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Ann Thorac Surg 2004;78:1200-1205
© 2004 The Society of Thoracic Surgeons

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Original article: general thoracic

Pulmonary Resection After Curative Intent Radiotherapy (>59 Gy) and Concurrent Chemotherapy in Non–Small-Cell Lung Cancer

^a Division of Cardiothoracic Surgery, Columbia University Medical Center, New York Presbyterian Hospital, New York, New York, USA
^b The Thoracic Oncology Program, Greenebaum Cancer Center, University of Maryland, School of Medicine, Baltimore, Maryland, USA

Accepted for publication April 20, 2004.

^* Address reprint requests to Dr Sonett, Division of Cardiothoracic Surgery, Columbia Presbyterian Medical Center, 622 W 168th St, PH 14, New York, NY 10032, USA
js2106{at}columbia.edu

Presented at the Thirty-Seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

	Abstract

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BACKGROUND: Pulmonary resection after chemotherapy and concurrent full-dose radiotherapy (>59 Gy) has previously been associated with unacceptably high morbidity and mortality. Subsequently neoadjuvant therapy protocols have used reduced and potentially suboptimal radiotherapy doses of 45 Gy. We report a series of 40 patients with locally advanced non–small-cell lung cancer who successfully underwent pulmonary resection after receiving greater than 59 Gy radiation and concurrent chemotherapy. Operative results and midterm survival follow-up are presented.

METHODS: Data were reviewed from 40 consecutive patients who underwent lung resection after receiving high-dose radiotherapy and concurrent platinum-based chemotherapy between January 1994 and May 2000. The follow-up closing interval for this study was until August 2003 or time of death.

RESULTS: Preoperative stage was IIb (7 patients), IIIA (21 patients), IIIB (10 patients), and IV (2 patients with isolated brain metastasis). Thirteen patients exhibited Pancoast tumors. Median time from completion of induction therapy to surgery was 53 days. Twenty-nine lobectomies and 11 pneumonectomies (7 right, 4 left) were performed. There were no postoperative deaths. Intercostal muscle flaps were used prophylactically in all but one pneumonectomy patient. Seven patients required perioperative transfusions. Median intensive care unit (ICU) time averaged 2 days and the total length of stay was 6 days. One patient exhibited postpneumonectomy pulmonary edema and a bronchopleural fistula developed in another patient (not receiving an intercostal muscle flap). Thirty-four of 40 patients (85%; 95% CI: 70%–94%) were downstaged pathologically, 33 out of 40 patients (82.5%, 95% confidence interval [CI]: 67%–93%) indicated no residual lymphadenopathy, and 18 out of 40 patients (45%, 95% CI: 29%–61%) exhibited a complete pathologic response. Median follow-up was 2.8 years. The 1-, 2-, and 5-year overall survival rates were 92.4%, 66.7%, and 46.2%, respectively. Disease-free 1-, 2-, and 5-year survival rates were 73.0%, 67.2%, and 56.4%, respectively. Median disease-free survival has not been reached.

CONCLUSIONS: Pulmonary resection may be performed safely after curative intent concurrent chemotherapy and radiotherapy to greater than 59 Gy. High pathologic complete response rates and sterilization of mediastinal lymph nodes were observed accompanied by highly favorable survival rates. This experience, though promising, will require confirmation in a prospective multiinstitutional clinical trial.

	Introduction

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The treatment of locally advanced (stage IIIa, IIIb, Pancoast) non–small-cell lung cancer (NSCLC) with either surgery alone or definitive chemoradiotherapy yields disappointing results with long-term survival rates of only 5%–25% [1–3]. In an attempt to improve overall survival clinical studies have focused on the use of neoadjuvant treatment protocols using either preopera-tive chemotherapy or combined chemotherapy and radiotherapy succeeded by surgery [4]. The results of combined modality therapy have been encouraging and long-term survival may, in part, be predicted by the pathologic response of the tumor to induction therapy [5–8]. Although the definitive benefit of surgical resection after induction therapy is still in question [9], long-term survival of patients receiving induction therapy has primarily been seen in patients where mediastinal nodal (N2) disease was eradicated [5–8]. Thus neoadjuvant therapy strategies that increase pathologic response may ultimately improve overall long-term survival in these patients.

