Two-year Survival Rates Research Articles

A phase I/II trial of brentuximab vedotin plus rituximab as frontline therapy for patients with immunosuppression-associated CD30+ and/or EBV + lymphomas

Treatment strategies for post-transplant lymphoproliferative disorders (PTLD) consist of response-adapted risk-stratified methods using immunosuppression reduction, immunotherapy, and chemotherapy. We investigated the efficacy of Brentuximab vedotin given concurrently with Rituximab (BV + R) once weekly for four weeks, followed by optional consolidation, and up to one year of maintenance. Among 20 assessable patients, BV + R therapy resulted in an overall response rate of 75% (95% CI 51 to 91, p = 0.044) with 60% achieving a complete response. Median time to best response was 28 days. Two-year progression-free survival and overall survival rates were 75 and 90%, respectively. Most common severe grade 3/4 treatment-related toxicities included neutropenia (40%), hypertension (30%), infection (25%), and peripheral neuropathy (15%). BV + R is a novel and effective therapeutic strategy that achieved rapid and durable remissions in previously untreated PTLD patients; however, this treatment platform requires further modification due to the high rates of treatment-related toxicity. Key points Brentuximab vedotin + Rituximab showed ORR and CR rates of 75 and 60% in patients with immunosuppression-associated lymphoid malignancies High rates of treatment delay were attributed to treatment-related toxicity; further dosing optimization of this regimen is required

Indications, functional and quality of life outcomes of new pouch creation during re-do ileal pouch anal anastomosis: A comparative study with existing pouch salvage

BackgroundSalvage of the existing ileal pouch is favored during re-do ileal pouch anal anastomosis if the pouch is not damaged after pelvic dissection and there are no other mechanical reasons that may necessitate construction of a new pouch. Excision of the existing pouch may be associated with some concerns for short-bowel syndrome and poor functional outcomes. This study aimed to report indications and compare functional and quality of life outcomes of new pouch creation versus salvage of the existing pouch during re-do ileal pouch anal anastomosis. MethodsPatients who underwent re-do ileal pouch anal anastomosis between September 2016 and June 2020 were included. The reasons for pouch excision and new pouch creation were reported. Perioperative, functional outcomes and quality of life were compared between patients who had creation of a new pouch versus salvage of existing pouch. ResultsA total of 105 patients with re-do ileal pouch anal anastomosis (new pouch, n = 63) were included. Most common indications for a new pouch creation were chronic pelvic infection that compromised the integrity and viability of the existing pouch (n = 32) and small pouch (n = 21). No patient developed short-bowel syndrome. The number of bowel movements, daily restrictions and Cleveland Global Quality of Life score scores were similar between 2 groups. Day-time seepage, day-time and night-time pad usage were more common after new pouch creation. Two-year pouch survival rates were comparable (new pouch: 92% versus existing pouch: 85%, P = .31). ConclusionNew pouch creation can be safely performed at the time of re-do ileal pouch anal anastomosis. It provides acceptable functional and quality of life outcomes if existing pouch salvage is not feasible.

Adherence to Attendance at Outpatient Clinic and Longterm Survival of Patients after Stroke in Outpatient Setting: the Data of REGION-M Registry

Aim. Assess the two-year survival rate of patients who have undergone acute cerebral circulation disorder, depending on their commitment to visiting the district polyclinic before and after discharge from the hospital.Material and methods. The outpatient part of the REGION-M register included 684 patients attached to the Moscow City Polyclinic №64, discharged from the Moscow City Clinical Hospital n.a. F.I. Inozemtsev of from 01.01.2012 to 04.30.2017 with a confirmed diagnosis of acute cerebral circulation disorder (cerebral stroke / transient ischemic attack).Results. Of the entire cohort, 83.2% of patients and 84.2% after hospital discharge attended the clinic during the year before the development of reference acute cerebral circulation disorder. Patients who attended the clinic before and after the reference stroke were older, more likely to have diabetes, comorbid disease and disability. For 22 months of follow-up, mortality was 28.8% (197 out of 684 people). Among those who applied and did not apply to the clinic before the reference acute cerebral circulation disorder, the difference in mortality tended to be reliable (27.4% versus 35.7%, p <0.1), while mortality was almost twice as low among patients who applied to the clinic at least 1 time after discharge (25.7%) than among patients who did not apply after discharge - 45.4%, p<0.0001. When adjusting for sex and age (the relative risk of death for them was 1.009, 95% confidence interval 1.005-1.01 2, p<0.0001 ), the statistical validity of reducing the risk of death was maintained when patients were committed to visiting the clinic after discharge - the relative risk of death 0.366 (95% confidence interval 0.269-0.500, p<0.0001 ).Conclusion. Lower mortality among those who visited the district polyclinic after undergoing stroke confirms the important role of medical observation in the posthospital period. At the same time, there is a reserve in improving the long-term prognosis of the lives of patients who have suffered a cerebral stroke or transient ischemic attack, due to greater coverage of patients with medical supervision in the clinic.

