Poor Prognostic Factor For Overall Survival Research Articles

Comparison of oncologic outcomes between patients with Lynch syndrome and sporadic microsatellite instability-high colorectal cancer.

PurposeLong-term oncologic differences in outcome between groups of patients with Lynch syndrome (LS) colorectal cancer (CRC) and sporadic CRC with microsatellite instability-high (MSI-H) are the focus of investigation in the current study.MethodsPatients registered in the Korean Hereditary Tumor Registry and 2 tertiary referral hospitals treated for stage I–III CRC between 2005 and 2015 were retrospectively analyzed. Detection for both groups was performed using pedigree, microsatellite instability, and mismatch repair (MMR) gene testing. Multivariate analyses for overall survival (OS) and disease-free survival (DFS) were conducted.ResultsCases of LS (n = 77) and sporadic CRC with MSI-H (n = 96) were identified. LS CRC patients were younger in age and displayed tumor sidedness, typically involving left-sided colon and rectum, compared to patients with sporadic CRC with MSI-H. OS and DFS were lower for LS CRC relative to CRC with MSI-H (OS, 72.7% vs. 93.8%, P = 0.001; DFS, 71.4% vs. 88.5%, P = 0.001). In multivariate analyses, tumor sidedness, stage, and chemotherapy were independent factors for OS and DFS. LS CRC was a prognostic factor for poorer OS (hazard ratio, 2.740; 95% confidence interval, 1.003–7.487; P = 0.049), but not DFS.ConclusionOur findings indicate that LS CRC is associated with poorer outcomes compared to sporadic CRC with MSI-H, presenting distinct clinical features. In view of the current lack of knowledge on genetic and molecular mechanisms, appropriate management taking into consideration the difficulty of identification of CRC with hypermutable tumors harboring heterogeneity is essential.

Clinical Significance of Kinetics of Low-Density Lipoprotein Cholesterol and Its Prognostic Value in Limited Stage Small Cell Lung Cancer Patients.

Objectives:To investigate the clinical significance of dynamic alteration of serum lipids in limited stage small cell lung cancer (LS-SCLC) patients and the risk that different lipid profiles poses to patients’ health.Methods:We retrospectively analyzed the variation trends and prognostic values of serum lipids in 310 LS-SCLC patients who had received standard chemotherapy between 2002 and 2017. In addition to serum lipid level, which were measured at the time of pretreatment, after-chemotherapy and during disease progression and later analyzed, the dynamic lipid alteration trend and its correlation to progression-free survival (PFS) and overall survival (OS) were also statistically analyzed using Log-rank test and COX regression analyses.Results:A significant decrease in HDL-C level was observed after standard chemotherapy (Post-CT baseline = −0.08 ± 0.34, P < 0.001), and this trend of reduction was further enhanced by thoracic radiotherapy (P = 0.046). Increase in LDL-C level was also observed to be associated with higher likelihood of disease progression (P = 0.003). Moreover, the extent of the increase in LDL-C was also associated with the number of progression sites, as patients with higher increase in LDL-C in exhibiting a progression at more than 2 sites outside thorax (P = 0.037). The patients’ median PFS and OS were 14.04 months (95%CI: 25.12-33.81) and 22.40 months (95%CI: 33.19-42.13), respectively. For both PFS and OS, LDL-C elevation remained an independent prognostic factor in the multivariate model (P = 0.007 and P = 0.022, respectively).Conclusion:Overall, for LS-SCLC patients, standard chemotherapy decreases the level of HDL-C, the level of increase in LDL-C could predict disease progression and even the number of progression sites, and LDL-C elevation could be an independent prognostic factor for poor OS and PFS.

Significance of Glasgow Prognostic Scores in NSCLC Patients Treated With Immunotherapy After Platinum-based Cytotoxic Chemotherapy.

Little is known about the prognostic role of the Glasgow prognostic score (GPS) in non-small cell lung cancer (NSCLC) patients treated with immunotherapy after platinum-based cytotoxic chemotherapy. This study used a lung cancer cohort of the Catholic Medical Center of Korea between January 2018 and September 2020. A total of 78 patients with NSCLC treated with immunotherapy as second or further-line therapy were included. Higher GPS values were significant predictors of shorter immune-related progression-free survival (irPFS) and overall survival (OS). The hazard ratios for irPFS were 0.249 for programmed death-ligand 1 (PD-L1) expression ≥50% and 9.73 for a GPS of 2. Older age, lower PD-L1 expression and higher GPS values were independently associated with shorter OS. Higher GPS values were identified as a poor prognostic factor for OS and irPFS in NSCLC patients who received immunotherapy as second or further-line therapy.

