Five-year Overall Survival For Patients Research Articles

The clinical regimens and cell membrane camouflaged nanodrug delivery systems in hematologic malignancies treatment.

Hematologic malignancies (HMs), also referred to as hematological or blood cancers, pose significant threats to patients as they impact the blood, bone marrow, and lymphatic system. Despite significant clinical strategies using chemotherapy, radiotherapy, stem cell transplantation, targeted molecular therapy, or immunotherapy, the five-year overall survival of patients with HMs is still low. Fortunately, recent studies demonstrate that the nanodrug delivery system holds the potential to address these challenges and foster effective anti-HMs with precise treatment. In particular, cell membrane camouflaged nanodrug offers enhanced drug targeting, reduced toxicity and side effects, and/or improved immune response to HMs. This review firstly introduces the merits and demerits of clinical strategies in HMs treatment, and then summarizes the types, advantages, and disadvantages of current nanocarriers helping drug delivery in HMs treatment. Furthermore, the types, functions, and mechanisms of cell membrane fragments that help nanodrugs specifically targeted to and accumulate in HM lesions are introduced in detail. Finally, suggestions are given about their clinical translation and future designs on the surface of nanodrugs with multiple functions to improve therapeutic efficiency for cancers.

Beyond Total Mesorectal Excision (TME)-Results of MRI-Guided Multivisceral Resections in T4 Rectal Carcinoma and Local Recurrence.

Rectal cancer invading adjacent organs (T4) and locally recurrent rectal cancer (LRRC) pose a special challenge for surgical resection. We investigate the diagnostic performance of MRI and the results that can be achieved with MRI-guided surgery. All consecutive patients who underwent MRI-based multivisceral resection for T4 rectal adenocarcinoma or LRRC between 2005 and 2019 were included. Pelvic MRI findings were reviewed according to a seven-compartment staging system and correlated with histopathology. Outcomes were investigated by comparing T4 tumors and LRRC with respect to cause-specific survival in uni- and multivariate analysis. We identified 48 patients with T4 tumors and 28 patients with LRRC. Overall, 529 compartments were assessed with an accuracy of 81.7%, a sensitivity of 88.6%, and a specificity of 79.2%. Understaging was as low as 3.0%, whereas overstaging was 15.3%. The median number of resected compartments was 3 (interquartile range 3-4) for T4 tumors and 4 (interquartile range 3-5) for LRRC (p = 0.017). In 93.8% of patients with T4 tumors, a histopathologically complete (R0(local)-) resection could be achieved compared to 57.1% in LRRC (p < 0.001). Five-year overall survival for patients with T4 tumors was 53.3% vs. 32.1% for LRRC (p = 0.085). R0-resection and M0-category emerged as independent prognostic factors, whereas the number of resected compartments was not associated with prognosis in multivariate analysis. MRI predicts compartment involvement with high accuracy and especially avoids understaging. Surgery based on MRI yields excellent loco-regional results for T4 tumors and good results for LRRC. The number of resected compartments is not independently associated with prognosis, but R0-resection remains the crucial surgical factor.

Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis.

10032 Background: Treatment options for relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK)-inhibitors. However, there is no standard treatment and limited published data evaluating their use in this patient population. Methods: We conducted a retrospective, multi-institutional study of patients &lt;22 yrs old at initial diagnosis with R/R ALCL treated between 2011-2021 across 18 institutions. Results: We identified 85 patients with R/R ALCL (median age at initial diagnosis 12 yrs, 67% male, 96% ALK+). Treatment for initial diagnosis included ALCL99 (31%), ANHL12P1 + BV (32%), ANHL12P1 + crizotinib (CZ) (11%), ANHL0131 (14%), or other (13%). Median time from diagnosis to relapse was 0.7 yrs (range 0.2-10.8 yrs) with sixteen patients (18%) relapsing on initial chemotherapy. Stage at relapse for 82 ALK+ patients: I (9%), II (15%), III (41%), IV (35%). Initial re-induction regimens shown in the table. Fifty-nine (72%) patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 49 allogeneic with one receiving both. Of 59 transplanted patients, 10 relapsed (6 allo 4 auto) and 7 died. All but one of the patients who relapsed post-HSCT responded to additional therapy and remain alive. Of 23 ALK+ patients who never had a transplant, 4 patients died and 19 are alive in remission. Eleven remain on active therapy (6 CZ, 3 BV, 1 BV+CZ, 1 vinblastine) with eight off therapy. Patients who received a transplant more likely to be off therapy and alive. Duration of treatment for patients receiving BV or the ALK-inhibitor CZ varied widely (BV 1-11 yrs; CZ 2-10 yrs) with 20 patients continuing on therapy at the time of data collection. Five-year overall survival for patients with or without transplant was 91% (CI 84-99%) and 86% (CI 73-100%) respectively. Conclusions: This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy. Transplant may not be necessary for all R/R patients including those with high-risk disease. [Table: see text]

