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BALTIMORE -- Pediatric patients who underwent limb salvage surgery (LSS) for lower extremity sarcomas had a substantial risk of undergoing late amputation, a researcher reported.

In a retrospective analysis of data from the Childhood Cancer Survivor Study (), the cumulative incidence of late amputation at 20 years after LSS was almost one out of every five patients, according to Rosanna L. Wustrack, MD, of the University of California San Francisco.

These patients, as well as patients who underwent primary amputation instead of LSS, were also at higher risk of having poor physical and social outcomes, she said in a presentation at the hybrid Musculoskeletal Tumor Society annual meeting, held virtually and in-person

Most pediatric patients with lower extremity sarcoma can be successfully treated with LSS, yet some will eventually undergo amputation. While infection and tumor recurrence are responsible for most early failures of LSS, "the incidence and causes of late amputation more than 5 years after limb salvage surgery, as well as the resulting psychosocial and physical outcomes, are not well defined," Wustrack explained.

Wustrack and colleagues used CCSS data to evaluate the incidence and risk factors for secondary amputation after initial LSS among long-term survivors of lower extremity sarcoma, along with psychosocial and functional outcomes in patients treated with successful LSS, primary amputation, and late amputation.

CCSS is a cohort of 5-year survivors of childhood cancer who were diagnosed when under age 21 years, and treated at 31 collaborating centers between 1970-1999. The current analysis included 547 patients treated with primary amputation and 51o with primary LSS for lower extremity bone sarcoma or rhabdomyosarcoma.

Wustrack's group calculated that at a follow-up of 20 years, the cumulative incidence of late amputation was 17.9% (95% CI 14.4-21.3). They found no statistical difference in overall survival between patients who underwent LSS and those who underwent primary amputation at 88.1 % (95% CI 85.0-91.2) and 86.6% (95% CI 82.1-91.1), respectively.

On multivariable analysis they found that factors associated with late amputation were:

• Male sex: relative risk 2.06 (95% CI 1.16-3.64)
• Vinca alkaloid exposure: RR 1.95 (95% CI 1.05-3.60)
• Joint replacement: RR 2.64 (95% CI 1.47-4.72)
• Development of grade 3-4 chronic health condition: RR 1.86 (95% CI 1.04-3.33)

The cumulative incidence of late amputation was lower in patients in more recent treatment eras, while patients treated in the 1970s had an increased risk of late amputation that approached statistical significance, Wustrack reported.

Why the increased risk with treatment in the 1970s? "It seems that patients in the '70s were treated with vinca alkaloids at a much higher proportion than in other decades," Wustrack said. "The late effects of vinca alkaloids include stiffness, neurotoxicity, neuropathies, and muscle wasting, so maybe it's a combination of older techniques, but also the long-term effects of the type of therapy they received."

For physical and social outcomes based on CCSS questionnaire and SF-36 physical health survey data, Wustrack and colleagues found that survivors treated with a primary amputation (RR 2.04, 95% CI 1.15-3.64), and those with LSS complicated by late amputation (RR 3.85, 95% CI 1.66-8.92), were more likely to be unemployed or unable to attend school versus patients who had successful LSS, In addition, a primary amputation (RR 2.76, 95% CI 1.29-5.89) or late amputation (RR 4.45, 95% CI 1.44-13.7) also resulted in an increased risk of needing help with routine activities of daily living.

Patients having a primary or late amputation were also more likely to have worse physical performance scores, report impaired physical health scores, and have worse bodily pain scores. However, there was no difference between mental and social health outcomes between treatment groups, according to the researchers.

They noted that mitigating the risks demonstrated in the study "will be critical to enhance sarcoma survivorship." And while all survivors of pediatric sarcoma will require lifelong surveillance and support, Wustrack emphasized that survivors treated initially with primary amputation, and those who undergo late amputation, "represent groups at higher risk of poor outcomes, particularly in physical domains."

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