Clinical Impact of Herpesvirus Entry Mediator (HVEM) in Malignant Liver Tumors

Background: Herpes virus entry mediator (HVEM), also known as tumor necrosis factor receptor (TNFR) superfamily 14, regulates a variety of physiological and pathological responses in both innate and acquired immunity. Recently, HVEM is also suggested to be a critical regulator in tumor immunity. This study aimed to clarify clinical importance of HVEM in human hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). Methods: This study examined 150 patients with HCC and 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO. Results: High HVEM expression was observed in 66 of 150 patients (44.0%) with HCC, and 49 of 104 patients (47.1%) with CRLM. Expression of HVEM was not associated tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (HCC: P=0.002, CRLM: P = 0.002). Multivariate analysis showed that independent poor prognostic factors of OS for HCC were high HVEM expression in HCC and tumor size >5 cm, while in CRLM, high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors were prognostic factors of OS. HVEM status was inversely correlated with tumor-infiltrating CD8+ and CD45RO+ lymphocytes in both HCC and CRLM. Conclusions: Tumour-expressing HVEM might play a critical role in human HCC and CRLM, possibly through regulating immune evasion. Therefore, targeting HVEM may be a novel promising therapeutic strategy for HCC and CRLM.

Deep and partial immunoparesis is a poor prognostic factor for newly diagnosed multiple myeloma patients

We retrospectively analyzed immunosuppression status in 287 newly diagnosed multiple myeloma (MM) patients and assessed the prognostic value of immunoparesis on survival. Deep immunoparesis was defined that one of uninvolved immunoglobulins was below 50% the lower limit of normal ranges, partial immunoparesis was defined at least two suppressed uninvolved immunoglobulins. We found that patients with deep and partial immunoparesis had a significantly shorter median overall survival (OS) and progression-free survival (PFS). Moreover, deep and partial immunoparesis was a poor prognostic factor for OS and PFS in univariate and multivariable analyses. To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis and found that patients with deep and partial immunoparesis also had shorter OS and PFS. Our study showed that deep and partial immunoparesis can be defined an independent poor prognostic factor for patients with newly diagnosed MM.

Early Loss of Fat Mass During Chemoradiotherapy Predicts Overall Survival in Locally Advanced Squamous Cell Carcinoma of the Lung, but Not in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

Background: Cancer cachexia is highly prevalent in advanced non-small cell lung cancer (NSCLC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC), and compromises treatment tolerance and overall survival (OS). NSCLC and LAHNSCC patients share similar risk factors, and receive comparable anti-cancer treatment regimens. The aim of this study was to determine the predictive value of body composition assessed by bioelectrical impedance analysis (BIA) and handgrip strength (HGS) (baseline and early changes during therapy) on OS in NSCLC and LAHNSCC patients treated with platinum-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (BRT). To elucidate potential underlying determinants of early changes in body composition and HGS, specific (fat and fat free) mass loss patterns of squamous NSCLC (sNSCLC) were compared to human papilloma virus negative (HPV–) LAHNSCC patients treated with CRT.Methods: Between 2013 and 2016, BIA and HGS were performed at baseline and after 3 weeks of CRT/BRT in LAHNSCC and NSCLC patients treated with curative intent.Results: Two hundred thirty-three patients were included for baseline measurements. Fat free mass index (FFMI) and HGS<10th percentile of reference values at baseline were both prognostic for poor OS in NSCLC and LAHNSCC [HR 1.64 [95%CI 1.13–2.39], p = 0.01 and HR 2.30 [95%CI 1.33–3.97], p = 0.003, respectively], independent of Charlson Comorbidity Index, cancer site, and gross tumor volume. Early fat mass (FM) loss during CRT was predictive for poor OS in sNSCLC (n = 64) [HR 3.80 [95%CI 1.79–8.06] p ≤ 0.001] but not in HPV– LAHNSCC (n = 61). In patients with significant weight loss (>2%) in the first 3 weeks of CRT (sNSCLC n = 24, HPV– LAHNSCC n = 23), the FM change was −1.4 ± 14.5% and −8.7 ± 9.0% in sNSCLC and HPV– LAHNSCC patients, respectively (p < 0.05). Fat fee mass change was −5.6 ± 6.3% and −4.0 ± 4.3% for sNSCLC and HPV– LAHNSCC, respectively (p = 0.31).Conclusion: FFMI and HGS<10th percentile at baseline are independent prognostic factors for poor OS in NSCLC and LAHNSCC patients treated with CRT/BRT. The specific composition of mass loss during first 3 weeks of CRT significantly differs between sNSCLC and HPV– LAHNSCC patients. Early FM loss was prognostic in sNSCLC only.

