Pathologic complete response after neoadjuvant tislelizumab and chemotherapy for Pancoast tumor: A case report.

A 60-year-old man was hospitalized because of numbness and weakness in the right upper limb. Magnetic resonance imaging revealed a large mass in the right upper lobe invading the right eighth cervical and first thoracic nerve root. Biopsy pathology confirmed primary lung adenocarcinoma with a clinical stage of cT4N0M0 IIIA, negative for anaplastic lymphoma kinase fusion gene and epidermal growth factor receptor mutations but positive for programmed death ligand 1 (3%). Neoadjuvant tislelizumab and chemotherapy were offered to this patient with Pancoast tumor, and tumor shrinkage of 71% was achieved. After the operation, surgical pathology indicated pathologic complete response (pCR). Circulating tumor cells testing was negative after the first adjuvant treatment. In this case, we provide real-world evidence of encouraging pCR with neoadjuvant tislelizumab and chemotherapy for a patient with Pancoast tumor.

Elevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment.

AIM: Elevated neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to be a poor prognostic factor in multiple types of malignancies, whereas the effect of NLR on the prognosis of epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) is not fully addressed. METHODS: 81 metastatic NSCLC patients harboring EGFR mutation treated with first-line EGFR TKIs were retrospectively included. The associations between baseline clinical characteristics, including NLR, and tumor response, progression and survival were investigated. RESULTS: Elevated NLR (≥3.5) was observed in 33 of 81 patients. The progression-free and overall survival of the patients with increased NLR was significantly worse than that of the patients with decreased NLR (8.20 vs 10.60 months, P < 0.001 and 17.20 vs 23.20 months, P < 0.001, respectively). Elevated NLR was confirmed to be an independent prognostic factor for worse progression-free and overall survival in Cox multivariate analysis. CONCLUSION: Elevated NLR is likely to be associated with poor outcome in EGFR-mutated advanced NSCLC patients treated with first-line EGFR TKIs.

Chemotherapy Near the End of Life for Chinese Patients with Solid Malignancies.

INTRODUCTION: There are increasing concerns about the negative impacts of chemotherapy near the end of life (EOL). There is discrepancy among different countries about its use, and little is known about the real-world situation in China. PATIENTS AND METHODS: This retrospective study was conducted at six representative hospitals across China. Adult decedents with a record of advanced solid cancer and palliative chemotherapy were consecutively screened from 2010 through 2014. The prevalence of EOL chemotherapy within the last 1 month of life was set as the primary outcome. The correlations among EOL chemotherapy, clinicopathological features, and overall survival (OS) were investigated. RESULTS: A total of 3,350 decedents who had had cancer were consecutively included; 2,098 (62.6%) were male and the median age was 56 years (range, 20-88). There were 177 (5.3%), 387 (11.6%), and 837 (25.0%) patients who received EOL chemotherapy within the last 2 weeks, 1 month, and 2 months of life, respectively. We identified inferior OS (median OS, 7.1 vs. 14.2 months; hazard ratio, 1.37; 95% confidence interval [CI], 1.23-1.53; p < .001), more intensive treatments (e.g., admitted to intensive care unit [ICU] in the last month of life, received cardiopulmonary resuscitation and invasive ventilation support), and hospital death (odds ratio, 1.53; 95% CI, 1.14-2.06; p = .005) among patients who received continued chemotherapy within the last month compared with those who did not. However, subgroup analyses indicated that receiving oral agents correlated with fewer ICU admissions and lower rates of in-hospital death. CONCLUSION: This study showed that EOL chemotherapy is commonly used in China. Intravenous chemotherapy at the EOL significantly correlated with poor outcomes and the role of oral anticancer agents warrants further investigation. The Oncologist 2017;22:53-60Implications for Practice: The role of chemotherapy toward the end of life (EOL) in patients with solid cancers is debatable. This article is believed to be the first to report the current prevalence of EOL chemotherapy in China. This study found that, compared with oral anticancer agents, intravenous chemotherapy at the EOL was significantly associated with poor outcomes. Therefore, the role of oral anticancer agents at the EOL stage deserves further investigation.

