Complete Response Research Articles

Outcomes After Stereotactic Body Radiation for Hepatocellular Carcinoma in Patients With Child-Pugh A Versus Child-Pugh B/C Cirrhosis

For patients with hepatocellular carcinoma (HCC), stereotactic body radiation therapy (SBRT) has emerged as a locoregional treatment. Our purpose was to report outcomes in patients with HCC with Child-Pugh A (CP A) versus Child-Pugh B or C (CP B/C) liver dysfunction treated with SBRT. A retrospective analysis of 80 patients with HCC, with a total of 94 tumors treated with SBRT, was conducted at a single institution. Outcomes were compared between patients with CP A (n = 51) and CP B/C (n = 29) liver dysfunction. Outcomes of interest included local control, overall survival (OS), and toxicity. Median tumor size was 3.2 cm. There were 59 tumors included in the CP A cohort and 35 tumors in the CP B/C cohort. Median radiation dose was 50 Gy in 5 fractions for the CP A cohort and 40 Gy in 5 fractions for the CP B/C cohort. The rates of pathologic complete response were similar between the 2 groups at 63% for the CP A group and 61% for the CP B/C group. The estimated 1-year local control rates were similar between the 2 groups at 93% for the CP A group and 91% for the CP B/C group (P = .59). The 1-year OS for the CP A group was 85%, whereas the 1-year OS for the CP B/C group was 61% (P = .19). There was a 5.9% rate of grade 3+ toxicity in the CP A group and a 20.7% rate of grade 3+ toxicity in the CPB/C group. Our findings suggest that SBRT is feasible and effective in patients with both CP A and CP B/C liver dysfunction with similar rates of local control and pathologic complete response despite lower radiation doses in the CP B/C cohort. In patients with more advanced CP B/C cirrhosis, toxicities were higher and must be weighed against possible treatment benefits. Further studies characterizing the optimal role of SBRT in patients with advanced cirrhosis are warranted.

Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial.

A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose-escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre-treated HL entered dose-escalation, with nine patients experiencing treatment-emergent adverse events (TEAEs) considered to be related to study treatment-primarily hematological toxicities. MTD was 100mg/m2 tinostamustine over 60min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine-related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression-free survival 3.8months (95% CI: 2.2-9.4months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT02576496.

Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO

BackgroundIn resectable gastric/gastroesophageal junction adenocarcinoma (GAC/GEJAC), microsatellite instability (MSI-H) confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need of chemotherapy or surgery. Patients and methodsINFINITY is a multicentre, multicohort phase II trial (NCT04817826) investigating in Cohort 1 the activity and safety of tremelimumab+durvalumab (T300/D) as neoadjuvant treatment for dMMR/MSI-H, resectable GAC/GEJAC. Primary endpoint was pathologic complete response (pCR) rate; Secondary endpoints: progression-free survival (PFS), overall survival (OS), quality of life (QoL), and translational analyses. In Cohort 2, the activity and safety of T300/D was explored as definitive treatment in patients achieving clinical complete response (cCR). Primary endpoint was 2-year cCR rate, Secondary endpoints: PFS, OS, QoL, gastrectomy-free survival (GFS) and translational analyses. ResultsIn Cohort 1, 18 patients were recruited and 15 evaluable. pCR and major-complete pathological response were 60% and 80%. Since pCR rate in T4 tumors was 17%, this subgroup of patients was excluded from enrollment in Cohort 2. At 28.1 months median follow-up, 24-month GC-specific PFS and OS rates were 85% and 92%. In Cohort 2, 18 patients were enrolled and 17 evaluable, 13 had cCR and started non-operative management (NOM). At 11.5 months median follow up, 1 patient had local regrowth and underwent salvage surgery, 12-month GFS was 64.2%. ConclusionsThe INFINITY study provided promising activity results of a chemo-free T300/D combination regimen as pre-operative treatment in dMMR/MSI GAC/GEJAC and the first available feasibility results of a NOM strategy in this disease setting, worth of further validation in larger cohorts.

