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Induction Chemoradiation and Surgical Resection for Superior Sulcus Non–Small-Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160)

Valerie W. Rusch, Dorothy J. Giroux, Michael J. Kraut, John Crowley, Mark Hazuka, Timothy Winton, David H. Johnson, Lawrence Shulman, Frances Shepherd, Claude Deschamps, Robert B. Livingston, David Gandara

From the Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Cancer Research and Biostatistics; Department of Medical Oncology, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; Hematology/Oncology, Providence Hospital, Southfield, MI; Department of Radiation Oncology, Memorial Hospital, Colorado Springs, CO; Department of Surgery, University of Alberta, Edmonton, Alberta; Division of Hematology/Oncology, Princess Margaret Hospital, Toronto, Canada; Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN; Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Thoracic Surgery, Mayo Clinic, Rochester, MN; and the Department of Hematology/Oncology, University of California Davis Cancer Center, Sacramento, CA

Address reprint requests to Southwest Oncology Group, 14980 Omicron Dr, San Antonio, TX 78245-3217; e-mail: bgranados{at}swog.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
PURPOSE: Traditional treatment for superior sulcus non–small-cell lung cancers (SS NSCLC), radiation plus surgery, yields a 50% rate of complete resection and a 30% 5-year survival. On the basis of improved outcomes in other subsets of stage III NSCLC, this trial tested the feasibility of induction chemoradiotherapy for SS NSCLC.

PATIENTS AND METHODS: Patients with T3-4, N0-1 SS NSCLC received two cycles of cisplatin and etoposide concurrently with radiation (45 Gy). Patients with stable or responding disease underwent thoracotomy. All patients received two more cycles of chemotherapy. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed by Cox regression analysis.

RESULTS: From April 1995 to November 1999, 110 eligible patients (76 men, 34 women) were entered onto the study (78 T3, 32 T4 tumors). Induction therapy was completed by 104 (95%) patients. Of 95 patients eligible for surgery, 88 (80%) underwent thoracotomy, two (1.8%) died postoperatively, and 83 (76%) had complete resection. Pathologic complete response (CR) or minimal microscopic disease was seen in 61 (56%) resection specimens. Five-year survival was 44% for all patients and 54% after complete resection, with no difference between T3 and T4 tumors. Pathologic CR led to better survival than when any residual disease was present (P = .02). Disease progression occurred mainly in distant sites.

CONCLUSION: This combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Non–small-cell lung carcinomas (NSCLC) of the superior sulcus (SS) are among the most challenging thoracic tumors to treat because of their involvement of adjacent vital structures including the brachial plexus, subclavian vessels, and spine. Originally described by Henry Pancoast in 1932,¹ SS NSCLC were believed to be uniformly fatal until the 1950s, when preoperative radiation and en-bloc resection was found to be potentially curative.^2,3 During the next 40 years, this approach remained the standard of care, with improve-ments limited to the development of novel surgical techniques for T4 tumors.^4-6 However, complete resection was achieved in only 60% of patients and overall survival at 5 years remained 30%, indicating a clear need for novel therapy.⁷ During the 1990s, increasing experience with combined-modality therapy suggested that induction chemoradiotherapy followed by resection was an effective treatment strategy for stage III NSCLC.⁸ Small studies suggested that this approach might be appropriate for SS NSCLC.⁹ These experiences led us to test induction chemoradiotherapy plus resection in SS NSCLC.

	PATIENTS AND METHODS

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Eligibility Criteria
Patients were eligible if they had solitary, previously untreated T3 or T4, N0-1 SS NSCLC. This included patients with an apical tumor and the Pancoast syndrome, or SS tumors with invasion of the chest wall, spine, or subclavian vessels by computed tomography (CT scan) or magnetic resonance imaging (MRI) with or without an associated Pancoast syndrome. Prestudy staging included a CT scan of the chest and upper abdomen through the adrenals, CT or MRI of the brain, bone scan, and mediastinoscopy. Thoracic spine and brachial plexus MRI was recommended. Positron emission tomography scans were not required because this trial predated the routine use of positron emission tomography for NSCLC staging. A Southwest Oncology Group (SWOG) performance status of 0 to 2 and adequate cardiopulmonary, renal, and neurologic function to tolerate the planned treatment were required. Tumors were stratified by T3 versus T4 status at study entry.

