Texas Oncology

Stereotactic radiosurgery (SRS) is used for arteriovenous malformations (AVM), but the risk for secondary malignancy (SM), radiation necrosis (RN), obliteration rates (ObR), and late neurologic toxicities in pediatric patients is not well defined. To address this, we reviewed our two-decade-long institutional experience treating pediatric AVMs with SRS. Retrospective review of patients receiving single-fraction SRS for AVM between 1/2006 and 12/2023. ObR and RN were determined on neuroimaging, and toxicities by clinical evaluation. Overall follow-up was 56months (range 6-193); 59 patients had follow-up > 36months (median 85months). Eighty-nine patients/101 AVMs were treated at average age of 12.9years (range 2.36-20.1). Median follow-up was 56months (range 6-193); 59 patients (66.3%) had > 36months of follow-up (median 85months). Average AVM volume was 2.85 cm3 (range 0.034-24.95 cm3), and 80.4% were < 3cm. Eloquent areas were involved in 65.3%; 56.4% had deep venous drainage. Most had Spetzler-Martin (SM) grade 2 or 3 (39.6 and 36.6); SM grade 1 (12.9%), 4 (8.9%), and unknown (2.0%) were also treated. Most had pre-SRS hemorrhage (70.8%), neurologic deficit (37.1%), or seizure (21.3%); few were incidental (12.4%). Before SRS, 13.5% were embolized, 7.9% resected, and 6.7% both; most (71.9%) had no intervention. Radiographic obliteration by imaging was 55.0% at 3years, 73.1% at 4years, and 83.0% at 5years. In patients with long-term follow-up, ObR after SRS alone was 90.6%. Eight AVMs (7.9%) failed to obliterate by 3years and were retreated: five with SRS, two with embolization, and one with resection. Obliteration was achieved in 7/8 (87.5%) of these residual AVMs; overall ObR was 97.6%. No patients developed SM, hemorrhage, or died post-SRS, but 13% had residual seizures, 14.6% had persistent headaches, and 39% had neurologic deficits. Seven (8.5%) developed symptomatic RN. Single-fraction SRS for AVMs is effective, with a high obliteration rate and low radionecrosis rates. No secondary malignancies, hemorrhages, or deaths occurred.

Abstract Background: Latin American (LA) women are more likely to be diagnosed with aggressive early-stage breast cancer (EBC) compared to Non-Hispanic White (NHW) women, yet population-specific tumor biology remains underexplored. Previously, we reported elevated immune gene expression in BluePrint® (BP) Luminal B tumors in LA patients (pts) with EBC and obesity compared to Black and NHW cohorts. Here, we present updated clinical comparisons between LA, NHW and Black pts with EBC and whole transcriptome analysis (WTA) between BP Luminal B and Basal BC in pts with obesity. Methods: Clinical and WT data were analyzed from 15,577 EBC pts self-identified as LA, Black, or NHW enrolled in FLEX (NCT03053193), a prospective observational study with MammaPrint® risk of recurrence and BP molecular subtyping assays, and WT profiles. ImPrint, 53-gene immune signature, results (+/-) were generated for pts with hormone receptor positive (HR+) EBC. Chi-square and t-tests were conducted on clinical groups using arsenal R package. For WT comparisons, 215 obese LA pts with BP Luminal B and 77 with BP Basal EBC were matched to corresponding NHW and Black pts by age, T and N status. Differentially expressed genes (DEGs) were evaluated using limma, and pathway enrichment was performed using gene set enrichment analysis with Hallmark gene sets. Significant results were reported with adjusted p &amp;lt; 0.05. Results: Compared to Black and NHW pts, LA pts were younger and more often premenopausal (Table). Both LA and Black pts had statistically significantly higher rates of obesity compared to NHW pts. Significantly higher rates of MP High Risk 2, BP Basal and ImPrint+ tumors were observed in LA and Black pts vs NHW. WT comparisons among the obese subpopulations revealed that metabolic pathways, including adipogenesis, angiogenesis, epithelial-mesenchymal transition, and oxidative phosphorylation were significantly downregulated in EBC in LA pts vs NHW and Black cohorts. Conversely, immune-related pathways such as allograft rejection and interferon gamma response were enriched among LA pts with Basal cancers compared to NHW and Black groups. These coordinated pathway alterations suggest unique metabolic and immune profiles in LA EBC subtypes with a median absolute fold change of 1.3 among DEGs. Conclusion: The data suggest that signals from metabolic pathway alterations from modest immune-related gene upregulation may contribute to more aggressive tumor behavior in obese LA pts with EBC. Clinical and transcriptomic analyses demonstrated differences in Luminal B and Basal EBC biology among self-identified LA pts compared to NHW and Black cohorts, consistent with prior research. With further research, these findings may offer treatment targets which may enhance outcomes and reflect the importance of including racially and ethnically diverse pts in clinical trials to characterize population-specific differences in EBC outcomes. Citation Format: M. Mazo Canola, A. Santillan, J. Alberty-Oller, E. Dias, V. Kaklamani, A. Elkhanany, K. Hoskins, M. Habibi, R. Hampton, J. L. Barone, N. M. Johnson, N. Gordon, N. Sookhan, T. Bah, P. John, E. Aponte, S. Diab, V. Klimberg, N. Stivers, C. Page, S. Uygun, W. Audeh, J. O'Shaughnessy. Distinct Immune and Metabolic profiles in Latin American breast cancer patients with obesity enrolled in FLEX [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-09.

