Predictors Of Better Overall Survival Research Articles

Predictive value of red blood cell distribution width level on histological response and prognosis in colorectal liver metastases.

The red blood cell distribution width (RDW) level is a potential prognostic factor for solid tumours. We aimed to investigate the predictive value of pre-neoadjuvant chemotherapy (pre-NAC) RDW, preoperative RDW and the change in RDW on the pathological response and prognosis of patients with colorectal liver metastasis (CRLM), which was helpful for treatment decision-making, surveillance and prognostication. This retrospective study analyzed clinicopathologic data, treatments and outcomes of 150 CRLM patients treated with NAC followed by liver resection at our hospital. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The secondary outcome was postoperative major complications. The RDW level was presented as the RDW-SD level and the RDW-CV level. The optimal cut-off of RDW level was determined by X-tile analysis. The change in RDW was scored as 0 (decreased pre-NAC RDW and decreased preoperative RDW), 2 (elevated pre-NAC RDW and elevated preoperative RDW), or 1 (all other combinations). Multivariable logistic regression analysis was performed to determine the relationships between the tumour characteristics and pathological response and the postoperative major complications. A multivariate Cox proportional hazards model was used to evaluate the prognostic factors associated with survival. The optimal cut-off values of the RDW-CV and RDW-SD levels for survival were 13.5% and 42.2 fl, respectively. The multivariate analysis showed that a preoperative RDW-CV ≥13.5% (OR =3.215, 95% CI: 1.299-7.958, P=0.012) significantly predicted a favorable pathological response. The multivariate analysis revealed that a pre-NAC RDW-CV ≥13.5% (OR =2.462, 95% CI: 1.080-5.615, P=0.032) significantly predicted postoperative major complications. In the multivariate analysis, an RDW-CV change =2 (HR =0.487, 95% CI: 0.309-0.768, P=0.002) was a significant predictor of better PFS. The multivariate analysis also revealed that an RDW-SD change =2 (HR =0.532, 95% CI: 0.332-0.854, P=0.009) were an independent predictor of better OS. This study revealed that pre-NAC RDW, preoperative RDW and RDW changes may be reliable markers that could predict a pathological response and prognosis in CRLM patients receiving NAC followed by liver resection.

Clinical Outcomes of Salvage Endoscopic Nasopharyngectomy for Patients With Advanced Recurrent Nasopharyngeal Carcinoma.

BackgroundSalvage endoscopic nasopharyngectomy has better survival prognosis and fewer complications in the management of early stage rNPC, compared to re-irradiation. However, the treatment modality of advanced recurrent nasopharyngeal carcinoma (rNPC) remains controversial. Thus, the purpose of this study was to investigate the demographics, clinical outcomes, and prognostic factors associated with salvage endoscopic nasopharyngectomy in advanced rNPC.MethodsThis study conducted a retrospective analysis of advanced rNPC patients who underwent salvage surgery betweenm January 2014 and December 2019. The overall survival (OS) and progression-free survival (PFS) were analyzed. Univariable and multivariable analyses of OS and PFS were performed using the Cox regression model. The predicted values of the parameters were determined by means of the receiver operating characteristic (ROC) curve analysis.ResultsAmong the 120 patients included, there were 75 patients with rT3 stage and 45 patients with rT4 stage. With the median follow-up time of 18 months,the 3 -year OS and PFS were 55.2% and 29.4%, respectively. Multivariate analyses showed that the rNPC patients with older age, low BMI (Body Mass Index), rT4 stage, tumor necrosis, and tumor invasion into the ICA was predictive of worse OS, whereas low BMI and rT4 stage were associated with worse PFS. In addition, the rT stage was identified as a better predictor of OS (area under the ROC curve: 0.669; P=0.003) than the other clinical features.ConclusionsSalvage treatment using endoscopic nasopharyngectomy appears to be an effective treatment in the management of patients with advanced rNPC. In addition, case matching studies and prospective studies with larger clinical samples are required to further evaluate the efficacy of endoscopic surgery compared with re-irradiation in advanced rNPC.

