Additional Independent Prognostic Factors Research Articles

Influence of stage and age on survival of patients with vulvar cancer in Germany: a retrospective study

ObjectivesTo evaluate the 5-year survival rate of patients with vulvar cancer, taking into account prognostic factors (International Federation of Gynecology and Obstetrics (FIGO) stage and age) and the influence of...

Analysis of survival rates and evaluation of prognostic factors in patients with lung metastases from renal cell carcinoma

In patients with lung metastases from renal cell cancer (RCC), it is necessary to search for new prognostic factors influencing survival rates. Aim: To analyze survival rates and identify prognostic factors in patients with lung metastases from RCC. Material and methods. We retrospectively analyzed the data from 655 patients with lung metastases from RCC, who were treated at Moscow city oncology Hospital No. 62 (Moscow) and city clinical oncology center (Saint Petersburg) from 2006 to 2022. Of these patients, 241 (36.8 %) were classified into the intermediate prognosis group, and 278 (42.2 %) into the unfavorable prognosis group. The study investigated clinical and morphologic prognostic factors influencing survival rates in patients with lung metastases from RCC. Statistical analysis was performed using Statistica 10.0 software packages (StatSoft, USA) by constructing Kaplan-Meier curves and survival tables, building a mathematical model of survival. Results. The 3- and 5-year OS rates in patients with lung metastases from RCC (N=655) were 48 % [95 % ci 45–53 %] and 27 % [95 % ci 23–31 %], respectively, with a median OS of 34.9 months [95 % ci 30.4–37.4]. in univariate analysis, ECOG status (p<0.001), histological subtype (p<0.001), Fuhrman grade of tumor differentiation (p<0.001), type and number of metastases (p<0.001), metastases to the bones and liver (p<0.001), lymph nodes (p=0.001), prognosis according to IMDC(p<0.001), nephrectomy and metastasectomy (p<0.001) had a negative impact on OS in patients with lung metastases from RCC. In multivariate analysis, ECOG status 3.66 (2.10–6.39, p<0.001), histological subtype 1.49 (1.10–2.01, p=0.009), grade of tumor differentiation according to Fuhrman 1.54 (1.13–2.09, p=0.006), number of metastases 3.63 (1.44–9.16, p=0.006), prognosis according to IMDC2.27 (1.63–3.17, p<0.001), and nephrectomy 1.87 (1.29–2.70, p=0.001) and metastasectomy 0.69 (0.53–0.88, p=0.003) were additional factors influencing OS rates in patients with lung metastases from RCC. Conclusion. In our study, ECOG status, histologic subtype of RCC, Fuhrman grade of tumor differentiation, number of metastases, IMDC prognosis, and nephrectomy and metastasectomy were additional independent prognostic factors affecting OS in patients with lung metastases from RCC. Further studies are needed to investigate prognostic factors in patients with RCC lung metastases to improve the effectiveness of personalized treatment and survival rates.

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Risk of relapse and patient selection for metastatic colorectal cancer liver surgery.

