Event-free Survival Rates Research Articles

Role of therapeutic drug monitoring of intravenous Busulfan for prevention of sinusoidal obstructive syndrome in children.

Therapeutic drug monitoring (TDM) of intravenous busulfan (Bu) has been recommended for safe engraftment and decreased toxicity in children undergoing hematopoietic stem cell transplantation (HSCT). This study aims to compare HSCT-related outcomes, such as acute or chronic graft-versus-host disease (GvHD), sinusoidal obstructive syndrome (SOS), event-free survival (EFS), and overall survival (OS) in children with and without TDM for busulfan. This retrospective study conducted between February 2012 and February 2021 at our Bone Marrow Transplantation Unit included 172 patients (34% girls) with a median age of 4.70years (IQR 2.41-10.01). Group A consisted of 46 patients whose Bu doses were adjusted according to actual body weight, and group B consisted of 126 patients whose Bu dose adjustments made according to TDM. Totally, 32 patients (19%) developed moderate or severe SOS. The incidence of SOS was significantly higher in the group without TDM (29% vs. 15%, p=.041). A multivariable analysis showed that the presence of acute GvHD and one alkylating drug-containing conditioning regimen compared with two or three were associated with SOS (p=.03 and p=.002, respectively). In patients with TDM, cumulative Bu dose and area under curve also were not associated with SOS. Other HSCT-related outcomes such as acute or chronic GvHD, relapse and graft rejection rates, OS and EFS rates did not differ between the groups. TDM and making dose adjustments with Bayesian forecasting over four days of Bu therapy optimizes exposure and reduces the risk of SOS in children undergoing HSCT.

Bypass Surgery Provides Better Outcomes Compared with Endovascular Therapy in the Composite Endpoint Comprising Relief from Rest Pain, Wound Healing, Limb Salvage, and Survival after Infra-inguinal Revascularisation in Patients with Chronic Limb Threatening Ischaemia

The present study aimed to determine the factors related to relief from rest pain, wound healing, major adverse limb events (MALEs), and prognosis after infrainguinal revascularisation in patients with chronic limb threatening ischaemia (CLTI). The data of patients who underwent infrainguinal revascularisation for CLTI between 2010 and 2020 was analysed retrospectively. The endpoint was the composite of relief from rest pain, wound healing, MALE, or death. A total of 234 limbs in 187 patients with CLTI were analysed. Of the 234 limbs, 149 (63.7%) underwent bypass surgery and 85 (36.3%) underwent endovascular therapy (EVT). The event free survival rates with respect to the composite endpoint at two years were 30.4% in the EVT and 48.5% in the bypass groups, respectively (p= .005). The event free survival rates at two years were 56.7% in bypass surgery and 29.5% in EVT in the indeterminate subgroup (p= .051). Multivariable analysis revealed that age (hazard ratio [HR] 1.03; 95% confidence interval [CI] 1.01 - 1.05; p < .001), coronary artery disease (CAD) (HR 1.45; 95% CI 1.01 - 2.07; p= .042), haemodialysis (HR 1.74; 95% CI 1.22 - 2.48; p= .002), Wound, Ischaemia and foot Infection stage (HR 1.34; 95% CI 1.07 - 1.68; p= .012), Global Limb Anatomical Staging System stage (HR 1.31; 95% CI 1.01 - 1.72; p= .043), EVT (HR 1.90; 95% CI 1.31 - 2.74; p < .001), Geriatric Nutritional Risk Index (HR 0.98; 95% CI 0.97 - 0.99; p= .021), and non-ambulatory status (HR 1.89; 95% CI 1.31 - 2.74; p < .001) were risk factors for the composite endpoint. Bypass surgery is superior to EVT with respect to the composite endpoint including relief from rest pain, wound healing, MALE, or death. Bypass surgery may be considered as the treatment of choice, instead of EVT, in patients in the indeterminate group according to the Global Vascular Guidelines preferred revascularisation method.

Prognostic Significance of Comprehensive Gene Mutations and Clinical Characteristics in Adult T-Cell Acute Lymphoblastic Leukemia Based on Next-Generation Sequencing.

BackgroundAdult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignant tumor with poor prognosis. However, accurate prognostic stratification factors are still unclear.MethodsData from 90 adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients were collected. The association of gene mutations detected by next-generation sequencing and clinical characteristics with the outcomes of T-ALL/LBL patients were retrospectively analyzed to build three novel risk stratification models through Cox proportional hazards model.ResultsForty-seven mutated genes were identified. Here, 73.3% of patients had at least one mutation, and 36.7% had ≥3 mutations. The genes with higher mutation frequency were NOTCH1, FBXW7, and DNMT3A. The most frequently altered signaling pathways were NOTCH pathway, transcriptional regulation pathway, and DNA methylation pathway. Age (45 years old), platelet (PLT) (50 G/L), actate dehydrogenase (LDH) (600 U/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and hematopoietic stem cell transplantation (HSCT) were integrated into a risk stratification model of event-free survival (EFS). Age (45 years old), white blood cell (WBC) count (30 G/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and HSCT were integrated into a risk stratification model of overall survival (OS). According to our risk stratification models, the 1-year EFS and OS rates in the low-risk group were significantly higher than those in the high-risk group.ConclusionsOur risk stratification models exhibited good prognostic roles in adult T-ALL/LBL patients and might guide individualized treatment and ultimately improve their outcomes.

