Two-year Survival Rates Research Articles

Prognostic impact of branch vessel involvement on organ malperfusion and mid-term survival in patients with acute type A aortic dissection

BackgroundThis study aimed to investigate the impact of branch vessel involvement on organ malperfusion and mid-term survival in patients with acute type A aortic dissection (ATAAD). MethodsBetween January 2019 and December 2020, 493 consecutive patients with angiographically confirmed ATAAD were retrospectively analysed. Preoperative computed tomography angiography parameters (branch artery involvement, longitudinal extent of dissection) were reviewed. The incidence of organ malperfusion, in-hospital mortality, and mid-term outcomes of patients with and without branch vessel involvement were compared. ResultsBranch vessel involvement was detected in 407 patients (82.6%), and organ malperfusion was observed in 234 patients (47.5%). The incidence of organ malperfusion was significantly higher in patients with branch vessel involvement compared with patients without it (52.6% vs. 23.3%, p < 0.001). Patients with coronary artery involvement (32.5%) were more likely to manifest as clinical malperfusion, whereas it occurred only 19.4% in patients with renal artery involvement. In-hospital mortality was higher in patients with branch vessel involvement (19.9% vs. 8.1%, p = 0.010). Median follow-up time was 16.1 months. Two-year survival rate was lower in patients with branch vessel involvement (76.3% vs. 84.5%, p = 0.085) or organ malperfusion (68.3% vs. 86.0%, p < 0.001). Multivariable analysis identified cardiac, cerebral, visceral and renal malperfusion as independent predictors for in-hospital mortality. ConclusionsOnly a small proportion of branch vessel involvement was associated with corresponding organ malperfusion in patients with ATAAD. Branch vessel involvement had a greater effect on short-term outcomes than mid-term survival, and organ malperfusion was related to a worse prognosis beyond it.

Yoğunluk Ayarlı veya 3 Boyutlu Konformal Radyasyon Tedavisi Kullanılarak Definitif Kemoradyoterapi İle Tedavi Edilen Servikal Özofagus Kanserinin Sağkalım Sonuçları: Tek Merkez Deneyimi

Abstract&#x0D; Objective: The aim of this study is to report the survival and treatment results of patients with cervical esophageal cancer treated with definitive chemoradiotherapy, whose incidence is very low in the population and there is not enough information about treatment and toxicity results in the literature. &#x0D; Material and Method: Between 2013 and 2022, 10 patients (six males and four females) with cervical esophageal cancer treated with definitive chemoradiotherapy were included. Among these patients, seven had stage II disease, one stage III, and 2 stage IVA. All patients received radiotherapy at a median dose of 50.4 Gy and concurrent weekly chemotherapy.&#x0D; Results: The median follow-up period was 18 months. The two-year and 5-year overall survival rates were 42.2% and 21.1%, respectively. The two-year and 5-year disease-free survival rates were 45.7% and 22.9%, respectively. Disease progression was noted in 3 out of 10 patients (30%). Three patients were still alive during analyze. Percutaneous enteral gastrostomy was performed in 3 of 10 patients. These requirement occured in 1 due to local progression, and in the remaining 2 patients due to the side effect of RT. &#x0D; Conclusions: Overall survival rates were low, as similar findings appear in the literature. It was remarkable that the need for a percutaneous enteral gastrostomy was not observed in the IMRT group. All patients with complete remission were in stage 2.

Long-term survival of patients with cerebrovascular accident in different age groups in the REGION-M registry

