Excellent study demonstrating the value of evaluation of ctDNA/molecular disease and impact of adjuvant chemotherapy. Guidelines will change rather significantly (for different cancers) in this decade, as to who actually needs post-operative chemotherapy. More prolonged follow-up is warranted.
The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.
We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use.
Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, −4.1 to 6.2 [noninferiority margin, −8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.
A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583. opens in new tab.)
Epi and nivo for mismatch repair-deficient (dMMR) colon cancer had 98% response rate with 68% complete response, non-recurred with a median of follow up of 26 months. Does this mean bye-bye surgery??? Probably. We will need to assess those who have complete response and have a close follow up. CtDNA may play big role here, along with a need for randomized trials.
COLOXIS is an interesting computer-based learning model that seems to be able to predict which patients are likely to benefit from adjuvant chemotherapy in colorectal cancer. This, along with ctDNA tests, may change whom we choose to offer adjuvant chemotherapy.
Negative study for the use of HIPEC in the adjuvant setting of high-risk or locally advanced colorectal cancers, including those with perforation and peritoneal invasion. HIPEC doesn’t seem to reduce the risk of peritoneal recurrence after potentially curative resection.
Stopping oxaliplatinum and cont. of 5FU is better than stopping all chemotherapy. An option for patients with worsening neuropathy or other oxaliplatinum toxicity.
Get your patients moving, even in the adjuvant setting! Of course, a lot of bias is possible here, but there was nearly a 10% difference in cure at three years.
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