Myelodysplastic Syndromes/Myeloproliferative Neoplasms Treated with 5-Azacytidine. Results from the Hellenic 5-Azacytidine Registry

IntroductionMyelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) comprise a distinct category of hematologic diseases according to the 2008 WHO classification. The treatment of MDS/MPN remains challenging due to lack of large clinical trials evaluating this group of disorders, since they are usually grouped with MDS. Supportive treatment with blood transfusions and erythropoietin are often used due to lack of efficacy of most therapies. Hypomethylating agents have been approved for the treatment of CMML and are widely used in the treatment of the remaining types of MDS/MPN.AimThis retrospective study aims to analyze the survival, prognostic characteristics, and treatment response to 5-azacytidine in patients with MDS/MPN included in the Hellenic 5-azacytidine registry.Patients and MethodsAdult patients diagnosed with MDS/MPN treated with 5-azacytidine were included in the study. Demographic, clinical, hematological and treatment data were collected through the Hellenic 5-azacytidine registry and analyzed with IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA).ResultsNinety-two (92) patients with MDS/MPN were included in the study. The main characteristics of the patients are shown in the table of Figure 1A.The cytogenetic analysis at diagnosis showed that 56 (69.1%) patients had a normal karyotype, while only 1 (1.1%) had a complex karyotype. The more common isolated chromosomal aberration was trisomy of chromosome 8 (9 patients (11.1%) - 7 patients with CMML and 2 patients with MDS/MP-U), followed by chromosome 7 monosomy (2 patients with CMML1, 2.5%) and loss of the Y chromosome (2 patients (2.5%), 1 with CMML1 and 1 with MDS/MPN-U).All patients were treated with 5-azacytidine (89.1% with a regimen of 75 mg/m² SC/IV per day for 7 days every 4 weeks and 10.9% with 75 mg/m2 SC/IV per day for 5+2 days every 4 weeks). Twenty-one patients (11 with CMML1, 7 with CMML2, and 3 with MDS/MPN-U) had been previously treated with chemotherapeutic regimens. Response to 5-azacytidine was as follows: Failure, 25 (27.8%) patients; stable disease, 23 (25.6%); partial response, 5 (5.6%); complete response, 16 (17.6%); hematologic improvement, 21 (23.3%).The median follow-up of the patients was 19.3 months and the overall survival (OS) of the group was 26.0 months (95%CI: 14.4-37.6). OS differed significantly among the different types of MDS/MPN (Figure 1B). IPSS-R was a good predictor of OS (Log Rank (Mantel-Cox), p<0.0001). Patients with high serum ferritin levels at diagnosis (over 375 ng/dL that was the median value for the cohort) had a median OS of 22.0 months, while patients with low ferritin levels had a median overall survival of 58.2 months (Log Rank (Mantel-Cox), 0.002). Higher IPSS-R score, presence of peripheral blood blasts and high serum ferritin levels retained their prognostic significance in multivariate analysis, while hemoglobin below 9.9 g/dL (median value for the group) lost its predictive value in multivariate analysis. The age of the patients at diagnosis and the karyotype risk were not predictive of OS. Moreover, OS of patients with chromosome 8 trisomy did not differ from that of patients with a normal karyotype or other chromosomal abnormalities. None of the above-mentioned factors were predictive of response to 5-azacytidine.DiscussionThis is, to our knowledge, the largest retrospective series of patients with MDS/MPN treated with 5-azacytidine. The following are the main conclusions derived from the analysis of this cohort's data. Patients with MDS/MPN-U have a significantly lower OS in comparison to patients with CMML1/2; a favorable response to 5-azacytidine (PR, CR, HI) is achieved in about 45% of the patients (about one fourth of them had already been previously treated); high IPSS-R scores, presence of peripheral blood blasts and high serum ferritin levels are independent predictors of a low OS, while in our cohort, age at diagnosis, hemoglobin levels and karyotype risk could not predict prognosis. The median OS of our group is comparable to that of other recent studies. Our study supports the use of 5-azacytidine in patients with MDS/MPN, who can benefit from an effective treatment with less toxicity than classic chemotherapeutic regimens, that in younger patients may serve as a bridge to allogeneic bone marrow transplant. The clinical significance of serum ferritin levels is highlighted and should be further investigated. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Worse prognosis for IDH wild-type diffuse gliomas with larger residual biological tumor burden.

