VETC, Prognostic and Predictive Value in Renal Cell Carcinoma and Adrenal Carcinoma

NCT04666220 | Unknown FDA Drug

• 1 other identifier: Predictive VETC
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Metastasis is the main cause of death in cancer patients and often epithelial-to-mesenchymal transition (EMT) is advocated as the basic mechanism. Recently Fang and colleagues described an EMT-independent process of metastasis in hepatocellular carcinoma (HCC): endothelium covers small cluster of tumor cells allowing tumor dissemination. This process of angiogenesis, named VETC (vessels that encapsulate tumor clusters) in HCC literature, has been described under different names in other cancer types. Furthermore, the investigators confirmed the negative impact of VETC on patients' prognosis on a large multicenter cohort of HCCs. Moreover, Fang et al demonstrated that patients affected by VETC-positive HCC benefit more from sorafenib therapy. Interestingly, this type of angiogenesis was also found in renal cell carcinoma, adrenal gland pheochromocytoma, thyroid follicular carcinoma and alveolar soft part sarcoma (ASPS) and associated to prognosis. Moreover, the distinction between benign and malignant neoplasms of the adrenal gland is a complex matter, being the established criteria still lacking a strong reproducibility. Several tyrosine kinase inhibitors are available for different cancer types; among them, HCC, RCC, ASPS, and TC may benefit from the so-called antiangiogenic tyrosine kinase inhibitors (aTKI) (such as sunitinib, sorafenib, pazopanib). A general (histotype-independent) validation of the prognostic role of VETC is missing. Moreover, inhibitors of tyrosine-kinase vascular endothelial growth factor receptors (VEGFR-TKI), represent an effective treatment for different cancer types, but predictive markers are still needed. In addition, novel systemic immunotherapy agents are being approved in many cancer types, as alternative to angiogenesis inhibitors. A broader frame including metastatic mechanisms, tumor microenvironment (TME, i.e. angiogenesis and immune infiltrate) and treatment response could answer to several needs currently unmet. Bayesian networks and causal models can be employed to effectively draw conclusions from retrospective data. The aim of the present study is to investigate in patients with RCC and adrenal carcinoma (AC) the VETC-expression on tumor tissue, correlating the results with clinical data, patients characteristics, and outcome.

Conditions

Renal Cell Carcinoma; Adrenal Carcinoma

Outcome Measures

Primary Outcomes (1)

• VETC in RCC and AC.

  To identify the expression of VETC in Renal Cell Carcinoma and Adrenal Carcinoma.

  2-3 months

Secondary Outcomes (3)

• Predictive VETC (OS)

  2-3 months

• Predictive VETC (PFS)

  2-3 months

• Predictive VETC (control)

  2-3 months

Study Arms (2)

Renal cell carcinoma (RCC)

For all series, clinical and epidemiological features will be recorded, all available histological slides will be reviewed and, on the primary tumor slides, histological characteristics will be re-assessed. Whenever multiple samples of tumors would be present, those having the tumor-surrounding tissue interface will be selected and stained with CD34 antibody. VETC will be evaluated independently by, at least, two pathologists, blinded to clinical data. VETC will be recorded as positive or negative, being VETC defined as CD34 unequivocal immunoreactivity of a continuous lining of endothelial cells around tumor clusters. VETC will be considered alternative to the common capillary pattern, consisting in small circular or linear blood vessels.

Other: VETC evaluation

Adrenal carcinoma

see (RCC)

Other: VETC evaluation

Interventions

VETC evaluation OTHER

We will evaluate VETC presence on tissue specimens

Also known as: Tumor vasculature evaluation

Adrenal carcinoma; Renal cell carcinoma (RCC)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In order to evaluate VETC effects on prognosis, this study will include series of patients who underwent surgery at our institution for RCC (from 2005 to 2007) and for adrenal carcinoma (2000-2018). Moreover, to investigate the possible role of TME, in particular of VETC, in predicting TKIs benefit, this study will consider series of RCC, selected from a prospectively maintained database of patients treated with first line TKIs at our center. Estimated sample size: 160 patients for RCC and 20 patients for AC.

You may qualify if:

• Histological diagnosis of Renal Cell Carcinoma;
• Histological diagnosis of Carcinoma of the adrenal gland;
• Availability of histological material;
• For the evaluation of the prognostic role: no systemic treatment with TKI administered before surgery.

You may not qualify if:

• Unavailable histological material;
• For RCC: histological diagnosis different from Clear Cell histotype.

Sponsors & Collaborators

• Humanitas Clinical and Research Center: lead

Study Sites (1)

Humanitas Clinical and Research Hospital

Rozzano, MI, 20089, Italy

RECRUITING

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Biospecimen

Retention: SAMPLES WITH DNA

Formalin fixed paraffin embedded blocks from biopsies or surgical procedures.

MeSH Terms

Conditions

Carcinoma, Renal Cell; Adrenal Cortex Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Salvatore L Renne, MD

  Humanitas Clinical and Reseach Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Salvatore L Renne, MD

CONTACT

+39028224 7743; salvatore.renne@hunimed.eu

Paolo A Zucali, MD

CONTACT

+398224 4061; paolo.zucali@hunimed.eu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 14, 2020
• Study Start: January 2, 2021
• Primary Completion: February 1, 2021
• Study Completion: May 1, 2021
• Last Updated: February 12, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: as soon as the data are uploaded they will be public indefinitely
• Access Criteria: public

Locations

IT (1)