5-year Progression-free Survival Rates Research Articles

Refining MR-guided thermal ablation for HCC within the Milan criteria: a decade of clinical outcomes and predictive modeling at a single institution

BackgroundThe appropriateness of ablation for liver cancer patients meeting the Milan criteria remains controversial.PurposeThis study aims to evaluate the long-term outcomes of MR-guided thermal ablation for HCC patients meeting the Milan criteria and develop a nomogram for predicting survival rates.MethodsA retrospective analysis was conducted from January 2009 to December 2021 at a single institution. Patients underwent MR-guided thermal ablation. Factors influencing progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression and stepwise regression. A nomogram was developed for survival prediction, followed by risk stratification and internal validation. Adverse events (AEs) were also analyzed.ResultsA total of 181 patients were included, with a mean follow-up of 73.8 ± 31.7 months. The cumulative local tumor progression rates at 1, 3, and 5 years were 0.80%, 1.27%, and 1.86%, respectively. The 1-, 3-, and 5-year PFS rates were 81.8%, 57.4%, and 38.1%, and OS rates were 98.3%, 87.8%, and 62.9%. Poorer outcomes were associated with age ≤ 60 years, tumor size > 2 cm, multiple tumors, cirrhosis, proximity to major vessels, and narrow ablation margins (P < 0.05). The nomogram accurately predicted 3- and 5-year survival, and internal validation confirmed the results. AEs occurred in 33.7% of patients, with pain being the most common.ConclusionMR-guided ablation is effective for HCC patients within the Milan criteria, especially for those with smaller tumors and better liver function. The nomogram and risk stratification model are valuable tools for predicting patient outcomes and guiding treatment.

Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy

PurposesPrevious studies have demonstrated that proliferation, stroma or immunity strongly influence the prognosis and therapeutic resistance of diffuse large B-cell lymphoma (DLBCL). Herein, we aimed to integrate proliferation, stromal, and immune (PSI) features to systematically evaluate the risk stratification and explore novel therapeutic targets in DLBCL.MethodsUsing data from multiple researches, we comprehensively evaluated the characteristics and prognostic impact of PSI features in DLBCL, and developed a novel risk stratification model (PSI score) with a consistent cutoff value to stratify the risk of 3,229 DLBCL patients from different cohorts. Mechanisms underlying adverse prognosis in the high-risk DLBCLs were investigated through transcriptomic (n = 3,229), genomic (n = 576), and scRNA-seq (n = 20) analyses.ResultsWe identified a high-risk DLBCL subgroup (HPSI, 36.1% of DLBCL). HPSI was characterized by upregulation of spermidine synthase (SRM) and cold tumor microenvironment (TME). Compared to low-risk group, HPSI exhibited poorer prognosis, with lower 3-year OS (51.7% vs. 78.1%, P < 0.0001) and PFS (48.9% vs. 72.6%, P < 0.0001) rates. HPSI shared malignant proliferative phenotype resembling Burkitt lymphoma. Genomic analysis revealed extensive copy-number loss in the chemokine and interleukin coding regions within HPSI. Bulk and scRNA-seq analyses indicated that upregulation of SRM might mediate cold TME in DLBCL, potentially through suppressing immune activation pathways, promoting dendritic cells (DCs) transformation into tolerogenic DCs, and facilitating M2 polarization of macrophages. Finally, for eventual clinical translation, we integrated the model with other clinical features to develop a comprehensive database for DLBCL.ConclusionOur study effectively simplifies risk stratification of DLBCL, revealing that immune microenvironment and SRM jointly shape a subgroup of DLBCL with extremely poor prognosis. Targeting SRM may become a potential strategy for modulating immunotherapy in DLBCL, providing new insight for immunotherapy.

Nomogram models for predicting outcomes in thyroid cancer patients with distant metastasis receiving 131iodine therapy

This study aimed to establish and validate prognostic nomogram models for patients who underwent 131I therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first 131I administrated activity, and lesion 131I uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first 131I administrated activity, 131I uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first 131I treatment.

Multicenter study of thermal ablation versus partial thyroidectomy for paratracheal papillary thyroid microcarcinoma.