Randomized comparator-controlled study evaluating efficacy and safety of pembrolizumab plus Bacillus Calmette-Guérin (BCG) in patients with high-risk nonmuscle-invasive bladder cancer (HR NMIBC): KEYNOTE-676 cohort B.

TPS597 Background: Cohort A of the phase 2 KEYNOTE-057 study showed that pembrolizumab monotherapy provided effective antitumor activity and acceptable safety in patients with BCG-unresponsive HR NMIBC with carcinoma in situ (CIS). Pembrolizumab in combination with BCG at earlier stages of HR NMIBC might provide benefit superior to that of BCG monotherapy. The open-label, comparator-controlled, phase 3 KEYNOTE-676 study (NCT03711032) will be conducted to investigate the efficacy and safety of pembrolizumab + BCG versus BCG monotherapy in patients with HR NMIBC. Cohort A will enroll patients with persistent or recurrent HR NMIBC after BCG induction. Cohort B is a new, randomly assigned cohort that will help evaluate pembrolizumab + BCG in BCG treatment–naive patients who either never received BCG treatment or received BCG treatment &gt; 2 years before enrollment. Methods: Cohort B of KEYNOTE-676 will enroll approximately 975 patients with blinded independent central review (BICR)–confirmed HR NMIBC (T1, high-grade Ta CIS) and Eastern Cooperative Oncology Group performance status score 0-2 who underwent cystoscopy/transurethral resection of bladder tumor ≤12 weeks before randomization and had not received BCG within the past 2 years. Patients will be randomly assigned 1:1:1 to receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) + BCG reduced maintenance (≤6 months), pembrolizumab 400 mg IV Q6W + BCG full maintenance (≤18 months), or BCG monotherapy (BCG full maintenance). Stratification factors include NMIBC stage (CIS or no CIS) and PD-L1 expression (combined positive score [CPS] ≥10 or CPS &lt; 10), determined by central laboratory. Disease status will be assessed by use of cystoscopy, urine cytology, and biopsy (as applicable) every 12 weeks (Q12W) through year 2, then every 24 weeks through year 5; imaging with computed tomography urography will occur every 72 weeks. Adverse events (AEs) will be monitored throughout the study and up to 30 days after cessation of study treatment (90 days for serious AEs). The primary end point is event-free survival (EFS). Secondary end points include complete response rate by BICR, duration of response (DOR), 12-month DOR rate (CIS only), 24-month EFS rate, disease-specific survival, time to cystectomy, overall survival, and safety. The study is enrolling or planning to enroll at sites in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT03711032.

Abstract OT1-18-03: The neoIRX trial:locoregional cytokine therapy to promote immunologic priming and enhanced response to neoadjuvant pembrolizumab plus chemotherapy in triple negative breast cancer (TNBC)

Abstract Background: In stage II/III TNBC, pembrolizumab when combined with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel [ACT], and carboplatin) improves event free survival and pathologic complete response (pCR) rate (Keynote-522 study).1 Novel combination immunotherapy strategies may further improve outcome and/or afford the opportunity to de-escalate the chemotherapy backbone. We have previously reported safety and feasibility of pre-operative IRX-2, a novel cytokine-based therapeutic that can be administered locoregionally to enhance immune response.2 In a phase Ib study in stage I-III breast cancer, IRX-2 was safe, well tolerated, and associated with increased tumor infiltrating lymphocytes (sTILs, by H&amp;E and multispectral immunofluorescence [mIF]), PD-L1 expression (Ventana SP142 assay, mIF), and lymphocyte activation (by RNA sequencing). These potential immunomodulatory effects support further study of IRX-2 in combination with ICI and chemotherapy in the neoadjuvant setting. Methods: Patients are randomized to a phase II, open-label trial to evaluate the clinical and immunological activity of pembrolizumab plus de-escalated chemotherapy (ACT) when combined with IRX-2 for TNBC. All patients (n=30) will receive pembrolizumab induction (single dose 200mg IV), followed by pembrolizumab every three 3 weeks in conjunction with ACT as neoadjuvant therapy prior to surgery. Patients randomized to arm A (n=15) will additionally receive peri-lymphatic locoregional injections of IRX-2 (1mL SQ x 2 daily, x 10 days) during the induction phase. Eligible subjects will have previously untreated, resectable stage II/III TNBC. The primary endpoint is pCR. The secondary endpoint is safety. On-treatment biopsies following induction (pembrolizumab +/- IRX-2) will permit a prospective, randomized validation of previously reported immunomodulatory effects of IRX-2 (sTILs, PD-L1, lymphocyte RNA signatures). As of 7/8/2021, n=6/30 subjects are enrolled (Providence Cancer Institute, Portland, OR, Providence St. John’s Cancer Institute, Santa Monica, CA, Baylor College of Medicine, Houston, TX). NCT04373031. 1Schmid, P. N Engl J Med 2020; 382:810-821. 2Page, DB. Clin Cancer Res 2020; 26.7:1595-1605. Citation Format: Katherine Sanchez, Alison Conlin, Parvin Peddi, Sasha Stanton, Janet Ruzich, Kelly Perlewitz, Yaping Wu, Nicole Moxon, Staci Mellinger, Zhaoyu Sun, William Redmond, David B Page. The neoIRX trial:locoregional cytokine therapy to promote immunologic priming and enhanced response to neoadjuvant pembrolizumab plus chemotherapy in triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-18-03.