96 Background: Previous data on surgery for colorectal cancer (CRC) liver metastases (CRLM) documented improvement in overall survival (OS) and low perioperative mortality, but patient (pt) selection requires complex multidisciplinary work. Predictive scores such as the Comprehensive Evaluation of Relapse Risk (CERR) estimate relapse risk after surgery and help in the pre-operative decision. Objectives: This study aims to evaluate OS and progression-free survival (PFS) in a population of pts who had surgery for CRLM, and to analyse survival outcomes by risk groups, according to the CERR score. We identified individual, anatomic and biological factors with potential prognostic impact. Methods: We retrospectively analysed the medical records of pts who had CRLM surgery between January 2012 and December 2021 in two Portuguese reference centres. Outcomes for CRLM surgery were analysed by risk groups according to the CERR score of each pt (based on nodal status, preoperative CEA/CA 19.9 values, KRAS/BRAF status, presence of extrahepatic disease and modified tumour burden score). Univariate and multivariate survival analyses were performed with the log-rank test and Cox proportional-hazards regression models. Results: A total of 174 pts were included: 66,1% (n=115) male, mean age at CRLM diagnosis 62,1 (±11,5) years, 80,5% (n=140) with isolated liver metastases. Thirty-three pts (19%) had a second surgery, independently of the CERR score (chi-square p = 0,60). Eighteen (10,3%) pts had a CERR score of 0-1 (low-risk, LR), 96 (55,2%) of 2-3 (medium-risk, MR) and 60 (34,5%) of 4-5 (high-risk, HiR). With a median (MED) follow-up of 85,1 (15,6-186,5) months (mo), 100 (57.5%) pts have died. MED OS was 88,0 mo (95% confidence interval [CI] 40,6-135,4) for LR, 46,4 mo (95% CI 38,7-54,1) for MR and 30,7 mo (95% CI 23,1-38,4) for HiR pts (p=0,02); ECOG performance status was an independent prognostic factor (p=0,002) for OS. Median PFS was 88,0 mo (95% CI 6,9-169,0) for LR, 12,9 mo (95% CI 9,1-16,7) for MR and 7,7 mo (95% CI 5,9-9,4) for HiR pts (p<0,001); positive resection margins and prior induction chemotherapy (CT) were additional independent negative prognostic factors for PFS (p<0,001). Conclusions: These results suggest a significant association between relapse risk after surgery for CRLM and both OS and PFS. The CERR score can be used to select potential candidates for CRLM surgery and improve the impact of this intervention in pts with CRC. The link between induction CT and worse survival may reflect selection bias as these pts possibly had a higher volume of disease and therefore received initial systemic therapy. Prospective studies are required to confirm these results.

Abstract 2485: RAB31 interacts with AGR2 to respond to oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer cells via the EGFR-independent pathway

Abstract In the process of colonic epithelial carcinogenesis, the epithelial-mesenchymal transition may occur and bring metastatic ability and drug resistance. These events will affect patient outcomes and clinical treatment strategies. To this end, we investigated differentially expressed genes between several chemotherapy regimens in colon cancer cells through available transcriptomics datasets. We identified a member of the Rab family, RAB31, which is overexpressed after oxaliplatin treatment, while the other option is not (Irinotecan). We confirmed that RAB31 can enhance resistance to oxaliplatin in some overexpression models and that RAB31 has the ability to promote exocytosis and vesicle trafficking. Using shRNA as complementary models, we observed consistent trends when RAB31 function was discarded. Moreover, our evidence determined epithelial-mesenchymal transition (EMT)-related molecules responsive in the RAB31 bidirectional models, including CDH2, SNAI1, SNAI2 and TWIST1. The expression of RAB31 has an independent prognostic value in patients with colon cancer and is significantly positively correlated with mesenchymal markers. Furthermore, the interactome analysis selected RAB31 and AGR2 to form a direct protein interaction. This result differs from previous studies that did not rely on EGFR binding and signaling. Taken together, our study found that RAB31 can modulate oxaliplatin sensitivity and EMT status, which are additional chemotherapeutic strategies and independent prognostic factors for the treatment of colorectal cancer. Citation Format: Chi-Long Chen, Michael Hsiao. RAB31 interacts with AGR2 to respond to oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer cells via the EGFR-independent pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2485.

Systemic Inflammatory Response as a Prognostic Factor in Breast Cancer. Part II. Hematological Markers of Inflammation

