Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients

Predictive Value of Progastrin Titer at Diagnosis and of Progastrin Kinetics During Treatment in Cancer Patients

Progastrin is a pro-hormone that, in physiological conditions, is maturated in gastrin in G cells of the stomach. The role of the gastrin is to stimulate the secretion of gastric acids during digestion. It is also important for the regulation of cell growth of the gastric mucosal.

In a healthy person, progastrin is not detectable in the peripheral blood. However, progastrin is abnormally released in the blood of patients with different cancers (colorectal, gastric, ovarian, breast, cervix uterus, melanoma…) The gene GAST coding for progastrin is a direct target gene of the WNT/ß-catenin oncogenic pathway. The activation of this oncogenic pathway is an early event in cancer development.

Chronic activation of the WNT/ß-catenin oncogenic pathway occurs in almost all human solid tumors and is a central mechanism in cancer biology that induces cellular proliferation, blocking of differentiation leading to primary tumor growth and metastasis formation.

Progastrin measured in the peripheral blood of patients on treatments, could be a new powerful marker for diagnosis and prognosis at different stages.

• Histologically and/or cytologically documented (documentation obtained before or after diagnostic surgical procedure when clinical suspicion is strong), cancers for the following cohorts:

  o Breast carcinomas

  o Gastric carcinomas

  o Renal carcinomas

  o Prostate carcinomas

  o Lung carcinomas: NSCLC and SCLC

  o Hepatocellular carcinomas

  o Colorectal carcinomas

  • Head and neck carcinomas
  • Thyroid cancer
  • Pancreatic carcinomas
  • Ovarian adenocarcinomas
  • Glioblastoma
  • Endometrial adenocarcinomas
  • Bladder carcinoma
  • Superficial Oesophago-gastric carcinomas
  • Diffuse Large B-cell Lymphomas

• Patient older than 18 years.

• Patients who gave its written informed consent to participate to the study

• Patients affiliated to a social insurance regime

Specific inclusion criteria for curative treatment strategy cancer patients:

• Indication of a treatment strategy with curative intent (surgery; radiotherapy; chemotherapy; hormonotherapy; targeted agents…)
• Patient naïve of anticancer treatments for the considered cancer
• A prior anti-cancer treatment is allowed if this treatment was performed with curative intent, and if it did not include systemic chemotherapy, and if a complete remission ≥ 6 months was observed in between the end of treatment and relapse. Previous local treatments for superficial lesions are allowed without any time restriction (for example among others, intravesical treatment for superficial bladder cancer lesions).

Specific inclusion criteria for non-curative treatment strategy cancer patients:

• Indication of a treatment strategy with no curative intent (radiotherapy; chemotherapy; hormonotherapy; immunotherapy; targeted agents, non-curative surgery, …)
• Patient naïve of anticancer treatments in non-curative setting (except for metastatic hormone-sensitive prostate cancer, see specific inclusion criteria).

The following tumor type specific inclusion criteria must be met in addition to the inclusion criteria listed above:

Breast carcinomas

• All cohorts:

• Invasive breast ductal carcinoma, or

• Invasive breast lobular carcinoma

  • Curative intent treatment patient cohort:

• Planned to be treated with surgery, with/without neo-adjuvant and/or adjuvant chemotherapy and/or anti-hormone treatment

Gastric carcinomas

• All cohorts:

  o Intestinal-type adenocarcinoma, or

  o Diffuse cell type adenocarcinoma

• Curative intent treatment patient cohort:

  • Planned to be treated with surgery with/without neo-adjuvant treatment, with/without adjuvant treatment

Renal carcinomas • All cohorts:

• Any histology of renal cancer is accepted (non-clear cell renal cancer could be included)

• A pathology proof of renal cell carcinoma is not necessarily provided if patients present typical radiologic characteristics of renal cancer on imaging

  • Curative intent treatment patients cohort:

• Planned to be treated with partial or total nephrectomy

Prostate carcinomas

• Curative intent treatment patients cohort:

  o Localized prostate cancer with high risk features : StageT2b , T2c or T3 and/or Gleason >= 4+3 and/or PSA >= 20 and/or N+

  o Planned to be treated with radical prostatectomy or radiotherapy (potentially associated with androgen deprivation therapy). Brachytherapy and/or focused ultrasounds are not allowed.

• Non-curative intent treatment patients cohort:

  • Patients with metastatic castration resistant prostate cancer (mCRPC) defined by validated criteria of EAU, planned to be treated with doceteaxel or cabazitaxel or second generation hormone (i.e. abiraterone or enzalutamide). Patients have to be naïve of treatment for the castration resistant mCRPC. Patients that previously received docetaxel or a 1st or 2nd generation hormonotherapy for their hormone-sensitive prostate cancer in metastatic setting can be included.

