Negative Prognostic Factors For OS Research Articles

Nivolumab or Atezolizumab in the Second-Line Treatment of Advanced Non-Small Cell Lung Cancer? A Prognostic Index Based on Data from Daily Practice

The efficacy of nivolumab and atezolizumab in advanced pre-treated NSCLC was documented in prospective trials. We aim to confirm the benefits and indicate predictive factors for immunotherapy in daily practice. This study was a retrospective analysis. The median PFS and OS were estimated using the Kaplan-Meier method. The log-rank test was used for comparisons. Multivariate analyses were performed using the Cox regression method. A total of 260 patients (ECOG 0-1) with advanced NSCLC (CS III-IV) were eligible to receive nivolumab or atezolizumab as second-line treatment. Median PFS and OS were three months (95% confidence interval [CI] 2.57-3.42) and 10 months (95% CI 8.03-11.96), respectively, for the overall population. The median OS for the atezolizumab arm was eight months (95% CI 5.89-10.1), while for the nivolumab group, it was 14 months (95% CI 10.02-17.97) (p = 0.018). The sum of all measurable changes >100.5 mm (p = 0.007; HR = 1.003, 95% CI 1.001-1.005), PLT > 281.5 G/l (p < 0.001; HR = 1.003, 95% CI 1.001-1.003) and bone metastases (p < 0.004; HR = 1.58, 95% CI 1.04-2.38) were independent negative prognostic factors for OS in multivariate analysis. Based on preliminary analyses, a prognostic index was constructed to obtain three prognostic groups. Median OS in the subgroups was 16 months (95% CI 13.3-18.7), seven months (95% CI 4.83-9.17) and four months (95% CI 2.88-5.13), respectively (p < 0.001). Nivolumab and atezolizumab provided clinical benefit in real life. Clinical and laboratory factors may help to identify subgroups likely to benefit. The use of prognostic indices may be valuable in clinical practice.

The prognostic value of positron emission tomography/computed tomography-based parameters in locally advanced esophageal squamous cell carcinoma treated with chemoradiation therapy.

To assess the prognostic value of PET/computed tomography-based parameters in patients with locally advanced esophageal squamous cell carcinoma (ESSC). Sixty-seven patients with ESSC undergoing definitive chemoradiotherapy (dCRT) were retrospectively enrolled. PET/CT parameters (maximum standardized uptake value (SUVmax) metabolic tumor volume (MTV), and total glycolysis (TLG) were obtained from 18F-fluorodeoxyglucose (18F-FDG) PET/CT studies. The correlation between overall survival and PET/CT parameters was analyzed using a Cox proportional hazards model. There were no differences in TLG, MTV, and SUVmax values across age, sex, tumor location, and lymph node status. However, for patients with cT3-4 disease, TLG and SUVmax were significantly higher (P = 0.019 and P = 0.018, respectively), and MTV showed an increasing trend (P = 0.068). There were significant correlations among TLG, MTV and SUVmax. According to the receiver-operating curve, the cutoff values of TLG, MTV and SUVmax dichotomized by survival status at 2 years were 64.00 g, 9.63 ml and 9.97 g/ml, respectively. In univariate analysis, increased TLG, MTV and SUVmax were significant negative prognostic factors for OS. However, in multivariate analysis, only SUVmax was an independent prognostic factor for overall survival (hazard ratios = 2.857, 95% confidence intervals: 1.837-4.442; P = 0.017). PET/CT is a useful tool for predicting the prognoses in patients with locally advanced ESSC treated with dCRT. Future prospective studies with a large number of samples should be conducted to confirm these results.

Therapeutic strategy analysis of patients with advanced stage high-grade neuroendocrine cervical cancer: A real-world multicenter study.

To explore the management of high-grade neuroendocrine cervical cancer (HGNECC) since there has been no standard treatment for it. Data on the management of HGNECC were retrospectively analyzed. Patients with FIGO stage IIB to IVB HGNECC from six hospitals were enrolled. The Kaplan-Meier method was used for survival analysis. Prognostic factors were determined using a Cox proportional-hazards regression model. A total of 43 patients were included in the study. The multivariate analysis showed that chemotherapy was the preferred treatment as it improved progression-free survival (PFS; P=0.008) and overall survival (OS; P=0.005). Distance metastasis was a significant negative prognostic factor for OS (P=0.002), while radical surgery was a significant positive prognostic factor for PFS (P=0.05). Compared with those who had received cisplatin and etoposide (≥5 cycles), patients who had received paclitaxel plus platinum-based chemotherapy showed better PFS and OS. Five patients (two at stage IIB and three at stage IV) showed relatively long-term survival. Of these patients, four had undergone radical surgery including tumor-debulking, while three also received adjuvant chemotherapy. Paclitaxel plus cisplatin or paclitaxel plus carboplatin may be more effective than etoposide plus cisplatin. Radical surgery followed by chemotherapy may be a favorable alternative intervention for selected patients with advanced stage cancer.