Concurrent Taxol-Based Doublet Chemotherapy as an Alternative for Intracavitary Brachytherapy Boost in Locally Advanced Carcinoma Cervix- Retrospective Analysis From a Tertiary Care Center

ObjectiveIn light of the dogma that brachytherapy is irreplaceable for the successful treatment of cervical cancer, and the limited availability of brachytherapy facilities in developing countries, we sought to evaluate the toxicity and efficacy of taxol- and platinum-based doublet chemotherapy delivered concurrently with external beam radiotherapy (EBRT) in locally advanced cervical cancer as an alternative to brachytherapy, which is mandated as the standard of care according to current guidelines.MethodsThe records from our institution were reviewed to identify patients who underwent chemoradiation with two doses of tri-weekly docetaxel (80mg/m2) and carboplatin (AUC 5) concurrent with EBRT between January 2017 and 2019 for locally advanced cervical carcinoma. Here, 48 cases were analysed, with a median follow-up period of two years.ResultsThe two groups were homogenously matched, and the patients who received EBRT boost and brachytherapy boost achieved complete pathological response rates of 68% and 83%, respectively (p=0.243). The odds ratio was 0.45 (95% confidence interval, 0.09-2.08), indicative of non-significance and non-inferiority based on the analysis using the chi-squared test (with Pearson’s correlation) and Student's t-test. The disease-free survival durations calculated using Kaplan-Meier estimates were 22 and 24 months, two-year disease-free survival rates were 83% and 91.3%, and two-year overall survival (OS) were 85.6% and 94% for the EBRT boost and brachytherapy boost groups, respectively (p=0.657).ConclusionIn this retrospective analysis, we concluded that EBRT boost was non-inferior to brachytherapy boost and could be considered as a reasonable alternative in locally advanced cervical cancer when used concurrently with more dose-intense chemotherapy.

Are Incidental Minute Pulmonary Nodules Ultimately Determined to Be Metastatic Nodules in Esophageal Cancer Patients?

Purpose: Esophageal cancer patients may simultaneously have resectable esophageal cancer and undiagnosable incidental minute solid pulmonary nodules. While the latter is rarely metastatic, only a few studies have reported on the outcomes of such nodules after surgery. In this retrospective study, we assessed the incidence of such nodules, the probability that they are ultimately metastatic nodules, and the prognosis of patients after esophagectomy according to the metastatic status of the nodules. Methods: Data of 398 patients who underwent esophagectomy for resectable esophageal cancer between January 2012 and December 2016 were collected. We reviewed computed tomography (CT) images from the first visit and searched for incidental minute pulmonary nodules <10 mm in size. We followed the outcomes of these nodules and compared the characteristics of metastatic and nonmetastatic nodules. We also assessed the prognosis of patients whose minute pulmonary nodules were metastatic. Results: Among the patients who underwent esophagectomy, 149 (37.4%) had one or more minute pulmonary nodules, with a total of 285 nodules. Thirteen (4.6%) of these nodules in 12 (8.1%) patients were ultimately diagnosed as being metastatic. Thirteen (8.7%) patients experienced recurrence at a different location from where the nodules were originally identified. Characteristics of the metastatic nodules were not unique in terms of size, SUVmax, or location in the lungs. Two-year and 5-year overall survival rates of patients whose nodules were metastatic were 64.2 and 32.1%, respectively. Conclusion: The rate of minute pulmonary nodules which were ultimately metastatic was 4.6%. Our findings suggest that esophagectomy followed by the identification of minute pulmonary nodules is an acceptable strategy even if the nodules cannot be diagnosed as being metastatic on the first visit CT due to their small size.

