Prognostic Groups Of Patients Research Articles

Molecular classification of endometrial carcinoma on endometrial biopsy: an early prognostic value to guide personalized treatment

ObjectiveMolecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the...

Baseline volumetric parameters of PET/CT <sup>18</sup>F-FDG and international prognostic index at patients with diffuse B-cell large cell lymphoma

INTRODUCTION: Metabolic tumor volume (MTV) and Tumor lesion glycolysis (TLG) are used in 18F-fluorodeoxyglucose Positron-Emission Tomography combined with Computed Tomography (18F-FDG PET/CT) as biometric markers in whole tumor. International prognostic index (IPI) has been used during 30 years at patients with diffuse B-cell large cell lymphoma (DLBCL) for prognosis, use MTV and TLG was unknown. Our aims were to determinate the best statistical relationship between MTV, TLG and IPI in patients with DLBCL.OBJECTIVE: Complex study of baseline volumetric parameters PET/CT with 18F-FDG at patients with DLBCL and assessment of their correlation with prognostic groups.MATERIALS AND METHODS: Baseline 18F-FDG PET/CT performed in 31 primary patients with DLBCL and evaluated SUVmax, MTV, TMTV, TLG, TTLG at different involved anatomic zones; correlation between PET biomarkers and prognostic groups of patients.Statistics: The research materials were subjected to statistical processing using the methods of correlation and regression analyses.RESULTS: SUVmax mean level didn’t discerned at patients of low and high-risk groups, but TMTV has been less in favorable prognostic, than in unfavorable groups (152±3.0 sm3 vs 890±178 sm3 p<0,01); the same TTLG (1291±474 g/ml×sm3 vs 7640±2067 g/ml×sm3 , p<0.01) and IMA (6.7±0.7 vs 9.2±0.6; p<0,01). All volumetric parameters have been less at patients with supradiaphragmatic lymph nodes, than infradiaphragmatic lymph nodes and bones too. Significant positive correlation was found between the TMTV u TTLG (p=0.965; p<0,001), between TMTV, TTLG and progressive disease risk (p=0.735; p=0.747; p<0,001). The regression analysis was derived to estimate the connection PET biomarkers and progressive disease risk.DISCUSSION: The 30-year experience of using IPI in assessing the prognosis of patients with DLBCL has shown its insufficient effectiveness in many clinical situations, and the R-IPI prognostic model has been tested on a smaller number of patients and can only be considered additionally. We studied in detail the initial volumetric parameters of patients with DLBCL in different regions of the lesion and their relationship with the level of prognosis according to the IPI criteria. Our data on large values of volumetric parameters in the infradiaphragmatic areas and bones may be related to the worse prognosis in patients with these localizations. Further broader studies of the initial volumetric biomarkers of PET in DLBCL patients will contribute to the development of approximate boundaries of specific volumetric parameters for different tumor localizations.CONCLUSION: The results obtained showed that the baseline volumetric parameters PET/CT at patients with DLBCL have significant connection with prognostic groups of patients and can be additional factors to influence of tactics of therapy.

Эффективность неоадъювантной терапии в лечении больных местнораспространенным раком молочных желез

Aim: to assess the severity of the pathomorphological response according to the classification of Residual Cancer Burden (RCB) in patients with breast malignancies depending on the surrogate molecular biological subtype after neoadjuvant drug therapy (chemotherapy ± anti- HER2 therapy). Design: Retrospective comparative study. Materials and methods. The retrospective study included 90 patients with breast cancer (T0-3, N0-1, M0) with luminal In HER2-negative, luminal In HER2-positive, HER2-positive non-luminal, thrice negative subtypes who were on complex treatment. The age of women ranged from 26 to 39 years (median age — 36 years). A retrospective analysis of the evaluation of residual tumor load in 85 patients according to the RGB system after neoadjuvant drug therapy and subsequent surgical treatment was performed. Results. In patients with luminal B HER2-negative breast cancer, a complete pathomorphological response was noted in 20% of cases, in 16% — RCB-I, in 36% — RCB-II, in 28% — RCB-III. Among women with luminal B HER2-positive breast cancer, a complete response was achieved in 26.67%, RCB-I was noted in 33.33%, RCB-II — in 13.33%, and RCB-III — in 26.67%. Among the patients with HER2-positive breast cancer, 46.16% had RCB-0, 23,08% had RCB-I, 15.38% each had RCB-II and RCB-III. In participants with thrice negative breast cancer, a complete response was achieved in 41.94% of cases, RCB-I was noted in 22.58%, RCB-II — in 19.35% and RCB-III — in 16.13%. The frequency of complete pathomorphological response (RCB-0) after neoadjuvant chemotherapy significantly differed among the more aggressive subtypes of breast cancer (thrice negative and HER2-positive), compared with HER2-negative (p < 0.0001). Conclusion. The unified assessment of the residual tumor after neoadjuvant therapy makes it possible to clearly identify prognostic groups of patients with different treatment responses and plan additional drug therapy for them. Keywords: neoadjuvant chemotherapy, targeted therapy, breast cancer, HER2.