Prognostic significance of the pre-chemotherapy lymphocyte-to-monocyte ratio in patients with previously untreated metastatic colorectal cancer receiving FOLFOX chemotherapy.

BACKGROUND: As a surrogate marker of systemic inflammation, the lymphocyte-to-monocyte ratio (LMR) is an independent prognostic factor for various malignancies. This study investigated the prognostic significance of the pre-chemotherapy LMR in patients with previously untreated metastatic colorectal cancer (mCRC) receiving chemotherapy. METHODS: The present study included newly diagnosed mCRC patients treated between January 2005 and December 2013 with FOLFOX chemotherapy, specifically oxaliplatin 180 mg/m(2) on day 1, with leucovorin 400 mg/m(2) administered as a 2-hour infusion before the administration of 5-fluorouracil 400 mg/m(2) as an intravenous bolus injection, and 5-fluorouracil 2400 mg/m(2) as a 46-h infusion immediately after 5-fluorouracil bolus injection. The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes. COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes. RESULTS: A total of 488 patients were included. Patients with high pre-chemotherapy LMR experienced significant improvements in progression-free survival (PFS, 9.2 vs. 7.6 months, P < 0.001) and overall survival (OS, 19.4 vs. 16.6 months, P < 0.001) compared with patients with low pre-chemotherapy LMR. Subsequent COX multivariate analysis showed that high pre-chemotherapy LMR (≥3.11) was an independent favorable prognostic factor for PFS and OS. Additionally, patients whose LMR remained high (high-high subgroup), increased (low-high subgroup), or decreased (high-low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low (low-low subgroup) after chemotherapy. CONCLUSIONS: For patients with previously untreated mCRC receiving FOLFOX chemotherapy, an elevated pre-chemotherapy LMR is an independent favorable prognostic factor for PFS and OS, and changes in the LMR before and after chemotherapy seem to predict the benefit of chemotherapy.

Hepatitis B Virus Infection Is Associated with Poor Prognosis in Patients with Advanced Non Small Cell Lung Cancer.

BACKGROUND: Hepatitis B virus (HBV) infection has been reported to be associated with inferior prognosis in hepatocellular and pancreatic carcinoma cases, but has not been studied with respect to non small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic significance of HBV infection in advanced NSCLC patients. MATERIALS AND METHODS: A retrospective cohort of 445 advanced NSCLC patients was recruited at our hospital from January 1, 2003 until August 30, 2014. Serum HBV markers were tested by enzyme-linked immunosorbent assay. COX proportional hazards analysis was used to evaluate associations of HBV infection with overall survival (OS). RESULTS: Of 445 patients who were qualified for the study, 68 patients were positive for HBsAg, also considered as HBV infection. Patients in HBsAg negative group were found to have better OS (12.6 months [12.2-12.9]) than those in HBsAg positive group (11.30 months [10.8-11.9]; p=0.001). Furthermore, COX multivariate analysis identified HBV infection as an independent prognostic factor for OS (HR 0.740 [0.560, 0.978], p=0.034). CONCLUSIONS: Our study found that HBsAg-positive status was an independent prognostic factor for OS in patients with advanced NSCLC. Future prospective studies are required to confirm our findings.

Increased lymphocyte to monocyte ratio is associated with better prognosis in patients with newly diagnosed metastatic nasopharyngeal carcinoma receiving chemotherapy.