Re-evaluation of prophylactic cranial irradiation in limited-stage small cell lung cancer: a propensity score matched analysis.

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups’ backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve.

Selected Vancouver B2 periprosthetic femoral fractures around cemented polished femoral components can be safely treated with osteosynthesis.

We aimed to compare the implant survival, complications, readmissions, and mortality of Vancouver B2 periprosthetic femoral fractures (PFFs) treated with internal fixation with that of B1 PFFs treated with internal fixation and B2 fractures treated with revision arthroplasty. We retrospectively reviewed the data of 112 PFFs, of which 47 (42%) B1 and 27 (24%) B2 PFFs were treated with internal fixation, whereas 38 (34%) B2 fractures underwent revision arthroplasty. Decision to perform internal fixation for B2 PFFs was based on specific radiological (polished femoral components, intact bone-cement interface) and clinical criteria (low-demand patient). Median follow-up was 36.4 months (24 to 60). Implant survival and mortality over time were estimated with the Kaplan-Meier method. Adverse events (measured with a modified Dindo-Clavien classification) and 90-day readmissions were additionally compared between groups. In all, nine (8.01%) surgical failures were detected. All failures occurred within the first 24 months following surgery. The 24-month implant survival was 95.4% (95% confidence interval (CI) 89.13 to 100) for B1 fractures treated with internal fixation, 90% (95% CI 76.86 to 100) for B2 PFFs treated with osteosynthesis-only, and 85.8% (95% CI 74.24 to 97.36) for B2 fractures treated with revision THA, without significant differences between groups (p = 0.296). Readmissions and major adverse events including mortality were overall high, but similar between groups (p > 0.05). The two-year patient survival rate was 87.1% (95% CI 77.49 to 95.76), 66.7% (95% CI 48.86 to 84.53), and 84.2% (95% CI 72.63 to 95.76), for the B1 group, B2 osteosynthesis group, and B2 revision group, respectively (p = 0.102). Implant survival in Vancouver B2 PFFs treated with internal fixation was similar to that of B1 fractures treated with the same method and to B2 PFFs treated with revision arthroplasty. Low-demand, elderly patients with B2 fractures around well-cemented polished femoral components with an intact bone-cement interface can be safely treated with internal fixation. Cite this article: Bone Joint J2021;103-B(7):1222-1230.

P-166 Operative versus nonoperative treatment for stage 0 rectal cancer following chemoradiation therapy

In locally advanced rectal cancer, preoperative chemoradiotherapy (pCRT) is the standard care, aiming at downstaging and downsizing the tumor prior to potential radical surgery (1, 2). However, response to pCRT is highly variable, with only 8-20% of the patients exhibiting a complete pathological response (3). Surgical resection of the rectum may be associated with significant morbidity and mortality. Moreover, surgical resection may not lead to increased overall and disease-free survival in these patients. For this reason, we aimed to compare 2 groups of patients submitted to pCRT: one group without total clinical response therefore needing surgery (ypT0), and another with total clinical response, that did not need surgery (ycT0). Forty-six patients with rectal adenocarcinoma considered resectable were treated by pCRT. Complete and incomplete clinical responses were defined based on pelvic resonance magnetic, thoracic and abdominal tomography and endoscopic findings. Patients with incomplete clinical response were submitted to surgery resulting in stage ypT0. This group was compared to patients with complete clinical response with pCRT alone (ycT0) The statistical analysis was performed with Statistical Package for Social Sciences, version 26 (SPSS Inc., Chicago, IL, USA). Statistical analysis was performed using X2, Mann-Whitney U test and Kaplan-Meier curves. Three-year disease-free survival rate was 92.5%. In 13 patients (28.3%) complete clinical response was observed following pCRT (Non-surgical group). Thirty-three patients (71.7%) showed incomplete clinical response and were submitted to surgery. Anatomopathological results revealed ypT0N0M0 (Surgical group). Mean time until surgery was 10.7 weeks. There were no differences in patient demographics or tumor characteristics between groups. In the Surgical group, 18 definitive colostomies and 7 diverting temporary ileostomies were performed. Mean follow-up was 45.1 months in the Non-surgical group and 37.5 months in the Surgical group. There were 3 systemic recurrences and 1 endorectal recurrence in the Surgical group, with no recurrences in the Non-surgical group. Three patients in the Surgical group died of the disease. Two-year disease-free survival rates were 89.3% in the Surgical group and 100% in the Non-surgical group. Stage 0 rectal cancer disease is associated with excellent long-term results regardless of treatment strategy.

