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Ann Thorac Surg 1999;68:201-207
© 1999 The Society of Thoracic Surgeons

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Original Articles

Lung cancer staging and treatment in multidisciplinary trials: cancer and leukemia group B cooperative group approach¹

^a Division of Thoracic Surgery, University of Maryland Medical School, Baltimore, Maryland, USA
^b Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
^c Division of Cardiothoracic Surgery, Dartmouth University, Hanover, New Hampshire, USA
^d Lutheran General Hospital, Park Ridge, Illinois, USA
^e Division of Thoracic Surgery, Brigham and Women’s Hospital, Boston, Massachusetts, USA
^f Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
^g Division of Cardiothoracic Surgery, State University of New York, Syracuse, New York, USA

Address reprint requests to Dr Krasna, Division of Thoracic Surgery, N4W94, University of Maryland Hospital, 22 South Greene St, Baltimore, MD 21201
e-mail: mkrasna{at}surgery1.ab.umd.edu

	Abstract

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

 
Background. Aggressive routine surgical staging is necessary to evaluate patients to be treated on cooperative oncology protocols. Less than 1% of lung cancer patients in the United States are currently being treated in a clinical trial. Only with results from large, prospective trials can the questions of neoadjuvant and adjuvant therapy be answered.

Methods. An outline describing the schema of preoperative patient evaluation, surgical staging, and the definition of surgical staging and resection procedures appropriate for patients considered for cooperative group protocol is presented. Current Cancer and Leukemia Group B (CALGB) protocols are used in the discussion as examples of this systematic approach.

Conclusions. Over the next few years, it will be important to enter the maximum number of patients into combined modality studies to identify the role of neoadjuvant treatment in lung cancer. Entry of patients into protocols will also make their pathological specimens and clinical information available for basic science research related to treatment results. Adherence to a logical sequence of patient evaluation as outlined above will optimize patient care, as well as accrual to cooperative group studies.

	Introduction

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

 
Since the demise of the Lung Cancer Study Group (LCSG), responsibility for multi-institutional clinical research studies in lung cancer has become the province of the Cooperative Groups. The LCSG made outstanding advances in proving the value of surgical staging (in particular mediastinoscopy) to allow accurate grouping of potentially resectable lung cancer patients [1]. This, in turn, led to important refinements in treatment and staging techniques as well as increased recognition of the importance of staging in the prognosis of these patients [2]. With the advent of neoadjuvant therapy in the

treatment of locally advanced non–small cell lung cancer (NSCLC), and its apparent effect on long-term survival, preresection pathologic staging of the mediastinum has taken on new importance [3–5]. Aggressive routine surgical staging is necessary to evaluate patients to be treated on these protocols. Only with results from large, prospective trials can the questions of neoadjuvant and adjuvant therapy be answered.

To facilitate the uniform evaluation of lung cancer patients, and to maximize the potential accrual to thoracic surgical clinical studies, we have codified the appropriate work-up and assignment of patients referred to Cancer and Leukemia Group B (CALGB) thoracic surgeons. This experience will help surgeons, within and outside cooperative groups, to proceed in a coherent fashion in evaluating patients with NSCLC and to seek out appropriate protocols for the majority of their patients. With the advent of the American College of Surgeons Oncology Group, such trials should be accessible to all surgeons even if they do not belong to multidisciplinary groups.

	Methods

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

 
An outline describing the schema of preoperative patient evaluation, surgical staging, and the definition of surgical staging and resection procedures appropriate for patients considered for cooperative group protocol is presented (Figs 1, 2). Current CALGB protocols will be used in the discussion as examples of this systematic approach.

View larger version (29K): [in this window] [in a new window]   Fig 1. Flow of patients through the staging and onto protocols.

View larger version (28K): [in this window] [in a new window]   Fig 2. Current NSCLC studies per tumor stage.

1. Preliminary patient evaluation
   1. Smoking cessation intervention
      1. Counseling
         
      2. Consideration of nicotine patch or bupropion
         
      
      
   2. Screen for metastatic disease (history regarding neurological or bone symptoms, liver function tests, follow-up skeletal survey). Magnetic resonance imaging (MRI) or computed tomography (CT) of liver or brain if indicated by labs or history and physical exam.
      