Constitutive modelling of deformation rate dependent response of steel timber shear connections

This paper presents experimental and numerical investigations into the deformation rate-dependent constitutive response of steel-timber shear connections with screws. After describing the test specimens and experimental arrangement, a detailed account of the complete deformation response and main mechanical parameters of the tested shear connections under three applied displacement rate levels are given. Specimens with small screw diameters had a relatively brittle response, failing shortly after yielding, whilst those with higher diameters showed ductile failure modes, with plastic hinges forming in the screws and concurrent extensive timber crushing. It was observed that the stiffness increases with the deformation rate due to the viscoelastic response of wood materials, whilst the peak load is largely constant. Nonlinear finite element simulations were carried out to validate the main numerical parameters for steel, timber, and interaction characteristics. After gaining confidence in the ability of the numerical models to predict closely the stiffness and peak load, numerical investigations were carried out to examine the influence of key material and geometric parameters on the stiffness, load resistance and deformation response. The studies showed that higher timber strength increases the initial stiffness and the peak load, while higher screw grades improved both stiffness and strength. Based on the results and observations, code-modified expressions for evaluating the stiffness and load resistance, as a function of the deformation rate, are proposed within the ranges considered, and validated against a collated database. Comparative assessments with existing literature indicate that the proposed equations provide improved estimates. Suggested closed-form relationships enable the characterisation of the full constitutive response of steel-timber shear connections, that can be adopted for discrete nonlinear modelling of connectors.

Exploring early kinetic profiles of CEA, ctDNA and cfDNA in patients with RAS-/BRAF-mutated metastatic colorectal cancer

IntroductionPatients with metastatic colorectal cancer (mCRC) respond differently to first-line chemotherapy. Early identification of patients with limited or no clinical benefit could prompt a timelier introduction of second-line therapy and potentially lead to improved overall outcomes. Carcinoembryonic antigen (CEA) is currently the only blood-based marker in clinical use for disease control monitoring in mCRC. Circulating cell-free DNA (cfDNA), including circulating tumor DNA (ctDNA) could become a useful surrogate for oncological outcomes. Materials and methodsForty patients with RAS-/BRAF-mutated mCRC from the prospective NORDIC-VII trial (NCT00145314) were included. An exploratory model system was made to describe the early on-treatment kinetics of CEA, cfDNA and ctDNA during first-line oxaliplatin-based chemotherapy, and investigate the associations with radiological response, progression-free survival (PFS) and overall survival (OS). ResultsSummary metrics were made, representing percentage change from treatment start to time-grid day 7 (P7), day 14 (P14), and day 49 (P49); slope from time-grid day 0 to 7 (S7), day 8 to 14 (S14), and day 15 to 49 (S49); and area under the curve from time-grid day 0 to 49 (AUC). Notably P49 and S49 for ctDNA and CEA were associated with radiological response and/or PFS. The early dynamics of the two markers differed substantially, with faster and more marked changes in ctDNA compared with CEA. Nine patients did not reach complete/near complete molecular ctDNA response close to first evaluation (∼week 8), a state associated with a short PFS (HR 2.72; 95% CI 1.22 – 6.06; P = 0.01) and OS (HR 3.12; 95% CI 1.35 – 7.23; P < 0.01). Contrary, twenty-two patients did not reach radiological response (i.e., complete or partial response) at first evaluation, but this was not associated with PFS (HR 1.21; 95% CI 0.64 – 2.30; P = 0.55) nor OS (HR 1.37; 95% CI 0.70 – 2.68; P = 0.37). ConclusionEarly dynamics of ctDNA during first-line oxaliplatin-based chemotherapy hold prognostic value, supporting the idea of prospectively validating a ctDNA-RECIST framework in the early care pathway of mCRC patients. Micro AbstractMetastatic colorectal cancer (mCRC) patients respond differently to chemotherapy, and early identification of patients with limited or no clinical benefit could prompt treatment switching with improved outcomes. We examined CEA and circulating tumor DNA (ctDNA) dynamics during first-line oxaliplatin-based chemotherapy, and their association with radiological response/survival (N=40). ctDNA dynamics hold prognostic value, supporting the idea of prospectively validating a ctDNA-response framework early in the care pathway.

