Risk Factors For Progression-free Survival Research Articles

Prognostic Value of Prognostic Nutritional Index in Patients With Colorectal Cancer Undergoing Surgical Treatment

BackgroundTo investigate the relationship between prognostic nutritional index (PNI) and the survival of patients with colorectal cancer (CRC) undergoing surgical treatment.MethodsIn total 1,014 CRC patients who underwent surgical treatment were enrolled. Logistic regression analysis was used to identify the features that influenced postoperative complications in CRC patients. Restricted cubic spline was used to assess the dose-response relationship between PNI and survival in CRC patients. Kaplan-Meier method and log-rank test were used to compare survival differences between groups of CRC patients. Cox proportional risk regression models was used to assess independent risk factors for progression-free survival (PFS) and overall survival (OS) of CRC patients.ResultsLow PNI was associated with high tumor burden, invasive pathological features, and poor host status. Compared with patients with high PNI, patients with low PNI have a higher incidence of complications and longer hospital stay. Low PNI was an independent risk factor for postoperative complications in CRC patients. for every SD increased in PNI, the risk of poor prognosis for CRC patients was reduced by 2.3% (HR = 0.977, 95%CI = 0.962–0.993, p = 0.004) in PFS, and 2.3% (HR = 0.977, 95%CI = 0.962–0.993, p = 0.004) in OS. PNI was an independent prognostic factor affecting the PFS and OS of CRC patients. Finally, we constructed the PNI-based nomograms to predict postoperative complications, 1–5 years PFS and OS in CRC patients. Concordance index and calibration curve indicated that the PNI-based nomograms have moderate prediction accuracy.ConclusionPNI is an independent risk factor affecting postoperative complications, PFS and OS of CRC patients, and is a useful supplement to the TNM stage.

Co-Expression and Combined Prognostic Value of CSPG4 and PDL1 in TP53-Aberrant Triple-Negative Breast Cancer.

BackgroundIn triple-negative breast cancer (TNBC), PDL1/PD1-directed immunotherapy is effective in less than 20% of patients. In our preliminary study, we have found CSPG4 to be highly expressed together with PDL1 in TNBCs, particularly those harboring TP53 aberrations. However, the clinical implications of co-expressed CSPG4 and PDL1 in TNBCs remain elusive.MethodsA total of 85 advanced TNBC patients treated in the Hunan Cancer Hospital between January 2017 and August 2019 were recruited. The expressions of CSPG4 and PDL1 in TNBC tissues were investigated using immunohistochemistry (IHC). The RNA-seq dataset from the TCGA-BRCA project was further used to analyze the mRNA expression of CSPG4 and PDL1 in TP53-aberrant TNBCs. Cox proportional hazards model and Kaplan–Meier curves with Logrank test was used to analyze the effects of CSPG4 and PDL1 on survival. TNBC cell lines were further used to investigate the molecular mechanism that were involved.Results TP53 aberrations occurred in more than 50% of metastatic TNBCs and were related to higher tumor mutation burden (TMB). In TCGA-BRCA RNA-seq dataset analysis, both CSPG4 and PDL1 levels were high in TNBCs, especially in TP53-aberrant TNBCs. IHC assay showed nearly 60% of advanced TNBCs to be CSPG4-positive and about 25% to be both CSPG4-positive and PDL1-positive. The levels of CSPG4 and PDL1 were high in TNBC cell lines as revealed by flow cytometry and immunoblotting compared with non-TNBC cells. Univariate Cox regression analysis indicated that CSPG4 positivity was a significant risk factor for progression-free survival in metastatic TNBCs, with a hazard ratio (HR) of 2.26 (P = 0.05). KM curves with Logrank test also identified high level of CSPG4 as a significant risk factor for overall survival in advanced breast cancers in TCGA-BRCA samples (P = 0.02). The immunoblotting assays showed that EMT-related pathways were involved in CSPG4-mediated invasion.ConclusionsCSPG4 expression level is associated with PDL1 positivity in TP53-aberrant TNBC cells. Patients with CSPG4 expression have poor treatment response and poor overall survival. Co-expressed CSPG4 and PDL1 may have an important prognostic value and provide new therapeutic targets in TNBC patients. CSPG4 might mediate tumor invasion and PDL1 overexpression through EMT-related pathway.