   3. Bronchoscopy with appropriate biopsies, brushings, and washings may be performed at any point in evaluation, including immediately preoperatively.
      
   4. CT scan is done routinely within 6 weeks of planned surgical staging. Although intravenous contrast helps to differentiate mediastinal lymph nodes (LN) from surrounding vessels, this is not mandatory. Although MRI can be performed, it may not replace chest CT on current protocols.
      1. CT scans are considered negative if no mediastinal nodes are identified that are 1.0 cm or more in greatest dimension (including paratracheal, subcarinal, anterior mediastinal, and aortopulmonary window nodes).
         
      2. CT scans are positive if any mediastinal node 1.0 cm or more in greatest dimension is present.
         
      
      
   
   
2. Surgical staging including cervical mediastinoscopy and/or mediastinotomy or thoracoscopy are performed:
   1. For tumors in the right lung or left lower lobe:
      1. If the CT is positive, cervical mediastinoscopy is required.
         1. If all nodes are negative, then one can proceed directly to thoracotomy. These patients can then be entered into a study comparing adjuvant chemotherapy to observation for early NSCLC (CALGB 9633).
            
         2. If ipsilateral nodes are positive but the contralateral nodes are negative, the patient should be entered into an induction therapy protocol (eg, CALGB 9531), with surgery to follow neoadjuvant therapy. Alternatively, the patient can be entered into a study to evaluate the place of surgery in such patients. (eg, CALGB 9592/Intergroup 0139).
            
         3. If the contralateral nodes are positive, then the patient should be entered onto a nonsurgical protocol for treatment of locally advanced disease (eg, CALGB 9431 or 9531, a stage IIIA/IIIB study evaluating the response to high-dose neoadjuvant therapy with stem cell treatment).
            
         
         
      2. If the CT is negative, cervical mediastinoscopy is still strongly recommended. Treatment would then be based on the results of LN pathology as in 1a, b, or c above, depending on findings.
         
      
      
   2. For tumors in the left upper lobe:
      1. If the CT is positive, cervical mediastinoscopy is required.
         1. If the right sided node is positive: entry onto a nonsurgical protocol for treatment of locally advanced disease (eg, 9431) is appropriate. Alternatively, patients can be placed on a new protocol evaluating the effect of neoadjuvant therapy for stage IIIA/IIIB (CALGB 9531).
            
         2. If the right-sided nodes are negative and a left-sided node is positive; patient could be entered onto an induction therapy protocol (eg, CALGB 9531), with surgery to follow neoadjuvant therapy if appropriate. Alternatively, entry onto a neoadjuvant versus nonsurgical protocol is appropriate (CALGB 9592/INT 0139).
            
         3. If mediastinal LN from both sides are negative but level 5 and 6 LN are not sampled, a left anterior mediastinoscopy or thoracoscopy with biopsy [6] of levels 5 and 6 nodes is required to go on study.
            1. If this is negative, one can proceed directly to thoracotomy.
               
            2. If this is positive, entry onto an induction therapy protocol (eg, CALGB 9531), with surgery to follow neoadjuvant therapy, is recommended. Alternatively, the patient should be placed on a neoadjuvant therapy versus no surgery protocol (CALGB 9592/Intergroup 0139).
               
            
            
         
         
      2. If the CT scan is negative, cervical mediastinoscopy is still highly recommended. Left anterior mediastinoscopy or thoracoscopy are recommended with treatment as in B1 and C above, depending on the findings.
         
      
      
   
   
3. Thoracotomy
   1. All protocols require performance of an appropriate anatomic resection (lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy). Wedge or segmental resections are generally not acceptable, due to known higher incidence of local recurrence, the inability to obtain full sampling of intralobar, interlobar, and hilar lymph nodes, and possible difference in survival in these patients [7]. Poor-risk patients should be considered for protocols evaluating limited resection or those protocols that evaluate the respiratory reserve (eg, CALGB 9335, 9238, respectively).
      
   2. Complete mediastinal node dissection should be done at the time of resection on all patients. LN should be labeled according to the American Thoracic Society (ATS) map or Naruke staging system [8, 9], as recently modified by Mountain and Dresler [10].
      