Effect of Change Management on Employee Performance in Nepalese Commercial Banks

Purpose: The study intends to analyze the effect of change management on employee performance in commercial banks. Method: Data collection meticulously employed a simple random sampling technique. Data is collected from 300 bank employees via adopted questionnaire on a 7-point Likert scale. 240 complete responses received, yielding an 80% response rate. Descriptive and causal-comparative research design utilized with independent sample t-test, one-way ANOVA, Mann-Whitney U test, Krushkal-Wallis H Test, correlation, and regression analysis. Findings: Beta coefficients indicate higher influence of Change in organizational structure on employee performance. Implications: It is recommended that organizations should reformulate their policies and strategies promoting supportive work culture, clear guidelines regarding roles and responsibilities, fostering a culture of transparency and communication to enhance employee commitment. Managers should provide support to increase satisfaction and better employee morale.

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma.

Breast cancer remains a significant cause of mortality globally, necessitating effective treatment strategies. Neoadjuvant chemotherapy (NAC) is widely employed to minimize tumor burden and prevent local spread, with treatment efficacy varying based on molecular subtypes. Despite advancements, resistance to conventional therapies persists, prompting the exploration of alternative approaches, including immune cell therapy. Tumor-infiltrating lymphocytes (TILs) have emerged as immunological biomarkers in breast cancer, exhibiting associations with molecular subtypes and treatment response. This retrospective study assessed the clinico-pathological relationship between stromal TILs and AR expression across molecular subtypes of invasive breast carcinoma in an Indian cohort. Thirty-seven patients receiving NAC followed by modified radical mastectomy were analyzed for TILs and molecular subtyping. Immunohistochemistry was used to determine hormone receptor status and AR expression. A higher AR positivity was observed in hormone receptor-positive/Her2neu-negative and hormone receptor-positive/Her2neu-positive tumors compared to triple-negative breast cancers (TNBCs). Significant associations were observed between AR expression and tumor grade, but not with age or Her2neu status. Although no significant correlation was found between AR and complete response to NAC, a weak negative correlation between AR and TILs was noted. Notably, TNBCs with negative AR and Ki67 index exhibited poorer responses to NAC, emphasizing the need for adjuvant therapy. These findings underscore the complex interplay between AR, TILs, and treatment response in breast cancer, highlighting the potential of personalized therapeutic approaches. Further research is warranted to elucidate the prognostic significance of AR and its implications for tailored treatment strategies in breast cancer management.

Clinical and Preclinical Activity of EGFR Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer Harboring BRAF Class 3 Mutations.

Patients with tumors harboring BRAF class 3 mutations lack targeted therapies. These mutations are characterized by low/absent BRAF kinase domain activation and are believed to amplify already active RAS signaling, potentially triggered by receptor tyrosine kinases like EGFR. Two patients with BRAF class 3-mutated metastatic non-small-cell lung cancer (NSCLC) were treated with erlotinib at our Institution after failure of standard therapies. Two cell lines were established from patients with BRAF class 3-mutated NSCLC, and their sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was assessed using EGFR-mutated, BRAF class 1 and 2-mutated, and KRAS-mutated NSCLC cell lines as controls. Patient 1, a 60-year-old male with BRAFD594N-mutated NSCLC, achieved complete response to erlotinib after progression on first- and second-line chemotherapy. Patient 2, a 60-year-old female with BRAFD594G-mutated NSCLC, achieved partial response to erlotinib after progression on first-line chemoimmunotherapy. High baseline phosphorylated EGFR values and reduced EGFR activation following erlotinib were observed in BRAF class 3-mutated and EGFR-mutated cell lines, but not in BRAF class 1-mutated, BRAF class 2-mutated, or KRAS-mutated lines. Erlotinib inhibited 2-dimensional growth in BRAF class 3-mutated cell lines (IC50 6.33 and 7.11 µM) and in the BRAF class 2-mutated cell line (IC50 5.51 µM), albeit at higher concentrations than in EGFR-mutated lines, whereas it showed no effect on BRAF class 1-mutated (IC50, >25 µM) or KRAS-mutated (IC50, >25 µM) lines. These findings were corroborated by 3-dimensional and sphere formation assays. In the Cancer Cell Line Encyclopedia, BRAF class 3-mutated NSCLC cell lines showed greater sensitivity to EGFR-TKIs compared with BRAF class 2-mutated and KRAS-mutated lines. BRAF class 3 mutations in NSCLC may identify a novel targetable population sensitive to EGFR-TKIs.