Comparison of prognostic factors that affect the survival of patients with metachronous and synchronous metastases of renal cell carcinoma

Introduction. The differences in progression-free survival (PFS) and overall survival (OS) depending on the line of systemic therapy, the timing of the onset of metastases, and Heng prognostic groups in patients with metastatic renal cell carcinoma (mRCC) remain unclear. This leads to the search for new prognostic factors or their combinations, depending on the characteristics of the metastatic disease.Objective. To identify prognostic factors affecting survival rates in patients with synchronous and metachronous renal cell carcinoma metastases.Materials and methods. A retrospective analysis of 934 patients with mPCC treated in the period 2006 to 2020 was performed, of which 319 (34.2%) patients were assigned to the intermediate prognosis group, and 388 (41.5%) to the unfavorable prognosis group. Synchronous metastases (Smts) and metachronous metastases (Mmts) were detected in 380 (40.7%) and 554 (59.3%) patients, respectively. The clinical and morphological characteristics of the tumor were analyzed, as well as laboratory parameters. Statistical analysis was carried out using Statistica 10.0 software («StatSoft Inc.», Tulsa, OK, USA ) by constructing Kaplan-Meyer curves and survival tables, building a mathematical survival model.Results. The 3-year and 5-year OS of Smts-patients and Mmts-patients were 40.3% and 82.5%, 18.8% and 64.3% respectively. The median OS was 25 and 88 months, respectively (p < 0.001). The 3-year and 5-year PFS rates in Mmts-patients were 60.5% and 55.7%, respectively. In Smts-patients, PFS was only 9 months, compared with a median PFS of 60 months in Mmts-patients (p < 0.001). Anemia and elevated erythrocyte sedimentation rate were observed more frequently in Smts-patients. Mmts-patients were more likely to have normal platelet and alkaline phosphatase counts. Smts-patients more often had an unfavorable prognosis according to Heng and ECOG status, a higher T stage, a low tumor differentiation, and histologically, non-clear cell carcinoma variants, the presence of lymphogenous metastases, and an increased number of organs with metastatic lesions (p < 0.001). In univariate and multivariate analyses, OS in Smts- and Mmts-patients, anemia, and poor Heng prognosis were the only statistically significant prognostic factors. In a univariate analysis of OS of Smts-patients, increases in elevated erythrocyte sedimentation platelets, and alkaline phosphatase were significant adverse prognostic factors (p < 0.001).Conclusion. Research into new prognostic factors and their combinations, focusing on the specifics of the metastatic disease itself, will improve prediction outcomes and optimize systemic treatment outcomes.

Pathological prognosis classification of patients with neuroblastoma using computational pathology analysis

Neuroblastoma is the most common extracranial solid tumor in early childhood. International Neuroblastoma Pathology Classification (INPC) is a commonly used classification system that provides clinicians with a reference for treatment stratification. However, given the complex and subjective assessment of the INPC, there will be inconsistencies in the analysis of the same patient by multiple pathologists. An automated, comprehensive and objective classification method is needed to identify different prognostic groups in patients with neuroblastoma. In this study, we collected 563 hematoxylin and eosin-stained histopathology whole-slide images from 107 patients with neuroblastoma who underwent surgical resection. We proposed a novel processing pipeline for nuclear segmentation, cell-level image feature extraction, and patient-level feature aggregation. Logistic regression model was built to classify patients with favorable histology (FH) and patients with unfavorable histology (UH). On the training/test dataset, patient-level of nucleus morphological/intensity features and age could correctly classify patients with a mean area under the receiver operating characteristic curve (AUC) of 0.946, a mean accuracy of 0.856, and a mean Matthews Correlation Coefficient (MCC) of 0.703,respectively. On the independent validation dataset, the classification model achieved a mean AUC of 0.938, a mean accuracy of 0.865 and a mean MCC of 0.630, showing good generalizability. Our results suggested that automatically derived image features could identify the differences in nuclear morphological and intensity between different prognostic groups, which could provide a reference to pathologists and facilitate the evaluation of the pathological prognosis in patients with neuroblastoma.