Induction Therapy Regimen
Induction chemotherapy and radiation began within 24 hours of each other. Chemotherapy consisted of cisplatin 50 mg/m² on days 1, 8, 29, and 36, and etoposide 50 mg/m² on days 1 through 5 and 29 to 33. The total radiation dose was 45 Gy administered in 1.8-Gy daily fractions during 5 weeks. The radiation target, defined by CT scan, included the primary tumor and ipsilateral supraclavicular region, but not the mediastinum or hilum.

Induction treatment and boost chemotherapy toxicities were recorded according to the National Cancer Institute Common Toxicity Criteria, version 2.0.

Evaluation After Induction Therapy and Guidelines for Surgical Resection
Two to 4 weeks after induction therapy, patients were reassessed by history, physical examination, and CT scans of the chest, upper abdomen, and brain. Bone scan was done if new bone pain or elevated alkaline phosphatase or lactate dehydrogenase were present. Patients without distant metastases or local progression underwent thoracotomy. Patients with disease progression were removed from the study but were observed in follow-up visits. Response determinations were required at this point in the study. A complete response (CR) was complete radiologic disappearance of all measurable or assessable disease. A partial response (PR) was a 50% or greater decrease under baseline in the sum of products of perpendicular diameter of all measurable lesions. Progression was a 25% or greater increase in the sum of products of all measurable lesions. Patients with stable disease had lesions that did not meet the criteria for CR, PR, or progression.

Thoracotomy was performed 3 to 5 weeks after induction chemoradiotherapy. A lobectomy or pneumonectomy was required for resection. Areas of direct tumor extension into the chest wall or spine were resected en-bloc with the involved lung. For right-sided tumors, lymph nodes at levels 2R, 4R, 7, 8, 9, and 10R were removed; for left-sided tumors, nodes at levels 5, 6, 7, 8, 9, and 10L were removed.

Boost Chemotherapy and Follow-Up
All patients, whether or not they had a resection, were to receive two additional cycles of cisplatin and etoposide chemotherapy, without additional radiation. Patients were then observed every 3 months during the first 2 years, then every 6 months with history, physical examination, chest x-ray, and blood tests. CT scans of the brain, chest, and upper abdomen were required every 6 months for the first 3 years postoperatively.

Data Quality Control and Statistical Analyses
All data forms, chemotherapy flow sheets, radiology reports, and operative and pathology reports were reviewed by the study chair (V.R.) and the medical oncology coordinator (M.K.). T4 stage was verified by imaging studies documenting spine invasion or encasement of subclavian vessels.

Survival, calculated from the date of study entry, was estimated by the product-limit method,¹⁰ and survival curves were compared via log-rank tests. Prognostic factors were assessed for their significance in predicting survival via Cox regression analysis.¹¹ Groups of continuous data were compared using the Wilcoxon rank sum test. Data were analyzed using Statistical Analysis Software, version 6.12 (SAS Institute, Cary, NC). All reported significance values were two tailed.

	RESULTS

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Demographic and Clinical Characteristics
From April 15, 1995 to August 1, 1999, 116 patients entered onto the study. All of the North American cooperative groups participated in this trial, including the Eastern Cooperative Oncology Group (33 patients), the Cancer and Leukemia Group B (29 patients), the National Cancer Institute of Canada (26 patients), SWOG (19 patients), and the North Central Cancer Treatment Group (nine patients). Of 116 total patients, 110 were ultimately deemed eligible. Five patients had metastatic disease and one patient with pneumonia were removed from the study before treatment. Seventy-six surgeons operated on patients entered onto this trial; the mean number of patients per surgeon was 1.42. Prestudy characteristics are outlined in Table 1. Most patients were male (69%), white (88%), had T3 tumors (71%), and a performance status of 0 to 1 (98%). The median patient age was 56 years (range, 36 to 77 years). Primary tumors were usually large, with a median tumor size of 6 cm (range, 2 to 14.5 cm).