Computed Tomography Scan and Clinical-based Complete Response Prediction in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Machine Learning Approach

Abstract Background: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy (nCRT), followed by total mesorectal excision. Examining the response to treatment is one of the most important factors in the follow-up of patients; therefore, in this study, radiomics patterns derived from pretreatment computed tomography images in rectal cancer and its relationship with treatment response measurement criteria have been investigated. Methods: Fifty patients with rectal adenocarcinoma who were candidates for nCRT and surgery were included. The information obtained from the tumor surgical pathology report, including pathological T and N, the degree of tumor differentiation, lymphovascular invasion, and perineural invasion along with radiomics characteristics to each patient, was assessed. Modeling with disturbed forest model was used for radiomics data. For other variables, Shapiro–Wilk, Chi-Square, and Pearson Chi-square tests were used. Results: The participants of this study were 50 patients (23 males [46%] and 27 females [54%]). There was no significant difference in the rate of response to neoadjuvant treatment in between age and gender groups. According to the modeling based on combined clinical and radiomics data together, area under the curves for the nonresponders and complete respond group (responder group) was 0.97 and 0.99, respectively. Conclusion: Random forests modeling based on combined radiomics and clinical characteristics of the pretreatment tumor images has the ability to predict the response or non-response to neoadjuvant treatment in LARC to an acceptable extent.

Additional expression of T-cell engager in clinically tested oncolytic adeno-immunotherapy redirects tumor-infiltrated, irrelevant T cells against cancer cells to enhance antitumor immunity

BackgroundOncolytic adenoviruses (OAds) are the most clinically tested viral vectors for solid tumors. However, most clinically tested “Armed” OAds show limited antitumor effects in patients with various solid tumors even...

Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial

In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial (NCT00490139), we identify and characterize five molecular subtypes associated with the risk of distant recurrence: immune-enriched, proliferative/metabolic-enriched, mesenchymal/stroma-enriched, luminal, and ERBB2-dependent. Additionally, we validate the biological profiles of the subtypes and explore their prognostic/predictive value in external cohorts, namely the NeoALTTO trial (NCT00553358), SCAN-B (NCT02306096), I-SPY2 (NCT01042379), METABRIC and TCGA. Immune-enriched tumors present better survival outcomes, in contrast to mesenchymal/stroma-enriched and proliferative/metabolic-enriched tumors, while luminal and ERBB2-dependent tumors are characterized by low and high rates of pathological complete response, respectively. Of note, these molecular subtypes provide the rationale for treatment approaches leveraging the heterogeneous biology of HER2-positive breast cancer.