To compare the clinical outcomes of patients with unifocal paratracheal papillary thyroid microcarcinoma (PTMC) after thermal ablation (TA) vs. partial thyroidectomy (PT). This retrospective multicenter study included 436 patients with unifocal, clinical N0 paratracheal PTMC who underwent TA (210 patients) or PT (236 patients) between June 2014 and December 2020. The propensity score matching method was used to mitigate confounding factors between the two groups. Disease progression, progression-free survival (PFS), complications, and treatment variables were compared. Adjusted Cox regression models were utilized to assess the impact of treatment on disease progression. After matching, a comparable incidence of disease progression (3.3% vs. 2.2%, p = 0.79) and comparable 5-year PFS rates (97.0% vs. 97.4%, p = 0.75) were observed between the TA and PT groups. Adjusted Cox regression models showed no significant correlation between TA and disease progression. TA was associated with shorter hospitalization (0 vs. 6.0 days), less estimated blood loss (0 vs. 15.0 mL), shorter incision length (0.3 vs. 6.0 cm), and lower costs ($1748.3 vs. $2898.0) compared with PT (all p < 0.001). The complication rate was 1.1% after TA and 3.3% after PT (p = 0.28), with permanent complications were exclusively observed in the PT group. The mid-term incidence of disease progression and PFS rates were similar between TA and PT in patients with unifocal paratracheal PTMC. TA might represent a promising alternative treatment to PT for eligible patients with paratracheal PTMC. Question Is thermal ablation a viable alternative treatment to partial thyroidectomy for treating paratracheal papillary thyroid microcarcinoma? Findings Comparable incidence of disease progression and 5-year progression-free survival rates were observed between thermal ablation and partial thyroidectomy. Clinical relevance Thermal ablation, as a minimally invasive procedure, provides a promising alternative to partial thyroidectomy, with comparable clinical outcomes for patients with paratracheal papillary thyroid microcarcinoma.

Effectiveness and safety of hypofractionated gamma knife radiosurgery for large meningiomas and those adjacent to the optic pathway and brainstem: preliminary therapeutic outcomes.

Recent technologic advancements have facilitated the use of hypofractionated Gamma Knife-based radiosurgery (HF-GKRS) to treat large lesions or those in eloquent areas. This study aimed to analyze the preliminary results of HF-GKRS for these meningiomas, and to determine its effectiveness and safety.This single-center retrospective study analyzed data of patients who underwent HF-GKRS for large meningiomas or those in eloquent areas with > 6 months of follow-up. The primary outcome was progression-free survival (PFS). The secondary outcomes were neurological deterioration, post-treatment T2 signal changes following HF-GKRS, and tumor volume changes. Volumetric analysis of the tumors after treatment was also performed to assess changes in tumor size after HF-GKRS.Overall, 24 patients with a median follow-up period of 22 months (range: 6-49 months) were included. Among them, 18 (75%) patients had tumors in close proximity to the optic pathway, and 15 (63%) patients had large lesions (> 10 cm3). The cumulative 1- and 3-year PFS rates were 100% and 92%, respectively. The cumulative 3-year rate of adverse radiation effects was 9%. Overall, 12 patients (50%) showed tumor reduction, with a median tumor reduction rate of 45% (range: 25-58%).Our preliminary results revealed that HF-GKRS for large meningiomas or those in eloquent areas is safe and effective, with satisfactory short- and mid-term PFS and low adverse radiation effects. Further research with more patients and longer follow-up periods is required.

Distinct patterns of osteoradionecrosis after photon-based radiotherapy and carbon ion radiotherapy for unresectable adenoid cystic carcinoma of the head and neck: case series from two institutions.