Aim. To study the two-year survival rate of patients with cerebrovascular accident (CVA) in different age groups.Material and methods. The outpatient part of the REGION-M registry included 684 patients assigned to the City Polyclinic № 64 in Moscow, discharged from the F. I. Inozemtsev City Clinical Hospital (Moscow) in the period from January 1, 2012 to April 30, 2017 with a confirmed diagnosis of stroke or transient ischemic attack. All patients were divided into 5 age groups: group 1 — from 18 to 50 years old (n=72 (10,5%)), group 2 — from 51 to 60 years old (n=122 (17,8%)), group 3 — from 61 to 70 years old (n=156 (22,8%)), group 4 — from 71 to 80 years old (n=185 (27,0%)) and group 5 — 81 years and above (n=149 (21,8%)). Patient survival was assessed after 2 years of follow-up.Results. The mortality rate of patients during the follow-up period significantly increased with age as follows: in patients of 18-50 years old — 4%, 51-60 years old — 9,8%, 61-70 years old — 23,7%, 71-80 years old — 34%, 81-100 years old — 55% (p&lt;0,0001). The relative death risk was 2,3 in group 2 (NA), 6,8 in group 3 (p&lt;0,001), 9,8 in group 4 (p&lt;0,0001) and 18,5 in group 5 (p&lt;0,0001) compared with group 1. With increasing age in the study cohort, the proportion of women increased as follows: from 47,2% in group 1 to 77,9% in group 5 (p&lt;0,0001). However, mortality among men and women in the groups did not differ. Patients in older age groups were more likely to have comorbidities and disability before the CVA. With increasing age, ischemic stroke was significantly more common and transient ischemic attack was less common (p&lt;0,001).Conclusion. Mortality of patients who underwent stroke was significantly higher in older age groups and did not differ among men and women.

Laryngeal Cancer in Iranian Women

Laryngeal cancer is the most common malignant neoplasm in respiratory tract after lung cancer. The incidence is very different and male to female ratio has been decreased in previous decades. Different characteristics of laryngeal cancer in men and women have been described based on previous studies, so we decided to study its characteristics in Iranian women. This study's design is cross-sectional retrospective from 2010 to 2019 in Amir-Alam Hospital, Tehran University of Medicine. All patients with laryngeal cancer admitted to this hospital, were included. Females` records were studied exclusively. Among 1456 patients included in this study, 1391 were male and 65 were female(M/F=21.4:1). The mean age of males was 60.6 years and for females was 56.6. From 65 females, 60 were Squamous cell carcinoma and 5 were Sarcoma. Findings of 60 female SCC patients: The main risk factors were cigarette smoking and opium abuse. The subsite of tumor was supraglottic in 40%, glottis in 31% and transglottic in 29%. Treatment options were surgical (55%) and non-surgical (45%). Survival rates for one, two and five years were 84.3%, 67.4% and 44% respectively. Two-year survival of surgically treated patients is significantly better than non-surgically treated patients (P=0.048). The mean age of females was less than males. Two-year survival rate was better in surgically treated patients. The five-year survival of female patients was 44% and there is an emerging need for survival studies of male patients for comparison.

Biomarkers for Outcome in Metastatic Melanoma in First Line Treatment with Immune Checkpoint Inhibitors.

A high proportion of metastatic melanoma patients do not respond to immune checkpoint inhibitors (ICI), and until now, no validated biomarkers for response and survival have been known. We performed a retrospective analysis of outcomes in patients with metastatic melanoma treated with first-line ICI at the Institute of Oncology Ljubljana from January 2018 to December 2020. The immune-related adverse events (irAEs) and serum immune-inflammation parameters (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (LR), systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV)) were analyzed as potential biomarkers for response and survival. Survival rates were calculated using the Kaplan-Meier method and then compared with the log-rank test. Multivariate regression Cox analysis was used to determine independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Median follow-up was 22.5 months. The estimated median progression-free survival (PFS) was 15 months (95% CI 3.3-26.2). The two-year survival rate (OS) was 66.6%. Among 129 treated patients, 24 (18.6%) achieved complete response, 28 (21.7%) achieved partial response, 26 (20.2%) had stable disease and 51 (39.5%) patients experienced a progressive disease. There was a higher response rate in patients with irAEs (p < 0.001) and high NLR before the second cycle of ICI (p = 0.052). Independent prognostic factors for PFS were irAE (HR 0.41 (95% CI 0.23-0.71)), SII before the first cycle of ICI (HR 1.94 (95% CI 1.09-3.45)) and PLR before the second cycle of ICI (HR 1.71 (95% CI 1.03-2.83)). The only independent prognostic factor for OS was SII before the first cycle of ICI (HR 2.60 (95% CI 0.91-7.50)). Patients with high pre-treatment levels of SII had a higher risk of progression and death; however, patients with irAEs in the high-SII group might respond well to ICI. Patients who develop irAEs and have high NLRs before the second ICI application have higher rates of CR and PR, which implicates their use as early biomarkers for responsiveness to ICI.

