Favorable Response Rates Research Articles

Effectiveness and safety of therapeutic plasma exchange in neurological diseases: An 11-year report from a tertiary care center.

Therapeutic plasma exchange has been a well-known treatment method for many years and is widely available. It leads to the improvement of neurological symptoms in autoimmune neurological diseases by the removal of antibodies. The aim of this study was to present therapeutic plasma exchange responses and procedure-related adverse events in patients with autoimmune neurological diseases based on our 11-year experience. A retrospective evaluation was conducted on adult patients who underwent a therapeutic plasma exchange procedure due to neurological diseases between January 2013 and January 2024. Data were gathered from electronic and written hospital and apheresis unit records. A total of 265 patients underwent 1274 procedures with a preliminary diagnosis of autoimmune neurological disease. Five patients were excluded from the analysis due to their final diagnoses. The most common clinical indications were Guillain-Barré syndrome (45.4%), myasthenia gravis (26.1%), and multiple sclerosis (19.2%). The overall response rate was 81.3%, with 21.7% exhibiting a complete response and 59.6% demonstrating a partial response. With the exception of one patient (hypertensive crisis), no complications necessitating the termination of the procedure were observed. The most prevalent complication was an easily manageable allergic reaction. Therapeutic plasma exchange has been demonstrated to be an efficacious and safe treatment option in autoimmune neurological diseases, with a favorable overall response rate and a manageable mild-to-moderate side effect profile.

Microbiological aspects of cancer progression: A systematic review conducted according to the PRISMA 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.

The complex interplay between the gut microbiota, cancer treatments and patient characteristics has emerged as a significant area of research. This study sought to examine these relationships in the context of colorectal cancer (CRC).A comprehensive search of relevant studies was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The studies included a variety of treatment modalities and microbiological parameters. A data extraction form, designed specifically for this review, was used to assess a range of variables across all studies.The analysis revealed a multifaceted interaction between the gut microbiota, genetic factors and treatment outcomes. Elderly patients with CRC frequently received single-agent chemotherapy, with outcomes that were comparable to those of younger patients. The presence of tumorigenic bacteria, including Escherichia coli and Bacteroides fragilis, was associated with early colon neoplasia. Additionally, an abundance of Fusobacterium spp. was observed in colonic adenomas, contributing to a pro-inflammatory environment. Although the FcγRIIIa-158 V/V genotype was associated with higher cetuximab-mediated antibodydependent cellular cytotoxicity (ADCC), no direct influence of FcγR polymorphisms on treatment response was noted. Furthermore, the combination of programmed cell death protein-1 (PD-1), BRAF and MEK inhibition showed favorable response rates. The gut microbiome, especially the presence of Fusobacterium spp., had a notable influence on the therapeutic response in CRC.These findings underscore the role of the gut microbiota and genetic factors in cancer treatment outcomes, emphasizing the potential of a holistic approach to cancer management. Future research should exploit these findings in order to develop microbiota-modulating strategies and personalized medicine approaches for the purpose of improving the efficacy of cancer treatment.

Response to platinum-based therapies in second-line after immunotherapy in advanced or metastatic non-small-cell lung cancer PD-L1 ≥50.