Eight-year survival rates by baseline prognostic groups in patients with metastatic hormone-sensitive prostate cancer (mHSPC): An analysis from the ECOG-ACRIN 3805 (CHAARTED) trial.

5081 Background: To date there is no prospective survival data beyond 5 years for patients treated with ADT with or without docetaxel (D) when analyzed by well-defined baseline prognostic risk groups and treatment arms. In this updated analysis of the CHAARTED trial, we report the 8-year survival rate based on disease volume and metachronous vs. de novo metastatic disease status with ADT without or with docetaxel. Methods: An updated survival sweep was conducted in February 2022. Patients were prospectively identified by the state of metastatic disease as metachronous (prior local therapy) vs. de novo and low volume (LV) vs. high volume (HV; visceral and/or ≥4 bone metastases with one lesion beyond the vertebral bodies or pelvis) disease. Overall survival (OS) was defined as time from randomization to death or date last known alive and calculated using the Kaplan-Meier method. Results: Of the 790 patients randomized (last patient enrolled December 2012), 238 patients were still alive with a median follow up of 9.7 years for patients still alive. Median OS in the overall population was 60.4 and 47.2 mos in the ADT+ D and ADT arms respectively (Table; HR: 0.77; 95% CI: 0.65, 0.92; p=0.004). ADT+ D was associated with significantly higher 8-yr OS rate (28.5%) compared to ADT arm (15.4%; HR: 0.67; 95% CI: 0.53, 0.84; p=0.0005) in the de novo HV group (n=421). Notably, the 8-yr OS rates were almost doubled for patients with HV disease with early docetaxel (16% vs.30.2%, p<.0001) and this was seen in patients with both de novo and metachronous HV mHSPC. Conclusions: In this long-term updated analysis, ADT+D continued to demonstrate significantly improved OS in the overall population and this is still most clearly evident in patients with de novo HV mHSPC. Our findings highlight the role of baseline prognostic risk groups in predicting longer term survival and benefits from treatment intensification. Clinical trial information: NCT00309985. [Table: see text]

Markers of tumor inflammation as prognostic factors for overall survival in patients with advanced pancreatic cancer receiving first-line FOLFIRINOX chemotherapy

Background Identifying pretreatment blood markers that distinguish prognostic groups of patients with advanced pancreatic ductal adenocarcinoma (PDAC) under first-line FOLFIRINOX chemotherapy has the potential to improve management of this condition. Aim of this study was to determine the prognostic utility of a range of pretreatment, inflammation-related, blood cell markers in this group of patients. Material and methods Data from a training cohort were analyzed to identify potential pretreatment blood markers correlating to survival outcomes. The most informative markers were further analyzed in a validation cohort comprised patients from a geographically separate cancer center undergoing the same treatment. Results A total of 138 consecutive patients receiving FOLFIRINOX chemotherapy between 2010 and 2019, constituted the training cohort. Neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte ratio (PLR) as well as the systemic inflammatory response index (SIRI) and CA19.9 showed prognostic significance in addition to tumor stage. A pretreatment SIRI score cutoff of 2.35 differentiated between a poor prognostic group with median overall survival (mOS) 5.1 months and a better prognostic group, mOS 12.5 months. SIRI ≤/> 2.35 was predictive of mOS in patients with locally advanced and metastatic PDAC. SIRI was confirmed as a prognostic marker in a validation cohort of 67 patients with mOS of 13.4 months and 6.3 months for those with SIRI ≤ 2.35 and >2.35, respectively. Additional analysis revealed baseline SIRI as being prognostic within additional subgroups of patients in both cohorts. Conclusions This large, retrospective, analysis of real-world patients receiving first-line FOLFIRINOX chemotherapy for advanced PDAC has identified the pretreatment blood SIRI as a strong prognostic marker for survival. This will allow better counseling of patients with regards to the benefits of treatment, improved stratification within clinical trials, and potentially identify groups of patients for novel therapy trials as first-line treatment.