Adjuvant chemoradiotherapy in resected gallbladder cancer: A SEER-based study

BackgroundThe prognosis of gallbladder cancer (GBC) is dismal. This study aimed to compare the outcomes of adjuvant chemoradiotherapy (ACR) with those of surgery alone (S) and adjuvant chemotherapy (AC). MethodThe Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with GBC and undergoing surgery between 2004 and 2015. The patients were divided into the S, AC, and ACR groups according to their treatment. Categorical variables were compared by Pearson’s chi-square test, and a 1:1:1 propensity score matching analysis (PSM) was performed. Overall survival was assessed by Kaplan-Meier curves with log-rank tests. Subgroup analyses were conducted. ResultA total of 5451 patients were identified in the SEER database. After PSM, the two-year survival among patients who received S, AC, and ACR was 36%, 39%, and 45%, respectively. ACR was associated with improved two-year survival (p < 0.001), while the survival rates were similar in the AC and S groups (p = 0.127) but better in the ACR group than in the AC group (p = 0.012). Subgroup analyses indicated that while the two-year survival rates did not differ significantly in stage II GBC patients between the groups (all p > 0.05), ACR was associated with significantly improved two-year survival in stage Ⅲa (p = 0.008), Ⅲb (p < 0.001), and Ⅳb (p < 0.001) GBC patients. ConclusionThe combination of surgery and ACR as the treatment modality provided greater survival benefits for GBC patients, particularly for those with advanced tumor staging.

Clinical Experience of Intra-tumoral Central-Dose Escalated Volumetric Modulated Arc Therapy for Lymph Node Metastases in Patients With Advanced Cancer.

Background Lymph node metastases (LN mets) are radioresistant, and high-dose irradiation is preferred for their control. The volumetric-modulated arc therapy technique makes it possible to perform intra-tumoral dose escalation without increasing the total prescribed dose of fractionated irradiation. We report its clinical experiences with intra-tumoral central-dose escalated volumetric-modulated arc therapy (ICE-VMAT) for LN mets. Materials and methods This study retrospectively evaluated 31 patients with 50 LN mets from stage III and IV advanced cancers who received ICE-VMAT. The total described dose was 50 Gy, and the median intra-tumoral central dose was 66 Gy (range, 54-79 Gy). Results The median follow-up period was 21 months. The two-year local control and overall survival (OS) rates were 95% and 56%, whereas univariate analysis revealed that the KPS ≥ 80 group had a significantly better OS compared to the KPS < 80 group. Conclusion ICE-VMAT was effective for LN mets. Patients with good KPS may benefit from therapeutic intervention with ICE-VMAT, even if they have multiple distant LN mets.

Same-Day Digital Dentistry Restorative Workflow for Single Immediate Provisionalization of Narrow-Diameter Implants: An Exploratory Prospective Study

This study evaluated the two-year clinical outcomes of 3.1 mm diameter dental implants, immediately provisionalized and later restored using same-day dentistry, in 10 patients receiving 11 narrow-diameter (3.1 mm) single implants. Each implant was placed and immediately restored with a provisional crown after placement. At least 2 months after placement, the implant was restored with a prefabricated titanium abutment and an all-ceramic crown using a same-day dentistry protocol. Clinical outcomes, including apical bone loss, probing depths, gingival index, and surgical and prosthetic complications, were documented. There was no implant failure over the course of two years. No surgical complications were reported. Two cases lost provisional crowns. One crown needed to be remade due to esthetic concern. The cumulative two-year survival rate of the implants was 100%. Implant bone loss after two years of functional loading was −0.56 ± 0.54 mm and −0.32 ± 0.68 mm for mesial and distal crestal bone, respectively. Two prosthetic complications included recementation of a crown and remaking of a crown. This exploratory study suggests that immediate provisionalization and a same-day restorative dentistry digital workflow protocol for narrow-diameter implants appear to be predictable clinical procedures with no reported surgical complications and minimal prosthetic complications.

Thiotepa, Busulfan, Cyclophosphamide: Effective but Toxic Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Central Nervous System Lymphoma.