   3. LN sampling must include the following stations (Fig 3):
      1. 2, 4, 7, 8, 9, 10, 11, 12 for tumors on the right.
         
      2. For tumors on the left, dissection should include L2*, L4*, 5, 6, 7, 8, 9, 10, 11, 12 (L2* and L4 may not be accessible; and this should be noted on the staging forms).
         
      3. If N1 or N2 nodes are noted to be positive after complete resection has already been performed, the patient should be entered onto an appropriate postoperative adjuvant protocol (eg, CALGB 9795, NCIC BR-10).
         
      4. If all nodes are negative, the patient should be considered for an adjuvant trial for high-risk stage I (eg, CALGB 9633).
         
      
      
   4. Superior sulcus tumors Histologic diagnosis and negative mediastinoscopy are required for entry onto the intergroup induction therapy protocol (eg, CALGB 9495/INT 0160).
      
   5. Malignant pleural effusion Patients with a known malignancy and pleural effusion without prior intrapleural treatment may participate in CALGB 9334.
      
   
   
4. Evaluation for adjuvant postoperative protocols
   1. Resected patients referred for postresection protocols (such as CALGB 9633, 9795, 9734) may be entered in the following circumstances:
      1. If the preoperative CT scan was positive and the mediastinoscopy was positive, they are not eligible for adjuvant protocols. Such patients should be entered on induction protocols.
         
      2. If the CT scan was positive and the mediastinoscopy was negative, the patient will be eligible for a stage-appropriate adjuvant protocol based on nodal requirements of the individual protocol.
         
      3. If the CT scan was negative and the mediastinoscopy negative, patient is eligible as in 2.
         
      4. If the CT scan was negative but no mediastinoscopy was done, then completeness of intraoperative nodal staging will dictate eligibility for adjuvant protocols based on the staging requirements of the individual protocol. Mediastinoscopy is recommended in all cases.
         
      
      
   2. Surgically staged patients referred from other surgeons for preresection IIIA protocols may be acceptable as follows:
      1. If the ipsilateral nodes are positive and contralateral nodes are negative, this may be acceptable at the discretion of the surgical study chair.
         
      2. If the ipsilateral nodes are positive at mediastinoscopy, but no contralateral biopsy was done, the patient is unacceptable. Some of these patients may be converted to acceptable, at the discretion of the surgical chair, as follows:
         1. For tumor on the left with a positive node obtained at left anterior mediastinotomy, a cervical mediastinoscopy may be done. If right-sided nodes are then negative, the patient can be entered onto a neoadjuvant study.
            
         2. For tumors on the right side, if positive right paratracheal nodes were obtained at cervical mediastinoscopy, repeat mediastinoscopy may be done to obtain contralateral nodes. If these are negative, the patient is a candidate for neoadjuvant trials. Left anterior mediastinotomy or thoracoscopy may not be substituted in this case.
            
         
         
      
      
   
   
5. Technique For a thorough description of the operative techniques of bronchoscopy, mediastinoscopy, and thoracoscopy, see the recently published CALGB Thoracic Procedures Manual [11]. Cervical mediastinoscopy biopsy of LN stations R2, R4, 7, L2, and L4 should be done. Any node obtained by mediastinoscopy is by definition an N2 node for the purposes of clinical trials. R10 nodes are those obtained at thoracotomy in the subazygos regions only and are classified as N1 nodes. Tracheobronchial angle LN sampled by mediastinoscopy are N2 nodes whether listed as R4 or R10, even if they are subazygos, as long as they are within the pleural envelope. Subcarinal LN currently are considered as ipsilateral (N2), not contralateral, disease. It may not be possible to get a node from all seven stations in every case, but most protocols require at least ipsilateral 2, 4, 7, and at least one contralateral node. Thoracoscopy may not be substituted for cervical mediastinoscopy. Left anterior mediastinotomy should be performed for LN biopsy of stations 5 and 6 that are not accessible by mediastinoscopy. Thoracoscopic biopsy of these stations may be substituted [6, 12]. Bronchoscopic biopsy of lymph nodes is generally unacceptable. Bronchoscopy, mediastinal node sampling, and resection may all be accomplished at one sitting. Frozen section evaluation of lymph nodes is acceptable for the majority of studies.
   