Using chemotherapy against metastatic pancreatic neuroendocrine neoplasm: how aggressively do we treat it? Real world data from a Brazilian Cancer Center

INTRODUCTION: Pancreatic neuroendocrine neoplasms (pNEN) have poor prognosis. Available treatment options are limited. We aimed to evaluate the clinical characteristics and outcomes in patients with pNEN undergoing systemic chemotherapy. METHODS: Retrospective study of patients with metastatic pNEN diagnosed between January 2000 and April 2018 in A.C. Camargo Cancer Center. We evaluated epidemiological characteristics and outcomes of patients who received systemic chemotherapy between the first and third-lines. RESULTS: 35 patients with median age of 54.4 years; 51.4% had diabetes mellitus and 62.9% had smoking history. Most primary tumors were located in pancreatic body or tail and 34.3% were described as well or moderately differentiated, 40% were of high grade. Overall, chemotherapy from first to third-line was prescribed 50 times, 62% consisted of platin doublet, the chosen schema 50% of times when Ki-67<20%, 55.5% for Ki-67 between 20% and 55% and 66.7% for Ki-67>55%. The median PFS and RR were 7.8 months and 40.7%; 13 months and 33.3% and 3 months and 0% in the first, second and third-line, respectively. The estimated OS was 53.4 months. We found that female (HR 2.8, p=0.034), DM (HR 4.5, p=0.004), smoking (HR 3.5, p=0.017), high grade tumors (HR 3.8, p=0.025) and tumors localized in head/neck of the pancreas (HR 7.1, p<0.001) were negative prognostic factors for OS in univariate analysis. CONCLUSION: Our real world data shows that doublet platin is a preferred and active schema for treating pNEN, especially in first and second line. It brings the greatest benefit for undifferentiated tumors. Nevertheless, the prognosis remains poor and some factors may contribute to worse outcomes, such as female gender, silent tumors that do not manifest DM, poorly differentiated tumours, smoking and location in the head and neck of the pancreas.

Low psoas muscle index as independent poor prognostic factor for diffuse large B-cell lymphoma in elderly patients

Sarcopenia is associated with poor clinical outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, the clinical significance and optimal assessment of sarcopenia remain unclear. We retrospectively evaluated the prognostic value of low skeletal muscle mass based on the psoas muscle index (PMI) in patients with DLBCL aged 70 years and older treated with R-CHOP therapy. We included 71 patients, including 27 classified under low PMI. There were no differences in baseline characteristics (body mass index, lactate dehydrogenase, performance status [PS], stage, revised-IPI, relative dose intensity) and overall response rate between the low and high PMI groups. The low PMI group had a significantly worse overall survival (OS, p=0.015), but not progression-free survival (PFS, p=0.252), compared with the high PMI group. On multivariate analysis, low PMI and PS were independent negative prognostic factors for OS. Subgroup analysis revealed that the low PS groups had significantly worse PFS regardless of the PMI status. The low PMI and low PS group had markedly poorer OS than all the other groups. However, the poor prognosis associated with low PS was overcome by a high PMI.

Impact of Neoadjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Population Based Analysis.