Abstract 1189: Association of RAS pathway mutations with lower CD8+ T cell infiltration and 2-year survival rate in Stage-III colorectal adenocarcinoma patients

Abstract Background: The oncogenic pathways, including WNT, TP53, RAS, PI3K and TGFβ, were associated with tumor progression in colorectal adenocarcinomas (CRC). However, a majority of CRC patients have mutations from multiple pathways simultaneously, which makes it difficult to identify the key pathway influencing prognosis of CRC. Herein, we aimed to evaluate the novel dominant pathway-typing method in predicting the prognosis of Stage-III CRC. Methods: Clinicopathologic and molecular variation data of Stage-III CRC patients (n=152) were obtained from The Cancer Genome Atlas database (TCGA). Immune cell infiltration level of the tumor was calculated by xCell (https://xcell.ucsf.edu/). Oncogenic pathway genes were classified according to a TCGA study (PMID: 29625050). In each patient, the dominant pathway-typing were based on which pathway the genes with the highest variant-allele-frequency (VAF) belongs to. Results: In all, 124/152 (82%) patients had mutation on at least one of the oncogenic pathway genes and 120/124 (97%) patients harbored mutations from two or more pathways simultaneously. According to their dominant pathway-typing method, the patients were classified into five groups: WNT (n=45), RAS (n=26), TP53 (n=36), PI3K (n=8) and TGFβ (n=9) groups. There was no significant difference in OS among the five groups. However, the two-year survival rate of RAS group was significantly lower than that of WNT (p=0.042) and TP53 (p=0.035) groups. Further, we found that the infiltration of CD8+ T cell was significantly lower in RAS group compared to WNT group (with median infiltration score: 0.005 vs 0.013, p=0.024). Importantly, we found that among the RAS group without CD8+ T-cell infiltration, 63% (5/8) patients were died within two years after diagnosis. While the two-year death rate of WNT and TP53 groups without CD8+ T cell infiltration were zero (0/6) and 14% (1/7). And the two-year death rate of RAS, WNT and TP53 groups with CD8+ T cell infiltration were 17% (1/6), 11% (3/27) and 8% (1/13), respectively. Conclusion: RAS pathway mutation may be associated with low CD8+ T cell infiltration and promote the two-year death rate of stage-III CRC patients using dominant pathway-typing method. And further larger cohorts are needed to validate these findings and the underlying mechanisms. Citation Format: Zhipeng Jiang, Feilong Zhao, Hui Chen, Xiaochen Zhao, Yuezong Bai. Association of RAS pathway mutations with lower CD8+ T cell infiltration and 2-year survival rate in Stage-III colorectal adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1189.

Abstract 7: Modeling cell-cell crosstalk in TNBC brain metastasis

Abstract Brain metastasis (BrM) is a difficult clinical problem in triple-negative breast cancer (TNBC) patients: it occurs in 25% to 40% of metastatic patients while two-year survival rate stubbornly remains a single digit. TNBC usually spreads to the brain rapidly at earlier stages or before the diagnosis of primary cancer. The shorter development time of BrM in TNBC and shorter survival time after BrM diagnosis may indicate a unique innate ability of TNBC tumor cells in adapting to the brain. Indeed, emerging data including ours indicates that TNBC tumor cells have intrinsic brain-like traits resulting in brain-tropism metastasis. Our preliminary studies identified enriched and diverse expressions of receptors and transporters of various neuro-active substances in brain metastatic TNBC cells, including neurotransmitters, gliotransmitters, neurotrophic factors and neural cytokines. By immunopanning astrocytes and microglia/macrophages from mouse brains bearing TNBC brain metastatic tumors at day 3 post tumor cell injection through left cardiac ventricle, and use the CCCExplorer software in modeling the interactions among tumor cells, astrocytes, and microglia/macrophage with cell-type specific RNAseq data, we identified several novel crosstalk signaling, including tumor autocrine TPH1-HTR2, astrocyte→tumor PCDH7-EGFR, IL6-IL6R, CCL5-CCR5 and VGF-C3AR1, and microglia/macrophage→tumor ARTN-GFAR3. Functional experiments demonstrated that cell type-specific depletion of the secreted neuro-active substances deactivated the activities of corresponding receptor and downstream signaling in co-cultured BrM tumor cells. Given that more complex paracrine/autocrine signaling network may dynamically evolve during BrM development, we are characterizing the spatiotemporal cell-cell crosstalk in the BrM metastatic niche that will have important implications for novel therapeutics development. Citation Format: Hong Zhao, Xin Wang, Nikola Liu, Jianting Sheng, Stephen Wong. Modeling cell-cell crosstalk in TNBC brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 7.

The Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI): A Three-Factor Comorbidity Model.

Comorbid medical conditions define a subset of patients with chronic lymphocytic leukemia (CLL) with poor outcomes. However, which comorbidities are most predictive remains understudied. We conducted a retrospective analysis from 10 academic centers to ascertain the relative importance of comorbidities assessed by the cumulative illness rating scale (CIRS). The influence of specific comorbidities on event-free survival (EFS) was assessed in this derivation dataset using random survival forests to construct a CLL-specific comorbidity index (CLL-CI). Cox models were then fit to this dataset and to a single-center, independent validation dataset. The derivation and validation sets comprised 570 patients (59% receiving Bruton tyrosine kinase inhibitor, BTKi) and 167 patients (50% receiving BTKi), respectively. Of the 14 CIRS organ systems, three had a strong and stable influence on EFS: any vascular, moderate/severe endocrine, moderate/severe upper gastrointestinal comorbidity. These were combined to create the CLL-CI score, which was categorized into 3 risk groups. In the derivation dataset, the median EFS values were 58, 33, and 20 months in the low, intermediate, and high-risk groups, correspondingly. Two-year overall survival (OS) rates were 96%, 91%, and 82%. In the validation dataset, median EFS values were 81, 40, and 23 months (two-year OS rates 97%/92%/88%), correspondingly. Adjusting for prognostic factors, CLL-CI was significantly associated with EFS in patients treated with either chemo-immunotherapy or with BTKi in each of our 2 datasets. The CLL-CI is a simplified, CLL-specific comorbidity index that can be easily applied in clinical practice and correlates with survival in CLL.

Proton Therapy for Major Salivary Gland Cancer: Clinical Outcomes.

PurposeTo report clinical outcomes in terms of disease control and toxicity in patients with major salivary gland cancers (SGCs) treated with proton beam therapy.Materials and MethodsClinical and dosimetric characteristics of patients with SGCs treated from August 2011 to February 2020 on an observational, prospective, single-institution protocol were abstracted. Local control and overall survival were calculated by the Kaplan-Meier method. During radiation, weekly assessments of toxicity were obtained, and for patients with ≥ 90 days of follow-up, late toxicity was assessed.ResultsSeventy-two patients were identified. Median age was 54 years (range, 23-87 years). Sixty-three patients (88%) received postoperative therapy, and nine patients (12%) were treated definitively. Twenty-six patients (36%) received concurrent chemotherapy. Nine patients (12%) had received prior radiation. All (99%) but one patient received unilateral treatment with a median dose of 64 GyRBE (relative biological effectiveness) (interquartile range [IQR], 60-66), and 53 patients (74%) received intensity-modulated proton therapy with either single-field or multifield optimization. The median follow-up time was 30 months. Two-year local control and overall survival rates were 96% (95% confidence interval [CI] 85%-99%) and 89% (95% CI 76%-95%], respectively. Radiation dermatitis was the predominant grade-3 toxicity (seen in 21% [n = 15] of the patients), and grade ≥ 2 mucositis was rare (14%; n = 10 patients). No late-grade ≥ 3 toxicities were reported.ConclusionProton beam therapy for treatment of major SGCs manifests in low rates of acute mucosal toxicity. In addition, the current data suggest a high rate of local control and minimal late toxicity.

Treatment patterns and disease course of previously untreated Primary Central Nervous System Lymphoma: Feasibility of MTX-based regimens in clinical routine.