High resection rates of colorectal liver metastases after standardized follow-up and multimodal management: an outcome study within the COLOFOL trial

BackgroundOutcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy. MethodsIn the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS. ResultsOf 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46–0.85). ConclusionA high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients.

Prevalence and risk factors of disseminated intravascular coagulation in childhood acute lymphoblastic leukemia.

Few studies have examined disseminated intravascular coagulation (DIC) in childhood acute lymphoblastic leukemia (ALL). Our aims were to evaluate the prevalence, risk factors and outcomes of DIC at ALL presentation and during induction chemotherapy. The medical records of ALL patients aged <15 years were retrospectively reviewed. Logistic regression analysis was used to identify risk factors. The Kaplan-Meier method was used to depict survival. Of the 312 patients, 48 (15.4%) and 76 (24.4%) had DIC at presentation and during induction chemotherapy, respectively. Risk factors for DIC at presentation (OR and 95% CI) were antibiotics prior to admission 2.34 (1.17-4.89), white blood cell count ≥100 × 109/L 2.39 (1.04-5.72), platelets <100 × 109/L 5.44 (1.84-23.4) and high National Cancer Institute (NCI) risk 2.68 (1.08-6.62). Risk factors for DIC during induction chemotherapy were antibiotics prior to admission 1.86 (1.07-3.27), high peripheral blasts 1.01 (1.00-1.02) and transaminitis 2.02 (1.18-3.48). Five-year overall survival of patients who had DIC was significantly lower than those who did not (45.0% vs. 74.1%, p <0.001). Antibiotics prior to admission, hyperleukocytosis, thrombocytopenia and high NCI risk were risk factors of DIC at presentation. Antibiotics prior to admission, high peripheral blasts and transaminitis were risk factors of DIC during induction chemotherapy. There are only two studies, both published before 2000, evaluating risk factors of DIC in pediatric ALL patients without reporting outcomes. DIC was associated with lower remission and survival rates in pediatric ALL patients. We identified the risk factors of DIC at presentation as antibiotics prior to admission, hyperleukocytosis, thrombocytopenia and high NCI risk. The risk factors of DIC during induction chemotherapy were antibiotics prior to admission, high peripheral blasts and aspartate transaminitis. Pediatric ALL patients who have the aforementioned risk factors should be closely monitored for DIC secondary to infection, and early treatment with appropriate antimicrobial agents is recommended.

Has_circ_0000069 expression in breast cancer and its influences on prognosis and cellular activities.

Circular RNA (circRNA), as a newly discovered non-coding RNA with important regulatory potential, is closely related to the occurrence and progression of various tumors. This study aimed to investigate has_circ_0000069 expression in breast cancer and its influence on cellular activities. Using real-time quantitative polymerase chain reaction, has_circ_0000069 levels were measured in 137 pairs of tissue specimens, as well as cancer cell lines. The cellular activities of cell lines were determined by cell counting kit-8 (CCK-8) and Transwell assays. The potential targeting miRNAs were predicted and verified using an online database and dual-luciferase reporter assay. Has_circ_0000069 was highly expressed in breast cancer tissues and cells. The expression of has_circ_0000069 was associated with the five-year overall survival of patients. After silencing has_circ_0000069 in breast cancer cells, its expression reduced, and the ability of cell proliferation, migration, and invasion decreased. MiR-432 was verified as a targeting miRNA of has_circ_0000069. Has_circ_0000069 expression increased in breast cancer and was negatively related to patient's prognosis. Has_circ_0000069 may facilitate breast cancer tumor progression by sponging miR-432. These findings revealed that has_circ_0000069 may be a biomarker for predicting prognosis and a therapeutic target for treating patients with breast cancer.

