Catherine Spina

• Columbia University

Background: Spatial integration of metabolic pathways with single cell-level transcriptomic data in human tumor and normal tissue may elucidate mechanisms supporting tumorigenesis for therapeutic targeting. The suppressive adenosine signaling pathway is an emerging potential target for combination with radiotherapy. This study aims to create an in...

Introduction: Radiation therapy (RT) induces adenosine signaling by releasing ATP in the tumor microenvironment (TME), promoting immune suppression and tumor progression. This study investigates how RT impacts adenosine signaling and immune cell infiltration in a preclinical model of non-small cell lung cancer (NSCLC). Using immunophenotyping of tu...

Men with high-risk localized prostate cancer exhibit high rates of post-surgical recurrence. In these patients, androgen deprivation therapy (ADT) is immunomodulatory, however increased infiltration of regulatory T cells (Tregs) may limit the antitumor immune effects of ADT. We designed a neoadjuvant clinical trial to test whether BMS-986218, a nex...

Background: Men with high-risk localized prostate cancer are at significant risk for disease recurrence and there is currently no role for neoadjuvant therapy. Although androgen deprivation therapy (ADT) is immunomodulatory and can increase CD8 T cell infiltration, these effects are counterbalanced by the expansion of suppressive regulatory T cells...

Background: More than half of all cancer patients undergo radiation therapy (RT) with curative or palliative intent. With the widespread use of immunotherapy to treat cancer, immune effects of radiation are an important consideration in design of sequential and combination therapies. While radiation has been found to deplete lymphocytes, less is kn...

TPS240 Background: Oligometastatic hormone-sensitive prostate cancer (omHSPC) represents a distinct disease state that can benefit from local therapy. For patients (pts) with metachronous omHSPC, metastasis-directed therapy (MTD) demonstrates benefit in prospective studies. In the randomized phase 2 STOMP trial of MDT versus observation, MDT improv...

Purpose The emerging online adaptive radiation therapy (OART) treatment strategy based on cone beam computed tomography allows for real-time replanning according to a patient's current anatomy. However, implementing this procedure requires a new approach across the patient's care path and monitoring of the “black box” adaptation process. This study...

Purpose To maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially among those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failu...

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinc...

Background: In response to cellular death and hypoxia, ATP is passively released into the extracellular space. ATP undergoes rapid stepwise conversion to the potent, immune-suppressive adenosine by ectoenzymes CD39 and CD73. Engagement of adenosine with the A2A and A2B receptors (A2AR, A2BR) promote the suppressive effects of adenosine. Early-phase...

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To better capture the dynamic and compartmentalized nature of antitumor immune responses, we generated longitudinal “temporal atlases” of productive versus non-productive antitumor immune responses in murine tumor models....

Background: The relationship between radiation therapy, immunosuppressive myeloid populations and adenosine is not well characterized. Here we test the hypothesis that radiation-induced adenosine signaling promotes tumor growth and causes suppression of T cell function and that therapeutic targeting may improve response to radiotherapy. Methods: Or...

187 Background: Intraprostatic radiation dose escalation is an area of clinical interest. Dose escalation within the prostate must be balanced with maintaining acceptable dose to the organs at risk, OAR (bladder, rectum, and urethra). Treatment planning therefore requires simultaneous consideration of multiple competing plan optimization goals, for...

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinc...

TPS5115 Background: Roughly 20%-30% of prostate cancer patients experience biochemical recurrence (BCR), rising prostate-specific antigen (PSA) levels, after definitive therapy with radical prostatectomy (RP) or radiation therapy (RT). The optimal therapy and timing of treatment for BCR is unknown, however, for patients who are not eligible for sal...

Purpose/Objective(s) Tumor irradiation causes pro-inflammatory changes in the tumor microenvironment (TME). We have shown that these changes may be countered by the induction of immunosuppressive changes that drive therapy resistance. Here, we test the hypothesis that radiation activates adenosine signaling and induces immunosuppressive myeloid cel...

Radiation is a known immune modulator that drives both local and systemic immunologic effects. There is increasing interest and investigation into harnessing the pro-immunogenic effects of radiation for patients with metastatic cancer to improve systemic disease control and clinical outcomes. Here, we review fundamental immunology concepts in the c...

2588 Background: Immune checkpoint inhibitors (ICIs) are potent new cancer therapies but can cause serious immune-related adverse events. Radiation therapy (RT) also induces systemic immunologic effects, and data on the interaction and safety of combining ICIs and RT are limited. Methods: In this retrospective cohort study using a large medical cla...

Introduction/Purpose: Radiation therapy drives pro-inflammatory changes to the tumor microenvironment (TME). We have shown that this may be countered by the induction of immunosuppressive changes that drive therapy resistance. Here, we test the hypothesis that radiation therapy induces immunosuppressive myeloid cells in the TME in an adenosine-depe...

Objective We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy. Methods Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer plac...

Background Immune checkpoint inhibitors (ICIs) are important new therapeutic options for the treatment of malignancy. Existing data on the relative safety of ICI treatment in patients with pre-existing autoimmune disease (AID) are limited. Methods In this retrospective study utilizing an oncology medical claims database, we determined the rates of...

Purpose: Intratumoral immunosuppression mediated by myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) represents a potential mechanism of immune checkpoint inhibitor (ICI) resistance in solid tumors. By promoting TAM and MDSC infiltration, Interleukin-1 beta (IL-1b) may drive adaptive and innate immune resistance in re...

Purpose Radiation therapy (RT) modulates the immune characteristics of the tumor microenvironment (TME). It is not known whether these effects are dependent on the type of RT used. Methods and Materials We evaluated the immunomodulatory effects of carbon-ion therapy (CiRT) compared with biologically equivalent doses of photon therapy (PhRT) on sol...

Objective Sarcopenia has been shown to correlate with poor oncologic outcomes, but the optimal method to evaluate sarcopenia and its use as a prognostic tool in glioblastoma multiforme (GBM) remain unclear. We developed a method to reproducibly quantify sarcopenia using the temporalis muscle and correlated sarcopenia with overall survival (OS) in G...

Background: Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our inst...

e14140 Background: Immune checkpoint inhibitors (ICIs) are known to cause immune-related adverse events. Patients with autoimmune diseases (AID) were excluded from most ICI clinical trials due to the potentially high risk of adverse effects. Data on the safety of ICIs in patients with a diagnosis of AID is therefore limited. Methods: A retrospectiv...

Intratumoral injection of a hydrogel impregnated with radioisotope-labelled catalase and an immunostimulant, along with systemic immune checkpoint blockade, inhibits tumour growth in mouse models of localized cancer and metastatic cancer.

Androgen deprivation therapy (ADT), combined with definitive radiation therapy, is the standard of care for locally advanced prostate cancer. Here, we describe the clinical development of ADT for prostate cancer, from the initial report of surgical castration for palliation of metastatic prostate cancer through the accumulated evidence derived from...

Purpose: To implement Velocity-based image fusion and adaptive deformable registration to enable treatment planning for preclinical murine models of fractionated stereotactic radiosurgery (fSRS) using the small animal radiation research platform (SARRP). Methods and materials: C57BL6 mice underwent 3 unique cone beam computed tomography (CBCT) s...