6. The following are current or recent CALGB Protocols for NSCLC (see Appendix 2):
   1. "Sclerosis of Pleural Effusions by Talc Thoracoscopy Versus Talc Slurry." This is a comparison of sclerosis by talc slurry through a chest tube versus talc insufflation via thoracoscopy (CALGB 9334).
      
   2. "Video-assisted Wedge Resection and Local Radiation Therapy for High-Risk T1 NSCLC" (CALGB 9335).
      
   3. "A Phase III Study of Adjuvant Chemotherapy After Resection for Patients With T2N0 Stage I Non-Small Cell Carcinoma of the Lung" (CALGB 9633).
      
   4. "Phase III Double-Blind Randomized Trial of 13-Cisretinoic Acid (13-CRA) to Prevent Second Primary Tumors in Stage 1 Non-Small Cell Lung Cancer" (CALGB 9335).
      
   5. "Detection of Occult Micrometastases in Patients With Clinical Stage I NSCLC: A Prospective Analysis" (CALGB 9761).
      
   6. "A Phase III Prospective Randomized Study of Adjuvant Chemotherapy With Vinorelbine and Cisplatin in Completely Resected Non-Small Cell Lung Cancer With Companion Tumor Marker Evaluation" (CALGB 9795/NCIC BR-10).
      
   7. "Pulmonary Exercise Testing as a Tool for Operative Selection in Patients With Lung Cancer" (CALGB 9238).
      
   8. "Intergroup Trial for Superior Sulcus Lung Cancer (Pancoast Tumor) With Concurrent Chemoradiation as Induction Therapy" (CALGB 9495/INT 0160).
      
   9. "Comparison Between Concurrent Chemo Plus XRT, and Concurrent Chemo Plus XRT Followed by Surgical Resection for Stage IIIA (N2) NSCLC." An intergroup prospective randomized trial of chemoradiation in stage IIIA (N2) NSCLC (CALGB 9592/INT 0139).
      
   10. "High Dose Carboplatin & Paclitaxel With G-CSF & Peripheral Blood Stem Cell Support Followed by Surgery and/or Radiotherapy" (CALGB 9531).
       
   11. "A Phase III Study of Surgical Resection and Chemotherapy (Paclitaxel and Carboplatin) With or Without Adjuvant Radiotherapy for Resected Stage IIIA Non-small Cell Lung Cancer" (CALGB 9734).
       
   12. "Sequential & Concomitant Chemoradiotherapy With New Agents in Combination With Cisplatin for Inoperable Stage IIIA & IIIB NSCLC" (CALGB 9431).
       
   
   

View larger version (29K): [in this window] [in a new window]   Fig 3. Mediastinal lymph node map for NSCLC. Reprinted with the permission of the authors, Mountain and Dresler [10].

	Discussion

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

Thoracic surgeons from all of the major cooperative groups and cancer centers (CALGB, Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group (SWOG), Radiation Therapy Oncology Group (RTOG), North Central Cancer Treatment Group (NCCTG) Memorial Sloan-Kettering, MD Anderson) meet together on a regular basis to discuss common problems and facilitate the orderly and collaborative development of protocols. Thoracic surgeons from all groups likewise participate in semi-annual National Cancer Institute–sponsored strategy meetings to prioritize evolving protocols concerning thoracic malignancies.

One of the first goals in evaluating patients with lung cancer is to rule out evidence of M1 or distant metastatic disease. Patients entered onto chemotherapeutic neoadjuvant protocols need to have M1 disease ruled out with standard scanning techniques. Certainly, patients who have evidence of mediastinal involvement by CT scan need to have M1 disease ruled out with scanning before mediastinoscopy and/or resectional surgery, given the higher incidence of M1 disease in these patients. This is also necessary to clearly define response to therapy and correctly document progression of disease in these patients with a high risk of distant failure. Bony metastasis from lung cancer is best detected with technetium 99 bone scanning. The indication for bone scanning in most clinical series is clinical suspicion of bony metastasis. Routine scanning of patients before resectional surgery is performed in many centers in patients with adenocarcinoma [13]. The cost-effectiveness of this routine procedure remains in doubt. The presence of intracranial metastasis is best detected by CT or MRI of the head [14]. Routine use of head CT scans before surgical staging, chemotherapy, and subsequent resectional surgery in class IIIA disease seems appropriate, especially in patients with adenocarcinoma of the lung.