Heterogeneity of outcomes of endometrial cancer patients included in prospective clinical trials

ObjectiveTo assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. MethodsThe National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. ResultsA total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%–81.7% for patients meeting GOG-249 inclusion criteria, 40.2%–81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%–75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. ConclusionsRecent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.

Ninety Percent or Greater Tumor Necrosis Is Associated With Survival and Social Determinants of Health in Patients With Osteosarcoma in the National Cancer Database.

The histologic response of osteosarcoma to chemotherapy is commonly cited as a prognostic factor and typically graded as the percent necrosis of the tumor at the time of surgical resection. Few studies, to our knowledge, have examined the relationship of tumor necrosis relative to other factors. Existing studies are limited by prolonged enrollment periods or analysis of patient subsets without the strongest predictor of mortality: metastasis at diagnosis. Additionally, the definitive threshold value for a good histologic response is commonly set at more than 90% tumor necrosis with little evidence; some authors advocate other values. (1) Are there alternative cutoff values for a good response to chemotherapy in a large, national cohort of contemporarily treated patients with osteosarcoma? (2) How does the association of histologic response to survival in osteosarcoma compare with other clinicopathologic factors? (3) What patient and clinical factors are associated with the histologic response? We identified 2006 patients with osteosarcoma diagnosed between 2010 and 2015 in the National Cancer Database (NCDB), a registry that includes 70% of all new cancers diagnosed in the United States with 90% follow-up. Patients were excluded for missing documentation of percent tumor necrosis (21% [425 of 2006]) or if definitive resection was not performed (< 1% [1 of 2006]). A total of 1580 patients were included in the analysis, with a mean follow-up duration of 37 ± 22 months. A Kaplan-Meier survival analysis, stratified by the percent tumor necrosis after chemotherapy, was performed for the 5-year period. Other covariates examined were sex, race, socioeconomic score composite, insurance type, Charlson/Deyo score, distance from the hospital, and location (metropolitan, urban, or rural). Clinical and sociodemographic data including patient-identified race from the patient's medical record is input into the NCDB by certified registrars. The NCDB only allows coding of one primary race for each patient; thus, most of our patients were grouped as White or Black race and the remaining were grouped as Other for our analysis. A multiple Cox regression analysis was performed to evaluate the effect of percent necrosis compared with other demographic, clinicopathologic, and treatment effects on survival. Finally, a multiple logistic regression analysis was performed to assess demographic and clinicopathologic characteristics associated with percent necrosis. Five-year overall survival for patients with histologic gradings of 90% to 94% necrosis (70% [95% confidence interval (CI) 60.6% to 79.7%) and 95% to 100% necrosis (74% [95% CI 68% to 80.3%) was not different between groups (p = 0.47). A comparison of histologic responses below 90% necrosis found no difference in survival between patients with decreasing histologic response (p > 0.05). Necrosis of less than 90% was associated with worse survival (HR 2.00 [95% CI 1.58 to 2.52]; p < 0.001 compared with more than 90% necrosis), and factors most associated with poor survival were metastasis (HR 2.85 [95% CI 2.27 to 3.59]; p < 0.001) and skip metastasis at the time of diagnosis (HR 2.52 [95% CI 1.64 to 3.88]; p < 0.001). On multivariate analysis, adjusting for demographic, clinicopathologic, and treatment factors, social determinants of health were negatively associated with percent necrosis of 90% or more, including uninsured status (OR 0.46 [95% CI 0.23 to 0.92]; p = 0.02 compared with private insurance) and lower socioeconomic status composite (OR for the lowest first and second quartiles were 0.63 [95% CI 0.44 to 0.90]; p = 0.01 and 0.70 [95% CI 0.50 to 0.96]; p = 0.03, respectively). Race other than White or Black (OR 0.61 [95% CI 0.40 to 0.94]; p = 0.02 compared with White race) was also negatively associated with percent necrosis of more than 90% after controlling for available covariates. This study suggests that a cutoff of 90% necrosis provides the best prognostic value for patients with osteosarcoma undergoing chemotherapy. Other threshold values did not show different survival benefits. Sociodemographic factors were associated with histologic response less than 90%. These associations must be carefully understood not as cause and effect but likely demonstrating the effects of health disparities and access to care. Although we controlled for multiple variables in our analysis, broad variables such as race may have been associated with histologic response due to unaccounted confounders. Medical providers should be aware of these associations to ensure equitable access and delivery of care because access to care may be responsible for these associations. Future studies should examine potential drivers of this observation, such as a delay in presentation or deviation from standard of care practices. Level III, therapeutic study.