Abstract P2-13-12: High CD36 expression predicts worse event free survival in HER2-positive breast cancer patients treated with neoadjuvant trastuzumab-based therapy: An exploratory analysis of the NeoALTTO study

Abstract Background: Despite great efforts to identify tumor-related prognostic biomarkers in early-stage Human Epidermal growth factor Receptor 2 (HER2)-positive Breast Cancer (HER2+ BC), reliable determinants of long-term clinical outcomes are lacking. HER2+ BC is a lipogenic malignancy, and HER2-driven fatty acid (FA) biosynthesis plays a crucial role in sustaining cancer cell growth, proliferation, and metastatization. Recently, FA uptake, a process mediated by the transmembrane transporter CD36, has emerged as a new determinant of acquired resistance to anti-HER2 treatments in preclinical studies. Methods: The phase III NeoALTTO (NCT00553358) trial randomized 455 HER2+ BC patients to receive lapatinib, trastuzumab, or the combination of both drugs with weekly paclitaxel, followed by surgery, adjuvant fluorouracil, epirubicin, and cyclophosphamide and the same anti-HER2 therapy received before surgery. In the present analysis, we tested the hypothesis that higher intratumor CD36 mRNA levels could be associated with worse Event Free Survival (EFS) in a cohort of NeoALTTO patients for whom global gene expression analysis of baseline tumor samples through ClariomS platform was available. Results: A total of 180 patients were included (trastuzumab arm: n=66; lapatinib arm: n=65; combination arm: n=49). Higher baseline CD36 expression levels were associated with significantly worse EFS in patients treated with trastuzumab-based therapy, at both univariate (continuous scale, HR:1.73, 95% CI 1.20-2.49) and multivariable (HR:1.72, 95% CI 1.20-2.46) analysis, but not in patients treated with lapatinib- or trastuzumab plus lapatinib (HR:1.01; 95% CI: 0.69-1.47; p=0.98 and HR:1.02; 95% CI:0.54-1.95; p=0.94, respectively). CD36 levels did not predict pathological Complete Response (pCR) probability, while combining CD36 expression (based on median levels) with pCR status identified two subsets of patients with especially bad or good prognosis (7-year EFS rates in patients with high CD36/no pCR: 47%, 95% CIs: 0.26-0.66 vs. 79%, 95% CIs: 0.62-0.88 in patients with low CD36/any pCR status (Yes/No) OR high CD36/pCR; Log-Rank test p= 0.006). Conclusions: This is the first study to show that high CD36 expression is independently predictive of worse long-term clinical outcomes in HER2+ BC patients treated with neoadjuvant trastuzumab-based therapy. Along with recent preclinical data highlighting CD36 role in tumor resistance to anti-HER2 therapies, our findings point to CD36 as a novel promising target for HER2+ BC treatment. Citation Format: Francesca Ligorio, Serena Di Cosimo, Paolo Verderio, Chiara Maura Ciniselli, Sara Pizzamiglio, Lorenzo Castagnoli, Tiziana Triulzi, Elda Tagliabue, Sarra El-Abed, Miguel Izquierdo, Evandro de Azambuja, Paolo Nuciforo, Jens Huober, Luca Moscetti, Wolfgang Janni, M Coccia-Portugal, Paola Corsetto, Antonino Belfiore, Daniele Lorenzini, Maria Grazia Daidone, Andrea VIngiani, Serenella M Pupa, Giancarlo Pruneri, Claudio Vernieri. High CD36 expression predicts worse event free survival in HER2-positive breast cancer patients treated with neoadjuvant trastuzumab-based therapy: An exploratory analysis of the NeoALTTO study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-12.