The preoperative and the postoperative neutrophil-to-lymphocyte ratios both predict prognosis in gastric cancer patients

BackgroundBoth the preoperative and postoperative neutrophil-to-lymphocyte ratios (NLRs) have been proposed to predict the long-term prognosis in some cancers, including gastric cancer. The present study investigated the prognostic impact of postoperative NLR, and its preoperative to postoperative changes, in patients with gastric cancer.MethodsFrom 2009 to 2012, 1227 consecutive patients who underwent curative surgery for gastric cancer were enrolled in this study. The optimal cut-off value for the postoperative 6-month NLR was 1.7, as determined by receiver operating characteristic curve analysis. Patients were categorized into low- and high-NLR groups based on their postoperative NLR. Four additional groups (low to low, low to high, high to low, and high to high groups) were defined based on the preoperative to postoperative change in the NLR.ResultsThe 5-year overall survival (OS) rates of the low- and high-NLR group were 90.7% and 83.0%, respectively (P < 0.001). The differences in OS were significant in stage I and stage III gastric cancer patients (P< 0.001 and 0.012, respectively). Postoperative NLR was an independent prognostic factor for OS (hazard ratio [HR] = 1.556; P = 0.010). The high to high NLR change was a significant predictor of OS (HR = 1.817; P = 0.003).ConclusionsHigh preoperative and postoperative NLRs, and especially the persistent elevation of preoperative to postoperative NLR, were significant poor prognostic factors for OS in patients with gastric cancer.

Outcomes and Prognostic Scoring System for Elderly Patients with Acute Myeloid Leukemia

Background: The prognosis of elderly patients with acute myeloid leukemia (AML) remains poor. Elderly patients are frequently intolerant to intensive chemotherapy due to poor performance status and co-morbidities. Moreover, considering the increase of genetic abnormalities, it is disputable whether conventional chemotherapy improves the prognosis of elderly AML patients. The purpose of this study is to identity patients who would benefit from conventional chemotherapy. Patients and Methods: We retrospectively analyzed the outcome of patients with AML aged over 65 years who received conventional chemotherapy based on the JALSG GML 200 protocol at our institution between December 2011 and January 2020. Patients with acute promyelocytic leukemia were excluded. No patients underwent hematopoietic cell transplantation (HCT). Dose reduction of each regimen was considered in patients over 70 years of age. MEC regimen was used for reinduction therapy in 70% of patients with induction failure. The primary end point was overall survival (OS) after induction therapy. Factors associated with the achievement of complete remission (CR) and overall mortality were analyzed using logistic regression and Cox proportional hazards models, respectively. Results: A total of 74 patients were analyzed. The median age was 72.8 years (range, 65-85). Nine patients (12%) had an ECOG performance status of 3-4. The most common AML subtype was AML with myelodysplasia-related changes (n=30, 41%) followed by AML with maturation (n=11, 15%). Twenty patients (27%) were previously diagnosed with myelodysplastic syndromes (MDS). According to the 2017 ELN stratification, 3 patients (4%) were classified as favorable-risk, 44 (60%) as intermediate-risk, and 27 (37%) as adverse-risk. Overall, 21 patients (28%) achieved CR after induction therapy. Among 53 patients with induction failure, 37 received reinduction therapy and 14 (38%) achieved CR. The ELN favorable- or intermediate-risk (OR, 23.2; 95% CI, 4.59-117.0, p&amp;lt;0.001) and age under 70 years (OR, 7.62; 95% CI, 1.54-37.8, p=0.013) were important factors associated with the achievement of CR. Median OS was 10.3 months for all patients and 19.3 months for patients who achieved CR after induction therapy. The probability of 3-year survival was 20.9% in the total patients. The day 100 and 1-year NRM incidences were 4% and 8%, respectively. In multivariate analysis, lower performance status (3-4) (HR, 3.93; 95% CI, 1.81-8.49, p&amp;lt;0.001), age 70 and older (HR, 3.38; 95% CI, 1.76-6.47, p&amp;lt;0.001), the ELN adverse-risk (HR, 3.16 95% CI, 1.83-5.47, p&amp;lt;0.001), and previous MDS diagnosis (HR=2.36, 95% CI=1.29-4.30, p&amp;lt;0.001) were the significant independent prognostic factors for poor OS. On the basis of the number of these four factors, the prognostic score was calculated for each patient and patients were categorized into five groups (score 0-4). The score was significantly correlated with OS (p&amp;lt;0.001, Figure). The probability of 1-year survival was 85.7% for score 0, 59.4% for score 1, and 5.9% for score 2. All patients for score 3 and 4 died within 1 year and their median OS was 2.8 months for score 3 and 0.4 months for score 4. Conclusions: Each two patient (age, performance status) and disease (ELN disease risk, history of MDS) factors were significantly associated with survival in elderly patients with AML. The prognostic scoring system based on the four factors clearly stratified survival, suggesting that it will be useful for making a treatment decision. Further large-scale studies are required to validate this system and a combination therapy with molecular targeted drugs should be established for patients with poor prognosis. Disclosures Seo: Janssen Pharmacuetical K.K.: Consultancy; Novartis: Speakers Bureau; Bristol Myers Squibb K.K.: Speakers Bureau; Meiji Seika Pharma.: Speakers Bureau. Ichikawa:Novartis, Takeda: Honoraria. Mitani:KYOWA KIRIN: Consultancy, Research Funding; CHUGAI: Research Funding; Takeda: Research Funding.