GLIM Criteria-Defined Malnutrition Informs on Survival of Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy

Studies regarding malnutrition in patients with nasopharyngeal carcinoma (NPC) using the Global Leadership Initiative in Malnutrition (GLIM) criteria are still limited. Our study aimed to investigate the prevalence of malnutrition using the GLIM criteria in NPC patients receiving radiotherapy and explore the relationship between pre-radiotherapy (pre-RT) malnutrition and survival. A total of 113 NPC patients were enrolled for nutritional assessment using the GLIM criteria at different radiotherapeutic time points, and related toxicities were graded. Regarding the results, 19 patients (16.8%) were malnourished before radiotherapy and 103 patients (91.2%) were malnourished at the end of radiotherapy. Among the phenotypic GLIM criteria, low fat-free muscle index (FFMI) before radiotherapy was associated with mucositis and radiodermatitis (p < 0.05). Importantly, patients with malnutrition before radiotherapy had significantly poorer 2-year progression free survival (PFS) than the patients being well-nourished (62.1% vs. 88.9%, p = 0.015). From the multivariate Cox regression model, being-well nourished before radiotherapy was the protective factor for PFS (HR: 0.27; 95%CI: 0.089-0.85; p = 0.023) and male was the risk factor for PFS (HR: 7.25; 95%CI: 1.548-34.00; p = 0.012). In conclusion, malnutrition according to the GLIM criteria is common in NPC patients undergoing radiotherapy, and pre-RT malnutrition is correlated with survival. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2044059.

Predictive Factors Affecting Metastasis of Small Renal Mass and Its Prognostic Analysis

Background:The incidence of small renal mass (SRM) increases, and the prognosis of SRM is poor once metastasized. Therefore, we conducted this study to assess the clinical and pathological characteristics of SRM to determine the risk factors that influence the metastasis and prognosis of SRM.Methods:A small renal mass is defined as a solid tumor mass with the largest diameter of 4 cm or less on the pathological diagnosis. The metastasis is confirmed by imaging or pathological examination. We retrospectively included 40 patients with metastatic SRM (mSRM) treated in the department of urology of Peking University Third Hospital from October 2002 to October 2020. Meanwhile, 358 patients with nonmetastatic SRM treated in our hospital from January 2015 to December 2017 were selected as controls. Clinicopathologic features were compiled.Results:Multivariate logistic regression analysis showed that age (P = .027, odds ratio [OR] = 1.037, 95% confidence interval [CI] 1.004-1.070), clinical symptoms (P < .001, OR = 4.311, 95% CI 1.922-9.672), World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade 3/4 (P = .004, OR = 7.637, 95% CI 1.943-30.012; P = .004, OR = 20.523, 95% CI 2.628-160.287), and lymphatic invasion (P = .030, OR = 15.844, 95% CI 1.314-191.033) were risk factors for distant metastasis of SRM. Once metastasis occurs, the prognosis of SRM is poor. Multivariate Cox regression analysis of the prognosis of mSRM showed that age (P = .016, hazard ratio [HR] = 1.125, 95% CI 1.022-1.239), preoperative serum creatinine (P = .041, HR = 1.003, 95% CI 1.000-1.005), vascular invasion (P = .041, HR = 1.003, 95% CI 1.000-1.005), and metastasis (P < .001, HR = 24.069, 95% CI 4.549-127.356) were risk factors for overall survival (OS), and only metastasis (P < .001, HR = 9.52, 95% CI 5.43-16.7) was a risk factor for progression-free survival (PFS) of SRM.Conclusions:SRM with advanced age, clinical symptoms, high pathological nuclear grade, and lymphatic invasion are more likely to have distant metastasis. And SRM with older age, poor preoperative basic renal function, pathological vascular invasion, and metastasis have worse OS.

Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression.

Purpose: The present retrospective study aimed to evaluate the efficacy and safety of camrelizumab addition to transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC) with TACE-related untreatable progression (UP). Methods: Patients with HCC who received addition of camrelizumab due to UP after initial TACE treatment were enrolled at our institution between May 2019 and January 2021. Patients were assessed for tumor response, progression-free survival (PFS), and adverse events (AEs). Risk factors for PFS were evaluated with logistic regression analysis. Results: A total of 41 patients were included. The objective response rates (ORR) and disease control rates (DCR) were 24.4% and 61.0% at 2 to 3 months, and 12.2% and 58.5% at 6 months, respectively. The median PFS of the patients were 6 months (95% confidence interval [CI]: 3.8 months, 8.2 months). Of the 41 patients, 23 received camrelizumab combined with TACE (hereafter, camrelizumab–TACE) on whom 52 combined TACE procedures were performed, with a median of 2 procedures (range: 1-6) per patient. The remaining 18 patients received camrelizumab alone due to TACE contraindications. Multivariable analysis indicated that camrelizumab–TACE was an independent prognostic factor for PFS. Subgroup analysis showed a median PFS of 8 months in the camrelizumab–TACE group and 3 months in the camrelizumab monotherapy group (P < .001). No treatment-related mortalities occurred. Seventeen patients (41.5%) developed at least 1 type of AE after treatment with camrelizumab, with reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 14, 34.1%) being the most common AE. Conclusion: Addition of camrelizumab to TACE offered an effective and safe treatment for HCC with UP.