To present the clinical outcomes of two series of patients treated with carbon-ion radiotherapy (CIRT) and definitive photon radiotherapy (RT) for adenoid cystic carcinoma of the head and neck (HN-ACC). The first cohort of six patients was referred from Oslo University Hospital (OUS) to Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) for CIRT in 2014-2017. The second cohort included 18 patients treated with definitive photon RT at OUS in 2005-2017. The primary endpoint was an evaluation of osteoradionecrosis (ORN) in the two cohorts. The secondary endpoints were treatment efficacy by local control (LC), progression-free survival (PFS), and overall survival (OS). The tumor stage was T4 for all the patients in the CIRT group and 15 (84%) in the photon group. There were three (50%) patients with grade 3 ORN in the CIRT group compared to one (6%) with grade 3 ORN in the photon group (p = 0.05). The 5-year LC (95% CI), PFS, and OS rates in the CIRT group and the photon group were 33% (11-100) and 39% (19-76), 17% (9-100) and 23% (2-59), and 80% (52-100) and 50% (31-82), respectively. Half of the patients in the CIRT cohort experienced ORN requiring surgical management during the follow-up. Patients with ACC referred for CIRT often have a worse prognosis and more advanced disease than patients treated with photons. When returning from the referring center, these patients need close follow-up often in collaboration with treating centers to manage toxicity that impacts quality of life.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel. The primary endpoints were dose-limiting toxicity (DLT) and incidence and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of the 48 patients infused prizlon-cel, 44 had large B-cell lymphoma (LBCL). No patient experienced DLT. Cytokine release syndrome occurred in 93.8% of patients, with only one case of grade 3. Immune effector cell-associated neurotoxicity syndrome occurred in 6.3% of patients, with no grade 3 or higher events. The most common grade 3 or higher TEAEs were neutropenia (83.3%) and leukopenia (50%). The ORR and complete response (CR) rates in all patients were 91.5% and 85.1%, respectively, and in LBCL patients, ORR was 90.7% with 86.0% CR. With median follow up of 30.0 months, median DOR, PFS, and OS were all not reached. The Kaplan-Meier estimate of 2-year DOR, PFS and OS rates were 66.0%, 62.6%, and 76.5%, respectively. Prizlon-cel showed a favorable safety profile and a high and durable response in patients with r/r B-NHL, suggesting a promising treatment option for patients with r/r B-NHL. (ClinicalTrials.gov number: NCT04317885, NCT04655677, NCT04696432, NCT04693676).

Nivolumab Combined with Chemotherapy in FGFR2 and PD-L1 Co-Expressing Metastatic Gastric Cancer: A Prospective Phase 2 NIVOFGFR2 Study.

Immunotherapy is increasingly significant in treating metastatic gastric cancer. This prospective phase 2 study investigates the efficacy and safety of combining nivolumab with chemotherapy in patients with metastatic gastric cancer co-expressing FGFR2 and PD-L1. Eligible patients were aged 18years or older, with previously untreated HER-2 negative, PD-L1 positive, and FGFR2 positive metastatic gastric adenocarcinoma. Patients received nivolumab (360mg every 3weeks) in combination with chemotherapy (CAPOX: capecitabine 1000mg/m2 twice daily on days 1-14 and oxaliplatin 130mg/m2 on day 1, every 3weeks). Tumor assessments were conducted using RECIST v1.1 every 8weeks for 48weeks, then every 12weeks. The primary endpoint was the 1-year progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), objective response rate (ORR), and grade ≥ 3 adverse events (AEs). From June 2022 to October 2023, 194 patients were assessed for eligibility, with 23 patients enrolled and treated. At a median follow-up of 17.3months, the 1-year PFS rate was 30.4%, with a median PFS of 6.0months (95% CI, 4.3-7.7). The median OS was 15.1months (95% CI, 13.2-16.8). The ORR was 21.7%, with one complete response and four partial responses. Grade 3 or higher TRAEs were reported in 34.8% of patients, primarily associated with chemotherapy. No treatment-related deaths occurred. While the primary endpoint of improved 1-year PFS rate was not met, the study offers valuable insights into the potential benefits of combining nivolumab with chemotherapy in FGFR2 and PD-L1 co-expressing metastatic gastric cancer. Future research should optimize patient selection, assess combined immunotherapy and targeted anti-FGFR2 therapy, and further investigate the role of subsequent treatments to maximize therapeutic benefits.

Concurrent versus sequential immunotherapy with chemoradiotherapy for unresectable stage III non-small-cell lung cancer: a retrospective study.