In primary central nervous system lymphoma, two-year progression-free survival rates of up to 63 percent have been reported for first-line autologous stem cell transplantation after conditioning with the thiotepa busulfan cyclophosphamide regimen. However, 11 percent of the patients died due to toxicity. Besides conventional survival, progression-free survival and treatment related mortality analyses, a competing-risk analysis was applied to our cohort of twenty-four consecutive patients with primary or secondary central nervous system lymphoma who underwent autologous stem cell transplantation after thiotepa busulfan cyclophosphamide conditioning. The two-year overall survival and progression-free survival rates were 78 percent and 65 percent, respectively. The treatment-related mortality rate was 21 percent. The competing risks analysis demonstrate that age 60 or over and the infusion of less than 4.6 × 106/kg CD34+ stem cells were significant adverse prognostic factors for overall survival. Autologous stem cell transplantation with thiotepa busulfan cyclophosphamide conditioning was associated with sustained remission and survival. Nevertheless, the intensive thiotepa busulfan cyclophosphamide conditioning regimen was highly toxic, especially in older patients. Thus, our results suggest that future studies should aim at identifying the subgroup of patients who will really benefit of the procedure and/or to reduce the toxicity of future conditioning regimen.

Assessment of survival outcomes among lung cancer patients at the National and Referral Hospital in Kenya.

Lung cancer has a low overall survival rate linked to late diagnosis and metastasis. Unfortunately, comprehensive data within the African continent are limited due to the lack of a registry, low public awareness of lung cancer, financial constraints, and inadequate screening and treatment facilities. In addition, there was a lack of conclusive data in our setting. Therefore, this study aimed to assess survival outcomes among lung cancer patients at Kenyatta National Hospital. A hospital-based retrospective cohort study was performed to examine the survival outcomes of 151 lung cancer patients. All eligible lung cancer patients diagnosed and treated in the facility between January 1, 2018, and December 31, 2020, were included. The patients were retrospectively followed from the date of primary cancer diagnosis until death or the last follow-up period. The Statistical Package for the Social Sciences (SPSS) version 20.0 statistical software was used to enter and analyze the data. Kaplan-Meier survival and Cox regression analysis were employed to determine median survival and predictors of mortality, respectively. The mean and median follow-time was 18.2 and 17.5months, respectively. Most (98%) of the patients had non-small cell lung cancer. The 2-year survival rate was 66.7%, with 59.6% of patients having developed distant metastasis during the follow-up, while 25.1% were deceased. The median cancer-specific survival time among the study population was 18.0 ± 3.40 months. Cox regression analyses showed that patients with distant metastasis had five times more risk of dying (AHR: 4.74, 95% CI: 2.1-10.8, p < 0.001) than patients without distant metastasis. The overall two-year survival rate of lung cancer patients at the Kenyatta National Hospital was 66.7%, with most patients developed distant metastasis during the follow-up period. Distant metastasis was the only significant predictor of mortality among lung cancer patients in our setting.

Long-term survival of patients with various types of cerebrovascular accident: data from the outpatient part of the REGION-M registry

Aim. To study the two-year survival rate of patients with various types of cerebrovascular accident according to the outpatient part of the REGION-M registry.Material and methods. The outpatient part of the REGION-M registry included 684 patients assigned to the City Polyclinic № 64, discharged from the F. I. Inozemtsev City Clinical Hospital (Moscow) in the period from January 1, 2012 to April 30, 2017 with a confirmed diagnosis of stroke or transient ischemic attack (TIA). Of these, 514 (75,1%) patients had an ischemic stroke, 52 (7,6%) — a hemorrhagic stroke, and 118 (17,2%) — a TIA.Results. The lowest two-year mortality (11%) was observed in patients who underwent TIA (p&lt;0,001) compared with ischemic and hemorrhagic stroke. The relative risk of death for ischemic stroke was 2,0 (95% confidence interval (CI): 1,13-3,55) (p&lt;0,05), and for hemorrhagic stroke — 2,51 (95% CI: 1, 22-5,15) (p&lt;0,05) relative to patients with TIA. Mortality in patients with ischemic or hemorrhagic stroke did not differ significantly — 32,3 and 36,6% (p&gt;0,05). The mean age of patients who underwent TIA was significantly less than the age of patients with hemorrhagic or ischemic stroke. With increasing age, the survival of patients significantly worsened in all types of strokes. In addition, multivariate analysis adjusted for age showed remained significant effect of the stroke type on survival as follows: the relative risk of death for ischemic and hemorrhagic stroke was 1,99 (95% CI: 1,12-3,53) (p&lt;0,05) and 2,45 (95% CI: 1,19-5,02) (p&lt;0,05).Conclusion. Mortality in patients with stroke was significantly lower after TIA than in any type of stroke and did not differ between subgroups of patients with ischemic and hemorrhagic stroke.