Clinical characteristics and prognosis of 83 children with newly treated hepatoblastoma

Objective: To investigate the clinical features, survival and prognostic risk factors of children with hepatoblastoma (HB). Methods: Clinical data of 83 children with newly treated HB at the Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2019 were analyzed retrospectively. The sex, age, first clinical manifestations, pretreatment extent of disease (PRETEXT) stages, pathological types, initial alpha-fetoprotein (AFP), treatment methods and treatment outcome of all patients were summarized. The children diagnosed before 2018 were treated with "Wuhan Protocol", and those who diagnosed after 2018 were treated with the "Expert Consensus for Multidisciplinary Management of Hepatoblastoma"(CCCG-HB-2016) protocol. Kaplan-Meier survival analysis was used to calculate the survival rate, Log-Rank test was used in univariate analysis, and the Cox regression model was used in multivariate prognosis analysis. Results: Among 83 cases, there were 51 males and 32 females. The age of onset was 25.2 (9.0, 34.0) months old, and 64 cases (77%) were under 3 years old. The most common first clinical manifestation was abdominal mass in 45 cases (54%). There were 8 cases of PRETEXT stage Ⅰ, 43 cases of stage Ⅱ, 20 cases of stage Ⅲ and 12 cases of stage Ⅳ. During the follow-up period of 40 (17, 63) months, the 1-year overall survival (OS) rate and event-free survival (EFS) rate were (84±4) % and (79±5) %, respectively, and 5-year OS rate and EFS rate were (78±5) % and (76±5) %, respectively. Fifty-five cases were treated with "Wuhan Protocol", and the 5-year OS and EFS rate were (73±6) % and (71±6) %, respectively. Twenty-eight cases were treated with CCCG-HB-2016 protocol, and the 5-year OS and EFS rate were (88±7) % and (82±9) %, respectively. Multivariate COX regression analysis showed that AFP did not turn negative after 3 courses of postoperative chemotherapy (HR=9.228, 95%CI 1.017-83.692) and PRETEXT stage Ⅳ (HR=6.587, 95%CI 1.687-25.723) were independent risk factors affecting the prognosis of children with HB. Conclusions: The "Wuhan Protocol" and CCCG-HB-2016 protocol were effective in the treatment of children with HB. AFP did not turn negative after 3 courses of postoperative chemotherapy and PRETEXT stage Ⅳ were independent risk factors affecting the prognosis of children with HB.

Clinical Characteristics and Prognosis of Children with Myelodysplastic Syndrome

To analyze the clinical characteristics and prognosis of 40 children with myelodysplastic syndrome (MDS), and provide ideas for clinical diagnosis and treatment. The clinical characteristics, risk stratification, and different treatment regimens of 40 cases with MDS admitted in Department of Hematology of Children's Hospital of Soochow University from January 1, 2011 to December 31, 2017 was retrospectively analyzed. Kaplan-Meier survival curve were used to estimate 3-year overall survival (OS) rate and event-free survival (EFS) rate. In 40 cases, the ratio of male to female was 1.4∶1.0, male was more than female, and median age was 6.0 years old. Among them, refractory cytopenia (MDS-RCC) was the most common type, and 11 cases were chromosomal abnormalities, 21 cases genetic abnormalities. Fifteen cases accepted hematopoietic stem cell transplantation (HSCT) treatment, while 25 cases did not but drug therapy alone. The 3-year OS rate of the cases who accepted HSCT or not was (72.2±12.2)% and (35.3±10.2)% (P=0.039), 3-year EFS rate was (65.0±12.9)% and (19.2±8.4)% (P=0.012), respectively. Cox regression analysis showed that age < 7 years old (P=0.0333), initial diagnosed platelet < 50×109/L (P=0.007), presence of complex karyotypes and/or gene mutations (P=0.0002), and treatment without HSCT (P=0.016) were the high-risk factors of prognosis. All the children were classified according to IPSS, WPSS and IPSS-R, while analysis result showed that the above three risk assessment had limitations for risk assessment of MDS in children, they could not comprehensively assess the prognosis of children with MDS. MDS-RCC in children is more common. Cox multivariate analysis shows that age < 7 years old, initial diagnosed platelet < 50×109/L, presence of complex karyotypes and/or gene mutation, and treatment without HSCT are the high-risk factors of prognosis in children with MDS. HSCT is the most effective treatment to cure children with MDS at present. The current methods such as IPSS-R commonly used in assessment of prognosis in children with MDS show obvious limitation.

Clinical features and prognosis in 20 children with rhabdomyosarcoma

To study the clinical features of children with rhabdomyosarcoma (RMS) and the influencing factors for prognosis. A retrospective analysis was performed on the clinical and follow-up data of 20 children with RMS who were admitted to the Department of Pediatric Hematology, Xiangya Hospital of Central South University, from June 2014 to September 2020. The most common clinical symptoms of the 20 children with RMS at the first visit were painless mass (13/20, 65%), exophthalmos (4/20, 20%), and abdominal pain (3/20, 15%). According to the staging criteria of Intergroup Rhabdomyosarcoma Study Group (IRSG), there was 1 child (5%) with stage I RMS, 4 (20%) with stage II RMS, 9 (45%) with stage III RMS, and 6 (30%) with stage IV RMS. The median follow-up time was 19 months for the 20 children (range: 3-93 months), with a 2-year overall survival (OS) rate of 79.5% (95%CI: 20.1-24.3) and a 2-year event-free survival (EFS) rate of 72.0% (95%CI: 19.5-23.9). Pleomorphic RMS was associated with the reduced 2-year OS rate (P<0.05), and distant metastasis, IRSG stage IV RMS, and high-risk RMS were associated with the reduced 2-year EFS rate (P<0.05). RMS has no specific clinical symptoms at the first visit, with painless mass as the most common symptom. Distant metastasis, IRSG stage, and risk degree may be associated with the prognosis of children with RMS.

