Median Progression-free Survival Time Research Articles

Efficacy and Safety of Isatuximab, Carfilzomib, and Dexamethasone (IsaKd) in Multiple Myeloma Patients at the First Relapse After Autologous Stem Cell Transplantation and Lenalidomide Maintenance: Results from the Multicenter, Real-Life AENEID Study.

Background: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1-3 prior treatments. Methods: Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: After a median follow-up time of 12.9 months (range, 1-77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.

Surgical Resection Versus Microwave Ablation for Colorectal Liver Oligometastases: A Multicenter Cohort Study of 1027 Patients

BackgroundThe choice between surgical resection (SR) and microwave ablation (MWA) as first-line treatments that prolong survival duration for colorectal liver oligometastases (CRLOM) remains controversial.ObjectiveThis study aimed to compare survival outcomes, therapeutic parameters, and safety between SR and MWA in patients with CRLOM.MethodsFrom January 2012 to December 2022, we identified 1027 eligible patients with CRLOM who underwent either SR (n = 464) or MWA (n = 563) as hepatic local-region treatment. The cumulative 1-, 3-, 5-, and 8-year overall survival (OS) and progression-free survival (PFS) rates between the two modalities were compared using the Kaplan–Meier method with the log-rank test. The propensity score matching (PSM) method was used to improve the selective bias. Univariate and multivariate analyses of clinicopathological variables were conducted to identify risk factors affecting long-term survival.ResultsAfter PSM, all baseline variables were balanced between the SR (n = 393) and MWA groups (n = 393). After a median follow-up of 39.8 months, no significant differences in the long-term survival outcomes were observed between the two groups (median OS time, MWA: 70.6 months vs. SR: 83.2 months; P = 0.124; median PFS time, MWA: 18.5 months vs. SR: 22.3 months; P = 0.680). PSM-adjusted analyses revealed similar results. The presence of 3–5 intrahepatic nodules (hazards ratio [HR] 1.65; 95% CI 1.31–2.06; P < 0.001) and SR (HR 1.28; 95% CI 1.11–1.69; P = 0.028) were independent prognostic risk factors for OS. A significant interaction effect of therapeutic modality and age, pathological differentiation, diameter, and number was observed (P = 0.039, 0.004, 0.031, and 0.032).ConclusionsMWA offers comparable long-term survival benefits to SR for patients with CRLOM.

Effects of Antibiotics on First-line Immunotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma.

Immunotherapy combined with chemotherapy has become the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the impact of antibiotic (ATB) use on the efficacy of immunotherapy in RM-NPC remains unclear. A total of 200 patients with RM-NPC who started first-line immunotherapy between October 2021 and September 2023 were included. Forty-six patients received ATB within 60 days before and 42 days after the first infusion of immunotherapy (group ATB+), and the remaining 154 patients were in group ATB-. The median progression-free survival (PFS) times of the ATB+ and ATB- groups were 11.20 and 19.87 months, respectively (P = 0.061). The 2-year overall survival (OS) rates of the ATB+ and ATB- groups were 52.6% and 76.7%, respectively (P = 0.001). In multivariate analysis, ATB use was significantly associated with worse OS (hazard ratio = 2.549, P = 0.002). No significant differences were observed between the 2 groups in terms of grade 3+ treatment-related adverse events. ATB use in RM-NPC may reduce the effectiveness of first-line immunotherapy.

Immune checkpoint inhibitors plus chemotherapy in the first-line treatment of young unresectable gastric cancer patients: a multicentre real-world study.

