Local Therapy Research Articles

Enhanced systemic antitumor efficacy of PD-1/PD-L1 blockade with immunological response induced by photodynamic therapy.

Photodynamic therapy (PDT) is an antitumor therapy and has traditionally been regarded as a localized therapy in itself. However, recent reports have shown that it not only exerts a direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized that the immunological response induced by PDT could potentially enhance the efficacy of programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) blockade. The cytotoxic effects of PDT on colon 26 cells were investigated in vitro using the WST assay. We investigated whether the antitumor effect of anti-PD-1 antibodies could be amplified by the addition of PDT. We performed combination therapy by randomly allocating tumor-bearing mice to four treatment groups: control, anti-PD-1 antibodies, PDT, and a combination of anti-PD-1 antibodies and PDT. To analyze the tumor microenvironment after treatment, the tumors were resected and pathologically evaluated. The viability rate of colon 26 cells decreased proportionally with the laser dose. In vivo experiments for combined PDT and anti-PD-1 antibody treatment, combination therapy showed an enhanced antitumor effect compared with the control. Immunohistochemical findings of the tumor microenvironment 10 days after PDT indicated that the number of CD8+ cells, the area of Iba-1+ cells and the area expressing PD-L1 were significantly higher in tumors treated with combination therapy than in tumors treated with anti-PD-1 antibody alone, PDT alone, or the control. PDT increased immune cell infiltration into the tumor microenvironment. The immunological response induced by PDT may enhance the efficacy of PD-1/PD-L1 blockade.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Nomogram for predicting post-therapy recurrence in BCLC A/B hepatocellular carcinoma with Child-Pugh B cirrhosis

IntroductionThis study conducts a retrospective analysis on patients with BCLC stage A/B hepatocellular carcinoma (HCC) accompanied by Child-Pugh B cirrhosis, who underwent transarterial chemoembolization (TACE) in combination with local ablation therapy. Our goal was to uncover risk factors contributing to post-treatment recurrence and to develop and validate an innovative 1-, 3-, and 5-year recurrence free survival (RFS) nomogram.MethodsData from 255 BCLC A/B HCC patients with Child-Pugh B cirrhosis treated at Beijing You’an Hospital (January 2014 - January 2020) were analyzed using random survival forest (RSF), LASSO regression, and multivariate Cox regression to identify independent risk factors for RFS. The prognostic nomogram was then constructed and validated, categorizing patients into low, intermediate, and high-risk groups, with RFS assessed using Kaplan-Meier curves.ResultsThe nomogram, integrating the albumin/globulin ratio, gender, tumor number, and size, showcased robust predictive performance. Harrell’s concordance index (C-index) values for the training and validation cohorts were 0.744 (95% CI: 0.703–0.785) and 0.724 (95% CI: 0.644–0.804), respectively. The area under the curve (AUC) values for 1-, 3-, and 5-year RFS in the two cohorts were also promising. Calibration curves highlighted the nomogram’s reliability and decision curve analysis (DCA) confirmed its practical clinical benefits. Through meticulous patient stratification, we also revealed the nomogram’s efficacy in distinguishing varying recurrence risks.ConclusionThis study advances recurrence prediction in BCLC A/B HCC patients with Child-Pugh B cirrhosis following TACE combined with ablation. The established nomogram accurately predicts 1-, 3-, and 5-year RFS, facilitating timely identification of high-risk populations.

Comparative Study of Systemic vs. Local Antibiotics with Subgingival Instrumentation in Stage III–IV Periodontitis: A Retrospective Analysis

To improve the clinical and microbiological outcomes of non-surgical mechanical periodontal therapy, the adjunctive use of antimicrobials has been utilized in treating moderate-to-severe periodontitis. In our study, the retrospective design included previously collected health-related patient data, obtained from the printed and digital charts of patients who received systemic or local antibiotic adjuncts to SI (subgingival instrumentation). A total of 34 patients (diagnosed with generalized Stage III/IV periodontitis) met the inclusion and exclusion criteria and were evaluated. The samples were tested for the following bacterial strains: Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), Prevotella intermedia (P. intermedia), Tanererella forsythia (T. forsythia), and Treponema denticola (T. denticola). The inter-group comparisons of the bacterial species did not show statistically significant differences between groups. The present study aimed to evaluate the clinical effects after SI and the adjunctive use of systemically administered (SA) AMX (amoxicillin) + MET (metronidazole) (administered for 7 days), with locally delivered (LDD) piperacillin + tazobactam in step 2 of periodontal therapy. Results: Overall, all parameters were improved in the groups, with a significant difference in inter-group comparison regarding the full-mouth bleeding score (FMBS) (p < 0.05) in favor of the SA group, and the p-value < 0.05 was considered to be statistically significant. Statistically significant PPD (probing pocket depth) reductions and CAL (clinical attachment level) gains were observed in both groups at the 3-month follow-up. In conclusion, within the limitations, the outcomes of this study suggest that SI, with adjunctive local or systemic antibiotic therapy, provided comparable clinical improvements. Systemic AMX + MET protocols were more efficacious with regard to the reduction in FMBS. Follow-up studies with larger patient numbers are needed to further investigate this effect.

A Comprehensive Review of a particular Skin Injury: Pathogenesis, triggers, and current Treatment Options

By definition, an open injury is any severe break in the continuity of the skin and deep tissue. Because contusions are healed injuries, the term given above does not apply to them. The classification of injuries is essential for both therapeutic and medico-legal purposes. Burn injuries are comparable to other injuries in that they require the same basic principles for healing and care, but they differ in that they have a greater impact on the patient's overall health and are essential to the patient's eventual survival, the development of deformity, and rehabilitation. Treatment of burn injuries has always been the responsibility of burn specialists. Both local and systemic therapy have long been advised for treating burn injuries and minimizing burn scars. This review summarizes the treatment of burn injuries brought on by a variety of physical and chemical agents requires unique regimens that are completely different from those used to treat any other traumatic injuries. Other acute injuries that undergo entire blood loss result in shock, but major burns that experience significant plasma loss due to increased capillary permeability result in distress. Burn injuries are initially sterile compared to the majority of other injuries, however, due to the immunocompromised state of burn patients and injury infection frequently ends in death in serious burns. We have discussed the pathophysiology, primary care therapies, nanomaterials used in injury healing therapy and various nanoparticles in injury healing process for burn injuries in this review.

