Lawrence B. Marks, MD

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Association Between the Rates of Synchronous and Metachronous Metastases: Analysis of SEER Data

June 1st 2007

Patients with cancer are usually staged based on the presence of detectable regional and/or distant disease. However, staging is inexact and cM0 patients may have microscopic metastases (cM0pM1) that later cause relapse and death. Since the clinical tools used to stage patients are fairly similar for different tumors, the ratio of the rates of metachronous to synchronous metastases should be similar for different tumors (hypothesis #1). Improvements in diagnostic tools should have caused the ratio of metachronous-to-synchronous metastases to have decreased over time (hypothesis #2). Finally, the fraction of patients with either metachronous or synchronous metastases should have declined over time due to increased screening and earlier diagnoses (hypothesis #3). To test these hypotheses, Surveillance, Epidemiology, and End Results (SEER) data from 1973-1998 were analyzed for 19 solid tumors. A linear relationship was seen between the rates of metachronous and synchronous metastases, with modestly strong correlation coefficients, consistent with hypothesis #1. Over time, changes in staging methods have not significantly altered the ratio of metachronous/synchronous metastases, contrary to hypothesis #2. Also over time, a decrease in the number of patients with metastases was found, consistent with hypothesis #3. Therefore, the rate of anticipated metachronous metastases can be estimated from the rate of clinically evident metastases at presentation. Changes in screening/staging of disease over time may have reduced the overall fraction of patients with metastases.

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Stage III Lung Cancer: Two or Three Modalities?

September 1st 2006

Lung cancer is the leading cause of cancer mortality in the United States. A significant number of patients present with disease involving mediastinal lymph nodes. As survival after surgery alone for stage III disease is poor, radiation therapy and chemotherapy have been evaluated in the neoadjuvant and adjuvant settings to improve outcomes. The benefit of adjuvant chemotherapy in the subgroup of patients with N2 disease is uncertain. Small randomized trials enrolling patients with stage III disease have shown a benefit of neoadjuvant chemotherapy over surgery alone. Whether neoadjuvant chemotherapy is superior to adjuvant chemotherapy is under investigation. Furthermore, whether neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy is controversial, and few randomized studies comparing these approaches have been reported. Nevertheless, neoadjuvant chemoradiotherapy appears to be associated with higher rates of resection, higher rates of clearance of mediastinal nodal disease, and better local/regional control. The use of postoperative radiation therapy (PORT) has declined since the publication of the 1998 meta-analysis suggested a detriment in survival with this strategy. However, radiation techniques are improving and emerging data support the use of carefully delivered PORT. Finally, it remains unclear whether surgical resection offers an advantage over definitive chemoradiotherapy alone for stage III disease. In summary, locally advanced NSCLC remains a formidable challenge with few cures, and optimal treatment requires the careful use of surgery, chemotherapy, and radiation therapy.