The association of overall survival (OS) with tumor burden, including contrast enhanced (CE) volume on CE T1-weighted images, fluid-attenuated inversion recovery (FLAIR) hyperintense volume, and 3, 4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) hypermetabolic volume, in isocitrate dehydrogenase (IDH) wild-type gliomas remains unclear. This study aimed to assess the association between biological tumor burden in pre- and post-operative status and OS in IDH wild-type gliomas, and evaluated which volume was the best predictor of OS. Thirty-four patients with treatment-naïve IDH wild-type gliomas (WHO grade II 6, III 15, IV 13) were retrospectively included. Three pre-operative tumor regions of interest (ROIs) were segmented based on the CE, FLAIR hyperintense, and FDOPA hypermetabolic regions. Resected ROIs were segmented from the post-operative images. Residual CE, FLAIR hyperintense, and FDOPA hypermetabolic ROIs were created by subtracting resected ROIs from pre-operative ROIs. Cox regression analysis was conducted to investigate the association of OS with the volume of each ROI, and Akaike information criterion was used to assess the fitness. Residual CE volume had a significant association with OS [hazard ratio (HR) = 1.26, p = 0.039], but this effect disappeared when controlling for tumor grade. Residual FDOPA hypermetabolic volume best fit the regression model and was significantly associated with OS (HR = 1.18, p = 0.008), even when controlling for tumor grade. FLAIR hyperintense volume showed no significant association with OS. Residual FDOPA hypermetabolic burden predicted OS for IDH wild-type gliomas, regardless of the tumor grade. Furthermore, removing hypermetabolic and CE regions may improve the prognosis.

Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models

BackgroundThe effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients.MethodsA retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed.Results A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival.ConclusionsWe demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.

Tumor growth inhibition modeling of individual lesion dynamics and interorgan variability in HER2-negative breast cancer patients treated with docetaxel.

Information on individual lesion dynamics and organ location are often ignored in pharmacometric modeling analyses of tumor response. Typically, the sum of their longest diameters is utilized. Herein, a tumor growth inhibition model was developed for describing the individual lesion time‐course data from 183 patients with metastatic HER2‐negative breast cancer receiving docetaxel. The interindividual variability (IIV), interlesion variability (ILV), and interorgan variability of parameters describing the lesion time‐courses were evaluated. Additionally, a model describing the probability of new lesion appearance and a time‐to‐event model for overall survival (OS), were developed. Before treatment initiation, the lesions were largest in the soft tissues and smallest in the lungs, and associated with a significant IIV and ILV. The tumor growth rate was 2.6 times higher in the breasts and liver, compared with other metastatic sites. The docetaxel drug effect in the liver, breasts, and soft tissues was greater than or equal to 1.2 times higher compared with other organs. The time‐course of the largest lesion, the presence of at least 3 liver lesions, and the time since study enrollment, increased the probability of new lesion appearance. New lesion appearance, along with the time to growth and time‐course of the largest lesion at baseline, were identified as the best predictors of OS. This tumor modeling approach, incorporating individual lesion dynamics, provided a more complete understanding of heterogeneity in tumor growth and drug effect in different organs. Thus, there may be potential to tailor treatments based on lesion location, lesion size, and early lesion response to provide better clinical outcomes.

Prognostic value and association of sarcopenic obesity and systemic inflammatory indexes in patients with hepatocellular carcinoma following hepatectomy and the establishment of novel predictive nomograms.

The specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction. We retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS. SO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte-monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001). Both SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.

Complete remission of metastatic osteosarcoma using combined modality therapy: a retrospective analysis of unselected patients in China

BackgroundComplete surgical remission (CSR) is the best predictor of overall survival (OS) for patients with metastatic osteosarcoma. However, metastasectomy has not been widely implemented in China in the last decade due to various factors, and instead, most physicians choose hypofractionated radiotherapy to treat pulmonary lesions. This study aimed to retrospectively evaluate the outcomes of different local treatments for pulmonary lesions and identify the best local therapy strategies for these patients.MethodsWe reviewed the clinical courses of osteosarcoma patients with pulmonary metastases who were initially treated in two sarcoma centres in Beijing, China, from June 1st, 2009, to March 26th, 2020. With a median follow-up of 32.4 (95% confidence interval (CI): 30.8, 36.1) months, a total of 127 patients with 605 pulmonary nodules, all of whom had received local therapy and firstly achieved CSR or complete radiated/metabolic remission (CRR), were included in the analysis. A total of 102 patients with 525 nodules were initially diagnosed with resectable lung metastases, while 25 patients had 80 indeterminate nodules at presentation and relapsed with pulmonary metastases within 6 months after the completion of adjuvant chemotherapy.ResultsEighty-eight of 127 (69.3%) patients had fewer than 5 nodules at the time of local therapy, with 48 of 127 (37.8%) located in the unilateral pleura. No patient underwent thoracotomy, and 42 of 127 patients (85 nodules) received video-assisted thoracoscopic surgery (VATS). In addition, 79 of 127 patients (520 nodules) received hypofractionated stereotactic body radiotherapy (RT), such as Gamma Knife radiosurgery or CyberKnife radiosurgery. The twelve-month event-free survival (EFS) (from local therapy to progression) rate of this entire study cohort was 35.6% (95% CI: 26.8, 44.4%), without a significant difference between the two groups (44.7% for VATS vs. 28.4% for RT, P = 0.755). Radiation-induced pneumonitis was observed in 62 of 86 (72.1%) patients, with one patient (1/86, 1.2%) in grade 4.ConclusionsOur past data showed a similar prognosis with the use of hypofractionated radiotherapy and VATS for the treatment of pulmonary metastasis and no inferiority to thoracotomy regarding historical outcomes. Currently, high-resolution chest computed tomography (CT) provides sufficient information on nodules, and less invasive modalities can thus be considered for treatment.