Outcomes of Popliteal Stent-Graft Placement at the Artery Hinge Point for Popliteal Artery Aneurysm

To assess whether stent-grafts crossing the hinge point (HP) in the popliteal artery are associated with increased complications and decreased patency rates, after endovascular treatment of the popliteal artery aneurysm. This was a single-center, case-control study. Patients were allocated to either the HP group (subjects with stent-grafts crossing the HP) or the control group (subjects with stent-grafts above and/or below the HP) based on stent-graft location in the femoropopliteal artery. HP was defined as the main curve in the popliteal artery in the most acute angle toward the femur that appeared during knee flexion, which was identified by reviewing postoperative angiograms. Independent, blinded reviews were performed for all imaging data. Graft evaluation by CTA or duplex ultrasound was performed at 1, 3, 6, and 12 months and annually thereafter. Outcomes measured included: stent-graft patency, stent-graft fracture, other stent-related complications, and major adverse events, including reintervention, death, amputation, stroke, and myocardial infarction. A total of 44 limbs treated with placement of heparin-bonded Viabahn endoprostheses were included in this study. Twenty and twenty-four patients were allocated to the HP group and the control group, respectively. Primary patency rates of the HP group at 1, 2, 3, and 5 years were 84.1 ± 8.4%, 84.1 ± 8.4%, 84.1 ± 8.4%, and 72.1 ± 13.3%, respectively. The primary patency rates of the control group were 87.0 ± 7.0%, 82.4 ± 8.0%, 82.4 ± 8.0%, and 82.4 ± 8.0%, respectively. There was no significant difference between the 2 groups (P=0.81). No reintervention was performed in the control group. In the HP group, 5 limbs (25.0%) developed endoleak, 3 (15.0%) developed thrombosis, and 1 (5.0%) developed a stent fracture followed by thrombosis. Thrombosis occurred in 2 limbs (8.3%) of the control group, and stent-graft migration was observed in another 2 cases (8.3%). Neither group demonstrated stent-graft infection or acute popliteal artery embolism. Overall, incidence of stent-related complications were significantly higher in the HP group (P= 0.04). Event-free survival rates of the HP group at 1, 2, 3, and 5 years were 75.0 ± 9.7%, 69.6 ± 10.4%, 61.9 ± 11.8%, and 29.0 ± 12.8%, respectively. Corresponding rates in the control group were 79.2 ± 8.3%, 79.2 ± 8.3%, 79.2 ± 8.3%, and 79.2 ± 8.3%, respectively. The difference was not statistically significant between the 2 groups (P=0.20) CONCLUSIONS: crossing the HP with femoropopliteal artery stent-grafts increased the risk of stent-related complications and reinterventions but did not decrease stent patency or event-free survival.

Efficacy and safety comparison between R-CHOP and modified NHL-BFM-90 regimens in children and adolescents with diffuse large B-cell lymphoma.

Studies comparing the efficacy and safety of R-CHOP and modified non-Hodgkin lymphoma Berlin-Frankfurt-Münster-90 (NHL-BFM-90) regimens in children and adolescents with diffuse large B-cell lymphoma (DLBCL) are lacking. Thus, we retrospectively analyzed 85 DLBCL patients aged ≤18 years from 2000 to 2020; 74 patients received the modified NHL-BFM-90 regimen, and 11 received the R-CHOP regimen. The 5-year OS and event-free survival (EFS) rates between the modified NHL-BFM-90 and R-CHOP regimens were 91.0% vs. 90.9% (P = 0.466) and 89.8% vs. 68.6% (P = 0.055), respectively. In the stratified analysis, the survival outcome of pediatric patients treated with the modified NHL-BFM-90 regimen was not significantly different from that of adolescent patients. The OS and EFS rates of patients with early-stage disease were both 100%. Patients in the advanced-stage group who were treated with the modified NHL-BFM-90 regimen had superior EFS rates (P < 0.05). The frequency of severe adverse events from the two regimens was similar. There were no treatment-related deaths. We concluded that the modified NHL-BFM-90 regimen has better efficacy than R-CHOP in DLBCL patients with advanced-stage disease. However, the R-CHOP regimen might be an option for early-stage DLBCL. Further prospective studies are needed to guide clinical decisions about treatment.