Development of Chlorhexidine-Loaded Lipid Nanoparticles Incorporated in a Bioceramic Endodontic Sealer.

This study aimed to assess BioRoot RCS (BR) incorporating liposomal chlorhexidine digluconate (CHX) for its antibacterial activity, drug release capacity, and physicochemical properties. Drug release of CHX liposomal formulations in combination with BR was evaluated spectrophotometrically and through mathematical release models for 30 days. A selected combination was evaluated for antimicrobial properties against Enterococcus. faecalis (E. faecalis) biofilm growth on human dentin. Cytotoxicity was assessed following the ISO 10993-5:2019 standard on days 1, 3, and 7. Physicochemical properties were evaluated through setting time, Fourier transform infrared spectroscopy (FTIR), solubility, contact angle, and film thickness. From BR, liposomal CHX released up to 7-fold higher CHX than CHX solution (p<0.05), following a triphasic drug release pattern compared to the CHX solution, which followed a quasi-Fickian diffusion. BR combined with a selected liposomal CHX completely inhibited E. faecalis biofilm growth compared to the combination of BR with CHX solution and the control group (p<0.05). Liposomal CHX decreased the contact angle (p<0.05) and solubility but increased cytotoxicity (p<0.05) of BR, staying above the ISO threshold. None of the other physicochemical characteristics tested differed from BR (p>0.05). This liposomal formulation improved CHX release from BR, enhancing the antibacterial effectiveness. It presents a promising approach for local anti-biofilm therapy in endodontics without substantially altering the physicochemical characteristics of BR.

Abstract PS11-02: Clinical risk factors of Central Nervous System (CNS)-related death in patients with HER2-positive metastatic breast cancer

Abstract Background: Central nervous system (CNS) relapse represents a challenge in the management of patients with HER2-positive (+) metastatic breast cancer. Data regarding the impact of brain metastases (BrM) and CNS involvement on mortality are sparse. In this study we sought to determine the proportion of HER2+ MBC patients in which CNS disease is the cause of death and identify risk factors associated with CNS-related mortality. Methods: We reviewed medical records of 294 consecutive patients with HER2+ MBC and diagnosis of CNS disease including parenchymal BrM, leptomeningeal disease (LMD) or dural metastases (DM), treated at Memorial Sloan Kettering Cancer Center between August 2010 and April 2022. HER2-positivity was assessed at the first diagnosis of metastatic disease (any site). Clinicopathologic characteristics including disease burden at presentation, timing of CNS disease and extracranial metastases (ECM), neurologic complications, and local and systemic treatments were collected. CNS-related death was defined as any death caused by BrM or LMD or DM progression or CNS treatment-associated complications. CNS-related death was estimated using cumulative incidence in the competing risks setting (with death due to other causes as a competing event) and overall survival (OS) was estimated using Kaplan Meier methodology. Risk factors associated with CNS-related death were assessed using sub-distribution hazards regression modeling. Treatments given after CNS disease diagnosis were treated as time-varying variables. Tests were two-sided with statistical significance &amp;lt; 0.05. Results: After excluding 19 patients (11 for discordant HER2 status, 5 for concomitant second solid tumor, and 3 for missing data), 275 patients were included in these analyses (258 patients with parenchymal BrM +/- LMD, 8 patients with DM only, 2 patients with DM concomitantly with LMD, and 6 patients with LMD only). Overall, 63/275 (23%) presented with CNS as first and only site of metastasis, 210 (76%) patients developed CNS disease synchronously with or following ECM, and 2 had unknown timing. 125/275 (45%) had de novo MBC, and nearly all patients were treated with CNS local therapies (92% ≥1 radiation treatment and 28% underwent ≥1 BrM resection). The median number of lines of systemic therapy after CNS disease diagnosis was 1 (range: 0-14); 105/275 (38%) patients received a HER2 tyrosine kinase inhibitor (lapatinib: 21%, neratinib: 4.4%, and tucatinib: 12%). The median follow-up was 3.6 years for survivors (range: 0.22 years-12 years). 193/275 (70%) patients died, of whom 105 (54%) died of CNS-related cause. The 3-year OS rate was 40% (95% CI=34%-46%), which varied for patients with BrM only at the diagnosis of metastatic disease [56% (95% CI=43%-69%] compared to patients with ECM +/- BrM [35% (95% CI=28%-42%] (p=0.05). The cumulative incidence of CNS-related death at 3 years was 33% (95% CI=27%-39%). Upon univariable modeling, LMD and CNS radiation treatment (RT) were associated with CNS-related death, and these associations remained statistically significant in a multivariable model [LMD: HR=2.49 (95% CI=1.62-3.83), p&amp;lt; 0.0001, and RT: HR=2.91 (95% CI=1.27-6.64), p=0.01]. Conclusions: Greater than half of patients with HER2+ with CNS involvement suffered of CNS-related death, with greatest risk among patients with LMD. We hypothesize that the association between radiotherapy and CNS-related death may reflect upfront response to systemic cancer-directed treatments of those in patients with DM only or limited CNS disease extension. CNS-only relapse at metastatic presentation portended improved survival than intra- plus extracranial progression, supporting an approach of aggressive local therapy for selected patients. Multimodality approaches using HER2-directed agents effective against parenchymal BrM, LMD along with extracranial metastases, in combination with local CNS-directed therapies need to be optimized. Citation Format: Emanuela Ferraro, Rabih Bou Nassif, Anne Reiner, Samantha Brown, Umberto Tosi, Katherine Panageas, Chau Dang, Andrew D Seidman, Nelson Moss. Clinical risk factors of Central Nervous System (CNS)-related death in patients with HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS11-02.

