DNA entering the bloodstream from colon cancer successfully guides chemotherapy after surgery: Helps clarify the benefit of chemotherapy in stage II cancers

A new research study found that circulating tumor DNA (ctDNA) — genetic material that enters the bloodstream from tumors — can identify patients with stage II colon cancer who will benefit most from chemotherapy after surgery and other patients needing this form can save on treatment.

The multi-institutional, international study, led by researchers from the Johns Hopkins Kimmel Cancer Center and WEHI in Melbourne, Australia, found that testing for ctDNA after surgery and directing chemotherapy on ctDNA-positive patients reduced the use of chemotherapy in the generally decreased without compromising recurrence. survive freely.

There are several previous studies showing that circulating tumor DNA can be detected in blood and that the presence of ctDNA after surgery predicts a risk of cancer coming back. However, this is believed to be the first clinical trial to demonstrate that measurement of circulating tumor DNA prior to therapy may benefit patients.

These findings are published in the New England Journal of Medicine and presented at the annual meeting of the American Society of Clinical Oncology on June 4.

“Previous studies have theorized that ctDNA measurements may be helpful in guiding patient management, and this study provides real-world clinical evidence supporting these theories,” said Bert Vogelstein, MD, Clayton Professor of Oncology, co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator. Vogelstein and his group were the first to show that colon cancer is caused by a sequence of genetic mutations and showed that DNA secreted by tumors can be detected in blood, stool and other body fluids.

Currently, the use of chemotherapy in stage II colon cancer, which is defined as a colon cancer that has grown through the wall of the colon but does not extend to the lymph nodes or other organs, is controversial. There is no consensus among cancer experts about its benefit. This study aimed to help resolve the controversy by assessing whether ctDNA could be used to more accurately predict recurrence risk after surgery. Patients who were ctDNA negative could be spared the toxicity of chemotherapy, and those who still had cancer could receive chemotherapy to attack the lingering malignant cells.

In the study, 455 patients with stage II colon cancer were randomized 2:1 to standard or ctDNA-guided treatment after surgery. Of these patients, 153 received standard treatments, including time monitoring for recurrence or chemotherapy. Another 302 patients had blood tests to look for ctDNA within seven weeks of surgery. If ctDNA was detected, patients received fluoropyrimidine or oxaliplatin-based chemotherapy. If ctDNA was not detected, patients did not receive chemotherapy.

The ctDNA-guided approach reduced the use of chemotherapy compared to the standard treatment group (15.3% of patients in the ctDNA-guided group received chemotherapy versus 27.9% in the standard treatment group). The two- and three-year survival without cancer recurrence was comparable between the ctDNA-guided group and the standard management group.

“Stage II colorectal cancer presents a unique challenge,” explains Anne Marie Lennon, MBBCh., Ph.D., professor of medicine and director of the division of gastroenterology and hepatology. “In stage I colon cancer, patients do not receive chemotherapy because their survival prognosis is over 90%. The risk of discomfort and toxicities from the therapy outweigh the benefits it may provide. On the other hand, every patient with stage III colon cancer is currently on chemotherapy because the risk of relapse is high.”

The goal of chemotherapy for colon cancer is to eradicate micrometastases, cancer cells not yet visible on radiographic images that travel through the bloodstream and cause the cancer to come back or spread to other parts of the body. Using ctDNA to detect these invisible cells can now identify which patients are most likely to have micrometastases and are therefore likely to benefit most from chemotherapy.

“By using ctDNA to guide treatment, a patient with stage II colon cancer who is negative for ctDNA has a lower chance of cancer recurrence than the average patient with stage I colon cancer, so we have the opportunity to improve clinical practice.” change,” said Joshua Cohen, a lead author of the study and MD/Ph.D. candidate at Johns Hopkins University School of Medicine.

The researchers hope these findings will stimulate the study of ctDNA in patients with other stages of colon cancer and other cancers. In future studies, the researchers will examine patients with early-stage pancreatic cancer and stage III colon cancer to see if ctDNA can similarly identify patients most likely to benefit from more aggressive chemotherapy than is currently used. They also plan to explore whether the presence of residual ctDNA can be used to optimize the treatment of individual patients after surgery or other forms of therapy.

Using ctDNA to stratify treatments in patients is part of the movement toward precision medicine – individualized care that tailors therapies to the unique characteristics of cancer.

The researchers also believe the findings will provide opportunities to test promising new drugs in patients with earlier stages of cancer.

“All drugs work better in patients with cancers that are detected relatively early, before they have given rise to large metastatic masses. However, new drugs are usually tested first in patients whose cancers are advanced,” says Vogelstein. “We hope that ctDNA analysis will enable testing of new drugs in patients with early-stage cancer and micrometastases, when the new drugs are likely to save lives.”

In addition to Vogelstein, Cohen, Lennon, other researchers included Kamel Lahouel, Ph.D., Yuxuan Wang, MD, Ph.D., Janine Ptak, MS, Natalie Silliman, BS, Lisa Dobbyn, BA, Maria Popoli, MS, Ralph Hruban, MD, Nicholas Papadopoulos, Ph.D., Kenneth Kinzler, Ph.D., and Cristian Tomasetti of Johns Hopkins, and Jeanne Tie, MD, Serigne Lo, Ph.D., Suzanne Kosmider, MBBS, Jeremy Shapiro, MBBS, Margaret Lee, MBBS, Sam Harris, MBBS, Adnan Khattak, MBBS, Matthew Burge, MBBS Marion Harris, MBBS, James Lynam, MBBS, Louise Nott, MBBS, Fiona Day, Ph.D., Theresa Hayes, MBBS, Sue -Anne McLachlan , MBBS, Belinda Lee, MBBS, and Peter Gibbs, MD, of the Walter and Eliza Hall Institute of Medical Research, Peter MacCallum Cancer Center of University of Melbourne in Melbourne, Australia.

This research was supported by the Australian National Health and Medical Research Council, the Marcus Foundation, the Virginia and DK Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, National Institutes of Health (CA62924, CA009071, GM136577, CA06973) and the Eastern Health Research Foundation Linda Williams Memorial Grant.

Bert Vogelstein, Kenneth Kinzler and Nickolas Papadopoulos are founders and shareholder of Thrive Earlier Detection, an Exact Sciences Company. Kenneth Kinzler and Nickolas Papadopoulos are advisors to Thrive Earlier Detection, an Exact Sciences Company. Bert Vogelstein, Kenneth Kinzler, Nickolas Papadopoulos and Joshua Cohen are advisors to and own shares in Haystack Oncology. Nickolas Papadopoulos and Kenneth Kinzler serve on the board of directors of Haystack Oncology. The companies listed above have licensed previously described technologies related to the work described in this article from The Johns Hopkins University. Bert Vogelstein, Kenneth Kinzler, Nickolas Papadopoulos and Joshua Cohen are inventors of some of these technologies. Licenses for these technologies have been or will be associated with royalty payments to the inventors and to Johns Hopkins University.

#DNA #entering #bloodstream #colon #cancer #successfully #guides #chemotherapy #surgery #Helps #clarify #benefit #chemotherapy #stage #cancers

Leave a Comment

Your email address will not be published.