Primary central nervous system lymphoma (PCNSL) is a rare type of aggressive lymphoma of the central nervous system. Treatment strategies improved significantly over the past decades differ regionally but mainly consist of rituximab and high-dosed methotrexate (MTX)-based therapies. We assessed clinical outcomes of 100 patients with newly diagnosed PCNSL between 2010-2020 at the University Hospital of Cologne, Germany. Patients were 23-88years of age and either treated with MTX-based regimens (PRIMAIN, MARTA, MATRix), individual regimens, or best supportive care, respectively. Overall response rates were generally high (66,7-83,8%), but different organ toxicities required dose adjustments in most groups. Two-year overall survival rates were 57,9% (PRIMAIN), 63,6% (MARTA), 65,4% (MATRix), and 37,5% (Other), respectively. Out of 9 patients suffering from relapse >12months from primary diagnosis, 7 patients (77,8%) received methotrexate-based salvage therapy with 2-year overall survival of 4/6 patients (66,7%). Although a relevant proportion of patients are not eligible for clinical trials due to age, performance status, or comorbidities, these results prove feasibility of different MTX-based treatment strategies in clinical routine. Even elderly patients displayed surprisingly favorable outcomes. However, with compromising organ toxicities, reduction of intensity should be part of strategies in future clinical trials.

Radiosensitization using hydrogen peroxide in patients with cervical cancer.

The purpose of the present study was to analyze the feasibility and safety of radiosensitization using hydrogen peroxide for cervical cancer. In superficial tumors, breast cancer and hepatocellular carcinoma, the safety and effectiveness of radiosensitization has been reported; to the best of our knowledge, however, there are no reports on cervical cancer. A total of 20 patients with cervical cancer were recruited. Inclusion criteria were as follows: Patients who required radical external beam radiotherapy (RT); ineligible for or refused brachytherapy; age, ≥20 years; no hematogenous metastasis; Eastern Cooperative Oncology Group Performance Status up to 2; and had not undergone prior treatment. Hydrogen peroxide was used twice a week in combination with RT. A 3% hydrogen peroxide solution-soaked gauze was inserted into the vagina during RT. A total of 45 Gy was delivered in 25 fractions to the whole pelvis with a boost of 10 Gy in 5 fractions if pelvic or para-aortic metastatic lymph nodes were observed. Ultimately, 18 patients were evaluated. Among the 17 patients (excluding one patient with tumor in situ), the one- and two-year overall survival rates were both 90% in patients with stage I/II and 86% in stage III/IV cervical cancer. The adverse events were well tolerated with no severe acute or late adverse events. Although limited by small sample size, short observation time and low radiation dose, the present study demonstrated that radiosensitization treatment may be an option for patients who cannot undergo brachytherapy. The study was retrospectively registered at the university hospital medical information network center (no. UMIN000039045) on January 6, 2020.

Age-related treatment patterns for stage I NSCLC in three European countries

IntroductionSurgery is the preferred treatment for patients with early-stage non-small cell lung cancer (NSCLC) while stereotactic body radiation therapy (SBRT) may be applied in patients with major comorbidity or high age. We evaluated the association between age and treatment utilization for early-stage NSCLC in patients diagnosed in 2015–2016 in three European countries. Patients and methodsInformation was retrieved from population-based registries in England, Norway and the Netherlands. Treatment patterns and two-year overall survival rates for 105,124 patients with clinical stage I were analysed by age-group. ResultsSurgical resection rates were higher in Norway (55%) and England (53%) than in the Netherlands (47%), and decreased with increasing age. SBRT use was highest in the Netherlands (41%), followed by Norway (29%) and England (12%). In the Netherlands, SBRT was the prevailing treatment in patients aged 70 years or older. In octogenarians, the proportion not receiving curative intent treatment was 53% in England, versus 35% in Norway and 22% in the Netherlands. Two-year survival rates were better for surgery than for SBRT and slightly better in Norway. ConclusionIn patients aged 70 years or older, the proportion not receiving any curative treatment remains substantial, and differs significantly between countries. Measures to address these disparities are needed.