Recent large prospective studies have validated the use of concurrent chemotherapy and radiotherapy in non–small-cell lung cancer, which yields a superior long-term survival advantage as compared with sequential approaches [10, 11]. Radiotherapy delivered for curative intent in nonsurgical studies has generally been delivered in doses greater than 59 Gy (in contrast doses of 30–45 Gy are generally employed in neoadjuvant approaches). The rationale toward more conservative radiotherapy in this setting has been based on previous reports that revealed unacceptable rates of postoperative complications when higher radiotherapy doses were administered [12]. Our group has previously reported the ability to safely perform pulmonary resection in a limited group of patients who received greater than 59 Gy of radiation [13, 14]. We update and supplement these reports with extended follow-up data in a series of 40 consecutive patients who underwent lobectomy or pneumonectomy after receiving concurrent platinum-based chemotherapy and radiotherapy greater than 59 Gy.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment References

 
Between January 1994 and May 2000, 40 consecutive patients at the University of Maryland Medical Center (Baltimore, MD) and Baltimore Veterans Administration Hospital (Baltimore, MD) underwent pulmonary resection after receiving concurrent chemotherapy and radiation therapy of greater than 59 Gy. Patients included in this study met the following criteria: (1) histologic diagnosis of non–small-cell lung cancer, (2) locally advanced disease amenable to potentially curative resection, (3) physiological capability to undergo trimodality therapy, and (4) patients who either declined or were ineligible to enter national clinical protocols. Patients with locally advanced disease were defined as having T3 with nodal involvement or T4 disease (excluding pleural effusion), T3 or T4 Pancoast tumors of the apical sulcus (± accompanying symptoms), or greater than N2 nodal disease. In addition 2 Pancoast (T3) patients with M1 disease, in which the brain was the sole site of metastasis, were also included.

Inclusion of patients in this aggressive regimen was highly selective. Patients were considered only if they achieved an outstanding performance status and a predicted postoperative forced expiratory volume in 1 second (FEV1) as well as a diffusing capacity for carbon monoxide (DLCO) of greater than 40%. A thoracic surgeon, medical oncologist, and radiation oncologist evaluated each patient before the onset of therapy. This was not a prospective clinical trial thus only patients identified as having surgical resection after high-dose radiotherapy and concurrent chemotherapy were analyzed (however data was collected prospectively as part of a thoracic surgery database used to monitor the outcome of all patients). All patients provided informed consent for chemotherapy, radiotherapy, surgery, and the collection of data. The patients evaluated include each patient who met the abovementioned criteria.

Chemotherapy was administered at several institutions and was not standardized. Radiation treatment planning was based on pretherapy computed tomography (CT) scans for all patients. Three-dimensional (3D) conformal radiotherapy was delivered starting in 1996. A shrinking-field technique was commonly employed with parallel opposed anteroposterior–posteroanterior (AP–PA) large fields designed to encompass the primary tumor plus a 2-cm margin, the ipsilateral hilar and supraclavicular regions, and bilateral upper and mid-mediastinal nodal chains. Off-cord boost fields were designed to include the primary tumor plus a 1.5-cm margin. The cumulative spinal cord dose from both fields was limited to 50 Gy. Dose analysis was performed throughout the entire treatment volume and lung inhomogeneity correction factors were used for dose computations. A total dose of 45–50.4 Gy was prescribed to the primary tumor, ipsilateral hilum, and mediastinum. In addition a small field boost of 14.4–21.6 Gy was given to the primary tumor alone and involved nodal fields. The final boost dose was, in part, based on the dose limitations of the spinal cord. The total dose delivered to the primary disease ranged between 59.6 and 66.6 Gy.