Platinum-based therapies for patients with advanced non-small-cell lung cancer (NSCLC) have classically provided overall survival (OS) rates of six to nine months and objective response rates (ORRs) of 20-30%. Whether prior immunotherapy determines a different response to platinum is currently unknown. This study aimed to analyse the current response characteristics to platinum as a second-line treatment for advanced NSCLC (PD-L1 ≥50%) after first-line immunotherapy. This retrospective study was conducted at the University Hospital of Salamanca (CAUSA) between 2016 and 2023 with patients who had advanced NSCLC (PD-L1 ≥50%) treated with second-line platinum-based therapies after immunotherapy (without mutations in EGFR, ALK or ROS1 and with Eastern Cooperative Oncology Group (ECOG) ≤1 during the first- and second-line treatments). Survival and response correlation analyses (Kaplan-Meier and log rank tests in SPSS v. 25) were performed. Subsequently, the results were compared with historical cohorts (PubMed, COCHRANE, ScienceDirect, Embase, and the clinical trial registry) who had received platinum-based therapies for advanced NSCLC. Seventeen patients were analysed (11 male and 6 female). Their median age was 67 years (interquartile range, 50-77 years). Fifteen patients (88.2%) were smokers or former smokers. The patients' main histology was adenocarcinoma (9 patients, 52.9%). All first-line treatments applied pembrolizumab (median dose: 12 cycles). Second-line platinum-based therapy achieved OS of 25 months (95% CI: 7-45 months) and progression-free survival (PFS) of 6 months (95% CI: 2.5-95 months). The ORR was 47.1% [seven patients with a partial response (PR) and one patient with a complete response (CR)]. Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed. The one-year survival rate was 58.8%. The historical OS for first-line platinum-based doublets is 7 to 12 months, with PFS of three to five months and an ORR of 17-30%. The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients' platinum response, though future confirmatory studies are necessary.

The interplay of knowledge, motivation, and treatment response in medication adherence among patients with chronic myeloid leukemia treated with Imatinib

Chronic Myeloid Leukemia (CML) requires consistent medication adherence to Imatinib (IM) for optimal outcomes, however, adherence to oral chemotherapy is challenging. This observational study explores the relationship between patient knowledge, motivation, and adherence to IM therapy, and their collective impact on clinical outcomes. A prospective, observational study was conducted with 101 CML patients. The 6-Item Morisky Medication Adherence Scale (MMAS-6) was used to assess adherence, motivation, and knowledge levels. The study found that high motivation was significantly associated with lower BCR-ABL expression (p = 0.025). Patients with high knowledge and motivation had a 71% favorable response rate, compared to 0% in those with low knowledge and motivation (p = 0.01). As conclusion both patient motivation and knowledge are crucial for favorable treatment outcomes in CML. High levels of both significantly correlate with better clinical responses. Tailored interventions to enhance patient knowledge and motivation are essential.

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

Treatment of malignant melanoma with coxsackievirus A21 (V937): An emerging oncolytic virotherapy.

Despite rising melanoma incidence in recent decades, there is a trend towards overall decreased mortality, reflecting multiple factors including improved treatment options for metastatic disease. While local treatments are the mainstay for early-stage melanoma, metastatic disease necessitates systemic treatment, with oncolytic virotherapy emerging as a promising option. For this review, articles were retrieved from PubMed from 1964 through 2024. We conducted title, abstract and full-text screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify articles describing the use of coxsackievirus A21 (V937), either as monotherapy or as part of combination therapy for malignant melanoma. Fifteen articles met inclusion criteria, offering preclinical and clinical data on V937's efficacy in reducing tumour burden. In addition to reporting manageable safety profiles, clinical trial data examining intratumoral V937 combination therapy with pembrolizumab and ipilimumab also endorsed favourable objective response rates compared to immune checkpoint inhibitor monotherapy (47% vs. 38% and 21% vs. 10%, respectively). In contrast, intravenous V937 monotherapy failed to yield additional benefit in a cohort of patients with Stage IIIC/IV melanoma (n = 3) despite achieving detectable levels in tumour tissue (1 × 109 TCID50). Although small subsets of patients experienced severe adverse effects and study design limitations imposed constraints on collected data, evidence for the efficacy of V937 remains encouraging. With few clinical trials evaluating V937 in melanoma, additional data is required before routine usage in standard treatment for metastatic lesions.

Anlotinib reversed resistance to PD-1 inhibitors in recurrent and metastatic head and neck cancers: a real-world retrospective study

Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6–66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3–4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs.