Prognostic analysis of radiotherapy for cervical lymph node recurrence after curative resection of thoracic esophageal squamous cell carcinoma.

To identify efficacy and prognosis of radiotherapy (RT) for cervical lymph node recurrence (CLNR) in thoracic esophageal squamous cell carcinoma (TESCC) after curative resection. The clinical data from 65 patients were retrospectively analyzed. The Kaplan-Meier method was employed to analyze the survival of patients. The Cox proportional hazards model was then exploited for multivariate analysis. The median overall survival (OS) was 20months; one-year, two-year, three-year and five-year survival rates were 68.3%, 47.3%, 33.4% and 10.6%. The median progression-free survival (PFS) was 14months. Univariate analysis indicated that time from surgery to recurrence, number of recurrent lymph nodes and dose of RT were significant prognostic factors, whereas multivariate analysis showed that number of recurrent lymph nodes and radiation dose were independent factors. RT was an effective salvage treatment for patients with CLNR after surgery. Those patients who showed single lymph node recurrence and who were exposed to ≥60Gy of RT experienced a favorable prognosis.

Incidence of Acute Kidney Injury and Risk Factors of Prognosis in Patients with Acute Stanford Type A Aortic Dissection.

We aimed to investigate the prognosis and impact of postoperative acute kidney injury (AKI) in acute Stanford type A aortic dissection (ATAAD) patients, and to analyze the predictors of short- and medium-term survival. A total of 192 patients who underwent ATAAD surgery were included between May 2014 and May 2019. Perioperative data of these patients were analyzed. All of the discharged patients were followed up for 2 years. Postoperative AKI was identified in 43 of 192 patients (22.4%). The two-year survival rate of patients with AKI after discharge was 88.2% and that without AKI was 97.2%.The difference was statistically significant (χ2 = 5.355, log-rank P = 0.021). Cox hazards regression showed that age (hazard ratio [HR], 1.070; P = 0.002), cardiopulmonary bypass (CPB) time (HR, 1.026; P = 0.026), postoperative AKI (HR, 3.681; P = 0.003), and red blood cell transfusion (HR, 1.548; P = 0.001) were independent risk factors for the short- and medium-term total mortality of ATAAD patients. The incidence of postoperative AKI is high in ATAAD, and the mortality of patients with AKI increases significantly within 2 years. Age, CPB time, and red blood cell transfusion were also independent risk factors for short-and medium-term prognoses.

Value of a 18F-FDG PET/CT Semi-quantitative Parameter (SUVmax) in Predicting the Survival of Patients with Esophageal Cancer Subtypes

