Months For High-risk Patients Research Articles

Predictors And Associated Outcomes Of Adherence To Treatment In Russian Patients Undergoing Corneal Transplantation

Corneal blindness affects approximately 8 million people worldwide. The effectiveness of keratoplasty depends on several factors, including surgical technique, clinical characteristics of the patients, and social factors such as their adherence to treatment. Objective — To analyze nonattendance of doctor’s appointments and associated clinical outcomes in Russian patients who underwent high-risk and low-risk penetrating keratoplasty (PKP). Material and Methods — We conducted a retrospective cohort study to analyze the pre- and postoperative records of patients who underwent PKP. The low-risk group included 28 people with keratoconus (their mean age was 33±3 years), while high-risk group included 54 people with corneal opacity of various etiologies (their mean age was 67±13 years). The study assessed adherence to treatment by examining attendance at postoperative physician visits. Successful corneal transplant engraftment was considered favorable outcome, whereas graft failure or opacification was considered adverse outcome. The duration of observation was 12 months. Results — Patients in the low-risk group were twice as likely to attend postoperative appointments compared with patients in the high-risk group (p=0.0001). Patients over 70 years of age showed lower adherence to treatment (p=0.016), while those with higher education had significantly improved appointment attendance (p=0.017). Moreover, poor adherence increased the odds of adverse PKP outcome at 12 months in high-risk patients (OR=4.31; p=0.045). Conclusion — Failure to attend postoperative appointments in the high-risk group was associated with older patient age and lower education level, and correlated with adverse clinical outcome in Russian patients.

Real-world study on the characteristics, post-nephrectomy journey, and outcomes of patients with early-stage renal cell carcinoma based on risk groups.

To examine real-world characteristics, journey, and outcomes among patients with locoregional, nonmetastatic renal cell carcinoma (RCC). A retrospective analysis of medical records from the ConcertAI Oncology Dataset was performed on adults in the United States with newly diagnosed nonmetastatic RCC between January 2012-December 2017 who received surgical treatment, and were followed until August 2021. Patients were stratified based on the risk of recurrence after nephrectomy. Recurrence rate and survival outcomes were assessed. The cohort (n = 439) had a median age of 64 years, 66.1% were male, and 76.5% had clear-cell histology. The median follow-up time from nephrectomy was 39.3 months overall, 41.0 months for intermediate-high-risk patients (n = 377; 85.9%) and 24.1 months for high-risk patients (n = 62; 14.1%). For intermediate-high- and high-risk patients, respectively, 68.4% and 56.5% had ≥1 medical oncologist visit after nephrectomy. Of 260 patients with documentation of postoperative imaging assessments, 72% were ordered by medical oncologists, and the median time from initial nephrectomy to the first scan was 110 days (intermediate-high-risk) and 51 days (high-risk). Provider-documented recurrence occurred in 223 (50.8%) patients, of whom 41.7% had ≥1 medical oncologist visit before the recurrence. Three-year disease-free survival (DFS), and overall survival rates were 49.4% and 80.8% (all patients): 27.7% and 64.7% (high-risk); and 52.9% and 83.3% (intermediate-high-risk). Our study reports low DFS after nephrectomy for patients with intermediate-high- and high-risk RCC. Subsequent approval and use of new and newly approved adjuvant therapeutic options could potentially delay or prevent recurrence.

Improved Outcome of Allogeneic Transplantation in Older Patients Treated for Myeloid Malignancies Using Post-Transplantation Cyclophosphamide and Reduced Duration of Immune Suppression

BackgroundAllogeneic stem cell transplantation (alloSCT) offers curative potential for older patients with myeloid malignancies. We evaluated the efficacy and safety of alloSCT using post-transplantation cyclophosphamide (PTCy) in combination with a very short duration of immune suppression (IS) in this population. MethodsWe retrospectively analyzed 92 consecutive patients aged 65 years and older who underwent an alloSCT for myeloid malignancies between February 2018 and December 2022 at our institution. Data on patient characteristics, treatment modalities, and outcomes were collected. ResultsNinety-two patients received an alloSCT with PTCy-based GVHD prophylaxis. The majority had minimal comorbidities and were diagnosed with acute myeloid leukemia (AML). Patients mostly received conditioning regimens with low to intermediate TCI scores. In 43% of patients, IS could be permanently stopped at day +90, resulting in a median time of IS of 2.93 months in high-risk patients. At a median follow-up of 21.3 months, the 1- and 2-year overall survival rates were 89% and 87%, respectively. Relapse-free survival rates were 88% and 84% at 1 and 2 years, respectively. The 1- and 2-year cumulative incidences of relapse were 8% and 13%, while transplant-related mortality (TRM) estimates were 9% at both time points. Acute GVHD grade 3-4 occurred in 7% within the first 180 days and severe chronic GVHD in 6% of patients. This all resulted in a 1- and 2-year graft versus host and relapse free survival (GRFS) of 74% and 70%, respectively. ConclusionAlloSCT using PTCy in combination with a short duration of IS in older patients with myeloid malignancies demonstrates favorable survival outcomes due to low relapse rates and a low TRM. The low incidence of relapse and acceptable rates of graft-versus-host disease suggest the efficacy and safety of this approach. Further studies are warranted to validate these findings and optimize transplant strategies for older patients with myeloid malignancies.

