First-line Treatment For Patients Research Articles

Predicting response to CCRT for esophageal squamous carcinoma by a radiomics-clinical SHAP model

BackgroundRadical concurrent chemoradiotherapy (CCRT) is frequently used as the first-line treatment for patients with locally advanced esophageal cancer. Unfortunately, some patients respond poorly. To predict response to radical concurrent chemoradiotherapy in pre-treatment patients with esophageal squamous carcinoma (ESCC), and compare the predicting efficacies of radiomics features of primary tumor with or without regional lymph nodes, we developed a radiomics-clinical model based on the positioning CT images. Finally, SHapley Additive exPlanation (SHAP) was used to explain the models.MethodsThis retrospective study enrolled 105 patients with medically inoperable and/or unresectable ESCC who underwent radical concurrent chemoradiotherapy (CCRT) between October 2018 and May 2023. Patients were classified into responder and non-responder groups with RECIST standards. The 11 recently admitted patients were chosen as the validation set, previously admitted patients were randomly split into the training set (n = 70) and the testing set (n = 24). Primary tumor site (GTV), the primary tumor and the uninvolved lymph nodes at risk of microscopic disease (CTV) were identified as Regions of Interests (ROIs). 1762 radiomics features from GTV and CTV were respectively extracted and then filtered by statistical differential analysis and Least Absolute Shrinkage and Selection Operator (LASSO). The filtered radiomics features combined with 13 clinical features were further filtered with Mutual Information (MI) algorithm. Based on the filtered features, we developed five models (Clinical Model, GTV Model, GTV-Clinical Model, CTV Model, and CTV-Clinical Model) using the random forest algorithm and evaluated for their accuracy, precision, recall, F1-Score and AUC. Finally, SHAP algorithm was adopted for model interpretation to achieve transparency and utilizability.ResultsThe GTV-Clinical model achieves an AUC of 0.82 with a 95% confidence interval (CI) of 0.76–0.99 on testing set and an AUC of 0.97 with a 95% confidence interval (CI) of 0.84–1.0 on validation set, which are significantly higher than those of other models in predicting ESCC response to CCRT. The SHAP force map provides an integrated view of the impact of each feature on individual patients, while the SHAP summary plots indicate that radiomics features have a greater influence on model prediction than clinical factors in our model.ConclusionGTV-Clinical model based on texture features and the maximum diameter of lesion (MDL) may assist clinicians in pre-treatment predicting ESCC response to CCRT.

1460P GALLANT-1: GB1211 galectin-3 (Gal-3) inhibitor plus atezolizumab (atz) for first line treatment in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC)

1460P GALLANT-1: GB1211 galectin-3 (Gal-3) inhibitor plus atezolizumab (atz) for first line treatment in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC)

Pulmonary sarcoidosis: A comprehensive review: Past to present

Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2–160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis.Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%–80% of cases. Stage III only has a 10%–40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years.First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20–40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6–18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography. ConclusionThe mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%–40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.

LBA69 Aumolertinib plus apatinib versus aumolertinib as first-line treatment in patients with EGFR mutation positive locally advanced or metastatic non-small cell lung cancer (NSCLC): A randomized multicenter study

LBA69 Aumolertinib plus apatinib versus aumolertinib as first-line treatment in patients with EGFR mutation positive locally advanced or metastatic non-small cell lung cancer (NSCLC): A randomized multicenter study

921P HB-200 arenavirus-based immunotherapy plus pembrolizumab as a first-line treatment of patients with recurrent/metastatic HPV16 positive head and neck cancer

921P HB-200 arenavirus-based immunotherapy plus pembrolizumab as a first-line treatment of patients with recurrent/metastatic HPV16 positive head and neck cancer

LBA14 Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial

LBA14 Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial

1340P Propensity score matching analysis for osimertinib versus comparator first-generation EGFR tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non–small cell lung cancer: A Chinese, multicenter, real-world cohort study

1340P Propensity score matching analysis for osimertinib versus comparator first-generation EGFR tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non–small cell lung cancer: A Chinese, multicenter, real-world cohort study

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

929P Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with with recurrent/ metastatic head and neck squamous-cell carcinoma (R/M SCC) of the nasal cavity and paranasal sinuses

929P Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with with recurrent/ metastatic head and neck squamous-cell carcinoma (R/M SCC) of the nasal cavity and paranasal sinuses

1428P Clinical benefit of combination chemo-immunotherapy in first-line treatment for patients over the age of 65 or 75 with metastatic NSCLC

1428P Clinical benefit of combination chemo-immunotherapy in first-line treatment for patients over the age of 65 or 75 with metastatic NSCLC

Biomechanical behavior of carbon fiber-reinforced polyetheretherketone as a dental implant material in implant-supported overdenture under mandibular trauma: A finite element analysis study.