Inflammation has been demonstrated to be widely involved in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the prognostic significance of lymphocyte to monocyte ratio (LMR) in metastatic NPC is not fully addressed. The purpose of the study is to investigate the prognostic impact of pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR on patients with newly diagnosed metastatic NPC undergoing chemotherapy. Between January 2006 and December 2010, patients with newly diagnosed metastatic NPC undergoing chemotherapy were retrospectively collected. The prognostic significance of baseline clinical features and inflammatory markers was investigated. A total of 256 patients were eligible for the study. The best cut-off value of ALC, AMC, and LMR was 2.25 × 10(9)/L, 0.35 × 10(9)/L, and 5.07, respectively. Patients in the high LMR group had a significantly longer overall survival (OS) (25.0 months [24.50-25.49]) than patients in the low LMR group (16.0 months [15.51-16.49]; p < 0.001). In addition, ALC ≥ 2.25 × 10(9)/L (HR, 0.59; 95% CI, 0.43-0.81; p = 0.001) and LMR ≥ 5.07 (HR, 0.42; 95% CI, 0.30-0.59; p < .001) remained as independent prognostic factors for superior OS, while AMC did not retained its prognostic significance in COX multivariate analysis. Pre-treatment ALC and LMR were demonstrated to be independent prognostic factors in patient with newly diagnosed metastatic NPC receiving chemotherapy. Future prospective studies are needed to validate the findings.

Prognostic significance of the peripheral blood absolute monocyte count in patients with locally advanced or metastatic hepatocellular carcinoma receiving systemic chemotherapy.

BACKGROUND: The prognostic significance of the circulating absolute monocyte count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is uncertain. This study was designed to assess the association of circulating AMC with survival outcomes in patients diagnosed with locally advanced or metastatic HCC receiving systemic chemotherapy. MATERIALS AND METHODS: Between January 1, 2005 and December 30, 2012, locally advanced or metastatic HCC patients who had Child-Pugh stage A or B disease and received systemic chemotherapy were retrospectively enrolled. Patient features including gender, age, extrahepatic metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were collected to investigate their prognostic impact on overall survival(OS). RESULTS: A total of 216 patients were eligible for the study. The optimal cut-off value of AMC for OS analysis was 0.38×109/L. Median OS was 5.84 months in low-AMC group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI, 1.120 to 2.223, p=0.009). CONCLUSIONS: Our results indiicate that circulating AMC is confirmed to be an independent prognostic factor for OS in patients with locally advanced or metastatic HCC receiving systemic chemotherapy.

Hepatitis B virus reactivation in hepatitis B surface antigen seropositive patients with metastatic non-small cell lung cancer receiving cytotoxic chemotherapy: the efficacy of preemptive lamivudine and identification of risk factors.

Little is known about the likelihood and degree of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) seropositive patients with disseminated non-small cell lung cancer (NSCLC) receiving chemotherapy. Between January 2003 and December 2013, all HBsAg seropositive patients with metastatic NSCLC receiving cytotoxic chemotherapy were retrospectively evaluated. The morbidity and mortality of HBV reactivation, risk factors associated with reactivation, as well as the efficacy of preemptive lamivudine were investigated. Of 258 patients who were eligible for the present study, 176 were treated without antiviral prophylaxis and 82 received preemptive lamivudine. Patients without lamivudine prophylaxis had a significantly higher prevalence of HBV reactivation (19.3 vs 6.1 %, p = 0.006) and severe hepatitis attributable to reactivation (11.8 vs 3.7 %, p = 0.034) than those with preemptive lamivudine. However, no significant difference in mortality due to reactivation was noted between patients with or without prophylactic lamivudine (0 vs 2.3 %, p = 0.310). Furthermore, patients who developed HBV reactivation were indentified to have a higher rate of HBeAg seropositivity (74.4 vs 43.4 %, p < 0.001), serum HBV-DNA level of 10(4) copies/ml or greater (76.9 vs 47.9 %, p = 0.001), coexisting liver metastasis (50.0 vs 40.6 %, p = 0.033) and treatment with more than 4 cycles of chemotherapy (56.4 vs 39.3 %, p = 0.046) than those who did not experienced reactivation. The current study has demonstrated that preemptive lamivudine significantly reduced the prevalence of HBV reactivation in HBsAg seropositive patients with metastatic NSCLC receiving systemic chemotherapy.

Prognostic impact of circulating monocytes and lymphocyte-to-monocyte ratio on previously untreated metastatic non-small cell lung cancer patients receiving platinum-based doublet.