Performance of LI-RADS Version 2018 on CT for Determining Eligibility for Liver Transplant According to Milan Criteria in Patients at High Risk for Hepatocellular Carcinoma.

BACKGROUND. LI-RADS has been investigated primarily in terms of detection of hepatocellular carcinoma (HCC), with less attention given to its performance, particularly on CT, in determining eligibility for liver transplant (LT). OBJECTIVE. The purpose of our study was to assess the performance of LI-RADS version 2018 (v2018) on CT for the diagnosis of HCC and determination of LT eligibility according to the Milan criteria (MC). METHODS. This retrospective study included 136 patients (110 men, 26 women; mean age, 53.9 ± 8.1 [SD] years) at high-risk for HCC who underwent liver protocol CT within 3 months before LT between January 2010 and December 2018. Two radiologists independently reviewed CT examinations using LI-RADS v2018; Organ Procurement and Transplantation Network (OPTN) classes were constructed from the LI-RADS interpretations. Histopathologic analysis of liver explants served as the reference standard for determining the presence of HCC and LT eligibility based on MC. Diagnostic performance was evaluated. Overall survival (OS) was assessed based on medical record review. RESULTS. Based on histopathologic evaluation of liver explants in the 136 patients, 27 patients had no malignancy, 77 were eligible for LT due to HCC within MC, and 32 were unsuitable for LT (i.e., HCC beyond MC in 16 patients, HCC with macrovascular invasion in 12, non-HCC malignancy in four). LR-5 exhibited per-lesion sensitivity and PPV for HCC of 55.9% and 92.8%, respectively, for reader 1 and 39.8% and 86.5% for reader 2. When considering LR-5 observations to represent HCC in assessing MC, LI-RADS had accuracy for determining LT eligibility of 92.7% for reader 1 and 85.3% for reader 2; OPTN criteria had accuracy for determining LT eligibility of 89.0% for reader 1 and 84.4% for reader 2. Five-year OS for patients within MC versus 5-year OS for patients unsuitable for LT was 92.2 months versus 56.0 months for LI-RADS, 92.6 months versus 47.6 months for OPTN criteria, and 93.3 months versus 55.1 months for histopathologic assessment of liver explants. CONCLUSION. LI-RADS v2018, as evaluated on CT in high-risk patients, shows high PPV for HCC detection and high accuracy for determining LT eligibility based on MC. LT eligibility based on preoperative LI-RADS evaluation is associated with post-LT survival. CLINICAL IMPACT. These findings support the use of LI-RADS on CT in assessing eligibility in patients who are candidates for LT.

Long-term survival after treatment for primary anal cancer– results from the Swedish national ANCA cohort study

Background Squamous cell carcinoma of the anus is increasing in incidence but remains a rare disease with good 3- and 5-year recurrence free and overall survival rates of 63%–86%. The treatment includes chemoradiotherapy, mainly with 5-fluoruracil (5FU) and mitomycin. The aim of this study was to describe long-term (up to 9 years after treatment) oncological outcome and the types of treatments given, in a Swedish national cohort of patients diagnosed with anal cancer between 2011 and 2013. Method Patients were identified in the Swedish Cancer Registry. Patients still alive were contacted and asked for consent. Clinical data were retrieved from National Patient Register at the Swedish National Board of Health and Welfare and from medical records. Unadjusted and adjusted analyses were performed for overall survival. Results Three hundred and eighty-eight patients were included in the study of which 338 patients (87%) received treatment with a curative intent. Follow up was 85 months (0–113 months) for patients treated with curative intent (information missing in one patient) 7.5 months (0–55) for patients with treated with a palliative intent. Curative treatment varied and consisted of both chemoradiotherapy and radiotherapy (46–64 Gy) alone. 5-FU, mitomycin and cisplatin were the most used chemotherapy agents. Five-year overall survival for patients treated with curative intent was 73%. In an adjusted analysis 5-FU and mitomycin is associated with a lower mortality than 5-FU and cisplatin but the association was weaker (HR 1.61 (95% CI: 0.904; 2.85) than in the unadjusted analysis Conclusions In this national cohort overall five-year survival was 73% for patients treated with curative intent. As reported by others our results indicate that 5-FU and mitomycin C should be the preferred chemotherapy in treatment for cure.

