Early-onset colorectal cancer may not be biologically different from mid-onset disease

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August 18, 2021

4 minutes to read

Source / Disclosures

Disclosures: Cercek reports advisory board roles with Array BioPharma and Bayer and research funding from Rgenix, Seattle Genetics and Tesaro / GlaxoSmithKline. Please see the study for relevant financial information from all other authors. Eng and Hochster do not report any relevant financial disclosures.


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According to the results of a retrospective analysis of a single establishment published in Journal of the National Cancer Institute.

The results indicate that more aggressive treatment for early-onset colorectal cancer is neither necessary nor effective, the researchers noted.

Andrea Cercek, MD, medical oncologist, section head of colorectal cancer and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancers at Memorial Sloan Kettering Cancer Center

“This suggests that, biologically, the tumors are the same” Andrea Cercek, MD, medical oncologist, section chief of colorectal cancer and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancers at Memorial Sloan Kettering Cancer Center, told Healio. “What we still don’t know, and what research should focus on, is why there are changes in the intestinal lining that lead to the development of colorectal cancer much earlier in life.”

Cercek and his colleagues continued their work due to the increase in cases of colorectal cancer in people under the age of 50 over the past quarter century.

“It’s a global phenomenon, and the reasons for this increase are unknown,” Cercek said. “In order to determine why this is happening – and, more importantly, how we can identify those at risk and improve outcomes in those patients – we need to know if this is the same disease that we see in older people with “mid-onset” occurring decades earlier than before, or if this is a completely new disease.

The analysis included 1,446 patients under the age of 50 with a pathologic diagnosis of colorectal cancer from January 2014 to June 2019 at Memorial Sloan Kettering Cancer Center. Researchers assessed the clinical characteristics of three groups to elucidate differences in age at diagnosis: two groups included people with early-onset disease diagnosed at age 35 or younger 35; 51% women; 74.8% white) or between 36 and 49 years (n = 608; median age, 44; range, 36-49; 57.1% men; 78.1% white). The third group included people with mid-onset colorectal cancer diagnosed at age 50 or older (n = 687; median age, 61; range, 50-93; 53.9% of male; 81.7% white).

Cercek and colleagues excluded patients with mismatch-repair deficient tumors, inherited colorectal cancer syndromes, and inflammatory bowel disease from all but germline tests.

The results showed that significantly higher percentages of patients with early-onset disease had tumors on the left side (aged 35, 80.8%; 36-49 years, 83.7%; 50, 63.9%), rectal bleeding (41.1% and 41% vs. 25.9%) and abdominal pain (37.1% and 34% vs. 26.8%).

However, the researchers did not observe any difference in the histopathological characteristics of the tumors among the tumors stable to microsatellites. Although researchers initially observed differences in the TP53 and alterations in the receptor tyrosine kinase signaling pathway by age, multivariate analysis showed no statistically significant difference in gene or pathway.

By comparing the clinical outcomes of the three groups in response to treatment and survival – focusing on patients with stable microsatellite tumors who presented with metastatic disease – Cercek and colleagues found that the cohorts had a use and type similar first-line chemotherapy, site of first metastasis and frequency of metastastectomies, so these factors did not confuse survival data.

Radiographic response to first-line chemotherapy and median OS did not differ statistically between the three cohorts.

The researchers identified pathogenic variants in 23.3% of patients aged 35 and under compared to 14.1% of patients with moderate-onset disease (P = .01)

“These findings have several important clinical implications,” Cercek told Healio. “Often, young patients receive more aggressive chemotherapy because of concerns about more aggressive disease; however, we have shown that responses to chemotherapy are similar to those in patients of average onset and therefore more aggressive therapy only adds toxicity and does not alter results. This has also been supported by other studies, including the recent analysis of IDEA data in early stage disease. “

Future research should target the why, what, and how questions that result from these findings, Cercek said.

“If we accept that the disease is not ‘new’ but rather the same disease that occurred decades earlier, the research should focus on elucidating why this is happening, what potential environmental changes are to be found. the origin of the formation of these cancers and how we can identify individuals at risk, “she said.

The results also reaffirm “the importance of germ line testing in young adults”, as well as the need for a referral for genetic counseling for evaluation, with physicians from all specialties diligently reviewing the family history of their young. patients, Cathy ing, MD, FACP, FASCO, Co-Head of the Gastrointestinal Cancer Research Program, David H. Johnson Chair in Surgical and Medical Oncology, and Director of the Young Adult Cancer Initiative at the Vanderbilt-Ingram Cancer Center, and Howard S. Hochster, MD, FACP, A distinguished professor of medicine, associate director of clinical research and director of gastrointestinal oncology at the Rutgers Cancer Institute in New Jersey, and director of oncology research at RWJBarnabas Health, wrote in an editorial accompanying the study.

“It is our duty as medical providers to discuss real world topics that are often underestimated and can be difficult to discuss, such as family planning, fertility, sexual dysfunction, psychosocial issues, safety employment, mental health, overall quality of life and longevity. Wrote Eng and Hochster. “For many of us who have helped care for these young adults, we serve as a voice within the medical community. “

The references:

Cercek A, et al. J Natl Cancer Inst. 2021; doi: 10.1093 / jnci / djab124.
Eng C and Hochster H. J Natl Cancer Inst. 2021; doi: 10.1093 / jnci / djab127.

For more information:

Andrea Cercek, MARYLAND, can be contacted at the Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: [email protected]


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