Comparison of efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA–IIIB non-small-cell lung cancer in real-world practice

ObjectiveThere is currently no consensus over whether neoadjuvant immunochemotherapy is more effective in young patients than in elderly patients with IIA–IIIB non-small-cell lung cancer (NSCLC). In this study, we compare the efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA–IIIB NSCLC.MethodsThis retrospective study consecutively included IIA–IIIB NSCLC patients who received 2–4 cycles preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2022. The 1:1 propensity score match analysis was conducted to balance the confounding factors between the young patient group (< 65 years old) and elderly patient group (≥ 65 years old). The follow-up period would not end until at least 1 year after surgery or patient’s decision to abandon treatment. The primary endpoint was pathological response, while the secondary endpoints were objective response rate (ORR), adverse events (AEs), disease-free survival (DFS) and overall survival (OS).ResultsA total of 179 patients were included in our study: <65 years group (71 patients) and ≥ 65 years group (108 patients). After a 1:1 propensity score matching,132 patients (66 pairs) were analyzed to compare the efficacy and safety between the two groups. The ORR in the young patient group and elderly patient group was 72.7% and 71.2% (P = 1.000), respectively. The incidence of grade 3–4 AEs in the elderly patient group was similar to the young patient group (13.6% vs. 16.7%, P = 0.627). About 62.1% (41/66) in the young patient group and 54.5% (36/66) in the elderly patient group eventually underwent surgery. The rate of major pathological response (MPR) in the young patient group and elderly patient group was 68.3% and 55.6% (P = 0.903), respectively. The rate of pathological complete response (pCR) in the young patient group was significantly higher than that in the elderly patient group (46.3% vs. 22.2%, P = 0.027). The median DFS in the young patient group was not reached and 32.2 months in the elderly patient group (P = 0.071). The 1-year DFS rate, 2-year DFS rate and 3-year DFS rate in the young patient group were 90.2%, 85.4% and 80.5%, with that in the elderly patient group 86.1%, 69.4% and 66.7%. The median OS in the young patient group was 42.4 months and not reached in the elderly patient group (P = 0.067). The 1-year OS rate, 2-year OS rate and 3-year OS rate in the young patient group were 97.6%, 90.2% and 90.2%, with that in the elderly patient group 88.9%, 80.6% and 72.2%.ConclusionsFor IIA–IIIB NSCLC, neoadjuvant immunochemotherapy in young patients can produce a higher percentage of patients with a pCR than in elderly patients. However, the survival benefits and incidence of AEs are similar in young and elderly patients.

Adjuvant Immunotherapy Does Not Improve Survival in Non-small Cell Lung Cancer with Major/Complete Pathological Response after Induction Immunotherapy

In patients with resectable non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI)-based regimens in both neoadjuvant and perioperative settings demonstrate survival benefit. To date, no study has compared the efficacy between pure neoadjuvant and perioperative approaches, especially in patients who achieve substantial pathological responses. In this retrospective study, patients with clinical stage II-IIIB NSCLC who achieved either major (MPR) or complete (pCR) pathological response after induction ICI plus chemotherapy followed by resection between 2019 and 2023 were identified from multicenter databases. Inverse probability of treatment weighting-adjusted Cox regression was performed to compare disease-free survival (DFS) and overall survival (OS) between patients who did and did not receive ICIs postoperatively. One hundred thirty-six patients who achieved pCR and seventy-two patients who achieved MPR were enrolled. Three-quarters of them had squamous cell cancer. The inverse probability-weighted cohort represented 208 weighted patient cases (adjuvant ICI, 117; control, 91). The weighted DFS/OS rates did not differ between the adjuvant-ICI group and the control group (3-year DFS rates: 90.2% vs. 93.2%, hazard ratio [HR]= 2.47, 95% confidence interval [CI]: 0.74 to 8.22; 3-year OS rates: 89.1% vs. 93.9%, HR=2.44, 95% CI: 0.71 to 8.34). Adverse events during the postoperative ICI treatment were found in 19 of 120 patients (15.8%) and led to adjuvant ICI termination in 18 patients (15.0%). Adjuvant ICI does not improve survival in NSCLC patients who achieve pCR/MPR following neoadjuvant immunochemotherapy. A de-escalation strategy could be considered given the adverse events associated with postoperative ICI treatment.