Salvage Radiation for Oligometastatic Recurrent Cholangiocarcinoma

Outcomes for recurrent cholangiocarcinoma (CCA) after surgical resection treated with chemotherapy alone are poor with few long-term survivors. Some recurrences, however, are limited and might benefit from aggressive local therapy in addition to systemic therapy. We analyzed patients with recurrent oligometastatic cholangiocarcinoma managed with ablative radiation. We performed a retrospective review of patients in a single institution that had upfront resection of cholangiocarcinoma and exhibited oligometastatic recurrence treated with radiotherapy. Baseline characteristics were obtained, and patients were analyzed for overall survival (OS), progression free survival (PFS), and local control (LC) after receiving radiation. Descriptive statistics were used to analyze patient characteristics. OS, PFS and LC were assessed using the Kaplan-Meier method and the Cox proportional hazards model. We identified 30 patients with oligometastatic CCA treated with radiation of which 25 had ≥ 1 month of follow imaging to assess response and were used for analysis. Median follow-up was 43 months (range, 17-118). 8 (32%) patients had recurrences at the resection margin, 11 (44%) patients had elsewhere within liver, 5 (20%) in regional lymph nodes, and one (4%) in the lung. Median time to recurrence after surgery was 16 months (range, 4-74). 19 (76%) patients received chemotherapy at recurrence. Intensity-Modulated Radiation Therapy (IMRT; 54.5 Gy median dose) was used in 12 (48%) patients and 13 (52%) had Stereotactic Body Radiation Therapy (SBRT; 48 Gy median dose). Concurrent chemotherapy was given for 8 of the IMRT patients. Median OS from diagnosis was 42.6 months (range, 17-118) and 22.6 months (range, 3-65) from the time ablative radiation was given. Median PFS after salvage radiation was 8.9 months (range, 2-40). LC was 67.5% at 1 year. On univariate analysis, poor prognostic factors for OS included non-white race (n = 14, HR, 3.9; 95% confidence interval, 0.99-15.8; P = 0.05), pre-primary resection CA19-9 ≥200 (5.8; 1.4 to 24.8; P = 0.02), and distal location of CCA (vs. intrahepatic, 14.6; 3.2-67.1; P<0.001). CA19-9 at diagnosis ≥ 200 (4.08; 1.01-16.5; P = 0.049) and distal CCA (12.47; 2.4-64.4; P = 0.003) were also poorly associated with PFS. SBRT, compared to IMRT, showed a trend towards a positive prognostic factor for OS and PFS (0.32; 0.1-1.05; P = 0.06). Use of chemotherapy prior to RT, use of concurrent chemotherapy, tumor characteristics at diagnosis such as TNM criteria, positive margins or perineural/lymphovascular invasion, site of recurrence, age or gender and time to recurrence after surgery were not associated with neither OS nor PFS. Salvage radiation for well selected recurrent oligometastatic cholangiocarcinoma is associated with favorable OS and PFS compared to historical controls. Further study of this rare population is warranted.

Outcomes in Patients with Chronic Kidney Disease After Liver Resection for Hepatocellular Carcinoma.