Renal cell carcinoma with tumor thrombus growing against the direction of venous return: an indicator of complicated surgery and poor prognosis

PurposeTo explore the effect of tumor thrombus growing against the direction of venous return (GADVR) tumor thrombus on the choice of surgical approach, the impact on the complexity of the surgery and the prognosis.MethodsWe retrospectively analyzed the clinicopathological data of 213 patients, who underwent surgery in a single center of Peking University Third Hospital between January 2016 and June 2020. For right renal cell carcinoma (RCC) and venous tumor thrombus (VTT), imaging revealed a filling defect in the left renal vein, which was significantly enhanced in enhanced imaging, suggesting that the tumor thrombus grew against the direction of venous return into the left renal vein. For left RCC and VTT, at least one of the left renal vein branches has tumor thrombus. The branches include the left adrenal vein, the left gonadal vein (testicular vein or ovarian vein), and the left ascending lumbar vein. The patients were divided into two groups according to whether they were GADVR tumor thrombus, and we compare the clinicopathological characteristics of GADVR tumor thrombus and non-GADVR tumor thrombus. Univariate and multivariate Cox regression analyses were performed to explore the risk factors that affect the prognosis of patients with RCC and VTT. Kaplan–Meier plots were conducted to evaluate the effect of GADVR on progression-free survival (PFS).ResultsCompared with non-GADVR tumor thrombus, patients with GADVR tumor thrombus had a higher proportion of open surgery (76.2% vs. 52.1%, P = 0.035), a higher proportion of tumor thrombus adhering to the inferior vena cava (IVC) vessel wall (81% vs. 45.8%, P = 0.002), a higher proportion of segmental resection of the IVC vessel wall (61.9% vs. 15.6%, P < 0.001); higher preoperative serum creatinine value (110.0 μmol/L vs. 91.0 μmol/L, P = 0.015), a higher proportion of tumor thrombus combined with bland thrombus (non-tumor thrombus) (57.1% vs. 19.8%, P < 0.001). In terms of surgical complexity, patients with GADVR tumor thrombus had a longer median operation time (379 min vs. 308 min, P = 0.038), more median surgical blood loss (1400 mL vs. 600 mL, P = 0.018), and more postoperative complications (52.4% vs. 30.7%, P = 0.045). Multivariate Cox regression analysis showed that GADVR tumor thrombus, symptoms, postoperative serum creatinine, distant metastasis, sarcomatoid feature, pathological type, lymph node dissection were independent risk factors for PFS. Patients with GADVR tumor thrombus’s median survival time was 14.0 months, while patients with non-GADVR tumor thrombus were 32.0 months (P = 0.016). GADVR tumor thrombus is an independent risk factor for PFS in patients with RCC and VTT.ConclusionGADVR tumor thrombus is a characteristic feature of tumor thrombus, with an incidence of 9.9%. It has a higher proportion of open surgery and higher surgical complexity, which is an independent risk factor for PFS.

Changes in serum lactate dehydrogenase levels as markers of pathological response and prognosis in colorectal liver metastases patients receiving neoadjuvant chemotherapy followed by resection.