RETRACTED: Research on the optimization strategy of innovation and entrepreneurship education teaching mechanism

Contemporary college students are the main group that will create a new kind of China and promote China's economic development. This requires them to have a unique and sensitive perspective of development, education is not only the demand of China's economic structure transformation, but also in line with the development trend of global higher innovation education. 1000 college students from different grades and regions have fully understood the innovation education of our country through the questionnaire survey. In the past ten years, the government, universities in some regions and the society have analyzed the investment in education. In addition, this paper also compares the two-year survival rate of entrepreneurship projects between graduates with and without education from 2010 to 2017. Through the post-processing, statistics and comparison of the data, we find that most of the students have different degrees of willingness to start a business, but relatively few can put it into action. The main reasons are the lack of a reliable platform, innovative ideas can not be achieved, the lack of guidance of relevant economic theory knowledge, and the inability to implement scientific research achievements into specific entrepreneurial projects.

Percutaneous Irreversible Electroporation for Treatment of Small Hepatocellular Carcinoma Invisible on Unenhanced CT: A Novel Combined Strategy with Prior Transarterial Tumor Marking.

Simple SummaryIrreversible electroporation (IRE) is an effective alternative for the ablation of small hepatocellular carcinoma (HCC) less than 2 cm, which is often poorly visible under unenhanced computed tomography (CT) and/or an ultrasound resulting in the difficulties of complete ablation. In this study, to achieve successful ablation on these small target HCCs with poor invisibility, the combination of transarterial ethiodized oil tumor marking with sequential computed tomography (CT)-guided IRE was performed. After marking, all 11 target-HCCs demonstrated complete visualization in post-marking CT, which were invisible in pre-marking CT. Technically successful ablation was achieved in all sequential IRE procedures. In the follow-up, no residual unablated tumor was observed and the two-year local tumor progression was 27.3%. Thus, ethiodized oil tumor marking with sequential CT-guided IRE is a safe and feasible combination to treat small HCC which was invisible in unenhanced CT.Introduction. To explore the feasibility, safety, and efficiency of ethiodized oil tumor marking combined with irreversible electroporation (IRE) for small hepatocellular carcinomas (HCCs) that were invisible on unenhanced computed tomography (CT). Methods. A retrospective analysis of the institutional database was performed from January 2018 to September 2018. Patients undergoing ethiodized oil tumor marking to improve target-HCC visualization in subsequent CT-guided IRE were retrieved. Target-HCC visualization after marking was assessed, and the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNR) were compared between pre-marking and post-marking CT images using the paired t-test. Standard IRE reports, adverse events, therapeutic endpoints, and survival were summarized and assessed. Results. Nine patients with 11 target-HCCs (11.1–18.8 mm) were included. After marking, all target-HCCs demonstrated complete visualization in post-marking CT, which were invisible in pre-marking CT. Quantitatively, the SNR of the target-HCCs significantly increased after marking (11.07 ± 4.23 vs. 3.36 ± 1.79, p = 0.006), as did the CNR (4.32 ± 3.31 vs. 0.43 ± 0.28, p = 0.023). In sequential IRE procedures, the average current was 30.1 ± 5.3 A, and both the delta ampere and percentage were positive with the mean values of 5.8 ± 2.1 A and 23.8 ± 6.3%, respectively. All procedures were technically successful without any adverse events. In the follow-up, no residual unablated tumor (endpoint-1) was observed. The half-year, one-year, and two-year local tumor progression (endpoint-2) rate was 0%, 9.1%, and 27.3%. The two-year overall survival rate was 100%. Conclusions. Ethiodized oil tumor marking enables to demarcate small HCCs that were invisible on unenhanced CT. It potentially allows a safe and complete ablation in subsequent CT-guided IRE.

Long-Term Clinical Outcomes and Carotid Ultrasound Follow-Up of Transcarotid TAVI. Prospective Single-Center Registry.

This study aimed to prospectively evaluate the safety and long-term clinical outcomes of cerebral-oximetry-guided transcarotid transcatheter aortic valve implantation (TC-TAVI) with systematic follow-up with carotid ultrasound. Thirty-three TCTAVI procedures were performed in our center from 2017 to 2019. Our analysis includes in-hospital outcomes and long-term follow-up data on mortality, echocardiographic parameters, carotid Doppler ultrasound, and VARC-2 defined clinical events. Intraoperatively, one patient died, and one had a transient ischemic attack (TIA). The following events occurred in-hospital postoperatively: myocardial infarction (3.0%), cardiac tamponade (3.0%), new-onset atrial fibrillation (6.3%), need for temporary pacing (27.3%) and need for pacemaker implantation (15%). The mean follow-up was 19.5 ± 9.52 months. In the long-term follow-up, the two-year survival rate was 83% ± 14. The echocardiographic parameters did not differ significantly from the postprocedural values, and the ultrasound did not show any cases of significant vessel narrowing. The mean peak systolic velocity (PSV) was 71.6 cm/s in the left common carotid artery and 70.6 cm/s in the right common carotid artery. In conclusion, cerebral oximetry-guided TC access is safe, has a favorable long-term outcome, and does not increase the risk of plaque formation in the carotid artery. In a carefully selected group of patients, it might be considered as a first-choice alternative to TF access.