Histopathologic, Molecular, and Clinical Profiling of Lymphoepithelioma-like Carcinoma of the Bladder

Lymphoepithelioma-like carcinoma of the bladder (LELC-B) is a rare histologic subtype characterized by strong immune cell (IC) infiltrates. A better prognosis and favorable response rates to immune checkpoint inhibitors have been described. We aimed to characterize the molecular profiles and IC infiltration of LELC-B for a better understanding of its therapeutic implications. We identified 11 muscle-invasive bladder cancer cases with pure and mixed LELC-B. Programmed cell death ligand-1 (PD-L1) expression and mismatch repair proteins were evaluated using immunohistochemistry. We calculated the tumor mutational burden and characterized mutational profiles using whole-exome DNA sequencing data. Transcriptomic signatures were detected using the NanoString nCounter PanCancer IO360 Panel. Multiplex immunofluorescence of tumor microenvironment (PD-L1, PanCK, α-SMA, vimentin, CD45, and Ki67) and T cells (CD4, CD3, PD-1, CD163, CD8, and FoxP3) was used to quantify cell populations. All LELC-B cases were highly positive for PD-L1 (median tumor proportion score/tumor cell, 70%; range, 20%-100%; median combined positive score, 100; range, 50-100) and mismatch repair proficient and negative for Epstein-Barr virus infection. IC infiltrates were characterized by a high CD8+ T-cell count and high PD-1/PD-L1 expression on immune and tumor cells. LELC-B showed upregulation of signaling pathways involved in IC response. Most common mutations were found in chromatin remodeling genes causing epigenetic dysregulation. All LELC-B cases showed high tumor mutational burden with a median of 39 mutations/Mb (IQR, 29-66 mutations/Mb). In conclusion, LELC-B is a highly immunogenic tumor, showing strong upregulation of PD-1/PD-L1 and making immune checkpoint inhibitors a promising treatment option.

Real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and laboratory parameters in patients across metastatic tumor sites

Objectives: PacliALLTM is the first and only indigenously developed brand of nab-paclitaxel in India that has shown bioequivalence to the global reference (Abraxane®). However, real-world Evidence is scarce about the use of it in different tumor sites beyond approved indications. This study assessed the effects of nab-paclitaxel (PacliALLTM) on clinical outcomes in patients diagnosed with different metastatic cancers in a tertiary care hospital in India. Material and Methods: In this retrospective study, data on demographics, medical history, and laboratory investigations were collected from medical records of patients with metastatic cancer. Patients on nab-paclitaxel were included, and data on laboratory findings, including hematological, liver, and kidney function tests and prognostic outcomes, were evaluated. Results: The study population consisted of 73 patients with metastatic cancer (mean age- 54.6 years). Primary sites of cancer in most patients were the oral cavity (40.8%), followed by breast and ovary (15.3%, each). The Eastern Cooperative Oncology Group score was 0 in 84.3% and 1 in 14.3% of patients. Weekly analyses showed no significant differences in hemoglobin, neutrophil, creatinine, random blood glucose (RBG), and serum glutamic-oxaloacetic transaminase levels. A significant proportion of patients reported anemia and RBG >125 mg/dL at baseline (97.1% and 63.4%, respectively) and week 17 (85.1% and 88.1%, respectively). Most patients had a partial response at week 17 (76.8%), respectively. No serious adverse reactions were reported, requiring a change in treatment. Conclusion: Nab-paclitaxel showed manageable tolerability and favorable response rates in metastatic cancer patients. It is widely used beyond approved indications in a significant proportion of patients across various tumor sites.

A retrospective study of the efficacy of sulbactam in the treatment of patients with extensively drug-resistant Acinetobacter baumannii infections.

Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6g/day), for XDR-AB infection. A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5g per vial. Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported. The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

Treatment of lichen sclerosus with hydroxychloroquine: a Mayo Clinic experience.