Data were entered on an Excel spreadsheet (Microsoft, Redmond, WA) and calculations were performed using GraphPad Prism software (GraphPad, San Diego, CA). Statistical analysis was performed using SPSS (version 10.0 for Windows; SPSS, Inc., Chicago, IL). Rates are reported with exact 95% confidence intervals (CI) (where appropriate) and survival rates were calculated using the Kaplan–Meier method [15]. The follow-up closing interval for this study was until August 2003 or time of death.

	Results

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Patient Characteristics
Characteristics of these 40 patients are detailed in Table 1. Diagnosis was confirmed by bronchoscopic biopsy or transcutaneous needle biopsy. All patients underwent a base line CT of the chest, CT and/or magnetic resonance image (MRI) of the brain, bone or positron emission tomography (PET) scan, and full pulmonary function tests. Sixteen of the 26 patients with clinical N2 disease had documented malignant adenopathy by mediastinoscopy pretreatment; the remaining 10 patients exhibited bulky adenopathy radiologically.

Chemotherapy
All patients received platinum-based chemotherapy using several regimens including carboplatin (AUC 6) and paclitaxel (45–50 mg/m²) in 30 out of 40 patients (75%), cisplatin/etoposide (100 mg/m²) in 5 out of 40 patients (12.5%), cisplatin/navelbine (100/25–30 mg/m²) in 4 out of 40 patients (10%), and 1 patient received carboplatin (AUC 6) alone on a weekly basis.

Surgery
All patients were restaged using a computed axial tomography (CAT) scan of the chest 4 weeks after therapy and 14 patients underwent mediastinoscopy after concurrent chemoradiotherapy. Median time to surgical resection after cessation of chemoradiotherapy was 52.5 days (range 20–258 days).

All patients underwent anatomic lobectomy or pnuemonectomy with mediastinal lymph-node dissection. Intraoperative fluid administration was carefully limited and barotrauma during single lung ventilation to the contralateral lung was minimized as much as possible by limiting peak pressure and limiting volume of ventilation. After the first broncho-pleural fistula developed in a pneumonectomy patient, all pneumonectomy stumps were covered with an intercostal muscle flap as described previously by our group [13].

Surgical resection procedures included 29 lobectomies (72.5%) and 11 pneumonectomies (27.5%). Seven right pneumonectomies and four left pneumonectomies performed. Thirteen patients diagnosed with Pancoast tumors underwent en-bloc chest wall resection as part of their procedure. There was no operative or postoperative mortality. Seven patients required perioperative blood transfusions. Median intensive care unit (ICU) stay was 2 days (range 0–13 days) and the median length of total hospital stay was 6 days (range 3–25 days).

Considerable complications were seen in 7 patients. Postpneumonectomy pulmonary edema developed in 1 patient who received a substantial fluid load (2 U blood, 8 L crystalloid) intraoperatively after a right pneumonectomy and en-bloc resection of her first through fifth ribs. She recovered and is now free of disease 3 years after resection. A broncho-pleural fistula complicated the first pneumonectomy in the series. The bronchial stump was not covered with a muscle bundle, although the patient was ultimately managed with an Eloesser flap. A subarachnoid-pleural fistula developed in 1 patient undergoing a Pancoast resection. Two patients exhibited prolonged atelectasis and postoperative pneumonias developed in 3 patients. One patient has remained on supplemental oxygen as an outpatient.

Response to Therapy
Pathologic samples were reviewed on all patients. Thirty-four out of 40 patients (85%) were pathologically downstaged (Fig 1). Figure 1 depicts the overall downstaging effect of the induction therapy; Table 2 matches and tracks each patient's tumor response. No patient experienced progression of disease during induction therapy, however 6 patients remained in the same stage. Eighteen out of 40 patients (45%) exhibited a complete pathologic response with no evidence of viable tumor at resection. Thirty-three out of 40 patients (82.5%) exhibited no pathologic N1 or N2 adenopathy at the time of resection. Preoperatively 26 out of 40 patients (65%) exhibited clinical N2 disease, of which 16 were pathologically proven by mediastinoscopy before surgical resection. Postoperatively 22 out of 26 of these patients (84.6%) exhibited pathologically confirmed sterilization of their mediastinal nodes, 3 patients exhibited persistent N2 disease, and 1 patient exhibited residual N1 disease. Of those 16 patients with path-proven N2 disease, 14 patients (87.5%) were sterilized by the induction protocol.

