Predictive Factors Of Response Research Articles

Non-Small Cell Lung Cancer Metastatic Without Oncogenic Alterations.

This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non-small cell lung cancer. We also address pertinent clinical decision-making queries encountered in everyday practice, such as the optimal treatment strategy for PD-L1-high patients, predictive factors for response to immune checkpoint inhibitors (ICI) both in terms of patient and cancer characteristics, the potential benefits of dual checkpoint blockade, and the unresolved issue of safe discontinuation strategies for long-term responders. Around one in five patients falls into this latter category while the majority develop either primary or acquired resistance to ICI-based first-line therapy, necessitating effective subsequent lines of treatment. Docetaxel, with or without combination of antiangiogenic agents, serves as the backbone of treatment, although evidence in the post-ICI setting is limited. Given that an inflamed tumor microenvironment (TME) is crucial for ICI responses, targeting the TME in cases of acquired resistance alongside continued ICI administration appears rational, although clinical trials so far have failed to confirm this hypothesis. Antibody-drug conjugates have emerged as a promising treatment modality, offering the potential for reduced toxicity and improved efficacy by targeting specific cancer antigens. Moreover, several chemotherapy-free approaches are currently under investigation for treatment-naïve patients, including alternative ICI and drugs targeting epitopes on both cancer and immune cells.

Treatment outcomes and adherence to treatment in patients with immune thrombocytopenia in two Ethiopian teaching hospitals: a retrospective cohort study

The treatment of immune thrombocytopenia (ITP) is challenging and treatment outcomes depend on numerous unknown and patient-specific factors. Corticosteroids are the cornerstone of ITP treatment, but they are associated with many side effects. In this retrospective cohort study, treatment outcomes and treatment adherence in patients with ITP were investigated in 214 ITP patients from November 15, 2022 to March 15, 2023. Multinomial regression analysis models were used to identify predictive factors for treatment outcomes. A p value of less than 0.05 was considered statistically significant. Most study participants were female 161 (75.5%), and the majority 172 (80.4%) of them were taking prednisolone only. In terms of treatment adherence, 178 (83.2%) of the study participants adhered well to their ITP medications. The complete response rate at 3 months was 139 (65.0%). Predictive factors for partial response were increased negative impact of ITP on health-related quality of life (AOR = 1.221, 95% CI 1.096–1.360), being treated at Tikur Abessa Sepcialazed Hospital (AOR = 0.431, 95% CI 0.197–0.941) and the presence of heavy menstrual bleeding (AOR = 2.255, 95% CI 0.925–5.497) compared to patients with complete response. Hepatitis B virus-infected ITP patients (AOR = 0.052, 95% CI 0.004–0.621) were also a predictive factor for no response compared to complete response.

QRS length/left ventricular mass index: a novel predictive factor of response to cardiac resynchronization therapy

Abstract Introduction The length of QRS interval is an extensively studied predictor of response to CRT. There is little evidence of the probability of response in patients with QRS between 130 and 150 ms and its relationship with LV mass. (1,2) Objective Evaluation of the QRS length/LV mass index (QRS/LVMi) as a "relative dyssynchrony" marker and its correlation to response after CRT implantation. Methods Retrospective study that included patients over 18 years of age with HFrEF (LVEF ≤ 35%) and CRT implantation between years 2018 – 2022 (n = 92). QRS length (ms) was measured with CardioLab 3.0 Software and divided by LV mass (g), according to Deveraux equation using echocardiography measurements. Primary outcome was response to CRT defined by: Improvement of at least 1-point in NYHA functional class + (i) increase of at least 5% in LVEF or (ii) decrease of at least 15% in LVESD. Results QRS/LVMi value ≥ 0.6 was associated with a higher frequency of response to CRT than values < 0.6 (83% responders vs 17% non responders; OR 5.1; CI 2.7–12.1, p < 0.05). There was no difference in response to CRT between QRS > 150 ms and 130 – 150 ms in patients with QRS/LVMi ≥ 0.6 (80% vs 82% of responders, p = 0.8). A multivariate analysis showed a significantly higher probability of response to CRT in patients with QRS/LVMi ≥ 0.6 compared to other known predictive factors (OR 4.1; CI 1.2–12, p < 0.05). Conclusions The use of QRS/LVMi was associated with a better prediction of response to CRT than other traditional factors. There was no difference in response between QRS > 150 ms and 130 - 150 ms in patients with QRS/LVMi ≥ 0.6, suggesting the efficacy of CRT in patients with shorter QRS interval length and less LV mass, highlighting the importance of the concept of relative dyssynchrony.Total Response according QRS/LMViMultivariate analysis

#622 Baseline inflammatory indexes and clinicopathological features to predict the outcome of acute interstitial nephritis

