Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Surgical resection and stereotactic body radiation therapy (SBRT) are generally regarded as mutually exclusive treatment options for the local management of pulmonary malignancies. This Phase 2 prospective trial is a collaborative effort between the divisions of Thoracic Surgery and Radiation Oncology to evaluate the effects of dual treatment of pulmonary metastasis amenable to curative resection with neoadjuvant SBRT followed by surgical resection.

Surgical resection and stereotactic body radiation therapy (SBRT)

Dr. John Agzarian, MD, MPH

Housne Begum, MSc, PhD

John Agzarian, MD, FRCSC

John Agzarian, MD, MPH

The goal of this study is to determine the effectiveness of SBRT on reducing tumor viability at a pathologic level and also to evaluate the effects of combined modality treatment on low volume pulmonary metastases, in hopes of extrapolating this information to both primary and secondary lung cancer.

The role of SBRT as a potentially non-invasive treatment for small-volume tumors in the lung is well established, but the effectiveness of tumor eradication has yet to be determined. This prospective Phase 2 trial will provide several novel contributions to the literature: 1) the assessment of SBRT effectiveness in metastatic tumor control (radiotherapeutic metastasectomy), 2) the evaluation of pathologic response to SBRT by surgical resection, 3) identification of histologic predictors of radiation effect and toxicity (i.e. what are the effects of SBRT on different type of metastatic disease), and 4) the effect of combined modality SBRT and surgery on survival and local recurrence as compared to either modality alone. This trial will uniquely assess whether surgery as an adjunct to radiotherapy offers better tumor control as compared to SBRT alone, and whether it decreases locoregional recurrence. The study is an open-label unblinded single-arm prospective trial evaluating induction SBRT followed by pulmonary metastasectomy. This is a collaborative effort between the divisions of Thoracic Surgery and Radiation Oncology to evaluate the effects of dual treatment of pulmonary metastasis amenable to curative resection with neoadjuvant SBRT followed by surgical resection. Study recruitment and analysis will be conducted at St. Joseph Healthcare Hamilton and the Juravinski Cancer Center. Institutional data suggests that the Division of Thoracic Surgery at McMaster University performs an average of 450 pulmonary resections per year with approximately 10-15% being pulmonary metastasectomies for a spectrum of malignancies (including colorectal carcinoma, renal cell carcinoma and soft tissue sarcoma).

Surgical resection and stereotactic body radiation therapy (SBRT) are generally regarded as mutually exclusive treatment options for the local management of pulmonary malignancies. The Primary Outcome will be measured as the Rates of complete pathologic response (pCR) in surgical specimens post SBRT as assessed using the Junker grading scale for lung malignancies: Grade I, no regression or only spontaneous tumor regression; Grade II, morphologic evidence of tumor regression with at least 10% (grade IIa) or \<10% (grade IIb) viable tumor tissue; and Grade III, complete tumor regression with no viable tumor. The Secondary Outcomes: Overall survival (OS) at 3 years, Disease-free survival (DFS) at 3 years, local recurrence rates, radiation related toxicity, postoperative pulmonary complication rate (including prolonged air leak, need for invasive or noninvasive mechanical ventilation, postop pneumonia and empyema), the effect on time-to-resection and tumour histology on pCR. In addition, it will be explored whether cancer specific tumor biomarkers correlate with SBRT effects and related toxicity. Based on institutional data from other local prospective trials, the Thoracic Surgery division at McMaster averages a study accrual rate of 25-30% and retention rate of approximately 80%. The most pertinent metric in determining the necessary sample size is the effect size estimate of pCR. The MISSILE study preliminary data demonstrated a pCR of 60%. This serves as the only representative value in the literature, even though our study evaluates SBRT and surgery for metastatic disease and NOT primary lung cancer. In contrast, the SBRT literature (using post-treatment CT scan surveillance only) reports local control rates of nearly 90%. Using the Fleming procedure, in order to measure the true pCR with a 95% confidence interval ± 10% using an estimated true pCR of 70%, estimated dropout rate of 20%, and 80% power, the calculated sample size requirement is 39 patients. It is estimated being able to recruit approximately 1-2 patients per month.

This innovative study is an open-label unblinded single-arm prospective trial evaluating induction SBRT followed by pulmonary metastasectomy. As a Phase 2 trial, the primary purpose is to assess the efficacy of SBRT on metastatic tumor viability and the safety of SBRT as induction treatment prior to surgery

Post SBRT Pulmonary Metastasectomy (PSPM) Trial

Evaluating the Histologic Effects of Neoadjuvant Stereotactic Body Radiation Therapy (SBRT) Followed by Pulmonary Metastasectomy-Post SBRT Pulmonary Metastasectomy (PSPM) Trial

pCR in surgical specimens post SBRT as assessed using the Junker grading scale for lung malignancies: Grade I, no regression or only spontaneous tumor regression; Grade II, morphologic evidence of tumor regression with at least 10% (grade IIa) or \<10% (grade IIb) viable tumor tissue; and Grade III, complete tumor regression with no viable tumor.