The surgeons of the CALGB have enthusiastically and uniformly accepted labeling of LN stations according to the numbering systems put forth by the American Thoracic Society and the American Joint Committee on Cancer. CALGB surgeons have worked with surgeons from other cooperative groups to resolve the disparities between the two existing mapping systems and create a single new and unambiguous LN staging map [10].

Mediastinoscopy remains the most sensitive and most specific way of pathologic staging of the mediastinum. Indeed, it is the only reliable way of pathologically staging the mediastinum before resectional surgery. The use of the transbronchial needle biopsy, while effective at detecting enlarged malignant nodes, does not allow for systematic staging of the mediastinum for patients entering new adjuvant protocols (ie, stage IIIa versus IIIb), unless contralateral LN are also documented. It is clear that mediastinoscopy, however, can effectively differentiate between patients with class IIIa (ipsilateral nodes) and IIIb (contralateral nodes). Although previous reports of aortopulmonary (AP) window biopsy have shown an overall 5-year survival at 28% with isolated level 5 and 6 LN metastases, routine inclusion of these patients in clinical N2 trials seems appropriate in order to improve further the survival of these patients.

Less than 1% of lung cancer patients in the United States are currently treated in a clinical trial. This is an especially important concept at the present time, with the rising use of neoadjuvant therapy for N2 disease. Although some authors have described improved survival with neoadjuvant therapy for N2 disease [3, 4], such treatment is currently advisable only within the confines of a prospective protocol. Chemotherapy may be beneficial even for the surgical patient with an earlier stage of disease, but such information is far from proven. Over the next few years, it will be important to enter the maximum number of patients on combined modality studies to find the answer to these questions. The smoking epidemic is not yet over; lung cancer will continue to kill more women and men than any other cancer for years to come.

In an ideal situation, each patient with a diagnosed or suspected lung cancer seen by a treating physician would fall into a category suitable for consideration of entry onto one of the CALGB (or other cooperative group) or intergroup protocols. Entry of patients onto protocols will also make their pathological specimens and clinical information available (through tumor banks and laboratory companion studies) for basic science research addressing the genetic and molecular correlates and predictors of disease and response to treatment. The CALGB has recently opened protocol 9761, which is a prospective trial to detect occult micrometastases in patients with stage I NSCLC. This study will use immunohistochemistry and reverse transcriptase polymerase chain reaction to detect cytokeratin and MUCI, and determine the relationship of these markers to survival. Studies like this may lead to improved diagnostic, prognostic, and therapeutic modalities.

In an editorial entitled "Thoracic Surgery Participation in Cooperative Group Studies of Cancer Therapy," Dr. Richard H. Feins emphasized the importance of thoracic surgeons developing and performing thoracic surgical protocols. He emphasized quality assurance in surgical protocols as one of the new goals in future trials [15]. Rusch noted that despite thoracic surgeons being in leadership roles in many of the cooperative groups, the efforts were "uncoordinated, duplicative and (often) counterproductive" [16]. She described an eight-point manifesto with which to improve the involvement of and service in thoracic surgical protocols. Since then, we have made many initiatives to answer these concerns. 1) An attempt is now made to discuss protocols among thoracic surgeons from all the groups and exchange information before opening new trials in a vacuum. 2) Expert advice is gleaned in the development of new protocols from the multidisciplinary groups with oncology and radiation oncology representation. 3) Uniform authorship policies are now available in some of the groups. 4) Dr. Rusch’s demand for "peer review" has been met with enthusiasm by the National Cancer Institute. All new protocols not authored by thoracic surgeons at least have a surgical principal investigator. 5) Several changes have occurred to allow funding of thoracic data managers since the above editorials. The CALGB has designated 24 centers with half-time funding for surgical data managers based on a U-10 National Cancer Institute grant. In addition, a per patient reimbursement allowing institutions from all the cooperative groups to support data management based on accrual has been initiated with the current "Minimally Invasive Protocols." Although this is only a beginning, it is hoped that with the advent of the American Cancer Society oncology group, funding will continue to improve. 6) We still need to educate ourselves, our residents, and fellows. With annual discussions at the American Association of Thoracic Surgery (AATS), Society for Thoracic Surgeons (STS), and General Thoracic Surgical Club (GTSC) meetings and published progress reports, hopefully, this will continue to improve.