The link between circulating lymphocyte-to-monocyte ratio (LMR) and newly diagnosed metastatic non-small cell lung cancer (NSCLC) is not fully defined. The study was conducted to evaluate the prognostic impact of LMR on survival outcomes in previously untreated metastatic NSCLC patients receiving platinum-based doublet. Chemotherapy-naive metastatic NSCLC patients undergoing platinum-based doublet were retrospectively enrolled. Clinical features regarding gender, age, Eastern Cooperative Oncology Group (ECOG) performance status, histology, absolute lymphocyte count (ALC), absolute monocyte count (AMC) and LMR were collected to determinate their prognostic impact on progression-free survival (PFS) and overall survival (OS). Up to 370 patients were eligible for the study. By univariate analysis, ECOG performance status, histology, ALC, AMC and LMR were showed to be significantly associated with PFS and OS. In subsequent Cox multivariate analysis, non-squamous cell carcinoma, ALC ≥ 2.45 × 10(9)/L, AMC <0.45 × 10(9)/L and LMR ≥ 4.56 were demonstrated to be independently correlated with better PFS. In addition, independent favorable prognostic factors for OS were only limited to LMR ≥ 4.56 and non-squamous cell carcinoma, whereas ECOG performance status of 2 and AMC ≥ 0.45 × 10(9)/L remained as independently inferior prognostic indicators for OS. Our findings implicate that circulating AMC and LMR are regarded as independent prognostic factors for PFS and OS in previously untreated metastatic NSCLC patients receiving platinum-based doublet.

Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy.

AIM: The effect of transcatheter arterial chemoembolization (TACE) therapy on hepatitis B virus (HBV) reactivation in hepatocellular carcinoma (HCC) patients with prior resolved hepatitis B is not fully understood. METHODS: From January 2006 to December 2010, 43 hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core antigen (HBc) positive patients with newly diagnosed unresectable HCC were enrolled in the study. All underwent TACE therapy. RESULTS: Four patients (9.3%) developed HBV reactivation with mild/moderate hepatitis. The median number of TACE cycles received was 3.5 (range 3-4 cycles). The median time interval between the occurrence of HBV reactivation and the completion of TACE therapy was 3 months (range 1-5 months) and their median HBV DNA level was 1.58 × 10(4) IU/mL (range, 1.65 × 10(3) -6.42 × 10(4) IU/mL). After the introduction of lamivudine at the occurrence of HBV reactivation, all had resolution of hepatitis. An exploratory analysis indicated that significant predictors of HBV reactivation included increased serum total bilirubin coexisting with cirrhosis and the total number of cycles of TACE received. CONCLUSION: The administration of TACE therapy may increase the risk of HBV reactivation in HBsAg-negative/anti-HBc-positive patients diagnosed with unresectable HCC. Further studies are warranted to explore the optimal management of HBV reactivation in patients with prior resolved hepatitis B.

The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy.

The association of prolonged rituximab therapy and hepatitis B virus (HBV) reactivation in diffuse large B-cell lymphoma (DLBCL) and the role of lamivudine prophylaxis remain undefined. The prevalence and mortality of HBV reactivation in HBsAg-positive patients with DLBCL undergoing rituximab-based treatment, who received prophylactic treatment with or without lamivudine, were retrospectively analyzed. From January 2003 to December 2009, there were 50 patients enrolled in the study, among of which 30 received the prophylactic treatment of lamivudine and 20 without prophylactic treatment of lamivudine. Among of the 50 patients, seven patients received further rituximab maintenance, once every 3 months for 2 years. Compared with lamivudine treatment group, it showed that there was significantly higher prevalence of HBV reactivation (60.0% vs 13.3%, P = .001), severe hepatitis (45.0% vs 6.7%, P = .004), and mortality (25.0% vs 3.3%, P = .032) in non-lamivudine prophylactic group; however, there was no statistically significant difference in the HBV DNA levels at reactivation (3.94 × 10(6) vs 8.30 × 10(5) copies/ml, P = .47) and the time from first dose of rituximab to HBV reactivation(207 vs 386 days, P = .28). For patients undergoing further rituximab maintanence treatment, the prevalence and mortality of HBV reactivation were 71.4 and 28.6%, respectively. The prevalence and mortality of HBV reactivation are 66.7% vs 75.0% (P = 1.00) and 0 vs 50.0% (P = .43) in lamivudine prophylactic and non-lamivudine prophylactic groups, respectively. The effect of lamivudine prophylaxis on preventing HBV reactivation was found to be less in patients undergoing longer duration of rituximab treatment. A longer duration of rituximab treatment contributed to higher morbidity and mortality of HBV reactivation in HbsAg-positive patients with DLBCL. Further study is warranted for the optimal management of hepatitis caused by HBV reactivation.