Abstract Backgrounds-and-aims Acute tubulointerstitial nephritis(AIN) is a rare cause of acute kidney injury(AKI). We aimed to investigate the characteristics of AIN patients and predictive factors for treatment response. Method 31 patients diagnosed with AIN by biopsy between 2006-2021 were included in this retrospective study. Baseline clinical, pathological, and laboratory findings, including CBC(complete blood count), creatinine, serum-immune-inflammation-index(SII), neutrophil-to-lymphocyte ratio(NLR), and platelet-to-lymphocyte ratio(PLR) were evaluated. Also, treatment response and creatinine levels at the last follow-up were noted. Results Median age was 46 years, and 80.6% of the patients were female. Median baseline creatinine and proteinuria levels were 4.1 mg/dL and 0.84 g/g or g/day. Median follow-up was 14 months. 93.5% of patients received immunosuppressives. End-stage-kidney-disease(ESKD) developed in five patients. Renal recovery(creatinine < 1.4 mg/dL) was observed in 17 (54.8%) patients. Global glomerulosclerosis percentage, interstitial fibrosis(IF), tubular atrophy(TA), granuloma formation, and higher baseline hemoglobin levels were associated with poor renal outcomes(non-responder). Also, ESKD-developed patients had higher baseline hemoglobin(p = 0.033) and lymphocyte(p = 0.044) and lower PLR levels(p = 0.016), as well as higher degrees of global glomerulosclerosis(p = 0.014), IF(p = 0.042), and TA(p = 0.030). Conclusion Treatment rates are low for AIN, which may lead to ESKD. Besides chronicity in pathology specimens, higher baseline hemoglobin levels and lower PLR might be prognostic for AIN. Further studies should be conducted on new markers for AIN.

Endocrine therapy in advanced high-grade ovarian cancer: real-life data from a multicenter study and a review of the literature.

In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor prognosis. When platinum resistant, subsequent lines of chemotherapy are of limited effect and often poorly tolerated, leading to quality of life deterioration. Various studies suggest a hormonal role in ovarian carcinogenesis, with a rationale for endocrine therapy in these cancers. This multicenter, retrospective study assessed the use of endocrine treatment for high-grade ovarian epithelial carcinomas treated between 2010 and 2020. Eighty-one patients with ovarian cancers were included. The median duration of platinum sensitivity was 29 months. We observed a 35% disease control rate with endocrine therapy, and 10% reported symptom improvement. For 19 patients (23.5%), the disease was stabilized for more than 6 months. Median overall survival from diagnosis was 62.6 months. Regarding endocrine therapy predictive factors of response, in a multivariate analysis, 3 factors were statistically significant in favoring progression-free survival: platinum sensitivity (P = .021), an R0 surgical resection (P = .020), and the indication for hormone therapy being maintenance therapy (P = .002). This study shows real-life data on endocrine therapy in ovarian cancer. As it is a low-cost treatment with many advantages such as its oral administration and its safety, it may be an option to consider. A perspective lies in the search for cofactors to aim as future therapeutic targets to improve the effectiveness of hormone treatment by means of combination therapy.

Medical treatment of functional pituitary adenomas, trials and tribulations.

Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very rare. Despite their benign histological nature (aggressive tumors are rare and malignant ones exceptional), FPAs could cause significant morbidity and increased mortality due to complications associated with hormonal excess syndromes and/or mass effect leading to compression of adjacent structures. This mini review will focus on the increasing role of medical therapy in the multimodal treatment, which also includes transsphenoidal surgery (TSS) and radiotherapy. Most patients with prolactinomas are treated only with medications, but surgery could be considered for some patients in a specialized pituitary center, if higher chances of cure. Dopamine agonists, especially cabergoline, are efficient in reducing tumor size and normalizing prolactin. TSS is the first-line treatment for all other FPAs, but most patients require complex adjuvant treatment, including a combination of therapeutic approaches. Medical therapy is the cornerstone of treatment in all patients after unsuccessful surgery or when surgery cannot be offered and includes somatostatin receptor ligands and dopamine agonists (almost all FPAs), growth hormone receptor antagonists (acromegaly), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers (Cushing's disease). Novel medical treatments, especially for acromegaly and Cushing's disease are under research. An enlarged panel of effective drugs available with increased knowledge of predictive factors for response and/or adverse effects will enhance the possibility to offer a more individualized treatment. This would not only improve disease control and prognosis, but also quality of life.

Chemical Investigation on the Volatile Part of the CO2 Supercritical Fluid Extract of Infected Aquilaria sinensis (Chinese Agarwood).

