Image-Guided Superficial Radiation Therapy for Basal and Squamous Cell Carcinomas Produces Excellent Freedom from Recurrence Independent of Risk Factors.

Background/Objectives: Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are non-melanoma skin cancers (NMSCs) and the most prevalent cancers in the United States. Image-guided superficial radiotherapy (IGSRT) is a relatively new treatment option that uses high-resolution dermal ultrasound integrated with superficial radiotherapy to improve tumor visualization. IGSRT is a clinically equivalent non-surgical alternative to Mohs micrographic surgery at 2 years of follow-up in early-stage NMSC, but larger cohort studies with longer follow-up periods that allow for analysis of patient outcomes by demographic and disease characteristics are needed. Methods: This large, retrospective cohort study was conducted to determine the effect of risk factors (tumor location, tumor stage, and sex) on 2-, 4-, and 6-year freedom from recurrence rates in 19,988 NMSC lesions treated with IGSRT, including lesions with complete treatment courses. Results: Overall freedom from recurrence rates were 99.68% at 2 years, 99.54% at 4 years, and 99.54% at 6 years; rates did not differ significantly by tumor location (head/neck versus other locations, p = 0.9) or sex (male versus female, p = 0.4). In contrast, there was a significant difference in freedom from recurrence rates when analyzed by tumor stage (p = 0.004). Conclusions: There was no significant effect of tumor location or sex on freedom from recurrence in IGSRT-treated NMSC. Although there was a significant difference according to tumor stage, freedom from recurrence rates exceeded 99% at all stages.

The confluence of stereotactic ablative radiotherapy and tumor immunology.

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses.

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

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.

Cellular immunotherapy for soft tissue sarcomas.

Soft tissue sarcomas are rare neoplasms, with approximately 9000 new cases in the USA every year. Unfortunately, during the past two decades, there has been little progress in the treatment of metastatic soft tissue sarcomas beyond the standard approaches of surgery, chemotherapy and radiation. Immunotherapy is a modality complementary to conventional therapy. It is appealing because functional antitumor activity could affect both local-regional and systemic disease, and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies that are being developed, including several tumor vaccine, antigen vaccine and dendritic cell vaccine strategies.

Serial assessment of lymphocytes and apoptosis in the prostate during coordinated intraprostatic dendritic cell injection and radiotherapy.

Local radiotherapy plus intratumoral syngeneic dendritic cell injection can mediate apoptosis/cell death and immunological tumor eradication in murine models. A novel method of coordinated intraprostatic, autologous dendritic cell injection together with radiation therapy was prospectively evaluated in five HLA-A2(+) subjects with high-risk, localized prostate cancer, using androgen suppression, 45 Gy external beam radiation therapy in 25 fractions over 5 weeks, dendritic cell injections after fractions 5, 15 and 25 and then interstitial radioactive seed placement. Serial prostate biopsies before and during treatment showed increased apoptotic cells and parenchymal distribution of CD8(+) cells. CD8(+) T-cell responses to test peptides were assessed using an enzyme-linked immunosorbent spot IFN-γ production assay, demonstrating some prostate cancer-specific protein-derived peptides associated with increased titer. In conclusion, the technique was feasible and well-tolerated and specific immune responses were observable. Future trials could further test the utility of this approach and improve on temporal coordination of intratumoral dendritic cell introduction with particular timelines of therapy-induced apoptosis.