Detection of human papillomavirus infection in laryngeal and hypopharyngeal carcinoma using droplet digital PCR and its correlation with prognosis

ABSTRACT Objective To use droplet digital polymerase chain reaction (ddPCR) to detect human papillomavirus (HPV) infection in squamous cell carcinoma of the larynx and hypopharynx (SCCLHP) and to analyze its association with the prognosis of patients with HPV. Methods We used ddPCR for HPV detection in 114 patients with SCCLHP; clinical data were collected, and the patients were followed-up for prognosis analysis. Univariate and multivariate Cox regression analyses were used to complete the analysis of risk factors. This clinical study was registered (clinical trial registration no. ChiCTR2000033032). Result Of the total cases, 15.79% (18/114) were HPV-positive and 8 (8/18, 44.4%) patients had tumors with HPV-16. There was a significant correlation between HPV-16 and the T classification and Tumor-Node-Metastasis (TNM) (P = 0.025 and 0.036, respectively). The 3-year overall survival rates in the HPV-positive and HPV-negative patients were 39.8% and 48.6% (P = 0.776), respectively. In the univariate analysis, HPV infection was not associated with the relative risk of progression (hazard ratio [HR] = 1.109, P = 0.778). Patients with laryngeal carcinoma (HR = 1.805, P = 0.037), no alcohol consumption (HR = 0.430, P = 0.009), well-differentiated tumors (HR = 2.570, p = 0.006), TNM I–II (HR = 2.482, P = 0.003), and no lymph node metastasis (HR = 2.615, P = 0.001) had better prognoses. In the multivariate analysis, tumor location (HR = 3.044, P = 0.001), alcohol consumption (HR = 0.474, P = 0.022), tumor differentiation (HR = 2.131, P = 0.030), and lymph node metastasis (HR = 4.179, P < 0.001) were independent predictors of better overall survival in SCCLHP. Conclusion ddPCR is an advanced technology that can accurately diagnose HPV infection with high specificity and sensitivity. The HPV infection rate in SCCLHP was low, and there was no significant difference in the prognosis of SCCLHP.

In Comparison to PSA, Interim Ga-68-PSMA PET/CT Response Evaluation Based on Modified RECIST 1.1 After 2nd Cycle Is Better Predictor of Overall Survival of Prostate Cancer Patients Treated With 177Lu-PSMA.

BackgroundProstate-specific membrane antigen (PSMA) targeting radioligands have transformed treatment of prostate cancer. Radioligand therapy (RLT) with 177Lu-PSMA in metastasized castration resistant prostate cancer (mCRPC) achieves objective response and disease stabilization in roughly two third of patients, whereas one third of patients progress. This study was performed to assess the role of interim PSMA PET/CT after the 2nd cycle of RLT for early prediction of overall survival in patients undergoing RLT with 177Lu-PSMA.Methods38 mCRPC patients (68.9 ± 8.1 y) treated with at least two cycles of RLT at 8 week intervals and interim 68Ga-PSMA PET/CT (PET) at 8–10 weeks after the 2nd cycle of RLT were included in this study. Prostate-specific antigen (PSA) response was evaluated according to the Prostate Cancer Working Group 3 criteria. Radiographic response assessment of soft tissue, lymph node, and bone lesions was performed according to RECIST 1.1 including the PET component. Patients’ data were collected for follow-up from the local Comprehensive Cancer Center Register.ResultsMedian follow-up was 19.7 months (4.7–45.3). PSA response after the 2nd therapy cycle showed partial remission (PR) in 23.7%, stable disease (SD) in 50%, and progressive disease (PD) in 26.3% of patients. In comparison, 52.6, 23.7, and 23.7% of patients showed PR, SD, and PD respectively on PET/CT. The strength of agreement between PSA response and PET/CT response criteria was only fair (kappa 0.346). Median overall survival (OS) was 22.5 months (95% CI: 15.8–29.2). Median OS stratified to PSA/PET response was 25.6/25.6 months for PR, 21.7/30.6 months for SD and 19.4/13.1 months for PD (p = 0.496 for PSA and 0.013 for PET/CT response).ConclusionsInterim PSMA PET/CT based response evaluation at 8–10 weeks after the 2nd cycle of RLT is predictive of overall survival and PD in patients treated with 177Lu-PSMA. On the contrary, PSA appears to have only limited predictive value.