This work is focused on the characterization of the composition of a CO2 supercritical fluid extract of Aquilaria sinensis (Chinese agarwood) collected in the Dongguan area (China) and infected by mechanical methods. The constituents of this extract were analyzed by gas chromatography-mass spectrometry (GC-MS) and quantified accurately by gas chromatography with a flame ionization detector (GC-FID), using an internal reference and predicted response factors. Since a significant number of components of this extract remained non-identified after the initial GC-MS analysis of the whole extract, its fractionation by chromatography on silica gel helped to characterize several additional constituents by isolation and structural analysis by NMR spectroscopy. The main components are the classical agarwood chromones (Flindersia chromone and its mono-, di-, and trimethoxylated analogues (respectively, 11.01% and 0.11-4.02%) along with sesquiterpenic constituents typically found in agarwood essential oils, like baimuxinal (1.90%) and kusunol (1.24%), as well as less common selinane dialdehydes (1.58-2.27%) recently described in the literature. Moreover, the structure and stereochemistry of a new sesquiterpenic alcohol, 14β,15β-dimethyl-7αH-eremophila-9,11-dien-8β-ol (0.67%), was determined unambiguously by the combination of structural analysis (NMR, MS), hemisynthesis, and total synthesis, leading to dihydrokaranone and a neopetasane epimer.

Prediction model for treatment response of primary membranous nephropathy with nephrotic syndrome.

To investigate the predictors and establish a nomogram model for the prediction of the response to treatment in primary membranous nephropathy (PMN) with nephrotic syndrome (NS). The clinical, laboratory, pathological and follow-up data ofpatients withbiopsy-proven membranous nephropathy at the Affiliated Hospital of QingdaoUniversity were collected. A total of 373 patients were randomly assigned into development group (n = 262) and validation group (n = 111). Logistic regression analysis was performed in the development group to determine the predictors of treatment response. A nomogram model was established based on the multivariate logistic regression analysis and validated in the validation group. The C-index and calibration plots were used for the evaluation of the discrimination and calibration performance, respectively. Serum albumin levels (OR = 1.151, 95% CI 1.078-1.229, P < 0.001) and glomerular C3 deposition (OR = 0.407, 95% CI 0.213-0.775, P = 0.004) were identified as independent predictive factors for treatment response in PMN with NS, then a nomogram was established combining the above indicators and treatment regimen. The C-indices of this model were 0.718 (95% CI 0.654-0.782) and 0.789 (95% CI 0.705-0.873) in the development and validation groups, respectively. The calibration plots showed that the predicted probabilities of the model were consistent with the actual probabilities (P > 0.05), which indicated favorable performance of this model in predicting the treatment response probability. Serum albumin levels and glomerular C3 deposition were predictors for treatment response of PMN with NS. A novel nomogram model with good discrimination and calibration was constructed to predict treatment response probability at an early stage.

Abstract PO5-02-02: LyKi1: a highly predictive immune-based score of pathological response to chemotherapy in luminal breast cancer