View larger version (14K): [in this window] [in a new window]   Fig 1. Comparison of clinical stage pre-therapy versus post-surgical pathologic stage. = pre-therapy; = post-surgery.

View larger version (16K): [in this window] [in a new window]   Fig 2. Overall survival (OS) (A) and disease-free survival (DFS) (B) after trimodality therapy.

View larger version (33K): [in this window] [in a new window]   Fig 3. Patterns of recurrence.

	Comment

Top Abstract Introduction Material and Methods Results Comment References

Limited published series have reported pulmonary resection after higher dose radiotherapy (> 59 Gy) and concurrent chemotherapy [12–14, 19]. In 1993 Fowler and associates reported an excessively high morbidity and mortality rate after pneumonectomy but not lobectomy in a phase II trial using 5 fluorouracil (5-FU), cisplatin, etoposide, and concurrent thoracic radiation to 60 Gy [12]. Six patients underwent lobectomy with no perioperative mortality, whereas 3 out of 7 (42%) pneumonectomy patients died from postoperative complications. Deutch and associates reported a similar series in 16 patients undergoing resection after radiation to 60 Gy and concurrent chemotherapy with carboplatin and etoposide. Of the patients undergoing lobectomy there were no postoperative deaths, whereas 2 out of 6 pneumonectomy patients died [19]. This current series corroborates the feasibility of lobectomy in patients who have received higher doses of radiation preoperatively (> 59 Gy) with no mortality or extended ventilation required in 29 patients undergoing lobectomy. Additionally we were able to safely perform pneumonectomy (including 7 right pneumonectomies) with no operative deaths in 11 patients.

The ability to safely perform lobectomy and pneumonectomy after higher doses of radiotherapy in this series may be attributed to several factors. First the development of sophisticated 3D-radiation treatment planning systems over the last decade has provided us with the opportunity to maximize radiation doses to the intended targets minimizing exposure to surrounding normal tissue [14]. Second the institution of routine coverage of all bronchial stumps with a vascularized muscle flap (primarily an intercostal muscle) seems to have eliminated the risk of bronchopleural fistula. Finally the low rate of postoperative acute respiratory distress syndrome may, in part, be attributed to both surgical management and improved radiotherapy techniques. We attempted to deliver no greater than 1 L of fluid during the operative procedure, to avoid high oxygen concentration levels, and to minimize barotrauma. Postoperatively fluid administration is severely limited using neosynepherine for postoperative hypotension (rather than fluid administration) and we commenced aggressive diuretic therapy shortly after surgery to maintain a considerable negative fluid balance (> l L) daily for at least 3 days.

The rationale for optimizing induction therapy is to offer patients the most beneficial medical therapy possible in an attempt to downstage and sterilize their mediastinal nodes before surgery. Multiple large studies have now documented that the sterilization of mediastinal nodes is the single most important prognostic sign with regard to long-term survival. The downstaging of the nodes as a maker of improved survival has been documented for both chemotherapy protocols and combined induction protocols of chemotherapy and radiotherapy. In the SWOG 8805 trial (induction chemotherapy and radiotherapy to 45 Gy) the strongest predictor of long-term survival after resection was the absence of tumors in mediastinal nodes (3-year survival rates are 44% for lymph-node negative patients [LN^–] vs 18% for lymph-node positive patients [LN⁺], p < 0.005). This study reported a 53% rate of sterilization of the mediastinal nodes [16]. In a recent analysis of prognostic factors in 103 patients reported by Bueno and associates, the downstaging of nodal disease was again determined to be the best predictor of long-term survival after induction therapy [20]. Patients in whom all nodal disease was eradicated indicated a 5-year survival rate of 35.8% versus patients with persistent N1 or N2 disease who indicated a 5-year survival rate of only 9% (p < 0.023). In that analysis 74 out of 103 patients (72%) received induction chemotherapy alone and 27 out of 103 patients (26%) received induction chemotherapy and radiotherapy. The rate of nodal sterilization was 26% (18 out of 67 patients). A similar rate was seen in the Cancer and Leukemia Group B (CALGB) prospective study of chemotherapy induction in stage IIIa disease (study 8935) in which the proven downstaging of N2 disease was 22% (10 out of 46 patients) [6]. The prognostic consideration of sterilization of mediastinal nodes was again confirmed in the large induction chemotherapy and radiation therapy (45 Gy) Intergroup trial 0139 in which superior results were seen in surgical patients who underwent complete mediastinal sterilization [9]. Two European trials, one by Betticher and associates and one by Voltolini and associates, indicate strikingly similar results of superior survival for patients in whom induction therapy sterilized mediastinal nodes as well [7, 8]. In this current study complete nodal sterilization was seen in 14 out of 16 patients (87.5%) with pathologically proven mediastinal adenopathy preoperatively. An encouraging overall survival rate of 46% at 5 years was observed. This improvement in nodal response may be, in part, attributed to the use of higher dose radiotherapy with concurrent chemoradiotherapy.