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.

Socioeconomic Position and Risk of Disease Progression and Death in Patients with Myelodysplastic Syndromes: A Danish Nation-Wide Population-Based Cohort Study

Background:Five-year overall survival for patients with myelodysplastic syndromes (MDS) is around 30%. Adverse prognostic factors include advancing age, higher blast cell percentage, poor risk cytogenetics, two or more cytopenias, high burden of comorbidity, and transfusion-dependency. The impact of socioeconomic position on clinical outcomes in MDS patients is however unclear. In this nationwide population-based cohort-study, we therefore examined the associations between the individual-level socioeconomic markers education level, cohabitation status, and income, and the risk of progression to acute myeloid leukemia (AML), and all-cause mortality among MDS patients.Methods:Using the Danish Myelodysplastic Syndromes Database, we identified all patients with incident MDS diagnosed between January 1st 2010 and December 31th 2018. The database holds valid and detailed patient- and disease-characteristics on all Danish MDS patients diagnosed since 2010. We linked the study-population with individual-level information on education, cohabitation status, income, comorbidity, progression to AML, and vital status retrieved from high-quality Danish population-based registries. We computed absolute risks of progression to AML and all-cause mortality using the cumulative incidence (risk) function accounting for death as competing risk when AML was the outcome. Also, 1-year, 3-year, and 5-year relative risks (RRs) of progression to AML and death were computed using the pseudovalue approach. All results were given crude and adjusted for age, sex, socioeconomic position (SEP), comorbidity and subtype of MDS according to the “International Prognostic Scoring System” (IPSS) and with 95% confidence intervals (CIs).Results:The final cohort comprised 2233 MDS patients (median age 75 years, 63% males). Median follow-up time was 1.7 years. The 1-year risks of progression to AML was similar across education levels (long education (>13 years): 5%, medium education (9-12 years): 6%, short education (<9 years): 6%. In adjusted models, there were no associations between education, income or cohabitation status and risk of progression to AML (Table 1). Still, patients with a short education had higher 1-year all-cause mortality (33%) compared to those with medium (22%) and longer education (21%) (Figure 1). In adjusted models the risk of death one year from diagnosis was higher in patients with short vs. longer education [RR=1.26 (95% CI: 1.03-1.55)], in patients with lower vs. higher income [RR=1.43 (95% CI: 1.17-1.75)], and among patients who were living alone compared to those who lived with someone [RR=1.19 (1.02-1.39)]. The increased risk of death among patients with short education, low income, and those who lived alone persisted after 3-year and 5-years of follow-up (Table 1).Conclusion:In a real world setting, shorter education, living alone, and lower income were not associated with increased risk of progression to AML but with inferior survival in Danish MDS patients. These results suggest that in spite of “free and equal access” to healthcare and cancer treatment in Denmark, short education, living alone, and low income are adverse prognostic factors for patients with MDS. Further analyses are ongoing to get insight into the mechanisms driving these socioeconomic disparities in MDS patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Survival and Treatment of Lung Cancer in Taiwan between 2010 and 2016.

Background: Lung cancer is the leading cause of cancer-related death, and its incidence is still growing in Taiwan. This study investigated the prognostic factors of overall survival between 2010 and 2016 in Taiwan. Methods: Data from 2010 to 2016 was collected from the Taiwan Cancer Registry (TCR). The characteristics and overall survival of 71,334 lung cancer patients were analyzed according to the tumor, node, metastasis (TNM) 7th staging system. Univariate and multivariate analysis were performed to identify the prognostic factors. Results: The five-year overall survival (n = 71,334) was 25.0%, and the median survival was 25.3 months. The five-year overall survival of patients receiving any kind of treatment (n = 65,436; 91.7%) and surgical resection (n = 20,131; 28.2%) was 27.09% and 69.93%, respectively. The clinical staging distribution was as follows: stage IA (9208, 12.9%), stage IB (4087, 5.7%), stage IIA (1702, 2.4%), stage IIB (1454, 2.0%), stage IIIA (5309, 7.4%), stage IIIB (6316, 8.9%), stage IV (41458, 58.1%). Age, sex, Charlson comorbidity index, cell type, clinical T, clinical N, clinical M, grading and treatment strategy are independent prognostic factors in the multivariate analysis. Conclusion: The outcome for lung cancer patients was still poor. The identification of prognostic factors could facilitate in choosing treatment strategies and designing further randomized clinical trials.