Abstract Background: Identifying which luminal breast cancer (BC) patients will benefit from (neo)adjuvant chemotherapy still remains a challenge. Efficient predictive tests and genomic signatures are still lacking. Because neoadjuvant chemotherapy (NACT) constitutes an in vivo chemotherapy-sensitivity test, we used the pre-treatment core biopsies to identify predictive factors of pathological response in luminal HR+/Her2- BC. Analyses on sTILS and TIL subtypes (CD3, CD4, CD8, CD20) are rare in luminal BC while a predictive value has been reported in TNBC and Her-2 positive BC. Patients and Methods: We performed a retrospective analysis of 211 patients treated with NACT followed by surgery for a T0-T4 luminal (HR+/Her-2-) breast cancer. Association of anthracyclin and taxane was used in 99% of cases. Median age was 48.4 yo (28 – 76). Initial clinical stage was: I: 0.5%, II: 67%; III: 33%. Biopsy analyses were the followings: NST carcinomas: 90%; luminal B: 82%; E&amp;E grade I/II/III: 10%/57%/32%; KI-67 &amp;gt; 20%: 74%. After NACT, RCB 0-1 was observed in 32 cases (15.2%) and pCR in 19 (9.0 %) cases. All pre-therapeutic biopsies were reviewed for pathological factors, blinded to the patients’ outcomes. Clinico-pathological analyses were performed using standard methods. sTILs were estimated on H&amp;E slides. Intratumoral CD3, CD4, CD8 and CD20 infiltrates were carried out by an independent laboratory using a machine learning model for automated and quantitative evaluation based on digital IHC stains. Correlation between sTILs and TIL subtypes were assessed by Spearman’s coefficient. Predictive factors of RCB 0/1 were explored using unconditional logistic regression analysis. After selection on univariate analysis (p&amp;lt; 0.05), multivariate prognostic models were developed using stepwise backward variable elimination process and compared using area under the curve (AUC). Results: sTILs levels ≥ 10% were observed in 15.2% of biopsies. 42 % of tumors had ≥ 10 % CD3-positive cells, 46% for CD4, 38% for CD8, and 8% for CD20. A high level of correlation was observed between these different markers (Spearman’s coefficient ≥ 0.73 for each comparison). By univariate analysis, significant factors (p&amp;lt; 0.05) associated with RCB 0-1 were: age, mitotic index (1 vs 2 vs 3), aneuploidy (1-2 vs 3), differentiation (1-2 vs 3), E&amp;E grade (1-2 vs 3), mitotic count, Ki-67, Magee equation 3, phenotypic group (luminal A vs B), ER, sTILs and each TIL subtype. Age, E&amp;E grade, Ki-67, Magee equation 3, sTILs and all TIL subtypes were selected for multivariate analysis. As TIL subtypes were highly correlated, different predictive models could be performed. The model we selected (called LyKi1) was constructed based on CD8 [OR 2.24 (95%CI 1.55-3.25; p&amp;lt; 10-4)], E&amp;E grade [OR 3.00 (95%CI 1.22-7.42; p=0.017)] and Ki-67 [OR 1.74 (95%CI 1.09-2.76; p=0.019)]. It was highly significantly associated with RCB 0-1, with an AUC value of 0.856 (95%CI 0.756-0.916). For instance, LyKi1 could isolate a group of 30% of patients that achieved RCB 0-1 in 39.7% of cases vs 4.7% for the 70% of patients with lowest LyKi1 scores. pCR rates were 25% and 2%, respectively. Importantly, prediction value of LyKi1 remained very high if restricted to luminal B tumors (AUC 0.817; 95% CI: 0.741-0.894). Ability to predict pCR was also very high (AUC 0.837 (95%CI: 0.750-0.924) in this phenotype). Conclusion: This retrospective analysis clearly highlights the important predictive role of sTILs and TIL subpopulations for the response to an anthracyclin-taxane based regimen in a neoadjuvant setting for luminal breast cancer. Within this cohort, LyKi1 score (combining CD8, grade and Ki-67) has a very high value to predict pathological response to NACT in luminal breast cancer. Importantly, such score has to be validated in a multicentric prospective cohort and investigated in adjuvant setting. Citation Format: Marc Debled, Hugo Deboissy, Coralie Cantarel, Chloé Delfour, Léonie Alran, Marion Fournier, Nathalie Quenel-Tueux, Valérie Velasco, Foucault Chammings, Véronique Brouste, Monica Arnedos, Gaétan MacGrogan. LyKi1: a highly predictive immune-based score of pathological response to chemotherapy in luminal 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 PO5-02-02.

Abstract PO3-15-02: TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY

Abstract Introduction: Breast cancer is one of the most prevalent in women in the world and has shown extensive changes in treatment in recent decades. More patients are undergoing neoadjuvant chemotherapy in order to achieve pathological complete response (CPR) and perform less aggressive surgeries. CPR increases overall and disease-free survival and the decrease in tumor size increases the chances of conservative surgery. We have numerous studies that propose to discover CPR markers. Predictive factors of response to chemotherapy are important for treatment planning and the P53 gene, apoptosis-inducing gene, plays a role in inducing response to chemotherapy drugs that act by inducing apoptosis. The presence of mutations and genetic polymorphisms act by modulating this response. Among these, the codon 72 polymorphism is one of the most studied, as its polymorphic variants Arg/Arg, Arg/Pro and Pro/Pro encode a p53 with different functioning at the cell level. So, individuals with different polymorphisms will have different apoptotic action and different response to chemotherapy treatments. Objectives: Based on this knowledge, the study sought to correlate the polymorphism variants at codon 72 with the complete pathological response to neoadjuvant chemotherapy. Casuistic and Methods: The study was carried out at an oncology center in the state of Sergipe, in northeastern Brazil. A total of 206 patients with breast cancer who underwent neoadjuvant chemotherapy and core needle biopsy of the breast at the beginning of treatment were included in the stud,in the period from 2019 to 2022. From these patients, oral swab samples were collected for PCR evaluation of the P53 polymorphism at codon 72. The polymorphisms were studied using the Sanger technique at the Sao Paulo School of Medicine of the Federal University of São Paulo (UNIFESP). Patients were prospectively evaluated after surgery to verify the surgical pathological response after chemotherapy. Pathologic response was assessed using the RECIST criteria. The study was evaluated and approved by the ethics and research committee of UNIFESP and all patients signed an informed consent form. Results: Of the 206, 18.4% met the exclusion criteria (did not undergo surgery, interrupted chemotherapy treatment, insufficient genetic material in the swab, loss of follow-up). Of the 168 patients analyzed, 44.6% were Arg/Arg, 17.3% Pro/Pro and 38.0% Arg/Pro. Complete pathological response (PCR) was obtained in 21.4% of the patients, 10.1% had progressive disease (PD), 13.7% had stable disease (SD) and 54.2% had partial pathological response (PPR). Of the patients who achieved RPC, 47.2% were Arg/Arg, 38.9% Arg/Pro and 13.9% Pro/Pro without statistical significance, among the variants of polymorphisms. The only predictor of CPR in multivariate regression was immunohistochemistry (p&amp;lt; 0.001). The only predictor of CPR in multivariate regression was immunohistochemistry (p&amp;lt; 0.001) Conclusion: The P53 polymorphism at codon 72 is not a predictor of complete pathological response, but the Arg/Pro and Pro/Pro polymorphisms increase the chances of stable disease after neoadjuvant chemotherapy. Citation Format: Jussane Vieira, Afonso Nazário, João Pesquero. TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY [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 PO3-15-02.