Chronic inflammation is one of the recognized factors contributing to the onset and progression of malignant neoplasms. At the systemic level, a chronic inflammatory process is accompanied by an increased levels of inflammatory mediators and a change in hematological parameters of peripheral blood. According to numerous clinical studies, the change in the ratio of blood cell populations in cancer patients is an independent prognostic factor in malignant tumors of various localizations. This review is devoted to hematological parameters of the systemic inflammatory response (SIR) in breast cancer (BC). The review presents the characteristics of blood cells used for calculations of hematological indices (neutrophils, lymphocytes, monocytes, platelets); approaches for assessing SIR using these indices (NLR, PLR, LMR, etc.); comparative analysis of data on the association of the hematological indices with the clinical and morphological features of BC, patient survival and tumor response to chemotherapy. The data indicating the benefit of SIR hematological markers investigation during monitoring after treatment are summarized. Complex algorithms, including clinical, morphological and hematological factors, which are proposed to improve the quality of prognosis assessment, are considered. The information accumulated to date suggests that hematological indices reflecting SIR activity in BC patients can serve as additional independent prognostic factors. The development of the prognostic algorithms that are informative for certain clinical groups of BC patients is a promising area of research.

RDW Is an Independent Prognostic Biomarker in Patients with Chronic Graft-Versus-Host-Disease

Background Chronic graft-versus-host disease (cGVHD) is an important immunologic sequelae of allogeneic hematopoietic stem cell transplantation (HCT) that can lead to increased morbidity and mortality in long-term survivors. Red cell distribution width (RDW) is a measure of the variation of the mean corpuscular volume of red blood cells reflecting the degree of anisocytosis. Multiple epidemiological and longitudinal observational studies have shown that higher RDW values are associated with increased all-cause, cardiovascular and cancer-related mortality in different populations including patients as well as healthy participants but limited data exists in patients after HCT. Although RDW is affected to some degree by any type of anemia, the etiology of variation in RDW is considered to be multifactorial and overall incompletely understood. Whether RDW is affected by cGVHD activity or retains its prognostic significance for mortality is unknown. Patients and Methods The present study analyzed patients enrolled on the NIH cGVHD natural history study (NCT00092235) with existing measures of RDW (n=404). In addition to RDW, previously described laboratory markers of inflammation (Grkovic L. et al. Leukemia. 2012;26:633) significantly associated with cGVHD disease activity and other known prognostic factors associated with survival in cGVHD patients were considered. Results The median age of the cohort was 47.2 years (IQR 32-57) and male patients were slightly overrepresented (n=231, 57%). Information about the NIH global score was available in 98.5% of patients who had predominantly severe (72.4%) and moderate (25.6%) cGVHD (Table 1). The median potential follow-up of the total cohort was 11.9 years (IQR 8.4-14.5) and the 5-year overall survival (OS) 77.9% (95% CI, 68.3-77.0%), but the median OS was not reached. A clear split was identified between the first quartile and the remaining overlapping quartiles of RDW distinguishing two groups with statistically different OS: <13.4% vs ≥13.4% (p=0.0024, adjusted for 3 implicit cut-points). Five-year OS was 84.1% (95% CI, 75.3%-89.9%) and 69.1% (95% CI, 63.6%-74.0%) for patients with RDW <13.4% and ≥13.4%, respectively. In univariate analyses, RDW ≥13.4% was statistically associated with Karnofsky performance status (KPS) <80 (39% vs 19%; p=0.0003), cGVHD global score severe (77.6% vs 62%; p=0.0046), increasing involvement of skin (p=0.0023) and mouth (p=0.0043), steroid (70% vs 46%; p<0.0001) and mTOR inhibitor treatment (24% vs 7%; p=0.0002), extracorporeal photopheresis (22% vs 10%; p=0.0077), increased inflammatory markers CRP, C3 and C4 (all p≤0.0002, respectively) and lower IgG (p=0.0031) but not age, sex, kidney function (eGFR CKD-EPI 2021) or time from HCT to study consent. The multiple logistic model established oral cGVHD (OR 1.77; 95% CI, 1.2- 2.60), mTOR inhibitors (OR 3.49; 95% CI, 1.5- 8.30), LDH (OR 1.01; 95% CI, 1.01-1.02), Hb (OR 0.68; 95% CI, 0.57-0.80) and ANC (OR 1.21; 95% CI, 1.07-1.36) as independent factors associated with dichotomized RDW groups. The Cox proportional hazards model confirmed the independent association of RDW ≥13.4% with worse OS (HR 1.61; 95% CI, 1.05-2.47) and identified albumin <3.45 mg/dL (HR 1.78; 95% CI, 1.41-2.24) and IgG <6.3 g/L (HR 1.67; 95% CI, 1.20-2.31) as independent factors in addition to KPS <80 (HR 1.51; 95% CI, 1.06-2.14), eGFR <45 mL/min/1.73m2 (HR 2.27; 95% CI, 1.41-3.66) and lung cGVHD NIH grade 3 (HR 2.92; 95% CI, 1.86-4.57). Moreover, RDW ≥13.4% was associated with decreased relapse-free survival (5-year; 72.8% vs 87.8%; p=0.0062 for comparison of the full curves) and increased non-relapse mortality (5-year; 20.8% vs 7.6%; p=0.0082 for comparison of the full curves) but not with cumulative incidence of relapse (5-year; 6.5% vs 4.6%; p=0.45). Conclusion Patients with chronic GVHD and RDW ≥13.4% have a statistically worse overall survival due to higher risk of non-relapse mortality. Hypoalbuminemia and hypogammaglobulinemia — laboratory markers of increased inflammation and B-cell dysfunction — are additional independent poor prognostic factors identified by this study. It seems prudent that future therapeutic clinical trials should measure these laboratory markers to investigate whether they serve as surrogate biomarkers of chronic GVHD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Deep Learning–Based Nuclear Morphometry Reveals an Independent Prognostic Factor in Mantle Cell Lymphoma