View larger version (14K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. Study schema of Southwest Oncology Group (SWOG) 9416. *Percentages calculated based on the total number of eligible patients. Reprinted with permission.12 CR, complete response; PR, partial response; NSCLC, non–small-cell lung cancer; CT, computed tomography.

Induction therapy was well tolerated (Appendix Table A1, online only). Leukopenia, neutropenia, and anemia were the most common grade 3 or higher toxicities. Five patients had grade 3 or higher esophagitis. After induction therapy, no patients had a CR, 46 (42%) had a PR, and 40 (36%) had stable disease.

Surgery
Surgical data are summarized in Appendix Table A2 (online only). The most frequent operation was a lobectomy and chest wall resection. The 13 patients who had only a pulmonary resection performed had such marked tumor regression after induction therapy that chest wall resection was no longer considered necessary. A small number of patients undergoing more complex procedures, such as vertebral body resection, are listed under "other." Resections were pathologically complete (R0) in 61 of 65 patients (94%) with T3 tumors and 22 of 23 (96%) with T4 tumors.

Postoperative complications are listed in Appendix Table A3 (online only). Two patients (2.3%) died postoperatively of multisystem failure. Pulmonary complications were the most common, with pneumonia occurring in 13.6% of patients. Arrhythmias, myocardial infarction, bronchopleural fistula, hemorrhage requiring reoperation, and empyema were other major but infrequent complications. The median length of hospital stay was 7 days (range, 3 to 64 days).

Review of postinduction therapy CT scan reports and pathology reports showed that many patients had a large residual mass on CT but only a few scattered foci of tumor within mostly residual fibrosis at operation. Therefore, the final pathologic response was divided into three categories: pathologic CR (no residual microscopic tumor), minimal microscopic residual (few scattered tumor foci within a mostly necrotic or fibrotic mass), and gross residual disease (mostly or entirely viable tumor). Each of these categories included roughly one third of the resected specimens, with 61% of patients having either a pathologic CR or minimal microscopic residual tumor. Appendix Table A4 (online only) shows the substantial discrepancy between radiologic and pathologic response. Of 46 patients considered to have a radiologic PR, 33 (72%) had pathologic CR or minimal microscopic residual disease. Of the 40 patients deemed to have stable disease, 26 (65%) had either pathologic CR or minimal microscopic residual disease.

Boost Chemotherapy
Sixty patients were registered to receive boost chemotherapy, including 59 who had surgery and one who did not. Among 28 patients registered to surgery but not to boost chemotherapy, the reasons for no boost chemotherapy were postoperative death (two patients), disease progression after surgery (three patients), patient too frail to continue chemotherapy (11 patients), change in histologic diagnosis after tumor resection (two patients), patient refusal (four patients), and other reasons (eight patients). Of patients registered to boost chemotherapy, only 49 (81% of patients registered to this step, 45% of all eligible patients) received the two planned cycles of chemotherapy, and six patients received one cycle of chemotherapy.

Survival and Relapse Information
As of June 22, 2006, 44 patients, observed for a median of 82 months, are still alive. Overall survival for all eligible patients (by T status) and for patients who had an R0 resection is shown in Figure 2. The median survival for all eligible patients is 33 months and 94 months for the patients who had an R0 resection (Fig 3).

View larger version (14K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2. Overall survival of all eligible patients and by T status.

View larger version (11K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3. Survival after surgery: patients with complete resections.

View larger version (14K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 4. Postoperative survival by pathologic response (complete response [CR] v not) for patients who underwent surgery. NR, no response.