There is a dearth of studies investigating the efficacy of hydroxychloroquine in the treatment of either anogenital lichen sclerosus or extragenital lichen sclerosus, a condition that, if left untreated, could lead to a greater degree of scarring and malignant transformation. This study aims to analyze the demographic characteristics, clinicopathological features, treatment response, and outcomes of patients diagnosed with either anogenital or extragenital lichen sclerosus who received hydroxychloroquine therapy. A retrospective analysis was conducted involving 70 patients diagnosed with lichen sclerosus who underwent treatment with hydroxychloroquine at our institution between 2018 and 2023. Among the cohort, 67 patients were female, and 3 were male. Extragenital lichen sclerosus was diagnosed in 23 patients, with 16 exhibiting concomitant morphea overlap. Itching was the predominant clinical presentation (67%). A notable proportion of patients (36%) had a connective tissue disorder, prompting hydroxychloroquine therapy. Among the 30 patients treated solely for lichen sclerosus, 21 demonstrated response and 9 had no response. From a broader comparison of response to hydroxychloroquine, the overall anogenital response rate was 84.6% as opposed to 50% in extragenital lichen sclerosus. The median time to initial response was 4 months. Adverse effects, predominantly mild, were observed in 10 (14.3%) patients. This study is constrained by its retrospective nature and reliance on data from a single center, resulting in a limited sample size. Hydroxychloroquine demonstrates promise as a therapeutic option for anogenital lichen sclerosus because of its favorable response rates and low incidence of adverse effects. However, further investigations, including larger-scale or prospective studies, are imperative to ascertain its definitive efficacy.

Antibody-Drug Conjugates: The New Treatment Approaches for Ovarian Cancer.

Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.

Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis orsteroid-resistant nephrotic syndrome in children after kidney transplantation.

Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

Exploring the safety reporting culture among healthcare practitioners in Saudi hospitals: a comprehensive 2022 national study

BackgroundWith the rise in medical errors, establishing a strong safety culture and an effective incident reporting system is crucial. As part of the Saudi National Health Transformation Vision of 2030, multiple projects have been initiated to periodically assess healthcare quality measures and ensure a commitment to continuous improvement. Among these is the Hospital Survey on Patient Safety Culture National Project (HSPSC), conducted regularly by the Saudi Patient Safety Center (SPSC). However, comprehensive tools for assessing reporting culture are lacking. Addressing this gap can enhance reporting, efficiency, and health safety.ObjectiveThis paper aims to investigate the reporting practices among healthcare professionals (HCPs) in Saudi Arabian hospitals and examine the relationship between reporting culture domains and other variables such as hospital bed capabilities and HCPs’ work positions.MethodsThe study focuses on measuring the reporting culture-related items measures and employs secondary data analysis using information from the Hospital Survey on Patient Safety Culture conducted by the Saudi Center for Patient Safety in 2022, encompassing hospitals throughout Saudi Arabia. Data incorporated seven items in total: four items related to the Response to Error Domain, two related to the Reporting Patient Safety Events Domain, and one associated with the number of events reported in the past 12 months.ResultsThe sample for the analyzed data included 145,657 HCPs from 392 hospitals. The results showed that the average positive response rates for reporting culture-related items were between 50% and 70%. In addition, the research indicated that favorable response rates were relatively higher among managerial and quality/patient safety/risk management staff. In contrast, almost half had not reported any events in the preceding year, and a quarter reported only 1 or 2 events. Pearson correlation analysis demonstrates a strong negative correlation between bed capacity and reporting safety events, response to error, and number of events reported (r = -0.935, -0.920, and − 0.911, respectively; p < 0.05), while a strong positive correlation is observed between reporting safety events and response to error (r = 0.980; p < 0.01).ConclusionsAlmost 75% of the HCPs reported fewer safety events over the last 12 months, indicating an unexpectedly minimal recorded occurrence variance ranging from 0 to 2 incidents.

Comparing the effectiveness of letrozole versus methotrexate for treatment of ectopic pregnancy: A randomized controlled trial