We examined pathologic complete response (pCR) and pathologic downstaging (pDS) rates after neoadjuvant chemotherapy (NAC) in high-risk upper tract urothelial carcinoma, as well as their predictors. We further sought to determine their effects on overall survival and examine prognosticators of survival after NAC. The National Cancer Database was used to identify all patients from 2004 to 2016 with nonmetastatic high grade upper tract urothelial carcinoma who received NAC followed by nephroureterectomy. pCR and pDS rates were examined, and univariate and multivariate logistic regression was performed to identify clinical predictors. Kaplan-Meier and Cox proportional hazard methods were used to estimate overall survival. 309 patients met inclusion criteria. 27 patients (8.74%) had pCR, and 92 (29.77%) had pDS. pCR and pDS rates for N+ subgroup were 6.82% and 47.73% respectively, and for N0 subgroup, 9.50% and 22.62%. Female sex (OR 2.94, p = 0.010) was the only predictor of pCR. Node-positive disease (cN1 vs. cN0: OR 6.40, p < 0.001; cN2 vs. cN0: OR 7.46, p < 0.001) was a positive predictor of pDS, and the presence of lymphovascular invasion (LVI) (OR 0.14, p < 0.001) was a negative predictor of pDS. The median OS for all patients was 45.5 months. pCR and pDS were both associated with improved OS, (p < 0.001 for both); median was 99.1 months for both. LVI was the strongest negative prognostic factor for OS (HR 2.85, p < 0.001). Overall pathological complete response and downstaging rates were 8.74% and 29.77% respectively after multi-agent neoadjuvant chemotherapy. Node-negative and node-positive disease had equivalent rates of complete response, but node-positive disease had a significantly higher rate of downstaging. The presence of LVI was associated with worse overall survival.

Prognostic Impact and Functional Annotations of KIF11 and KIF14 Expression in Patients with Colorectal Cancer

Genomic instability (GIN) has an important contribution to the pathology of colorectal cancer (CRC). Therefore, we selected mitosis and cytokinesis kinesins, KIF11 and KIF14, as factors of potential clinical and functional value in CRC, as their aberrant expression has been suspected to underlie GIN. We examined the expression and the prognostic and biological significance of KIF11 and KIF14 in CRC via in-house immunohistochemistry on tissue microarrays, public mRNA expression datasets, as well as bioinformatics tools. We found that KIF11 and KIF14 expression, at both the protein and mRNA level, was markedly altered in cancer tissues compared to respective controls, which was reflected in the clinical outcome of CRC patients. Specifically, we provide the first evidence that KIF11 protein and mRNA, KIF14 mRNA, as well as both proteins together, can significantly discriminate between CRC patients with better and worse overall survival independently of other relevant clinical risk factors. The negative prognostic factors for OS were high KIF11 protein, high KIF11 protein + low KIF14 protein, low KIF11 mRNA and low KIF14 mRNA. Functional enrichment analysis revealed that the gene sets related to the cell cycle, DNA replication, DNA repair and recombination, among others, were positively associated with KIF11 or KIF14 expression in CRC tissues. In TCGA cohort, the positive correlations between several measures related to GIN and the expression of KIFs were also demonstrated. In conclusion, our results suggest that CRC patients can be stratified into distinct risk categories by biological and molecular determinants, such as KIF11 and KIF14 expression and, mechanistically, this is likely attributable to their role in maintaining genome integrity.

The Role of Cytoreductive Radical Prostatectomy in the Treatment of Newly Diagnosed Low-volume Metastatic Prostate Cancer. Results from the Local Treatment of Metastatic Prostate Cancer (LoMP) Registry

BackgroundRadiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). Objectiveto evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. Design, setting, and participantsA multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16–49). InterventioncRP was compared with RTp and NLT. Outcome measurements and statistical analysisOverall survival (OS), cancer-specific survival (CSS), and local event–free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. Results and limitationsThe 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. ConclusionsFor selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. Patient summaryPatients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression.

Associations between tumor mutations in cfDNA and survival in non-small cell lung cancer

IntroductionStudies have indicated that detection of mutated KRAS or EGFR in circulating tumor DNA (ctDNA) from pre-treatment plasma samples is a negative prognostic factor for non-small cell lung cancer (NSCLC) patients. This study aims to investigate whether this is the case also for NSCLC patients with other tumor mutations. MethodsTumor tissue DNA from 107 NSCLC patients was sequenced and corresponding pre-treatment plasma samples were analyzed using a limited target next-generation sequencing approach validated in this study. Patients without detected mutations in tumor samples were excluded from further analyses. ResultsMutations were detected in tumor samples from 71 patients. Median age was 68 years, 51% were female, and 88% were current/former smokers, 91% had adenocarcinoma, 4% had squamous cell carcinoma and 6% had other NSCLC. The distribution between stage I, II, III and IV was 33%, 8%, 30%, and 29%, respectively. Between one and three tumor mutation(s) were detected in ctDNA from corresponding plasma samples. Patients with detected ctDNA had shorter PFS (9.6 vs. 41.3 months, HR: 2.9, 95% CI: 1.6–5.2, p = 0.0003) and OS (13.6 vs. 115.0 months, HR: 4.0, 95% CI: 2.1–7.6, p = 0.00002) than patients without detected ctDNA. ctDNA remained a significant negative prognostic factor for OS (HR: 2.5, 95% CI: 1.1-5.7, p=0.0327), but not PFS, in the multivariable analyses adjusting for baseline patient and disease characteristics including stage of disease. ConclusionsThis study adds further evidence supporting that detectable tumor mutations in cfDNA is associated with a worse prognosis in NSCLC harboring a variety of tumor mutations.