	DISCUSSION

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Evolutions in the management of SS NSCLC during the last 70 years can be classified into four eras. These tumors were first described in 1932 by a radiologist, Henry Pancoast, as "a peculiar neoplastic entity found in the upper portion of the pulmonary sulcus of the thorax...its exact origin is uncertain... .It produces constant and characteristic clinical phenomena of pain in the eighth cervical and first and second thoracic trunk distribution, wasting of the muscles of the hand and Horner's syndrome."¹ During the ensuing 20 years, these tumors became recognized as primary lung carcinomas but were believed to be incurable. In 1956, Chardack and MacCallum² reported prolonged survival after en-bloc resection of a superior sulcus NSCLC along with the involved chest wall and nerve roots, and adjuvant radiation. In 1956, Shaw referred for radiotherapy a patient presenting with the Pancoast syndrome. When 30 Gy of radiation led to resolution of the pain and a decrease in tumor size, Shaw undertook resection. The complete resection and long-term survival achieved in this patient prompted additional evaluation of this treatment strategy.¹³ In 1961, Shaw et al³ reported 18 patients who received 30 to 35 Gy of radiation during 2 weeks, followed by en-bloc resection of the involved lobe, chest wall, and nerve roots, with excellent local control and prolonged survival.

For the next 30 years, induction radiation and en-bloc resection via an extended posterolateral thoracotomy became standard care for SS NSCLC. Multiple series confirmed the original results of Shaw et al.^14-24 The largest series, from Memorial Sloan-Kettering Cancer Center,^7,25 included 225 patients and reported an operative mortality of 4%; a complete resection rate of 64% in T3, N0; and 39% in T4, N0 tumors. Locoregional recurrence was the most common form of relapse.⁷ Lobectomy was associated with a better overall survival than limited pulmonary resection and the addition of intraoperative brachytherapy to resection did not improve survival.²⁵ Overall survival at 5 years was 46% for T3, N0; 13% for T4, N0; and 0% for tumors with N2 disease.⁷ These results emphasized the need for new treatment strategies.

During the late 1980s and the 1990s, novel approaches were developed for the resection of tumors involving the spine and subclavian vessels. Dartevelle et al⁴ described an anterior transcervical-thoracic approach for tumors involving the subclavian vessels. Several improvements were later made to this approach.^26-29 For tumors involving the spine, techniques for multilevel vertebrectomy and spine reconstruction were developed.^5,6,30-32 New techniques for complete resection of T4 tumors were important advances in surgical management, but survival at 5 years remained approximately 30%.

During this same time, other studies reported the results of treatment with radiation only. These are difficult to interpret because they are retrospective, include small numbers of patients who were only clinically staged and were treated in a highly variable manner.^33-36 In general, local control and survival seem inferior to those reported in surgical series, but this may reflect patient selection and variable treatment.

The success of combined-modality therapy for stage IIIa (N2) NSCLC during the 1980s and 1990s led directly to the development of this study, the only prospective multicenter trial to date for SS NSCLC. Induction chemoradiotherapy followed by resection is a logical strategy for a group of tumors that present a formidable challenge in local control. The induction regimen in this trial was feasible and effective in previous multicenter studies. The trial design is particularly important, with inclusion of a homogeneous group of patients through systematic staging including mediastinoscopy and stratification of T3 versus T4 tumors. The excellent results obtained with respect to response to induction treatment, low operative mortality, R0 resection, local control rates, and long-term survival effectively establish the treatment regimen used as a new standard of care, for both T3 and T4 tumors. Recent single-institution studies corroborate our results.^9,37

The long-term results of this study confirm and also clarify our previously reported initial results.¹² Early analysis showed that induction chemoradiotherapy and resection were feasible, and were associated with higher rates of R0 resection than previously reported. The mature results now show that overall survival at 5 years is far better than in previous series using preoperative radiation and resection without chemotherapy. Initial analyses suggested that minimal microscopic residual disease at surgery was associated with an overall survival intermediate between that seen with either a pathologic CR or gross residual disease. Current results show that any amount of residual disease, even when completely resected, is associated with a significantly worse survival than when a pathologic CR occurs. However, the 5-year survival for patients who had residual disease substantially exceeds the approximate 30% survival historically reported for patients treated with induction radiation and resection. Moreover, in patients with SS NSCLC, local recurrence has a marked impact on patient quality of life because it causes excruciating pain and loss of arm function. The patterns of disease recurrence in this study, namely a very low rate of local relapse, are different from those reported with radiation alone plus resection, and have important implications for patient quality of life.

