Chemotherapy Infrequently Used in High-Risk Sarcoma, Despite Proven Benefit

The overall use of chemotherapy in high-risk soft tissue sarcomas (STS) has been found to be significantly low, according to results from a National Cancer Database (NCDB) analysis published in the Journal of the National Comprehensive Cancer Network.¹

Of 19,969 adult patients whose cancer had not yet spread to other organs, results showed that only 22% (n = 4377) received some form of chemotherapy. Of those who received chemotherapy, 85% (n = 3505) were given multiagent treatment and 47% (n = 1734) of patients were given neoadjuvant treatment. Notably, even among those with the largest and most aggressive tumors, less than half, or 45%, were treated with chemotherapy.

“Although experts have debated the benefit of chemotherapy for [patients] with localized sarcoma, several studies, including a recent randomized clinical trial, have demonstrated that chemotherapy can prolong the survival of patients with larger, more aggressive sarcomas,” according to a research brief issued by UCLA.²

Because chemotherapy targets the cancer cells that have spread from the tumor to other areas of the body, such as the lungs or liver, this approach is often the only way to prevent or reduce the risk of cancer spread. Despite the adverse effects associated with its use, such as nausea and hair loss, chemotherapy can prolong survival or even potentially cure patients with the disease. However, other studies have failed to demonstrate a clear benefit with chemotherapy in localized sarcoma; as such, there is a lack of guidance on its use in the management of those with high-risk disease.

Investigators launched the analysis in order to determine the rate of chemotherapy, multiagent chemotherapy, and neoadjuvant chemotherapy use in adult patients with primary high-grade STS, as well as to identify the factors associated with each treatment regimen at Commission on Cancer (CoC)–accredited facilities in the United States through the use of the NCDB.

A total of 19,969 patients were included in the chemotherapy analysis. Those who were included were diagnosed with 1 of the following subtypes: undifferentiated pleomorphic sarcoma (UPS), high-grade myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, leiomyosarcoma, liposarcoma, angiosarcoma, fibrosarcoma, fibromyxosarcoma, epithelioid sarcoma, and other undifferentiated or unclassified sarcomas.

The number of chemotherapy drugs used was available for 94% (n = 4109) of patients and all were included in the subgroup analysis of single-agent versus multiagent use. Data pertaining to the timing of chemotherapy were available for 85% (n = 3699) of patients, all of whom were included in the subgroup analysis of neoadjuvant versus adjuvant chemotherapy use.

The primary end point of the analysis was chemotherapy use, with a particular focus on the demographic, clinical, patient, treatment, and facility factors linked with its use. Secondary focuses included the use of multiagent versus single-agent chemotherapy and the use of neoadjuvant versus adjuvant treatment.

The majority of the patients included in the study cohort were white (80%), and had either commercial insurance (45%) or Medicare (44%). Seventy-six percent of patients were treated at low-volume facilities and 88% lived less than 100 miles from the treatment facility. The most common disease histology was UPS (30%) and the most common primary site of disease was extremity (62%). Patients in the subgroup analyses were more likely to be younger, carry commercial insurance, have received treatment at high-volume facilities, and have larger tumors compared with the primary study cohort.

Multivariate analysis revealed that factors linked with chemotherapy use included younger age, academic facility type, high-volume facility, larger tumors, greater tumor depth, positive surgical margins, and receipt of radiotherapy.

Patients with synovial sarcoma and angiosarcoma experienced the highest rates of chemotherapy at 50% and 31%, respectively, while those with fibromyxosarcoma and liposarcoma experienced the lowest rates, at 14% and 18%, respectively. The primary tumor site associated with the highest rate of chemotherapy use was the heart (56%) and the lowest was the trunk (16%).

Of those included in the multiagent versus single-agent chemotherapy analysis, 85% (n = 3505) received multiagent treatment. Factors linked with multiagent use included younger age, tumor histology, primary disease site, and treatment at a high-volume facility. Multiagent chemotherapy use was lowest among patients who had angiosarcoma, at 49%, and highest in leiomyosarcoma and synovial sarcoma, both at 90% each.

“This high rate of use noted in our study may be an expected finding,” noted the study authors. “Notably, older age (≥70 years) was associated with decreased rates of multiagent chemotherapy use, possibly due to [concerns] related to treatment morbidity, given that patients in this age group had the highest [Charlson-Deyo comorbidity condition] scores of ≥2 (7.7% vs 1.5% in patients aged 18-49 years and 4.1% in patients aged 50-69 years; P < .001).”

Of those included in the neoadjuvant versus adjuvant chemotherapy analysis, 47% (n = 1734) received neoadjuvant treatment. Patients with UPS (53%) were found to be more likely to receive neoadjuvant chemotherapy, while those with angiosarcoma (27%) were the least likely to receive neoadjuvant treatment. Patients with tumors in the extremities (57%) were the most likely to receive neoadjuvant chemotherapy; those with tumors in the heart (8%) were least likely.

“Although neoadjuvant chemotherapy provides an opportunity to evaluate treatment response and for downstaging, the availability of surgical pathology in the adjuvant setting may result in more refined patient selection,” the authors wrote. “In our cohort, neoadjuvant chemotherapy use was more frequent in patients with larger tumors, presumably for the potential downstaging impact.”

The study was not without its limitations. For one, the analysis was restricted to CoC-accredited facilities in the United States. Additionally, the NCDB only represents about 70% of annual new cancer diagnoses. When considered together, these limitations may restrict the generalizability of the findings from the analysis, noted the authors. Moreover, the NCDB does not have data available for referral patterns or patient preferences.

“The study highlights the infrequent use of chemotherapy for [patients] with sarcoma, especially at medical centers that treat fewer [patients with sarcoma; it paves the way for a future study [during] which, patients might benefit most from chemotherapy as part of their treatment for sarcoma,” according to the brief.

References

1. Graham DS, Onyshchenko M, Eckardt MA, et al. Low rates of chemotherapy use for primary, high-grade soft tissue sarcoma: a National Cancer Database analysis. J Natl Compr Canc Netw. 2020;18(8):1055-1065. doi:10.6004/jnccn.2020.7553
2. Chemotherapy is used to treat less than 25% of people with localized sarcoma. News release. UCLA. August 6, 2020. Accessed August 30, 2020. https://bit.ly/2EIUGzn.