PD-1 inhibitors combined with chemotherapy have become the standard first-line treatment for advanced gastric cancer (GC), but their efficacy in young GC patients is unknown. This study aimed to evaluate the efficacy of immunotherapy in young GC patients and explore new treatment strategies for this population. Clinicopathological data of young unresectable GC patients were collected from multiple centres. We defined young as ≤45 years. Statistical analyses were conducted with SPSS IBM for Windows version 24.0. In total, 225 young unresectable GC patients were registered. Their clinicodemographic characteristics included female predominance (60.9%), poor differentiation (86.7%), high family history of cancer (14.2%), low HER2 expression (12.2%), PD-L1 expression (43.0%) and mismatch repair (MMR) deficiency (1.0%), and a high proportion of peritoneal metastasis (49.3%). After screening, 134 patients were included for analysis: 63 received dual chemotherapy (mFOLFOX6, XELOX, SOX and two-drug containing paclitaxel), 32 PD-1 inhibitors plus dual chemotherapy (mFOLFOX6, XELOX, SOX and two-drug containing paclitaxel), and 39 triple regimens (two-drug chemotherapy combined with apatinib or trastuzumab, or triple chemotherapy based on platinum, fluorouracil and paclitaxel). The effectiveness analysis revealed no significant difference in the disease control rate (DCR) between the dual chemotherapy group and the PD-1 inhibitor plus dual chemotherapy group (P=0.787), but triple regimens led to the best DCR (71.4% vs. 68.8% vs. 94.9%, all P<0.05). Kaplan-Meier curves showed median progression-free survival (PFS) times of the three groups of 4.7, 4.7 and 9.2 months, respectively. The median overall survival (OS) was 13.9, 11.0 and 15.9 months, respectively. Multivariate analyses showed that triple regimens were an independent prognostic factor for PFS [hazard ratio (HR) 0.430, 95% confidence interval (CI) 0.263-0.700; P=0.001]. Detailed survival analysis demonstrated that patients receiving intraperitoneal infusion of paclitaxel followed by intravenous paclitaxel combined with S-1 and apatinib oral therapy had better PFS (P=0.014) and OS (P=0.013) than those receiving other regimens. Young patients with GC have unique clinical characteristics and are not sensitive to immunotherapy. Triple regimens, especially intraperitoneal infusion of paclitaxel followed by intravenous paclitaxel combined with S-1 and apatinib oral therapy, deserve to be studied as first-line therapies.

Bronchial Arterial Chemoembolization With Drug-eluting Beads Versus With Gelfoam Particles for Advanced Nonsmall-cell Lung Cancer.

Bronchial arterial chemoembolization (BACE), as a safe and effective minimally invasive treatment method, is increasingly being accepted by more and more patients with advanced nonsmall-cell lung cancer (NSCLC). In recent years, drug-eluting beads (DEB)-BACE has also been applied in the field of lung cancer. It is still unclear which is more recommended due to the limited number of comparative studies between conventional BACE (C-BACE) and DEB-BACE. To compare the safety and efficacy of C-BACE (BACE with gelfoam particles) and DEB-BACE for advanced NSCLC. From January 2021 to April 2023, 48 consecutive patients (37 males and 11 females) with advanced NSCLC treated with DEB-BACE (group A) or C-BACE (group B) at our center were collected retrospectively in this study. There were 18 patients in group A and 30 patients in group B. The technical success rate, adverse events, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between the 2 groups. The technical success rate in both groups was 100%. The median OS times were 19.5 months and 12.5 months in group A and group B, respectively (P=0.0062). The median PFS times were 13 months and 7 months in group A and group B, respectively (P=0.0072). The ORRs at 6 months were 72.2% and 46.7% in group A and group B, respectively (P=0.084). The DCRs at 6 months were 88.9% and 63.3% in group A and group B, respectively (P=0.043). Grade 1 adverse events like chest pain, and cough were common, while serious adverse events did not occur. BACE with DEB or gelfoam particles were equally safe. The DEB-BACE showed better survival and tumor response than C-BACE for advanced NSCLC.

Efficacy and Survival Analysis of Chidamide Combined with DICE Regimen in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Efficacy and Survival Analysis of Chidamide Combined with DICE Regimen in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Clinical Characteristics and Prognosis of Primary Pulmonary Lymphoma

Clinical Characteristics and Prognosis of Primary Pulmonary Lymphoma

Randomized Phase III Study of EGFR Tyrosine Kinase Inhibitor and Intercalated Platinum-doublet Chemotherapy for Non-small Cell Lung Cancer Harboring EGFR Mutation.