Abstract PO2-04-05: FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES

Abstract Background Brain metastases (BM) are a severe complication of HER2-positive metastatic breast cancer. In the absence of any immediate indication for local therapy, the tyrosine-kinase inhibitor tucatinib combined with trastuzumab and capecitabine (TTC) is regarded as the preferred systemic treatment option for active BM, while data on the activity of antibody-drug conjugates (ADC) is limited. In the primary outcome analysis of TUXEDO-1, an intracranial response rate (RR) of 73.3% was reported with the ADC trastuzumab-deruxtecan (T-DXd). Here, we report final progression-free survival (PFS) and overall survival (OS) results of this study. Patients and Methods: TUXEDO-1 is a prospective, single-centre, single-arm phase 2 trial. Adult patients with HER2-positive BC and active BM (newly diagnosed untreated or progressing after prior local therapy), prior treatment with trastuzumab and pertuzumab, ECOG performance status 0 or 1 without indication for immediate local therapy were accrued and received T-DXd until progression, inacceptable toxicity, or withdrawal for any other reason. The primary endpoint was intracranial RR centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria in the intention-to-treat population; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population (PPP). Results A total number of 15 patients were accrued; one patient was found to have dural metastases only upon restaging, resulting in a PPP of 14 patients. Patients had received a median number of two prior treatment lines (range, 1-5), 60% had progressive brain metastases and 60% had received prior T-DM1. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). A total of 238 cycles of T-DXd were administered (median 11.5 cycles; range 4-42). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event (AE) was fatigue (n=3; 20%). A total of 8 serious AEs were reported in 8 patients. Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL and neurocognitive functioning were maintained over the entire treatment duration and a significant deterioration of global QoL was observed upon progression (p=0.036). Most patients received TTC (n=5) or local therapy (n=4) as next subsequent treatment line. Ancillary biomarker studies are ongoing, and results will be presented at the meeting. Discussion In TUXEDO-1, T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive breast cancer BM. The safety profile was consistent with previous reports. T-DXd did not impair QoL and neurocognitive functioning was maintained. Results therefore support the concept of ADCs as systemic therapy for active BM. Citation Format: Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Angelika Maria Starzer, Maximilian Mair, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian F. Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser. FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-05.

Abstract PO5-20-02: Secondary BRain metastases prevention after Isolated intracranial progression on trastuzumab/pertuzumab or T-DM1 in pts with aDvanced human epidermal Growth factor receptor 2+ brEast cancer with addition of Tucatinib (BRIDGET)

Abstract Background: Despite treatment with trastuzumab-based therapy, up to half of patients with HER2+ advanced/metastatic breast cancer (MBC) will develop brain metastases (BrM). First-line therapy for advanced HER2+ MBC remains a taxane, trastuzumab, pertuzumab (TP) which demonstrates poor brain permeability. Isolated brain relapse with stable or absent extracranial disease remains a clinical problem in both the adjuvant (Untch et al., ESMO 2019 Congress) and metastatic settings (Noteware et al., Breast Cancer Res Treat. 2023). Current guidelines recommend continuing current systemic therapy in the setting of first isolated brain relapse following local therapy. Tucatinib, a brain-penetrable HER2-targeting tyrosine kinase inhibitor, when added to trastuzumab and capecitabine improves intracranial progression free survival (PFS) and overall survival (OS) in patients with stable or active HER2+ BrMs. We hypothesize that adding tucatinib to TP or T-DM1 in patients with HER2+ MBC with isolated brain relapse or progression could delay or prevent the development of further intracranial lesions and improve OS. Methods: BRIDGET (NCT05323955) is a single arm, phase II, multicenter study of tucatinib added to TP or T-DM1 after local therapy in patients with isolated brain relapse or progression. A total of 48 patients at 9 U.S. sites as part of the Hoosier Cancer Research Network (HCRN) with metastatic HER2+ breast cancer will be enrolled after 1st or 2nd BrM relapse or progression within 8 weeks of local therapy. Patients must currently be receiving standard of care treatment with TP or T-DM1 in the metastatic setting, or adjuvant trastuzumab-based or T-DM1 therapy with isolated brain recurrence. Extracranial disease must be stable per RECISTv1.1 or absent. Patients may not have leptomeningeal disease or untreated brain lesions over 5 mm. Patients will receive continuous tucatinib added to their current therapy (TP or T-DM1). The primary objective is intracranial PFS compared to a historical control (H0: PFS &amp;lt; 5 months (mos), HA: PFS &amp;gt; 8 mos) of the HER2CLIMB clinical trial where patients could continue on trial with isolated brain progression. In these patients, median time from brain progression to second progression or death was 7.6 mos (95% CI, 3.9 to 11.3 mos) in the tucatinib arm versus 3.1 mos (95% CI, 1.2 to 4.1 mos) in the control arm (Lin et al., J Clin Onc 2020). Secondary endpoints include PFS by RECISTv1.1, PFS of extracranial disease, locally treated versus new distant intracranial metastasis PFS, site of first progression (brain versus non-brain), OS, and toxicity in patients with BrM. Collection of correlative specimens including archival tissue, cerebrospinal fluid (optional), whole blood for ctDNA are planned. Patient-reported outcomes surveyed utilizing the FACT-BR and FACIT-Fatigue questionnaires are also included for future analyses. As of 7/06/23, accrual is 5 patients of the anticipated 48 patients overall, across 5 sites (Duke University, Dana Farber Cancer Institute, Ohio State University, Providence Portland Medical Center, and Washington University in St. Louis) currently open. An additional 4 sites are pending opening. Those interested in this trial can reach out to the study Principal Investigators, Carey Anders, MD (carey.anders@duke.edu) or Sarah Sammons, MD (sarahl_sammons@dfci.harvard.edu). Citation Format: Sarah Sammons, Amanda Van Swearingen, Laura Noteware, Nusayba Bagegni, Kelly Moulton, Stevie Threatt, Denise Jaggers, Shannon Shea, Eric Lipp, Erin Riley, Sin-Ho Jung, Gloria Broadwater, Masey Ross, Kimberly Strickland, Sasha Beyer, Alison Conlin, Aki Morikawa, Rashmi Murthy, Carey Anders. Secondary BRain metastases prevention after Isolated intracranial progression on trastuzumab/pertuzumab or T-DM1 in pts with aDvanced human epidermal Growth factor receptor 2+ brEast cancer with addition of Tucatinib (BRIDGET) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-02.

