP70/90 will be analysed and also the profile of Th1 and Th2 type cytokines (IFN-γ, IL-12 (p40/p70), IL-15, IL-17, IL-2, IL-7, IP-10, IL-13, IL-5, IL-4), pro-inflammatory cytokines (IL-1α, IL-1β, IL- 6, TNF-α, IL-1RA, IL-2R, IL-8, CRP, IL-17, IFN-α), immunosuppressive cytokines (TGF-β1, IL-10, PGE2), chemokines (CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL9/MIG, CCL11/Eotaxin). Immune cell subsets will be characterized by flow cytometry: besides the conventional immune cell subsets (NK, Monocyte, Granulocyte, T and B cells), specific T cell subsets (Treg, naïve, memory, central effector) will be characterized and also the expression of immune markers associated to activation (CD137) or suppression/exhaustion (PD1, CTLA4, TIM3, LAG3).

Secondary endpoints are:

1. Cryoablation treatment efficacy and safety

   We will evaluate Recist criteria rate of complete response to cryoablation with breast ultrasound and breast MRI. Incidence vand severity of complications related to cryoablation will be monitored to establish safety profile ablating breast cancer with 10 mm margins around the primary tumor.
2. Cryoablation treatment capability to induce immunogenic tumor cell death.

   The presence and the extent of tumor necrosis / apoptosis on surgical specimen sections stained with hematoxylin-eosin will be evaluated. Immunohistochemical tests will be used to verify the activation of apoptotic mechanisms and Immunogenic cell death activation.
3. Tumor microvesicles release following Cryoablation treatment. During cell death, microvesicles (MVs) released by the cell transport a complex molecular cargo that can act as source of antigen repertoire and activatory signals to Antigen Presenting cells (APCs). Tumor derived MVs released in the serum of the patients will be isolated by ultracentrifugation steps as preliously described. The isolated MVs will be tested for the expression of Calreticulin and HMGB1.

All enrolled patients will undergo series of check as shown below (ICE-STUDY STEPS) :

enrollment check (STEP 0), breast MRI pre-cryoablation treatment (STEP 1) and post-cryoablation treatment (STEP 4), breast cancer US-guided cryoablation

(STEP 2), blood test to assess immune response (STEP 1, STEP 3, STEP 4, SURGERY and STEP 5) and surgical specimen immuno-histopathological analysis.

Enrollment check (STEP 0) will be conducted by a radiologist and an oncologist, where the patient's medical history will be collected and a breast examination of the affected site will be performed. The patient will also undergo breast US to evaluate cryoablation treatment feasibility (distance \>1 cm between the tumor and the skin, the nipple or the chest wall). If the patient is considered eligible to the study, the protocol will be illustrated in detail and informed consent will be collected.

Breast MRI will be performed pre-cryoablation (STEP 1) and post-cryoablation (STEP 4) to assess Visual-ICE ablation rate of success. Artificial intelligence algorithms will also be used for this purpose. Cryoablation treatment efficacy will also beevaluated with ultrasound (STEP 4).

STEP 2 consists in US-guided cryoablation treatment of the breast lesion.

Within 21 days from the enrollment the patient will undergo breast surgery and blood test.

During the Final STEP, the patient will undergo clinical breast examination, blood test to assess immune response and patient satisfaction questionnaire.

ICE-STUDY STEPS:

STEP 0: enrollment check

* Imaging: US
* Assessment:

  1. consent
  2. breast biopsy with histological result
  3. clinical history
  4. laboratory results
  5. clinical breast examination
  6. pharmacological therapy

STEP 1: Within 10 days from STEP 0

* Imaging: MRI (pre-cryoablation treatment)
* Assessment:

  1. blood test for immune response
  2. side effects

     STEP 2: CRYOABLATION (At least 24h after MRI)
* Assessment:

  1. cryoablation complications and side effects

     STEP 3: Blood test for immune response (48/72 h after cryoablation)

STEP 4: After 7 days from cryoablation and before surgery

* Imaging: MRI and/or US (post-cryoablation treatment)
* Assessment:

  1. patient satisfaction questionnaire.
  2. Side effects
  3. pharmacological therapy
  4. clinical breast examination
  5. blood test for immune response

SURGERY: Within 21 days from STEP 0

* Assessment:

  1. surgery
  2. complications
  3. specimen histological evaluation
  4. blood test for immune response

     STEP 5 - FINAL: At least 10 days after surgery
* Assessment:

  1. patient satisfaction questionnaire
  2. side effects
  3. pharmacological therapy
  4. clinical breast examination
  5. blood test for immune response

All cryoablation sessions will be performed under US-guidance by a single board-certi¿ed interventional radiologist. Biopsy, percutaneous cryoablation will be carried out using an argon-based cryoablation unit (BTG Cryoablation System).