Accrual to this trial was completed successfully within the planned time frame, but required the efforts of 76 surgeons from all of the North American cooperative groups to enroll 110 eligible patients. This experience makes it unlikely that future randomized trials including resection could be completed within an acceptable length of time for this uncommon NSCLC subset. However, several questions could be studied in future single-arm or randomized phase II trials. First, other induction chemotherapy regimens (ie, cytotoxic or targeted therapies) leading to a higher rate of pathologic CR may improve results. Whatever newer drugs are used, however, will have to be not only more effective but also no more toxic when combined with radiation and surgery. The induction regimen could be intensified by adding a third cycle of chemotherapy or by increasing the dose of radiation. Recently, Suntharalingam et al³⁸ and Kwong et al³⁹ reported using a median preoperative radiation dose of 59.4 Gy in combination with platinum-based chemotherapy, with a resulting pathologic CR of 46% and a 5-year survival of 49% in 23 patients. It is not clear that the higher radiation dose improves survival or is safe in the multi-institutional setting.

Our trial emphasizes the difficulty of delivering cisplatin-based therapy postoperatively to this group of NSCLC patients. On the basis of the results of other SWOG trials in patients with locally advanced NSCLC, docetaxel currently is being tested as single-agent adjuvant therapy in an ongoing phase II intergroup trial. In the future, other agents or targeted therapies may prove to be less toxic and more effective adjuvant therapy. Given the patterns of relapse seen in this study, improved systemic therapy, either induction or adjuvant, is needed to achieve improved outcomes. Finally, the high risk of brain relapse seen in this trial is similar to what has been reported in other combined-modality trials for patients with locally advanced NSCLC, and raises the issue of whether patients should be considered for prophylactic cranial radiation. It is hoped that the results of an ongoing randomized trial testing the use of prophylactic cranial radiation in patients with locally advanced NSCLC will answer this question. Certainly, at present, the combined-modality regimen used in this trial offers patients with SS NSCLC substantially better treatment results than seen previously.

	AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: N/A Consultant: David Gandara, Bristol-Myers Squibb Co Stock: N/A Honoraria: John Crowley, Ligand, Pierre Fabre Oncology; Timothy Winton, Amgen, GlaxoSmithKline, Ortho Biotec, Roche, Bristol-Myers Squibb Co, Johnson & Johnson, Bristol-Myers Squibb Co; Robert B. Livingston, Amgen, Pfizer Inc, Novartis Research Funds: N/A Testimony: N/A Other: N/A

	AUTHOR CONTRIBUTIONS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Conception and design: Valerie W. Rusch, Dorothy J. Giroux, John Crowley, David H. Johnson, Lawrence Shulman, Claude Deschamps, Robert B. Livingston

Administrative support: John Crowley, Robert B. Livingston, David Gandara

Provision of study materials or patients: Valerie W. Rusch, Michael J. Kraut, Mark Hazuka, Timothy Winton, Lawrence Shulman, Frances Shepherd, Claude Deschamps, Robert B. Livingston

Collection and assembly of data: Dorothy J. Giroux, John Crowley

Data analysis and interpretation: Valerie W. Rusch, Dorothy J. Giroux, Michael J. Kraut, John Crowley, David H. Johnson

Manuscript writing: Valerie W. Rusch

Final approval of manuscript: Valerie W. Rusch, Dorothy J. Giroux, Michael J. Kraut, John Crowley, Mark Hazuka, Timothy Winton, David H. Johnson, Lawrence Shulman, Frances Shepherd, Claude Deschamps, Robert B. Livingston, David Gandara

	Appendix

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View larger version (16K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig A1. Postoperative survival by pathologic response for patients who underwent surgery. CR, complete response; NR, no response.