Improvements of the damage responses and failure modes of an RC vehicle over pass bridge under contact explosion using FEM-SPH coupled computational frameworks

Winds, earthquakes, and blasts are unpredictable and most challenging dynamic loads. However, the blast is relatively new, and its protection over infrastructure is a vital concern. Conversely, bridges play a critical role in the transport system, and their loss may affect the Nation’s growth. However, the literature says that experimental and numerical simulation is an excellent option to predict the blast impacts. Most of the data from the experiments are collected by photos or videography at high temperatures. Therefore, the reliability of those data is a genuine concern, particularly for bridges. Conversely, if correctly explored, numerical simulation is an option to get into the blast field with high accuracy. A mesh-based method like Finite Element Method (FEM) is excellent for numerical simulation up to a specific temperature. Beyond that, it starts a mesh tangling. Element erosion and remeshing processes may overcome this issue if the mesh-free method simulates. Smoothed Particle Hydrodynamics (SPH) is a mesh-free particle method that can naturally handle massive deformation due to adaptive features. Finally, the current study has coupled two discretisation systems to avoid instability and increase run time. Therefore, FEM-SPH coupling has been adopted to explore the direct damage-reduction, complete damage-time response, damaged contours of the shock wave propagations, damaged contours of particle formation, the effective plastic strain (EPS) and different failure modes of the Vehicle Over Pass typed bridge without and with the protective layer of non-Explosive Reactive Armour (nERA). Finally, the improvement of the bridge is eye-catching as the nERA effectively reduces the deformation, damage, particle formation, EPS, and failure modes.

Molecular biomarkers for predicting complete response to preoperative chemoradiation in people with locally advanced rectal cancer.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: Primary objectives To identify and estimate the prognostic value of molecular biomarkers as predictors of pathological complete response to neoadjuvant chemoradiotherapy in people with locally advanced rectal cancer. summarises the review question in population, index prognostic factor, comparator prognostic factor(s), outcome, timing, and setting (PICOTS) format. [Table: see text] [Figure: see text] Secondary objectives To explore the following biomarker measurement, treatment, and study design factors as possible sources of heterogeneity in the association between the prognostic factor and pathological response: type of assay/measurement method, biomarker positivity criteria or cut-off point, chemotherapy regimen, and radiotherapy regimen.

Phase 2, Multicenter, Open-label, Nonrandomized Study of Neoadjuvant Chemotherapy Liposomal Irinotecan With 5-Fluorouracil, Leucovorin, and Oxaliplatin, Followed by Chemoradiotherapy in Patients With Rectal Cancer in a Watch-and-Wait Program.

To evaluate the efficacy of neoadjuvant chemotherapy combination with liposomal irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin in patients with locally advanced rectal cancer. This was a phase 2, nonrandomized, multicenter study in adults with stage II or III rectal cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1. Total neoadjuvant therapy (TNT) consisted of neoadjuvant chemotherapy combination with liposomal irinotecan (60mg/m2), oxaliplatin (60mg/m2), leucovorin (400mg/m2), and fluorouracil (2400mg/m²), followed by chemoradiotherapy [ie, capecitabine (825mg/m2) and radiotherapy according to the standard of care]. The primary efficacy endpoint was the proportion of patients who achieved clinical complete response (cCR), defined as the normalization of pelvic magnetic resonance imaging, rectoscopy, computed tomography scan, and tumor markers. The median follow-up was 32.3 months. Of the 30 patients who underwent TNT and were evaluated, 6 (20.0%; 95% CI: 5.2%-34.8%) patients achieved a cCR. There were no deaths. The median disease-free survival (DFS) for patients with cCR was not reached after a follow-up of 32 months; the 1-year DFS rate was 90.0% (95% CI: 71.0%-100%), and the 2-year and 3-year DFS rates were 80.0% (95% CI: 55.0%-100%). No grade ≥4 adverse events (AEs) were observed. Grade 3 AEs occurred in 18 patients (60%), most frequent was diarrhea (n = 9, 30%). Eleven (36.7%) patients experienced serious AEs, with diarrhea being the most frequent (n = 6, 20.0%). TNT with 5-fluorouracil, leucovorin, and oxaliplatin and chemoradiation is a safe and effective therapeutic alternative for the management of locally advanced rectal cancer.