Immunotherapy combined with chemoradiotherapy has demonstrated promising efficacy in stage III non-small-cell lung cancer (NSCLC). However, the optimal timing for immunotherapy intervention during radiotherapy remains unclear. This study aimed to compare the efficacy and safety of immune checkpoint inhibitors (ICIs) administered concurrently or sequentially with chemoradiotherapy in unresectable stage III NSCLC. A retrospective analysis of 98 patients with unresectable stage III NSCLC, treated between January 1, 2019, and June 30, 2023, was conducted. Patients were grouped based on concurrent or sequential administration of ICIs with chemoradiotherapy. Median progression-free survival (mPFS), median overall survival (mOS), 1 and 2-year PFS rates, 2 and 3-year OS rates, objective remission rate (ORR), and disease control rate (DCR) were evaluated. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and Cox proportional hazards model. Treatment-related adverse effects were assessed and graded. A total of 98 patients with unresectable stage III NSCLC treated with chemoradiotherapy and ICIs were included. The mPFS and mOS were 19.0 (14.2-23.8) months and 31.5 (24.3-38.7) months, 12.8 (9.5-16.1) months and 28.5 (19.3-37.7) months in the concurrent and sequential ICI groups, respectively, and mPFS showed a significant difference (P=0.047). The estimated 1 and 2-year PFS rates were 79.6% (95% confidence interval [CI]: 67.6-91.6) and 40.4% (95% CI: 15.8-49.2) for the concurrent group, compared to 51.0% (95% CI: 35.9-66.1) and 31.6% (95% CI: 14.5-48.7) for the sequential group. The estimated 2 and 3-year OS rates were 65.7% (95% confidence interval [CI]: 48.6-82.8) and 40.0% (95% CI: 16.1-63.9) for the concurrent group, compared to 54.6% (95% CI: 35.8-73.4) and 28.7% (95% CI: 4.8-52.6) for the sequential group. The Eastern Cooperative Oncology Group Performance Status Scale (ECOG) score and tumor differentiation were identified as independent factors associated with PFS and OS. Distant metastasis occurred in 13.8% and 25.5% of patients in the concurrent and sequential ICI groups, respectively (P=0.049). The incidence of any grade of pneumonitis was 43.1% and 38.3% in two groups, with grade 3 or higher in 7.8% and 8.5% of patients, respectively. Hematologic toxicity of any grade was observed in 29.4% and 34.0% of the two groups, with grade 3 or higher toxicity identified in 3.9% and 2.1% of patients, respectively. Concurrent immunotherapy combined with chemoradiotherapy demonstrated superior efficacy than sequential immunotherapy, with good safety and tolerability in patients with unresectable stage III NSCLC.

Real-world experiences with brentuximab vedotion-based regimens in systemic anaplastic large cell lymphoma: a multi-center retrospective study.

Brentuximab vedotin (BV) has demonstrated high remission rates in clinical trials for systemic anaplastic large cell lymphoma (sALCL), yet its real-world effectiveness in China remains unconfirmed. This retrospective observational study evaluates BV-based regimens in patients with sALCL, treated from 2020 to 2023. A multi-center observational retrospective study was conducted on patients with sALCL received BV plus cyclophosphamide, doxorubicin, and prednisone (CHP) upfront or BV plus gemcitabine, oxaliplatin(GemOx), gemcitabine, cisplatin, dexamethasone(GDP), or isocyclophosphamide, carboplatin, etoposide (ICE)for later lines. Primary endpoints were complete response rate (CRR) and overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and the incidence of adverse events (AEs). Among the 38 patients (28 newly diagnosed and 10 with refractory/relapsed disease), the ORR were 100% (with 89.3% CR) for newly diagnosed patients and 70% (with 50% CR) for refractory/relapsed patients. The median duration of response was 14 months for newly diagnosed patients and 23.8 months for those with refractory/relapsed disease. 2-year Survival rates were 100% for newly diagnosed patients and 80% for refractory/relapsed patients, with 2-year PFS rates of 92.8% and 70%, respectively. Neurological toxicities were commonly observed but resolved following the completion of treatment. BV has proven to be effective and well-tolerated in real-world settings for the treatment of sALCL, reinforcing its potential as a promising option for first-line or subsequent therapy. The sustained efficacy observed post-CR suggests that these patients may have a prolonged disease control.