ObjectiveTo evaluate the efficacy of two different regimens of Letrozole, an aromatase inhibitor, in the management of ectopic pregnancy compared to methotrexate. Study DesignThis randomized controlled trial was conducted on 88 women diagnosed with ectopic pregnancy with a baseline level of serum beta-human chorionic gonadotropin under 3000 mIU/mL between June 30, 2023, and December 30, 2023, at the Department of Obstetrics and Gynecology of the Vali-e-Asr Hospital affiliated with Tehran University of Medical Sciences. Participants were allocated into either methotrexate (n = 43), 5-day course Letrozole (n = 24), or 10-day course Letrozole (n = 21) treatments. The methotrexate group received a single dose of 50 mg/m2 dosage intramuscular methotrexate. The 5-day Letrozole group received a 2.5 mg Letrozole tablet three times daily for 5 days, whereas the 10-day Letrozole group received a 2.5 mg Letrozole tablet twice daily for 10 days. The primary outcome was the treatment response, defined as the achievement of a negative serum beta-human chorionic level without the need for additional methotrexate treatment or surgery. The secondary outcomes were the need for additional methotrexate dose or laparoscopic surgery intervention. The trial protocol was prospectively registered in ClinicalTrials.gov with code NCT05918718. ResultsThe treatment response rates in methotrexate, 5-day Letrozole, and 10-day Letrozole groups were 76.7 %, 75.0 %, and 90.5 %, respectively, with no significant differences between the groups (P-value = 0.358). A total of 10 (23.3 %) patients from the methotrexate group, 3 (12.5 %) from the 5-day Letrozole group, and 2 (9.5 %) from the 10-day Letrozole group required an additional methotrexate dose, with no significant differences between the groups (P-value = 0.307). Furthermore, only 3 (12.5 %) patients, all from the 5-day Letrozole group, were suspected of tubal rupture and underwent surgery (P-value = 0.016). ConclusionOur findings suggest Letrozole as a safe alternative to methotrexate in treating stable ectopic pregnancies, with a favorable treatment response rate. However, there is still a need for future larger studies to determine the applicability of Letrozole in the EP management. Also, the non-significant higher effectiveness of the 10-day Letrozole regimen than the 5-day Letrozole group underscores the need for future research to determine the optimal Letrozole regimen for the management of ectopic pregnancy.

Weekly paclitaxel (P), carboplatin (CP) plus pembrolizumab (PMB) as first-line treatment of recurrent or metastatic (R/M) or locally very advanced (LVA) head and neck squamous cell carcinoma (HNSCC): A retrospective study in 39 patients (pts).

e18018 Background: Since the results of the KN-048 trial, the combination of platinum/5FU plus PMB has become the standard of care (SOC) for R/M HNSCC pts. The KN-B10 study shows that 5FU can be replaced by P with a favorable response rate and toxicity profile. Weekly use of P reduces hematologic toxicity and increases dose-intensity. Methods: We retrospectively reviewed all records of patients with R/M or LVA (T4b and/or N3b) HNSCC, ECOG-PS 0 to 2, PDL1 CPS ≥ 1, treated in first-line with weekly P (80 mg/m2) and CP (AUC 2: maximum total dose of 250 mg and systematic G-CSF at D3 and D4) for up to 12 infusions plus PMB every 3 weeks for up to 35 administrations. Results: From July 2020 to April 2023, 39 pts (median age 63 years, 74% male, 18% PS2) were treated. Primary tumors: oropharynx 44%, larynx 23%, hypopharynx 18% and oral cavity 15%. Disease setting: LVA 20%, local recurrence in irradiated area 54%, local recurrence and distant metastases 10% distant metastases only15%. With a median follow-up of 19 months (m), median Overall Survival (mOS) was 17.2 m (95%CI: 10.8-NR). 31/39 (79%) pts achieved an objective response (OR): 7 CR and 24 PR. For the 8 LVA pts, all achieved an OR, with a median Event Free Survival of 10 m (95%CI: 6.27-NR): the 4 progression-free pts (8.6 m+ to 25 m+) were treated with radiotherapy after neoadjuvant immuno-chemotherapy. For the 31 R/M pts, ECOG-PS was a significant prognostic factor of OS, mOS: 19.3 m (95%CI: 14.4-NR) for ECOG-PS 0-1 pts vs. 10.3 m (95%CI: 5.4-13.9) for ECOG-PS 2 pts (p = 0.02). For R/M pts, median Progression Free survival was 6.9 m (95%CI: 4.4-8.6) and the ORR was 74%, with a median duration of response of 6.5 m (95%CI: 3.13-8.56). Toxicity was manageable, with 20 (51%) pts experiencing at least one grade 3-4 adverse event: hematologic 18% (including one febrile neutropenia), infection 5%, neuropathy 8%, diarrhea 8%, infusion reaction 8%, electrolyte disturbances 8%, renal failure 3% and no toxic deaths. Conclusions: The combination of weekly P and CP plus PMB produces a high ORR and increased OS consistent with the results of the Frail-Immune study (J. Fayette ASCO 2023). This regimen deserves further consideration not only in the R/M setting, but also in the neoadjuvant setting for locally advanced patients.

