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In Reply

Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY

Dr Leo and colleagues voice concerns about the efficacy and benefit of the combined modality treatment utilized for patients with superior sulcus non–small-cell lung carcinomas (SS NSCLC) in Intergroup trial 0160 (Southwest Oncology Group 9416).¹ They question whether the patients entered onto this study had a better performance status than patients treated with preoperative radiation and surgery in several retrospective series including a large one previously reported from Memorial Sloan-Kettering Cancer Center (New York, NY).² Like many surgical series, these retrospective studies do not include specific data on performance status. However, it is unusual for thoracic surgeons to consider doing a resection for SS NSCLC in patients with a performance status of 2 or higher because of the scope and risk of the operation. Therefore, it is highly unlikely that the patients entered onto this trial had a substantially better performance status relative to patients undergoing surgery in earlier reports.

A question is raised about treatment toxicity. In fact, the frequency of adverse events is comparable with that reported in virtually all other studies of combined-modality therapy in patients with locally advanced NSCLC. Notably, induction therapy was well-tolerated and was completed by 95% of patients entered onto study. Dr Leo and colleagues appear to have missed the point clearly made in the last paragraph of the Discussion section that only the postoperative chemotherapy was poorly tolerated. Again, virtually all published studies of adjuvant therapy have shown the difficulty of delivering cisplatin-based chemotherapy in this setting, especially in patients with locally advanced NSCLC who have undergone the type of extensive resection required for the removal of SS tumors. In the Discussion section, we emphasized that the use of adjuvant therapy for these patients is an area for future investigation.

Dr Leo and colleagues indicate that the adverse role of mediastinal nodal disease is not addressed in our article. This is indeed addressed in the Methods section (eligibility criteria) at the end of the second paragraph of the Discussion section. The adverse prognostic impact of N2 disease in patients with SS NSCLC is well-documented in previous studies² and was the rationale for excluding such patients from this trial.

Finally, Dr Leo and colleagues suggest that it might be feasible and appropriate to use a higher dose of preoperative radiotherapy in order to reduce the risk of local recurrence. We agree and addressed this point in the next to last paragraph of the Discussion section. In the mid-1990s when this trial was designed, a radiation dose of 45 Gy delivered concurrently with cisplatin-based chemotherapy was known to be safe and effective in multicenter trials in locally advanced NSCLC and was therefore the dose used in this trial. As we noted, contemporary radiotherapy techniques might permit the safe delivery of higher doses of induction radiation, but the small single institution studies utilizing higher radiation doses need to be confirmed in multicenter trials. It is also important to remember that the predominant form of relapse in this trial was distant metastatic disease and that, as indicated at the end of the Results section, only 10 patients developed local recurrence in the absence of metastases. Undoubtedly small improvements can be made to the locoregional therapy used in our study, but the predominant problem now remains systemic disease, particularly brain metastases.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author indicated no potential conflicts of interest.

REFERENCES

1. Rusch VW, Giroux DJ, Kraut M, et al: 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). J Clin Oncol 25: 313-318, 2007[Abstract/Free Full Text]

2. 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]

Related Correspondence

• Induction Chemoradiotherapy for Superior Sulcus Non–Small-Cell Lung Cancer: An Answer for Few
  Francesco Leo, Piergiorgio Solli, Giulia Veronesi, Gianpiero Catalano, Tommaso De Pas, Francesco Petrella, and Lorenzo Spaggiari
  JCO 2007 25: 2146 [Full Text]

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