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Ann Thorac Surg 1996;61:183
© 1996 The Society of Thoracic Surgeons
Department of Thoracic Surgery Beth Israel Medical Center First Ave at 16th St New York, NY 10008
In recent years MAb identification of cancer cells has been used to enhance the recognition of smaller numbers of cancer cells in thoracic lymph nodes and in bone marrow samples. The identification of these so-called micrometastases (m) appears to be an improvement to our TNM system when using standard pathologic methods.
Passlick and associates used Ber-Ep4 as a monoclonal antibody technique to supplement the pathologic study of 125 NSCLC patients, 565 thoracic lymph nodes removed, and 91 marrow samples from either rib or iliac crest. By conventional pathologic study they found 70 had N0 disease, 25 N1, and 30 N2. With MAb pathologic study, 70 N0 became 59 N0 (3 were N1, 8 were N2), 25 N1 became 21 (4 were N2), and 30 N2 thereby became 42 N2. Thus 27 of 125 were up-staged.
The MAb study of 91 marrow samples examined found 36 (39.6%) positive for metastatic cancer (m1). Passlick and associates state that with m0 finding, 18.2% had N positive tumors. In 36 m1 marrows, the incidence of N positive was 27.8%. Or, stated differently, N1 patients were 18.2% m1, whereas, N2 patients were 50% m1. The N0 patients had more distant metastases than local recurrence. The N1-2 patients had more local recurrence than distant metastases. One hundred seventeen patients had a 42-month median observation period. Lymph node involvement was the most significant variant in reduced disease-free survival, with p values ranging from 0.0001 to 0.001. Passlick and associates conclude that the MAb technique is more accurate in N staging and that these patients found by MAb (presumably having lower tumor burden) might benefit more from adjuvant therapy.
About their marrow results Passlick and associates state, ``In early-stage lung cancer lymphatic tumor cell dissemination was not correlated with systemic tumor cell dissemination as indicated by the presence of tumor cells in the bone marrow..., supporting the view that different determinants appear to exist for homing tumor cells to lymphoid tissue as compared with bone marrow tissue.''
This conclusion is debatable. My colleagues and I [1] studied 43 resected NSCLC, TNM-staged patients with MAb (AE-1, CAM 5.2) study of marrow samples from a portion of the ipsilateral sixth rib. Follow-up was for approximately 36 months. Twenty-three m0 patients were 60% free of recurrence, and 17 m1 patients were 5% free of recurrence (p = 0.0009). Fifteen stage I plus 2 stage II were by MAb study found to be 12 m0 with 90% tumor free at 28 months, compared with 5 who were m1 with 0% free of recurrence at 7 months (p = 0.0004). Our data suggest m1 is an important additional stage, and we believe further confirming study is needed.
The MAb technique finds more metastases in thoracic lymph nodes than conventional pathologic study. These metastases further subdivided the survivors and failures. Passlick and associates thought that MAb marrow micrometastases differed from lymph node metastases, but did not specifically relate this to prognosis.
More prospective studies should be done on NSCLC with accurate TNM staging using standard pathologic and the MAb techniques. Bone marrow samples should be studied, preferably from a nearby rib along with iliac marrow so that absence or presence of micrometastasis (m0 versus m1) can be added to the TNM staging system, eg, TNMm. This more complete staging system may confirm the stage I m1 cases to receive adjuvant therapy, and it may identify stage III cases where aggressive attempts should be made for ``cure.''
Reference
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