Publications by authors named "Xuanye Zhang"

23 Publications

  • Page 1 of 1

A CT-based radiomics model to predict subsequent brain metastasis in patients with ALK-rearranged non-small cell lung cancer undergoing crizotinib treatment.

Thorac Cancer 2022 Apr 18. Epub 2022 Apr 18.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: Brain metastasis (BM) comprises the most common reason for crizotinib failure in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We hypothesize that its occurrence could be predicted by a computed tomography (CT)-based radiomics model, therefore, allowing for selection of enriched patient populations for prevention therapies.

Methods: A total of 75 eligible patients were enrolled from Sun Yat-sen University Cancer Center between June 2014 and September 2019. The primary endpoint was brain metastasis-free survival (BMFS), estimated from the initiation of crizotinib to the date of the occurrence of BM. Patients were randomly divided into two cohorts for model training (n = 51) and validation (n = 24), respectively. A radiomics signature was constructed based on features extracted from chest CT before crizotinib treatment. Clinical model was developed using the Cox proportional hazards model. Log-rank test was performed to describe the difference of BMFS risk.

Results: Patients with low radiomics score had significantly longer BMFS than those with higher, both in the training cohort (p = 0.019) and validation cohort (p = 0.048). The nomogram combining smoking history and the radiomics signature showed good performance for the estimation of BMFS, both in the training (concordance index [C-index], 0.762; 95% confidence interval [CI], 0.663-0.861) and validation cohort (C-index, 0.724; 95% CI, 0.601-0.847).

Conclusion: We have developed a CT-based radiomics model to predict subsequent BM in patients with non-brain metastatic NSCLC undergoing crizotinib treatment. Selection of an enriched patient population at high BM risk will facilitate the design of clinical trials or strategies to prevent BM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.14386DOI Listing
April 2022

Optimizing the tumor shrinkage threshold for evaluating immunotherapy efficacy for advanced non-small-cell lung cancer.

J Cancer Res Clin Oncol 2022 Mar 18. Epub 2022 Mar 18.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Purpose: The rise of immune checkpoint inhibitors (ICIs) in recent years has coincided with unusual clinical response patterns. Modification of the sum of longest diameters (SLD)-based threshold that reflecting dynamic change of the tumor burden and predicting response to ICIs, may markedly improve current treatment regimens.

Methods: The baseline and post-treatment SLD of target lesion was recorded and the maximum percent change of the SLD from baseline was designated as SLD-change score. The optimal cut-off value was obtained using the X-tile program. The relationship between SLD-change score and survival outcome (PFS, OS) was evaluated.

Results: 10% cut-off value of SLD-change score was found to be most distinctive for PFS. Responders defined according to this cut-off value showed a significant improvement for PFS and OS. Bone metastasis and brain metastasis were also two independent prognostic factors of PFS and OS, respectively.

Conclusions: 10% SLD change score could discriminate for ICIs treatment response, which holds great promise in promoting the development of precise immunotherapeutic strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-022-03978-3DOI Listing
March 2022

Reducing number of target lesions for RECIST1.1 to predict survivals in patients with advanced non-small-cell lung cancer undergoing anti-PD1/PD-L1 monotherapy.

Lung Cancer 2021 Dec 31;165:10-17. Epub 2021 Dec 31.

State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Objectives: The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 provides conventional and standardized response assessment for multiple solid tumors. We investigated the smallest number of target lesions that can be measured without compromising response categorization and survival prediction in patients with advanced non-small-cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 monotherapy.

Material And Methods: 125 aNSCLC patients with at least two measurable lesions undergoing PD-1/PD-L1 inhibitor treatment were retrospectively studied. Tumor measurements allowing up to two lesions per organ and five lesions in total were reviewed. Inter-individual agreement and κ values for inter-method concordance on response status were evaluated based on up to five target lesions versus the largest one through four lesions. C-index was calculated to evaluate the prognostic accuracy of response categorization based on the selected number of target lesions for predicting overall survival (OS). Cox regression analysis was conducted for survival analysis.

Results: The highly consistent response assignment (99.2%) could be obtained when measuring the largest two lesions versus up to five lesions. Using the largest two through four lesions produced κ values of 0.986, 1.000 and 1.000 for response assessment, values significantly higher than those obtained when measuring the largest single lesion (κ = 0.850). C-index for overall survival (OS) was similar when assessing the largest one through five lesions, ranging from 0.646 to 0.654. Cox regression analyses showed that radiological response significantly predicted OS, irrespective of the number of target lesions selected.

Conclusions: Reducing the number of target lesions does not affect OS prediction in aNSCLC patients treated with anti-PD-1/PD-L1 therapy. Considering the high intra-individual and inter-method concordance, using the largest two lesions in total is proposed to assess response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2021.12.015DOI Listing
December 2021

Correction to: Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus.

Cancer Immunol Immunother 2022 May;71(5):1257

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-021-03112-1DOI Listing
May 2022

PD-1/PD-L1 inhibitor plus chemotherapy versus bevacizumab plus chemotherapy in first-line treatment for non-squamous non-small-cell lung cancer.