	NOTES

 
Supported in part by the following Public Health Service Cooperative Agreement grants awarded by the National Cancer Institute, Department of Health and Human Services: Grants No. CA38926, CA32102, CA37981, CA46282, CA14028, CA20319, CA46368, CA46441, CA35176, CA12644, CA46113, CA22433, CA58882, CA52772, CA49957, CA23318, CA66636, CA21115, CA25224, and CA32291.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

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1. Pancoast HK: Superior pulmonary sulcus tumor. JAMA 99:1391-1396, 1932

2. Chardack WM, MacCallum JD: Pancoast tumor (five year survival without recurrence or metastases following radical resection and postoperative irradiation). J Thorac Surg 31:535-542, 1956[Medline]

3. Shaw RR, Paulson DL, Kee JL Jr: Treatment of the superior sulcus tumor by irradiation followed by resection. Ann Surg 7:29-40, 1961[Medline]

4. Dartevelle PG, Chapelier AR, Macchiarini P, et al: Anterior transcervical-thoracic approach for radical resection of lung tumors invading the thoracic inlet. J Thorac Cardiovasc Surg 105:1025-1034, 1993[Abstract]

5. Bilsky MH, Vitaz TW, Boland PJ, et al: Surgical treatment of superior sulcus tumors with spinal and brachial plexus involvement. J Neurosurg 97:301-309, 2002 (suppl 3)[Medline]

6. Gandhi S, Walsh GL, Komaki R, et al: A multidisciplinary surgical approach to superior sulcus tumors with vertebral invasion. Ann Thorac Surg 68:1778-1785, 1999[Abstract/Free Full Text]

7. Rusch VW, Parekh KR, Leon L, et al: Factors determining outcome after surgical resection of T3 and T4 lung cancers of the superior sulcus. J Thorac Cardiovasc Surg 119:1147-1153, 2000[Abstract/Free Full Text]

8. Albain KS, Rusch VW, Crowley JJ, 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 13:1880-1892, 1995[Abstract/Free Full Text]

9. Martínez-Monge R, Herreros J, Aristu JJ, et al: Combined treatment in superior sulcus tumors. Am J Clin Oncol 17:317-322, 1994[Medline]

10. Kaplan EL, Meier P: Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958[CrossRef]

11. Cox DR: Regression models and life tables [with discussion]. J R Stat Soc B 34:187-220, 1972

12. Rusch VW, Giroux DJ, Kraut MJ, et al: Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group trial 9416 (Intergroup trial 0160). J Thorac Cardiovasc Surg 121:472-483, 2001[Abstract/Free Full Text]

13. Shaw RR: Pancoast's tumor. Ann Thorac Surg 37:343, 1984[Abstract]

14. Paulson DL: Carcinomas in the superior pulmonary sulcus. J Thorac Cardiovasc Surg 70:1095-1104, 1975[Abstract]

15. Hilaris BS, Martini N, Wong GY, et al: Treatment of superior sulcus tumor (Pancoast tumor). Surg Clin North Am 67:965-976, 1987[Medline]

16. Sartori F, Rea F, Calabrb F, et al: Carcinoma of the superior pulmonary sulcus: Results of irradiation and radical resection. J Thorac Cardiovasc Surg 104:679-683, 1992[Abstract]

17. Maggi G, Casadio C, Pischedda F, et al: Combined radiosurgical treatment of Pancoast tumor. Ann Thorac Surg 57:198-202, 1994[Abstract]

18. Attar S, Krasna MJ, Sonett JR, et al: Superior sulcus (Pancoast) tumor: Experience with 105 patients. Ann Thorac Surg 66:193-198, 1998[Abstract/Free Full Text]