This study was performed to confirm the superiority in overall survival (OS) of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) (gefitinib or osimertinib) monotherapy versus EGFR-TKI with intercalation of cisplatin plus pemetrexed as the first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSqNSCLC) harboring EGFR mutation. This was an open-label, multicenter, randomized phase III study. Patients with chemotherapy-naïve advanced or recurrent NSqNSCLC harboring EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were randomly assigned (1:1) to EGFR-TKI monotherapy or EGFR-TKI plus intercalated chemotherapy group. The primary endpoint was OS, and the secondary endpoints included progression-free survival (PFS). From December 2015 to October 2020, 501 patients were randomized. The EGFR-TKI was changed from gefitinib to osimertinib in October 2018 (gefitinib cohort: n=308, osimertinib cohort: n=193). There was no survival advantage in the EGFR-TKI plus intercalated chemotherapy group; the median survival time of both groups was 48.0 months (hazard ratio, 0.985; 91.4% confidence interval, 0.796-1.219; one-sided P=0.4496). The median PFS time was 12.0 months in the EGFR-TKI monotherapy group and 18.0 months in the EGFR-TKI plus intercalated chemotherapy group (hazard ratio, 0.762; 95% confidence interval, 0.628-0.925; one-sided P=0.003). The OS and PFS trends in both gefitinib and osimertinib cohorts were identical to those in the entire population. The intercalation of cisplatin plus pemetrexed after the response to EGFR-TKI improved PFS but not OS compared with EGFR-TKI monotherapy as the first-line treatment for advanced NSqNSCLC harboring EGFR mutation.

Effect of Bortezomib Treatment in Multiple Myeloma on Blood Coagulation Function, Renal Function, Immune Function, and the NF-κB Pathway-Associated Indicators.

Aims/Background Multiple myeloma (MM) presents several underlying mechanisms of immune dysfunction. Advanced research on these mechanisms has introduced new drugs for MM into clinical practice. However, several challenges occur, particularly in cases of relapsed and refractory MM. In recent years, bortezomib has been recognized, for its anti-myeloma effect in both newly identified and refractory MM patients, but its mechanism of action on MM remains unexplored. Consequently, this study aims to explore the influence of bortezomib on coagulation function, renal function, immune function, and related indexes of nuclear transcription factor-κB (NF-κB) pathway in MM patients. Methods This retrospective study analyzed 120 MM patients admitted to the First People's Hospital of Nantong, China, between August 2018 and August 2023. Based on different treatment methods, patients were divided into a control group (thalidomide, cyclophosphamide, and dexamethasone (TCD), 58 cases) and an observation group (TCD regimen and bortezomib, 62 cases). The therapeutic efficacy of the drug was observed, and the levels of blood indexes, coagulation function indexes, NF-κB related indexes, renal function indexes and immunosuppressive factors were compared between the groups both before and after treatment. Results There were no significant differences in disease control rate (DCR) between the two groups (p > 0.05). After treatment, the objective response rate (ORR) and the hemoglobin levels were significantly higher in the observation group than in the control group, with lower M protein levels (p < 0.05). Furthermore, the prothrombin time (PT), the activated partial thromboplastin time (APTT), fibrinogen (FIB) values, NF-κB expression levels, β2-microglobulin (β2-MG) levels, blood urea nitrogen (BUN), serum creatinine (Scr), transforming growth factor-β (TGF-β), interleukin-6 (IL-6) and interleukin-17 (IL-17) levels were substantially decreased in the observation group compared to the control group (p < 0.001). Additionally, the progression-free survival rate was significantly higher in the observation group than in the control group (p < 0.001). However, no significant difference was observed in the overall survival (OS) rate between the two groups (p > 0.05). Moreover, the median progression-free survival (PFS) time was 11.95 months in the observation group and 9 months in the control group, while the median OS time was 11.7 months in the control group. Conclusion In summary, bortezomib treatment improves coagulation and renal function in MM patients. Furthermore, it helps reduce immune suppression, prolong survival time, and inhibit the NF-κB pathway activation.

Use of Cyclophosphamide, Vincristine, Prednisolone andVinblastine for the Treatment of Large Cell Lymphomain Cats.