\u201cDecision tree analysis for assessing the risk of post-traumatic haemorrhage after mild traumatic brain injury in patients on oral anticoagulant therapy\u201d

BackgroundThe presence of oral anticoagulant therapy (OAT) alone, regardless of patient condition, is an indication for CT imaging in patients with mild traumatic brain injury (MTBI). Currently, no specific clinical decision rules are available for OAT patients. The aim of the study was to identify which clinical risk factors easily identifiable at first ED evaluation may be associated with an increased risk of post-traumatic intracranial haemorrhage (ICH) in OAT patients who suffered an MTBI.MethodsThree thousand fifty-four patients in OAT with MTBI from four Italian centers were retrospectively considered. A decision tree analysis using the classification and regression tree (CART) method was conducted to evaluate both the pre- and post-traumatic clinical risk factors most associated with the presence of post-traumatic ICH after MTBI and their possible role in determining the patient’s risk. The decision tree analysis used all clinical risk factors identified at the first ED evaluation as input predictor variables.ResultsICH following MTBI was present in 9.5% of patients (290/3054). The CART model created a decision tree using 5 risk factors, post-traumatic amnesia, post-traumatic transitory loss of consciousness, greater trauma dynamic, GCS less than 15, evidence of trauma above the clavicles, capable of stratifying patients into different increasing levels of ICH risk (from 2.5 to 61.4%). The absence of concussion and neurological alteration at admission appears to significantly reduce the possible presence of ICH.ConclusionsThe machine-learning-based CART model identified distinct prognostic groups of patients with distinct outcomes according to on clinical risk factors. Decision trees can be useful as guidance in patient selection and risk stratification of patients in OAT with MTBI.

Réévaluation du score Pronopall : une étude rétrospective multicentrique

The Pronopall score, which distinguishes 3 prognostic groups in patients with advanced cancer, was initially proposed in 2008 and validated in a study published in 2018 but including patients between 2009 and 2010. Since the last decade, cancer management and therapeutic options have progressed. The objective of this study was to confirm the value of this score in patients with digestive and thoracic cancer. From July 2019 to November 2020, this retrospective multi-center study included patients with digestive or thoracic cancers who fulfilled the same inclusion criteria as those used in the initial study, and in whom the Pronopall score could be calculated using its four variables (albumin serum level, LDH level, ECOG score, number of metastatic sites). Survival curves were analyzed using the Kaplan-Meier method. One hundred patients were included. According to the Pronopall score, patients were separated into group A (score 8-10, 7 patients), group B (score 4-7, 41 patients) and group C (score 0-3, 52 patients). Median overall survival was 73 days, CI [17-129], 228 days, CI [128-328] and 575 days, CI [432-718] for groups A, B and C, respectively. Survival at 2 months was 28% for population A, 61% for population B, and 94% for population C. This study confirms that the Pronopall score still allows clinically relevant discrimination of patients, score C being associated with a good prognosis compared to scores A and B.

Decision tree analysis to predict the risk of intracranial haemorrhage after mild traumatic brain injury in patients taking DOACs.

Although the preliminary evidence seems to confirm a lower incidence of post-traumatic bleeding in patients treated with direct oral anticoagulants (DOACs) compared to those on vitamin K antagonists (VKAs), the recommended management of mild traumatic brain injury (MTBI) in patients on DOACs is the same as those on the older VKAs, risking excessive use of CT in the emergency department (ED). To determine which easily identifiable clinical risk factors at the first medical evaluation in the ED may indicate an increased risk of post-traumatic intracranial haemorrhage (ICH) in patients on DOACs with MTBI. Patients on DOACs who were evaluated in the ED for an MTBI from 2016 to 2020 at four centres in Northern Italy were considered. A decision tree analysis using the chi-square automatic interaction detection (CHAID) method was conducted to assess the risk of post-traumatic ICH after an MTBI. Known pre- and post-traumatic clinical risk factors that are easily identifiable at the first medical evaluation in the ED were used as input predictor variables. Among the 1146 patients on DOACs in this study, post-traumatic ICH was present in 6.5% (75/1146). Decision tree analysis using the CHAID method found post-traumatic TLOC, post-traumatic amnesia, major trauma dynamic, previous neurosurgery and evidence of trauma above the clavicles to be the strongest predictors associated with the presence of post-traumatic ICH in patients on DOACs. The absence of a concussion seems to indicate subgroups at very low risk of requiring neurosurgery. The machine-based CHAID model identified distinct prognostic groups of patients with distinct outcomes based on clinical factors. Decision trees can be useful as guides for patient selection and risk stratification.