Comparative analysis of the clinical characteristics and outcomes of patients with Wilms tumor in the United Kingdom and Japan.

Wilms tumor (WT) demonstrates epidemiological differences by world region and ethnicity. To enhance understanding of these differences, we retrospectively analyzed clinical trial data sets from the UK and Japan over a 20-year period. We used data from three consecutive clinical trials in the UK and a single study in Japan that enrolled patients diagnosed during 1996-2015, to compare clinical characteristics and outcomes between countries. During 1996-2015, 1395 patients in the UK and 537 in Japan were included. Japanese patients have a significantly younger median age at diagnosis than those in the UK (28months vs 39months). The proportion of patients with stage IV, large tumors, and anaplastic histology appears to be higher in the UK than in Japan (18%vs 11%, 62%vs 49%, 8%vs 3%, respectively). During 2005-2015, 77 hospitals treated WT in Japan compared with only 20 hospitals in the UK. Five-year overall survival of patients with WT was over 90% in both countries, but five-year event-free survival of patients with stage IV was significantly lower in Japan than in the UK (50.0%vs 76.2%, P=0.001). Differences in age of onset, tumor size at diagnosis, and histology may reflect differences in the genetic background of patients with WT between countries, but population-based phenotype-genotype data are lacking. The difference in survival probability for stage IV patients may be due to different diagnostic criteria or different treatment strategies. Prospective, international clinical studies including genomic analyses are needed to confirm these findings and improve clinical practice.

Validation of the Khorana Score for Prediction of Venous Thromboembolism After Robot-Assisted Radical Cystectomy.

Introduction: The Khorana score (KS) is used to predict the risk of venous thromboembolism (VTE) for cancer patients. We sought to assess the association between KS and VTE for patients who underwent robot-assisted radical cystectomy (RARC). Materials and Methods: We reviewed our prospectively maintained quality assurance RARC database between 2005 and 2020. KS was calculated for all patients (one point for each body mass index [BMI] ≥35 kg/m2, platelet count ≥350 × 109/L, leukocyte count >11 × 109/L, and hemoglobin level <10 g/dL, or use of erythropoiesis-stimulating agents). All patients received one point by default for the cancer type (bladder). Patients were divided into intermediate-risk (KS 1-2) or high-risk (KS ≥3) groups. Receiver operating characteristic curve was used to assess the ability of KS to predict VTE. Kaplan-Meier curves were stratified based on their KS risk and used to depict overall survival (OS). Multivariate analysis (MVA) was used to identify variables associated with VTE. Results: Out of 589 patients, 33 (6%) developed VTE (18 had deep vein thrombosis and 15 had pulmonary embolism). Five hundred forty-six (93%) patients had intermediate-risk KS and 30 (5%) of them developed VTE. Forty-three (7%) patients were classified as high-risk KS and 3 (7%) developed VTE. This difference was not significant (p = 0.73). The KS area under the curve for VTE prediction was 0.51. On MVA, BMI ≥35 kg/m2 (odds ratio [OR] 2.69, confidence interval [CI] 1.19-6.11, p = 0.02), longer inpatient stay (OR 1.04, CI 1.003-1.07, p = 0.03), and ≥pT3 disease (OR 2.29, CI 1.11-4.71, p = 0.03) were associated with VTE, whereas KS was not associated with VTE (p = 0.68). Five-year OS of patients with intermediate KS was 53% compared with 30% for high-risk KS (log rank p < 0.01). Conclusion: KS underestimated VTE risk after RARC and showed poor accuracy. This highlights the need to develop procedure-specific tools to estimate the risk of VTE after RARC.

The role of CD28 in adult T-cell leukaemia/lymphoma.

The role of CD28 in adult T-cell leukaemia/lymphoma.