Adherence to a logical sequence of patient evaluation as outlined above will optimize patient care, as well as accrual to cooperative group studies. All thoracic surgeons can easily follow such an outline, whether they now function in a cooperative group or not. Patients are eligible for many of the existing studies after their surgical procedure, if they are referred to a CALGB or other cooperative group medical oncologist or radiation oncologist (Appendix 1).

	Footnotes

 
¹ For editorial comment, see page 2.

	Appendix 1. Thoracic surgical subcommittee membership

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

 
Chair: David H. Harpole, MD, Duke University Medical Center, Durham, NC; Executive Officer: Ann M. Mauer, MD, University of Chicago Medical Center, Chicago, IL; Cadre Members: Todd L. Demmy, MD, University of Missouri/Ellis Fischel Cancer Center, Columbia, MO; Frank C. Detterbeck, MD, University of North Carolina at Chapel Hill, Chapel Hill, NC; Mark R. Green, MD, Medical University of South Carolina, Charleston, SC; Kemp H. Kernstine, MD, University of Iowa Hospitals, Iowa City, IA; Leslie J. Kohman, MD, ex-officio; SUNY Health Science Center at Syracuse, Syracuse, NY; Mark J. Krasna, MD, ex-officio; University of Maryland Cancer Center, Baltimore, MD; Michael A. Maddaus, MD, University of Minnesota, Minneapolis, MN; Jemi Olak, MD, Lutheran General Hospital, Park Ridge, IL; Hani Shennib, MD, Department of Oncology, McGill University, Montreal, PQ, Canada; Joshua R. Sonett, MD, University of Maryland Cancer Center, Baltimore, MD; Scott J. Swanson, MD, Brigham and Women’s Hospital, Boston, MA.

	Appendix 2. CALGB lung cancer protocols

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

 
9334. Sclerosis of pleural effusions by talc thoracoscopy versus talc slurry
ELIGIBILITY. History of malignant disease; pleural effusion requiring sclerosis. No previous chest tube, intrapleural therapy, or irradiation to affected hemithorax. Ability to undergo thoracoscopy; life expectancy > 2 months. Prior thoracentesis is allowed.

SCHEMA. Talc slurry via chest tube at bedside versus talc insufflation via thoracoscopy.

9335. Video-assisted wedge resection and radiation therapy for high-risk T1 NSCLC
ELIGIBILITY. Pulmonary dysfunction: FEV1 < 40% predicted or DLCO < 50% predicted or paC0₂ > 45 mm Hg or VO₂ max < 15 mL/kg/min or oxygen requirement. Peripheral, suspected T1 NSCLC; lesion accessible by thoracoscopy. No metastatic or N2 disease by CT scan. No prior chest irradiation. Negative bronchoscopy. Patients with LN > 1 cm must undergo mediastinoscopy first.

SCHEMA. Patients to undergo VATS resection. Incomplete resections will go to off-protocol irradiation. Complete resections will receive coned downfield irradiation to 50 Gy after documented NSCLC with no LN involvement.

9495. Intergroup trial for superior sulcus lung cancer (pancoast tumor) with concurrent chemoradiation as induction therapy
ELIGIBILITY. Superior sulcus NSCLC (Pancoast syndrome T3, T4); N0 or N1. No superior vena caval (SVC) syndrome or malignant effusion; no metastasis; mediastinoscopy is required.

SCHEMA. After surgical staging, patients are then treated w/cisplatin, etoposide, and concurrent irradiation to 45 Gy. Patients are restaged 2–4 weeks after induction therapy with repeat CT and bone scans. Patients with complete response (CR), partial response (PR), or stable disease will be resected and treated with two cycles of chemotherapy postoperatively. Unresectable patients will receive two cycles of additional chemotherapy.