Abstract Background: Brain metastases (BrM) are a frequent and clinically challenging manifestation of HER2-positive (HER2+) metastatic breast cancer (mBC), affecting up to 50% of patients (pts) over the course of their disease. Current guidelines recommend trastuzumab deruxtecan (T-DXd) as the preferred second-line therapy for HER2+ mBC overall, while the combination of tucatinib, trastuzumab, and capecitabine (TTC) remains an important option for pts with active or progressing BrM disease due to its proven intracranial activity. However, there is a lack of real-world data comparing treatment outcomes with these regimens specifically among pts with BrM involvement. This study evaluates real-world time to next treatment (TTNT) in pts with prior HER2+ therapy and documented BrM treated with second-line T-DXd vs TTC. Methods: We used the IntegraConnect PrecisionQ de-identified electronic health record database, which includes data on over 3 million cancer pts across more than 500 care sites, to identify individuals with HER2+ mBC who received either T-DXd or TTC as second-line therapy on or after January 1, 2020. Eligible pts had documented BrM prior to initiating second-line treatment. HER2+ status was inferred based on receipt of at least one HER2-targeted therapy during first-line metastatic treatment. Individuals who received T-DXd in their first-line of metastatic therapy were excluded from the analysis. The index date was defined as the start of second-line therapy with either TTC or T-DXd. Descriptive statistics were used to summarize demographic and clinical characteristics by treatment group, including age at index date, race, ethnicity, health insurance, BMI, ECOG performance status, estrogen receptor status, first-line metastatic regimen (grouped as ado-trastuzumab emtansine, trastuzumab (H) +pertuzumab (P) + taxane, endocrine therapy +/- HP, or other regimens), and presence of liver, bone, or lung metastases. TTNT was analyzed using Kaplan-Meier survival curves, with median estimates reported. Multivariable Cox proportional hazards regression was used to evaluate the association between treatment and TTNT, adjusting for the aforementioned demographic and clinical covariates. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are presented. Results: A total of 255 pts met study eligibility, of whom 138 (54%) received T-DXd as second-line therapy. Pts treated with T-DXd were slightly older than those who received TTC (median age: 58 vs 55 years; Wilcoxon p=0.026). A lower proportion of pts in the T-DXd group were classified as overweight (BMI 25-30) compared to the TTC group (17% vs 29%; chi-square p=0.026). No other significant differences in demographic or clinical characteristics were observed between treatment groups. Median TTNT was significantly longer among pts who received T-DXd compared to TTC (17 vs 11 months; log-rank p=0.006). This difference remained significant after adjustment for demographic and clinical covariates, with T-DXd associated with a 48% reduced likelihood of requiring subsequent therapy (HR: 0.52; 95% CI: 0.37-0.74; p&amp;lt;0.001). Conclusions: In this real-world analysis of pts with prior HER2+ therapy and documented BrM, second-line treatment with T-DXd was associated with significantly longer TTNT compared to TTC among pts with BrM. These findings may help inform treatment decisions in this high-risk population. However, interpretation is limited by the retrospective design, potential selection bias, and the use of treatment patterns to infer HER2 status. Most importantly, granular clinical data on BrM, including prior local therapies (radiation and/or surgery) and CNS-specific outcomes, were unavailable. Further prospective studies are needed to validate these findings. Citation Format: V. Gorantla, R. Choksi, F. Kudrik, D. Patt, S. Reddy, S. Reganti, S. Rosenfeld, G. Cioffi, T. Sura, D. Parris, A. Rui, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, R. Mahtani. Real-world time to next treatment in HER2+ breast cancer patients with brain metastases: trastuzumab deruxtecan vs tucatinib based therapy as second-line treatment [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-12.