The aim of this study was to clarify the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with chronic kidney disease (CKD). In all, 204 patients who underwent primary liver resection for HCC between 2011 and 2019 were analyzed. Short-term and long-term outcomes were compared between the CKD and control groups. The CKD group was defined by a preoperative estimated glomerular filtration rate (eGFR) < 45mL/min/1.73m2 and chronic kidney disease Stage 3B or higher. Twenty-eight patients (13.7%) had CKD. No significant differences were observed in the overall complication rates between the groups (46.4% vs. 34.7% p = 0.229). The incidence of bile leakage was significantly higher in the CKD group than in the control group (14.3% vs. 4.0% p = 0.048), and the median postoperative hospital stay was significantly longer in the CKD group (11 vs. 9days p = 0.031). No significant differences were found in the disease-free survival between the two groups (p = 0.763), but overall survival (OS) was significantly worse in the CKD group than in the control group (p = 0.022). In the multivariable analysis, a CKD diagnosis (hazard ratio, 2.261; 95% confidence interval (CI), 1.139-4.486 p = 0.020) was identified as an independent poor prognostic factor for OS. The percentage of patients who died from cardiovascular disease was significantly higher in the CKD group (27.3% vs. 2.3% p = 0.023). Liver resection for HCC in CKD patients is associated with acceptable perioperative outcomes. However, cardiovascular disease may negatively affect the OS of CKD patients after liver resection.

Prognostic significance of complete blood count parameters in castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitors

BackgroundThis study investigated the prognostic significance of complete blood count data in castration-resistant prostate cancer patients treated using androgen receptor pathway inhibitors (ARPIs). Patients and MethodsPatients treated with an ARPI, abiraterone or enzalutamide, as first-line therapy for castration-resistant prostate cancer from 2014 to 2018 were included. The association between complete blood count data and prognoses including progression-free survival and overall survival (OS) was investigated. ResultsHigh white blood cell counts (<median vs. ≥median; hazard ratio [HR], 1.82, 95% confidence interval [CI], 1.14–2.89; P = 0.012) and high neutrophil-to-lymphocyte ratios (<median vs. ≥median; HR, 1.90, 95% CI, 1.11–3.27; P = 0.020) were associated with a high risk of progression in univariate analysis. In univariate analysis, high hemoglobin (Hb) levels (<median vs. ≥median; HR, 0.41, 95% CI, 0.24–0.73; P = 0.0023) and high red cell distribution widths (<median vs. ≥median; HR, 2.41, 95% CI, 1.37–4.25; P = 0.0023) were associated with a low and a high risk of all-cause mortality, respectively. In multivariate analysis, high Hb levels (<median vs. ≥median; HR, 0.42, 95% CI, 0.22–0.79; P = 0.0076) were repeatedly associated with a low risk of all-cause mortality. ConclusionWe found that white blood cell counts and neutrophil-to-lymphocyte ratios may be prognostic for progression-free survival while red cell distribution widths may be prognostic for OS. In particular, a low Hb level was a robust prognostic factor for poor OS. These findings could be useful in predicting prognosis in CRPC patients treated with ARPIs.

Evaluation of short- and long-term outcomes following laparoscopic surgery for colorectal cancer in elderly patients aged over 80years old: a propensity score-matched analysis.

It remains controversial whether the advantages of laparoscopic surgery for colorectal cancer (CRC) are beneficial in elderly patients (EP, age ≥ 80years). The present study aimed to evaluate whether age itself is an independent risk factor for laparoscopic surgery by comparing short- and long-term outcomes between non-EP and EP groups. We retrospectively analyzed 730 consecutive patients with stage I-III CRC who had undergone elective surgery between 2010 and 2017, using propensity score-matched analysis. Median follow-up was 49months. After matching, we enrolled 228 patients. In the matched cohort, estimated operative time, estimated blood loss, lymph node dissection ≥ D3, number of lymph nodes harvested < 12, conversion rate, multivisceral resection rate, postoperative complication rate, and length of postsurgical stay were similar between the two groups. Before matching, compared with the non-EP group, the EP group had significantly shorter overall survival (OS) (p < 0.01), cancer-specific survival (CSS) (p < 0.01), recurrence-free survival (RFS) (p < 0.01), and higher frequency of local recurrence (LR) (p = 0.01); however, there was no significant difference in terms of incidence of LR or CSS between the two groups in the matched cohort. Prior to matching, multivariate analysis identified age ≥ 80years as an independent prognostic factor for OS (p < 0.01), CSS (p < 0.01), and RFS (p = 0.01); however, after matching, age ≥ 80years was not an independent poor prognostic factor for OS or CCS. Laparoscopic surgery offers a safe, effective option for CRC in EP aged ≥ 80years.

