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TOPLINE:

Among patients with locally advanced rectal cancer, concurrent chemoradiotherapy did not significantly increase second pelvic malignancies compared to chemotherapy alone, but it did raise the risk for nonpelvic cancers.

METHODOLOGY:

• The risk for second cancers after pelvic radiation in patients with locally advanced rectal cancer is unclear, with recent studies yielding conflicting results.
• To better understand the risk for second malignancies, researchers evaluated 2624 patients with stage II or III rectal cancer who received chemotherapy alone (n = 460) or radiation therapy concurrent with chemotherapy (chemoradiotherapy; n = 2164) between January 1995 and October 2019.
• Researchers analyzed the cumulative incidence of second malignancies, defined as a new cancer diagnosed more than 2 years after the initial rectal cancer diagnosis.
• Patients received adjuvant chemotherapy regimens, including FOLFOX (60%), 5-fluorouracil (32%), and capecitabine and oxaliplatin (4%), with median radiation prescription doses of 5040 centigrays for conventional treatments and 5000 centigrays for intensity-modulated radiation therapy.
• The median follow-up was 6.5 years in the concurrent chemoradiotherapy cohort and 5.6 years in the chemotherapy-alone cohort.

TAKEAWAY:

• Rates of second pelvic malignancies at 10 years were higher with chemoradiotherapy vs chemotherapy, but the differences were not significant: The 10-year cumulative incidence was 5.8% with chemoradiotherapy vs 4.2% with chemotherapy (P = .30). Overall, the most common second pelvic malignancies were prostate adenocarcinoma (31%), bladder cancer (31%), and uterine cancer (28%).
• The 10-year incidence of second nonpelvic malignancies was significantly higher with chemoradiotherapy: 11% vs 4.4% with chemotherapy alone (P = .017). Overall, the most common second nonpelvic malignancies were lung cancer (24%), breast cancer (15%), and hematologic malignancies (13%).
• Compared with conventional radiation therapy, intensity-modulated radiation therapy and volumetric modulated arc therapy were associated with a reduced risk for second pelvic malignancies (P = .014).
• Several factors appeared to impact the risk for second malignancies following treatment. Adults aged 50 and older had higher risks for second pelvic (hazard ratio [HR], 3.03; P = .005) and nonpelvic (HR, 2.48; P < .001) malignancies. Diabetes was linked to an increased risk for second nonpelvic malignancies (HR, 1.51; P = .028), whereas tobacco abstinence was associated with a decreased risk (HR, 0.63; P = .013).

IN PRACTICE:

Overall, patients who received chemoradiotherapy had a significantly higher cumulative incidence of developing second cancers outside the pelvis but not within the pelvis, the authors concluded. However, “the concern for radiation-induced second malignancies should not preclude from using [chemoradiotherapy]” in this patient population. 

Instead, “these data serve as a foundation for future prospective studies evaluating ways to further reduce the risk of second malignancies in high-risk patients undergoing [chemoradiotherapy] for rectal cancer.” 

SOURCE:

The study, led by Kathryn R. Tringale, MD, and Kush H. Patel of Memorial Sloan Kettering Cancer Center, New York City, was published online in the International Journal of Radiation Oncology, Biology, Physics.

LIMITATIONS:

Potential surveillance bias existed because patients who received concurrent chemoradiotherapy had more intensive follow-up than those who received chemotherapy alone. Median follow-up was short, and the retrospective design precluded comparing doses in organs at risk that developed second cancers with those that did not.

DISCLOSURES:

The study was partly funded by a National Institutes of Health/National Cancer Institute grant. Some authors reported receiving research funding and having other ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.