Robotic rectal resection: oncologic outcomes

Robotic surgery has progressively gained popularity in the treatment of rectal cancer. However, only a few studies on its oncologic effectiveness are currently present, with contrasting results. The purpose of this study is to report a single surgeon’s experience on robotic rectal resection (RRR) for cancer, focusing on the analysis of oncologic outcomes, both in terms of pathological features and long-term results. One-hundred and twenty-two consecutive patients who underwent RRR for rectal cancer from January 2013 to December 2019 were retrospectively enrolled. Patients’ characteristics and perioperative outcomes were collected. The analyzed oncologic outcomes were pathological features [distal (DM), circumferential margin (CRM) status and quality of mesorectal excision (TME)] and long-term outcomes [overall (OS) and disease-free survival (DFS)]. The mean operative time was 275 (± 60.5) minutes. Conversion rate was 6.6%. Complications occurred in 27 cases (22.1%) and reoperation was needed in 2 patients (1.5%). The median follow-up was 30.5 (5.9–86.1) months. None presented DM positivity. CRM positivity was 2.5% (2 cases) while a complete TME was reached in 94.3% of cases (115 patients). Recurrence rate was 5.7% (2 local, 4 distant and 1 local plus distant tumor relapse). OS and DFS were 90.7% and 83%, respectively. At the multivariate analysis, both CRM positivity and near complete/incomplete TME were recognized as negative prognostic factors for OS and DFS. Under appropriate logistic and operative conditions, robotic surgery for rectal cancer proves to be oncologically effective, with adequate pathological results and long-term outcomes. It also offers acceptable peri-operative outcomes, further confirming the safety and feasibility of the technique.

Paranasal Sinus Invasion Should Be Classified as T4 Disease in Advanced Nasopharyngeal Carcinoma Patients Receiving Radiotherapy.

In this study, we explored the association between paranasal sinus invasion and prognosis in patients with advanced nasopharyngeal carcinoma (NPC, (T3/T4N0–3M0), and we assessed the possibility of considering paranasal sinus invasion a T category in the 8th edition of the American Joint Committee on Cancer staging system. We enrolled 352 NPC patients who received intensity-modulated radiotherapy between 2008 and 2012. Clinical characteristics and follow-up data were collected. The incidence of paranasal sinus invasion was 36.4% (128 of 352 patients). Multivariate cox regression analysis indicated that paranasal sinus invasion and cervical lymphatic metastasis were independent negative prognostic factors for overall survival (OS, P=0.024, P=0.012), progression-free survival (PFS, P=0.007, P=0.007), and distant metastasis-free survival (DMFS, P=0.001, P=0.000). The gross tumor volume of the nasopharynx was an independent negative prognostic factor for OS (P=0.013). Cox regression analysis indicated that there were no significant differences in OS, PFS, DMFS, or local relapse-free survival (LRFS) between NPC patients with T4 stage disease and those with T3 and paranasal sinus invasion (P>0.05). The updated T + N staging system slightly improved the prediction of LRFS (0.649, 95% CI: 0.553–0.745) in NPC patients compared to the AJCC system (0.640, 95% CI: 0.545–0.736; P=0.023). Paranasal sinus invasion is independently associated with a poor prognosis in NPC patients. Thus, we recommend that the AJCC staging system upgrade paranasal sinus invasion to the T4 classification.