Retrospective evaluation of gestational trophoblastic disease - experience with ultrasounds.

Our study aims to determine the frequency and types of GTD (Gestational Trophoblastic Disease) in our clinic, to evaluate its relationship with clinical parameters, and the consistency of clinical prediagnosis and pathological definitive diagnosis. In the present study, hospital records of 120 patients with gestational trophoblastic disease between January 2019 and August 2022 were obtained and evaluated retrospectively. Demographic, hematological, biochemical, and clinical data were collected in detail, and the data were analyzed statistically. Our study included a total of 120 female patients, with an average age of 31.16±9.70. The average number of patients was 3. The average time for women to receive the diagnosis was 9.80±2.45 weeks, with the most frequent complaint on our part being bleeding (85.8%). When the pathology outcomes of the patients we included in our study were examined, it was found that the number of patients diagnosed with incomplete abortion was 34, the number of patients diagnosed with complete abortion was 82, the number of invasive moles diagnosed was 3, and the number of patient diagnosed with choriocarcinoma was 1. Kappa ratio was calculated as 0.419 (p<0.001) when the compliance of the clinical diagnosis was assessed. This value was consistent with median level alignment. In a study that examined the three years of our calism in our bulk, 1.8 per 1,000 births were followed frequently. We should inform patients in detail about gestational trophoblastic diseases and warn patients not to delay their consequences. We should recommend that pregnancy be avoided for 12 months for low-risk patients and 18 months for high-risk patients after GTD.

Does FDG PET-Based Radiomics Have an Added Value for Prediction of Overall Survival in Non-Small Cell Lung Cancer?

Objectives: Radiomics and machine learning are innovative approaches to improve the clinical management of NSCLC. However, there is less information about the additive value of FDG PET-based radiomics compared with clinical and imaging variables. Methods: This retrospective study included 320 NSCLC patients who underwent PET/CT with FDG at initial staging. VOIs were placed on primary tumors only. We included a total of 94 variables, including 87 textural features extracted from PET studies, SUVmax, MTV, TLG, TNM stage, histology, age, and gender. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables with the highest predictive value. Although several radiomics variables are available, the added value of these predictors compared with clinical and imaging variables is still under evaluation. Three hundred and twenty NSCLC patients were included in this retrospective study and underwent 18F-FDG PET/CT at initial staging. In this study, we evaluated 94 variables, including 87 textural features, SUVmax, MTV, TLG, TNM stage, histology, age, and gender. Image-based predictors were extracted from a volume of interest (VOI) positioned on the primary tumor. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to reduce the number of variables and select only those with the highest predictive value. The predictive model implemented with the variables selected using the LASSO analysis was compared with a reference model using only a tumor stage and SUVmax. Results: NGTDM coarseness, SUVmax, and TNM stage survived the LASSO analysis and were used for the radiomic model. The AUCs obtained from the reference and radiomic models were 80.82 (95%CI, 69.01-92.63) and 81.02 (95%CI, 69.07-92.97), respectively (p = 0.98). The median OS in the reference model was 17.0 months in high-risk patients (95%CI, 11-21) and 113 months in low-risk patients (HR 7.47, p < 0.001). In the radiomic model, the median OS was 16.5 months (95%CI, 11-20) and 113 months in high- and low-risk groups, respectively (HR 9.64, p < 0.001). Conclusions: Our results indicate that a radiomic model composed using the tumor stage, SUVmax, and a selected radiomic feature (NGTDM_Coarseness) predicts survival in NSCLC patients similarly to a reference model composed only by the tumor stage and SUVmax. Replication of these preliminary results is necessary.

