10 Trials and Growing: A Progress Update on the Thoracic Surgical Oncology Group Clinical Trials

10 Trials and Growing: A Progress Update on the Thoracic Surgical Oncology Group Clinical Trials

The Thoracic Surgery Oncology Group (TSOG) is a joint initiative between the American Association for Thoracic Surgery and the Fiona & Stanley Druckenmiller Center for Lung Cancer Research at Memorial Sloan Kettering Cancer Center (MSK). TSOG is a network of thoracic surgeons within North American Thoracic Surgery Academic Centers focused on improving patient care by conducting multi-site clinical trials of recent advances in thoracic malignancies.

The main goal of the National Cancer Institute National Clinical Trials Network is to conduct definitive, randomized controlled trials across a broad range of diseases, not focusing on one particular modality. As a result, there have not been any thoracic surgical oncology trials since its inception in 2011. TSOG formed in 2017 to address this gap and has made considerable progress. The number of clinical trial sites has grown from the initial nine in 2017 to 34 across North American sites today, including four in Canada. TSOG has launched eight clinical trials and accrued more than 1,180 patients since inception, with more than 875 patients participating in active trials. (1)

“TSOG created its own clinical trials platform to allow thoracic surgeons and associated disease management teams to lead trial initiation and accrual in a more grassroots manner than is possible with traditional platforms,” said thoracic surgeon David R. Jones, MD, Chief of the Thoracic Service, Department of Surgery and Co-Director of the Druckenmiller Center for Lung Cancer Research at MSK. “With four new trials planned to open in 2024, the future of thoracic surgical clinical trials looks bright indeed.”

Dr. Jones is a member of the TSOG Executive Committee, along with leading thoracic surgeons from Brigham and Women’s Hospital, Duke University, and MD Anderson Cancer Center. They recently published a paper in the Journal of Thoracic and Cardiovascular Surgery on behalf of TSOG investigators to provide an update on current TSOG trials and highlight plans for new trials in 2024.1 Details follow below: 

Status of Current TSOG Trials

The First Three Trials: TSOG-101, TSOG-102, and TSOG-103

  • TSOG-101: A prospective assessment of circulating tumor DNA (ctDNA) in patients receiving neoadjuvant therapy for resectable non-small cell lung cancer (NSCLC)

The primary objectives of TSOG-101 are to correlate the change in ctDNA variant allele fraction (VAF) with pathologic response before and after neoadjuvant therapy and examine ctDNA VAF after surgical resection and its ability to predict recurrence, disease-free survival (DFS), and overall survival (OS).

TSOG-101 has met its target accrual of 100 patients. Investigators continue to collect outcome data and perform ctDNA VAF analysis. The trial may provide high-impact, practice-changing insights into developing improved biomarker-driven therapies and assessing minimal residual disease for patients with resectable NSCLC.

  • TSOG-102: A prospective registry trial of patients with subsolid ground glass pulmonary nodules

As cross-sectional imaging has become more popular for evaluating a variety of routine medical issues, there has been a recent marked increase in ground glass opacifications identified on computed tomography (CT) scans that may or may not be associated with lung cancer. TSOG-102 actively surveilled patients with two or more subsolid lesions using serial CT imaging and documented any subsequent biopsies or surgeries.

TSOG-102 (NCT03802981) accrual began at MSK in 2019 and expanded in the following years to include 23 institutions. The trial is led by MSK thoracic surgeon James Huang, MD and met its target accrual of 330 patients in October 2023. (2) The highest numbers of patients were enrolled at MSK, Brigham and Women’s Hospital, and Massachusetts General Hospital. Insights from trial data analysis will help inform future surveillance algorithms and may reduce overtreatment for some lesions.

  • TSOG-103: A phase 2 trial of multimodality management of risk-stratified patients with lung-limited metastatic colorectal cancer

TSOG-103 sought to evaluate recurrence-free survival and OS in patients with “low risk” lung-limited metastatic colorectal cancer undergoing pulmonary metastasectomy with or without perioperative chemotherapy.

Despite extraordinary efforts by participating institutions and the principal investigator, only 46 of 365 patients were accrued. While TSOG closed the trial in September 2023 due to accrual issues, MD Anderson is continuing the study (NCT03599752). 

NIH-Sponsored Trials: TSOG-104, TSOG-105, and TSOG-106

The TSOG platform has also become useful to thoracic surgeons proposing clinical trials or multi-institutional biospecimen acquisition studies sponsored by the National Institutes of Health/National Cancer Institute or similar funding agencies.

  • TSOG-104: A prospective trial evaluating the diagnostic accuracy of the biomarker FBLN3 in differentiating mesothelioma from benign pleural effusions.