Usefulness of quantitative 99mTc-pyrophosphate SPECT/CT for predicting the prognosis of patients with wild-type transthyretin cardiac amyloidosis

PurposeWild-type transthyretin-related amyloidosis cardiomyopathy (ATTRwt-CM) is an increasingly recognized cause of heart failure especially in elderly patients. The purpose of the present study was to determine retrospectively whether the quantitative indices of 99mTc-pyrophosphate (PYP) SPECT/CT help to predict the prognosis of ATTRwt-CM patients when compared with other clinical parameters.Materials and methodsSixty-eight patients with biopsy-proven ATTRwt-CM who underwent PYP SPECT/CT were enrolled. Baseline clinical characteristics, echocardiographic parameters, and qualitative and/or quantitative indices of planar and SPECT/CT imaging in PYP scintigraphy for each patient were included. For quantitative analysis of SPECT/CT, the accumulation ratio of PYP in the septum, posterior, anterior, lateral, and apex walls to the cavity pool was calculated as the septal wall-to-cavity ratio (Se/C), lateral wall-to-cavity ratio (La/C), anterior wall-to-cavity ratio (An/C), inferior wall-to-cavity ratio (In/C), and apical wall-to-cavity ratio (Ap/C), respectively. Endpoints for prognostic accuracy evaluation were cardiac death or hospitalization due to heart failure. Event-free survival rate was evaluated through Cox proportional hazards regression analysis, providing estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and Kaplan–Meier curves.ResultsHigh-sensitivity cardiac troponin T (hs-cTnT), La/C, age, interventricular septal thickness in diastole, and E/e′ ratio in the septal wall were significantly associated with event-free survival (P < 0.05). For a multivariable Cox proportional hazards analysis, hs-cTnT (HR 1.153; 95% CI 1.034–1.286; P < 0.01), La/C (HR 2.091; 95% CI 1.012–4.322; P = 0.046), and age (HR 1.116; 95% CI 1.007–1.238; P = 0.037) were significant independent prognostic factors.ConclusionThis study indicated that the quantitative indices of PYP SPECT/CT can help to predict the prognosis of ATTRwt-CM patients.

Construction of a Prognostic Nomogram Based on Autophagy-Related Genes for Children With Neuroblastoma.

Neuroblastoma (NB) is the most common solid malignancy in children. MYCN gene amplification is the most relevant genetic alteration in patients with NB and is associated with poor prognosis. Autophagy plays specific roles in the occurrence, development, and progression of NB. Here, we aimed to identify and assess the prognostic effects of autophagy-related genes (ARGs) in patients with NB and MYCN gene amplification. Differentially expressed ARGs were identified in patients with NB with and without MYCN gene amplification, and the ARG expression patterns and related clinical data from the Therapeutically Applicable Research to Generate Effective Treatments database were used as the training cohort. Least absolute shrinkage and selection operator analyses were used to identify prognostic ARGs associated with event-free survival (EFS), and a prognostic risk score model was developed. Model performance was assessed using the Kaplan–Meier method and receiver operating characteristic (ROC) curves. The prognostic ARG mode l was verified using the validation cohort dataset, GSE49710. Finally, a nomogram was constructed by combining the ARGbased risk score with clinicopathological factors. Three ARGs (GABARAPL1, NBR1, and PINK1) were selected to build a prognostic risk score model. The EFS in the low-risk group was significantly better than that in the high-risk group in both the training and validation cohorts. A nomogram incorporating the prognostic risk score, age, and International Neuroblastoma Staging System stage showed a favorable predictive ability for EFS rates according to the area under the ROC curve at 3 years (AUC = 0.787) and 5 years (AUC = 0.787). The nomogram demonstrated good discrimination and calibration. Our risk score model for the 3 ARGs can be used as an independent prognostic factor in patients with NB and MYCN gene amplification. The model can accurately predict the 3- and 5-year survival rates.

Treatment of adult Burkitt lymphoma with the CALGB 1002 protocol: a single center experience in Jordan.

BackgroundThe treatment of adult Burkitt lymphoma with pediatric-based chemotherapy protocols usually results in high cure rates, although with significant toxicity. We report our experience with the Cancer and Leukemia Group B1002 (CALGB 1002) protocol.MethodsThe files of adult patients diagnosed with Burkitt lymphoma and treated with the CALGB 1002 protocol at King Hussein Cancer Center between 2008 and 2017 were reviewed. Baseline demographics, clinical laboratory features, treatment details, and responses were collected. The correlations between clinical and laboratory variables with event-free survival (EFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. EFS and OS were plotted using Kaplan‒Meier curves.ResultsThis study included 19 patients with a median age of 33 years (range, 19‒65). Eleven (58%) and two (10.5%) patients had advanced-stage and central nervous system disease, respectively. Among 106 administered cycles, the median interval between cycles was 23 days (range, 19‒84 days). Sixteen patients (84%) achieved a complete response. After a median follow-up of 40.8 months, the 3-year EFS and OS rates were 78.95%. Patients with a low-risk International Prognostic Index (IPI) had better survival than those with intermediate-or high-risk IPI. Grade III‒IV hematological toxicities occurred in 88% of patients, while 73% had grade III‒IV mucositis.ConclusionIn adult Burkitt lymphoma, the CALGB 1002 protocol provides high cure rates and can be administered promptly, but is associated with significant toxicity. Risk-adapted approaches and other, less toxic, chemotherapeutic regimens should be considered.