This study sought to evaluate the effects of pre-neoadjuvant chemotherapy lactate dehydrogenase (pre-NAC LDH) levels, preoperative LDH levels, and changes in LDH levels on the pathological response and outcomes of colorectal liver metastases (CRLM) patients treated with liver resection after NAC. This study included 152 colorectal CRLM patients, who underwent NAC followed by liver resection. Patients were excluded if they were diagnosed with other malignancies or lacked follow-up and clinical data. Demographic and clinicopathological data were collected from hospital records. Pathological response and postoperative complications were measured according to the tumor regression grade (TRG) and Clavien-Dindo classification system, respectively. The optimal cutoff values were determined by the receiver operating characteristic curve and the X-tile analysis. Changes in LDH levels were graded as 0, 1, and 2. A logistic regression analysis was conducted to identify the independent predictors of pathological response and postoperative major complications. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors of progression-free survival (PFS) and overall survival (OS). The multivariate analysis indicated that a grade 2 LDH level change was a risk factor of an unfavorable histological response [odds ratio (OR) 0.249, 95% confidence interval (CI): 0.066-0.942; P=0.041] and major postoperative complications (OR 2.523, 95% CI: 1.179-10.530; P=0.024), which were independent of other clinical covariates. A pre-NAC LDH level ≥145 IU/L [hazards ratio (HR) 0.584, 95% CI: 0.359-0.950; P=0.030], a grade 1 LDH level change (HR 0.584, 95% CI: 0.359-0.950; P=0.030) and a grade 2 LDH level change (HR 0.447, 95% CI: 0.231-0.864; P=0.017) were independent prognostic predictors of PFS. A preoperative a LDH level ≥231 IU/L (HR 0.405, 95% CI: 0.192-0.852; P=0.017) and a grade 2 LDH level change (HR 0.362, 95% CI: 0.157-0.834; P=0.017) were independent prognostic factors of OS, which were independent of other clinical covariates. LDH levels and changes in LDH levels are potentially useful biomarkers for predicting the pathological response and prognosis of CRLM patients receiving NAC followed by liver resection.

Clinical Characteristics and Prognostic Factors of Primary FL Patients with Grade 3 or Large B Cell Transformation

To investigate the clinical characteristics and prognostic factors of primary follicular lymphoma (FL) patients with grade 3 or large B cell transformation, so as to provide more reference for the subsequent clinical diagnosis and treatment. Forty-seven primary FL patients with grade 3 or large B cell transformation from March 2010 to March 2018 were selected, the clinical characteristics and survival of patients were analyzed. Cox regression model were used to evaluate the related prognostic factors. The cumulative progression-free survival rate and cumulative overall survival rate of 47 patients in 3-year follow-up reached to 55.32% (26/47) and 80.85% (38/47) respectively. There were significant differences in cumulative progression-free survival rate and cumulative overall survival rate among different subgroups of IPI, FLIPI-1 and FLIPI-2 in 3-year follow-up (P<0.05). The cumulative progression-free survival rate during follow-up for 3-year in the patients with Ann Arbor staging for III-IV stage, lymph node-involved site≥5, lymph node-involved site with diameter more than 3 cm≥3 and extranodal lesions≥3 was significantly lower than other subgroups (P<0.05). The cumulative overall survival rate in 3-year follow-up of patients with LDH levels≥240 U/ml was significantly lower than patients with LDH levels < 240 U/ml (P<0.05). Univariate analysis showed that Ann Arbor stage for III-IV, lymph node-involved site number≥5, >3 cm lymph node-involved site number≥3, extranodal lesion site number≥2, IPI score=2-3, FLIPI-1 score and FLIPI-2 score≥3 were the risk factors for progression-free survival (P<0.05); LDH≥240 U/ml, IPI score=2-3 and FLIPI-2 score≥3 were risk factors for overall survival (P<0.05). Cox regression model multivariate analysis showed that IPI score=2-3 was the independent risk factor for progression-free survival and overall survival (P<0.05). FLIPI-2 score≥3 was the independent risk factor for overall survival (P<0.05). Primary FL patients with grade 3 or large B cell transformation by using the existing treatment regimen might be possibly curable, and the current treatment strategies and IPI score can be used to predict the clinical prognosis of patients.

Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res &amp; Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to &lt; 0.01 pg/mL and TT: from 0.12 to &lt; 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR &gt; 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values &lt; 0.01 pg/mL were independent prognostic risk factors for OS (p &lt; 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

Prognostic Nutritional Index identifies risk of early progression and survival outcomes in Advanced Non-small Cell Lung Cancer patients treated with PD-1 inhibitors.