Abstract ED07-03: Novel Systemic Therapy Strategies for HER2+ Brain Metastases

Abstract More than 1/3 of patients with HER2+ metastatic breast cancer will develop brain metastases. Local therapies such as resection or radiation therapy continue to play a pivotal role in brain metastases treatment. However, receipt of HER2-directed systemic therapies lead to significant survival advances for both stable and active brain metastases and are integral to optimal outcomes. We will review clinical goals for stable and active brain metastases. In the last few years, novel early line systemic therapy regimens have improved outcomes for HER2+ brain metastases which will be reviewed. We will review evolving evidence that Antibody Drug Conjugates targeting HER2 have robust intracranial activity. We will review exciting HER2 directed tyrosine kinase inhibitors and combinations. Citation Format: S. Sammons. Novel Systemic Therapy Strategies for HER2+ Brain Metastases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED07-03.

Abstract PO5-26-04: The value of skin involvement in achieving of pCR in patients with locally advanced breast cancer

Abstract Objective: The management of patients with locally advanced breast cancer (LABC) with skin involvement (edema or thickening) continues to be one of the most controversial topics in mammology. The most recommended conventional treatment strategies include systemic therapy (chemotherapy/hormone therapy/biological agents) followed by local therapy (surgery and/or radiation therapy). However, approximately 1/3 of patients with locally advanced breast cancer are “resistant” to neoadjuvant chemotherapy (which is manifested by the persistence of skin involvement/edema/thickening). In this study, we aimed to identify the relationship between skin involvement and clinicopathological features of LABC patients. In particular, we sought to develop the algorithm for skin involvement measurement and examine the impact of skin involvement on the rate of pCR. Materials and methods: We performed a retrospective analysis of 182 patients diagnosed with LABC from 2010 to 2018 at N.N. Blokhin National Cancer Research Center. All patients were treated with neoadjuvant hormone- or chemotherapy and were considered as borderline for surgical resection because of partial skin edema. Ninety one women received surgery with consecutive radiotherapy (first group) and 50 women (second group) received radiotherapy (total dose 50 Gy) with consecutive surgery after systemic treatment. We developed the algorithm for skin involvement measurement, using a series of formulas. We further interrogated the impact of skin involvement on the rate of breast and lymph node pathological response in every group. Results: The median percentage of skin edema before systemic therapy was 76.3% in the first group and 70.1% in the second group. The median percentage of skin edema after systemic therapy was 62.3% in the first group and 69.1% in the second group. There wasn`t a statistically significant difference between the two groups (р=0,675 and р = 0,286, respectively). Breast pCR was seen in 19,7% (n=18) of the first group patients and partial response was seen in 72.6% (n=66). Breast pCR was seen in 30% (n=15) of the second group patients and partial response was seen in 70% (n=35). Results showed no significant differences between groups, р=0,342 and р = 0,12, respectively. Nodal pCR was reported in 23,9% (n=16) and partial response in 50,8% (n=34) of the 67 node-positive patients. Nodal pCR was reported in 31,6% (n=12) and partial response in 65,8% (n=29) of the 38 node-positive patients of the second group. There was no statistical difference in the groups, p &amp;gt;0,05. Conclusion: Increasing attention has been paid to LABC patients due to the clinical commonness and the complexity of treatment. Our study showed that LABC patients with incomplete clinical response to neoadjuvant systemic therapy can achieve pCR or partial response of tumor despite partial skin edema. In this study we developed the algorithm for skin involvement measurement. We hope that knowledge about volume of skin involvement revealed by this study might shed light on individualized therapies for these patients. In future, it allows to evaluate criteria of tumor resectability to improve patient selection. Therefore, prospective randomized trials are needed to improve optimization of the local treatment. Citation Format: Viktory Amosova, Alexander Petrovskiy, Oxana Trofimova, Mona Frolova, Alexey Rumyantsev. The value of skin involvement in achieving of pCR in patients with locally advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-04.

Abstract PS16-03: Intratumoral dosing of INT230-6 in Early-Stage Breast Cancer Patients Induces Tumor Cell Necrosis and Immunomodulatory Effects: A Phase II Randomized Window-Of-Opportunity Study – the INVINCIBLE Trial