Impact of Palliative Gastrectomy in Patients with Incurable Gastric Cancer

Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.

Tumor Shrinkage as a Prognostic Factor of Metastatic Renal Cell Carcinoma in the Era of Molecular Targeted Therapy

We evaluated the impact of tumor shrinkage (TS) induced by molecular targeted therapy as the first-line systemic therapy on the survival of patients with metastatic renal cell carcinoma (mRCC). A total of 67 patients with mRCC who received first-line molecular targeted therapy were included in this study. Sixty patients were evaluable by response evaluation criteria in solid tumors. Patients underwent the first evaluation at 8-12 weeks after the start of the therapy. Twenty patients had TS ≧30%, 32 from 30% to -20%, and 8 ≦-20%. The median overall survival periods of patients who achieved TS ≧30%, from 30% to -20%, and ≦-20% at first evaluation were 41.0, 35.0, and 11.5 months, respectively. Univariate and multivariate analyses showed that TS of≧0%, in addition to negative C-reactive protein and the absence of bone metastasis were good predictors of overall survival. The patients who achieved 0% or more at the initial evaluation had longer survival than those who had no tumor reduction (40.0 months vs 12.0 months, p<0. 001). These findings suggest that early TS affects overall survival in real practice. We should consider alternative therapies for patients who have not achieved tumor reduction at the initial evaluation.

Identification of a four-gene panel predicting overall survival for lung adenocarcinoma

BackgroundLung cancer is the most frequently diagnosed carcinoma and the leading cause of cancer-related mortality. Although molecular targeted therapy and immunotherapy have made great progress, the overall survival (OS) is still poor due to a lack of accurate and available prognostic biomarkers. Therefore, in this study we aimed to establish a multiple-gene panel predicting OS for lung adenocarcinoma.MethodsWe obtained the mRNA expression and clinical data of lung adenocarcinoma (LUAD) from TCGA database for further integrated bioinformatic analysis. Lasso regression and Cox regression were performed to establish a prognosis model based on a multi-gene panel. A nomogram based on this model was constructed. The receiver operating characteristic (ROC) curve and the Kaplan–Meier curve were used to assess the predicted capacity of the model. The prognosis value of the multi-gene panel was further validated in TCGA-LUAD patients with EGFR, KRAS and TP53 mutation and a dataset from GEO. Gene set enrichment analysis (GSEA) was performed to explore potential biological mechanisms of a novel prognostic gene signature.ResultsA four-gene panel (including DKK1, GNG7, LDHA, MELTF) was established for LUAD prognostic indicator. The ROC curve revealed good predicted performance in both test cohort (AUC = 0.740) and validation cohort (AUC = 0.752). Each patient was calculated a risk score according to the model based on the four-gene panel. The results showed that the risk score was an independent prognostic factor, and the high-risk group had a worse OS compared with the low-risk group. The nomogram based on this model showed good prediction performance. The four-gene panel was still good predictors for OS in LUAD patients with TP53 and KRAS mutations. GSEA revealed that the four genes may be significantly related to the metabolism of genetic material, especially the regulation of cell cycle pathway.ConclusionOur study proposed a novel four-gene panel to predict the OS of LUAD, which may contribute to predicting prognosis accurately and making the clinical decisions of individual therapy for LUAD patients.