Ovarian recurrence risk assessment using machine learning, clinical information, and serum protein levels to predict survival in high grade ovarian cancer

In ovarian cancer, there is no current method to accurately predict recurrence after a complete response to chemotherapy. Here, we develop a machine learning risk score using serum proteomics for the prediction of early recurrence of ovarian cancer after initial treatment. The developed risk score was validated in an independent cohort with serum collected prospectively during the remission period. In the discovery cohort, patients scored as low-risk had a median time to recurrence (TTR) that was not reached at 10 years compared to 10.5 months (HR 4.66, p < 0.001) in high-risk patients. In the validation cohort, low-risk patients had a median TTR which was not reached compared to 4.7 months in high-risk patients (HR 4.67, p = 0.009). In advanced-stage patients with a CA125 < 10, low-risk patients had a median TTR of 68 months compared to 6 months in high-risk patients (HR 2.91, p = 0.02). The developed risk score was capable of distinguishing the duration of remission in ovarian cancer patients. This score may help guide maintenance therapy and develop innovative treatments in patients at risk at high-risk of recurrence.

MP11-12 DEVELOPMENT OF A RISK MODEL FOR TIME TO SECOND PROGRESSION IN PATIENTS WITH HIGH-RISK METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER TREATED WITH ABIRATERONE ACETATE AND ANDROGEN DEPRIVATION THERAPY

You have accessJournal of UrologyCME1 Apr 2023MP11-12 DEVELOPMENT OF A RISK MODEL FOR TIME TO SECOND PROGRESSION IN PATIENTS WITH HIGH-RISK METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER TREATED WITH ABIRATERONE ACETATE AND ANDROGEN DEPRIVATION THERAPY Shintaro Narita, Takafumi Yanagisawa, Shingo Hatakeyama, Kenichi Hata, Hiromi Sato, Ryuichiro Sagehashi, Yuya Sekine, Mizuki Kobayashi, Taketoshi Nara, Kazuyuki Numakura, Mitsuru Saito, Chikara Ohyama, Takahiro Kimura, and Tomonori Habuchi Shintaro NaritaShintaro Narita More articles by this author , Takafumi YanagisawaTakafumi Yanagisawa More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Kenichi HataKenichi Hata More articles by this author , Hiromi SatoHiromi Sato More articles by this author , Ryuichiro SagehashiRyuichiro Sagehashi More articles by this author , Yuya SekineYuya Sekine More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Chikara OhyamaChikara Ohyama More articles by this author , Takahiro KimuraTakahiro Kimura More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003226.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Evidence on risk stratification in patients treated with doublet therapy with abiraterone acetate is limited. In this study, we developed a risk stratification model in patients with de novo high-risk mCSPC who received abiraterone acetate plus androgen deprivation therapy based on clinical risk factors. METHODS: Medical records of 224 high-risk patients with de novo mCSPC treated with abiraterone acetate plus androgen deprivation therapy at 11 centers between 2015 and 2022 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free, progression-free survival 2 (PFS2), and overall survival (OS) were estimated using the Kaplan–Meier method. The association of pretreatment clinical risk factors with PFS2 was evaluated by Cox proportional hazard models and survival outcomes were classified according to the number of risk factors. RESULTS: Median PFS2 was 43 months; second-progression occurred in 76 (34.2%) patients. On multivariable analysis, the following four risk factors were identified as independent predictors of PFS2: primary Gleason pattern 5 (HR 1.97, 95% CI 1.20–3.22), presence of liver metastasis (HR 2.05, 95% CI 1.02–4.13), extent of disease score ≥3 (HR 2.25, 95% CI 1.16–4.34), and abnormal hemoglobin (HR 1.73, 95% CI 1.02–2.92). Significant differences in PFS2 were observed among the three risk groups (low vs. intermediate; p=0.006, intermediate vs. high; p<0.001). Median PFS2 and OS of high-risk patients were significantly worse in the low- and intermediate-risk groups. The median PFS2 of low-risk patients with no or one factor was not reached, whereas that of intermediate-risk patients with two or three factors and high-risk patients with four factors were 42 months and 16 months, respectively. Median OS was 24 months in high-risk patients, whereas it was not reached in low- and intermediate-risk patients. CONCLUSIONS: We successfully classified patients with high-risk mCSPC treated with abiraterone acetate based on four clinical risk factors. Risk-adapted treatment may be beneficial for selected patients with mCSPC in this triplet therapy era. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e128 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shintaro Narita More articles by this author Takafumi Yanagisawa More articles by this author Shingo Hatakeyama More articles by this author Kenichi Hata More articles by this author Hiromi Sato More articles by this author Ryuichiro Sagehashi More articles by this author Yuya Sekine More articles by this author Mizuki Kobayashi More articles by this author Taketoshi Nara More articles by this author Kazuyuki Numakura More articles by this author Mitsuru Saito More articles by this author Chikara Ohyama More articles by this author Takahiro Kimura More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...