ETMR-14. TREATMENT OF EMBRYONAL TUMOURS WITH MULTILAYERED ROSETTES (ETMR) WITH CARBOPLATIN-ETOPOSIDE INDUCTION AND TANDEM HIGH-DOSE CHEMOTHERAPY WITHIN THE PROSPECTIVE HIT-TRIALS AND REGISTRIES

BACKGROUNDEmbryonal tumours with multilayered rosettes (ETMR) are highly aggressive tumors, mostly occurring in infants. Published clinical data refer to retrospective cohorts of inhomogeneously treated patients. Here, we describe the outcome of patients, who were prospectively treated within the P-HIT2000-trial, the subsequent HIT2000-interim-registry and earlier HIT-trials.PATIENTS AND METHODSNineteen patients from the P-HIT2000-trial (2001–2011), 12 patients from the subsequent HIT2000-interim-registry (2012–2014) and 4 patients from earlier HIT-trials with centrally reviewed neuropathological and molecularly-confirmed diagnosis of ETMR were included. Outcome of 18 patients treated with carboplatin-etoposide-induction followed by tandem-high-dose chemotherapy (“CARBO-ETO+HDCT”) with stage-stratified radiotherapy administered in case of persistant disease, relapse or progression were compared to patients treated with HIT-SKK chemotherapy ± radiotherapy (n=9) or other regimens (n=8).RESULTSMedian age at diagnosis was 2.9(1.0–5.3) years. Metastases at diagnosis were detected in 9 patients (26%). For the entire cohort of n=35, 5-year overall survival (OS) was 26.7%, and progression-free survival (PFS) was 18.5%. Five-year OS for patients with CARBO-ETO+HDCT, SKK chemotherapy or other regimens was 44.4%, 13.0% and 0%, respectively (p=0.006). Five-year PFS was 33.3%, 0% and 0%, respectively (p=0.119). Of 10 survivors, n=8 were treated with CARBO-ETO+HDCT; n=4 had craniospinal, n=2 local and n=4 no radiotherapy. Impact of initial gross-total-resection (p=0.231) and non-metastatic disease (p=0.097) was limited.CONCLUSIONSWe show improved survival with carboplatin-etoposide-induction followed by tandem-high-dose chemotherapy, indicating that a cure is possible for some patients. However, despite intensive treatment, outcome is unsatisfactory and innovative therapies urgently need to be included in an upfront setting.

Prognostic Role of C-Reactive Protein, C-Reactive Protein Kinetics and C-Reactive Protein/ Albumin Ratio in Newly Diagnosed B-Cell Chronic Lymphoproliferative Diseases

Introduction: C-reactive protein (CRP), the most commonly used clinical indicator of inflammation, plays an important role in disease diagnosis and efficacy evaluation. Recent studies identified elevated CRP level and CRP kinetics, dynamic change of CRP level throughout treatment, were associated with decreased clinical outcome in some malignancies. Because of increased catabolism and the reduce of hepatic synthesis, albumin is oppositely associated with inflammatory. CRP/ albumin ratio (CAR) is a novel and superior prognostic factor involving inflammatory and nutritional factors in various cancers. However, the prognostic role of CRP, CRP kinetics and CRA in B-cell chronic lymphoproliferative diseases (B-CLPD) were not well characterized yet. Our study focused on the prognostic role of CRP, CRP kinetics and CRA in newly diagnosed B-CLPD. Methods: In total, 243 newly diagnosed B-CLPD patients from January 2012 to December 2019 at the Shandong provincial hospital in China were analyzed for overall survival (OS) and disease-free survival (DFS), depending on CRP, CRP kinetics and CRA. OS and DFS were determined by Kaplan-Meier curves and log-rank test. Cox proportional analysis was performed to examine the prognostic significance of clinicopathological variables in multivariate analyses. Results: The five-year OS of patients with elevated pretreatment CRP level (94.3% vs. 56.7%, p&amp;lt;0.001) (Figure 1a), elevated post-treatment CRP level (81.7% vs. 39.4%, p&amp;lt;0.001) (Figure 1c), continuously elevated CRP level during the whole treatment process (80.0% vs. 47.1%, p&amp;lt;0.001) (Figure 1e) and elevated pretreatment CRA level (93.1% vs. 61.9%, p&amp;lt;0.001) (Figure 1g) were shorter than normal patients, respectively. Compared to normal patients, the five-year DFS of patients with elevated pretreatment CRP level (88.0% vs. 33.9%, p&amp;lt;0.001) (Figure 1b), elevated post-treatment CRP level (56.4% vs.35.7%, p=0.020) (Figure 1d), ever-elevated CRP level (62.9% vs. 35.3%, p&amp;lt;0.001) (Figure 1f), continuously elevated CRP level during the whole treatment process (80.2% vs. 35.3%, p&amp;lt;0.001) (Figure 1f) and elevated pretreatment CRA level (87.3% vs. 42.8%, p&amp;lt;0.001) (Figure 1h) were shorter, respectively. Multivariate analyses identified that elevated pretreatment CRP level (HR: 5.110, p=0.001) (Table 1), elevated post-treatment CRP level (HR: 5.826, p=0.006) (Table 2), continuously elevated CRP level (HR: 6.461, p&amp;lt;0.001) (Table 3) and elevated pretreatment CAR (HR: 3.768, p=0.008) (Table 4) had association with worse OS. Likewise, elevated pretreatment CRP level (HR: 3.767, p=0.001) (Table 1), post-treatment CRP level (HR: 2.384, p=0.043) (Table 2), ever-elevated CRP level (HR: 2.425, p=0.027) (Table 3), continuously elevated CRP level (HR: 4.748, p&amp;lt;0.001) (Table 3) and elevated pretreatment CAR level (HR: 2.824, p=0.007) (Table 4) were in independent significance with worse DFS. Conclusions : We demonstrate that CRP level, CRP kinetics and CAR could be potential prognostic indicators with independent significance in patients with B-CLPD. CRP and CAR make an implementation for prognostic evaluation more easily and effectively in B-CLPD patients. Disclosures No relevant conflicts of interest to declare.