Nivolumab in Non-Small Cell Lung Cancer: Real World Long-Term Survival Results and Blood-Based Efficacy Biomarkers.

ObjectivesWe aimed to examine clinical data and baseline blood test results as potential predictive biomarkers for benefit from nivolumab, in advanced non-small cell lung cancer patients (NSCLC).Materials and MethodsA chart review was performed of 108 advanced NSCLC patients who commenced treatment with nivolumab between 2015-6 at three Israeli cancer centers, and for whom laboratory tests results were available. Data collected included sex, age, ECOG-PS, histology and number of previous lines of treatment. Baseline blood test results collected: absolute lymphocyte and neutrophil count (ANC), white blood cells (WBC), hemoglobin, platelets, albumin and lactate dehydrogenase (LDH). Neutrophil to Lymphocyte Ratio and ‘derived NLR’ (dNLR = (ANC/[WBC-ANC])) were calculated. Disease control at six months (DC6) was defined as any tumor shrinkage or stable disease during the first six months of nivolumab treatment. The association between clinical/laboratory variables and survival was tested with a Cox proportional hazard model. Data cut-off occurred in November 2019.Results35 patients (32.4%) achieved DC6. Median overall survival (OS) of entire study population was 5.4 months. Four year survival rate was 16%. Achievement of DC6 strongly correlated with longer OS (HR 0.12, 95% C.I. 0.07-0.21, p<0.001). In univariate and multivariate analysis, dNLR, albumin and LDH correlated significantly with OS. No variables correlated significantly with DC6 in multivariate analysis. Based on albumin and LDH, we produced a score called CLAS (combined LDH and albumin score), including four prognostic groups of patients. Patients having low albumin and high LDH had the worst prognosis.ConclusionIn real-life setting, long-term efficacy of nivolumab in advanced line treatment of NSCLC is consistent with clinical trials. Response or stability of disease during first six months of treatment is associated with prolonged survival. We propose a novel score (CLAS) that may be useful for predicting outcome in nivolumab-treated NSCLC patients, but further validation is required.

Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial

ObjectivesTo compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years.MethodsPatients with RA completing the 2-year CareRA randomised controlled trial were eligible...

Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial

AbstractThe results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P = .044). A trend toward improved disease-free survival was also observed with midostaurin (67.3% vs 53.4%; P = .089), whereas overall survival (OS) was similar in the 2 groups. Patients with AML and NPM1mut/FLT3-TKDmut or core binding factor (CBF)–rearranged/FLT3-TKDmut genotypes had significantly prolonged OS with or without censoring at hematopoietic cell transplantation (HCT), compared with NPM1WT/CBF-negative AMLs. The multivariable model for OS and EFS adjusted for allogeneic HCT in first complete remission as a time-dependent covariable, revealed NPM1 mutations and CBF rearrangements as significant favorable factors. These data show that NPM1 mutations or CBF rearrangements identify favorable prognostic groups in patients with FLT3-TKD AMLs, independent of other factors, also in the context of midostaurin treatment.

The morphological characteristics of hippocampus and thalamus in mesial temporal lobe epilepsy

BackgroundMesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy, which is frequently characterized by hippocampal sclerosis (HS). Accumulating studies have suggested widespread cortico-cortical connections related to MTLE. The role of subcortical structures involved in general epilepsy has been extensively investigated, but it is still limited in MTLE. Our purpose was to determine the specific morphological correlation between sclerotic hippocampal and thalamic sub-regions, using quantitative analysis, in MTLE.MethodsIn this study, 23 MTLE patients with unilateral hippocampal sclerosis and 24 healthy controls were examined with three-dimensional T1 MRI. Volume quantitative analysis in the hippocampus and thalamus was conducted and group-related volumetric difference was assessed. Moreover, vertex analysis was further performed using automated software to delineate detailed morphological patterns of the hippocampus and thalamus. The correlation was used to examine whether there is a relationship between volume changes of two subcortical structures and clinical characteristics.ResultsThe patients had a significant volume decrease in the sclerotic hippocampus (p < 0.001). Compared to controls, obvious atrophic patterns were observed in the bilateral hippocampus in MTLE (p < 0.05). Only small patches of shrinkage were noted in the bilateral thalamus (p < 0.05). Moreover, the volume change of the hippocampus had a significant positive correlation with that of the thalamus (P < 0.001). Intriguingly, volume changes of the hippocampus and thalamus were correlated with the duration of epilepsy (hippocampus: P = 0.024; thalamus: P = 0.022). However, only volume changes of thalamus possibly differentiated between two prognostic groups in patients (P = 0.026).ConclusionsWe demonstrated the morphological characteristics of the hippocampus and thalamus in MTLE, providing new insights into the interrelated mechanisms between the hippocampus and thalamus, which have potential clinical significance for refining neuromodulated targets.

Analiza bolesnika s metastatskim rakom bubrega srednje i loše prognostičke skupine liječnih u Kliničkom bolničkom centru Zagreb

Analiza bolesnika s metastatskim rakom bubrega srednje i loše prognostičke skupine liječnih u Kliničkom bolničkom centru Zagreb

32 - Focused neck ultrasound and lymph node sampling by respiratory physicians can provide a rapid diagnosis in a poor prognostic patient group with suspected lung cancer

32 - Focused neck ultrasound and lymph node sampling by respiratory physicians can provide a rapid diagnosis in a poor prognostic patient group with suspected lung cancer

A Machine-Based Approach to Preoperatively Identify Patients with the Most and Least Benefit Associated withResection for Intrahepatic Cholangiocarcinoma: An International Multi-institutional Analysis of 1146 Patients.

Accurate risk stratification and patient selection is necessary to identify patients who will benefit the most from surgery or be better treated withother non-surgical treatment strategies. We sought to identify which patients in the preoperative setting would likelyderive the most or least benefit from resection of intrahepatic cholangiocarcinoma (ICC). Patients who underwent curative-intent resection for ICC between 1990 and 2017 were identified from an international multi-institutional database. A machine-based classification and regression tree (CART) was used to generate homogeneous groups of patients relative to overall survival (OS) based on preoperative factors. Among 1146 patients, CART analysis revealed tumor number and size, albumin-bilirubin (ALBI) grade and preoperative lymph node (LN) status as the strongest prognostic factors associated with OS among patients undergoing resection for ICC. In turn, four groups of patients with distinct outcomes were generated through machine learning: Group 1 (n = 228): single ICC, size ≤ 5cm, ALBI grade I, negative preoperative LN status; Group 2 (n = 708): (1) single tumor > 5cm, (2) single tumor ≤ 5cm, ALBI grade 2/3, and (3) single tumor ≤ 5cm, ALBI grade 1, metastatic/suspicious LNs; Group 3 (n = 150): 2-3 tumors; Group 4 (n = 60): ≥ 4 tumors. 5-year OS among Group 1, 2, 3, and 4 patients was 60.5%, 35.8%, 27.5%, and 3.8%, respectively (p < 0.001). Similarly, 5-year disease-free survival (DFS) among Group 1, 2, 3, and 4 patients was 47%, 27.2%, 6.8%, and 0%, respectively (p < 0.001). The machine-based CART model identified distinct prognostic groups of patients with distinct outcomes based on preoperative factors. Survival decision trees may be useful as guides in preoperative patient selection and risk stratification.

Update on HPV-associated head and neck cancer-highlights from the 2019 ASCO Annual Meeting