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by Ki-67 in multivariate analysis. Herein, a nuclear segmentation model was developed using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared with those in classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) emerged as significant prognostic factors. Using multivariate analysis, Biologic MCL International Prognostic Index (bMIPI) risk group (P=0.025), low skewness of nuclear irregularity (P=0.020), and high mean of nuclear irregularity (P=0.047) emerged as independent adverse prognostic factors. Additionally, a morphometric score calculated from the skewness and mean of nuclear irregularity (P=0.0038) was an independent prognostic factor in addition to bMIPI risk group (P=0.025), and a summed morphometric bMIPI score was useful for risk stratification of patients with MCL (P=0.000001). These results demonstrate, for the first time, that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

Optimization of Tokuhashi Scoring System to Improve Survival Prediction in Patients with Spinal Metastases.

Introduction: Predicting survival time for patients with spinal metastases is important in treatment choice. Generally speaking, six months is a landmark cutoff point. Revised Tokuhashi score (RTS), the most widely used scoring system, lost its accuracy in predicting 6-month survival, gradually. Therefore, a more precise scoring system is urgently needed. Objective: The aim of this study is to create a new scoring system with a higher accuracy in predicting 6-month survival based on the previously used RTS. Methods: Data of 171 patients were examined to determine factors that affect prognosis (reference group), and the remaining (validation group) were examined to validate the reliability of a new score, adjusted Tokuhashi score (ATS). We compared their discriminatory abilities of the prediction models using area under receiver operating characteristic curve (AUC). Results: Target therapy and the Z score of BMI (Z-BMI), which adjusted to the patients’ sex and age, were additional independent prognostic factors. Patients with target therapy use are awarded 4 points. The Z score of BMI could be added directly to yield ATS. The AUCs were 0.760 for ATS and 0.636 for RTS in the validation group. Conclusion: Appropriate target therapy use can prolong patients’ survival. Z-BMI which might reflect nutritional status is another important influencing factor. With the optimization, surgeons could choose a more individualized treatment for patients.

Obesity contributes to the stealth peritoneal dissemination of ovarian cancer: a multi-institutional retrospective cohort study.

