Physical Activity and Sarcoma, Role and Impact on Outcome

NCT ID: NCT06565858

Last Updated: 2024-09-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 750 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2026-08-30

Brief Summary

The aim of this study is to evaluate the role/impact of physical activity (PA) in sarcomas, in their distribution and potentially also on their prognosis, as already demonstrated for other neoplasms. Type, intensity, frequency, duration and circumstance of both occupational and leisure physical activity will be collected through validated questionnaires and self-reported measurement methods.

Detailed Description

The protective role of physical activity (PA) has been demonstrated in numerous diseases, especially cardiovascular and metabolic ones, but also in various neoplastic pathologies.

It has been estimated that approximately 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. Regular moderate-intensity or greater physical activity is associated with a reduced risk of several types of cancer. Most studies have shown this association especially for breast, colon, and endometrial cancer.

The mechanisms through which PA may decrease cancer risk are numerous: physical activity might work through reducing the amount of adipose tissue, thereby lowering circulating levels of estrogens and other sex hormones, PA improves insulin resistance, reduces hyperinsulinaemia, might reduce inflammatory markers, thereby decreasing the exposure to these potentially carcinogenic hormones and peptides, reduces oxidative stress, reduces gastrointestinal transit time and improves immune system by increasing the phagocytic activity of macrophages and neutrophils, and increasing the proliferation of natural killer cells and lymphocytes. Other mechanisms under investigation pertain angiogenesis, DNA repair, and growth factors.

In addition to hormone-sensitive tumors and colon cancer, new evidence suggests that similar associations with PA might exist for other cancers for which less is known about the potential mechanisms underlying the physical activity association, suggesting that further mechanistic research is warranted.

Furthermore, in people who have already been diagnosed with cancer and are undergoing oncological therapy, regular exercise helps to counteract some typical and common side effects of anti-cancer therapies, thus improving treatment compliance and the overall quality of life. In particular, physical activity seems to reduce fatigue, arthralgia, nausea, improves cardiovascular and respiratory capacity, reduces the risk of osteoporosis, and anxiety.

Even more, several studies have shown that in patients already affected by cancer, physical activity could be associated with a better prognosis, reducing risk of recurrence and increasing survival. The most important and largest studies are mainly aimed at breast, colorectal, prostate and ovarian cancer [5-8].

Due to their rarity and extreme histological-molecular heterogeneity, little is known about sarcomas, particularly regarding potential risk factors and possible factors that may influence their clinical course.

Furthermore, starting from the evidence that cardiac tumors, both primary and secondary, are extremely rare, the possible mechanisms responsible for this favorable "refractoriness" of myocardial cells to neoplastic transformation and/or to the engraftment of other neoplastic cells will be studied.

The property of cardiomyocytes most likely related to this phenomenon is their contractility and continuous exposure to mechanical load that halt cardiomyocyte proliferation in the human heart. This project aims at improving knowledge about the molecular landscape and genetic aberrations involved in pathogenesis of cardiac tumors and assessing whether the mechanical forces generated by cardiomyocyte contraction in a beating heart inhibit the proliferation of cancer cells, thus protecting the heart from cancer.

Engineered heart tissue will be used to silence candidate mechanosensing genes. This should make the cell unresponsive to mechanical stimulation and thus allow it to proliferate even with increased afterload.

The expression levels of the mechanosensing genes eventually identified, will be tested in tumor tissue from sarcoma as located in the extremities of physically active individuals to assess whether they are downregulated, thus making the cells able to proliferate although located in actively contracting skeletal muscles.

Confirmation of the role of physical activity on cancer is awaited with interest. Understanding the mechanisms that link physical activity with cancer will be useful for several reasons. First, the identification of this mechanisms can give new clues to cancer biology, which might help in designing other cancer prevention and innovative treatment modalities. Second, if further data accumulate showing that increased physical activity can prevent some cancers or improve outcomes, this would constitute an excellent public health intervention to reduce the impact of cancer risks and costs.

Conditions

Sarcoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• age >18;
• diagnose of sarcoma;
• Written informed consent must be signed and dated by the patient and the investigator.

Exclusion Criteria

• Kaposi sarcoma.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paola Queirolo, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Europeo di Oncologia

Locations

Istituto Europeo di Oncologia

Milan, , Italy

Countries

Italy

Central Contacts

Paola Queirolo, MD

Role: CONTACT

paola.queirolo@ieo.it

+39 0294372480

Maristella Saponara, MD

Role: CONTACT

maristella.saponara@ieo.it

+39 0294371086

References

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Reference Type: BACKGROUND

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Reference Type: RESULT

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Reference Type: RESULT

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McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008 Mar;8(3):205-11. doi: 10.1038/nrc2325.

Reference Type: RESULT

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Ibrahim EM, Al-Homaidh A. Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. 2011 Sep;28(3):753-65. doi: 10.1007/s12032-010-9536-x. Epub 2010 Apr 22.

Reference Type: RESULT

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Meyerhardt JA, Giovannucci EL, Ogino S, Kirkner GJ, Chan AT, Willett W, Fuchs CS. Physical activity and male colorectal cancer survival. Arch Intern Med. 2009 Dec 14;169(22):2102-8. doi: 10.1001/archinternmed.2009.412.

Reference Type: RESULT

PMID: 20008694 (View on PubMed)

Meyerhardt JA, Giovannucci EL, Holmes MD, Chan AT, Chan JA, Colditz GA, Fuchs CS. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006 Aug 1;24(22):3527-34. doi: 10.1200/JCO.2006.06.0855. Epub 2006 Jul 5.

Reference Type: RESULT

PMID: 16822844 (View on PubMed)

Other Identifiers

L2-157

Identifier Type: -

Identifier Source: org_study_id