WT1 Gene Expression in Peripheral Blood Before and After Allogeneic Stem Cell Transplantation is a Clinically Relevant Prognostic Marker in AML – A Single-center 14-year Experience

BackgroundThis work summarizes our experience with WT1 monitoring before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and MethodsThe expression of WT1 gene was measured by real-time polymerase chain reaction in peripheral blood according to the European Leukemia Net recommendations. Between May 2005 and August 2019, we analyzed 147 consecutive patients with acute myeloid leukemia with high WT1 expression at diagnosis, transplanted in first (CR1) or second (CR2) complete remission. ResultsAt the time of allo-HSCT, 107 patients had WT1-normal expression (WT1 ≤ 50 copies), and 40 patients had WT1-high expression. The median follow-up was 21 months. The estimated 5-year overall survival and event-free survival was significantly better in the WT1-normal cohort (65% and 57% vs. 37% and 25%; P = .0003 and P < .0001, respectively) and 5-year cumulative incidence of relapse was significantly lower in the WT1-normal group (19% vs. 53%; P < .0001). Five-year non-relapse mortality was not significantly different (20% and 23%). Multivariate analysis revealed WT1-high expression and acute graft-versus-host disease grade 3/4 as significantly negative prognostic factors for OS. Overall, 49 patients developed WT1 molecular relapse in the post-transplant period; in 14 cases, the therapeutic intervention was done. In all but 1 relapsed patient where WT1 minimal residual disease (MRD) was monitored (38 patients), we detected WT1-high levels (sensitivity of 97%). ConclusionThe results of the analysis confirmed our previous experience that WT1 status before allo-HSCT is a strong prognostic factor for both OS and relapse risk. In addition, we confirmed the usefulness of this marker for MRD monitoring after allo-HSCT. The main advantage is the possibility of frequent MRD monitoring in peripheral blood and early bone marrow examination based on WT1-high expression.

Prognostic value of MRI-determined cervical lymph node size in nasopharyngeal carcinoma.

ObjectivesTo investigate the prognostic value of magnetic resonance imaging (MRI)‐determined cervical lymph node (CLN) size in nasopharyngeal carcinoma (NPC).MethodsWe retrospectively reviewed 2066 patients with NPC treated with intensity‐modulated radiotherapy, and randomly divided them into two groups, in a 1:1 ratio. One group was used for training (the training group), and the other one was for internal validation (the validation group). All patients had undergone MRI examination and the maximal axial diameters (MAD) of the axial plane of all positive nodes had been measured and recorded.ResultsOf 683 patients with CLN metastases in the training group (n = 1033), MAD = 4 cm was associated with worse OS (64.7% vs 84.6%, P < .001), DFS (55.9% vs 76.3%, P = .001), and DMFS (67.6% vs 86.1%, P = .001). Multivariate analysis showed that MAD = 4 cm was a significant negative prognostic factor for OS (HR = 2.058; P = .025), DFS (HR = 1.727; P = .049), and DMFS (HR = 2.034; P = .036). When MRI‐determined MAD = 4 cm was classified as N3 in the N classification, the OS, DFS, DMFS, and RRFS survival curves were well separated. The OS, DFS, DMFS, and RRFS concordance indexes were not statistically different between the proposed N staging system and the UICC/AJCC staging system in the training group, or between the training group and the validation group (all P = .05).ConclusionMAD = 4 cm on axial MRI slices can be recommended as a prognostic factor in future versions of the UICC/AJCC NPC staging system.

Oropharyngeal Squamous Cell Carcinoma in 390 Patients: Analysis of Clinical and Histological Criteria Which Significantly Impact Outcome.