The standard chemotherapy treatment for large-cell lymphoma in cats is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or COP (cyclophosphamide, vincristine, and prednisolone) chemotherapy protocols. Substituting vinblastine for vincristine might have similar efficacy, with lower severity of gastrointestinal adverse events. To evaluate whether the addition of vinblastine to a low-dose vincristine COP protocol could reduce the frequency and severity of adverse gastrointestinal effects while maintaining or increasing efficacy. Medical records of 41 cats with large-cell lymphoma treated with the modified COVP protocol at one veterinary referral institution. Retrospective case series study. All relevant clinical data were retrospectively collected. Median progression-free survival, disease-free interval, and survival time were calculated using the Kaplan-Meier Method. Differences between groups were analyzed using the log-rank test, and adverse events were graded using VCOG-CTCAE v2. Progression-free survival was 264 days (range, 6-1486 days), the disease-free interval was 812 days (range, 39-1486 days) and the median survival time for all cats was 412 days (range, 7-1772 days). Complete response was achieved in 59% of the cases, and partial response was observed in 17%. Cats that achieved CR lived significantly longer, 838 days (range, 81-1772 days) versus 143 days (range, 10-798 days; p = 0.0018). The COVP protocol was generally well tolerated, and the most common adverse effects were mild signs of gastrointestinal disease and hematological abnormalities that did not require a pause in treatment. Grade-1 vomiting was the most common (24%), followed by grade-2 (22%) and grade-1 reduced appetite (20%). Cats with lymphoma treated with COVP seem to achieve acceptable survival and response rates compared to traditional chemotherapy protocols.

Impact of Epstein-Barr virus and CD lymphocytes on the prognosis of patients with advanced nasopharyngeal carcinoma

BackgroundUnderstanding the factors influencing the occurrence and progression of nasopharyngeal carcinoma (NPC) is critical for reducing incidence rates and improving patient outcomes. The objective of this study is to preliminarily investigate the impact of Epstein-Barr virus (EBV) and cluster of differentiation (CD) lymphocytes on the prognosis of patients with advanced NPC.MethodA prospective cohort study design was employed, involving newly diagnosed patients with NPC confirmed by pathological diagnosis. Patients received standard radiotherapy and chemotherapy according to treatment guidelines, with regular follow-up assessments conducted. Prior to treatment initiation, patients underwent testing for EBV, blood biochemistry, and other parameters, while baseline data including patient age, pathology, and tumor node metastasis classification (TNM) staging were also collected. The primary outcome measure focused on disease progression.ResultsThe analysis included a total of 99 cases, with a median age of 52 years, all of whom were stage III or IV patients. The median progression-free survival time for the patients was 45.53 months. After adjusting for confounding factors such as age, T stage, and metastasis, patients with low levels of B cells exhibited a 1.503-fold increased risk of progression compared to those with high levels of B cells (adjusted hazard ratio [HR] = 2.503; 95% confidence interval [CI]: 1.062–5.899). Patients infected with EBV had a 1.739-fold increased risk of progression compared to uninfected patients (adjusted HR = 2.739; 95% CI: 1.222–6.125).ConclusionThis study observed that patients with advanced nasopharyngeal carcinoma, infected with EBV and exhibiting diminished B cell levels, display heightened susceptibility to disease deterioration and progression.

Five-year outcomes with gefitinib induction and chemoradiotherapy in EGFR-mutant stage III non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study

BackgroundWe previously showed the 2-year OS rate, the primary endpoint, of 90% in a phase II trial of gefitinib induction followed by chemoradiotherapy (CRT) in unresectable, stage III, EGFR-mutant, non-small-cell lung cancer (NSCLC). However, neither long-term survival data nor late-phase adverse event profiles have been presented.Patients and methodsPatients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy for 8 weeks. After confirming no disease progression during induction therapy, cisplatin and docetaxel on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy were subsequently administered.ResultsIn the enrolled twenty patients, the 5-year OS rate and median survival time were 70.0% [95% confidence interval: 45.1–85.3] and 5.5 years [4.91-NE], respectively, whereas 5-year PFS rate and median PFS time were 15.0% (3.7–33.5) and 1.4 years [0.69–2.29], respectively. Efficacy did not seem influenced even if radiation field was re-planed in response to the effect of gefitinib induction. As for late adverse events, pulmonary fibrosis occurred in 7 patients (35%). The median time from completion of CRT to the occurrence of the event was 245 days. All were grade 1, and there was no evidence of cavitation of the lesions or chronic infections such as Aspergillus infection during the course of the disease. One case of small cell lung cancer occurred during the period.ConclusionsWith longer follow-up time, we demonstrated favorable efficacy with tolerable toxicity profiles in the EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III, NSCLC.Trial registration numbersUMIN00005086. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000006047&type=summary&language=EjRCTs071180036. https://jrct.niph.go.jp/latest-detail/jRCTs071180036

Efficacy and Safety of BeEAM, a Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphoma

Efficacy and Safety of BeEAM, a Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphoma

Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma.