Implant-supported overdentures are well-known and widely accepted treatment modality to increase retention which is a crucial factor for determining patient satisfaction. The placement of two implants in the anterior region can be selected as a first-line treatment in patients with the atrophic mandibular ridge. The purpose of this research was to assess the biomechanical effects of carbon fiber-reinforced polyetheretherketone (CFR-PEEK) implant-supported overdenture in the event of 2,000 N forefront trauma to an atrophic edentulous mandible by using the finite element analysis method. Three types of mandible models were simulated; the first one was an edentulous atrophic mandible model; in the second model, 3.5 × 11.5 mm CFR-PEEK implants; and in the third model, 4.3 × 11.5 mm CFR-PEEK implants were positioned in the region of the lateral incisor of the identical edentulous atrophic mandible. Maximum Von Misses stresses 979.261 MPa, 1,454.69 MPa, and 1,940.71 MPa and maximum principal stresses 1,112.74 MPa, 1,249.88 MPa, and 1,251.33 MPa have been detected at the condylar neck area and minimum principal stresses - 1,203.38 MPa, -1,503.21 MPa, and - 1,990.34 MPa have been recorded at the symphysis and corpus regions from M1 to M3, respectively. In addition, the M2 and M3 models showed low-stress distributions around the implant-bone interface, particularly where the implants were in contact with cancellous bone. The results showed that the insertion of different diameters of CFR-PEEK implants led to low and homogenous stress distribution all around the implant-bone interface and stresses transferred directly to the condylar neck areas. Therefore, it was observed that CRF-PEEK implants did not change the basic behavior of the mandibula in response to frontal stresses.

667P Efficacy and safety of larotrectinib (laro) as first-line treatment for patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer

667P Efficacy and safety of larotrectinib (laro) as first-line treatment for patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer

1503TiP A phase II study of cemiplimab plus BNT116 versus cemiplimab alone in first-line treatment of patients with advanced non-small cell lung cancer with PD-L1 expression ≥50%

1503TiP A phase II study of cemiplimab plus BNT116 versus cemiplimab alone in first-line treatment of patients with advanced non-small cell lung cancer with PD-L1 expression ≥50%

Combination of Radiotherapy and Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study

Following the results of the IMbrave150 study, Atezolizumab plus bevacizumab (Atezo/beva) became the first-line treatment in patients with advanced hepatocellular carcinoma (HCC). However, its real-world efficacy has been less satisfied. In this study, we investigated the efficacy of radiotherapy (RT) combined with Atezo/beva in patients with advanced HCC. Twenty patients received combination of RT and Atezo/beva between December 2021 and December 2022 at our institution. RT was administered in 10 fractions of 5 Gy between Atezo/beva cycles. Tumor response were evaluated on both imaging and tumor marker basis. The iRECIST guideline was used to assess treatment response after the combination treatment of RT and Atezo/beva. Primary endpoints were disease control rate (DCR) and overall response rate (ORR), and secondary endpoint was treatment related toxicity. All patients were BCLC C with advanced tumors associated with lymph node metastasis (7, 35%) or distant metastasis (8, 40%). Patients received RT between cycles of Atezo/beva, mostly (14, 70%) between 2nd and 3rd cycles. After a median follow-up of 3.2 months, DCR was 65% and ORR was 20%. Significant decrease in tumor marker of over 2-fold was shown in 10 patients (50%). Regarding treatment related toxicity, only 1 patient (5%) showed grade 3 neutropenic fever, and no grade 4 or 5 toxicity was seen. Combination of radiotherapy and Atezo/beva showed high response rate with tolerable treatment related toxicity in advanced HCC patients. Further prospective studies with larger patient cohort are warranted.