The clinical significance of a higher BMI on the prognosis of ovarian cancer remains controversial; therefore, a more detailed analysis is demanded. This study investigated the impact of BMI on peritoneum-specific recurrence to clarify the involvement of adipose tissue in the proliferation of cancer cells at sites of peritoneal dissemination. Among 4,730 patients with malignant ovarian tumors, 280 diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIC epithelial ovarian cancer and who underwent complete resection in the primary surgery were included in the present study. There were 42, 201, and 37 women in the low, normal, and high BMI groups, respectively. Peritoneum-specific recurrence-free survival and overall survival were both significantly shorter in patients with a high BMI than in those with a normal BMI (p=0.028 and 0.018, respectively). No significant differences were observed in the distribution of sites of recurrence between these two groups. A multivariate analysis identified obesity as an independent prognostic factor in addition to pT3 tumor staging and positive ascites cytology. Patients with a high BMI had a significantly worse prognosis than those with a normal BMI, and peritoneal adipose tissue may have contributed to this difference.

Analysis of Clinicopathological Factors Influencing Survival in Patients with Renal Cell Carcinoma and Venous Tumor Thrombus.

This study aimed to define patients with renal cell cancer and coexisting tumor thrombus in order to address concerns regarding survival and prognostic factors after radical surgery. Several prognostic factors for overall survival (OS) were assessed in patients treated surgically at five institutions from 2012 to 2018. Univariate and multivariate analyses were used to determine the independent risk factors of OS. A total of 142 patients were eligible for further analysis (mean age of 64.75 years, 56% males). Most patients presented with clear cell carcinoma (95%). The Mayo stage was predominantly 0–1 (88%). Distant visceral metastases at the time of diagnosis were present in 36 patients (25%), whereas nodal metastases were present in 24 patients (16.9%). During the follow-up period (mean of 32.5 months), the 3-year OS rate reached 68.2%. The majority of patients received no adjuvant treatment (n = 107). In a multivariable model predicting OS, regional lymph node status (p < 0.001), distant metastases (p = 0.009), tumor grade (p = 0.002), duration of hospitalization (p = 0.016), and Clavien–Dindo grade (p = 0.047) were identified as independent prognostic factors. A subgroup of patients with specific clinicopathological factors may benefit most from the radical surgery, including patients without regional lymph node or distant metastases and with low tumor grades, whereas short hospitalization and low Clavien–Dindo grades represent additional independent prognostic factors.

Development and validation of a novel nomogram for predicting the prognosis of patients with resected pancreatic adenocarcinoma.

The survival prediction for patients with resected pancreatic adenocarcinoma by using the Tumor-Node-Metastasis (TNM) staging system remains limited. A nomogram is a efficient tool that can be used to predict the outcome of patients with various types of malignancy. The present study aimed to develop and validate a nomogram for patients with resected pancreatic adenocarcinoma. A total of 368 patients (258 in the training set and 110 in the validation set) who underwent pancreatic adenocarcinoma resection at the China National Cancer Center between January 2008 and October 2018 were included in the present study. The nomogram was established according to the results from Cox multivariate analysis, which was validated by discrimination and calibration. The area under the receiver operating characteristic curve (AUC) was determined to assess the accuracy of survival predictions. The results from multivariate analysis in the training set demonstrated that blood transfusion, T-stage, N-stage, tumor grade, capsule invasion, carbohydrate antigen 199, neutrophil percentage and adjuvant therapy were independent prognostic factors for overall survival (OS; all P<0.05). Subsequently, a nomogram predicting the 1-year, 3-year and 5-year OS rates, with favorable calibration, was established based on the independent prognostic factors. The concordance indices of the nomogram were higher compared with the TNM staging system in both training and validation sets. Furthermore, a clear risk stratification system based on the nomogram was used to classify patients into the three following groups: Low-risk group (≤168), moderate-risk group (168–255) and high-risk group (>255). The risk stratification system demonstrated an improved ability in predicting the 1-year, 3-year and 5-year OS rates compared with the TNM system (AUC, 0.758, 0.709 and 0.672 vs. AUC, 0.614, 0.604 and 0.568; all P<0.05). The present study developed and validated a nomogram for patients with resected pancreatic adenocarcinoma by including additional independent prognostic factors, including tumor marker, immune index, surgical information, pathological data and adjuvant therapy. Taken together, the results from the present study indicated an improved performance of the nomogram in predicting the prognosis of patients with resected pancreatic adenocarcinoma compared with the TNM staging system.