Breast-conserving surgery with or without irradiation in women with invasive ductal carcinoma of the breast receiving preoperative systemic therapy: A cohort study

PurposeTo investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival. Patients and methodsPatients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs). ResultsMultivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2–4) or nodal (ypN2–3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03–0.81), 0.32 (0.16–0.64), 0.43 (0.23–0.79), 0.23 (0.13–0.42), 0.52 (0.20–1.33), and 0.34 (0.13–0.87) in the ypT0, ypT1, ypT2–4, ypN0, ypN1, and ypN2–3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00–4.07), 0.46 (0.26–0.83), 0.18 (0.06–0.51), 0.28 (0.06–1.34), 0.25 (0.10–0.63), 0.47 (0.23–0.88), and 0.32 in the cT0–1, cT2, cT3, cT4, cN0, cN1, and cN2–3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST. ConclusionWBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.

Prognostic factors for survival in patients with metastatic lung adenocarcinoma: An analysis of the SEER database.

BackgroundLung adenocarcinoma (ADC) is the main cause of death related to lung cancer. The aim of this study was to identify poor prognostic factors for overall survival (OS) in patients with stage IV lung ADC in real‐world clinical practice.MethodsPatients were selected from the Surveillance Epidemiology and End Results (SEER) database. Chi‐square bivariate analysis was used for the association of binary qualitative variables. A multivariate Cox regression analysis was performed to determine the impact of these prognostic factors on OS.ResultsA total of 46 030 patients were included (51.3% men, mean age 67.03 ± 11.6), of whom 41.3% presented with metastases in bone, 28.9% in brain, 17.1% in liver and 31.8% in lung. Patients with liver metastases presented with two or more metastatic sites more frequently than patients without liver metastases (P < 0.001). Male sex (HR 0.78, 95% CI: 0.76–0.80), age ≥ 65 years (HR 1.37, 95% CI: 1.33–1.40), lack of family support (HR 0.80, 95% CI: 0.78–0.81) and presence of liver (HR 1.45, 95% CI: 1.40–1.50), bone (HR 1.21, 95% CI: 1.18–1.24) or brain metastases (HR 1.18, 95% CI: 1.15–1.21) were identified as poor prognostic factors for OS. Patients with liver metastasis showed the highest hazard ratio value (P < 0.001).ConclusionsThe presence of liver metastases was the worst prognostic factor for patients with metastatic lung ADC. This factor should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy.Key pointsSignificant findings of the study Regression analysis identified poor prognostic factors for overall survival. Factors were male sex, age ≥ 65 years, lack of family support and presence of liver, bone and brain metastases.Patients with liver metastasis showed the highest HR (HR = 1.45 95% CI: 1.40–1.50).This study included the highest number of adenocarcinoma patients analyzed so far (N = 46 030). What this study addsThe presence of liver metastases should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy.

Preoperative sarcopenia is associated with poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy.

To analyze the effect of preoperative body composition on survival in patients with pancreatic cancer following pancreaticoduodenectomy (PD). Between October 2005 and August 2018, 116 patients (68 men, 48 women, mean age 66.2 ± 11.9 years) diagnosed with pancreatic adenocarcinoma following PD were retrospectively enrolled. The preoperative CT on vertebral level L3 was assessed for total abdominal muscle area (TAMA), visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and mean skeletal muscle attenuation (SMD). The clinical data and pathological findings of tumors were collected. The impact of these factors on disease-free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier method and by univariable and multivariable Cox proportional hazards models. The 3-year DFS and OS rates were 8% and 25%, respectively. Of 116 patients, 20 (17.2%), 3 (2.6%), and 46 (39.7%) patients were classified as having sarcopenia, sarcopenic obesity, and myosteatosis, respectively. The VAT-TAMA ratio (1.2 ± 0.7 vs 0.9 ± 0.5, p = 0.01) and the visceral to subcutaneous adipose tissue area ratio (1.3 ± 0.7 vs 0.9 ± 0.5, p = 0.04) were higher in sarcopenic patients than in the nonsarcopenic group. Preoperative sarcopenia and sarcopenic obesity were associated with shorter OS (p = 0.012 and p = 0.041, respectively), but not shorter DFS. Myosteatosis was neither associated with DFS nor OS. On multivariable analysis, sarcopenia was the only significant prognostic factor for OS (p = 0.039). Preoperative sarcopenia assessed by CT is a poor prognostic factor for OS in pancreatic cancer patients after PD. • Sarcopenia and sarcopenic obesity can be evaluated by abdominal CT on L3 level. • Patients with diabetes mellitus (DM) had lower sex-standardized subcutaneous adipose tissue area index and skeletal muscle density and higher visceral to subcutaneous adipose tissue area ratio than did those without DM. • Preoperative sarcopenia, sarcopenic obesity, and new-onset diabetes mellitus may predict poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy.

Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells, especially PD-1+Tim3+terminal CD8+ T cells, leading to better nivolumab outcomes in patients with lung cancer.

As previously reported, hydrogen gas improves the prognosis of patients with cancer by restoring exhausted CD8+ T cells into active CD8+ T cells, possibly by activating mitochondria. As mitochondrial activators exhibit synergistic effects with nivolumab, the current study investigated whether hydrogen gas also affects the clinical outcomes of nivolumab. A total of 42 of 56 patients with lung cancer treated with nivolumab received hydrogen gas. Exhausted markers (PD-1 and Tim-3) on cell populations in the CD8+ T cell differentiation pathway were analyzed using flow cytometry. The concentration of coenzyme Q10 (CoQ10) was measured as a marker of mitochondrial function. The 42 patients treated with hydrogen gas and nivolumab (HGN) indicated a significantly longer overall survival (OS) compared with those treated with nivolumab only (n=14). In multivariate analysis, PD-1+Tim-3+terminal CD8+ T cells (PDT+) were an independent poor prognostic factor in OS, and CoQ10 showed a tendency to be associated with improved OS. The change in the rate of PDT+ and CoQ10 after vs. before HGN (PDT+ ratio and CoQ10 ratio, respectively) revealed that patients with low PDT+ ratio (<0.81) and high CoQ10 ratio (>1.175) had significantly longer OS compared with those with high PDT+ ratio and low CoQ10 ratio. Furthermore, PDT+, with a significant reverse correlation with CoQ10, was significantly lower in patients with high CoQ10 and/or CoQ10 ratio than in those low CoQ10 and/or CoQ10. Hydrogen gas has been suggested to enhance the clinical efficacy of nivolumab by increasing CoQ10 (mitochondria) to reduce PDT+, with PDT+ and CoQ10 as reliable negative and positive biomarkers of nivolumab, respectively.

Prognostic Value of C-Reactive Protein to Albumin Ratio in Gastric Cancer: A Meta-Analysis

Objective C-reactive protein to albumin ratio (CRP/Alb) is investigated as a prognostic marker in gastric cancer in previous studies, with presence of inconsistent data. Therefore, this study aimed to explore the prognostic role of CRP/Alb in gastric cancer through meta-analysis. Methods This meta-analysis systemically retrieved PubMed, Embase, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), and Wanfang up to July 4, 2020. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were conducted to evaluate the association between CRP/Alb and survival outcomes. Results A total of nine studies with 3346 patients were included in the present meta-analysis. The pooled HR and 95%CI were: HR = 1.89, 95%CI = 1.64–2.19, p < 0.001 for overall survival (OS) and HR = 2.15, 95%CI = 1.72–2.70, p < 0.001 for disease-free survival (DFS). Subgroup analysis demonstrate that an elevated CRP/Alb remain a significant prognostic factor for poor OS and DFS irrespective of sample size, nationality of patients, or cutoff value resource (p < 0.05 in all subgroups). Conclusions The present meta-analysis suggests that high CRP/Alb is predictive of poor OS and DFS in gastric cancer. CRP/Alb is therefore a potential prognostic factor in the management of patients with gastric cancer.

The PET-Derived Tumor-to-Liver Standard Uptake Ratio (SUV TLR ) Is Superior to Tumor SUVmax in Predicting Tumor Response and Survival After Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer.

Background: The maximum standardized uptake values (SUVmax) derived from 18F-fluorodeoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) have some well-known shortcomings in predicting treatment response and prognosis in oncology. The standardized SUVmax with an appropriate reference background may overcome this problem in some instances. This study explored the prognostic value of the tumor-to-liver SUVmax ratio (SUVTLR) and the tumor-to-blood pool SUVmax ratio (SUVTBR) in predicting the objective response (OR) and overall survival (OS) in patients with locally advanced esophageal cancer after concurrent chemoradiotherapy (CCRT).Methods: We retrospectively analyzed 128 newly diagnosed esophageal squamous cell carcinoma (ESCC) patients who were treated with CCRT. The SUVmax of primary tumor, SUVTLR, SUVTBR and clinicopathologic features data were analyzed. Univariate and multivariate analyses were used to determine the predictors of tumor response. Survival analysis was performed using the Kaplan–Meier method and Cox proportional hazards model.Results: Receiver operating characteristic (ROC) curve analysis demonstrated that SUVTLR was superior to SUVmax and SUVTBR in predicting treatment response. Univariate and multivariate analyses revealed that advanced tumor stage (hazard ratio [HR] = 9.67; 95% CI: 1.15-81.28; P = 0.037) and high SUVTLR (HR = 21.92; 95% CI: 2.26-212.96; P = 0.008) were independent predictors of poor treatment response. Cox regression analysis showed that good clinical tumor response (p < 0.014, HR =0.501; 95% CI: 0.288–0.871) was a favorable independent predictive factor for OS, while an advanced tumor stage (p = 0.018, HR = 1.796; 95% CI: 1.107-2.915) and a high SUVTLR (p < 0.002, HR = 2.660; 95% CI: 1.425–4.967) were prognostic factors for poor OS. The median OS of patients in the low SUVTLR and high SUVTLR groups was 13.47 vs. 19.30 months, respectively.Conclusions: PET-derived SUVTLR is superior to tumor SUVmax and SUVTBR in predicting treatment response and overall survival in patients with ESCC undergoing CCRT. High SUVTLR was an independent predictor of poor treatment response and shorter overall survival.