Assessment of prognostic factors in extracranial germ cell tumors in children

Germ cell neoplasms in the group of benign and malignant tumors heterogeneous in morphological structure, clinical features and prognosis. A special characteristic of germ cell tumors is their high sensitivity to platinum-containing chemotherapy, which allows cure of up to 80–90% patients. However 20–25% of patients with a common type have overall survival rate of less than 50%. The aim of the study is to assess the survival rate of children with extracranial germ cell tumors and to identify adverse risk factors. Methods. The study includes 116 children with extracranial germ cell tumors treated from 2013 to September 2009. Treatment consisted of tumor resection and platinum based on platinum chemotherapy. Survival rate was assessed by the Kaplan-Mayer method. Prognostic factors are determined according to IGCCCG, MaGIC, MAKEI, RODO. Results. Overall and event free survival rates were 79±5% and 76±4%, respectively. The worst overall survival had patients with extragonadal tumors, advanced stages of a disease, high initial level of AFP (≥10 000 ng/ml), non-seminoma version of state treasury bills and extra pulmonary metastases. Conclusion. Survival rate in children with extracranial germ cell tumors depends on the prognostic factors. Statistically significant predictors of the poor prognosis were extragonadal localization of a tumor and the AFP level ≥10 000 ng/ml.

Prognostic significance of the ratio of surgically resected to radiologically detected lung nodules in patients with metastatic osteosarcoma

The factors that affect the prognosis of patients’ metastatic osteosarcoma are still poorly understood. In this study, we investigated a new prognostic factor, the ratio of surgically resected to radiologically detected osteosarcoma lung nodules (SR/RD), which may have predictive value. Patients and methodsData from patients with metastatic osteosarcoma who underwent metastasectomy between January 2009 and December 2020, in a single center, were reviewed. The relationships between survival and the SR/RD ratio, timing of lung metastases, number of nodules, laterality, and presence of tumor necrosis at first metastasectomy were investigated. ResultsAmong the 125 metastatic osteosarcoma patients, 80 patients had an SR/RD ratio ≤1. The median duration of follow-up was 72 months, ranging from 6 to 118 months. The five-year overall survival (OS) and postmetastasectomy event-free survival (EFS) for all patients were 36.5% and 18.1%, respectively. The five-year OS of patients with a low SR/RD ratio was 49.6% and that of patients with a high SR/RD ratio was 11.8 (P = 0.001). The two-year postmetastasectomy EFS rates of the high and low ratio groups were 24.1% and 9.4%, respectively (P = 0.001). The SR/RD ratio, number of nodules, and tumor necrosis had significant effects on OS and postmetastasectomy EFS in univariate analysis. A Cox proportional hazard model demonstrated that tumor necrosis and an SR/RD ratio >1 were associated with OS (HR = 1.8 and 2.01) and postmetastasectomy EFS (HR = 1,69 and 1.97). ConclusionsA high SR/RD ratio of greater than 1 and poor tumor necrosis were significantly associated with poor survival among patients with metastatic osteosarcoma who had lung metastasectomy. The high SR/RD ratio may be a surrogate outcome for incomplete metastatic tumor resection.

Clinical picture, outcome and predictive factors of lymphoma in primary Sjögren's syndrome: results from a harmonized dataset (1981-2021).

Primary Sjögren's Syndrome (pSS) carries the highest risk for non-Hodgkin's lymphoma (NHL) development among systemic autoimmune diseases. However, the paucity of data on the long-term survival of those patients and the lack of established predictors for each lymphoma histologic subtype prompted our present study. We retrospectively analysed 121 patients diagnosed with NHL according to the WHO classification criteria. All patients fulfilled the 2016 ACR-EULAR classification criteria for pSS. Cumulative clinical, laboratory, radiologic, treatment regimens and histologic data were recorded, harmonized and analysed. Overall survival (OS) and event-free survival (EFS) curves were calculated. A mucosa-associated lymphoid tissue lymphoma (MALTL) prediction model was developed by applying innovative data-driven analysis of clinical features present at the time of pSS diagnosis. MALTLs constituted the majority of lymphomas (92/121, 76.0%) followed by diffuse large B-cell lymphomas (DLBCL) (11/121, 9.0%) and nodal marginal zone lymphomas (NMZL) (8/121, 7%). MALTLs show salivary glands localization, limited disease and often bone marrow and nodal involvement. The 10-year OS and EFS rates were 79% and 45.5% for MALTLs, 40.9% and 24.2% for DLBCL and 46% and 31% for NMZL. Cryoglobulinemia, focus score and the total EULAR SS Disease Activity Index (ESSDAI) composite index at pSS diagnosis were proven independent MALTL predictors. Even though MALTLs have a comparatively good survival outlook, they are accompanied by frequent events throughout their clinical course. Common features of pSS, present at diagnosis, can predict future lymphomagenesis meriting a more intensive follow-up plan.