Lung carcinomas treated by immunotherapy :

• Non-curative intent patients cohort:

o NSCLC stage IV according to 8th TNM classification planned to be treated with immunotherapy, with/ without chemotherapy

Lung carcinomas excluding those treated with immunotherapy:

• Curative intent treatment patients cohort:

  o NSCLC histology only

  o Stage I-II according to 8th TNM classification

  o Stage IIIA-B according to 8th TNM classification

  o Planned to be treated with radical treatment (surgery or radiotherapy with/without concurrent chemotherapy), potentially associated with neo-adjuvant or adjuvant treatment

• Non-curative intent patients cohort:

  • NSCLC or SCLC stage IV according to 8th TNM classification planned to be treated with a first line of chemotherapy, with/without associated treatments except immunotherapy (radiotherapy, targeted therapies…). Immunotherapy can be administrated for the subsequent lines of treatment.

Hepatocellular carcinomas A pathology proof of HCC is not necessarily provided if patients present typical radiologic characteristics of hepatocellular carcinoma on imaging

• Absence or chronic hepatic encephalopathy, absence of refractory ascites

  • Curative intent treatment patients cohort:

• Indication of a treatment strategy with curative intent, except liver transplantation: surgical resection, monopolar radiofrequency ablation for HCC (1 to 3 nodules ≤3 cm) or multibipolar radiofrequency if nodule ≤4 cm).

  • Non-curative intent patients cohort:

• Indication of a treatment strategy with no curative intent: transarterial intra-hepatic chemoembolization, targeted therapies (tyrosine kinase inhibitors or monoclonal antibodies) or immune therapy.

Colorectal carcinomas

• Curative intent treatment patients cohort:

o Lieberkühn adenocarcinoma associated with metastases planned to be treated with peri-operative chemotherapy +/- targeted agent and interval surgery

Head and neck carcinomas

• All cohorts

  o Head and neck squamous cell carcinoma from oral cavity, oropharynx, hypopharynx, larynx

• Curative intent treatment patients cohort:

  o Planned to be treated with a radical treatment (surgery and/or radiotherapy potentially associated with concurrent chemotherapy) with/without neo-adjuvant/adjuvant chemotherapy.

• Non-curative intent treatment patients cohort:

  o De novo metastatic or metastatic/loco-regional relapse planned to be treated with chemotherapy and/or immunotherapy

Thyroid cancer • Curative intent patient cohort o Thyroid carcinoma differentiated, poorly differentiated, papillary, vesicular, Hurthle Cell o For which a iodine treatment is indicated (Iodine treatment will be discussed after surgery. In the case the histological result does not confirm a high risk thyroid cancer, patient will be withdrawn from the study. In the same way, if a iodine treatment is not recommended after surgery, patient will be withdrawn from the study. In both cases, patient will be replaced).

Pancreatic carcinomas

• Curative intent patients cohort:

o Pancreas exocrine adenocarcinoma planned to be treated with initial surgery with/without neo-adjuvant chemotherapy and with/without adjuvant chemotherapy or radiotherapy

Ovarian adenocarcinomas • Non/uncertain curative intent patients cohort:

o 1st platinum-sensitive relapse

• High or low grade epithelial adenocarcinomas or carcinosarcoma
• Planned to be treated with chemotherapy and/or PARP inhibitors based treatment, +/- interval debulking surgery

Glioblastoma • Curative intent patients cohort:

o Planned to be treated with surgical resection, followed by adjuvant temozolomide and radiotherapy

Endometrial adenocarcinomas

• Non-curative intent patients cohort:

  o Type 1 (endometrioid or mucinous) or type 2 endometrial (serous, clear cell, undifferentiated carcinoma and carcinosarcoma) cancers

  o Planned to be treated with non-curative systemic treatment for metastatic or advanced disease

Bladder carcinoma

• Transitional cell carcinoma • Curative intent treatment patients:
• Patients with localized muscle invasive bladder cancer (>=PT2)
• Planned to be treated with neo-adjuvant cisplatin based chemotherapy, or immunotherapy or a combination of chemotherapy and immunotherapy

Superficial Oesophago-gastric cancer • Curative intent patients cohort:

o Superficial oesophago-gastric carcinomas (adenocarcinomas or epidermoid carcinomas) of Stage T1 planned to be treated by endoscopic surgery

Diffuse Large B-Cell Lymphoma (DLBCL)

• Curative intent patients cohort:

o Patients planned to be treated with R-CHOP (Rituximab-Cyclophosphamide, Hydroxyadriamycine, Oncovin, Prednisone)