Efficacy of microwave ablation for intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

Data on overall survival (OS) and progression-free survival (PFS) after microwave ablation (MWA) for intrahepatic cholangiocarcinoma (ICC) are scarce. We conducted a systematic review of the safety and efficacy of MWA for ICC. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies reporting the outcomes of MWA for ICC. Meta-analyses of the pooled OS, PFS, technical success, technical efficacy, and complication rates were conducted. Pooled hazard ratios (HRs) of common variables were calculated to identify the factors associated with OS. The analysis encompassed 168 entries, among which 8 observational studies comprising 423 patients were deemed eligible. The pooled results were as follows: The median OS was 22.0 months [95% confidence interval (CI): 15.1-28.9], with the 1-, 3-, and 5-year OS rates being 83.7% (95% CI: 75.8-91.6%), 51.0% (95% CI: 41.1-60.9%), and 33.3% (95% CI: 14.1-52.4%), respectively. The median PFS was 12.5 months (95% CI: 8.3-16.7), and the 1-year PFS rate was 61.2% (95% CI: 36.5-85.9%). The technical success, technical efficacy, and major complication rates were 100% (95% CI: 99.5-100%), 99% (95% CI: 92.1-100%), and 2.8% (95% CI: 1.1-5.2%), respectively. A cancer antigen 19-9 (CA 19-9) level >37 U/mL was associated with a shorter OS (HR =1.4; 95% CI: 1.2-1.7; P=0.001). MWA is a safe and effective alternative to chemotherapy, radiotherapy, and radiofrequency ablation (RFA) treatments, especially for patients with a CA 19-9 level ≤37 U/mL, and potentially has advantages over RFA. However, further studies are required to validate these findings.

Ovarian squamous cell carcinoma: clinicopathological features, prognosis and immunotherapy outcomes.

To explore the characteristics and survival outcomes of ovarian squamous cell carcinoma (SCC) and the treatment effectiveness of immune checkpoint inhibitors (ICIs). Patients diagnosed with ovarian SCC at Peking Union Medical College Hospital between January 2000 and September 2023 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analysis of OS were performed using the Cox proportional hazards model. A total of 42 patients were included, with a median age of 51.5 years (range, 23-74). The majority had SCC arising from teratomas (54.8%), followed by endometriosis (14.3%) and Brenner's tumor (2.4%). Patients undergoing molecular testing exhibited a median tumor mutation burden (TMB) of 10.00 mutations/Mb (range, 7.28-46.86), predominantly featuring PIK3CA mutations. Thirty-eight patients (90.5%) received adjuvant chemotherapy. The median OS was 42.0 months, with the 1- and 5-year OS rates were 73.7% and 48.7%, respectively. And the median PFS was 26.9 months, with the 1- and 5-year PFS rates were 57.5% and 43.8%, respectively. Five patients underwent first-line postoperative adjuvant therapy combining ICIs with chemotherapy. During the 9.5 to 25.1 months follow-up, 4 patients showed no evidence of disease, while 1 relapsed and received treatment. Late-stage disease and younger age at diagnosis were associated with worse survival outcomes. The prognosis for ovarian SCC remains unfavorable. The stage and age were prognostic predictors for survival. ICIs may be beneficial for patients with ovarian SCC, particularly those with a high TMB.

Cost-Utility Analysis of Stereotactic Body Radiation Therapy Versus Surgery for Patients With Stage I Non-small Cell Lung Cancer in Japan.

Stereotactic body radiation therapy (SBRT) for patients with operable stage I non-small cell lung cancer (NSCLC) is less invasive than surgery. However, differences in lifetime costs and patient outcomes remain unclear. In this study, a cost-utility analysis of SBRT compared with surgery for Japanese patients with operable stage I NSCLC was conducted. A partitioned survival model was constructed using each treatment arm's overall survival (OS) and progression-free survival (PFS) data. The data for the SBRT arm were extracted from the Japanese multicenter cohort study, which enrolled 678 medically operable patients with stage I NSCLC, and patient registry data were used for the surgery arm. The 5-year OS rate was 78.2% for SBRT and 74.8% for surgery from both studies. The 5-year PFS rate was 57.0% for SBRT and 63.4% for surgery. The quality of life values of PFS and progressive disease were obtained from domestic and overseas literature (PFS: 0.74, progressive disease: 0.65). The time horizon was set to 10 years. The expected costs and quality-adjusted life years for each treatment group were calculated. All costs are expressed in Japanese yen converted to US dollars (USD). SBRT was the dominant strategy, reducing treatment costs by 4,443.8 USD and increasing quality-adjusted life years by 0.131 compared with surgery. According to probabilistic sensitivity analysis, the probability of SBRT being dominant and cost-effective was 50.6% and 72.4%, respectively. Under the budget impact analysis, the total savings for the patients with stage I NSCLC in Japan was 6,252,870.0 USD (n = 1,407). SBRT is a more cost-effective option than surgery in patients with medically operable stage I NSCLC in Japan. Large-scale epidemiologic studies that reflect the latest clinical realities, such as OS/PFS, will be needed to validate this study's robustness.

