Primary Outcome
- Ability to accrue sufficient patients to draw conclusions about endpoints in a timely and expedient manner [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
The goal sample size will be 10 patients. - Incidence of acute and subacute toxicity defined as grade 4 or 5 adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]
- Incidence of chronic toxicity as assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: Yes ]
-
Secondary Outcome
- Disease Specific Survival (DSS) [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ] Cumulative incidence approach will be used to estimate DSS.
- Local Control (LC) [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
Cumulative incidence approach will be used to estimate the local failure rates. - Overall Survival (OS) [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue:
No] - Pathologic Complete Response Rate (pCR) [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
Detailed Description
Primary Objectives
- To determine the feasibility and toxicity (both acute and chronic) of accelerated hypofractionated neoadjuvant helical intensity modulated radiation therapy prior to pleurectomy/decortication for malignant pleural mesothelioma
Secondary Objectives
- To determine the pathologic complete response rate (pCR). II. To determine the tumor local control rate (LC). III. To determine the malignant pleural mesothelioma disease specific survival (DSS)
- To determine the overall survival (OS). V. To assess transforming growth factor beta (TGF-B), interleukin (IL)-1, and IL-6 levels as predictive biomarkers for treatment induced tissue injury.
- To assess the changes in the postoperative pleural immunological milieu in terms of chemo- and cytokine expression.
OUTLINE
Patients undergo 5 fractions of accelerated hypofractionated intensity-modulated radiation therapy (IMRT) over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. After completion of study treatment, patients are followed up at 6 weeks, and then every 3 months for 5 years.
Eligibility
- Inclusion Criteria
- Histologically confirmed epithelioid predominantly (> 70%) subtype malignant pleural mesothelioma.
- Patient must have been evaluated by a University of California Los Angeles (UCLA) thoracic surgeon, and deemed medically and technically suitable for a pleurectomy/decortication procedure.
- Karnofsky performance status (KPS) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2
- If a woman is of childbearing potential, a negative urine or serum pregnancy test must be documented; women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for duration of study participation and for up to 4 weeks following the study.
- Exclusion Criteria
- Patients who have previously received therapeutic radiation therapy to the chest.
- Active systemic, pulmonary, or pericardial infection.
- Use of chemotherapy within 4 weeks of the planned start of radiation therapy.
- Pregnant women, or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period and for up to 4 weeks after the study.
- Refusal to sign the informed consent.
- Patients who are participating in a concurrent treatment protocol.