Identification of Atezolizumab Plus Bevacizumab Prognostic Index via Recursive Partitioning Analysis in HCC: The ABE Index.

The purpose of this study was to ascertain a novel prognostic index via recursive partitioning analysis (RPA) in hepatocellular carcinoma (HCC) patients being treated with the combination of atezolizumab plus bevacizumab (ABE) in first-line setting. A total of 784 patients with HCC were included in the analysis. RPA identified three groups of patients: high-risk [Child-Pugh B (CP-B) patients; CP-A and Albumin-Bilirubin (ALBI)-2 patients; CP-A and ALBI-1 patients with macrovascular invasion (MVI), and alpha-fetoprotein (α-FP) ≥400 ng/ml]; intermediate-risk [CP-A and ALBI-1 patients with aspartate aminotransferase (AST) normal value (NV), and αFP ≥400 ng/ml, but without MVI; CP-A and ALBI-1 patients with AST increased value (IV), and neutrophil-lymphocyte ratio (NLR) ≥3, but without MVI]; low-risk (CP-A and ALBI-1 patients with AST NV, and αFP <400 ng/ml, but without MVI; CP-A and ALBI-1 patients with AST IV, and NLR <3, but without MVI; CP-A and ALBI-1 patients with MVI, and αFP <400 ng/ml). Overall survival was 7.0 months in high-risk patients (20.8%), 14.2 months in intermediate-risk patients (19.1%), and 22.5 months in low-risk patients (60.1%). The ABE index allows for easy stratification of HCC patients treated with the combination of ABE in first-line setting.

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Taiwan perspective.

Hepatocellular carcinoma (HCC) is the fourth most common cancer and the second leading cause of cancer-related death in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan developed and updated the guidelines for HCC management in 2020. In clinical practice, we follow these guidelines and the reimbursement policy of the government. In Taiwan, abdominal ultrasonography, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) tests are performed for HCC surveillance every 6 months or every 3 months for high-risk patients. Dynamic computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound have been recommended for HCC surveillance in extremely high-risk patients or those with poor ultrasonographic visualization results. HCC is usually diagnosed through dynamic imaging, and pathological diagnosis is recommended. Staging of HCC is based on a modified version of the Barcelona Clinic Liver Cancer (BCLC) system, and the HCC management guidelines in Taiwan actively promote curative treatments including surgery and locoregional therapy for BCLC stage B or C patients. Transarterial chemoembolization (TACE), drug-eluting bead TACE, transarterial radioembolization, and hepatic artery infusion chemotherapy may be administered for patients with BCLC stage B or C HCC. Sorafenib and lenvatinib are reimbursed as systemic therapies, and regorafenib and ramucirumab may be reimbursed in cases of sorafenib failure. First-line atezolizumab with bevacizumab is not yet reimbursed but may be administered in clinical practice. Systemic therapy and external beam radiation therapy may be used in specific patients. Early switching to systemic therapy in TACE-refractory patients is a recent paradigm shift in HCC management.

A multivariate parametric empirical Bayes screening approach for early detection of hepatocellular carcinoma using multiple longitudinal biomarkers.

The early detection of hepatocellular carcinoma (HCC) is critical to improving outcomes since advanced HCC has limited treatment options. Current guidelines recommend HCC ultrasound surveillance every 6 months in high-risk patients however the sensitivity for detecting early stage HCC in clinical practice is poor. Blood-based biomarkers are a promising direction since they are more easily standardized and less resource intensive. Combining of multiple biomarkers is more likely to achieve the sensitivity required for a clinically useful screening algorithm and the longitudinal trajectory of biomarkers contains valuable information that should be utilized. We propose a multivariate parametric empirical Bayes (mPEB) screening approach that defines personalized thresholds for each patient at each screening visit to identify significant deviations that trigger additional testing with more sensitive imaging. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial provides a valuable source of data to study HCC screening algorithms. We study the performance of the mPEB algorithm applied to serum -fetoprotein, a widely used HCC surveillance biomarker, and des- carboxy prothrombin, an HCC risk biomarker that is FDA approved but not used in practice in the United States. Using cross-validation, we found that the mPEB algorithm demonstrated moderate but improved sensitivity compared to alternative screening approaches. Future research will validate the clinical utility of the approach in larger cohort studies with additional biomarkers.