High C-reactive protein is associated with the efficacy of neoadjuvant chemotherapy for hormone receptor-positive breast cancer.

C-reactive protein (CRP) is a nonspecific biomarker for systemic inflammatory response and is linked to the prognosis of breast cancer (BC); however, few studies have investigated the correlation between CRP and the effectiveness of neoadjuvant chemotherapy treatment for BC. We recruited 177 patients with BC who underwent neoadjuvant chemotherapy in our clinical trial. the median CRP level (0.24 mg/L), patients were categorized into high and low groups. We examined the relationship between CRP levels and various clinicopathological factors, including pathological complete response (pCR), using the chi-square test or Fisher exact test. Furthermore, we evaluated the predictive capacity of CRP for different molecular subtypes by constructing receiver operating characteristic curves. To identify the independent variables associated with pCR, we conducted logistic regression multivariate analysis. No association was found between C-reactive levels at baseline and pCR rates. CRP level was significantly associated with higher body mass index, and the high CRP group had more overweight patients (47.06% vs. 16.30%, P < .001). In hormone receptor-positive patients, the high CRP group demonstrated a significantly higher pCR rate (OR = 4.115, 95% CI: 1.481-11.36, P = .009). The areas under the curve was 0.670 (95% CI: 0.550-0.792, P < .001). Multivariate logistic analysis showed that the CRP level was a significant independent predictor of pCR (OR = 5.882, 95% CI: 1.470-28.57, P = .017). High CRP levels were found to be associated with a higher pCR rate, indicating their independent predictive value in determining the efficacy of neoadjuvant chemotherapy in hormone receptor-positive BC patients.

Comparative Study of Two Thoracic External Beam Radiotherapy Regimen 30Gy in 10 Fractions Versus 20Gy in 5 Fractions for Palliation of Symptoms in Non-Small Cell Lung Cancer

Metastatic non-small cell lung cancer (NSCLC) frequently manifests with symptoms from the primary tumor within the chest, such as shortness of breath, chest pain, coughing, and hemoptysis. Thoracic palliative radiotherapy is a viable option for alleviating symptoms in these patients, who typically have a poor prognosis and are not candidates for curative treatment. Given their limited survival, a shorter treatment period that achieves adequate palliation is often preferred. Hypofractionated thoracic radiotherapy may meet this criterion. This quasi-experimental study, conducted at the Department of Radiotherapy, Rajshahi Medical College Hospital from January to December 2020, aimed to compare the response and acute toxicity of two thoracic external beam radiotherapy (EBRT) regimens—30 Gy in 10 fractions versus 20 Gy in 5 fractions—in the palliation of symptoms in NSCLC patients. Seventy-two diagnosed NSCLC patients with chest tumor-related symptoms (cough, dyspnea, hemoptysis, chest pain) unsuitable for radical treatment were enrolled and allocated into two groups by a non-randomized technique. Arm-A received 30 Gy in 10 fractions, while Arm-B received 20 Gy in 5 fractions. Patients were assessed before radiotherapy, at the end of treatment, and at 4 and 8 weeks post-treatment. The study found that both Arm-A and Arm-B showed highly significant improvement in all symptoms compared to pre-treatment status (p &amp;lt; 0.001), with no significant difference between the two arms (p &amp;gt; 0.05). In Arm-A, 22.22% of patients achieved complete symptomatic response and 44.44% showed improvement, while in Arm-B, 19.44% of patients achieved complete symptomatic response and 50% showed improvement. No statistically significant difference was observed between the two arms regarding clinical symptomatic response (p &amp;gt; 0.05) or treatment-related toxicities (p &amp;gt; 0.05), all of which were manageable. In conclusion, both treatment regimens were equally effective in symptom palliation and had comparable toxicity profiles, supporting the use of either regimen depending on patient needs and resource availability.