Modified score based on revised Tokuhashi score is needed for the determination of surgical intervention in patients with lung cancer metastases to the spine

BackgroundRevised Tokuhashi score (RTS) is no longer accurate to predict the survival of patients with lung cancer metastases to the spine. This study is to identify additional prognostic factors in those patients, develop a modified prognostic score based on RTS, and verify the accuracy of the score in prediction.MethodsOur study included patients with lung cancer metastases to the spine who underwent surgery for spine metastasis. Potential prognostic factors were analyzed. Points were allocated for prognostic factors obtained from survival analyses. A modified score was developed by including prognostic factors and their points to RTS. Accuracy of the modified score was evaluated by comparing the coincidence between predicted and observed survival. Kaplan–Meier analysis and Cox regression models were used. Predictive values of scores for 6-month survival were measured via receiver operating characteristic (ROC) curves.ResultsTargeted therapy and tumor markers were additional independent prognostic factors. In the modified score, 2 and 1 points were allocated to the new evaluation factors. The points for factors based on RTS remained the same, and two prognostic groups were redefined. For group A patients who were predicted to live for less than 6 months, conservative procedures would be recommended. For group B patients who were predicted to live for 6 months or more, palliative surgery would be recommended. When comparing the modified score to RTS, the area under the receiver operating characteristic curve (AUCROC) and accuracy of score were improved.ConclusionsThe modified RTS has improved prognostic accuracy in patients with lung cancer metastases to the spine.

Epidermal Growth Factor Receptor (EGFR) Cell Expression During Adjuvant Treatment After Transurethral Resection for Non-Muscle-Invasive Bladder Cancer: A New Potential Tool to Identify Patients at Higher Risk of Disease Progression.

The aim of the study was to investigate the feasibility of Epidermal Growth Factor Receptor (EGFR) measurement in bladder washings of patients affected by non-muscle-invasive bladder cancer (NMIBC) and its prognostic role in identifying risk subgroups and predicting disease recurrence and progression. Patients with NMIBC treated with transurethral resection of bladder tumor (TURBT) from 2012 to 2015 were enrolled. Samples of bladder washings were collected and stored at-80°C until RNA extraction. The cDNA obtained from RNA was used to perform a gene expression analysis by a real time polymerase chain reaction. An adequate cellular pellet was obtained in 50 (86.2%) of 58 patients and in 18 (85.7%) of 21 controls. Patients had a median 2.5-, a 1.6- and a 2.8-fold EGFR expression compared with controls before, during, and after adjuvant treatment, respectively. Patients at higher risk had a significantly higher EGFR expression compared with patients at low and intermediate risk when EGFR was measured during (P= .04) and after (P= .001) adjuvant therapy. At a median follow-up of 35.5 months (interquartile range, 19.0-54.8 months), in the high-risk group, patients with overexpression had a significantly lower recurrence-free survival (27.9% vs. 58%), progression-free survival (75.9% vs. 90.2%), and cancer-specific survival (77.7% vs. 93.3%). At multivariable analysis, EGFR overexpression was an additional independent prognostic factor to the European Organisation for Research and Treatment of Cancer scoring system of disease recurrence (hazard ratio, 1.98; 95% confidence interval, 1.32-2.97) and progression (hazard ratio, 1.84; 95% confidence interval, 1.27-2.65). EGFR overexpression might represent an additional parameter to the current clinical tools for an individualized risk stratification.

Surgery of the primary tumor improves survival in women with stage IV breast cancer in Southwest China: A retrospective analysis.