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1–Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial

IntroductionWe report the primary analysis from JAVELIN Lung 100, a phase 3 trial comparing avelumab (anti⁠–programmed death-ligand 1 [PD-L1]) versus platinum-based doublet chemotherapy as first-line treatment for PD-L1–positive (+) advanced NSCLC. MethodsAdults with PD-L1+ (≥1% of tumor cells; PD-L1 immunohistochemistry 73-10 pharmDx), EGFR and ALK wild-type, previously untreated, stage IV NSCLC were randomized to avelumab 10 mg/kg every 2 weeks (Q2W), avelumab 10 mg/kg once weekly (QW) for 12 weeks and Q2W thereafter, or platinum-based doublet chemotherapy every 3 weeks. Primary end points were overall survival (OS) and progression-free survival (PFS) per independent review committee. The primary analysis population was patients with high-expression PD-L1+ tumors (≥80% of tumor cells). ResultsA total of 1214 patients were randomized to avelumab Q2W (n = 366), avelumab QW (n = 322), or chemotherapy (n = 526). In the primary analysis population, hazard ratios (HRs) for OS and PFS with avelumab Q2W (n = 151) versus chemotherapy (n = 216) were 0.85 (95% confidence interval [CI]: 0.67–1.09; one-sided p = 0.1032; median OS, 20.1 versus 14.9 mo) and 0.71 (95% CI: 0.54–0.93; one-sided p = 0.0070; median PFS, 8.4 versus 5.6 mo), respectively. With avelumab QW (n = 130) versus chemotherapy (n = 129), HRs were 0.79 (95% CI: 0.59–1.07; one-sided p = 0.0630; median OS, 19.3 versus 15.3 mo) and 0.72 (95% CI: 0.52–0.98; one-sided p = 0.0196; median PFS, 7.5 versus 5.6 mo), respectively. No new safety signals were observed. ConclusionsLonger median OS and PFS were observed with avelumab versus platinum-based doublet chemotherapy in advanced NSCLC, but differences in OS and PFS were not statistically significant, and the trial did not meet its primary objective. ClinicalTrials.gov Identifier: NCT02576574.

Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment

Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFStargeted/PFSpre-chemotherapy) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.

Association Between Intermediate End Points, Progression-free Survival, and Overall Survival in First-line Advanced or Recurrent Endometrial Cancer

PurposeAdvanced/recurrent endometrial cancer is associated with poor long-term outcomes. Clinical studies of novel regimens are ongoing, but given that data on overall survival (OS) take a long time to mature, surrogate end points are often used to support clinical-research interpretation. The aim of this study was to explore the correlation between progression-free survival (PFS)/time to progression (TTP) and OS across multiple time points in the first-line treatment of advanced/recurrent endometrial cancer. MethodsThis study comprised meta-analyses of Phase 2/3 randomized, controlled trials of first-line treatments in patients with advanced primary or first-recurrent endometrial cancer identified via systematic literature review. The strength of the surrogacy relationship was assessed by correlation analyses (estimated with Spearman and Pearson correlation coefficients) and weighted linear regression. FindingsData from 15 studies were included. PFS and TTP (TTP was reported in one study only) were highly correlated with future OS at multiple time points (Spearman values, 0.83–0.90; Pearson values, 0.86–0.93), suggesting that a change in PFS/TTP would likely be correlated with a change in OS in the same direction. On weighted linear regression, a 10% increase in PFS/TTP probability was significantly associated with a 9.3% to 13.3% increase in the probability of future OS. The strong positive association between PFS/TTP and OS was supported by findings from sensitivity analyses based on identified sources of interstudy heterogeneity. ImplicationsPFS/TTP is a good potential candidate for predicting long-term OS outcomes in trials of first-line treatment in patients with advanced/recurrent endometrial cancer. The findings from this report may help to inform health-authority and clinical decision makers that PFS/TTP improvements are likely to translate into subsequent OS improvements once data mature.

Nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: a cost-effectiveness analysis

BackgroundThe aim of the study was to evaluate the cost-effectiveness of nivolumab plus chemotherapy as first-line treatment for patients with advanced gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma from the perspective of Chinese and US society.MethodsTo conduct the analysis, a state-transitioned Markov model, which included three mutually exclusive health states (progression-free survival (PFS), progressive disease (PD), and death), was developed. Cycle length was set at 3 weeks and lifetime horizon was set at 10 years. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated in the analysis. Willingness-to-pay (WTP) thresholds in the model were set at $37,653.00/QALY in China and $100,000.00/QALY in the US, respectively. Meanwhile, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the robustness of the model.ResultsOver a lifetime horizon, the ICERs of nivolumab plus chemotherapy versus chemotherapy alone were $430,185.04/QALY and $944,089.78/QALY in China and the US, respectively. Cost of nivolumab and utility for the PFS state had the most significant impact on ICERs both in the US and China based on the results of the one-way sensitivity analyses. In the probabilistic sensitivity analyses, the proportions of nivolumab plus chemotherapy being cost-effective compared with chemotherapy alone were 0%.ConclusionsIn conclusion, nivolumab plus chemotherapy is unlikely to be a cost-effective treatment option compared with chemotherapy alone in the first-line setting of advanced gastric, GEJ, or esophageal adenocarcinoma.

Are antiarrhythmic agents indicated in premature ventricular complex-induced cardiomyopathy and when?

Premature ventricular complexes (PVCs) are the most common ventricular arrhythmia that are encountered in the clinical practice. Recent data suggests that high PVC burden may lead to the development of PVC-induced cardiomyopathy (PVC-CM) even in patients without structural heart disease. Treatment for effective suppression of PVCs, can reverse PVC-CM. Both antiarrhythmic drugs (AADs) and catheter ablation (CA) are recognized treatment modalities for any cardiac arrhythmias. However, with increasing preference of CA, the role of AADs needs further defining regarding their efficacy, safety, indications and patient selection to treat PVC-CM. To ascertain the role of AADs to treat PVC-CM; whether they are indicated to treat PVC-CM, and if so, when, we interrogated PubMed and other search engines for English language publications with key words premature ventricular complexes (PVCs), cardiomyopathy, anti-arrhythmic drugs, catheter ablation, and pharmacological agents. All publications were carefully reviewed and scrutinized by the authors for their inclusion in the review paper. For illustration of cases, ethical standard was observed as per the 1975 Declaration of Helsinki, and the patient was treated as per the prevailing standard of care. Informed consent was obtained from the patient for conducting the ablation procedure. Our literature search specifically the pharmacological treatment of PVC-CM with AADs revealed significant paradigm shift in treatment approach for PVCs and PVC-induced cardiomyopathy. No major large, randomized control trials of AADs versus CA for PVC-CM were found. We found that beta-blockers and calcium channel blockers are particularly effective in the treatment of PVCs originating from right ventricular outflow tract. For Class Ic AADs - flecainide and propafenone, small clinical studies showed Class Ic AADs to be effective in PVC suppression, but their usage was not recommended in patients with significant coronary artery disease. Mexiletine was found to have modest effect on PVC suppression. Studies showed sotalol to significantly reduce PVCs frequency in patients receiving both low and high doses. Studies also showed amiodarone to have higher successful PVC suppression, but not recommended as a first-line treatment for patients with idiopathic PVCs in the absence of symptoms and left ventricular dysfunction. For dronedarone, no major clinical data were available. Based on the available data in the literature, we conclude that AADs play important role in the treatment of PVC-induced cardiomyopathy. However, appropriate patient selection criteria are vitally important, and in general terms AADs are indicated or polymorphic PVCs, epicardial PVCs; and when CA procedure is contraindicated, or not feasible or failed.

Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer.

Immune checkpoint inhibition combined with chemotherapy is currently approved as first-line treatment for patients with advanced PD-L1-positive triple-negative breast cancer (TNBC). However, a significant proportion of metastatic TNBC is PD-L1-negative and, in this population, chemotherapy alone largely remains the standard-of-care and novel therapeutic strategies are needed to improve clinical outcomes. Here, we describe a triple combination of anti-PD-L1 immune checkpoint blockade, epigenetic modulation thorough bromodomain and extra-terminal (BET) bromodomain inhibition (BBDI), and chemotherapy with paclitaxel that effectively inhibits both primary and metastatic tumor growth in two different syngeneic murine models of TNBC. Detailed cellular and molecular profiling of tumors from single and combination treatment arms revealed increased T- and B-cell infiltration and macrophage reprogramming from MHCIIlow to a MHCIIhigh phenotype in mice treated with triple combination. Triple combination also had a major impact on gene expression and chromatin profiles shifting cells to a more immunogenic and senescent state. Our results provide strong preclinical evidence to justify clinical testing of BBDI, paclitaxel, and immune checkpoint blockade combination.