Abstract Background: According to recent findings from the DESTINY-06 trial, HR-positive (HR+)/HER2-low metastatic breast cancer (mBC) patients (pts) who received trastuzumab deruxtecan (T-Dxd) following ≥1 line of endocrine therapy (ET) experienced improved progression-free survival (PFS) compared to those who received chemotherapy (chemo) in a second-line (2L) setting. To assess whether similar benefits are seen in a real-world setting, we evaluated overall survival (OS) and time to next treatment (TTNT). TTNT was used as a surrogate measure for PFS. Methods: We used the IntegraConnect PrecisionQ de-identified electronic health record database of &amp;gt;3 million cancer pts across &amp;gt;500 care sites, to identify pts. Eligible pts for the study were adults with a confirmed diagnosis of HR+/HER2-low mBC who had ≥2 documented visits and a CDK4/6 inhibitor(i) +/- ET in the first-line metastatic setting. Pts with a subsequent treatment (2L) with T-Dxd or chemo were identified and observed between 6-1-2022 and 4-30-2025. TTNT was defined as time from the 2L start to either the initiation of a subsequent line of therapy or death. We did not assess for the reason pts discontinued (e.g., toxicity or disease progression). TTNT and OS were analyzed using Kaplan-Meier analysis. Hazard ratios (HR) adjusting for age at treatment and race were estimated using Cox proportional hazard models. Results: Among 340 eligible pts, 82 received TDxd and 248 received chemo in the 2L setting. The median age at treatment was 64 (interquartile range 55, 70) years old with a composition of 70.0% White, 10.6% African American. Among pts with a reported Eastern Cooperative Oncology Group (ECOG) status at treatment, 91.5% had an ECOG score of ≤1. Median OS was not significantly different for pts who received T-Dxd compared to chemo (Table), but median TTNT was significantly longer for pts who received T-Dxd (10.1 months, 95% CI: 7.8, 13.1) compared to chemo (6.0 months, 95% CI: 5.1, 6.5). Pts using T-Dxd were significantly less likely to change treatment compared to chemo after adjusting for age, and race [HR (95% CI): 0.45 (0.30, 0.66), P&amp;lt;0.01)]. Treatment crossover occurred in both cohorts: 28% of pts in the chemo group utilized T-Dxd in a later line of therapy, and 19% of pts in the T-Dxd group utilized chemo in a later line of therapy. Conclusions: Consistent with findings from a subset of the Destiny-06 trial, HR+/HER2-low mBC pts previously treated with a CDK4/6i who then utilized T-Dxd in the 2L setting were associated with a significantly improved TTNT compared to 2L chemo utilization. OS was not statistically different between T-Dxd and Chemo. These results may be impacted by unmeasured factors such as, tumor burden, endocrine resistance, and access to care. Further studies are needed to confirm the optimal sequencing of TDxd in the real-world setting. Citation Format: R. Mahtani, R. Choksi, F. Kudrik, D. Patt, S. Reddy, S. Reganti, S. Rosenfeld, S. W. Champaloux, D. Parris, A. Rui, A. Sharma, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, V. Gorantla. Real-world comparison of time to next treatment for patients with HR-positive, HER2-low metastatic breast cancer treated with either chemotherapy or trastuzumab deruxtecan in the second-line [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-17.