Hypofractionated radiation therapy alone for human papillomavirus-related oropharyngeal cancer.

To report a single-institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)-positive oropharyngeal cancer. A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16-positive squamous cell carcinoma of the oropharynx. Sixty-seven patients (67%) were never smokers. The 3-year actuarial rates of overall survival, local-regional control, and progression-free survival were 94%, 93%, and 89%, respectively. Among never-smokers, the 3-year rates of overall survival and local-regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV-positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de-escalation is currently underway.

Efficacy and Safety of CART Cell Therapy in Aggressive B-Cell Lymphomas Involving the Gastrointestinal Tract.

Currently, chimeric antigen receptor T-cell (CART) therapy represents a highly effective approach for relapsed/refractory B-cell lymphomas. However, it also carries treatment-related risks. Limited data are available on the risks associated with CART therapy in patients with gastrointestinal involvement in B-cell lymphomas. Therefore, we conducted a retrospective cohort study to address this gap in knowledge. During the period from May 2019 to August 2022, a total of 26 patients recurrent/refractory with recurrent/refractory B-cell lymphoma involving the gastrointestinal tract enrolled. Pathology confirmed CD19 antigen expression in tumor tissues. The disease status of patients who failed multiple lines of therapy was progressive disease (PD). Before CART cell infusion, patients received an FC regimen (fludarabine and cyclophosphamide) lymphodepletion. Quantitative PCR and flow cytometry were adopted for monitoring CART cell kinetics and function, with a focus on gastrointestinal AEs during treatment. The overall response rate (ORR) of the 26 patients was 61.5% (16/26), while the complete response rate (CR) was 23.1% (6/26). Their median follow-up time was 22.49 months, while the medians of overall survival (OS) and progression-free survival (PFS) were 10.88 and 5.47 months, respectively. The 1-year OS and PFS rates were 45% and 42.3%, respectively. The prevalence of gastrointestinal complications was 21/26 (80.7%), including gastrointestinal hemorrhage in 11/26 (42.3%), emesis and diarrhea in 9/26 (34.6%), as well as intestinal obstruction in 2/26 (7.7%). A total of three patients (3/26, 11.5%) died of gastrointestinal hemorrhage. The gastrointestinal hemorrhage group exhibited markedly lower ORR and inferior OS compared to the non-hemorrhage group. Generally, the CART cell therapy is valid in relapsed/refractory B-cell lymphoma with gastrointestinal involvement, but gastrointestinal bleeding is a unique risk factor that requires special attention, particularly in patients with high gastrointestinal tumor burden, as it is associated with poor efficacy and survival.

Salvage Radiotherapy for Loco-regional Recurrence of Esophageal Cancer Following Surgery.

There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). The patients' median age was 65 years (range, 41 to 86 years). The median disease-free interval was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

A retrospective study of an irradiation-based conditioning regimen and chidamide maintenance therapy in T-ALL/LBL

ABSTRACT Objectives T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) are highly malignant and aggressive hematologic tumors for which there is no standard first-line treatment. Chidamide, a novel histone deacetylase inhibitor, shows great promise. We assessed the efficacy and safety of an irradiation-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplantation chidamide maintenance in patients with T-ALL/LBL. Methods We retrospectively analyzed the clinical data of six patients with T-ALL/LBL who underwent allo-HSCT with a radiotherapy-containing pretreatment regimen and post-transplant chidamide maintenance therapy. The endpoints were relapse, graft-versus-host disease (GVHD), transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results All of the patients had uneventful post-transplant hematopoietic reconstitution, and all achieved complete molecular remission within 30 days. All six patients survived, and two relapsed with a median relapse time of 828.5 (170–1335) days. The 1-year OS rate was 100%, the 2-year PFS rate was 66.7%, and the TRM rate was 0%. After transplantation, two patients developed grade I-II acute GVHD (2/6); grade III-IV acute and chronic GVHD were not observed. The most common AEs following chidamide administration were hematological AEs, which occurred to varying degrees in all patients; liver function abnormalities occurred in two patients (grade 2), and symptoms of malaise occurred in one patient (grade 1). Conclusion Chidamide maintenance therapy after T-ALL/LBL transplantation is safe, but the efficacy needs to be further investigated.