Abstract PO4-04-10: Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 trial

Abstract BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard of care for hormone receptor-positive (HR+)/Human Epidermal Growth Factor 2 negative (HER2-) metastatic breast cancer (MBC); no consensus actually exists for second-line (2L) treatments. The HERMIONE-13 trial evaluates the adopted therapeutic options after CDK4/6i failure and the potential factors that influence these choices. METHODS: HERMIONE-13 is a retrospective and prospective multicentric observational trial involving 15 Italian Centers. Information about therapies after disease progression to CDK4/6i from January 2016 until December 2020 was collected for the present analysis, aiming at evaluating which are the clinical criteria guiding the choice of 2L therapy after CDK4/6i failure. RESULTS: 114 pts have been enrolled: 14 pts (12.3%) received neoadjuvant treatment, 80 (70.2%) adjuvant therapy, of whom 46 (57.5%) chemotherapy (CT)+ endocrine therapy (ET) and 33 (41.3%) ET alone. Among the 79 pts treated with adjuvant ET, 44 pts (55.7%) showed primary or secondary endocrine resistance. 39 pts (34.2%) received first-line (1L) CDK 4/6i in combination with Fulvestrant (F), the remaining with aromatase inhibitors (AIs). Median duration of 1L CDK4-6i was 10.4 months (interquartile range (IQR) 4.7-17.4). Median age at 2L start was 59.5 years (IQR 51-68). As 2L therapy, 79 pts (69.3%) received CT±targeted therapy (TT) and 35 (30.7%) ET±TT. Visceral metastases at the beginning of 2L were documented in 46 pts (40.4%). Comorbidities were present in 48 (42.9%) of the pts, mainly cardiac diseases (25, 22.3%); 71 pts (63.4%) showed a 1L-related adverse events (AEs) (NA: 2 pts), mainly hematological toxicity (60, 53.6%). Among 79 pts treated with adjuvant ET, 60 (76%) were addressed to 2L CT±TT, while 19 (24%) to an ET-based therapy. A longer duration of 1L was observed in pts treated with 2L ET±TT (12.5 months, 7.2-22.2) in comparison with those treated with CT±TT (8.7 months, 4.2-14.9). The majority of pts treated with 1L F+CDK 4/6i underwent 2L CT-based treatment, as summarized in Table 1. Analyzing the population treated with 2L CT±TT, we observed that median age was 58 years (49-67), slightly lower than that of pts treated with ET±TT (63, 54-69). Among pts with visceral metastases, 30 pts (65.2%) were addressed to 2L CT±TT and 16 pts (34.8%) to ET±TT; CT±TT was also the favorite choice for the majority of pts with concomitant disease (33, 68.8%) and with previous CDK4/6i-related toxicity (47, 66.2%). Among age, visceral metastases, comorbidities, adjuvant treatment, duration of 1L therapy, use of 1L F and 1L related AEs, univariate analysis revealed that previous use of adjuvant ET (p=0.021), 1L F (p&amp;lt; 0.001), duration of 1L treatment (p=0.043) and age at 2L start (p=0.053) are all factors influencing the choice of 2L therapy. At the multivariate logistic regression model, only the use of F in association with CDK4/6i as 1L treatment and age at 2L therapy were associated with the choice between ET±TT vs CT± TT, with a backward selection, as summarized in table 2. CONCLUSION: The preliminary results of our study suggest that previous F in combination with CDK4/6i is a statistically confirmed predictor of choice for subsequent CT, whereas the increase in age is significantly associated with the choice for ET. Further research is needed to investigate the optimal sequencing of treatments following CDK4/6i and to determine predictive factors of response to 2L therapies. Table 1 2L choices in 1L F+CDK 4/6i pts. Table 2 Statistical model with the significant variables. Citation Format: Marina Elena Cazzaniga, Emanuela Rossi, Antonella Turla, Massimo Ambroggi, Alice Baggi, Rossana Berardi, Fulvio Borella, Serena Capici, Federica Cicchiello, Luigi Coltelli, Ugo De Giorgi, Antonella Ferro, Ornella Garrone, Monica Giordano, Elisabetta Landucci, Marco Mazzotta, Gabriella Moretti, Raffaella Palumbo, Francesca Fulvia Pepe, Patrizia Vici, Fable Zustovich, Viola Cogliati. Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 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 PO4-04-10.