A phase II trial of neoadjuvant nivolumab, docetaxel, and cisplatin followed by surgery and radiation therapy for resectable high-grade salivary gland carcinoma.

e18061 Background: High-grade resectable salivary gland carcinomas, typically treated with surgery and adjuvant therapies, often recur. This study explores combining an immune checkpoint inhibitor (ICI) with chemotherapy as neoadjuvant therapy to improve outcomes in high-risk, operable cases. Methods: This trial enrolled high-grade SGC patients with clinically positive lymph nodes. Participants received three cycles of nivolumab in conjunction with docetaxel and cisplatin every three weeks. The primary response was assessed three weeks post-treatment, and surgery followed at seven weeks in cases deemed operable. The pathologic outcomes determined the need for adjuvant radiotherapy, administered at 59.4Gy (R0) or 66.0Gy (R1 or R2). The study's primary endpoint was the major pathologic response rate (MPR). We aimed to recruit 50 patients. Herein, we present an interim analysis (NCT05727410). Results: Since November 2022, 19 patients have enrolled; predominantly male (89.5%) with a median age of 62 (range 42-75). Histologic analysis identified various subtypes, primarily salivary duct carcinoma (68.4%). Other histologies included high-grade adenocarcinoma (10.5%), mucoepidermoid carcinoma (10.5%), basaloid squamous cell carcinoma (5.3%), and secretary carcinoma (5.3%). At the time point of analysis, surgery was performed on 16 patients, and 3 patients are still under neoadjuvant therapy. Complete resection (R0) was achieved in 87.5% (n=14) of the cases, with one patient having R1 and another R2 resection. Pathologic analysis showed 12.5% (n=2) achieving pathological complete response and 18.8% (n=3) achieving MPR. Tumor viability varied, with 37.5% (n=6) presenting with 10% to 50% viability and 31.3% (n=5) presenting with 50% or higher viability. A patient with salivary duct carcinoma histology with tumor viability of 20% after neoadjuvant treatment experienced recurrence after 4.1 months from surgery. Notably, throughout the neoadjuvant treatment phase, no patients discontinued due to toxicity or intolerance, indicating a favorable tolerance profile for the combination therapy. An ongoing exploratory biomarker study includes PD-L1 expression and genomic profiling. Conclusions: The preliminary findings of this study demonstrate that the neoadjuvant combination of immune checkpoint inhibitor with chemotherapy significantly reduces tumor burden in salivary gland carcinoma, as evidenced by the high rate of complete resections (R0) and favorable pathologic responses. This treatment strategy not only facilitates surgical outcomes but also exhibits an acceptable safety profile, with no instances of treatment discontinuation due to toxicity or intolerance. These promising results underscore the potential of ICI combination therapy in the management of SGC and warrant further detailed investigations. Clinical trial information: NCT05727410 .

Interleukin-6 receptor blockade with tocilizumab to reduce immune-related toxicity with ipilimumab and nivolumab in metastatic melanoma.