Abstract Background: Larger tumors pose an increased risk for breast cancer (BC) recurrence post-surgery. In addition, most BC outside of the triple negative subtype are considered immunological quiescent and minimally responsive to immunotherapies. One potential method to combat disease recurrence risk and induce immune activation pre-surgery is through a local therapy that could cause cell death to expose tumor antigens, provide adjuvants for anti-tumor immune priming, and thus potentially increase responsiveness to immunotherapies or rates of pathological complete response in combination with chemotherapy. We have conducted a randomized, Phase 2 presurgical Window-Of-Opportunity trial for intratumoral (IT) INT230-6 comprising vinblastine, cisplatin and a diffusion enhancer (SHAO) in patients with early-stage operable BC, the INVINCIBLE trial (NCT04781725). Previous in vivo and clinical studies demonstrated that INT230-6 induces cancer cell death and halts replication while maturing dendritic cells and recruiting T-cells into the tumor. In this trial, IT injections of INT230-6 were conducted to 1) evaluate the safety of regional cytotoxic use on BC, 2) assess the drug’s ability to cause necrosis, 3) assess immune response within the tumor, microenvironment and systemically prior to surgical resection, and 4) understand the genetic pathways involved in immune activity. Methods: Women awaiting surgery for newly diagnosed early-stage intermediate or high-grade T1-T2 invasive BC were recruited to the trial. The study has two parts. Part I was a randomized (2:1) open label trial comparing 1-3 doses of INT230-6 injected weekly versus no treatment prior to surgery to evaluate safety, feasibility, and optimal drug dosing. Part II was a double-blinded randomized (2:1) trial where patients received one IT dose of INT230-6 vs saline injection IT. Results: We successfully recruited 91 patients with age ranges of 40-77 yrs (mean of 60 yrs) with tumor size ranging from 1.1 - 4.8 cm (mean 2.5 cm; SD 0.9 cm). The most common (&amp;gt;10%) AEs were injection site pain, injection site reaction and nausea/vomiting. Approximately 90% of AEs were grade 1. In the study INT230-6 induced necrosis in 64% of subjects (37 out of 58, range 0 to 100%); whereas saline induced partial necrosis in 25% of patients (5 out of 20, range 0 to 10%). The table below shows the results of necrosis for INT230-6 use in the entire study compared to saline injection for all subjects and those with tumors of size T2. A single injection of INT230-6 caused necrosis in various histologies, including invasive lobular carcinoma. Gene expression analysis showed significant differential gene expression between the baseline biopsy and surgical specimens using INT230-6. Pathway analysis identified genes associated with TCR signaling, B cells and T cell activation that were significantly upregulated in the post INT230-6 treatment samples. There was a relative increase in CD4 and CD8 T cells and B and mast cells. Conclusion: Preliminary evidence shows that a single dose of INT230-6 can cause significant intratumoral necrosis compared to saline especially in tumors &amp;gt;2. cm. INT230-6 stimulates an immune response in breast cancers prior to surgery with minimal adverse effects and good tolerability. Given its immune activation properties, INT230-6 shows promising potential in future breast cancer neoadjuvant studies. Table 1: INVINCIBLE Study Tumor Necrosis Results Intratumoral INT230-6 injection compared to IT saline injection Citation Format: Angel Arnaout, Lewis Bender, Megan Hopkins, Vanessa Lopez Ozuna, Linda Liao, Susan Robertson, Vida Talebian, Kianoosh Keyhanian, Arif Awan, Franco Abbate, Ian Walters, Gregory Pond, John Bartlett, Lazlo Radvanyi, Melanie Spears. Intratumoral dosing of INT230-6 in Early-Stage Breast Cancer Patients Induces Tumor Cell Necrosis and Immunomodulatory Effects: A Phase II Randomized Window-Of-Opportunity Study – the INVINCIBLE Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-03.

Abstract PO3-05-01: Locoregional Management Based on Mode of Progression for HR+/HER2- metastatic breast cancer Treated with Combined CDK4/6 inhibitor with Aromatase inhibitor

Abstract Background - Standard management for HR+/HER2- metastatic breast cancer (MBC) comprises concurrent aromatase inhibitor (AI) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), providing improved progression-free (PFS) and overall survival over anti-estrogen alone. Eventual resistance mechanisms potentially include phenotypic changes, clonal selection, and new mutations. We theorized that limited progressive disease (LPD) would be more common on combination therapy due to eventual new mutations or clonal selection, in comparison to generalized progressive disease (GPD) occurring more frequently on AI alone due to phenotypic cellular changes across all disease sites. Potentially loco-regional treatment (LRT) options could significantly extend disease control in selected patients on combined therapy. Methods - Patterns of progressive disease (PD) for 55 historical AI-only treated controls (group A) were compared to those for 60 patients on combined treatment with an AI and a CDK4/6 inhibitor (group B) for first-line management of HR+/HER2- MBC. Mode of progression was classified as general (GPD - PD in the majority of lesions) or limited (LPD - PD in up to three lesions in a single organ). All LPDs were assessed for suitability for LRT at time of progression. PFS was assessed for those with LPD who continued present treatment after locoregional therapy. Results - LPD occurred in 13 of 55 patients (23.6%) in group A compared to 26 of 60 (43%) in group B (p = 0.026). For LPD patients, all 13 cases in group A were considered appropriate for LRT but only 3 (23.1%) received it and all patients also switched systemic therapy. In group B, 23 of 26 LPD patients were considered suitable for LRT and 16 (57.7%) received it, of whom 11 then continued first line systemic treatment. For these 11 group B patients median PFS was 12+ months (range 3 to 36+ months). LRT consisted of RT in 14 cases (bone in 13 cases, lymph node in one case) and resection in one (isolated brain metastasis). Conclusion - Patients treated with combined CDK4/6i and AI for first line HR+/HER- MBC were significantly more likely to develop LPD than those on single agent anti-estrogen, where local therapy could often be delivered with no change to systemic therapy. This strategy, applied to 11 of 60 combination treated patients (18%), delivered a median PFS in excess of a year. In contrast more general PD was more commonly observed in patients treated with AI alone, warranting change in systemic therapy. Citation Format: Andrew Redfern, Ngie Law, Indunil Weerasena, Lisa Spalding, Hilary Martin. Locoregional Management Based on Mode of Progression for HR+/HER2- metastatic breast cancer Treated with Combined CDK4/6 inhibitor with Aromatase inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-01.