To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database. This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC. A total of 378 patients in the UCAN database underwent NAC. On final surgical pathology, 101 patients (26.8%) had ≤ypT1N0 disease and were defined as NAC treatment responders. Patients who responded to NAC had significantly longer overall survival (OS) and progression-free survival (PFS) compared to non-responders. At 5 years post-surgery, 81.5% of responders were alive compared to 59.8% of non-responders. The median OS and PFS times among non-responders were 7.0 years (95% confidence interval [CI] 5.6-9.7) and 6.0 years (95% CI 4.6-9.3) respectively, while the median OS and PFS were not reached among responders. Limitations of this study include its retrospective design, heterogeneity in chemotherapy regimens, and the absence of clearly defined patient selection criteria for treatment. These data suggest that NAC can play a pivotal role in the treatment of well-selected UTUC patients who respond positively. Non-responders had clearly inferior outcomes. More work is needed to find predictors of response which can improve patient selection.

Regimen Selection for Chemoimmunotherapy in Nonsquamous Non-Small Cell Lung Cancer with Low PD-L1 Expression: A Multicenter Retrospective Cohort Study.

Regimen Selection for Chemoimmunotherapy in Nonsquamous Non-Small Cell Lung Cancer with Low PD-L1 Expression: A Multicenter Retrospective Cohort Study.

Maintaining First-Line Therapy Plus Radiation Therapy May Prolong Progression-Free Survival and Delay Second-Line Therapy for Oligoprogressive Hepatocellular Carcinoma.

Maintaining First-Line Therapy Plus Radiation Therapy May Prolong Progression-Free Survival and Delay Second-Line Therapy for Oligoprogressive Hepatocellular Carcinoma.

Anlotinib as Maintenance Therapy After First-Line Chemotherapy Combined with Consolidation Radiation for Extensive-Stage Small Cell Lung Cancer.

Small cell lung cancer is sensitive to chemotherapy and radiotherapy, but local recurrence and distant metastasis occur shortly after treatment. This study aimed to evaluate the real-world value of anlotinib as a maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) after first-line chemotherapy and consolidative thoracic radiotherapy (CTRT). A total of 150 patients with ES-SCLC treated with first-line chemotherapy and CTRT from April 2017 to December 2021 were retrospectively analyzed. After the completion of chemoradiotherapy, patients received anlotinib according to their desire. The primary endpoints were progression-free survival (PFS) and overall survival (OS) after the first diagnosis, and the secondary endpoints were prognostic factors and safety. The ORR and DCR of patients with ES-SCLC were 50.0% and 80.3%, respectively, in the anlotinib group and 42.9% and 69.0% in the no-maintenance therapy group. The 3-year OS rates were 27.6% and 12.6% in the anlotinib and observation groups (HR = 2.52, P = 0.003), and the median OS times were 23.8 months and 15.3 months. The 3-year PFS rates were 18.2% and 8.8% in the anlotinib and observation groups (HR = 1.76, P = 0.034) with median PFS times of 11.5 months and 8.8 months. After stratification on the basis of clinical response, patients who achieved CR plus PR after chemoradiotherapy had a longer median OS in the anlotinib and observation groups (34.0 months vs 24.8 months, HR = 2.40, P = 0.009). There were higher incidence rates of hand-foot syndrome (27.3% vs 10.5%, P = 0.001), gingival bleeding/hemoptysis (18.5% vs 4.8%, P = 0.015) and rash (33.3% vs 4.8%, P < 0.001) in the anlotinib group than in the observation group. Maintenance therapy with anlotinib improved the survival of patients with ES-SCLC after first-line chemotherapy and CTRT. Owing to the small sample size of the real-world trial, the reliability of our study needs to be confirmed in more studies.