Background: The prognostic nutritional index (PNI) is related to the prognosis of multiple malignancies. This study investigated whether the PNI has prognostic value in advanced non-small cell lung cancer (NSCLC) patients treated with programmed death 1 (PD-1) inhibitors.Methods: We retrospectively analyzed advanced NSCLC patients treated with PD-1 inhibitors from July 2018 to December 2019. Pretreatment PNI was calculated by peripheral lymphocyte count and serum albumin level, and the cut-off value was determined. Subsequently, we investigated the relationship between PNI and early progression, and evaluated its prognostic role on survival outcomes. Ultimately, based on the results of survival analysis, a nomogram was established.Results: A total of 123 patients were included. Of these, 24 (19.5%) patients had experienced early progression. Multivariate logistic analysis indicated that low PNI (odds ratio, 3.709, 95% confidence interval [CI], 1.354-10.161; P = 0.011) was closely correlated with early progression. Moreover, multivariate Cox regression analysis confirmed that low PNI was an independent risk factor for progression-free survival (hazard ratio [HR], 2.698, 95% CI, 1.752-4.153; P < 0.001) and overall survival (HR, 7.222, 95% CI, 4.081-12.781; P < 0.001), respectively. The prediction accuracy of nomogram based on PNI is moderate.Conclusion: PNI was an independent predictor of early progression and survival outcomes in advanced NSCLC patients treated with PD-1 inhibitors.

Chronic Myeloid Leukemia: Comparison of Survival between Pregnant and Non-Pregnant Women

The management of chronic myeloid leukemia (CML) during pregnancy is a subject of continuous debate and there are few reports on CML outcomes in these women. The aim of the study is to compare progression-free survival (PFS) and overall survival (OS) between women who became pregnant after the diagnosis of CML and those who did not, as well as describing the treatments performed during pregnancy and maternal-fetal outcomes.Methods:Retrospective study, including women under 45 years of age and diagnosis of CML between 1991 and 2018, from the database of the Clinical's Hospital of the University of Medical School of São Paulo and the Cancer Institute of the State of São Paulo-Brazil.Results:100 cases were reviewed and 98 were included for analysis. The PFS and OS of groups A (63 non-pregnant women) and B (35 pregnant women, totaling 46 pregnancies) did not show statistical difference in a median of 11 years of follow-up (p=0.15). In the multivariate analysis, only poor adherence to treatment was identified as an independent risk factor for PFS and OS (HR: 9.7, 95% CI: 1.9-47.7). Comparing women with unplanned pregnancies (group B-UP, n= 21) with group A and considering adherence, PFS was worse in group B-UP without adherence (p&amp;lt;0.0001). The non-adherence rate in groups A, B and B-UP was 22%, 40% and 52%, respectively. Of the women who received treatment during pregnancy (60%), 2 underwent leukapheresis, 18 received alpha interferon (IFN) and 1 hydroxyurea. Among those who had a major molecular response/ deep molecular response at the beginning of pregnancy and discontinued the Tyrosine Kinase Inhibitor (ITK), 63% lost response and of these, 90% recovered after reintroduction. None evolved with progression or death. Complications occurred in 37% of all pregnancies: 9 abortions, 3 premature, 3 hypertensive disordes of pregnancy, 1 placental abruption and 1 fetal distress. The conception occurred in the presence of ITK in 60% of pregnancies and 52% of them evolved with complications, including 2 fetal malformations (encephalocefele with absence of cerebellar vermis and hydrocele).Discussion:Literature is scarce regarding the outcome of CML in women who become pregnant. This is the first study that evaluates pregnancy as a risk factor for progression/death, comparing pregnant women and non-pregnant women in the same cohort. Although pregnancy does not have an impact on outcomes, women who have unplanned pregnancies have a greater chance of non-adherence and, consequently, worse PFS. Several studies have already observed that non-adherence to treatment increases the chance of treatment failure, as well as the risk of progression. However, there are no reports that unplanned pregnancies are alert for non-adherence. The rate of loss of response and its recovery after reintroducing the ITK was similar to that found in the literature. With the current possibility of maintaining remission after treatment interruption, it opens up possibilities for planning pregnancy since the beginning of the diagnosis of CML. There is no consensus on the best treatment of CML during pregnancy, but leukapheresis and IFN are known to be safe; while hydroxyurea and ITK should be avoided due to the risk of teratogenicity and pregnancy complications.Conclusion:Pregnancy itself does not interfere with long-term outcomes of CML, however, women who have an unplanned pregnancy are at increased risk of non-adherence, as well as progression and death due to CML and deserve a special approach. Disclosures No relevant conflicts of interest to declare.

A Retrospective Cohort Study on Pretreated Neutrophil-to-Lymphocyte Ratio and Prognosis of Small Cell Lung Cancer: Evidence of Effect Modification by Chemotherapy Regimen.