Predictive Factors of Neoadjuvant Chemotherapy Response in Breast Cancer Validated by Three Anatomopathological Scores: Residual Cancer Burden, Chevallier System, and Tumor-Infiltrating Lymphocytes

Predictive Factors of Neoadjuvant Chemotherapy Response in Breast Cancer Validated by Three Anatomopathological Scores: Residual Cancer Burden, Chevallier System, and Tumor-Infiltrating Lymphocytes

Structural connectivity as a predictive factor for perampanel response in patients with epilepsy

ObjectivesThis study aimed to identify clinical characteristics that could predict the response to perampanel (PER) and determine whether structural connectivity is a predictive factor. MethodsWe enrolled patients with epilepsy who received PER and were followed-up for a minimum of 12 months. Good PER responders, who were seizure-free or presented with more than 50 % seizure reduction, were classified separately from poor PER responders who had seizure reduction of less than 50 % or non-responders. A graph theoretical analysis was conducted based on diffusion tensor imaging to calculate network measures of structural connectivity among patients with epilepsy. Results106 patients with epilepsy were enrolled, including 26 good PER responders and 80 poor PER responders. Good PER responders used fewer anti-seizure medications before PER administration compared to those by poor PER responders (3 vs. 4; p = 0.042). Early PER treatment was more common in good PER responders than poor PER responders (46.2 vs. 21.3 %, p = 0.014). Regarding cortical structural connectivity, the global efficiency was higher and characteristic path length was lower in good PER responders than in poor PER responders (0.647 vs. 0.635, p = 0.006; 1.726 vs. 1,759, p = 0.008, respectively). For subcortical structural connectivity, the mean clustering coefficient and small-worldness index were higher in good PER responders than in poor PER responders (0.821 vs. 0.791, p = 0.009; 0.597 vs. 0.560, p = 0.009, respectively). ConclusionThis study demonstrated that early PER administration can predict a good PER response in patients with epilepsy, and structural connectivity could potentially offer clinical utility in predicting PER response.

The Short-Term Efficacy of a Three-Week Pulmonary Rehabilitation Program among Patients with Obstructive Lung Diseases.

Introduction: The recommended duration for pulmonary rehabilitation stands at a minimum of six weeks; however, this stipulation may pose constraints in various countries due to financial limitations imposed by insurance companies and/or national health funds, as is the case in Poland. Consequently, our study endeavors to analyze the short-term outcomes stemming from a condensed three-week PR regimen administered to patients diagnosed with chronic obstructive pulmonary disease (COPD), asthma, and the concomitance of these conditions (COPD-A)-this is an approach that is standard in the rehabilitation protocols endorsed by our national health fund. Methods: Patients diagnosed with COPD, asthma, and COPD-A, referred to the PR program, underwent retrospective analysis to evaluate the short-term efficacy of a three-week PR program. Patients underwent comprehensive assessment by respiratory physicians and rehabilitation consultants, leading to individualized PR programs. Clinical evaluations occurred at program onset and completion. Results: 125 patients participated: 37 COPD, 61 asthma, and 27 COPD-A. Significant improvements were observed in the COPD Assessment Test (CAT), the consensus-based GINA symptom control tool (GINA-SCT), the Modified Medical Research Council (mMRC) scale, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and the 6-min walk test (6 MWT) distance, as well as in the St. George's Respiratory Questionnaire (SGRQ) scores. All groups experienced reduced dyspnea severity and improved exercise tolerance. FEV1 and FVC improved in asthma and COPD-A, but not significantly in COPD. Multivariable logistic regression identified predictive factors for PR response. Conclusions: The study supports the short-term efficacy of the three-week PR program in improving clinical outcomes, exercise tolerance, and quality of life in COPD and asthma patients. Tailoring interventions based on predictors of PR response can optimize outcomes. Further research, particularly of the COPD-A group, is needed for individualized approaches. Larger sample sizes are necessary to confirm our findings.

Retreatment with Immune Checkpoint Inhibitors in the New Scenario of Immunotherapy in Non-Small Cell Lung Cancer.

The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results that led to their approval in clinical practice. However, there is limited evidence on immunotherapy rechallenge after recurrence, with the majority of available knowledge coming from retrospective studies which involve heavily pretreated patients with advanced NSCLC. The recent introduction in the curative setting and the potential regulatory restrictions raise questions about the optimal choice of first-line and subsequent therapies for patients with systemic relapse. The role of immunotherapy readministration in this new scenario needs to be clarified, as well as the identification of patients for whom it is more appropriate, including clinical characteristics, duration of response, switching to other ICIs, reasons for discontinuation and immune-related toxicity. Here, we review literature on rechallenge with immunotherapy, including efficacy, safety profile and potential predictive factors of response.