Predictive Factors and Outcomes for Ibrutinib Therapy in Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study

Predictive Factors and Outcomes for Ibrutinib Therapy in Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter Cohort Study

P101 - Albumin lymphocyte index is a better predictor of overall survival than neutrophil lymphocyte ratio in bladder cancer patients treated by radical radiotherapy

P101 - Albumin lymphocyte index is a better predictor of overall survival than neutrophil lymphocyte ratio in bladder cancer patients treated by radical radiotherapy

The influence of subventricular zone involvement in extent of resection and tumor growth pattern of glioblastoma.

Objectives Isocitrate dehydrogenase (IDH1/2) mutations and O6-alkylguanine DNA methyltransferase (MGMT) promoter methylations are acknowledged survival predictors in patients with glioblastoma (GB). Moreover, tumor growth patterns like multifocality and subventricular zone (SVZ) involvement seem to be associated with poorer outcomes. Here, we wanted to evaluate the influence of the SVZ involvement and the multifocal tumor growth on the extent of surgical resection and its correlation with overall survival (OS) and molecular characteristics of patients with GB.MethodsAdult patients with primary GB who underwent surgery at our department between 2012 and 2014 were included. Preoperative magnetic resonance imaging findings were analyzed with regard to tumor location, presence of multifocality and SVZ involvement. The extent of surgical resection as well as clinical and molecular parameters was collected from electronic patient records. Univariate and multivariate analyses were performed.ResultsTwo hundred eight patients were retrospectively analyzed, comprising 90 (43.3%) female individuals with a mean age of 62.9 (±12.26) years and OS of 10.2 months (±8.9). Unifocal tumor location was a predictor for better OS with a mean of 11.4 (±9.4) months (vs. 8.0 [±7.4] months, p=0.008). Affection of the SVZ was also associated with lower surgical resection rates (p<0.001). SVZ involvement revealed with 7.8 (±7.0) months a significant worse OS [vs. 13.9 (±10.1) months, p<0.001]. All six IDH1/2 wildtype tumors showed an unifocal location (p=0.066). MGMT promoter methylation was not associated with multifocal tumor growth (p=0.649) or SVZ involvement (p=0.348). Multivariate analysis confirmed independent association between the SVZ involvement and OS (p=0.001).ConclusionThe involvement of the SVZ appears to have an influence on a lower resection rate of GB. This negative impact of SVZ on GB outcome might be related to lesser extent of resection, higher rates of multifocality and greater surgical morbidity but not inevitably to IDH1/2 mutation and MGMT promoter methylation status.

Multidisciplinary Approach in Improving Survival Outcome of Early-Stage Gastric Cancer

BackgroundThe necessity of extensive lymph node (LN) dissection/examination and adjuvant therapy for patients with early gastric cancer (EGC, Tis-T1, any N) remains controversial. We aim to refine treatment recommendations for patients with EGC through a reflective analysis for the survival gap between Eastern and Western countries. MethodsEGC patients diagnosed between 2004 and 2014 were identified from the National Cancer Database (NCDB) and a large medical center in China. Adequate LN yield was defined as ≥25 LNs examined. ResultsIn the US cohort, 14.4% of (1104/7641) patients with EGC had ≥25 LNs examined. The 5-y overall survival (OS) was significantly better than those with <25 LNs (78.9% versus 68.5%, P < 0.001). Examination of ≥25 LNs was an independent predictor of better OS after adjusting all known prognostic factors. Patients with ≥25 LNs examined had significantly higher chance of having LN-positive disease compared to patients with <25 LNs (14.9% versus 10.7%, P < 0.001). A similar stage migration phenomenon was observed in Chinese cohort (LN positive: 25.2% versus 18.4% in ≥25 LNs and <25 LNs examined group, respectively, P = 0.02). In the US cohort, adjuvant therapy was associated with a significant survival benefit for LN-positive patients (5-y OS: 71.0% versus 43.0% for with/without adjuvant therapy, respectively, P < 0.001) but not in LN-negative patients (5-y OS: 71.2% versus 71.5%, P = 0.90). ConclusionsAdequate lymphadenectomy and LN examination are critical components of EGC management. Adjuvant therapy should be strongly encouraged for all EGC patients with LN-positive disease in the United States.

Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial.

e16001 Background: The FRESCO phase 3 trial demonstrated a significant survival benefit with fruquintinib vs. placebo in the third-line or later therapy of mCRC patients. CEA levels are widely used in conjunction with imaging to monitor response to systemic therapy in patients with mCRC. Herein, we undertook post-hoc analyses of FRESCO patient data to investigate the early changes in CEA during treatment, as well as potential relationships with efficacy parameters. Methods: Patients were included if baseline CEA was abnormal according to local lab reference range. Serum CEA levels were measured at baseline and Day 1 of each cycle (except for Cycle 1). Early CEA change was analyzed at first radiological evaluation (C3D1, Week 8), CEA response was defined as ≥ 50% decrease from baseline, and CEA progression was defined as ≥ 100% increase from baseline. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated through Cox proportional hazards model; p-value was generated from log rank test. Results: 88.4% (245/277) and 94.9% (130/137) of patients had an abnormal baseline CEA in the fruquintinib group and placebo group, respectively. Median baseline CEA values were similar between treatment groups. After 2 cycles of treatment, the proportion of patients had CEA response was significantly higher in the fruquintinib group than placebo group (30.0% vs. 1.3%, p &lt; 0.001). In the fruquintinib group, patients with early CEA response (n = 63) had longer median OS (12.8 vs. 7.8 months, HR = 0.45, p &lt; 0.001) and median PFS (5.6 vs. 3.7 months, HR = 0.49, p &lt; 0.001) than patients without (n = 147). 66.7% (140/210) of patients in fruquintinib group had stable disease (SD), and fruquintinib in those patients with concomitant CEA response exhibited a significantly greater OS benefit than with CEA progression (14.4 vs. 8.7 months, HR = 0.38, p = 0.004). Conclusions: Fruquintinib increased early CEA response. CEA response at first radiological evaluation after cycle 2 could be considered as a predictor for better OS and PFS. Among patients with SD at first evaluation, those with CEA response seems benefit more from fruquintinib. Clinical trial information: NCT02314819 .

Comparisons of Clinical Outcomes in Women with Advanced Ovarian Cancer Treated with Frontline Intraperitoneal versus Dose-Dense Platinum/Paclitaxel Chemotherapy without Bevacizumab.

Background: We aimed to compare the clinical outcomes between intraperitoneal chemotherapy and dose-dense chemotherapy for the frontline treatment of advanced ovarian, fallopian tube and primary peritoneal cancer in women not receiving bevacizumab. Methods: All consecutive women with stage II~IV cancer treated with either frontline intraperitoneal or dose-dense platinum/paclitaxel chemotherapy and not receiving bevacizumab between March 2006 and June 2019 were reviewed. Results: A total of 50 women (intraperitoneal group, n = 22; dose-dense group, n = 28) were reviewed. Median progression-free survival (32.6 months versus 14.2 months; adjusted hazard ratio = 0.38; 95% CI = 0.16 to 0.90, p = 0.03) and overall survival (not reached versus 30.7 months; adjusted hazard ratio = 0.23, 95% CI = 0.07 to 0.79, p = 0.02) were significantly higher in the intraperitoneal group than in the dose-dense group. A multivariable Cox proportional-hazards model also indicated that the number of frontline chemotherapy cycles (adjusted hazard ratio = 0.66, 95% CI 0.47 to 0.94, p = 0.02) was a predictor of better overall survival. Nausea/vomiting and nephrotoxicity occurred more frequently in the intraperitoneal group (p = 0.02 and <0.0001, respectively). Conclusions: Intraperitoneal chemotherapy seems to be superior in progression free survival and overall survival to dose-dense chemotherapy in the frontline treatment of women with optimally resected advanced ovarian, fallopian tube or primary peritoneal cancer and not receiving bevacizumab.

Sorafenib vs. Lenvatinib as First-line Therapy for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis.

We aimed to compare the outcomes between sorafenib and lenvatinib as first-line therapy for advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (Vp3/4). This retrospective study enrolled 41 HCC patients with Vp3/4 and Child-Pugh A. The outcomes in the lenvatinib group (n=13) were significantly better than those in the sorafenib group (n=28) [best objective response rate according to the modified Response Evaluation Criteria in Solid Tumors: 53.8% vs. 14.3%; p=0.0193, best disease control rate: 92.3% vs. 35.7%; p=0.0008, median overall survival (OS): not reached vs. 187 days; p=0.0040, respectively]. Lenvatinib treatment was the only significant predictor of better OS and time to tumor progression. No patient needed to discontinue lenvatinib treatment due to drug-related adverse events. Compared with sorafenib, lenvatinib treatment for advanced HCC with Vp3/4 may lead to more favorable outcomes.