Malignant pleural mesothelioma is an asbestos-induced cancer with a dismal prognosis. Led by NYU Langone Health’s Perlmutter Cancer Center, TSOG-104 is open at MSK and six other sites with high volumes of patients with mesothelioma. In this noninterventional trial, the investigators are examining the diagnostic accuracy of the protein fibulin-3 (FBLN3) for differentiating mesothelioma from benign pleural effusions, with a view to stratifying patients and optimizing treatments.

  • TSOG-105: The SORT Trial – A comparative effectiveness trial using patient-reported outcomes to compare surgery versus stereotactic body radiation therapy for stage 1 NSCLC.

TSOG-105 seeks to address the lack of evidence comparing short- and long-term patient-reported outcomes (PROs) of surgery versus stereotactic body radiation therapy (SBRT). Washington University in St. Louis sponsors the trial (NCT05183932), which is currently enrolling at eight sites. The investigators will analyze the PROs and use the findings to develop and validate prediction models for treatment outcomes for patients with stage 1 NSCLC.

  • TSOG-106: The LEADER Neoadjuvant Screening TrialEvaluating Actionable Drivers in Early Stage Lung Cancers

A collaborative effort between the Lung Cancer Mutation Consortium and TSOG, the LEADER trial aims to test patients for the presence of 11 oncogenic drivers — EGFR, BRAF V600E, MET exon 14, and HER2 mutations, rearrangements in ALK, RET, NTRK, and ROS1, and amplification of MET and HER2 — using ctDNA and next generation sequencing to identify patients eligible for targeted therapy neoadjuvant trials.

The goal is to use screening test results to enroll patients in clinical trials testing genomically matched treatments or other appropriate trials if no actionable driver mutations are identified. The LEADER trial (NCT04712877) is open at 15 institutions, including seven TSOG sites, and seeks to enroll 1,000 patients. More than 100 patients were enrolled as of October 2023.1

Future TSOG Clinical Trials 

As of September 2023, TSOG approved four new clinical trials to open in 2024 as follows:

  • TSOG-107: An educational trial for improving pathological staging of N1 nodes. Brigham and Women’s Hospital sponsors this trial (NCT06252129). The researchers will compare the number of stations and lymph nodes between conventionally obtained dissections and a new standardized dissection method for obtaining more lymph nodes from specimens by emphasizing the intrapulmonary lymph node map. The investigators will also evaluate the number of cases upstaged to N1. The principal investigator for the trial is Paula Ugalde, MD, from Brigham & Women’s Hospital.
  • TSOG-108: An international, thoracic-surgeon-initiated, industry-sponsored trial of neoadjuvant therapy for resectable HER2-mutant or HER-amplified lung cancer. Patients with stage 2 or stage 3 NSCLC with a HER2 mutation or amplification will receive neoadjuvant trastuzumab followed by surgical resection. The TSOG and overall trial principal investigator is MSK thoracic surgeon James M. Isbell, MD.
  • TSOG-109: A pragmatic registry trial examining perioperative results and outcomes in patients undergoing pulmonary segmentectomy for stage 1 NSCLC. Notably, TSOG-109 will be TSOG’s first international trial, conducted in collaboration with the European Society for Thoracic Surgery. The co-principal investigators are Alper Toker, MD, from West Virginia University, Scott Swanson, MD, from Brigham & Women’s Hospital and Dr. Jones from MSK.
  • TSOG-110: An industry-sponsored phase 3 trial of an adjuvant therapy in patients with high-risk, completely resected stage 1 lung adenocarcinoma. TSOG will be the primary North American consortium conducting this trial, which is sponsored by AstraZeneca. Dr. Jones is the international clinical investigator for this study.

“Forming TSOG gave us organizational, inclusive strategy to advance thoracic surgical clinical trials,” Dr. Jones said. “However, we’ve grown to be truly multidisciplinary to include advances in medical oncology, radiation oncology, and pathology, all focused on improving outcomes for patients with thoracic malignancies. We thank the American Association for Thoracic Surgery as well as the huge effort by the TSOG Coordinating Center team at MSK to make TSOG possible. Finally, we thank all the patients and their families who have participated in these important clinical trials.” 

Access disclosures for Dr. Jones and Dr. Huang.  

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  1. Jones DR, Bueno R, Harpole DH Jr, Vaporciyan AA; Thoracic Surgical Oncology Group investigators.. Thoracic Surgical Oncology Group: An American Association for Thoracic Surgery Clinical Trials Initiative. J Thorac Cardiovasc Surg. Published online January 20, 2024.
  2. Huang J, Jones DR; TSOG 102 Investigators and the TSOG Executive Board. Completion of Accrual for TSOG 102-One Small Step Forward for Thoracic Clinical Trials. J Thorac Cardiovasc Surg. Published online January 29, 2024.