Background: Flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan is employed for initial staging and restaging of esophageal cancer patients. Objectives: The present study aimed to assess the value of a semi-quantitative parameter of 18F-FDG PET/CT scan, that is, maximum standardized uptake value (SUVmax), to determine its correlation with patient survival in two subtypes of esophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma. Patients and Methods: This cross-sectional study was performed on patients with esophageal SCC and adenocarcinoma, undergoing 18F-FDG PET/CT scan for initial staging before any treatment. The 18F-FDG PET/CT semi-quantitative parameter (SUVmax) was determined by reviewing the PET/CT images. The patients were reevaluated using 18F-FDG PET/CT scan for restaging within 12 - 24 months. Results: No significant difference was observed in the SUVmax values of the primary tumor, metastatic lymph nodes, or distant metastasis between the adenocarcinoma and SCC groups, regardless of response to treatment. Similarly, no significant association was found between the short-term survival of patients with adenocarcinoma and the SUVmax values of the primary tumor, metastatic lymph nodes, or distant metastasis. Based on the survival curve, one- and two-year survival rates were estimated at 75% and 63.9% in patients with SCC and at 80% and 60% in patients with adenocarcinoma, respectively. In the SCC group, a significantly higher SUVmax was detected in deceased patients with distant metastatic lesions compared to cancer survivors. According to the area under the ROC curve, the SUVmax of metastatic lesions showed high potential for predicting the mortality of SCC patients. Conclusion: The assessment of SUVmax in distant metastatic lesions by 18F-FDG-PET/CT may help predict the survival of patients with esophageal SCC. However, 18F-FDG-PET/CT findings were not associated with the survival of esophageal adenocarcinoma; therefore, further evaluations on a larger sample size and a longer follow-up are required.

Immigrant workers and firm resilience on the export market

This paper studies whether firms employing immigrant workers are more resilient to an increase in competition in their export markets. Exploiting the surge of Chinese imports following its accession to the World Trade Organization and using a sample of French manufacturing exporters from 2002 to 2015, we find that an increase in the growth rate of Chinese competition in a foreign market has a negative effect on both the two-year survival and growth rate of sales of French exporters on that foreign market. This negative effect on firm performance is mitigated by the employment of immigrant workers.

Two-Year Updated Results of Asciminib Managed-Access Program (MAP) in Russia

Background: Asciminib is a Specifically Targeting the ABL Myristoyl Pocket (STAMP) ABL. kinase inhibitor that has shown efficacy and a good safety profile in clinical trials in patients with Ph-positive chronic myeloid leukemia (CML) failing prior TKI lines. It was confirmed by real world data in Novartis approved Managed Access Program (MAP) in several countries.Aim: to present two-year updated results of asciminib use in clinical practice in the MAP program in 3 centers of Russia. Methods: In total the data of 50 CML pts who received asciminib for more than 9 months and did not undergo bone marrow transplantation was analyzed. Pts recruitment, dosing regimen, response monitoring, and toxicity control were performed according to the MAP treatment plan. All pts had a chronic phase (CP) CML, 8 pts had a second CP after accelerated phase (n=7) or blast crisis (BC). Complete cytogenetic response (CCyR) corresponding to BCR::ABL1 ≤1%, major molecular response (MMR) and deep molecular response (MR4) achievement was assessed by cumulative incidence function (CIF) with Gray's test for comparison responses in subgroups. Survival analysis was performed by Kaplan-Meier method. Results: All pts were divided into two groups: 20 pts received an initial dose of 200 mg BID (19/20 pts with BCR::ABL1 T315I ), 30 pts received 40 mg BID (1/30 pts with BCR::ABL1 T315I ). Baseline characteristics of the two dose groups are presented in table 1. The median follow-up among all pts was 17 months (range 10-37); 7(14%) pts discontinued asciminib (5 due to resistance, 2 due to progression). Two-year survival rate without treatment discontinuation was 83%. The 2-year OS was 100% and 93% in 400 mg and 80 mg dose groups, respectively, two (4%) pts progressed to BC and died. CIF of CCyR, MMR and MR4 by 24 month was 55%, 29% and 17% for 80 mg dose and 45%, 48% and 45% for 400 mg dose respectively. There was no significant difference in response rates between the two dose groups. In the 400 mg dose group, the cumulative incidence of MMR was significantly higher in ponatinib-naive patients (75% vs. 23% in ponatinib-pretreated patients, p=0.006) (figure 1). Twenty two (44%) pts experienced any adverse events (AEs) and 8 (16%) had AEs of grade 3-4. AEs of grade 3-4 connected with asciminib included neutropenia, thrombocytopenia and irregular menstruation. No pts stopped treatment due to toxicity; no difference in toxicity was found between doses of 80 and 400 mg/day. Conclusion: Asciminib shows promising results for the treatment of highly pre-treated CML pts and should be considered as therapeutic options for pts with failure to previous TKIs. The 400 mg dose was well tolerated and highly effective in ponatinib-naive pts with BCR::ABL1 T315I and should be investigated in clinical trials in patients without T315I as a potentially more effective and well tolerated dose. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of minimally invasive versus conventional thoracic aortic operations: Early and midterm results in a series of 624 patients.