Surgical resection versus thermal ablation after intra-arterial conversion therapy for unresectable hepatocellular carcinoma: a multicenter retrospective one as per the STROBE guidelines

Purpose Intra-arterial conversion therapy (ICT) is a promising option for patients with unresectable hepatocellular carcinoma (uHCC). However, the selection of sequential therapeutic modalities is still controversial. This study compared the efficacy and safety of surgical resection (SR) versus thermal ablation (TA) after patients with uHCC received ICT. Methods From May 2008 to November 2021, 3553 consecutive patients were reviewed and 791 patients were downstaged to receive TA or SR. Among them, 340 patients received SR, and 451 received TA after ICTs. The propensity score matching (PSM) method was applied to reduce selection bias between groups. Cumulative overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan–Meier method with the log-rank test. The occurrence of complications and adverse events (AEs) were compared using chi-square test. Results After PSM 1:1 (n = 185 in both groups), the 10-year OS and PFS rates for patients who underwent SR were comparable to those of patients who underwent TA (OS: 45.2% vs. 36.1%; p = 0.190; PFS: 19.3% vs. 15.9%; p = 0.533). A total of 237 (29.9%) patients (203 males; mean age:57.1 ± 11.0 years) received downstaging therapy, and long-term OS and PFS remained comparable between the two groups (p = 0.718, 0.636, respectively). However, the cumulative OS and PFS rates in the downstaged cohort were significantly higher than those in the nondownstaged cohort (both ps < 0.001). Additionally, there was no difference in major complications between the two groups (SR: 6.3% vs. TA: 8.6%; p = 0.320). Conclusions TA might be an acceptable first-line alternative to SR after patients with uHCC receive ICT, especially patients unsuitable for SR. Better long-term survival was observed among patients in the downstaged cohort compared to those who failed to downstage.

Retrospective, Non-Interventional, Multicenter Study on the Effectiveness and Safety of Intravesical Bacillus Calmette-Guerin in Patients with Non-Muscle-Invasive Bladder Cancer: Real-World Experience from Six Hospital Centers in Greece.

While the clinical application of SII-ONCO-Bacillus Calmette-Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC) is well established in Greece, there is a lack of real-world data on its effectiveness and safety. This retrospective, observational, multicenter, chart-review study aims to provide real-life data on the effectiveness and safety of SII-ONCO-BCG in patients with intermediate- and high-risk NMIBC. From January 2016 to December 2023, medical records from six hospital centers were reviewed for adult patients with histologically confirmed stage Ta or T1 NMIBC (with or without carcinoma in situ [CIS]) who received at least one maintenance course of SII-ONCO-BCG after induction. Tumor recurrence and progression were monitored at scheduled time intervals. Primary outcomes included recurrence-free survival (RFS) and progression-free survival (PFS), while adverse events (AEs) constituted secondary outcomes. A total of 162 patients receiving SII-ONCO-BCG were enrolled. Among all patients, 145 (89.5%) patients were men, 88 (54.3%) aged 70 years or older, 103 (63.6%) had T1, 43 (26.5%) Ta, and 21 (12.9%) concurrent CIS. The median follow-up duration was 28.9 months (range, 5-36) and the mean BCG intravesical instillation courses were 13.7 (range, 9-27). After 3-, 2-, and 1-year follow-up, RFS rates of 85.2% (95% CI, 79.7-90.7%), 85.8% (80.4-91.2%), and 87.0% (81.8-92.3%) were observed, respectively. The corresponding 3-, 2-, and 1-year PFS rates were 96.9% (94.2-99.6%), 96.9% (94.2-99.6%), and 97.5% (95.1-99.9%), respectively. During the whole follow-up period, 24 (14.8%) patients experienced at least one AE. This real-world study demonstrates that SII-ONCO-BCG is an effective and safe treatment for patients with intermediate- and high-risk NMIBC.

Efficacy and Safety of Three Cycles of TIP and Sequential High Dose Chemotherapy in Patients with Testicular Non-Seminomatous Germ Cell Tumors

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.