Abstract PO5-20-04: A Phase II Study of Ribociclib and Endocrine Treatment of Physician’s Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR Study)

Abstract Background Hormone receptor positive (HR+) breast cancer (BC) is the most common subtype of BC (70-80%). This subset tends to have good prognosis, therefore most patients with localized disease have excellent long-term survival, approaching 100% 5-year relative survival. However, 10% of patients experience loco-regional recurrence (LRR) within 5 year of final surgical management of the primary disease-well within the typical treatment window of adjuvant endocrine therapy. Few studies exists to guide the systemic treatment of patients who have suffered LRR of HR+ HER2 - BC. The randomized controlled CALOR trial demonstrated no benefit to systemic cytotoxic chemotherapy for this subgroup of patients and persistent high rate of subsequent recurrences (50% within 10 years on LRR event). There is no standard of care for managing this patient population. The combination of ribociclib and endocrine therapy (ET) (fulvestrant and aromatase inhibitors) is FDA approved for management of unresectable recurrences and metastatic HR+HER- BC (MONALEESA trials). CDK4/6 inhibitors have been investigated in early BC setting too, several trials showing positive results (monarchE, NATALEE). Data is needed to investigate their use in patients with LRR. Trial design This is a multicenter, single arm phase II study to evaluate efficacy and safety of ribociclib and ET in patients with LRR of HR+HER2- BC. Treatment includes ribociclib for 36 months, 600 mg daily for 21 days, 28-day cycle plus physician’s choice ET for 60 months (fulvestrant or AIs). Ribociclib dose was chosen based on approved dose in metastatic BC. Eligibility Criteria Patients ≥ 18 of age, with LRR of BC (ipsilateral breast, axilla, regional lymph nodes, chest wall), histologically confirmed estrogen receptor positive and/or progesterone receptor positive, HER 2 negative. Patients must have adequate local treatment for LRR (surgery and/or radiation) with negative microscopic margins, no evidence of distant metastatic disease. Prior treatment with neo-adjuvant and adjuvant chemotherapy and ET is allowed, no prior CDK 4/6 inhibitor in the last 12 months. Pre and post-menopausal women are allowed. Patient must enroll within 6 months of the last local therapy. Specific aims Primary objective: to estimate subsequent recurrence-free survival (RFS) at 3 years for ribociclib when administered with ET in patients with HR + HER2- BC with adequately resected local recurrence. Secondary objectives: to estimate distant metastasis-free survival and overall survival, to evaluate safety and tolerability, to identify predictors of LRR. Correlative analysis will explore prognostic and predictive biomarkers of treatment with ribociclib and ET and potential molecular mechanisms of resistance to treatment. Statistical Methods From previous published data (J Clin Oncol. 2018 Apr 10;36(11):1073-1079), we assume that patients receiving standard of-care management following recurrence would have a recurrence free survival (RFS) rate of 80% at 3 years and that treatment with ribociclib + ET will increase it by 7%. We wish to have at least 80% power at that significance level of 0.0487 to correctly detect that improvement in RFS rate at 3 years from 80 to 87%. Because only an improvement in RFS rate is of clinical interest, we have a directional hypothesis, and have used a 1-sided alpha. Using a one-sample survival study design, with assumed accrual duration of 3-years and additional follow-up time of 3 years, the minimum sample size requirement is N=180 patients. Target accrual The minimum sample size requirement is N=180 patients. A bigger sample size of N=200 patients will achieve a power of at least 84%. Current accrual is 6/200. This study will be open at up to 35 sites. Contact information The study is being administered through the HCRN, it can be identified as BRE20-468, NCT05467891, ocdanciu@uic.edu Citation Format: Oana Danciu, Nancy Chan, Kari Wisinski, Trish Millard, Kathleen Kemmer, Sneha Phadke, Zhengjia Chen, Ana Cuesta Fernandez, Melanie Clark, Alison Conlin, Coral Omene, Sima Ehsani, Stephanie Dublis, Vijayakrishna K. Gadi. A Phase II Study of Ribociclib and Endocrine Treatment of Physician’s Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR Study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-04.