Despite minimally invasive techniques having gained wider application in cardiac surgery, current evidence on minithoracic aortic surgery is still limited. The aim of this study was to compare early and midterm outcomes of patients undergoing operations of the proximal thoracic aorta through ministernotomy (MS) versus full sternotomy (FS). Data from 624 consecutive patients who underwent proximal aortic repair through MS (n = 214, 34.3%) and FS (n = 410, 65.7%) at two aortic centerswere analyzed. Treatment selection bias was addressed using propensity score matching (MS vs.FS). After matching, two well-balanced groups of 202 patients each were created. Median cardiopulmonary bypass and cross-clamp times were 88 and 68 min, respectively, with no difference between groups. Overall, 30-day mortality was 1% (n = 2) in MS and 0.5% (n = 1) in FS (p = .6). No difference was found in the rates of stroke (MS n = 5, 2.5%; FS n = 5, 2.5%), dialysis (MS n = 1, 0.5%; FS n = 4, 2%), bleeding (MS n = 7, 3.5%; FS n = 7, 3.5%), and blood transfusions (MS n = 67, 33.3%; FS n = 57, 28.4%). Patients receiving MS showed a lower incidence of respiratory insufficiency compared with FS (0% vs. 2.5%, p = .04). Intensive care unit and hospital stays were similar between groups. Two-year survival rate was 97.2% in MS and 96.5% in FS (p = .9). Mini proximal aortic operations can be performed successfully without compromising the proven efficacy and safety of conventional access. In selected patients, MS was associated with very low mortality and morbidity rates. Additionally, MS demonstrated superior clinical outcomes as regards respiratory adverse events, when compared with FS.

Preliminary Results of Penpulimab Combined with RMA (rituximab, methotrexate, and cytarabine) for Newly Diagnosed Primary Central Nervous System Lymphoma

Background: Primary central nervous system lymphoma (PCNSL) has been classified as large B-cell lymphomas (LBCL) of immune-privileged sites according to the 5th edition of the World Health Organization (WHO) Classification. The efficacy of high-dose methotrexate as a first-line treatment was suboptimal with a short effective remission time and low response rate. The recent discovery of the frequent copy number alterations in 9p24.1/PD-L1/PD-L2 and increased expression of PD-L1 in PCNSL provide the rationale to evaluate the efficacy of PD-1antibody in PCNSL. Methods: NCT05347641 is an ongoing Phase II, single-center, single-arm, open-label study, aimed to enrolled an estimated 23 newly diagnosed PCNSL patients. Enrolled patients first received the Pen-RMA induction treatment, including rituximab 375 mg/m2, d0; methotrexate 3.5g/m2, d1; cytarabine 1‒2g/m2, q12h, d2-3; penpulimab (an anti-PD1 antibody of IgG1 isotype) 200 mg, d5; 21d/cycle, for six cycles. Patients aged 60 years or younger, with complete response (CR)/unconfirmed complete response (CRu)/partial response (PR) after six cycles of induction treatment then underwent autologous stem cell transplantation (ASCT) before maintenance treatment. The maintenance regimen was administered based on patient response to ASCT, or to induction therapy for patients aged 60 years or older. Patients who achieved CR after ASCT or induction therapy then received 8 cycles of penpulimab as maintenance therapy, and those with PR after ASCT or induction therapy received whole brain radiotherapy (WBRT) combined with 8 cycles of penpulimab as maintenance. Treatment response was evaluated by brain MRI and FDG-PET and/or cerebrospinal fluid (CSF) examination every three cycles of the induction treatment. The primary endpoint of this study was two-year progression-free survival rate. Baseline tissue samples and sequential CSF or plasma samples were collected for targeted next-generation sequencing (NGS) at Nanjing Geneseeq Technology Inc. Results: Between April, 2022 and July, 2022, eleven newly diagnosed PCNSL patients has been enrolled. Treatment response was evaluable in eight patients. At the interim assessment point (after 3 cycles), six patients have achieved CR, with an overall response rate of 75.0%. Of these, three have completed 6 cycles of treatment and all achieved CR at the final assessment (Figure A). Adverse events of grade 3 or 4 occurred in five patients, including three neutropenia (27.3%), one thrombocytopenia (9.1%), and one renal dysfunction (9.1%). In the baseline samples, PIM1, MYD88L265P, and CD79B were the most common mutations, with a more comprehensive genomic landscape revealed by CSF than by blood (Figure B). All nine NGS-tested patients were classifier into the non-GCB subtype by the COO classification and the MCD subtype by the LymphGen classifier. CSF-based ctDNA monitoring was performed in two patients after 6 cycles of treatment. P01 had confirmed CR with ctDNA clearance in CSF. P07, was assessed as CR after 6 cycles, but the CSF ctDNA remained positive. This patient is currently receiving maintenance treatment and is being closely monitored for potential disease relapse. Interestingly, P02 and P04, who were PD and SD at interim evaluation, respectively, had markedly more mutations detected in their baseline plasma samples, indicating a poor prognosis (Figure A). Conclusion: The induction treatment of Pen-RMA has shown excellent responses in newly diagnosed PCNSL patients with mild hematologic toxicity. Our preliminary results also suggested that CSF-based ctDNA could facilitate diagnosis when tissue was inaccessible and show higher sensitivity than imageology in assessing the depth of remission. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Circulating Exosomal PD-L1 at Initial Diagnosis Predicts Outcome and Survival of Patients with Osteosarcoma.