This study evaluates the prognostic impact of several factors in oropharyngeal squamous cell carcinoma (OPSCC), controlling for human papillomavirus (HPV)-associated tumors and stage (American Joint Committee on Cancer 8th edition). All patients in Southern California Permanente Medical Group diagnosed with OPSCC between 2006 and 2012 tested for p16 immunohistochemistry were included. Review of all pathology materials was combined with central p16 testing. Multivariable analyses were performed. The cohort of 390 patients included 342 p16-positive and 48 p16-negative tumors. For all-comers, on univariate analysis, the following factors, when present, were associated with improved patient survival: p16-positive tumor (n = 324, p < 0.001); crypt versus surface tumor location (n = 312, p = 0.004); nonkeratinizing type (n = 309, p < 0.0001); nonkeratinizing with maturation type (n = 37, p < 0.0001); basaloid pattern (n = 284, p = 0.005); and a broad, pushing border of infiltration (n = 282, p = 0.004). Inferior survival outcomes were observed with: age ≥ 55years (p < 0.0001); ≥ 10 pack-year smoking history (n = 183, p = 0.003); increasing tumor stage (p < 0.0001); overt radiographic extranodal extension (ORENE) (n = 58, p < 0.0001); low level IV/Vb lymph node involvement (n = 45, p = 0.0002); a jagged pattern of infiltration (n = 76, p = 0.0004); tumor ulceration (n = 76, p = 0.0004); absent lymphocytic infiltrate (p < 0.0001); and concurrent dysplasia (n = 125, p = 0.009). On multivariable analysis, accounting for patient age, smoking history ≥ 10 pack-years, and TNM stage, for patients with p16-positive disease, advanced TNM stage (p = 0.007), the presence of ORENE (p = 0.0002), and low-neck lymphadenopathy (p = 0.0001) were independent negative prognostic factors for disease free survival (DFS). Older age (p < 0.0001), smoking history ≥ 10 pack-years (p = 0.02), advanced TNM stage (p = 0.0002), ORENE (p = 0.004), and low-neck lymphadenopathy (p = 0.002) were independent negative prognostic factors for OS. Among patients with p16-positive OPSCC, older age, smoking history, advanced stage, ORENE, and low-neck lymphadenopathy were significant negative prognostic factors for DFS and/or OS. Further refinement of staging to incorporate additional lymph node findings may be warranted.

Chronological changes in skeletal muscle mass following living-donor liver transplantation: An analysis of the predictive factors for long-term post-transplant low muscularity.

Sarcopenia is associated with high morbidity and mortality before and after liver transplantation (LT). The aim of the study was to evaluate the chronological changes in skeletal muscle mass (SMM) at different time points post-LT and to identify the risk factors for long-term low SMM. The skeletal muscle index at L3 level (L3-SMI) was used for muscle mass measurement, and the recommended cutoff values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity. Preoperative low SMM was recognized in 35.1% of cases. At 1year after LDLT, 28.9% of patients showed low SMM, without any significant prevalence change in comparison with the preoperative phase (35.1%) or 1month post-LT (30.7%). Post-LT intensive care unit (ICU) length of stay (OR 1.14, P=0.03), biliary complications (OR 5.88, P=0.02), pre-LT low SMM (OR 3.36, P=0.05), and 1month post-LT low SMM (OR 10.16, P<0.01) were found to be independent risk factors for low SMM at 1year post-LT in multivariate analysis. The development of de novo low SMM at 1year post-LT was a negative prognostic factor for OS (HR 9.08, P=0.001). Intensive care unit length of stay, biliary complications and preoperative and 1month post-LT low SMM were predictive factors for long-term low SMM. Newly developed low SMM at 1year post-LT was a prognostic factor for a poor patient survival.

The prognostic value of TP53 and its correlation with EGFR mutation in advanced non-small cell lung cancer, an analysis based on cBioPortal data base

ObjectivesThe prognostic value of TP53 in advanced non-small-cell lung cancer (NSCLC) is unclear. Whether different mutated exon has different prognostic value is unknown. We sought to reveal the prognostic value of TP53 in advanced NSCLC, as well as the correlation with EGFR mutation. Materials and MethodsInformation regarding TP53 and EGFR alterations and patients’ survival time in advanced NSCLC was downloaded from the Cancer Genome Atlas Database. We further subdivided TP53 and EGFR mutation into subgroups based on different mutation exon, and then evaluated the distribution of different mutation exon as well as the prognostic value. Results and ConclusionOverall, 1441 pieces of data from 1441 metastatic NSCLC patient were collected. Mutation rate of TP53 was 56.1% (809/1441). TP53 mutation was a negative prognostic factor for OS. The estimated survival time for wild type TP53 and mutated TP53 was 27.0 months (95% CI, not reached) and 19 months (95% CI, 16.62 to 21.38), respectively, (p < 0.001). We divided TP53 mutations into 4 groups, OS in these 4 groups was 27 months (95% CI, not reached), not reached, 21 months (95% CI, 17.16 to 24.84) and 13 months (95% CI, 10.39 to 15.61). The difference was statistically significant (p < 0.001). Patients with EGFR exon 19/21 or non-exon 19/21 mutation demonstrated a higher rate of mutated type TP53 than EGFR wild type patients. Survival curve in EGFR wild type patients indicated that TP53 wild type patients had the best prognosis. In patients with exon 19/21 mutated EGFR, the trend was the same (P < 0.001).TP53 mutation is a negative prognostic factor in advanced NSCLC, different mutated exon has different prognostic value. When coupled with EGFR mutation, we can predict the prognosis of advanced NSCLC patients more accurately.