9538 Background: Interleukin-6(IL-6) blockade has reversed steroid-refractory immune-related toxicity in patients receiving immune checkpoint blockade (ICB). IL-6 and its downstream acute phase reactants are also associated with short survival and therapeutic resistance in patients receiving single agent or combination ICB. We undertook a phase II trial of IPI, NIVO and the IL-6 receptor blocking antibody tocilizumab (TOCI) in unresectable melanoma. Methods: In a phase II, Simon-design two-stage trial, 70 patients with untreated metastatic melanoma received IPI at 1 mg/kg and NIVO at 3 mg/kg for 4 induction doses to week 12, and TOCI at 4 mg/kg every 6 weeks up to week 24. Maintenance NIVO was administered at 240 mg intravenously (IV) from weeks 12 to 24, then at a dose of 480 mg IV every 4 weeks for up to 2 years of treatment. To proceed past the first stage of 18 patients, 12/18 RECIST responses or more and/or a grade 3-5 treatment related immune-related adverse event (irAE) rate of ≤5/18 were required. Those criteria were both fulfilled, and in the second stage 49 patients were treated, with 3 additional patients accrued. Serum and peripheral blood samples were collected for biomarker assays at baseline and week 7. Results: There were 40/70 RECIST responders with a 57% best overall response rate (BORR), (exact 95% confidence interval (CI) of 44-68%) of partial response (PR) or complete response (CR); 6 patients had stable disease (SD), 24 with progression, at a median of 2.4 years of follow-up. A total of 46 patients had clinical benefit (CR+PR+SD) = 65% (exact 95% CI 37-81%). Median progression-free survival was 13 months. The expected BORR was 47% in the randomized Checkmate-511 trial at the same doses of IPI/NIVO. There have been 16 cases of grades 3-4 irAE including 3 episodes of colitis for a total of 16/71 patients eligible for toxicity = 22% (exact 95% CI: 12-31%), all grade 3/4; the expected rate of grades 3-5 TRAEs was 34% per Checkmate-511. The rate of irAE leading to discontinuation was 14%; it was 25% for CheckMate 511. Twenty-one deaths (30%) occurred, all due to progression. All grade 3-4 irAES were reversible and no grade 5 toxicity was seen. Osteopontin+IL6+CD45RAnegclassical monocytes were associated with response, and higher levels of naive CD8 T cells were associated with progression. CD16+CD56+CD57+ mature natural killer cells were significantly lower in patients with grade 3-4 immune-related toxicity. Conclusions: Prophylactic TOCI resulted in a low rate of grade 3-4 irAEs by week 24 in patients with stage IV melanoma receiving induction IPI 1 mg/kg and NIVO 3 mg/kg while maintaining a favorable overall response rate and survival. Novel biomarkers of response and toxicity including NK cells and monocytes as well as naïve and effector memory CD8 T cells were defined by high-resolution flow cytometry. Additional correlative data will be presented. Clinical trial information: NCT03999749 .

Abstract PO1-02-07: HER2 Low Non-Metastatic Breast Cancer in Qatar: A Nationwide Retrospective Cohort Study to Evaluate the Response to Neoadjuvant Chemotherapy: A Real-World Analysis