Atorvastatin Treatment Significantly Increased the Concentration of Bone Marrow-Derived Mononuclear Cells and Transcutaneous Oxygen Pressure and Lowered the Pain Scale after Bone Marrow Cells Treatment in Patients with "No-Option" Critical Limb Ischaemia.

The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation. Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant.

Efficacy and predictive factors of clinical response to hyaluronic acid ＋ chondroitin sulfate bladder instillations for the treatment of BPS/IC

Aim of the study:To assess the efficacy of intravesical hyaluronic acid and chondroitin sulfate (HACS) instillations in treating patients with bladder pain syndrome/interstitial cystitis (BPS/IC), as well as to identify predictive factors for clinical response. Materials and methods:Patients diagnosed with BPS/IC and treated with Ialuril® (HACS) bladder instillations between January 2018 and August 2020 were included. Data collected included Visual Analog Scale (VAS) scores, number of pain episodes, 3-day frequency volume chart measurements (at baseline and last follow-up), Patient Global Impression of Improvement (PGI-I) questionnaire responses, age, history of urinary tract infections (UTIs), and endoscopic findings from cystoscopy with hydrodistension. Statistical analyses included Mann–Whitney’s non-parametric U-test and chi-square test with a 95% confidence interval (p≤ 0.05) to identify predictive factors of treatment success. Results:A total of 104 patients were treated with a median follow-up of 29 months (IQR 14–40), predominantly female with a mean age of 60 ± 16 years. At the last follow-up, there was a median reduction of 1 point in the VAS score (IQR 1–1), whilst only 20% experienced a reduction of ≥2 points. A statistically significant correlation was observed in the reduction of days with pain per month before and after treatment (ΔDPV) (median reduction: 6 days, IQR 2–7, p < 0.001). No adverse events were reported during treatment. Regarding prognostic factors, three statistically significant correlations were found: between PGI-I success and age (p=0.050), between ΔVAS score and recurrent UTIs (p=0.044), and between ΔDPV and recurrent UTIs (p=0.04). Discussion:The study did not demonstrate any significant reduction of VAS score or diurnal and nocturnal voiding frequency after treatment, on the contrary it did show a reduction in the number of days with pain. Consequently, 88.3% of patients reported positive subjective improvement on the PGI-I questionnaire, and none discontinued treatment. Endoscopic findings did not appear to correlate with treatment response. Conclusions:Age and the presence of recurrent UTIs may influence the response to intravesical HACS therapy in terms of PGI-I, VAS score, and reduction in days with pain.

Predictive factors for response to viscosupplementation in patients with knee osteoarthritis: an analysis of clinical and imaging factors

IntroductionDespite the widespread use of viscosupplementation in the treatment of knee arthritis, the factors that may influence its effectiveness or failure are still controversial and little explored in the literature. ObjectiveTo identify clinical, radiographic, and magnetic resonance imaging (MRI) predictive factors associated with viscosupplementation failure in the treatment of knee osteoarthritis. DesignIn this prospective study, patients with knee osteoarthritis were evaluated for predictive factors before the intervention, including radiographic images (KL classification and femorotibial angle), magnetic resonance images (MRI) Osteoarthritis Knee Score (MOAKS) and meniscal extrusion), joint effusion, BMI, previous surgery, sex, and age. All patients received a single intra-articular dose of Synolis-VA® 4 ml (80 mg hyaluronic acid + 160 mg sorbitol). The WOMAC, VAS, and SF-12v2 questionnaires were administered at baseline, fifteen days, three months, and six months of clinical follow-up. ResultsThe results showed a significant reduction in WOMAC and VAS scores for all evaluated times after viscosupplementation compared to baseline. Using the OMERACT-OARSI criteria, 53 patients were classified as the "success group" and 55 patients as the "failure group." The KL classification and MOAKS score showed a significant difference between these two groups, p = 0.042 and p = 0.009, respectively. Univariate logistic regression analysis revealed that a KL classification of 3 or 4 and MOAKS score predicted a higher risk of failure. ConclusionPatients with a KL classification of 3 or 4 or a high MOAKS score were more likely to fail viscosupplementation, while the other analyzed factors showed no significant difference.

Abstract 2014: Tumor glycosylation impacts the efficacy of HER2 targeting therapies