It is difficult to predict prognosis of patients with osteosarcoma at initial diagnosis due to lack of efficient prognostic parameters. We evaluated the relationship between level of circulating serum exosomal PD-L1 (Sr-exosomal PD-L1) at initial diagnosis and oncologic outcome during the follow-up. Sixty-seven patients with newly diagnosed osteosarcoma were prospectively recruited. Fasting blood was collected and exosome isolation was performed using ultracentrifugation method. Evaluation of Sr-exosomal PD-L1 was performed respectively by immunogold labeling and ELISA method. Correlation between level of Sr-exosomal PD-L1 at initial diagnosis and clinical risk factors was assessed. Mean follow-up was 46.7 months. Two-year and 5-year overall survival (OS) rates were respectively 96.9% and 62.5%. Two-year and 5-year disease-free survival (DFS) rates were respectively 85.0% and 31.4%. Results revealed a significantly positive association between high PD-L1 cargo of circulating exosomes and clinicopathologic disease markers such as pulmonary metastasis, multiple metastasis, and death. Patients who died of disease at final follow-up had higher level of Sr-exosomal PD-L1 at initial diagnosis, which compared with patients who were still alive at last follow-up. Patients in group of ≥14.23 pg/mL Sr-exosomal PD-L1 at initial diagnosis had inferior DFS compared with patients in group of <14.23 pg/mL at initial diagnosis. Patients in group of ≥25.96 pg/mL at initial diagnosis had poor OS compared with patients in group of <25.96 pg/mL at initial diagnosis. Use of liquid biopsy of circulating exosomal PD-L1 at initial diagnosis provides a robust means of predicting prognosis for patients with a newly diagnosed osteosarcoma.

Benefits of an Immunogenic Personalized Neoantigen Nanovaccine in Patients with High-Risk Gastric/Gastroesophageal Junction Cancer.

Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumor immune response. Here, a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy is generated. PNVAC triggers superior protective efficacy against tumor recurrence and promotes longer survival than free neoantigens, especially when combined with anti-PD-1 treatment in a murine tumor model. A phase I clinical trial (ChiCTR1800017319) is initiated to evaluate the safety, immunogenicity, and prophylactic effect of PNVAC on preventing tumor recurrence in patients with high-risk gastric/gastroesophageal junction cancer after adjuvant chemotherapy of postsurgical resection. The one- and two-year disease-free survival rates are significantly higher than historical record. PNVAC induces both CD4+ and CD8+ T cell responses as well as antigen-experienced memory T cell phenotype. Furthermore, the immune response is persistent and remains evident one year after the vaccination. This work provides a safe and feasible strategy for developing neoantigen vaccines to delay gastric cancer recurrence after surgery.