Ventricular Assist Devices in Adults with Failing Systemic Right Ventricle: The Importance of Concomitant Tricuspid Valve Replacement

<h3>Purpose</h3> Ventricular assist device (VAD) for systemic right ventricular failure (SRVF) post atrial switch for transposition of the great arteries (TGA) and congenitally corrected TGA (ccTGA) has proven useful to reduce transpulmonary gradient (TPG) and bridge-to-transplantation. The hemodynamic impact of severe tricuspid regurgitation (TR), potential role of systemic tricuspid valve replacement (TVR) and long-term outcomes are still unknown. The purpose of this study is to describe our experience of VAD in SRVF and our move towards concomitant TVR. <h3>Methods</h3> Single-centre retrospective study of consecutive adult patients receiving HeartWare-VAD for SRVF between 2010 and 2020. From 2017, concomitant TVR was performed routinely. Demographic, clinical variables and echocardiographic and haemodynamic measurements pre and post VAD implantation were recorded. Complications on support, heart transplantation and survival rates were described. <h3>Results</h3> 24 patients underwent VAD implantation. Moderate or severe systemic TR was present in 83% of patients, and subpulmonic left ventricular (LV) impairment in 79%. One and two-year survival rates were 75% and 60% respectively. VAD implantation was technically feasible and successful in all but one. Post VAD, TPG fell from 16 (15-20) to 10 (7-13) mmHg; p=0.002. Patients with TVR (n=12) also demonstrated reduction in pulmonary and atrial pressures (figure). Subpulmonic LV end-diastolic dimension (50 vs 42mm; p=0.05) and systolic function improved in this group. On the other hand a high prevalence of subpulmonic LV failure was noted in the non TVR group (50% vs 8.3%; p=0.03) resulting in higher mortality. After six months on support, 63% of patients were suitable for transplantation. <h3>Conclusion</h3> VAD implantation for patients with SRVF in TGA or ccTGA is feasible, and significantly reduces the TPG to transplantable limits. Concomitant TVR at the time of implant associates better haemodynamic and echocardiographic results.

Population-level changes in outcomes and Medicare cost following the introduction of new cancer therapies.

To examine the population-level impacts of the introduction of novel cancer therapies with high cost in the United States, using immunotherapies in advanced nonsmall cell lung cancer (NSCLC) as an example. Surveillance, Epidemiology, and End Results data in 2012-2015 linked to Medicare fee-for-service claims until 2016. We examined population-level trends in treatment patterns, survival, and Medicare spending in patients diagnosed with advanced NSCLC, the leading cause of cancer death in the United States, between 2012 and 2015. We estimated the percentage of patients who received any antineoplastic therapy within two years of diagnosis, including novel immunotherapies. We compared the trends in overall survival and mean two-year Medicare spending per each patient before and after the introduction of immunotherapies in 2015. Not Applicable. The percentage of patients treated with any antineoplastic therapy remained the same at 46.7% in 2012 and 2015, whereas the use of immunotherapies increased from 0% to 15.2%. The two-year survival rate and median survival increased by 3.3 percentage points (95% CI: 2.0, 4.5) and 0.4months (CI: 0.0, 0.9), respectively, during the same period. The mean two-year total Medicare spending and outpatient spending per patient increased by $5735 (CI: 3479, 8040) and $7661 (CI: 5902, 9311), respectively, which were largely attributable to the increases in immunotherapy spending by $5806 (CI: 5165, 6459). The introduction of lung cancer immunotherapies was accompanied by improvements in survival and increases in spending between 2012 and 2015 in the Medicare population. As novel immunotherapies and other target therapies continue to change the clinical management of various cancers, further efforts are needed to ensure their effective and efficient use, and to understand their population-level impacts in the United States.