In designing an optimal induction protocol the addition of concurrent radiotherapy to systemic therapy has been indicated to improve survival versus both chemotherapy alone or sequentially delivered chemoradiotherapy [10, 11]. In a recent large nonoperative phase III study the West Japan Lung Cancer Group reported on patients with stage III non–small-cell carcinoma who were randomized to concurrent versus sequential chemoradiotherapy treatment. In the 323 patients that were studied the response rate (84% vs 66%, p = 0.0002) and the median survival rate (16.5 months vs 13.3 months, p = 0.039) were both improved with the delivery of concurrent versus sequential therapy. Of interest 35% (42 out of 117 patients) of the patients who failed in the sequential arm of the study recurred with local disease only, the highest single site of recurrence, an indication of the possible role of surgical resection after even optimal medical therapy [10]. Confirmation of improved survival rates using concurrent versus sequential chemoradiotherapy was recently reported in a large prospectively randomized Radiation Therapy Oncology Group (RTOG) trial [11]. In RTOG 9410 the median and 4-year survival rates were superior in patients receiving concurrent daily radiation to 60 Gy versus those receiving sequential therapy to 60 Gy (17 months versus 14.6 months median survival and 21% versus 12% 4-year survival).

There are notable limitations with regard to this study that warrant cautious interpretation and extrapolation of the results. This was a single institution retrospective analysis of a carefully selected cohort of patients with locally advanced non–small-cell lung cancer. This was not a prospective trial thus overall nodal sterilization, overall survival, and the ability to routinely deliver this therapy were not determined in an intent-to-treat manner. However the ability to safely bring this cohort of patients to surgical resection may allow future trials and treatment protocols to optimize the most advantageous medical therapy possible for patients with locally advanced disease and then also potentially randomize those patients toward either surgery or continued medical therapy without compromising the initial treatment.

Pulmonary resection, including lobectomy or pneumonectomy, after concurrent induction therapy with chemotherapy and radiation doses greater than 59 Gy may be performed with minimal morbidity or mortality. Advances in the delivery of radiation treatment fields, limited fluid administration, and vascularized bronchial stump coverage may all help to limit morbidity and mortality. The safety and effectiveness of neoadjuvant therapy with full-dose radiotherapy in the treatment of locally advanced non–small-cell lung cancer requires validation in prospective multiinstitutional clinical trails. Such a trial is currently planned by the Radiation Therapy Oncology Group.