At this year's Annual Meeting of the American Society for Clinical Oncology (ASCO), the keyword search "HPV-associated head and neck cancer" resulted in 920 hits-74% of the hits on human papillomavirus (HPV). This underlines the relevance of the topic. The spectrum ranged from validation and separation of the prognostic groups of patients with HPV-associated oropharyngeal carcinoma (OPSCC) according to TNM8, to the characterization of new tumor markers and tumor mutational burden for possible de-escalation strategies to avoid toxicity of standard multimodal treatments. It has been shown that the separation of p16-positive OPSCC into Union for International Cancer Control (UICC) stagesI andII with the current TNM8 classification without further markers is not sufficiently successful to justify de-escalation strategies. Following publication of the results of the De-ESCALaTE- and RTOG-1016 trials in 2018, which confirm the current standard of care for p16-positive OPSCC, no further phaseIII studies on de-escalation were presented. In apresented prospective phaseII study (NCT02281955), the radiotherapy dose was reduced to cumulative 60 Gy, whereby the simultaneous chemotherapy regimen with cisplatin 30 mg/m2 weekly is not standard of care and could be administered as an alternative to cisplatin cetuximab. Some work dealt with the oral and intestinal microbiota as prognostic markers or their treatment-related changes, particularly under immunotherapy. Modification seems to have apositive impact on the success of therapy. However, robust data are still lacking for the various modified treatments for HPV-associated OPSCC, which are needed before their implementation in daily practice.

Promoter Hypermethylation of Genes Encoding for RASSF/Hippo Pathway Members Reveals Specific Alteration Pattern in Diffuse Gliomas

Ras association domain family (RASSF)/Hippo pathway alterations are poorly characterized in diffuse gliomas. We assayed promoter methylation of LATS1/2, MST1(STK4)/MST2(STK3), RASSF1, RASSF2, Nore1A/RASSF5, RASSF6, and RASSF10 genes in 133 diffuse gliomas. The RASSF/Hippo pathway was highly silenced in gliomas, particularly RASSF1A (79.4%) and LATS2 (35.9%). The most frequent combination of promoter hypermethylation of one RASSF gene and one Hippo pathway member's gene was RASSF1/LATS2-coupled hypermethylation [n = 44 (33.08%)]. Hypermethylated profiles were related to IDH mutation, yet not randomly in IDH-mutated gliomas, because LATS2 promoter hypermethylation was more frequent in oligodendroglioma than in astrocytoma. RASSF1 and LATS2 promoter hypermethylation predicted a longer overall survival (OS). Considering hypermethylation of these two promoters, Cox proportional hazard regression analysis categorized the patients into three prognostic groups: i) high risk of death (n = 24; both RASSF1 and LATS2 unmethylated promoters; median OS, 13 months); ii) intermediate risk of death (n= 65; RASSF1 or LATS2 hypermethylated promoter; median OS, 50.5 months; HR=3.3; 95% CI, 1.6-6.4; P=0.001); and iii) low risk of death (n= 44; both RASSF1 and LATS2 hypermethylated promoters; median OS, 119 months; HR=75.1; 95% CI, 3.3-15.1; P=0.001). We have thus highlighted a simple two-gene (RASSF1/LATS2) methylation signature as a tool to stratify different prognostic groups of patients with diffuse glioma, adding further prognostic information within the IDH-mutated group.

PO-485 Low abundance circulating proteins in giant cell tumours of bone

IntroductionCirculating low-abundance proteins/fragments generating from tumour cells and tissues, represent the most important source of cancer biomarkers useful for early diagnosis and prognosis. Giant cell tumour of bone (GCT) is a benign neoplasm occurring in the long bone and in the axial skeleton of young adults. Approximately 5% of GCT develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict metastasis with a non invasive method.Material and methodsThe hydrogel nanoparticles technique followed by mass spectrometry was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in 10 healthy sera used as control. The most representative low-abundant de novo or differentially abundant proteins were submitted to String database in order to define protein-protein interaction network. Cluster analysis was performed to identify prognostic groups of patients with similar abundance of proteins that significantly discriminate between the groups.Results and discussionsFor the 25 low-abundant de novo or differentially abundant proteins identified, we recognised that the top interconnected pathways included protein activation cascade, wound healing, blood coagulation, cell-substrate adhesion. Proteoma cluster analysis separated metastasis-free from metastatic GCT patients in two well-defined groups where serum levels of signalling transduction mediators and regulators of kinase activity presented a high discriminatory power. Increased expression of proteins STAT5B, GRB2 and OXSR1 was related to a higher probability of metastasis.ConclusionIn conclusion, using a no invasive technique, we identified differentially abundant serum biomarkers, also providing prognostic information in patients with GCT of bone. Future studies are ongoing to establish the interplay between these biomarkers in order to fully understand the mechanism involved in tumour development and to focus on the planning of tailored therapies that should be more effective and less toxic.