Treatment of rhabdomyosarcoma in children and adolescent from four low health expenditures average rates countries

BackgroundSurvival of children with cancer in Eastern and Central Europe is 10–20% lower than in high income European countries. We evaluated outcome of children and adolescents with rhabdomyosarcoma (RMS) in Slovenia, Croatia, Slovakia and in Romania.Patients and methodsWe retrospectively analysed event-free survival (EFS) and overall survival (OS) for all patients treated in Slovenia and Croatia. Slovakia included patients from two centers, representing half of expected cases. Romania included patients from single institution, representing only 10% of expected patients. Joint database for analysis was established.ResultsOne hundred seventy-eight children and adolescent with RMS diagnosed from January 2000 to December 2015 were included. Mean patient age at diagnosis was 7.7 years, one third was older than 10 years. Twenty-five percent had alveolar histology and 72% unfavorable location. Higher than expected proportion of patients had nodal involvement (24%) or metastatic disease (27%). All patients received systemic chemotherapy, 57% had radiotherapy and 63% surgery as local control. Kaplan- Meier estimates for 5-year EFS and OS were 50.7% and 59.6%, respectively. Five-year OS for patients with localised disease was 72% compared to 24% for metastatic disease.ConclusionsChildren with RMS treated in Eastern and Central Europe have inferior outcome compared to their counterparts treated in high income European countries. Active participation of low health expenditures average rates (LHEAR) countries in international clinical trials may improve outcome of paediatric oncology patients.

Balanced and unbalanced chromosomal translocations in myelodysplastic syndromes: clinical and prognostic significance

Prognostic role of chromosomal translocations (CT) in myelodysplasia (MDS) was retrospectively analyzed in 77 patients from GROM-L registry. Forty (51.9%) balanced, 28 (36.4%) unbalanced and 9 (11.7%) concomitant balanced and unbalanced CT were identified. Five-year overall survival (OS) of the entire cohort was 34.5% (CI 95% 22.5−46.5). Five-year OS of patients with unbalanced CT was significantly shorter than that of patients carrying balanced CT [22.3% (CI 95% 4.0−40.6) vs 44.0% (CI 95% 26.7−61.3) (p = 0.042)]. Five-year OS of patients with CT included in complex karyotype (CK) was significantly shorter than that of patients with isolated CT or CT with another abnormality [5.5% (CI 95% 0−15.7) vs 42.9% (CI 95% 21.3−64.5) and vs 4% (CI 95% 31.6−79.2) (p < 0.001)]. Presence of CT in MDS characterizes a more aggressive outcome only when associated with CK.