Induction therapy using the MRC UKALLXII/ECOG E2993 protocol in Chinese adults with acute lymphoblastic leukemia.

Patients with newly diagnosed acute lymphoblastic leukemia (ALL) at a single institution were analyzed retrospectively. From 2006 to 2010, 47 patients were treated using the MRC UKALLXII/ECOG E2993 protocol. Prior to July 2005, 40 patients had been treated with the JALSG ALL 87 protocol. A complete remission (CR) rate of 91.5% was achieved with the E2993 protocol, which was not significantly higher than the 80% achieved using JALSG (P > 0.05). The median duration of CR in months was 19 for all patients treated with the MRC UKALLXII/ECOG E2993 protocol. Ph+ patients showed a median CR duration of 11.5 months, while Ph- patients had a significantly longer CR duration of 19 months (P = 0.019). Further, Ph- patients at standard risk (stratified on the basis of age and white blood cell count at diagnosis) had a CR duration of 21 months, which was significantly longer than the 12-month CR duration for the ten Ph- patients at high risk (P = 0.001). Significant differences were found in the 2-year event-free survival and overall survival rates between the MRC UKALLXII/ECOG E2993 and JALSG ALL 87 groups in the following three cohorts: all patients (P = 0.009 and 0.022, respectively), Ph- patients (P = 0.009 and 0.018, respectively), and standard-risk patients (P = 0.014 and 0.007, respectively). The overall mortality rate for induction therapy in the MRC UKALLXII/ECOG E2993 group was 2.1% (1 of 47 patients). One or more instances of grade IV myelosuppression occurred during induction therapy. Among the non-hematological toxicities, alopecia and elevated ALT and AST levels were the most common. The levels of ALT and AST could be reduced to less than twofold the normal values within 1-2 weeks. The data indicate that the MRC UKALLXII/ECOG E2993 regimen is well tolerated in Chinese adults with ALL and can improve survival compared with the JALSG ALL 87 protocol. Risk stratification at diagnosis based on age and WBC count is suitable for adults with ALL, and it is necessary to adopt different strategies as determined by diagnostic results. Lastly, Ph+ patients have an extremely poor prognosis.

Expression of ezrin correlates with poor prognosis of nasopharyngeal carcinoma.

A significant proportion of patients with nasopharyngeal carcinoma (NPC) will develop regional relapse or distant metastasis after treatment. So, to find valuable prognostic factors becomes very important. To elucidate the expression of ezrin in NPC and its correlation with patients' clinicopathologic characteristics, time to progression, and overall survival, immunohistochemistry stains for ezrin were applied to 200 tissue specimens of NPC. Ezrin expression had no significant correlation with sex, age, primary tumor stage (T), Epstein-Barr virus (EBV) VCA-IgA antibody, EBV EA-IgA antibody, and EBV DNA copy except primary nodal status (N; p= .032). Increased ezrin expression was significantly related to higher lymph nodal metastatic rate (p< .004). Among ezrin (negative/weak), ezrin (moderate), and ezrin (intense) groups, there was a significant difference for median time to progression (not reached vs. 63.2 months vs. 46 months, P< .001) and median overall survival (100.7 months vs. 80.8 months vs. 70.6 months, P< .001). Ezrin expression status was an independent prognostic factor in multivariate (Cox) analysis. Ezrin, which was significantly correlated to prognosis of disease, may be involved in the tumorigenesis, progression, and invasion of NPC. Thus, our data offer the possibility of future therapeutic targets.