PurposeNeutrophil-to-lymphocyte ratio (NLR) has been suggested as an independent risk factor for progression-free survival (PFS) and overall survival (OS) in small cell lung cancer (SCLC). However, it is still unknown whether there is a linear relationship between the NLR and the risk of death in SCLC. The objective of this study is to provide further results.Patients and MethodsA retrospective cohort study was performed among a total of 251 participants with SCLC. Smooth curve fitting and piecewise Cox regression model were used to determine the linear relationship between NLR and mortality risk. A multivariable Cox regression model was used to estimate the effects of NLR on OS. Interaction and stratified analyses were conducted according to covariates.ResultsThe analysis indicated no significant nonlinear relationship or threshold effect between NLR and hazard of death. Multivariate analysis revealed that every unit increase in NLR was associated with a 10% increase in mortality risk. High NLR (>3.5) at baseline was associated with poor OS (hazard ratio [HR]=1.97, P=0.009). The difference in median OS duration between the high and low NLR groups was statistically significant (9.1 months vs 14.6 months, P=0.0067). Furthermore, interaction analysis identified the chemotherapy regimen to play an interactive role in the association between NLR and hazard of death.ConclusionNLR was identified as an independent risk factor for OS in SCLC and the linear correlation was observed between them. Administration of etoposide plus cisplatin (EP) regimen in patients with low NLR resulted in better long-term outcome than that of etoposide plus carboplatin (EC) regimen, while administration of the EC regimen conferred longer OS than that of the EP regimen in patients with high NLR.

Baseline bone marrow ADC value of diffusion-weighted MRI: a potential independent predictor for progression and death in patients with newly diagnosed multiple myeloma.

To illuminate the prognostic value of ADC (apparent diffusion coefficient), an important quantitative parameter of diffusion-weighted MRI, for multiple myeloma (MM). A prospective single-center study which enrolled 114 consecutive newly diagnosed MM patients with baseline whole-body diffusion-weighted MRI (WB DW-MRI) results was conducted. Baseline clinical and MRI parameters were analyzed with univariate and multivariate approaches to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). Five different DW-MRI patterns were seen, and the mean ADC value of the representative background bone marrow was 0.4662 ± 0.1939 × 10-3 mm2/s. After a mean follow-up of 50.2 months (range, 15.7-75.8 months), twenty-four patients died and seven were lost to follow-up. The mean ADC value of the representative background bone marrow was showed to be an independent risk factor for both PFS (HR 4.664; 95% confidence interval (CI) 1.138-19.121; p = 0.032) and OS (HR 14.130; 95% CI 1.544-129.299; p = 0.019). Normal/salt-and-pepper pattern on DW-MRI was associated with PFS using univariate analysis (p = 0.035) but lost the significance with multivariate Cox regression. Mean ADC value of the representative background bone marrow predicts both PFS and OS which suggests the role of baseline DW-MRI for risk stratification in newly diagnosed MM patients. • Whole-body diffusion-weighted MRI (WB DW-MRI) might be helpful to improve the current risk stratification systems for newly diagnosed multiple myeloma (MM). • Morphological parameters as MRI pattern and focal lesion-associated parameters have been reported to be related to survival. However, important functional parameters such as apparent diffusion coefficient (ADC) values were not incorporated into the current risk stratification model. • This study is one of the first endeavors to delineate the correlation of baseline ADC values and survival in MM patients. It is revealed that the mean ADC value of the representative background bone marrow (L3-S1 and iliac bone) was an independent risk factor for both PFS and OS.

Plasma Epstein-Barr Virus-Deoxyribonucleic Acid Copy Number Predicts Disease Progression in Stage I–III Pulmonary Lymphoepithelioma-Like Carcinoma

Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)- deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC).Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre- and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival.Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52–7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8–99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, p < 0.001).Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

Abstract 3174: Genomic alterations of TGFβ signaling genes as novel biomarkers for immunotherapy in patients with non-small cell lung cancer