A-10-Year Review on Survival Rate and Prognostic Factors of Ewing Family Tumour in Children at Hospital Universiti Sains Malaysia

Introduction: Ewing Family Tumour (EFT) is a group of rare malignant and aggressive tumour, with a considerably improved prognosis. However, there is lack of study on the outcome of children with EFT in Malaysia. Objectives: The study aimed to evaluate the Overall Survival (OS) rate, Event Free Survival (EFS) rate and identify the prognostic factors that determined the EFT outcome at Hospital Universiti Sains Malaysia (USM). Methodology: A retrospective record review of children aged 0-18 years with EFT was done. Patients were identified from the registration data in the Oncology Unit and Record Office of Hospital USM. For patients with untraceable information or deceased, a letter was sent to State Registry to obtain the outcome of the patient. The association between demographics and patients’ clinical factors was determined using the Cox regression. Survival curves were estimated by the Kaplan-Meier method and were compared using the Log-rank test. Results: There were 51 patients identified but 29 of them were eligible for the study. The mean duration of follow-up was 21 months. The OS rate at 1, 2, 3 and 5 years were 62.1%, 44.8%, 30.2% and 21.6% respectively. The EFS rate at 1, 2, 3 and 5 years were 41.9%, 26.7%, 17.8% and 0% respectively. Multivariate Cox regression analysis showed that the presence of surgical intervention (p = 0.030) and major complications (p = 0.045) were the significant prognostic factors to the survival of EFT. Conclusion: The survival rate of EFT among our patients was comparable to other developing countries, with surgical intervention and the presence of major complications as independent prognostic factors.

Synovial sarcoma in children: A 15-YEAR experience at a tertiary pediatric center in Argentina

Synovial sarcoma (SS) is characterized by local invasiveness and a propensity to develop distant metastases. Current treatment for pediatric patients is based on the strategy used by the two main international groups, the Children's Oncology Group (COG) and the European group (EpSSG). Overall survival (OS) and event free survival (EFS) vary according to different publications; however, they tend to be dismal in initially metastatic patients, as well as relapsed patients. To describe the clinical, histopathological, molecular findings and outcome in a series of 22 pediatric patients treated at our institution over 15 years. A retrospective, descriptive study in patients with a histopathological or molecular diagnosis of SS between December 2005 and August 2019, treated according to the E pSSG NRSTS 2005 protocol. Median age at diagnosis was 138.1 months, 32.1% presented with a primary axial site, and 68% with a tumor larger than 5 cm. Initial metastatic disease was seen in 22.7%. Of initially localized patients, 70.6% were classified as high-risk. Chemotherapy was administered to 91% of our patients and 77.2% received radiotherapy. The 3-5- and 10-year OS and EFS was 66%, 58.7% and 48.9%, and 57%, 33%, 22.2% respectively. Localized patients had a 5- and 10-year OS of 73.3% and 61.1%, versus 40% and 0% in metastatic disease, respectively. The only statistically significant factors were presence of metastasis, tumor size and IRS group. Tumor relapse was seen in 31.8% of patients. Only patients with local recurrence that achieved a complete surgery are alive without disease. Treatment schemes after recurrence or progression included a combination of gemcitabine-docetaxel, vincristine-irinotecan-temozolomide, kinase tyrosine inhibitors, and metronomic therapy with cyclophosphamide or etoposide. A long progression free survival of 14 months was observed with etoposide. Although the sample size was not large enough to draw robust conclusions, in our series, OS and EFS rates were found to be lower than those reported in other studies, probably related to unfavorable prognostic factors, including a high incidence of metastasis and tumors larger than 5 cm. New therapeutic strategies are needed to improve outcome, especially in metastatic and relapsed disease. In addition, assessing the role of maintenance therapy in larger numbers of patients and broadening the use of metronomic chemotherapy would be necessary.

Vascular complications after transcatheter aortic valve implantation: treatment modalities and long-term clinical impact.

Vascular complications (VC) are the most frequent drawback of transcatheter aortic valve implantation (TAVI), affecting up to 20% of overall procedures. Data on the treatment and their long-term impact are scarce. The goal of this study was to report on the incidence, management and impact on the long-term outcomes of VC following TAVI. This was a multicentric retrospective analysis of consecutive patients undergoing TAVI. The primary endpoint was freedom from major adverse cardiac and cerebrovascular events at long-term follow-up. Adverse events were evaluated according to Valve Academic Research Consortium-2 criteria. A total of 2145 patients were included: VC occurred in 188 (8.8%); of which 180 were limited to the access site. Two-thirds of the VC were minor; 8% required surgical treatment; the remaining were repaired percutaneously. The major adverse cardiac and cerebrovascular events-free survival at 2 years was 83.0% for patients with VC and 86.7% for those without (P = 0.143), but 71.9% for patients with major compared to 89.0% in those with minor VC (P = 0.022). Major VC and diabetes mellitus independently predicted worse outcomes at 2 years. The major adverse cardiac and cerebrovascular events-free survival rate and the occurrence of vascular adverse events in the long term among patients with VC at the access site treated by endovascular techniques (covered stent implantation or angioplasty) were similar to those without VC (84.2% vs 86.7%; P = 0.635). Major but not minor VC impact long-term survival after TAVI. Covered stents implanted to manage VC at the access site have no impact on the long-term clinical outcome of TAVI.