Abstract Cancer progression remains a major obstacle to the successful treatment of cancer. In HER2+ breast cancer, targeting therapies against HER2 have revolutionized the treatment landscape. However, predictive factors for response are largely unknown and a significant number of patients develop resistance. An extensive body of work has revealed a plethora of mechanisms of resistance. However, a key aspect of cancer cells has been largely overlooked: their aberrant glycosylation profile. Aberrant glycosylation of proteins is a hallmark in cancer and has been linked to multiple processes such as invasion, angiogenesis and modulation of the immune response. Yet the influence of altered glycosylation on the efficacy of HER2-targeted therapies remains unknown. Therefore, here, we address this question using clinical data, 3D co-culture systems and advanced live microscopy. Bioinformatics analysis of SPY-2 clinical trial data reveals an association of specific glycogenes with response to HER2-targeting therapies in breast cancer patients. We validated these findings in resistance cell models generated in-vitro and in-vivo using gain and loss of function assays. Furthermore, to provide a more relevant cell model system, we implement the use of 3D co-cultures of cancer spheroids and immune cells. Thus, our research addresses a largely unexplored area in cancer biology combining clinical data from tumor biopsies, trastuzumab-resistant cancer cell models and, live imaging of 3D heterotypic cultures. This work holds the potential to identify new markers of response to therapies and highlights the importance of the interplay of cancer cells and their microenvironment on the efficacy of current treatments. Citation Format: Ana Ruiz-Saenz, Roos Vincken, Denise Wolf, Veronica Steri, Laura van't Veer, John Martens, Danny Huylebroeck, Mark M. Moasser. Tumor glycosylation impacts the efficacy of HER2 targeting therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2014.

Abstract 2493: Prospective evaluation of predictive biomarkers for Palbociclib (P) and endocrine therapy (ET) benefit in hormone receptor (HR)-positive [+]/human epidermal growth factor receptor 2 (HER2)-negative [-] advanced breast cancer (ABC) patients (pts) from PARSIFAL clinical trial: The transFAL sub-study

Abstract BACKGROUND Combining cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) with first-line ET is the standard of care for pts with HR[+]/HER2[-] ABC. PARSIFAL was a randomized, open-label, phase II trial that evaluated the efficacy and safety of first line P plus fulvestrant (F) or letrozole (L) in this pts population. Both treatments had comparable efficacy and safety results (JAMAOncol. 2021;7(12):1791-1799). Although multiple CDK4/6i clinical outcomes biomarkers have been reported, the only validated predictive factor for response is HR positivity. TransFAL, a translational study of PARSIFAL, assessed a comprehensive set of biomarkers of sensitivity/resistance to P plus ET. MATERIALS AND METHODS TransFAL employed a sample biorepository from PARSIFAL comprising formalin-fixed paraffin-embedded (FFPE) tissue and blood samples obtained from pts included in either study arm. Tumor samples (N=33) derived from the primary tumor at initial diagnosis or from primary tumor or metastatic lesions at study entry. Blood samples were obtained at baseline (N=73) and disease progression (N=22). Pts were categorized as sensitive or resistant based on progression-free survival (PFS). CDK4/6 pathway activation was assessed by immunohistochemistry for CDK4, CDK6, Rb, pRb, ER, PgR, and Ki67. Proteins extracted from FFPE slides were analyzed using hierarchical clustering, significance analysis of microarrays, and probabilistic graphical models. RNA expression and circulating tumor DNA (ctDNA) analysis were assessed by next-generation sequencing (NGS) and analysis of panel of 56 genes/gene regions, respectively. RESULTS A worse median PFS was found in pts with CDK6 positive (≥ 1% positive cells; p &amp;lt; 0.001) and high Ki67 (≥ 10% positive cells; p = 0.013)at baseline. ctDNA density at baseline was significantly higher for resistant (PFS &amp;lt; 9 months; 17.1 ng/mL) pts compared to sensitive (PFS &amp;gt; 31 months; 11.3 ng/mL) pts (p &amp;lt; 0.001). Most pts (83%) presented a genomic alteration detected in ctDNA, TP53 (28%) and PIK3CA (28%) being the most frequently mutated genes. Pts (9%) who harbored ARID1A mutation had lower PFS (p = 0.052). ESR1 mutations at progression were numerically higher in the L arm (37.5%) compared to F arm (14.3%); (p=0.31), but numbers were low. Proteomic and RNA analyses did not yield confirmable distinctive expression pattern between resistant/sensitive pts… CONCLUSIONS High Ki67 levels and CDK6 expression in the tumor and high ctDNA density, but not proteomic or RNA sequencing data, were associated to poor outcome in this analysis of pts treated with CDK4/6i and ET. This data adds to the growing evidence of poor prognosis biomarkers in this setting, highlighting the need of novel strategies for these pts. Citation Format: Joan Albanell, Angelo Gámez Pozo, Carlos L. Arteaga, Meritxell Bellet, Federico Rojo, Abel González, Beatriz Bellosillo, Violeta Serra, Petra Gener, José Antonio Guerrero, Laura López-Montero, Mario Mancino, Jose Rodríguez-Morató, Leonardo Mina, José Manuel Pérez-García, Javier Cortés, Antonio Llombart-Cussac. Prospective evaluation of predictive biomarkers for Palbociclib (P) and endocrine therapy (ET) benefit in hormone receptor (HR)-positive [+]/human epidermal growth factor receptor 2 (HER2)-negative [-] advanced breast cancer (ABC) patients (pts) from PARSIFAL clinical trial: The transFAL sub-study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2493.