A Novel Clinical-Radiomics Model Based on Sarcopenia and Radiomics for Predicting the Prognosis of Intrahepatic Cholangiocarcinoma After Radical Hepatectomy.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor with a poor prognosis. This study aimed to establish a novel clinical-radiomics model for predicting the prognosis of ICC after radical hepatectomy.MethodsA clinical-radiomics model was established for 82 cases of ICC treated with radical hepatectomy in our hospital from May 2011 to December 2020. Radiomics features were extracted from venous-phase and arterial-phase images of computed tomography. Kaplan-Meier survival analysis was generated to compare overall survival (OS) between different groups. The independent factors were identified by univariate and multivariate Cox regression analyses. Nomogram performance was evaluated regarding discrimination, calibration, and clinical utility. C-index and area under the curve (AUC) were utilized to compare the predictive performance between the clinical-radiomics model and conventional staging systems.ResultsThe radiomics model included five features. The AUC of the radiomics model was 0.817 in the training cohort, and 0.684 in the validation cohort. The clinical-radiomics model included psoas muscle index, radiomics score, hepatolithiasis, carcinoembryonic antigen, and neutrophil/lymphocyte ratio. The reliable C-index of the model was 0.768, which was higher than that of other models. The AUC of the model for predicting OS at 1, and 3 years was 0.809 and 0.886, which was significantly higher than that of the American Joint Committee on Cancer 8th staging system (0.594 and 0.619), radiomics model (0.743 and 0.770), and tumor differentiation (0.645 and 0.628). After stratification according to the constructed model, the median OS was 59.8 months for low-risk ICC patients and 10.1 months for high-risk patients (p < 0.0001).ConclusionThe clinical-radiomics model integrating sarcopenia, clinical features, and radiomics score was accurate for prognostic prediction for mass-forming ICC patients. It provided an individualized prognostic evaluation in patients with mass-forming ICC and could helped surgeons with clinical decision-making.

Cytogenetics-Based Risk Prediction of Blastic Transformation of CML Treated with Tyrosine Kinase Inhibitors

Background:Blast phase (BP) of chronic myeloid leukemia (CML) remains a major therapeutic challenge in the era of tyrosine kinase inhibitor (TKI) therapy. Given the lack of effective treatment for BP, a potential key to improve patient outcome lies in identifying patients at high risk of progression and preventing onset of BP. Additional chromosomal abnormalities (ACAs) are important determinants of patient outcome. Despite its rarity in TKI era, BP develops in most CML patients in pre-TKI era regardless of ACAs. It is unknown how the development of BP is differently affected by ACAs in the TKI era.Design:We investigated the value of ACAs in prediction of BP in a large cohort of CML patients. Inclusion criteria included: 1, received TKIs as part of therapy; 2, age at diagnosis > 18 years; 3, presence of t(9;22) or variant translocations detected by conventional karyotyping. All cytogenetic abnormalities in Ph+ cells except -Y were considered ACAs. We examined the latencies from initial CML diagnosis to ACA emergence (Interval 1), from ACA emergence to BP (Interval 2) and survival after BP (Interval 3).Results:A total of 2,326 patients were included in the study, including 1,322 men and 1,004 women with a median age at diagnosis of 49 years (range, 18-88 years). In total, 570 had ACAs, including 333 (58.4%) with a single ACA and 237 (41.5%) with multiple ACAs. The most common single ACAs were: +8, +Ph, 3q26.2 rearrangement, i(17q), and -7/7q-, with a frequency of 13.5%, 12.6%, 7.5%, 6.6%, 3.9%, respectively. Of 237 patients with complex ACAs, 18 had 3q26.2 rearrangement, 19 had -7/7q-, and 30 had i(17q) as a component of complex ACAs. Seven patients had two of these three ACAs in different combinations. These complex ACAs were grouped together as high-risk complex ACAs. Complex ACAs without these three chromosomal abnormalities were designated as other complex ACAs.Patients with 3q26.2 rearrangement, -7/7q-, i(17q) and high-risk complex ACAs had a significantly faster blastic transformation, with a median Interval 2 of 2.8, 0, 32.6, 0 months, respectively, compared with 19.2 months in patients with other complex ACAs, and unreached in patients with +8, +Ph, or other single ACAs, and (Fig 1A). Based on the frequency and velocity of blastic transformation, patients were stratified into four risk groups. Patients without ACA formed the standard-risk (SR) group, patients with isolated 3q26.2 rearrangement, -7/7q-, or i(17q) and high-risk complex ACAs formed the high-risk (HR) group, patients with +8, +Ph or other single ACAs formed the intermediate-1 risk (IR-1) group, and patients with other complex ACAs formed the intermediate-2 risk (IR-2) group. By risk group, the median Interval 2 was unreached for IR-1group, 19.2 months for IR-2 group, and 1.9 months for HR group. (Fig 1B), and the interval from CML diagnosis to BP (Interval 1 + Interval 2) was unreached for SR and IR-1, 83.7 months for IR-2 patients, and 58.2 months for HR patients (Fig 1C). This risk of BP correlated well with patient survival from CML diagnosis (Fig 1D).The disease course of CML patients with ACAs follows a triphasic course, that is, Interval 1, 2 and 3. There was no or little variation in Interval 1 among three ACA groups (Fig 1E). No significant difference in Interval 3 was observed among three ACA groups neither (Fig 1F). SR patients had only slightly better survival of 17.0 months, compared with 9.3 months in other 3 groups combined (Fig 1F). The lack of difference in Interval 1 and 3 indicate that the predominant determinant of CML disease course in TKI era lies in the duration of Interval 2, which is in turn highly ACA-dependent.Conclusions:Chromosomal alterations predict the risk of blastic transformation in CML patients treated with TKIs. Patients can be stratified into four different cytogenetic risk groups based on ACA-dependent risk of blastic transformation. This risk stratification highly correlates with patient survival. By prolonging the duration of Interval 2, TKI therapy mitigates the risk of blastic transformation associated with low-risk ACAs or no ACAs but does not alter the natural course of CML associated with high-risk ACAs: 3q26.2 rearrangement, -7/7q- and i(17q). Thus, we identify a group of patients who are at a high risk of rapid disease progression. These patients may benefit from alternative treatment approach including early allogeneic hematopoietic stem cell transplantation to prevent blastic transformation. [Display omitted] DisclosuresCortes:ARIAD: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Teva: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding. Kantarjian:Bristol-Meyers Squibb: Research Funding; Amgen: Research Funding; Pfizer: Research Funding; ARIAD: Research Funding; Novartis: Research Funding; Delta-Fly Pharma: Research Funding.