A real-world study of treatment patterns and survival outcome in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Crizotinib is an anti-cancer drug with a substantial beneficial effect in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, the real-world data currently available on this drug are limited. Thus, the present study aimed to retrospectively examine the treatment patterns and survival outcome of 83 advanced NSCLC patients with ALK rearrangement in a single center in China. Of the 83 patients enrolled, 33 (39.8%) patients received crizotinib and the remaining 50 (60.2%) patients received chemotherapy as the initial therapy. The first-line use of crizotinib prolonged the PFS1 (progression-free survival to the first detection of subsequent disease progression) compared with chemotherapy (median, 18.5 vs. 4.9 months; P<0.001), however, it did not prolong the overall survival (OS; P=0.802). At the last follow up, 71 (85.5%) patients had received crizotinib and 12 (14.5%) patients were crizotinib-naive. Patients who had received crizotinib exhibited a significantly longer OS as compared with those who were crizotinib-naive [hazard ratio (HR) for mortality, 0.279; 95% confidence interval, 0.107-0.727; P<0.05). Among the 71 patients who had received crizotinib, this was administered as a first-line therapy in 33 (46.5%) cases, as a second-line therapy in 22 (31.0%) cases and after the second-line therapy in 16 (22.5%) cases. No significant difference in the OS among the three groups was observed (P=0.577). The Cox multivariate analysis identified the following independent negative prognostic factors for OS: Smoking history (HR=4.565), liver invasion at diagnosis (HR=4.294) and bone invasion at diagnosis (HR=2.587). In addition, the use of crizotinib (HR=0.319) was identified as a positive prognostic factor for OS. In conclusion, the present real-world study revealed that the use of crizotinib improved the long-term survival of patients with ALK-positive advanced NSCLC. There was no difference in survival outcome between patients with initial use of crizotinib and those with subsequent use of crizotinib after first-line therapy.

Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer.

81 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use. Recently we reported early elevation of plasma VEGF-A was associated with shorter survival as a preliminary result. We will report the results of final analysis. Methods: Patients with advanced gastric cancer who received ramucirumab combined with paclitaxel or single use were enrolled. Plasma samples were collected at pre-treatment and day 8 after administration. Nine kinds of plasma biomarker involved in angiogenesis, VEGF-A, C, D, PlGF, VEGFR1, 2, Angiopoietin 1, stromal cell derived factor-1α (SDF1α), and Neuropirin-1, were measured by means of ELISA. Patients were dichotomized by optimal cut-off value. Univariate and multivariate analysis were done by Cox proportion hazard model. Results: Forty-one patients were enrolled. Thirty-nine patients (95.1%) received ramucirumab with paclitaxel. Plasma VEGF-A, D, PlGF, and VEGFR2 levels were significantly increased one week after administration compared with baseline levels, while plasma VEGFR1 and NRP1levels were significantly decreased. Median PFS and OS were 5.6 (95% CI 4.66-6.54) and 9.8 (95% CI 5.41-14.19) months, respectively. In univariate analysis, higher baseline SDF1α and PlGF levels resulted in shorter OS with HR 2.71 95% CI 1.23-6.00, p =0.013 for SDF1α and HR 2.78 95% CI 1.16-6.65, p =0.022 for PlGF. Higher D8 VEGF-A was associated with shorter PFS with HR 2.77 95% CI 1.39-5.51, p =0.004. While higher D8 VEGF-D was associated with better PFS with HR 0.39 95% CI 0.20-0.77, p =0.007. In multivariate analysis, higher baseline SDF1α and PlGF were independent negative prognostic factor for OS with HR 2.45 95% CI 1.10-5.42, p =0.028 for SDF1α and HR 2.48 95% CI 1.03-5.96, p =0.043. With respect to PFS, higher D8 VEGF-A was also independent negative prognostic factor with HR 2.32 95% CI 1.13-4.77, p =0.022, while higher D8 VEGF-D was favorable predictor for PFS with HR 0.47 95% CI 0.23-0.96, p =0.038. Conclusions: Higher base line SDF1α and PlGF levels may be negative prognostic marker. While early VEGF-A and D elevation after ramucirumab administration may be predictive marker of ramucirumab.