19. Hagan MP, Choi NC, Mathisen DJ, et al: Superior sulcus lung tumors: Impact of local control on survival. J Thorac Cardiovasc Surg 117:1086-1094, 1999[Abstract/Free Full Text]

20. Komaki R, Roth JA, Walsh GL, et al: Outcome predictors for 143 patients with superior sulcus tumor treated by multidisciplinary approach at the University of Texas M.D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys 48:347-354, 2000[Medline]

21. Martinod E, D'Audiffret A, Thomas P, et al: Management of superior sulcus tumors: Experience with 139 cases treated by surgical resection. Ann Thorac Surg 73:1534-1540, 2002[Abstract/Free Full Text]

22. van Geel AN, Jansen PP, van Klaveren RJ, et al: High relapse-free survival after preoperative and intraoperative radiotherapy and resection for sulcus superior tumors. Chest 124:1841-1846, 2003[Medline]

23. Alifano M, D'Aiuto M, Magdeleinat P, et al: Surgical treatment of superior sulcus tumors: Results and prognostic factors. Chest 124:996-1003, 2003[CrossRef][Medline]

24. Pfannschmidt J, Kugler C, Muley T, et al: Non-small-cell superior sulcus tumor: Results of en bloc resection in fifty-six patients. Thorac Cardiovasc Surg 51:332-337, 2003[CrossRef][Medline]

25. Ginsberg RJ, Martini N, Zaman M, et al: Influence of surgical resection and brachytherapy in the management of superior sulcus tumor. Ann Thorac Surg 57:1440-1445, 1994[Abstract]

26. Grunenwald D, Spaggiari L: Transmanubrial osteomuscular sparing approach for apical chest tumors. Ann Thorac Surg 63:563-566, 1997[Abstract/Free Full Text]

27. Spaggiari L, Pastorino U: Transmanubrial approach with antero-lateral thoracotomy for apical chest tumor. Ann Thorac Surg 68:590-593, 1999[Abstract/Free Full Text]

28. Fadel E, Missenard G, Chapelier A, et al: En bloc resection of non-small cell lung cancer invading the thoracic inlet and intervertebral foramina. J Thorac Cardiovasc Surg 123:676-685, 2002[Abstract/Free Full Text]

29. Ohta M, Hirabayasi H, Shiono H, et al: Hemi-clamshell approach for advanced primary lung cancer. Thorac Cardiovasc Surg 52:200-205, 2004[CrossRef][Medline]

30. Sundaresan N, Hilaris BS, Martini N: The combined neurosurgical-thoracic management of superior sulcus tumors. J Clin Oncol 5:1739-1745, 1987[Abstract/Free Full Text]

31. York JE, Walsh GL, Lang FF, et al: Combined chest wall resection with vertebrectomy and spinal reconstruction for the treatment of Pancoast tumors. J Neurosurg 91:74-80, 1999[Medline]

32. Mazel C, Grunenwald D, Laudrin P, et al: Radical excision in the management of thoracic and cervicothoracic tumors involving the spine: Results in a series of 36 cases. Spine 28:782-792, 2003[CrossRef][Medline]

33. Van Houtte P, MacLennan I, Poulter C, et al: External radiation in the management of superior sulcus tumor. Cancer 54:223-227, 1984[CrossRef][Medline]

34. Attar S, Miller JE, Satterfield J, et al: Pancoast's tumor: Irradiation or surgery? Ann Thorac Surg 28:578-586, 1979[Abstract]

35. Herbert SH, Curran WJ Jr, Stafford PM, et al: Comparison of outcome between clinically staged, unresected superior sulcus tumors and other stage III non-small cell lung carcinomas treated with radiation therapy alone. Cancer 69:363-369, 1992[CrossRef][Medline]

36. Komaki R, Derus SB, Perez-Tamayo C, et al: Brain metastasis in patients with superior sulcus tumors. Cancer 59:1649-1658, 1987[CrossRef][Medline]