Outcomes with loncastuximab tesirine following CAR T-cell therapy in patients with relapsed or refractory diffuse large B-cell lymphoma

The efficacy of loncastuximab tesirine (lonca) following chimeric antigen receptor T-cell therapy (CAR-T) progression/failure is unknown. Hence, we sought to examine real-world use and outcomes of lonca following CAR-T in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the USA. In this retrospective study, we included adults (age ≥ 18 years) with R/R DLBCL who received lonca monotherapy as third- (3 L) or fourth line (4 L) treatment after progressing on second line (2 L) or 3 L CAR-T, respectively. Post-CAR-T lonca outcomes included response rates (overall response rate [ORR] and complete response [CR] rate), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 118 patients were included in the analysis with 95 receiving lonca following 2 L CAR-T (median age:66 years; 61% male) and 23 following 3 L CAR-T (median age:57 years; 43% male). Patients with 2 L CAR-T/3 L lonca had an ORR of 73% (CR rate of 34%). With a median follow-up of 8.5 months following lonca initiation, median DOR, PFS, and OS were not reached. The DOR, PFS, and OS at 12 months were 68%, 77%, and 84%, respectively. Patients with 3 L CAR-T/4 L lonca had an ORR of 78% (CR rate of 17%). With a median follow-up of 13 months following lonca initiation, the median DOR and PFS were 7.6 and 12.0 months, while median OS was not reached. OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings including those who were resistant to or progressed after CAR-T.

Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study

Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma. This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients underwent lymphodepletion with fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 (intravenously daily for 3 days), followed by intravenous CTX130 infusion at dose levels ranging from 3 × 107 CAR+ T cells (dose level 1) to 9 × 108 CAR+ T cells (dose level 4). The primary endpoint was the incidence of adverse events, defined as dose-limiting toxicities occurring within 28 days post-infusion. Secondary endpoints included objective response rate. Safety and activity analyses were performed on data from all patients who received CTX130. The trial is registered with ClinicalTrials.gov (NCT04502446) and EudraCT (2019-004526-25) and is closed to enrolment. Between Aug 28, 2020, and May 30, 2023, 41 patients were enrolled and 39 (95%) received CTX130. The median patient follow-up was 7·4 months (IQR 3·1-12·2). 21 (54%) of 39 patients were female and 18 (46%) were male. 24 (62%) patients were White, eight (21%) were Black, three (8%) were Asian, three (8%) were from other racial or ethnic groups, and one (3%) was not reported. The median number of previous lines of anticancer therapy was 2·5 (IQR 1·3-4·0) for patients with peripheral T-cell lymphoma and 5·0 (IQR 5·0-7·0) for patients with cutaneous T-cell lymphoma. Cytokine release syndrome was the most common adverse event, occurring in 26 (67%) of 39 patients (23 were grade 1-2, two were grade 3, and one was a grade 4 dose-limiting toxicity at dose level 4). Grade 1-2 neurotoxic events were observed in four (10%) of 39 patients. The most common grade 3-4 adverse events were neutropenia (14 [36%]), anaemia (11 [28%]), and thrombocytopenia (six [15%]). Serious adverse events occurred in 25 (64%) patients, with CTX130-related serious adverse events in 14 (36%) patients, the most common related serious adverse event being cytokine release syndrome in 11 (28%) patients. 21 patients died, 16 from progressive disease and five from adverse events considered unrelated to CTX130 treatment. 18 of 39 patients (46·2% [95% CI 30·1-62·8) had an objective response. Of those treated at dose level 3 and higher, 16 of 31 patients (51·6% [33·1-69·8]) had objective responses, including six (19·4% [7·5-37·5]) with complete response and ten (32·3% [16·7-51·4]) with a partial response. In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development. CRISPR Therapeutics.