Abstract Background: Cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have shown remarkable effects in non-small cell lung cancer (NSCLC), but a limited number of patients derive durable benefit from it. Therefore, more accurate biomarkers are highly needed. The transforming growth factor β (TGFβ) signaling signature was associated with a lack of response to ICIs in metastatic urothelial cancer. Genomic alterations (GAs) of the TGFβ signature were frequently detected by targeted next-generation sequencing (NGS) in NSCLC, but their correlation with recognized immune biomarkers and predictive value for ICIs response remains unclear. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and matched blood samples of 3433 NSCLC patients (2859 lung adenocarcinoma (LUAD), 406 lung squamous cell carcinoma (LUSC), and 168 other histologic subtypes) from OrigiMed were collected for targeted NGS panel sequencing from December 2017 to January 2019. GAs including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. PD-L1 expression positive was defined as ≥1% of tumor cells with membranous staining (22C3, DAKO). Genomic data and ICIs treatment outcome of a cohort of 240 NSCLC patients were derived from cBioPortal (MSKCC, J Clin Oncol 2018). Results: GAs of the TGFβ signaling genes were found in 7.1% of patients (244/3433) in the OrigiMed database, including TGFBR1 (n = 34), TGFBR2 (n = 40), SMAD2 (n = 24), SMAD3 (n = 23), and SMAD4 (n = 130). TGFβ signaling GA sites were found scattered throughout the genes, and no significant difference was observed in the frequency of these GAs within the histologic subtypes. TGFBR1, TGFBR2, SMAD2, and SMAD4 GAs were associated with a significantly higher tumor mutational burden (TMB) compared with wild-type (WT) cases in LUAD (p&amp;lt;0.01, respectively), while SMAD3 GAs were associated with a significantly higher TMB in LUAD and LUSC (p=0.019 and p=0.038, respectively). PD-L1 expression was detected in 32.4% of patients (1111/3433), including 73 patients with TGFβ signaling gene GAs. TGFβ signaling gene GAs were not correlated with PD-L1 expression. Survival analysis from an independent cohort confirmed that patients with SMAD4 GAs had a poor clinical benefit to ICIs compared with WT in both progression free survival (PFS) (1.97 months vs 3.5 months, respectively, p=0.02) and durable clinical benefit (DCB) (0% vs 32.5%, respectively, p=0.03). Furthermore, SMAD4 GAs were independent risk factors of PFS (HR: 2.01, 95%CI: 1.05-3.86, p=0.036). Conclusion: This study's findings revealed that the GAs of SMAD4 occurred in a subgroup of patients with LUAD and were associated with an unfavorable response to ICIs. This suggests that GAs of SMAD4 may have implications as a biomarker for guiding ICI treatment. Keywords: non-small cell lung cancer, SMAD4, tumor mutational burden, immunotherapy Citation Format: Shuben Li, Chengzhi Zhou, Jian Huang, Shiyue Zhang, Jiqiang He, Hui Chen, Shaohua Yuan, Weiwei Shi. Genomic alterations of TGFβ signaling genes as novel biomarkers for immunotherapy in patients with non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3174.

SET Domain Containing 2 Deficiency in Myelodysplastic Syndrome

Recent studies have shown that myelodysplastic syndrome’s (MDS) progression to acute myeloid leukemia (AML) is associated with gene mutations. SET domain containing 2 (SETD2) variants were reported as a risk factor of poor prognosis in patients with AML. However, little is known about the potential contribution of the SETD2 gene in MDS. In this study, we investigated the roles of SETD2 gene mutations/variants on clinical features and prognosis in patients with MDS. A 43-gene panel was used for next-generation sequencing in 203 patients with primary MDS, and then the effects of SETD2 mutation on Wnt/β-catenin signaling was investigated during the different stages of MDS. At a median follow up of 33 months, 65 (32.0%) deaths and 94 (46.3%) leukemic transformations were recorded. The most frequent mutations/variants included TET2, DNMT3A, and ASXL1 mutations/variants. 37 patients had SETD2 gene mutations/variants, and these patients exhibited a significantly increased frequency of TP53 mutations. Multivariate survival analyses indicated that SETD2 mutations/variants were closely associated with overall survival (OS), and they were identified as risk factors for progression-free survival (PFS), especially with low expression of SETD2 gene. Further, we found that SETD2 loss could promote MDS progression via upregulation DVL3 mRNA level in BM cells and it could also cause genomic instability. Secondary mutations, such as TP53 and FLT3 mutations, were acquired at the time of progression to AML. In conclusion, we showed that SETD2 deficiency was associated with poor outcomes in patients with MDS. Moreover, SETD2 deficiency may upregulate DVL3 expression and modulate genomic stability that caused AML transformation.

CCND2 mRNA Expression Is Correlated With R-CHOP Treatment Efficacy and Prognosis in Patients With ABC-DLBCL.