	References

Top Abstract Introduction Material and Methods Results Comment References

 

1. Martini N, Flettinger BJ. The role of surgery in N2 lung cancer. Surg Clin North Am. 1987;67:1037–1049[Medline]
2. Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high dose radiation versus radiation alone in stage III non–small cell lung cancer. N Engl J Med. 1990;323:940–945[Abstract]
3. Edelman MJ, Gandara DR, Roach M, Benfield JR. Multimodality therapy in stage III non–small cell lung cancer. Ann Thorac Surg. 1996;61:1564–1572[Abstract/Free Full Text]
4. Green MR, Rocha Lima CM, Sheram AS. Radiation and chemotherapy for patients with stage III non–small cell lung cancer. Semin Radiat Oncol. 2000;10:289–295[Medline]
5. Rusch VW, Albain KS, Crowley JJ, et al. Surgical resection of stage IIIa and stage IIIb non–small-cell lung cancer after concurrent induction chemoradiotherapy. J Thorac Cardiovasc Surg. 1993;105:96–106
6. Sugarbaker DJ, Herndon J, Kohman LJ, Krasna MJ, Green MRCancer and Leukemia Group B Thoracic Surgery Group. Results of cancer and leukemia group B protocol 8935. A multiinstitutional phase II trimodality trial for stage IIIA (N2) non–small-cell lung cancer. J Thorac Cardiovasc Surg. 1995;109:473–483[Abstract/Free Full Text]
7. Voltolini L, Luca L, Ghiribelli C, Paladini P, Di Bisceglie M, Gotti G. Results of induction chemotherapy followed by surgical resection in patients with stage IIIA (N2) non–small cell lung cancer: the importance of the nodal down staging after chemotherapy. Eur J Cardiothorac Surg. 2001;20:1106–1112[Abstract/Free Full Text]
8. Betticher DC, Schmits S, Totsch M, et al. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non–small-cell lung cancer: a multicenter phase II trial. J Clin Oncol 21:1752–9
9. Albain KS, Scott CB, VR Rusch et al. Phase III comparison of concurrent chemotherapy plus radiotherapy (CT/RT) and CT/RT followed by surgical resection for stage IIIA (pN2) non–small-cell lung cancer (NSCLC): initial results from the intergroup trail 0139 (RTOG93–09). ASCO, Abstract 2003
10. Furuse K, Fukuoka M, Kawahaa M, Nishikawa H, Takada, Kudoh S. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non–small cell lung cancer. J Clin Oncol 1999;17 2692–9
11. Curran WJ, Scott C, Langer G, et al. Phase III comparison of sequential vs. concurrent chemo radiation for patients with unresectable stage III non–small-cell lung cancer. Initial report of RTOG 9410. Proc Am Soc Clin Oncol. 2000;19:484a
12. Fowler WC, Langer CJ, Curran WG, Keller SM. Postoperative complications after combined neoadjuvant treatment of lung cancer. Ann Thorac Surg. 1993;55986:9
13. Sonett JR, Krasna MJ, Suntharalingam M, Schuetz J, Doyle A, Lilenbaum R, et al. Safe pulmonary resection after chemotherapy and high-dose thoracic radiation. Ann Thorac Surg. 1999;68:316–320[Abstract/Free Full Text]
14. Suntharalingam M, Sonett JR, Haas ML, Doyle A, Hausner PF, Schuetz J, et al. The use of concurrent chemotherapy with high dose radiation prior to surgical resection in patients presenting with apical sulcus tumors. Cancer J Sci Am. 2000;6:365–371
15. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Asssoc. 1958;53:457–481
16. Albain KS, Rusch VW, Crowley JJ, Rice TW, Turrisi A, Weick JK, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of southwest oncology group phase II study 8805. J Clin Oncol. 1995;13:1880–1892[Abstract/Free Full Text]
17. Kraut MJ, Rusch VW, Crowley JJ, Gandara DR. Induction chemoradiotherapy plus surgical resection is a feasible and highly effective treatment for Pancoast tumors: initial results of SWOG 9416 (Intergroup 0160) Trial. Proc Am Soc Clin Oncol. 2000;19:487a
18. Perez CA, Pajak TF, Rubin P. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Cancer. 1987;59:1874–1881[Medline]
19. Deutch M, Crawford J, Leopold K, Wolf W, Foster W, Herndon J, et al. Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non–small cell cancer. Cancer. 1994;74:1243–1252[Medline]
20. Bueno R, Richards WG, Swanson SJ, Jaklitsch MT, Lukanich JM, Mentzer SJ, et al. Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival. Ann Thorac Surg. 2000;70:1826–1831[Abstract/Free Full Text]

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