Long-Term Clinical Responses of Neoadjuvant Dendritic Cell Infusions and Radiation in Soft Tissue Sarcoma

Shailaja Raj, Marilyn M Bui, Gregory Springett, Anthony Conley, Sergio Lavilla-Alonso, Xiuhua Zhao, Dungsa Chen, Randy Haysek, Ricardo Gonzalez, G Douglas Letson, Steven Eric Finkelstein, Alberto A Chiappori, Dmitry I Gabrilovitch, Scott J Antonia, Shailaja Raj, Marilyn M Bui, Gregory Springett, Anthony Conley, Sergio Lavilla-Alonso, Xiuhua Zhao, Dungsa Chen, Randy Haysek, Ricardo Gonzalez, G Douglas Letson, Steven Eric Finkelstein, Alberto A Chiappori, Dmitry I Gabrilovitch, Scott J Antonia

Abstract

Purpose. Patients with large >5 cm, high-grade resectable soft tissue sarcomas (STS) have the highest risk of distant metastases. Previously we have shown that dendritic cell (DC) based vaccines show consistent immune responses. Methods. This was a Phase I single institution study of neoadjuvant radiation with DC injections on 18 newly diagnosed high-risk STS patients. Neoadjuvant treatment consisted of 50 Gy of external beam radiation (EBRT), given in 25 fractions delivered five days/week, combined with four intratumoral injections of DCs followed by complete resection. The primary endpoint was to establish the immunological response to neoadjuvant therapy and obtain data on its clinical safety and outcomes. Results. There were no unexpected toxicities or serious adverse events. Twelve out of 18 (67%) patients were alive, of which an encouraging 11/18 (61%) were alive with no systemic recurrence over a period of 2-8 years. Favorable immunological responses correlated with clinical responses in some cases. Conclusions. This study provides clinical support to using dendritic cell injections along with radiation in sarcomas, which when used optimally in combination can help clinical outcomes in soft tissue sarcoma. Study registration number is NCT00365872.

Figures

Figure 1
Figure 1
(a) Kaplan Meir curves showing the disease-free survival at 1, 2, 3, and 4 years (94%, 83%, 72%, and 66%, resp.) of patients who received neoadjuvant intratumoral injection of dendritic cells and radiation in high-grade soft tissue sarcomas over 5 cm. (b) Kaplan Meir curve showing overall survival of patients in months on patients who received neoadjuvant intratumoral injection of dendritic cells and radiation in high-grade soft tissue sarcomas over 5 cm. (c) Kaplan Meir curves showing tumor necrosis less than 70% or ≥70% in patients who received intratumoral dendritic cell injections followed by radiation and then surgery with resection of tumors to determine the percentage of necrosis after surgery p = 0.76.
Figure 2
Figure 2
The eighteen patients who received neoadjuvant radiation and DC vaccine were divided into two groups based on their immune response (positive and negative) and then correlated with the overall survival in days and progression free survival.
Figure 3
Figure 3
Pre- and postsurgery CAT scan of a 46-year-old lady with history of dedifferentiated liposarcoma patient who completed the DC vaccine + RT treatment, underwent surgical resection, and approximately 10 months later presented with (a and b) pre- and post-CT scans showing the presence of the lung nodules (two) and then postsurgical imaging study after its resection. (c) Pathological analysis showed tissue necrosis, hyalinization, and infiltration of lymphocytes and is currently free of systemic or local recurrence over 8 years.

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