BackgroundModakafusp alfa is a novel immunocytokine comprising two attenuated interferon-α2b molecules fused to an anti-CD38 IgG4 monoclonal antibody. Modakafusp alfa has shown immune cell activation and antitumor activity in preclinical mouse models, including in combination with an anti-programmed cell death (PD-1) receptor in tumors that do not express CD38, and demonstrated clinical responses and immune activation in patients with relapsed/refractory multiple myeloma.MethodsIn phase Ib, adult patients with advanced/metastatic solid tumors received escalating doses of modakafusp alfa 0.1–1.5 mg/kg intravenously every 3 weeks (Q3W) across six dosing cohorts. In phase II, patients with unresectable/metastatic cutaneous melanoma and resistance to ≤2 anti-PD-1 therapies in the metastatic setting received modakafusp alfa 1 mg/kg Q3W in combination with pembrolizumab Q6W. Primary objectives were to determine the safety/tolerability as a single agent in phase I, and efficacy in combination with pembrolizumab in phase II.ResultsA total of 21 and 24 patients were enrolled across phases Ib and II, respectively. The recommended phase II dose of modakafusp alfa was 1 mg/kg. The most common drug-related adverse events were infusion-related reactions (IRRs; 52.4%) and thrombocytopenia (28.6%) in phase Ib; and headache (58.3%), fatigue (54.2%), IRRs (41.7%), neutropenia (37.5%), and nausea (33.3%) in phase II. In phase Ib, seven patients had a best response of stable disease (SD); in phase II, one patient had a confirmed complete response, one had a confirmed partial response, and seven had SD. All immunogenicity-evaluable patients were anti-drug antibodies (ADAs) positive following treatment with modakafusp alfa; neutralizing ADAs were reported in 82.4% and 90.9% of patients in phases Ib and II, respectively, which was associated with drug exposure reduction. Pharmacodynamic analyses demonstrated innate and adaptive immune activation in peripheral blood and within tumors. Paired biopsy analysis revealed two subgroups of patients defined by differences in CD38 upregulation, accompanied by differential intratumoral pharmacodynamic changes. Correlative analysis was inconclusive.ConclusionsModakafusp alfa induces innate and adaptive immune responses, supporting its hypothesized mechanism of action (MoA) in patients with advanced solid tumors. High immunogenicity and the potentially limited treatment effect of the interferon MoA may have contributed to limited efficacy in these patients.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04157517, identifier NCT04157517.

Radiation therapy (RT) has been one of the standard treatments for prostate cancer; however, its potential impact on nearby neural structures, such as the lumbosacral plexus (LSP), is often overlooked. The lack of contouring in treatment plans has led to unintended consequences. Radiation-induced lumbosacral plexopathy (RILSP) is a rare but serious complication that presents with progressive lower extremity sensory changes and weakness, mimicking radiculopathy. We report the case of a 66-year-old male who developed bilateral lower extremity neurological deficits post-pelvic radiation for prostate cancer. Radiographically, no compressive lesions were found, and the Electromyography (EMG) revealed involvement of nerves inconsistent with radiculopathy. This led to the diagnosis of RILSP. This case highlights the importance of recognition of RILSP in contrast to radiculopathy in patients with unexplained neurological symptoms after pelvic RT. This highlights the importance of incorporating the LSP as an organ at risk while planning for RT and reviewing retrospectively the dosimetry. It also emphasizes the need for improved contouring of LSP in radiation planning to minimize adverse effects. This sentiment is reflected in the literature, along with the consensus that more research is needed to address the true rate of RILSP.

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