Preoperative platelet-lymphocyte ratio is an independent factor of poor prognosis after curative surgery for colon cancer.

Interaction between tumour and host triggers a systemic inflammatory response. This situation has been associated to cancer progression. Several peripheral blood inflammatory scores have been recently developed, as PLR. Data about the relationship between these scores and cancer prognosis are contradictory. Therefore, the aim of our work is to evaluate the capability of PLR to predict long-term outcomes (OS and RFS) in patients who underwent curative surgery for colon cancer. A retrospective study was designed with patients who underwent curative surgery for colon cancer between September 2008 and January 2012 at Rio Hortega University Hospital, Valladolid (Spain). We analysed the influence of PLR and other clinical variables on OS and RFS. Finally, 201 patients were analysed. Optimal cut-off value for PLR, established with ROC curves, was 153. 1-, 3- and 5-year OS were: 99.0, 90.4 and 82.3% for low PLR, and 93.8, 74.9 and 61.9% for high PLR, p<0.001. 1-, 3- and 5-year RFS were: 92.4, 84.7 and 77.6% for low PLR, and 83.3, 64.5 and 52.6% for high PLR, p<0.001. In MVA, high PLR was an independent negative prognostic factor for OS (HR=2.11; 95% CI 1.22-3.66; p=0.008) and RFS (HR=1.99; 95% CI 1.19-3.34; p=0.009). PLR represents an independent negative prognostic factor for OS and RFS in our sample of patients who underwent curative surgery for colon cancer. However, further studies with a larger sample size from different populations are necessary to confirm this conclusion.

PS02.18 Characterization of Patients with KRAS-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Community Practice Setting: Topic: Medical Oncology

No targeted therapy is currently approved for KRAS-mutant NSCLC despite being the most common molecular-defined subset of NSCLC, and data are limited in real-world populations. The purpose of this study is to understand the demographic, pathologic, and clinical characteristics associated with KRAS testing and mutations among patients with NSCLC. This retrospective study using the Flatiron Health NSCLC cohort included community practice patients diagnosed with de novo or recurrent advanced NSCLC from 1 Jan 2011 to 31 Dec 2016. Patients were divided into KRAS tested and not tested groups, the former being further divided into KRAS mutated (KRASm+) and KRAS wild-type (KRASwt). PD-L1 status was abstracted exactly as stated in the test report; no additional interpretation based on staining percentage was applied by the data abstractor. Descriptive analyses were conducted and association between KRAS mutation and OS was evaluated by a multivariate Cox model. Of 29,903 patients meeting study criteria, 5588 (19%) were tested for KRAS mutations. KRAS testing was more commonly conducted in patients who were female (21% vs 17% for males, P<0.001), had non-squamous histology (23% vs 8% for squamous and 13% for NOS, P<0.001), and were <55 years (22% vs 21% for 55-65 years, and 17% for >65 years, P<0.001). Race, region, performance score and practice volume also had a significant effect on whether KRAS was tested. Non-smokers were more likely to be tested than smokers, regardless of sex (29% vs 19% in females P<0.001; 26% vs 16% in males, P<0.001). Over half (53%) of tested patients were tested prior to starting first-line therapy. Of patients tested for EGFR, ALK, ROS, and PD-L1, 97%, 92%, 58% and 21%, respectively, had KRAS tested concurrently. Patients with KRASm+ (n=1602, 29%) were more likely to have smoking history (90% vs 76%, P<0.001) and non-squamous histology (92% vs 82%, P<0.001) than patients with KRASwt. The prevalence of KRASm+ was 31%, 23%, and 13% for White, African-American/Black, and Asian patients, respectively. Prevalence of overlap mutations included: KRAS with EGFR 2.5%, ALK 0.5%, ROS 0.4%, and PD-L1 39.9%. Among treated patients, KRASm+ was a negative prognostic factor for OS from the start of first-line therapy (adjusted HR 1.24; 95% CI 1.13, 1.36). Our findings add to current knowledge by describing the adoption of KRAS testing and characteristics of KRASm+ patients in a community setting, particularly with respect to overlap of PD-L1 and KRAS and the prognostic significance of KRAS mutations.