The International Consensus Guidelines for advanced breast cancer (ABC) considers that the surgery of the primary tumor for stage IV breast cancer patients does not usually improve the survival. However, studies have showed that resection of the primary tumor may benefit these patients. The correlation between surgery and survival remains unclear.The impact of surgery and other clinical factors on overall survival (OS) of stage IV patients is investigated in West China Hospital. Female patients diagnosed with stage IV breast cancer between 1999 and 2014 were included (N = 223). Univariate and multivariate analysis assessed the association between surgery and OS.One hundred seventy-seven (79.4%) underwent surgery for the primary tumor, and 46 (20.6%) had no surgery. No significant differences were observed in age at diagnosis, T-stage, N-stage, histological grade, molecular subtype, hormone receptor (HR), and number of metastatic sites between 2 groups. Patients in the surgery group had dramatically longer OS (45.6 vs 21.3 months, log-rank P < .001). In univariate analysis, survival was associated with surgical treatment, residence, tumor size, lymph node, HR status, hormonal therapy, and radiotherapy. In multivariate analysis, surgery was an independent prognostic factor for OS [hazard ratio (HR), 0.569; 95% confidence interval (CI) 0.329-0.984, P = .044]. Additional independent prognostic factors were hormonal therapy (HR, 0.490; 95% CI 0.300-0.800) and radiotherapy (HR, 0.490; 95% CI 0.293-0.819). In addition, a favorable impact of surgery was observed by subgroup analysis.Our study showed that surgery of the primary breast tumor has a positive impact on OS in with stage IV breast cancer patients.

Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion

Background:Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI).Methods:In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival.Results:Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI.Conclusions:The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown.

Glasgow prognostic score after concurrent chemoradiotherapy is a prognostic factor in advanced head and neck cancer.

Objective This study aims to evaluate the impact and potential prognostic roles of the pre- and post-treatment Glasgow prognostic score (GPS) and the change thereof in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy (CCRT).Methods We collected GPS and clinicopathological data of 139 stage III, IVA, and IVB head and neck cancer patients who underwent CCRT between 2008 and 2011. Their GPSs pre- and post-CCRT and the change thereof were analyzed for correlations with recurrence and survival. Results The GPS changed in 72 (51.8%) patients, with worse scores observed post-CCRT in 65 (90.3%) of the GPS changed patients. Patients in the improved GPS group showed a tendency toward better survival. From the multivariate analysis, the post-CCRT GPS level was an independent prognostic factor in addition to tumor stage. Conclusions After CCRT, a high GPS was revealed to be an important predictor of survival for advanced head and neck cancer.

Gene Mutation Signature and Its Pathogenesis Role in Chronic Lymphocytic Leukemia in China: Different from the Western Reports