Abstract GS01-10: HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer

Abstract Background Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor approved in combination with trastuzumab and capecitabine for previously treated HER2+ locally advanced or metastatic breast cancer (LA/MBC). Trastuzumab emtansine (T-DM1) is a HER2-directed antibody-drug conjugate approved to treat HER2+ LA/MBC previously treated with trastuzumab and a taxane. This is the first report of HER2CLIMB-02 (NCT03975647), a randomized, double-blind, placebo-controlled phase 3 study assessing the efficacy and safety of tucatinib combined with T-DM1 in patients with previously treated HER2+ LA/MBC. Methods Eligible patients had HER2+ LA/MBC previously treated with trastuzumab and a taxane in any setting with ECOG performance status ≤1 and adequate hepatic, renal, hematologic, and cardiac function. Patients with previously treated stable, progressing, or untreated brain metastases (BMs) not requiring immediate local therapy were also eligible. Patients were randomly assigned 1:1 to receive 21-day cycles of either tucatinib (300 mg orally twice a day [PO BID]) or placebo (PO BID), combined with T-DM1 (3.6 mg/kg intravenously every 3 weeks). The primary endpoint was progression-free survival (PFS) by investigator assessment per RECIST v1.1. Alpha-controlled secondary endpoints included overall survival (OS) and objective response rate (ORR) per RECIST v1.1 for the overall population, and PFS and OS for the subset of patients with BMs at baseline. Safety was analyzed as a secondary endpoint. Results From October 8, 2019, to June 16, 2022, 463 patients were randomly assigned, comprising 228 to the tucatinib arm (tucatinib + T-DM1) and 235 to the control arm (placebo + T-DM1). The median duration of follow-up (OS) was 24.4 months for the overall population. Patient demographics and baseline characteristics were balanced between the 2 arms. Almost half (44.1%) of the overall population had either active or stable BMs at baseline. As of the data cutoff (June 29, 2023), the study met its primary endpoint with a statistically significant improvement in PFS in the tucatinib arm vs control arm. The risk of progression or death decreased by 24.1% in the tucatinib arm (hazard ratio [HR]=0.759 [95% CI, 0.607-0.950]; P=0.0163). Median PFS was 9.5 months (95% CI, 7.4-10.9) vs 7.4 months (95% CI, 5.6-8.1) for the tucatinib and control arms, respectively. HRs for PFS across all prespecified subgroups were consistent with the HR of the overall population, including patients with BMs at baseline (HR=0.639 [95% CI, 0.459-0.891]). The interim OS results were immature with 134 of 253 total required events (53%) and did not meet the prespecified crossing boundary. The confirmed ORR was numerically higher in the tucatinib arm (42.0%) vs the control arm (36.1%). The most common treatment-emergent adverse events (TEAEs) included nausea (65.4% vs 49.4% for tucatinib and control arms, respectively), diarrhea (56.7% vs 26.6%), and fatigue (48.9% vs 37.3%). The most common grade ≥3 TEAEs in the tucatinib arm were alanine and aspartate aminotransferase elevations, each reported in 38 patients (16.5%) in the tucatinib arm and 6 patients (2.6%) in the control arm. TEAEs associated with any treatment discontinuation occurred in 51 patients (22.1%) in the tucatinib arm and 27 (11.6%) in the control arm. TEAEs leading to deaths occurred in 3 patients (1.3%) in the tucatinib arm and 2 patients (0.9%) in the control arm. Conclusion HER2CLIMB-02 demonstrated that the addition of tucatinib to T-DM1 significantly improved median PFS in patients with previously treated HER2+ LA/MBC, including those with BMs. Although discontinuations due to TEAEs were more common in the tucatinib arm, no new safety signals emerged for the combination therapy. Citation Format: Sara Hurvitz, Sherene Loi, Joyce O'Shaughnessy, Alicia Okines, Sara Tolaney, Joo Hyuk Sohn, Cristina Saura, Xiaofu Zhu, David Cameron, Thomas Bachelot, Erika Hamilton, Giuseppe Curigliano, Antonio Wolff, Nadia Harbeck, Norikazu Masuda, Linda Vahdat, Khalil Zaman, Frances Valdes-Albini, Margaret Block, Timothy Pluard, Tira Tan, Chelsea Gawryletz, Arlene Chan, Philippe Bedard, Rinat Yerushalmi, Binghe Xu, Konstantinos Tryfonidis, Michael Schmitt, Joan Xie, Virginia Borges. HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-10.

Differential diagnosis and treatment of enthesopathies

The article provides a review of the literature on the pathology of the periarticular structure of the enthesis - the site of attachment of a tendon or ligament to the bone. The anatomical and functional features of the fibrocartilaginous enthesis are presented in detail from the position of the “enthesis organ”, which includes the enthesis and the adjacent synovial membrane, bursae and adipose tissue. The issues of the occurrence of degenerative changes against the background of mechanical stress and inflammatory rheumatic pathological processes in the above structural and functional anatomical unit are analyzed. The anatomical zones whose entheses are most often affected are given. The terminology of degenerative and inflammatory lesions of the enthesis is considered, including from the standpoint of ICD-10 codes. The advantages and disadvantages of modern terms are discussed, current concepts corresponding to the etiology of the pathological process are proposed: degenerative-dystrophic or traumatic enthesopathy and inflammatory enthesitis. This division of concepts is aimed at adopting the correct diagnostic and treatment tactics for a doctor of any specialization. The differential diagnosis of these nosologies and approaches to conservative treatment are considered. The possibilities of local injection therapy for enthesitis and enthesopathies, the use of  anti-inflammatory and reparative techniques are discussed in detail. Based on our own clinical experience, the features of the treatment of various enthesopathies with glucocorticoids, autologous plasma, microinductive collagen, linear hyaluronates and polynucleotides are considered. Issues of priority methods in different clinical situations and the possibility of prolonging the therapeutic effect, as well as a combination of local and non-drug methods, were discussed. The tactics for ineffective local treatment, methods for correcting therapy and the choice of a leading specialist for various pathologies are discussed.

Abstract PO4-15-01: A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer

Abstract Background: The presence of tumor cells (or their components) in the blood of women with a history of early breast cancer has the potential to herald the development of metastatic recurrence at its earliest stages. Such early detection could potentially lead to novel prevention strategies, but it requires a sensitive assay. Objective: To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from patients with an established diagnosis of metastatic breast cancer (MBC), prior to initiation of 1st line systemic therapy in the metastatic setting. Methods: We conducted a multi-center prospective cohort study to evaluate the presence of CTCs using the Epic Sciences platform among patients with a new diagnosis of MBC. Men or women age 18 to 85 were included, irrespective of breast cancer subtype. Patients with a prior or concurrent malignancy whose natural history or treatment had the potential to interfere with the detection of MBC in a liquid biopsy were excluded. A one-time blood draw was performed before patients received any local or systemic therapy in the metastatic setting. In addition, those with recurrent disease must have been off any systemic adjuvant therapy for ≥3 weeks prior to blood collection. Two 5 mL blood samples were obtained for CTC identification and enumeration. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical and pathological features, which were abstracted from medical records and pathology reports. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. Results: 100 patients were recruited between February 2021 and January 2023 at five academic oncology centres in Ontario and Quebec, Canada. 95 patients had evaluable blood for analysis and 5 did not due to blood age and/or insufficient blood volume. Six patients were excluded after providing a blood sample because tissue biopsy ultimately revealed a 2nd primary tumor (n=4) or benign tissue (n=2). Hence, 89 patients with a clinical diagnosis of MBC and with evaluable blood for CTC analyses were ultimately included in our cohort. The average age of patients was 61 years. Most patients (n=49, 55%) had a prior history of early breast cancer, 38 (43%) had de-novo metastatic disease and prior breast cancer history was unknown for 2 patients. 50 (66%) of patients had visceral metastatic disease. The most common sites of metastases included bone (62%), lung (30%), liver (29%) and lymph nodes (17%). 63 of 89 patients (71%) had detectable CTCs at baseline, prior to any local or systemic treatment in the metastatic setting. The median number of detectable CTCs per 5mL sample was 2 (IQR 8.5) and the range was 0 – 12,798. Twenty nine of 89 (33%) patients had 5 or more CTCs detected per 5ml blood. The proportion of patients with detectable CTCs was numerically highest (n=39/51, 76%) among patients with hormone receptor (HR)+/HER2-ve breast cancer, followed by HER2+ (n=16/22, 73%) and triple negative (n=8/13, 62%) disease. Associations between CTC detection with prior history of early breast cancer, sites of metastatic disease and disease burden will also be presented. Conclusions: Approximately 3 in 4 women with newly diagnosed metastatic breast cancer have detectable CTCs using the Epic Sciences platform prior to initiation of first line systemic therapy. CTCs may be a promising tool for the monitoring of breast cancer recurrence and will be investigated in an ongoing Canadian prospective observational study that aims to elucidate biomarkers of late breast cancer recurrence. Citation Format: Katarzyna Jerzak, Pamela Goodwin, Marguerite Ennis, Christine Brezden-Masley, Nathaniel Bouganim, Mark Basik, Arushi Jain, Giuseppe Di Caro, Rick Wenstrup, Nadine Hartmann, Megan Slade, Ana Elisa Lohmann. A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-01.