Followup over all survival (OS) at 3 years

Followup over all survival (OS) at 3 years. Based on 1. clinical 2. CT scan results

Follow Radiation Therapy Oncology Group (RTOG) Common Toxicity Criteria (Cox, 1995)

Using Society of Thoracic Surgery (STS) Database

Identify mRNA tumor markers for circulating tumor cell/CTC detection from blood sample to get cancer specific tumor biomarkers correlate with SBRT effects including different targeted gene such MUC1, HER2, EPCAM, ER/PR for Breast Cancer, PSA, PSMA, EGFR, AR for Prostate Cancer, EPCAM, EGFR, CEA for Colon Cancer, EPCAM, MUC1, CA125, ERCC1 for Ovarian Cancer and Stemcell . The CTC test will be doing to get information about whether or not disease has disseminated from the primary site and mainly as a prognostic and/or predictive marker in the metastatic settings. This test will be done in baseline or Pre SBRT, Post SBRT and Post Surgery.

McMaster University

Symptoms and General Pathology

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Neoplasms, Second Primary

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Minimally invasive parenchymal sparing pulmonary metastasectomy Surgical approach by means of video-assisted thoracic surgery (VATS), robot-assisted (RATS), or uniportal VATS

Gross tumor volume = tumor visible on CT (+/- PET) No CTV margin will be added (Clinical target volume (CTV) = Gross target volume (GTV)) Planning Target Volume (PTV): GTV plus margins of 3-5mm (varying depending on site, motion, SABR delivery approach)

Surgical margin is equal to tumor size, if possible The goal is a parenchymal-sparing resection

Minimally invasive pulmonary metastasectomy

Depending on tumor location, 54 Gy in 3 fractions, 55 Gy in 5 fractions, 60 Gy in 8 fractions.

Stereotactic ablative radiotherapy

Martijn van Dorp, MD

Simone Gooijer, MD

COPPER is an international, multicenter, parallel-arm, phase III randomized controlled trial comparing two local treatment strategies (SABR or metastasectomy) for patients with an indication for local treatment for limited (max. three) colorectal pulmonary metastases

The study is formally endorsed by the Dutch Society of Lung Surgery (NVvL), the Dutch Society of Cardiothoracic Surgery (NVT), the Dutch Society of Radiation Oncology (NVRO). The main objective of the proposed randomized trial is to compare efficacy of SABR to the efficacy of metastasectomy with regards to the primary endpoint (local recurrence free survival at 5 years) in patients with limited colorectal pulmonary metastases. This will determine the most effective local treatment modality. The investigators hypothesize that patients with limited colorectal pulmonary metastases will have non-inferior overall survival after pulmonary metastasectomy compared to SABR, however metastasectomy will result in superior local recurrence free survival at five years when compared to SABR. In addition, the investigators hypothesize that SABR is associated with lower morbidity, comparable quality of life and comparable health care costs compared to metastasectomy. Recurrent metastases are preferably treated by the index treatment to which the patient was randomized, local recurrent metastases are preferably treated by means of cross-over between both arms. Comparing metastasectomy to SABR for patients with colorectal pulmonary metastases will present the international community the evidence needed to better select patients for local radical treatment, while diminishing uncertainty for patients and care givers.

Multicenter, parallel-arm, phase III randomized controlled trial Patients will be randomized in a 1:1 manner to SABR or minimally invasive metastasectomy for the local treatment of three or less colorectal pulmonary metastases

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy: a Phase III Multicenter Randomized Controlled Trial

Data will become available for non-commercial scientific research (open access) after a period of 12 months after the last data collection.

Time from randomization to local recurrence or death from any cause

Time from randomization to death from any cause

Time from randomization to disease progression at any site or death

Proportion of treated metastases with local recurrence

\[0-5 for 5 dimensions, higher score = worse QoL\]

\[27 questions in 4 subscales, higher score = better QoL\]

Local, regional and distant disease control based on surveillance imaging

Frequency of adverse events and serious adverse events

Peripheral blood mononuclear cell (PBMC) concentration

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Post SBRT Pulmonary Metastasectomy (PSPM) Trial	NCT04160143	Surgical Resect... Stereotactic Bo... Lung Cancer Pulmonary Metas...	Surgical resect...	18 Years -	McMaster University
Post SBRT Pulmonary Metastasectomy (PSPM) Trial	NCT04160143	Surgical Resect... Stereotactic Bo... Lung Cancer Pulmonary Metas...	Surgical resect...	18 Years -	McMaster University
Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy	NCT05808790	Lung Metastases Colorectal Canc...	Minimally invas... Stereotactic ab...	18 Years -	Amsterdam UMC, location VUmc

Spots Global Cancer Trial Database for pulmonary metastasectomy