Transarterial therapy combined with bevacizumab plus immune checkpoint inhibitors as a neoadjuvant therapy for locally advanced HCC

BackgroundTransarterial therapy (TAT), bevacizumab (Bev), and immune checkpoint inhibitors (ICIs) have individually exhibited efficacy in treating advanced-stage hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of the combination of these three treatments as a neoadjuvant modality in patients with locally advanced HCC.MethodsThe primary endpoint is overall survival (OS). The second endpoint is progression free survival (PFS), objective response rate (ORR), pathological response rate and safety.ResultsA total of 54 patients received standard systemic therapy comprising Bev combined with ICIs (Bev-ICIs group), 113 patients received direct surgery (Surgery group), and 273 patients received neoadjuvant therapy of TAT combined Bev plus ICIs, among which 79 patients (28.9%) underwent surgical resection after successful tumor downstaging (Neo-surgery group) while the remaining 194 patients (71.1%) received maintenance systemic therapies (Neo-maintenance group). Neoadjuvant following surgery demonstrated a prolonged OS in contrast to direct surgery, with a median OS time not reached in the Neo-surgery group and 30.6 (95% CI: 26.4-34.7) months in the Surgery group (hazard ratio (HR)=0.29, P=0.0058). The median PFS time in the Neo-surgery and Surgery groups stood at 19.2 (95% CI: 16.1-22.2) and 6.3 (95% CI:4.7-8) months, respectively (HR=0.25, P&amp;lt;0.0001). In patients failed to receiving resection after neoadjuvant therapy, the median OS was 22.8 (95% CI: 22.3-23.1) months, whereas that for the standard care population was 19.7 (95% CI: 15.9-24) month (HR=0.53, P=0.023). The median PFS time in Neo-maintenance group and Bev-ICIs groups was 11.2 (95% CI: 10.4-11.9) and 6.4 (95% CI: 4.4-8.5) months (HR=0.60, P=0.024). The ORR and disease control rate (DCR) across all patients received TAT-Bev-ICIs were 38.8% and 89.4%, respectively. Additionally, the pathological complete response (pCR) rate and the major pathological response (MPR) rate were 22.8% and 48.1% in the Neo-surgery group. As for safety, neoadjuvant therapy did not increase the perioperative complications when compared to direct surgery, and demonstrated similar incidences and severity of AEs when compared to the standard systemic therapy.ConclusionThe triple therapy regimen comprising TAT-Bev-ICIs emerged as a promising therapeutic strategy for locally advanced hepatocellular carcinoma (HCC) as a neoadjuvant intervention.

Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases.

Background/Objectives: Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. Methods: This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. Results: Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (p = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. Conclusions: The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.

Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Recurrent Small Hepatocellular Carcinoma: A Randomized, Open-Label, Controlled Trial.

To assess the efficacy and safety of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) in treating recurrent small hepatocellular carcinoma (HCC). In this trial, patients with recurrent small HCC (single lesion ≤5 cm) were randomly assigned to receive either SBRT or RFA. The primary end point was local progression-free survival (LPFS), and secondary end points were progression-free survival (PFS), overall survival (OS), local control rate, and safety. Between August 2019 and April 2022, 166 patients were assigned to SBRT (n = 83) and RFA (n = 83) groups. After a median follow-up time of 42.8 and 42.9 months in the SBRT and RFA groups, respectively, SBRT demonstrated a significantly better LPFS than that of RFA (hazard ratio [HR], 0.45 [95% CI, 0.24 to 0.87]; P = .014). The 2-year LPFS rates were 92.7% (95% CI, 87.3 to 98.5) with SBRT and 75.8% (95% CI, 67.2 to 85.7) with RFA. The median PFS time of the SBRT and RFA groups was 37.6 (95% CI, 26.0 to 49.2) and 27.6 (95% CI, 20.3 to 34.8) months, respectively (HR, 0.76 [95% CI, 0.50 to 1.15]; P = .190). Nine patients in the SBRT group and 10 in the RFA group died during the follow-up. The 2-year OS rates were 97.6% (95% CI, 94.3 to 100.0) in the SBRT group and 93.9% (95% CI, 88.9 to 99.2) in the RFA group (HR, 0.91 [95% CI, 0.37 to 2.22]; P = .830). The incidences of both acute and late adverse events were comparable between the groups (P = .436 and P = .715, respectively). SBRT achieved better LPFS than that of RFA in patients with single recurrent HCC ≤5 cm, especially in HCC ≤2 cm, whereas PFS, OS, and safety were comparable between the two treatments.