Overall survival of myelodysplastic syndrome patients after azacitidine discontinuation and applicability of the North American MDS Consortium scoring system in clinical practice.

Azacitidine (AZA) is the standard treatment for myelodysplastic syndromes (MDS); however, many patients prematurely stop therapy and have a dismal outcome. The authors analyzed outcomes after AZA treatment for 402 MDS patients consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche, and they evaluated the North American MDS Consortium scoring system in a clinical practice setting. At treatment discontinuation, 20.3% of the patients were still responding to AZA, 35.4% of the cases had primary resistance, and 44.3% developed adaptive resistance. Overall survival (OS) was better for patients who discontinued treatment while in response because of planned allogeneic hematopoietic stem cell transplantation (HSCT; median OS, not reached) in comparison with patients with primary resistance (median OS, 4 months) or adaptive resistance (median OS, 5 months) or patients responsive but noncompliant/intolerant to AZA (median OS, 4 months; P = .004). After AZA discontinuation, 309 patients (77%) received best supportive care (BSC), 60 (15%) received active treatments, and 33 (8%) received HSCT. HSCT was associated with a significant survival advantage, regardless of the response to AZA. The North American MDS Consortium scoring system was evaluable in 278 of the 402 cases: patients at high risk had worse OS than patients at low risk (3 and 7 months, respectively; P < .001). The score was predictive of survival both in patients receiving BSC (median OS, 2 months for high-risk patients vs 5 months for low-risk patients) and in patients being actively treated (median OS, 8 months for high-risk patients vs 16 months for low-risk patients; P < .001), including transplant patients. Real-life data confirm that this prognostic scoring system for MDS patients failing a hypomethylating agent seems to be a useful tool for optimal prognostic stratification and for choosing a second-line treatment after AZA discontinuation.

AstraZeneca says its antibody drug prevents COVID-19 infection for six months in high-risk patients

A single injection of the long-acting antibody (LAAB) drug Evusheld (AZD7442) significantly reduced the risk of symptomatic COVID-19 infection for six months in immunocompromised patients, the drug’s manufacturer AstraZeneca has said. Evusheld is a combination of two LAABs: tixagevimab (AZD8895) and cilgavimab (AZD1061), both of which are derived from white blood cells donated by patients […]

The prognostic value of sarcopenia combined with hepatolithiasis in intrahepatic cholangiocarcinoma patients after surgery: A prospective cohort study

IntroductionIntrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer with dismal survival rates. This study aimed to explore the prognostic value of sarcopenia combine with hepatolithiasis in surgically treated ICC patients and develop a prognostic nomogram to help make clinical decisions. Materials and methodsA prospective cohort study was conducted including patients who underwent hepatectomy for ICC between August 2012 and October 2019. The association between the sarcopenia combined with hepatolithiasis and survival, including overall survival (OS) and recurrence-free survival (RFS) was investigated using the Kaplan-Meier (K-M) method. Univariable and multivariable Cox regression analysis was performed to determine the independent prognostic factors and a nomogram establishment was undertaken based on the multivariable analysis. ResultsA total of 121 ICC patients were included in the study. K-M analysis revealed that ICC patients with sarcopenia and hepatolithiasis have worse OS and RFS than those without sarcopenias and/or hepatolithiasis (p < 0.01). Multivariable analysis showed that age, serum CEA, hepatolithiasis, sarcopenia and diabetes were independent prognostic factors for OS(p < 0.05). Finally, a nomogram with good performance in survival prediction was established (C-index was 0.721; the area under the curve of OS was 0.837). The stratified analysis based on the nomogram disclosed that the median OS was 11.9 months in high-risk patients and 51.2 months in low-risk patients (p < 0.001). ConclusionsICC patients with sarcopenia and hepatolithiasis have worse OS and RFS. The nomogram we developed is a practical tool that can provide a more individualized risk assessment for surgically treated ICC patients.

Clinical Outcomes and Prognosis Factors of Nivolumab Plus Chemotherapy or Multitarget Tyrosine Kinase Inhibitor in Multi-Line Therapy for Recurrent Hepatitis B Virus-Related Hepatocellular Carcinoma: A Retrospective Analysis

Background: This study investigates the potential predictors of nivolumab plus chemotherapy or multitarget tyrosine kinase inhibitor (TKI) treatment response in patients with recurrent hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods: Patients with recurrent hepatitis B virus-related HCC who underwent nivolumab plus chemotherapy or TKI treatment between July 2017 and June 2019 at Jinling Hospital in China were retrospectively evaluated and included in this study. These patients also had both complete medical charts and follow-up data available. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of nivolumab initiation. Survival data were compared using log-rank tests, and the associations of patient characteristics with survival were estimated using Cox regression models.Results: A total of 22 HCC patients were included in this cohort and constituted the basis for this analysis. Twenty progressed cases (91%) and 16 deaths (73%) were identified at a median follow-up of 8.8 months (range 1–25). The median OS from the time of nivolumab initiation was 10.7 months (95% CI, 0.8–20.6 months), with a median PFS of 5.1 months (95% CI, 3.1–7.0 months). The patients were divided into two risk groups according to a nomogram built by age, Eastern Cooperative Oncology Group (ECOG) status, hepatectomy status, and transarterial chemoembolization (TACE) use. The median PFS was 8.2 ± 2.8 months in the low-risk group compared with 1.9 ± 0.4 months in the high-risk group (p = 0.0018). The median OS was estimated as 16.8 ± 4.9 months for low-risk patients vs. 8.6 ± 3.5 months for high-risk patients (p = 0.13).Conclusion: Nivolumab combined with chemotherapy or TKI treatment is effective in patients with recurrent hepatitis B virus-related HCC. It is observed that previous TACE treatment is associated with a better PFS, and worse PFS in those patients who received hepatectomy. Prospective studies are warranted to evaluate the effects of nivolumab combined chemotherapy or TKI on recurrent hepatitis B virus-related HCC.

TWILIGHT: A Randomized Trial of Ticagrelor Monotherapy Versus Ticagrelor Plus Aspirin Beginning at 3 Months in High-risk Patients Undergoing Percutaneous Coronary Intervention

A P2Y12 inhibitor-based monotherapy after a short period of dual antiplatelet therapy is emerging as a plausible strategy to decrease bleeding events in high-risk patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), a randomized double-blind trial, tested this approach by dropping aspirin at 3 months and continuing with ticagrelor monotherapy for an additional 12 months. The study enrolled 9,006 patients, of whom 7,119 who tolerated 3 months of dual antiplatelet therapy were randomized after 3 months into two arms: ticagrelor plus placebo and ticagrelor plus aspirin. The primary endpoint of interest, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, occurred less frequently in the experimental arm (HR 0.56; 95% CI [0.45–0.68]; p&lt;0.001), whereas the secondary endpoint of ischemic events was similar between the two arms (HR 0.99; 95% CI [0.78–1.25]). Transition from dual antiplatelet therapy consisting of ticagrelor plus aspirin to ticagrelor-based monotherapy in high-risk patients at 3 months after percutaneous coronary intervention resulted in a lower risk of bleeding events without an increase in risk of death, MI, or stroke.

Clinical outcomes and prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy: a retrospective multicenter study in Japan.

Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated. The medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan-Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors. Median follow-up was 2.95years, median CRPC-free survival was 21.9months and median OS was 5.37years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5months, 17.9months in intermediate-risk patients with two or three factors, and 11.0months in high-risk patients with four factors. Median OS was 4.72years in intermediate- and 2.44years in high-risk patients. It was not reached in low-risk patients. In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients.

Clinical outcome and toxicity evaluation of simultaneous integrated boost pelvic IMRT/VMAT at different dose levels combined with androgen deprivation therapy in prostate cancer patients.

BackgroundThe role of dose escalation in patients receiving long-term androgen deprivation therapy (ADT) is still a controversial issue. The aim of the current study was to evaluate whether dose escalation for ≥76–80 Gy had any advantage in terms of biochemical disease-free survival (BDFS), distant metastasis-free survival (DMFS), or overall survival outcomes over the dose levels from 70 to <76 Gy.Patients and methodsThe study included a cohort of 24 patients classified with high- and intermediate-risk localized prostate cancer. All patients received ADT, starting at 4–6 months before radiation therapy and continued for a total period of 12–24 months in high-risk patients. The treatment plan was given in two phases. In the first phase, the nodal planning target volume (PTV) and the prostate PTV received 48.6 and 54 Gy, respectively, over 27 fractions. The treatment was applied through intensity-modulated radiation therapy or volumetric modulated arc therapy with a simultaneous integrated boost technique.ResultsMore than half of the patients were in T3–T4 stage, 79.1% of the patients were in the high-risk category, and all patients received ADT. The rate of acute grade II gastrointestinal and genitourinary toxicities in all patients were 41.7% and 62.5%, respectively. The rate of freedom from grade II rectal toxicity at 2 years was 89% and 83% for patients treated with dose levels <76 and ≥76 Gy, respectively. The rate of BDFS at 2 years was 90% and 85% for doses <76 and ≥76 Gy, respectively. The DMFS at 2 years was 100% and 76% for dose levels <76 and ≥76 Gy, respectively.ConclusionIn the current study, there were no significant differences in the BDFS and DMFS between patients treated with a dose of <76 and ≥76 Gy, including elective pelvic lymph nodes irradiation combined with ADT.

LBPS 01–05 GANODERMA LUCIDUM POLYSACCHARIDE PEPTIDES AS ANTIOXIDANT, ANTI-INFLAMMATION, ANTI-HYPERTENSION AND ANTI-LIPID IN HIGH-RISK PATIENTS OF ATHEROSCLEROSIS

Objective: Ganoderma lucidum is a type of mushroom that has been used for thousands years throughout Asia. It is known to demonstrate numerous health benefiting properties including antioxidant, anti-inflammation, anticancer effects, hypoglycemic and blood cholesterol reducing properties. This research was conducted to determine the efficacy of Ganoderma lucidum polysaccharide peptides (PSP) as anti-inflammation and antioxidant in cardiovascular disease Design and Method: This is a prospective study with pre-test and post-test design of 37 high-risk patients of cardiovascular disease based on the Framingham Risk Score that was conducted for 3 months. Patients were advised to consume PSP 3×250 mg as an adjuvant to their previous medications. The primary endpoint was the change in cholesterol levels, blood pressure and antioxidant markers. Results: The administration of PSP 3x250 mg could reduce total cholesterol level by 3.48 ± 46.9 mg/dl (p = 0.672). Both pre- and post-test of total cholesterol are significantly correlated (r = 0.618, p = 0.000). PSP administration, however, increased the level of HDL cholesterol by 7.84 ± 10.79 (p = 0.000). The systolic blood pressure decreased from 130.14 ± 43.37 mmHg to 118.24 ± 55.68 (p = 0.109), and the diastolic blood pressure decreased from 80 ± 25.74 mmHg to 73.24 ± 33.85 mmHg (p = 0.102). Despite a great reduction of blood pressure to normal range, it was not statistically significant. The reduction of anti-inflammatory markers interleukin-6 (IL-6), from 279.75 ± 120.76 to 29.32 ± 26.44 (p = 0.000) and TNF alpha, from 13447.84 ± 2199.46 to 544.85 ± 292.06 (p = 0.000) were significant. Malondialdehyde (MDA) level also decreased significantly with PSP treatment for 3 months (p = 0.000). Conclusions: The administration of polysaccharide peptides of Ganoderma lucidum for three months in high-risk patients with hypertension can reduce the blood pressure within normal range, improve total cholesterol level and significantly play role as anti-inflammation and antioxidant in cardiovascular disease.