63-year-old man with hemoptysis

The patient, JR, was a 63-year-old man who presented around Thanksgiving 2008 with hemoptysis. On his workup, he was found to have a mass in his left lung on CT scan as well as in the left hilar area approximately 3 cm distal to the carina. He underwent an endobronchial ultrasound with biopsies that were positive for a poorly differentiated squamous cell carcinoma, lung primary. The patient went on to have a PET/CT scan revealing an SUV uptake of 17.3 in the left posterior perihilar mass as well as a soft tissue density near the left bronchus. He was diagnosed as having stage IIIa non–small cell lung cancer and was thought to be surgically unresectable.

Anne H. Blaes

He was started on treatment with combined chemotherapy and radiation. He received cisplatin with etoposide between January and March 2009 with concurrent radiation. He initially received 2,960 cGy over 22 fractions of radiation to the anterior and posterior fields and an additional 2,340 cGy over 13 fractions off cord for a total of 6,300 cGy over 35 fractions to the left hilum and mediastinum.

He tolerated the combined chemotherapy and radiation well. He had some fatigue, alopecia and mild nausea, but otherwise felt well. He had a PET/CT scan performed revealing no residual mass. The lymph nodes had some mild activity with an SUV of 4.1, felt to be related to his radiation and chemotherapy. He underwent a repeat endobronchial ultrasound after completion of his therapy with a biopsy of a lymph node at station 7. The final pathology revealed some residual malignancy of a station 7 lymph node approximately 2 cm from the carina.

He received an additional two cycles of carboplatin and etoposide. The patient was referred back to his surgeon where he underwent an additional endobronchial ultrasound in early June 2009. He had a repeat sampling at station 7 lymph nodes. The lymph node was 7 mm in diameter. Five to eight samples were taken and were positive for lymphocytes with no evidence of malignant cells.

He also had a subsequent PET/CT that was also negative with the largest SUV uptake value of 2.9, again, felt to be related to his previous chemotherapy and radiation. There is no other evidence of disease. He was felt to have achieved a complete remission.

The patient has tolerated his treatment well. He complained of some mild fatigue, but otherwise felt well. He had a history of hypertension and tobacco use; neither was currently an issue.

Physical examination: BP 120 mm Hg/70 mm Hg, heart rate 65. He was in no acute distress. Head, eye, ear, nose and throat examination revealed no icterus. Oropharynx was clear. There were no ulcers or lesions. Neck was supple. There was no lymphadenopathy. Heart was regular with no murmurs, rubs or gallops. His lungs were clear bilaterally. There were no crackles or wheezes and no dullness to percussion. Abdomen was soft, nontender and nondistended with no palpable hepatosplenomegaly. There was no peripheral edema, no clubbing or cyanosis and no spinal tenderness.

At this time, the most optimal choice of treatment is the following:

A. Observation.

B. Maintenance premetrexed.

C. Surgical resection with a left pneumonectomy.

D. Maintenance erlotinib (Tarceva, OSI).

Case Discussion

In stage IIIa NSCLC, the optimal choice of treatment is surgical resection whenever possible. In this particular case, it was not feasible and as a result, concurrent chemotherapy and radiation were felt to be the most appropriate choice for this otherwise healthy individual.

In a review of the literature, the Intergroup Trial 0139 tried to answer the question whether it is necessary to do surgical resection after concurrent chemotherapy and radiation. In this trial, 429 patients with potentially resectable stage IIIa (N2) NSCLC were randomized to concurrent radiation (45 cGy) with a platinum and etoposide for two cycles followed by surgical resection followed by two cycles of a platinum and etoposide, or to concurrent radiation (61 cGy) with four cycles of platinum and etoposide. The initial five-year progression-free survival appeared to be in favor of the surgical resection arm (22% vs. 11%); however, the overall survival data did not conclude this same point.

In fact, the overall survival was not statistically significant between the two treatment arms (27% vs. 20%). In a subsequent analysis of the data, there was a 26% postoperative mortality associated with pneumonectomy and it was felt that this high mortality rate in the surgical arm may have affected the overall results; a benefit was seen among those patients who underwent a lobectomy.

In a subsequent trial, the EORTC randomized 579 patients with stage IIIa (N2) NSCLC who had received three cycles of induction chemotherapy with a platinum and had not progressed to either radiation or surgery. In this trial, the five-year overall survival in the radiation arm was 14% and in the surgical arm was 16% (HR=1.06). In this trial as well, it did not appear that surgical resection after treatment with chemotherapy and radiation added any additional benefit. Additional smaller phase-2 trials have also tried to answer this question whether surgical resection in conjunction with chemotherapy and radiation would improve the overall outcome for patients. None of the results strongly conclude that surgical resection is the best choice.

In this particular case, with involvement of a lymph node at station 7, a left pneumonectomy was recommended. Despite our patient being healthy and very active, we would not recommend surgical resection after his definitive chemotherapy and radiation. In addition, because he was treated with doses of radiation of up to 63 cGy, he already received definitive therapy. In the published trials in which patients underwent surgery with combined chemotherapy and radiation, they also were not given this amount of radiation. As a result, it is hard to counsel the patient on the risks of surgery and wound healing after 63 cGy of radiation.

Finally, although maintenance chemotherapy with premetrexed and erlotinib are being investigated in the metastatic setting, it is not currently the standard of care in the adjuvant setting. Our patient was observed.

Anne H. Blaes, MD, is a Fellow at the University of Minnesota and a member of the HemOnc Today Editorial Board.

For more information:

• Albain KS. J Clin Oncol. 2005;23:624s.
• Van Meerbeeck JP. J Natl Cancer Inst. 2007;99:442-450.