Both preoperative US and MRI images will be compared in order to determine the correct positioning of the probe for tumor ablation. All the procedures will be carried out under local anesthesia given by injection of 2-5mL of 2% lidocaine proximal to the tumor lesion and along the course of the cryoprobes. One or more cryoprobes will be inserted into the targeted tumor using US guidance, through a small skin incision of 1-2mm. To avoid cryoinduced skin injury and facilitate the ablation of breast tissue at least 1cm beyond all apparent tumor margins, warming bags will be placed on the breast skin.

Due the relatively low heat load of breast parenchyma compared with internal organs, it was estimated that 1cm of visible ice beyond all the tumor margins would be necessary to generate cytotoxic temperatures (e.g.,-40¿C) throughout the breast tumor.

Each cryoablation treatment session consists in two cycles of 8 minutes of duration, followed by a 4-minute active thawing phase and a 4-minute passive thawing phase. The latter is considered useful to maximize cell death. US guidance will be also used to verify the formation of a homogeneous hypoechoic area, owing to the iceball, which encompassed the tumor all around and to detect early complications. The probes will be removed after the second phase of thawing, without the need for skin suture. After the procedure, the patients will be discharged in 2 hours a¿er the ablation, without any prescription.

The clinical outcome will be evaluated with US at the end of the cryoablation procedure and 7 days a¿er with clinical examination and MRI. The absence of such signs or symptoms will be interpreted as an optimal clinical result.

Immunogenic CELL DEATH and Inflammatory circulating Biomarkers will be analysed at different time points (5 time points:

before, 48 h and 7 days after cryoablation; before and after 10 days from surgery). Plasma will be isolated by EDTA treated blood (10 ml/sample) by centrifugation (4000 rmp/5'/4°C) and aliquoted and stored at -80°C.

The ICD biomarkers characterized will be: calreticulin, HMGB1, HSP70/90 (by ELISA and/or chemioluminescence immune sandwich tests).

Circulating Inflammatory mediators will also be analyzed by xMAP Multiplex platform including the following molecules:

Th1 and Th2 type cytokines (IFN-γ, IL-12 (p40/p70), IL-15, IL-17, IL-2, IL-7, IP-10, IL-13, IL-5, IL-4), pro-inflammatory

cytokines (IL-1α, IL-1β, IL-6, TNF-α, IL-1RA, IL-2R, IL-8, CRP, IL-17, IFN-α), immunosuppressive cytokines (TGF-β1, IL- 10, PGE2), chemokines (CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL9/MIG, CCL11/Eotaxin)\] will be analyzed.

The samples of each patient will be analysed for each biomarker simultaneously to avoid inter-experiment bias.

Microvesicles will be isolated by ultracentrifugation steps in micro-method scale (2 mL of plasma) and the analysis of calreticulin and HMGB1 will be performed by flow cytometry/ELISA (3 Time point: before, 48h and at the end of the procedure) Immune phenotyping will be performed by mulitparametric flow cytometry, characterizing the immune cell subsets(NK, T, B cells, granulocyte, monocytes). T cell subsets will be specifically characterized for Treg (CD25/foxp3), Naive/memory effector memory T cell (CCR7/CD45RA) and for activatory or exhausted phenotype (CD137, ICOS, PD1, CTLA4, TIM3, LAG3).

To Detect Cryoimmunologic Response Induced by Early Breast Cancer Ultrasound-guided Cryoablation (ICE-study)

Early Breast Cancer Ultrasound-guided Visual-ICE Galil Cryoablation; Can Tumor Cell Death Induced by Cryoablation be Detected by Specific Circulating Markers?

Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients.

Evaluation of serum modifications of the following molecules:

Th1 and Th2 type cytokines (IFN-γ, IL-12 (p40/p70), IL-15, IL-17, IL-2, IL-7, IP-10, IL-13, IL-5, IL-4)

Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients.

Evaluation of serum modifications of the following molecules:

pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α, IL-1RA, IL-2R, IL-8, CRP, IL-17, IFN-α),

Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients.

Evaluation of serum modifications of the following molecules:

immunosuppressive cytokines (TGF-β1, IL-10, PGE2),

Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients.

Evaluation of serum modifications of the following molecules:

chemokines (CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, CXCL9/MIG, CCL11/Eotaxin),

Characterization of the Immunogenic Cell Death induced by tumor cryoablation treatment in the serum of breast cancer patients.

Evaluation of serum modifications of the following molecules: ATP and HMGB1 are molecules released in the serum by cancer cells during immunogenic cell death.

Evaluate Recist criteria rate of complete response to cryoablation with breast ultrasound and breast MRI

Analyzing surgical specimen sections stained with hematoxylin-eosin, the presence and the extent of tumor (cm) necrosis will be evaluated.

ablating breast cancer with 5-10 mm margins around the primary tumor.