37. Wright CD, Menard MT, Wain JC, et al: Induction chemoradiation compared with induction radiation for lung cancer involving the superior sulcus. Ann Thorac Surg 73:1541-1544, 2002[Abstract/Free Full Text]

38. Suntharalingam M, Sonett JR, Haas ML, et al: The use of concurrent chemotherapy with high-dose radiation before surgical resection in patients presenting with apical sulcus tumors. Cancer J Sci Am 6:365-371, 2000

39. Kwong KF, Edelman MJ, Suntharalingam M, et al: High-dose radiotherapy in trimodality treatment of Pancoast tumors results in high pathologic complete response rates and excellent long-term survival. J Thorac Cardiovasc Surg 129:1250-1257, 2005[Abstract/Free Full Text]

Submitted July 13, 2006; accepted October 19, 2006.

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				J. F. Bruzzi, R. Komaki, G. L. Walsh, M. T. Truong, G. W. Gladish, R. F. Munden, and J. J. Erasmus Imaging of Non-Small Cell Lung Cancer of the Superior Sulcus: Part 1: Anatomy, Clinical Manifestations, and Management RadioGraphics, March 1, 2008; 28(2): 551 - 560. [Abstract] [Full Text] [PDF]

				J. F. Bruzzi, R. Komaki, G. L. Walsh, M. T. Truong, G. W. Gladish, R. F. Munden, and J. J. Erasmus Imaging of Non-Small Cell Lung Cancer of the Superior Sulcus: Part 2: Initial Staging and Assessment of Resectability and Therapeutic Response RadioGraphics, March 1, 2008; 28(2): 561 - 572. [Abstract] [Full Text] [PDF]

				H. Kunitoh, H. Kato, M. Tsuboi, T. Shibata, H. Asamura, Y. Ichonose, N. Katakami, K. Nagai, T. Mitsudomi, A. Matsumura, et al. Phase II Trial of Preoperative Chemoradiotherapy Followed by Surgical Resection in Patients With Superior Sulcus Non-Small-Cell Lung Cancers: Report of Japan Clinical Oncology Group Trial 9806 J. Clin. Oncol., February 1, 2008; 26(4): 644 - 649. [Abstract] [Full Text] [PDF]

				J. Huang, G. J. Riely, K. E. Rosenzweig, and V. W. Rusch Multimodality Therapy for Locally Advanced Thymomas: State of the Art or Investigational Therapy? Ann. Thorac. Surg., February 1, 2008; 85(2): 365 - 367. [Full Text] [PDF]

				C. D. Wright, N. C. Choi, J. C. Wain, D. J. Mathisen, T. J. Lynch, and P. Fidias Induction Chemoradiotherapy Followed by Resection for Locally Advanced Masaoka Stage III and IVA Thymic Tumors Ann. Thorac. Surg., February 1, 2008; 85(2): 385 - 389. [Abstract] [Full Text] [PDF]

				V. Evilevitch, W. A. Weber, W. D. Tap, M. Allen-Auerbach, K. Chow, S. D. Nelson, F. R. Eilber, J. J. Eckardt, R. M. Elashoff, M. E. Phelps, et al. Reduction of Glucose Metabolic Activity Is More Accurate than Change in Size at Predicting Histopathologic Response to Neoadjuvant Therapy in High-Grade Soft-Tissue Sarcomas Clin. Cancer Res., February 1, 2008; 14(3): 715 - 720. [Abstract] [Full Text] [PDF]

				F. Leo, P. Solli, G. Veronesi, G. Catalano, T. De Pas, F. Petrella, and L. Spaggiari Induction Chemoradiotherapy for Superior Sulcus Non-Small-Cell Lung Cancer: An Answer for Few J. Clin. Oncol., May 20, 2007; 25(15): 2146 - 2146. [Full Text] [PDF]

				V. W. Rusch In Reply J. Clin. Oncol., May 20, 2007; 25(15): 2147 - 2147. [Full Text] [PDF]

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