Abstract Background: Breast Cancer is the most diagnosed cancer type worldwide and the second leading cause of cancer-related death among women. HER2-low breast cancer is a newly defined molecular subtype of breast cancer in which tumors exhibit a minimal overexpression of HER2 or no gene amplification. To illustrate, HER2-low tumors typically have an IHC score of 1+ or a score of 2+ with negative amplification. However, emerging evidence suggests that even a minimal amplification of HER2 may significantly impact the response to therapy and prognosis. Our study aims to unveil the impact of HER2-low expression on the response to anthracycline and taxane-based neoadjuvant chemotherapy (NACT) in comparison to the HER2-negative group in non-metastatic breast cancer. The primary objective was evaluating the response to NACT comparing the favorable response (complete and partial response) in each of the two groups of HER2-low and HER2-negative patients. Methods: This is a retrospective cohort study. All patients’ profiles with non-metastatic, HER2-Low, and HER2-negative breast cancers who received neo-adjuvant chemotherapy and underwent surgery between the 1st of January 2018 and the 30th of August 2022 were included. Patients' response was evaluated using surgical pathology reports to compare the two study groups (HER2-low and HER2-negative). Results: The total number of patients included was 262 patients, the majority were HER2-low 89% (233/262) vs. 11% (29/262) HER2-negative. A favorable response to NACT was shown in 71% (185/262) of all patients. The favorable response rate was similar in both groups, 70% (164/233) in the HER2-low group vs. 72% (21/29) in the HER2-negative group, OR: 1 (95% CI: 0.8-1), p-value 0.8. Similarly, the pathological complete response (pCR) rate was the same in both study groups at 14%, OR: 0.7 (95% CI: 0.2-3), p-value: 0.6. Interestingly, patients with hormone-positive tumors across both study groups had a higher response rate as compared to hormone-negative patients. However, statistical significance was shown in the HER2-low group only. In the HER2-low cohort, 73% of the patients (119/164) with hormone-positive tumors showed a favorable response OR: 0.8 (95% CI: 0.8- 1), p-value: 0.001. Comparatively, in the HER2-negative cohort, 52% of the patients (11/21) with hormone-positive tumors had a favorable response OR: 2 (95% CI: 1– 5), p-value: 0.05. Conclusion: Our results did not show any significant impact of HER2-low expression on neoadjuvant chemotherapy response. Nonetheless, a statistically significant difference in response was observed in the hormone-positive HER2-low breast cancer patients. Further studies are needed to evaluate the influence of hormonal expression on the response rate to NACT in the HER2-low patient population. Citation Format: Ahmed Kardousha, Wafaa Shehada, Ahmed Basha, Sahar Nasser, Mufid el Mistiri, Anas Hamad, Salha Al-Bader, Shereen Elazzazy. HER2 Low Non-Metastatic Breast Cancer in Qatar: A Nationwide Retrospective Cohort Study to Evaluate the Response to Neoadjuvant Chemotherapy: A Real-World Analysis [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 PO1-02-07.

Exploration of prognostic and treatment markers in hepatocellular carcinoma via GPCR-related genes analysis

BackgroundG protein-coupled receptors (GPCRs), the biggest family of signaling receptors, account for 34 % of all the drug targets approved by the Food and Drug Administration (FDA). It has been gradually recognized that GPCRs are of significance for tumorigenesis, but in-depth studies are still required to explore specific mechanisms. In this study, the role of GPCRs in hepatocellular carcinoma (HCC) was elucidated, and GPCR-related genes were employed for building a risk-score model for the prognosis and treatment efficacy prediction of HCC patients. MethodsPatients’ data on HCC were sourced from the Liver Hepatocellular Carcinoma-Japan (LIRI-JP) and The Cancer Genome Atlas (TCGA) databases, while GPCR-related genes were obtained from the Molecular Signatures Database (MSigDB). Univariant and multivariant Cox regression analyses, as well as least absolute shrinkage and selection operator (LASSO) were performed with the aim of identifying differentially expressed GPCR-related genes and grouping patients. Differential expression and functional enrichment analyses were performed; protein-protein interaction (PPI) mechanisms were explored; hub genes and micro ribonucleic acid (miRNA)-target gene regulatory networks were constructed. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to evaluate immune infiltration levels and genetic variations. Sensitivity to immunotherapy and common antitumor drugs was predicted via the database Genomics of Drug Sensitivity in Cancer (GDSC). ResultsA GPCR-related risk score containing eight GPCR-related genes (atypical chemokine receptor 3 (ACKR3), C–C chemokine receptor type 3 (CCR3), CCR7, frizzled homolog 5 (FZD5), metabotropic glutamate receptor 8 (GRM8), hydroxycarboxylic acid receptor 1 (HCAR1), 5-hydroxytryptamine receptor 5A (HTR5A) and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6)) was set up. In addition, patients were classified into groups with high and low risks. Patients in the high-risk group exhibited a worse prognosis but demonstrated a more favorable immunotherapy response rate compared with those in the low-risk group. Distinct sensitivity to chemotherapeutic drugs was observed. A clinical prediction model on the basis of GPCR-related risk scores was constructed. Areas under the curves (AUC) corresponding to one-, three- and five-year survival were 0.731, 0.765 and 0.731, respectively. ConclusionsIn this study, an efficient HCC prognostic prediction model was constructed by only GPCR-related genes, which are all potential targets for HCC treatment.