Alliance leads thoracic surgery trials for lung cancer in 2012

Two lung surgery clinical trials are currently being conducted through the Alliance for Clinical Trials in Oncology. These two trials are highlighted in the accompanying diagram (see Figure) with an algorithm to assist in decision making and patient eligibility.

  Study information

Study information

The surgical standard of care for early-stage non-small cell lung cancer (NSCLC) is an anatomic lobectomy with mediastinal nodal staging in patients with acceptable perioperative risk. In 1995, the Lung Cancer Study Group (LCSG) published the results of a randomized trial in which 267 patients with peripheral T1N0 tumors were randomly assigned to lobectomy or limited resection. Based on this study, lobectomy was established as the standard of care.1

Several studies suggest that survival is related to tumor size; specifically, that survival is better in patients with tumors 2.0 cm or less. A study published in 2003 analyzed a series of 244 patients who underwent resection for confirmed Stage 1A NSCLC. That research showed a statistically significant difference in survival between patients with tumors < 2 cm (five year survival of 77.2 percent) when compared with patients having tumors greater than 2 cm (five year survival of 60.3 percent).2 Another study also found improved survival in patients with tumors < 1.5 cm.3 Yet another study indicated no statistically significant difference in overall five-year survival following lobectomy or segmentectomy in patients with tumors 2 cm or less.4,5 This evidence indicates the need for evaluation of lobectomy versus sublobar resection in this subset of tumors.

Lung surgery trial algorithm

Lung surgery trial algorithm

The management, as well as the definition, of high operative risk is controversial but important to evaluate. Stereotactic Ablative Radiotherapy (SABR) has been evaluated since the 1990s and has been demonstrated to control primary lung cancer. RTOG 0236 demonstrated a 56 percent overall three-year survival in medically inoperable patients with biopsy proven lung cancer.6 The American College of Surgeons Oncology Group clinical trial known as ACOSOG Z4099 is designed to evaluate management of patients deemed high risk for surgery but able to undergo sublobar resections and compare them with patients who have undergone SABR.

CALGB 140503

The Cancer and Leukemia Group B (CALGB) 140503 trial is currently evaluating the potential benefit of sublobar resection for peripheral NSCLC < 2 cm. The primary objective is to determine whether disease-free survival after sublobar resection (segmentectomy or wedge) is “non-inferior” to that after lobectomy in patients with small (< 2cm) NSCLC. The center of the tumor as seen with computed tomography (CT) must be located in the outer third of the lung in either the transverse, coronal, or saggital plane. Patients will be randomized intraoperatively once there is confirmation of non-small cell lung cancer and N0 status by frozen section examination. Nodes may be sampled at the time of operation or preoperatively by mediastinoscopy within six weeks of the definitive procedure.

The inclusion and exclusion criteria for participation in the clinical trial are as follows:

  • Inclusion criteria:
    • Patients with peripheral lung nodule < 2 cm on preoperative CT scan
    • Patients with a histologically confirmed diagnosis of NSCLC
    • Patients with confirmed N0 status by frozen section examination
    • Eastern Cooperative Oncology Group performance status of 0-2
  • Exclusion criteria:
    • Prior malignancy within five years (with the exception of non-melanoma skin cancer, superficial bladder cancer, or CIS of the cervix)
    • Prior chemotherapy or radiation for this malignancy
    • Locally advanced or metastatic disease
    • Age < 18 years

ACOSOG Z4099

ACOSOG Z4099 randomizes high perioperative risk patients into three fractions of SABR or sublobar resection (wedge or segmentectomy). Surgeons are given the ability to add brachytherapy to the sublobar resection at their discretion. Inclusion and exclusion criteria for participation in this trial are as follows.

    • Inclusion criteria:
      • Patients lung nodule < 3 cm on preoperative CT scan and clinically Ia or Ib (visceral pleural involvement)
      • Patients with a histologically confirmed diagnosis of NSCLC
      • Patients with confirmed N0 status if lymph nodes are > 1 cm on short axis
      • Tumors must be > 2 cm from proximal bronchial tree
      • High risk as defined by major and/or minor criteria listed in the protocol
    • Exclusion criteria:
      • Prior malignancy within three years (with the exception of non-melanoma skin cancer and in situ cancers)
      • No prior intra-thoracic radiotherapy (prior head and neck, breast, or other non-thoracic cancer is permitted)
      • Locally advanced or metastatic disease

More information regarding these trials, as well as contact information for participating institutions can be found through the NCI Cancer Trials Support Unit at http://www.ctsu.org/ as well as on the CALGB website at http://www.calgb.org, and the ACOSOG’s website at https://www.acosog.org.


References

  1. Ginsberg RJ, Rubenstein LV. Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thor Surg. 1995;60(3):615-622.
  2. Port JL, Kent MS, Korst RJ, Libby D, Pasmantier M, Altorki NK. Tumor size predicts survival within stage 1A non-small cell lung cancer. Chest. 2003;124(5):1828-1833.
  3. Gajra A, Newman N, Gamble GP, Abraham NZ, Kohman LJ, Graziano SL. Impact of tumor size on survival in stage IA non-small cell lung cancer: A case for subdividing stage IA disease. Lung Cancer. 2003; 42(1):51-57.
  4. Warren WH, Faber LP. Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma. Five year survival and patterns of intrathoracic recurrence. J Thorac Cardiovasc Surg. 1994;107(4):1087-1093.
  5. Keenan RJ, Landreneau RJ, Maley RH Jr., Singh D, Macherey R, Bartley S, Santucci T. Segmental resection spares pulmonary function in patients with stage 1 lung cancer. Ann Thor Surg. 2004;78(1):228-233.
  6. Timmerman R, Paulus R, Galvin J, Michalski J, Straube W. Bradley J. Fakiris A, Beziak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010;303(11):1070-1076.

Tagged as: , , ,

Contact

Bulletin of the American College of Surgeons
633 N. Saint Clair St.
Chicago, IL 60611

Archives

Download the Bulletin App


Get it on Google Play