University of Roma La Sapienza

Prof. Federica Pediconi

Digestive System Diseases

Infections

Colonic Neoplasms

Syndrome

Inflammation

Peritonitis

Systemic Inflammatory Response Syndrome

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Shock

Communicable Diseases

Intraabdominal Infections

Peritoneal Diseases

Herbal and Botanical

All Drugs and Chemicals

Cola

Patients undergoing robotic-assisted colectomy for colonic neoplasm

Patients undergoing conventional laparoscopic colectomy for colonic neoplasm

Robotic-assisted colectomy performed by usage of da Vinci Xi robotic technology

Robotic-assisted colectomy

Conventional laparoscopic colectomy

Pedja Cuk, MD

The current hypothesis is that robotic-assisted surgery results in a reduced systemic and peritoneal inflammatory response (SIRS) compared to laparoscopic surgery in the treatment of colon cancer. The purpose is to evaluate differences in the peritoneal and systemic inflammatory response in robot-assisted and laparoscopic surgery of patients undergoing resection for colon cancer in a randomized, blinded controlled trial.

Systemic and Peritoneal Inflammatory Response In Robotic-assisted And Laparoscopic Surgery for Colon Cancer

Systemic and Peritoneal Inflammatory Response In Robotic-assisted And Laparoscopic Surgery for Colon Cancer (SIRIRALS-trial): a Randomized Controlled Trial

Levels of cytokines are expressed by: Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A as well as IL-1RA and CRP. All cytokines are measured in pg/mL, CRP measured in mg/L

Recovery is measured according to quality of recovery 15 score (QoR-15). The score ranges from 0-150. A high score indicates a good recovery.

Number of mortality obtained from medical charts

The heart rate will continuously recorded by ECG intra- and postoperatively

The two surgical methods will be compared in order to obtain any differences in the local or metastatic cancer recurrence

The cytokine levels are expressed by: Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A and IL-1RA. All cytokines are measured in pg/mL

Number of complications obtained from medical records

Region of Southern Denmark

University of Southern Denmark

Nutritional and Metabolic Diseases

Behaviors and Mental Disorders

Wasting Syndrome

Cachexia

Weight Loss

Body Weight

Body Weight Changes

Thinness

Metabolic Diseases

Nutrition Disorders

Quality of Life

Barry JA Laird, MBCHB MD

Rebekah Patton

People with incurable cancer often have complex individual needs, however there are several common themes encountered when considering this group.

As cancer progresses there are series of interactions between the tumour and the patient, producing both local and systemic effects. This altered state of illness can have multiple ill effects including weight loss, fatigue, increased symptom burden and reduction in physical function which all contribute to a reduced quality of life.

These areas are often studied in isolation, giving an incomplete picture. A detailed, holistic characterisation of this group of people does not exist.

A robust characterisation of people with incurable cancer will allow identification and prioritisation of future research and has the potential to inform new therapeutics and provide justification for treatments.

This study aims to collect information about symptoms and quality of life, weight loss and body composition, physical activity and the body's immune response to cancer.

Participants with incurable cancer will be recruited to the study from oncology and palliative medicine services in the UK. Participants will answer questionnaires about quality of life and symptoms, have bloods taken for inflammatory marker and cytokine analysis and have their body composition measured by a variety of methods.

Blood samples - samples sent for routine inflammatory markers, plasma retained for analysis of cytokine levels and stored in a biobank for use in future ethically approved studies including potential genetic DNA analysis.

Archival tissue specimens (including fresh frozen and/or formalin fixed paraffin embedded biopsy/surgical specimens) that are no longer required by the local pathologist for diagnostic purposes, or are stored as part of ethically approved tissue collection/research studies, may be requested from patients in the course of establishing the biobank for further analysis in future studies

Routine Evaluation of People Living With Cancer

Routine Evaluation of People Living With Cancer - Body Composition, Physical Function, Systemic Inflammatory Response, Quality of Life and Symptoms

Correlation of serum levels of inflammatory cytokines with clinical parameters including skeletal muscle mass, symptom based scores and physical activity as measured by actigraphy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Detect Cryoimmunologic Response Induced by Early Breast Cancer Ultrasound-guided Cryoablation (ICE-study)	NCT05727813	Cancer, Treatme... Tumor of Breast Systemic Inflam... Stage I Breast ...	cryoablation	18 Years -	University of Roma La Sapienza
Systemic and Peritoneal Inflammatory Response In Robotic-assisted And Laparoscopic Surgery for Colon Cancer	NCT04687384	Colonic Neoplas... Colon Cancer Systemic Inflam... Inflammation Robotic Surgica... Laparoscopy Peritoneal Infl...	Robotic-assiste... Conventional la...	18 Years -	University of Southern Denmark
Routine Evaluation of People Living With Cancer	NCT04406662	Cachexia; Cance... Advanced Cancer Quality of Life		18 Years -	University of Edinburgh

Spots Global Cancer Trial Database for systemic inflammatory response