Abstract PO5-19-05: A Phase II Trial of Stereotactic Body Radiation Therapy and Fluoroestradiol Positron Emission Tomography in Patients with Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer

Abstract Background: The term oligoprogression (OP) refers to a clinical scenario in which patients with diffuse metastatic disease on systemic therapy have a limited number of metastases that have progressed or are new whereas the majority of metastases are stable or improved. OP disease is increasingly being encountered in clinical practice due to improvements in systemic therapy. Treating OP disease with local ablative therapies may therefore prolong the time to more diffuse progression necessitating a change in systemic therapy and may therefore lead to improved overall survival in these patients. Only one study has evaluated the role of SBRT in patients with OP MBC. This trial accrued 47 patients with OP MBC, with 2/3 having triple negative disease. There was no difference in PFS between patients that received SBRT versus those that did not (4.2 months vs. 4.4 months, p=0.2). Whether ablative therapies are beneficial in subtypes of breast cancer that have many effective systemic therapies available, such as ER+ breast cancer, remains an open question and an unmet clinical need. Design: Phase II study for patients with OP ER+ MBC (1-4 new and/or progressing metastatic lesions). Eligible patients will receive stereotactic body radiation therapy (SBRT) to the OP lesions. SBRT will be delivered to each lesion in 3-5 fractions. Each patient’s systemic therapy regimen will be held during study therapy and will resume upon completion of study therapy. Patients will then be restaged at 12 weeks post-SBSRT. Patients that have at least stable disease at that time point will continue on their systemic therapy and then be re-staged 12 weeks later (24 weeks after SBRT). This study will also study the role of ER-targeted positron emission tomography (PET) imaging with 16α-18F-Fluoro-17β-Fluroestradiol (FES) in the OP ER+ patient population with FES PET scans obtained at baseline, and at each of the 2 follow-up imaging timepoints. A key secondary hypothesis is that the use of FES PET in addition to standard imaging at baseline and in follow-up will help confirm patients have OP disease and will help assess for new lesions on subsequent restaging. Eligibility: Key inclusion criteria: age≥18 yo; histologically confirmed ER+/HER2- metastatic breast cancer; the presence of metastatic breast cancer at the time of study entry with progression in 1-4 lesions (including new lesions); SBRT must be feasible for all progressing lesions. Key Exclusion Criteria: &amp;gt;2 lines of systemic therapy for metastatic disease; intracranial disease progression Objective: To determine whether using SBRT to treat OP lesions allows ER+ breast cancer patients to continue on their current systemic therapy for at least 24 weeks post SBRT. Objective: To assess whether FES-PET increases the number of lesions found prior to SBRT; To determine the impact of SBRT on patient quality of life; time to next line systemic therapy; PFS Statistical Methods Simon 2 stage optimal design with α=0.05 and 1-β=0.80. The null hypothesis is that the proportion of patients that remain on their original systemic therapy ≥24 weeks (2 restaging scans) post-treatment is 20%. The alternative hypothesis is that the proportion of patients that remain on their original systemic therapy after 2 restaging scans is 50%. In stage 1, 8 patients that proceed to SBRT will be enrolled. The study will be terminated if only 0 or 1 subjects remain on original systemic therapy after 2 restaging scans. However, if ≥2 patients remain on original systemic therapy after 2 restaging, then an additional 10 patients would be enrolled for a total of 18 patients. The null hypothesis will be rejected if ≥6 patients remain on their original systemic therapy after 2 restaging scans. Contact Information: Jose G. Bazan (jbazan@coh.org) Funding Source: City of Hope Comprehensive Cancer Center Citation Format: Jose Bazan, Joanne Mortimer, Yun-Rose Li. A Phase II Trial of Stereotactic Body Radiation Therapy and Fluoroestradiol Positron Emission Tomography in Patients with Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-05.

Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study).

The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study. This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients. Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs. S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

Abstract ED11-03: Approaches to radiation therapy for inflammatory breast cancer

Abstract Inflammatory breasst cancer ((BC) is an uncommon and highly agressive form of breast cancer, with a predilection for both distant metastases and local regional recurrence. In this talk we will review challenges in radiation therapy planning and execution unique to IBC. These include staging studies and photographs to define the full extent of disease prior to systemic therapy, as well as current thoughts on dose and fractionation. We will also discuss pros and cons of local therapy in patients with metastatic disease, as well as ongoing research studying ways to optimize local regional control with concurrent systemic therapy and radiation. Citation Format: J. Bellon. Approaches to radiation therapy for inflammatory breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED11-03.