Classical Hodgkin Lymphoma: Clinicopathologic Features, Prognostic Factors, and Outcomes From a 28-Year Single Institutional Experience

IntroductionClassical Hodgkin lymphoma (cHL) is a curable malignancy, with a complete remission rate of approximately 90%. However, relapse remains a significant cause of mortality. Prognostic factors are useful in guiding therapy. This is a large, single-institution study defining the clinicopathologic features, prognostic factors, and treatment outcomes of patients with cHL. Patients and MethodsWe reviewed 727 patients with cHL treated at H. Lee Moffitt Cancer Center and Research Institute from 1990 to 2017. Data on demographics, laboratory studies, and disease statuses were collected from the institutional database and electronic medical records. Statistical analyses, overall survival (OS), progression-free survival (PFS), and multivariate analyses were performed. ResultsThe median age was 35 years. Fifty-four percent of patients were men; 45.6% had advanced stage disease; 82% were treated with ABVD (doxorubicin hydrochloride [adriamycin], bleomycin sulfate, vincristine, and dacarbazine) as frontline therapy; and 70% achieved complete response. The median PFS after first-line treatment was 16.8 years. The median OS of patients with early stage and advanced stage cHL was 19 and 12.9 years, respectively. Poor prognostic factors for OS included older age, advanced stage disease, presence of B symptoms, and a higher International Prognostic Score. ConclusionDespite high cure rates, cHL accounted for the cause of death in 47% of patients who died during follow-up. Prognostic factors, such as age, stage at diagnosis, International Prognostic Score, and B symptoms, are helpful to guide treatment. Outcomes observed in this study are comparable with those reported in previously published studies.

Development and Validation of a Clinicopathological-Based Nomogram to Predict the Survival Outcome of Patients with Recurrent Hepatocellular Carcinoma After Hepatectomy Who Underwent Microwave Ablation.

AimTo develop and validate a nomogram for predicting the overall survival (OS) in patients with recurrent hepatocellular carcinoma (HCC) after hepatectomy who underwent microwave ablation (MWA).MethodsThe training cohort included 299 patients with recurrent HCCs after hepatectomy who met the Milan criteria and received MWA from April 2007 to December 2017. Baseline characteristics were collected to identify risk factors for the determination of death after MWA. A multivariate Cox proportional hazards model based on significant risk factors was used to develop the nomogram, which was then assessed for its predictive accuracy using Harrell’s C-index and the area under the curve (AUC). The nomogram was validated by internal (n = 240) and external cohorts (n = 205) from another hospital.ResultsAfter a median follow-up of 32.3 months, 38.8% (116/299) of patients had died. Multivariate Cox proportional hazards analyses showed that comorbid disease, early recurrence, and albumin-bilirubin (ALBI) grades 2–3 were independent prognostic factors for poor OS. This nomogram accurately stratified patients into subgroups with low or high risk. The 1-, 3- and 5-year OS rates in the low-risk subgroup were 99.4%, 97.2%, and 86.1%, respectively, and they were 92.8%, 70.3%, and 45.8% in the high-risk subgroup (P < 0.001). The nomogram predicted OS in the training cohort with a C-index score of 0.801 (95% CI 0.761–0.841). The nomogram was validated by internal and external cohorts, with C-index scores of 0.792 (95% CI 0.738–0.846) and 0.744 (95% CI 0.703–0.785), respectively.ConclusionThe nomogram provides individualized risk estimates for long-term OS for patients with recurrent HCC after hepatectomy who underwent MWA.