In this study we investigated whether the expression of cyclin D2 (CCND2) mRNA in activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) was correlated with the efficacy of Rituximab combined with chemotherapy (R-CHOP) treatment and patient prognosis. Tissue microarray and RNAscope in situ hybridization were used to detect CCND2 mRNA expression in 117 ABC-DLBCL tumor tissues and associations between CCND2 expression and progression-free survival was analyzed. We also downloaded data from the Gene Expression Omnibus database to analyze CCND2 expression and the efficacy of R-CHOP treatment and prognosis of patients with newly diagnosed ABC-DLBCL. The positive expression rate of CCND2 mRNA in patients with ABC-DLBCL was 41%. Progression-free survival was significantly lower in patients with positive rather than those negative CCND2 expression (P = 0.005). Further, R-CHOP treatment was significantly more effective for patients with ABC-DLBCL with high CCND2 mRNA expression than those with low expression (P = 0.039). Multivariate regression analysis suggested that high CCND2 expression was an independent prognostic risk factor for progression-free survival for patients with ABC-DLBCL who achieved complete remission after R-CHOP treatment. CCND2 expression in ABC-DLBCL tumors, detected by RNA in situ hybridization, is closely related to the curative effect of R-CHOP and patient prognosis following R-CHOP treatment, and represents a potential biomarker for treatment efficacy and prognostic evaluation in patients with ABC-DLBCL.

Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab.

The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

Cell-free DNA as a biomarker for colorectal cancer: a retrospective analysis in patients before and after surgery

This study was aimed at investigating the potential of cell-free DNA (cfDNA) as a biomarker for colorectal cancer prognosis. Sixty patients with colorectal cancer who had not undergone surgery were enrolled as study group. Their peripheral blood samples were collected, and peripheral blood of 30 healthy volunteers (control) was collected. The cfDNA concentration and integrity were determined using q-PCR so as to ascertain if cfDNA was associated with clinical presentations of the disease. Then, the specificities and sensitivities of cfDNA, CFA and CA199 were determined with ROC curve. The level and integrity of cfDNA in patients with colorectal cancer before surgery were significantly higher than those in patients with colorectal cancer after surgery, and cfDNA concentration of colorectal cancer patients after surgery was also significantly higher than that in healthy control group. However, the integrity was not significantly different from that of control group. There was a significant correlation between cfDNA concentration and TNM stage, differentiation degree and CEA expression, while cfDNA integrity was significantly correlated with TNM stage and degree of differentiation. Moreover, specificity and sensitivity of cfDNA concentration and integrity were higher than those of CEA and CA199. The TNM stage and cfDNA concentration were independent risk factors for progression-free survival (PFS) in colorectal cancer patients. In conclusion, cfDNA concentration and integrity were more sensitive and specific than traditional tumor markers (CA199, CEA). Thus, changes in cfDNA changes can be effectively used to determine the prognosis of postoperative colorectal cancer patients.

Therapeutic Strategies and Prognostic Factors Based on 121 Spinal Neurenteric Cysts.

Limited data existed to guide the management of intraspinal neurenteric cysts (ISNECs). To evaluate the risk factors for progression-free survival (PFS), elucidate the radiological features of ISNECs, and propose a treatment protocol. From 2003 to 2015, 121 patients with pathologically confirmed ISNECs treated at our institute were included in this study. Pertinent risk factors were evaluated. Gross total resection (GTR) was achieved in 55 (44.6%) patients; 106 (87.6%), 12 (9.9%), and 3 (2.5%) ISNECs were classified as Wilkins A, B, and C, respectively. After a median follow-up duration of 64.2 mo, recurrence occurred in 25 (22.7%) patients, with a median PFS time of 43.1 mo. The actuarial PFS rates at 5 and 10 yr were 73.2% and 66.2%, respectively. The actuarial overall survival rates at 5 and 10 yr were 100% and 97.6%, respectively. Non-GTR (hazard ratio [HR], 5.836; 95% confidence interval [CI], 1.698-20.058; P=.005), Wilkins B/C (HR, 3.129; 95% CI, 1.009-9.702; P=.048), and a history of surgical resection (HR, 3.690; 95% CI, 1.536-8.864; P=.004) were adverse factors. GTR and Wilkins A were favorable factors for PFS. If tolerable, GTR alone was advocated as an optimal treatment. Because of the benign nature and favorable prognosis, non-GTR was an alternative if GTR failed. Close follow-up was needed because of the recurrent tendency of ISNEC. Future study with a large cohort is necessary to verify our findings.