9592. Comparing intergroup trial concurrent chemo plus XRT, and concurrent chemo plus XRT, followed by surgical resection for stage IIIA (N2) NSCLC
ELIGIBILITY. Stage IIIA NSCLC with T₁₂₃ N2 (ipsilateral mediastinal) lymph nodes; Mediastinal exploration must be done to establish eligibility. No distant metastases.

SCHEMA. All randomized patients receive induction irradiation to 45 Gy and chemotherapy (cisplatin/VP16). After induction, patients without local/distant progression will undergo resection followed by chemotherapy or will receive chemotherapy without resection.

9238. Pulmonary exercise testing as a tool for operative selection in patients with lung cancer
ELIGIBILITY. Documented NSCLC; patients must be eligible for thoracotomy, and able to free-peddle cycle ergometer for 2 min. No significant cardiac event within the past 6 months.

SCHEMA. All patients undergo pulmonary function tests, ventilation perfusion scan, and exercise test. Based on these results, patients will be offered thoracotomy (to evaluate low risk versus high risk) or will be treated at the physician’s discretion.

9431. Sequential and concomitant chemoradiotherapy with new agents in combination with cisplatin for inoperable stage IIIA and IIIB NSCLC
ELIGIBILITY. Histologically documented NSCLC; inoperable stage IIIA (T1–3, N2) or IIIB (T4, Nx, 3, or mediastinal, any N3). Contralateral LN are acceptable if in one radiation field; no scalene LN. Patients with resectable T3, N0-1 are not eligible. No prior chemotherapy or irradiation. No vertebral body invasion; no pleural effusion; performance status 0–1; weight loss < 5% in the past 3 months.

SCHEMA. Patients are randomized to cisplatin/vinorelbine versus cisplatin/paclitaxel versus cisplatin/gemcitabine for two cycles. Irradiation to 50 Gy is added during cycles 3 and 4.

9531. High-dose carboplatin and paclitaxel granulocyte colony-stimulating factor and peripheral blood stem cell support followed by surgery and/or radiotherapy
ELIGIBILITY. Histologically documented NSCLC; staged initially as unresectable IIIA (T1-3, N2) and/or IIIB (T4, Nx; or Tx, mediastinal N3). No malignant pleural effusion; no metastases; no vertebral body invasion. Performance status 0–1; no prior chemotherapy or irradiation; no scalene LN involvement.

SCHEMA. All patients receive high-dose carboplatin/paclitaxel with granulocyte colony-stimulating factor and peripheral stem cell (PBSC) for two cycles. Patients are restaged; surgical candidates receive resection followed by 50 Gy irradiation; nonsurgical patients receive 66 Gy irradiation.

9633. Adjuvant chemotherapy after resection for patients with T2N0 stage I NSCLC
ELIGIBILITY. Histologically documented NSCLC; after a complete resection (lobectomy or pneumonectomy) for stage I (T2N0M0). Randomization must occur within 4–8 weeks of resection. No prior chemotherapy or irradiation. Performance status 0–1.

SCHEMA. Patients are randomized to carboplatin and paclitaxel versus observation.

9761. Detection of occult micro-metastasis in patients with clinical stage I NSCLC: a prospective analysis
ELIGIBILITY. N1 or N2, LN < 1 cm on Chemotherapy or T1 or T2 primary.

SCHEMA. TS/thoracotomy for lobectomy; 5-10 mls bone marrow; L (5, 6, 7, 9, 10 & 11); R(4, 7, 9, 10 & 11); 1.0 cm of the primary tumor.

9795. A phase III prospective randomized study of adjuvant CT in completely resected NSCLC
ELIGIBILITY. Histologic proof of primary T1N1, N1

SCHEMA. Registration; tumor specimen submission; randomization to Arm 1 (observation) or Arm 2 (cisplatin and vinorelbine.

9734. A phase III study of surgical resection and CT with or without XRT for resected stage IIIA NSCLC
ELIGIBILITY. Histologic N2, PS = 0-1, surgical staging, no residual disease

SCHEMA. Surgery; registration; chemotherapy (paclitaxel/carboplatin); Randomization to observation or radiation therapy (50 Gy/25 tx/5 weeks).

	References

Top Abstract Introduction Methods Discussion Appendix 1. Thoracic surgical... Appendix 2. CALGB lung... References

 

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