Guest LCSC Info Posted May 22, 2012 Share Posted May 22, 2012 Refining Risk of Recurrence of a Resected NSCLC: The Importance of Tumor Size May 18th, 2012 - by Dr. Jack West http://blog.lungevity.org/2012/05/18/ou ... umor-size/ In my last post, I noted that there are several factors beyond the stage of a cancer that are appropriate to include in our consideration of which patients might be well served to receive post-operative chemotherapy to reduce their risk of the cancer recurring. I’d like to now delve into this topic more thoroughly, starting with a discussion about the clearest factor we use when considering recommending chemo for someone with a node-negative non-small cell lung cancer (NSCLC): the size of the primary tumor. A consistent finding in clinical research on early stage NSCLC has been that larger tumors have a greater risk of recurrence, as shown in this figure: (Click link above to view image) In fact, one of the more significant changes in the most recent staging system highlights the importance of tumor size. In version 6 of the staging system, which was replaced in 2010, the only place tumor size plays a role is in separating stage IA from 1B, depending on whether a node-negative cancer with no metastatic spread was smaller than 3 cm or >3 cm. However, as the figure shows, the association of tumor size with risk of recurrence is more continuous and more refined than that. And in the newest (version 7) staging system, there are cutoffs at 2, 3, 5, and 7 cm, highlighting the greater granularity of the association of tumor size with survival. In consideration of post-operative chemotherapy, the cut-off that has most commonly been used has been 4 cm. This isn’t to say that different cutoffs wouldn’t be helpful, but the only way the question has been shown to be relevant thus far has been whether the tumor is less than 4 cm or > 4 cm. This analysis by tumor size for stage I NSCLC became highlighted when the results of a trial just for stage IB patients, CALGB 9633, was reported. This study, in which patients with stage IB resected NSCLC were randomized to receive 4 cycles of post-operative carboplatin/Taxol (paclitaxel) or observation following surgery, was underpowered to show a significant overall survival benefit in the entire study population. The investigators, hoping to salvage something positive out of the results to be reported looked at the results when divided by tumor size with a 4 cm cutoff. Here, they saw a survival benefit from adjuvant chemotherapy for patients with larger tumors that was not seen in patients with smaller tumors: These results were accepted by some, but many people were rightly skeptical about the value of this analysis. It was, after all, an unplanned retrospective analysis. Essentially, the investigators looked at the results many different ways, from all different angles, and presented one angle that salvaged a positive result out of a trial that was otherwise considered negative. However, one thing that bolstered this argument was that the same 4 cm cutoff was useful when applied to another trial, called BR.10, that randomized patients with resected stage IB or II NSCLC to four cycles of cisplatin/Navelbine (vinorelbine) or observation after surgery. This study was positive, demonstrating a significant survival benefit for the group treated with adjuvant chemotherapy. However, it showed that the benefit was really present only in stage II, and that when they looked at stage IN patients, they also found that the patients with tumors 4 cm or larger fared better (strong trend, not statistically significant) with chemo, while those with smaller tumors actually had a nearly statistically significantly worse outcome with chemo than with observation: What this means is that the pooled results of a group that had a strong trend toward benefit and those from a group with a strong trend toward detriment canceled each other out. However, if we were to look at the group with larger tumors, the results strongly suggest a meaningful benefit from post-operative chemotherapy. There is still some controversy about whether patients with node-negative resected NSCLC should receive post-operative chemotherapy. However, the most commonly used factor that helps experts decide, and what has been incorporated into the large clinical trials done across North America, is a 4 cm cutoff for eligibility for adjuvant chemo. And now you know why. There are some other features of the cancer that can lead us to be more concerned about risk of recurrence, and we’ll turn to those next. Quote Link to comment Share on other sites More sharing options...
Join the conversation
You can post now and register later. If you have an account, sign in now to post with your account.