BackgroundRecently, the molecular aberration of chronic lymphocytic leukemia (CLL) has been widely investigated in the Western population. Genes mutation detecting by next generation sequencing (NGS) provided a fair-new view to explain the pathogenesis of CLL and guide the clinical practices. Limited primary data indicated the mutation signature of CLL in China might be different from the Western reports, which deserved further systematical investigation.MethodsA panel with 76 genes was designed to identify mutation status by NGS in 129 CLL patients. This 76 genes panel had been reported as recurrent mutation in CLL and other lymphoproliferative disorders. Whole exomes of each gene were sequenced with a mean read depth of 1957 and a coverage of target region of 99.6%.ResultsWe finally revealed the presence of recurrent mutations (n ≥ 2) in 63 genes. The most frequency of mutational genes were as follow: FAT1, 35 cases (27.1%); KMT2D/MLL2, 29 cases (22.5%); TP53, 26 cases (20.2%); FAT4 24 cases (18.6%); NOTCH1, 22 cases (17.1%); ATM, 19 cases (14.7%); FBXW7, 16 cases (12.4%); SPEN, 16 cases (12.4%); BRAF, 15 cases (11.6%); MYD88 14 cases (10.9%); SF3B1, 14 cases (10.9%); APC, 13 cases (10.1%); CREBBP 13 cases (10.1%); TET2, 13 cases (10.1%); POT1, 11 cases (8.5%); EP300, 10 cases (7.8%); KMT2B, 10 cases (7.8%); MAP3K14, 10 cases (7.8%); TCF3, 10 cases (7.8%); NOTCH2, 9 cases (7.0%); KLF2, 8 cases (6.2%); SMARCA4, 8 cases (6.2%); BIRC3, 7 cases (5.4%); EGR2, 7 cases (5.4%); KLHL31, 7 cases (5.4%); KLHL6, 7 cases (5.4%), et al.We compared the mutated sites of each gene in this study with other established studies, and found that the mutation sites distribution of each recurrent mutated gene were comparable to the well-known mutated sites, which indicated the similar function change. Then, we classified these recurrent mutation genes into different signaling pathway, according to their affected function. We found that chromatin modification pathway was the most affected pathway, accounting for 74 patients (57.4%), followed by NF-κB pathway (58 patients, 45.0%), NOTHC1 pathway (52 patients, 40.3%), Hippo pathway (50 patients, 38.8%), DNA damage pathway (48 patients, 37.2%), Wnt/β-catenin pathway (31 patients, 24.0%) and post-transcriptional modification (19 patients, 14.7%).The IGHV mutation rate in the 115 patients was 67.0%, which was significantly higher than the Western reports. In aspect of prognostic role of these mutation genes, IGHV mutation status, the TP53 abnormality (deletion and mutation) and mutated EGFR impacted both PFS and OS independently, while mutated FAT1 was additional independent prognostic factor for PFS and mutated POT1 and KLF2 were another two independent factors for OS. IGHV mutation status and mutated TRAF2 were both independent factors for TTT.Integrating the function of these high frequency mutated genes, high proportion of IGHV gene mutation and cell-of-origin of CLL model initiated recently, these prevalent mutation genes in this study were supposed to precipitate the pathogenesis of CLL from the initial tumor stem cell to germinal center B cell.ConclusionThe gene mutation signature of CLL in China is different from the Western population, which may skew the cell-of-origin of CLL in China towards the germinal center B cell maturation route, other than other maturation way, such as marginal zone B cell origin. DisclosuresNo relevant conflicts of interest to declare.

Body mass index and age are additional prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors

PurposeTyrosine kinase inhibitors (TKIs) are the preferred treatment drugs for metastatic renal cell carcinoma (mRCC). The aim of this study was to analyze prognostic factors for overall survival (OS) in patients with mRCC treated with TKIs. Materials and methodsClinical data on 155 patients enrolled in 5 clinical trials conducted at our hospital from 2006 to 2014 were reviewed retrospectively. All patients received first-line TKI therapy (sunitinib, sorafenib, pazopanib, or famitinib). Survival rates were determined by the Kaplan-Meier method. ResultsMedian OS (mOS) was 36.2 months. A total of 4 of the 5 adverse prognostic factors identified by the Memorial Sloan-Kettering Cancer Center (MSKCC) were found to be independent predictors of shorter survival, anemia, hypercalcemia, lactate dehydrogenase>1.5×upper limit of normal, and diagnosis to treatment time<1 year. In addition, we found that age≤45 years (P = 0.002), low or high body mass index ([BMI]<19 or>30kg/m2) (P = 0.003), and presence of≥3 metastatic sites (P = 0.000) were also independent adverse prognostic factors. According to the MSKCC model, the mOS time in the favorable-risk, intermediate-risk, and poor-risk groups were 46.6, 30.4 and 16.7 months, respectively (P = 0.005). When we integrated age and BMI into the MSKCC model to set up a 7-factor prognostic model, we found the mOS time for these 3 groups was 71.1, 41.6 and 15.3 months, respectively (P = 0.000). ConclusionAge and BMI are additional independent prognostic factors for patients with mRCC receiving vascular endothelial growth factor receptor-targeted TKI treatment, and the MSKCC prognostic model is also applicable to them. A 7-factor prognostic model might help to identify patients with the best prognosis. Further studies are needed to confirm these findings.

Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer.

PurposeTo determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis.Materials and MethodsWe included 223 patients who received staging laparotomy and were diagnosed with stage IIC–IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level.ResultsThe CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS).ConclusionAmong well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.