J Immunother Cancer 2021 11;9(11)

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China

Anti-PD-1)/programmed cell death-ligand 1 (PD-L1) antibody plus platinum-based chemotherapy (PBC) has replaced PBC as first-line treatment for patients with non-squamous (sq) non-small cell lung cancer (NSCLC) lacking targetable driver mutations. However, few studies have directly compared immune checkpoint inhibitor (ICI) plus chemotherapy with bevacizumab plus chemotherapy (beva +chemo) in this setting. Herein, we conducted an indirect comparison for anti-PD-1/PD-L1 antibody plus chemotherapy (ICI +chemo) versus beva +chemo in non-sq NSCLC using the frequentist methods. The main outcomes analyzed include progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Data were subtracted from randomized trials comparing ICI +chemo or beva +chemo against PBC. Fourteen trials involving 6165 patients were included. Direct meta-analyses showed that both ICI +chemo (PFS: HR 0.58, OS: HR 0.73, ORR: relative risk (RR) 1.66) and beva +chemo (PFS: HR 0.74, OS: HR 0.89, ORR: RR 1.62) improved clinical outcomes compared with PBC. Indirect comparison showed that ICI +chemo reduced the risk of disease progression (HR 0.78, 95% CI 0.60 to 1.00) and death (HR 0.82, 95% CI 0.71 to 0.94) compared with beva +chemo. The PFS benefits with ICI +chemo over beva +chemo were non-significant in those with negative PD-L1 expression and non-smokers. In conclusion, ICI +chemo is superior to beva +chemo in first-line treatment for non-sq NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2021-003431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576478PMC
November 2021

Unsatisfied Reporting Quality of Clinical Trials Evaluating Immune Checkpoint Inhibitor Therapy in Cancer.

Front Immunol 2021 5;12:736943. Epub 2021 Oct 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Background: More and more immune-oncology trials have been conducted for treating various cancers, yet it is unclear what the reporting quality of immune-oncology trials is,and characteristics associated with higher reporting quality.

Objective: This study aims to evaluate the reporting quality of immune-oncology trials.

Methods: The PubMed and Cochrane library were searched to identify all English publications of clinical trials assessing immunotherapy for cancer. Reporting quality of immune-oncology trials was evaluated by a quality score with 11 points derived from the Trial Reporting in Immuno-Oncology (TRIO) statement, which contained two parts: an efficacy score of 6 points and toxicity score of 5 point. Linear regression was used to identify characteristics associated with higher scores.

Results: Of the 10,169 studies screened, 298 immune-oncology trial reports were enrolled. The mean quality score, efficacy score, and toxicity score were 6.46, 3.61, and 2.85, respectively. The most common well-reported items were response evaluation criteria (96.0%) and toxicity grade (98.7%), followed by Kaplan-Meier survival analyses (80.5%). Treatment details beyond progression (12.8%) and toxicity onset time and duration (7.7%) were poorly reported. Multivariate regression revealed that higher impact factor (IF) (IF >20 vs. IF <5, < 0.001), specific tumor type ( = 0.018 for lung, = 0.021 for urinary system, vs. pan cancer), and a certain kind of immune checkpoint blocking agent ( < 0.001 for anti-PD-1 or multiagents, vs. anti-CTLA-4) were independent predictors of higher-quality score. Similar independent predictive characteristics were revealed for high-efficacy score. Only IF >20 had a significant high-toxicity score ( < 0.001).

Conclusion: Immune-oncology trial reports presented an unsatisfied quality score, especially in the reporting of treatment details beyond progression and toxicity onset time and duration. High IF journals have better reporting quality. Future improvement of trial reporting was warranted to the benefit-risk assessment of immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.736943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524036PMC
December 2021

Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus.

Cancer Immunol Immunother 2022 May 14;71(5):1247-1255. Epub 2021 Oct 14.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

The use of anti-programmed cell death-1 (PD-1) antibodies in treating malignancies is increasing; however, most registered clinical trials on anti-PD-1 antibodies exclude patients infected with hepatitis B virus (HBV). This retrospective study aimed to assess hepatotoxicity in cancer patients infected with HBV undergoing anti-PD1 antibody therapy and identify the associated risk factors. A total of 301 cancer patients positive for hepatitis B core antibodies (HbcAb) (negative or positive hepatitis B surface antigen [HBsAg]) who received PD-1 inhibitors were enrolled. The primary and secondary endpoints were the incidence rate of hepatotoxicity related to PD-1 inhibitor treatment, and risk factors associated with hepatic toxicity, respectively. Of the enrolled analyzed, 16.9% (n = 51) developed any grade and 4.7% (n = 14) developed grade 3-4 hepatotoxicity, respectively. Higher risk for any-grade hepatotoxicity development was associated with sero-positive HBsAg (OR = 6.30; P = 0.020), existence of liver involvement (OR = 2.10; P = 0.030), and detectable baseline HBV DNA levels (OR = 2.39; P = 0.012). Patients with prophylactic antiviral therapy decreased hazard for the incidence of grade 3-4 hepatotoxicity (OR = 0.10; P = 0.016). Our results suggested chronic (HBsAg-positive)/resolved (HBsAg-negative and HBcAb-positive) HBV-infected cancer patients are at an increased risk of hepatotoxicity following PD-1 inhibitor therapy. Cancer patients should be tested for HBsAg/HBcAb prior to the commencement of immune checkpoint inhibitor therapy. For patients with chronic/resolved HBV infection, ALT/AST and HBV DNA should be closely monitored during the whole immunotherapy period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-021-03082-4DOI Listing
May 2022

Association of hepatitis B virus infection status with outcomes of non-small cell lung cancer patients undergoing anti-PD-1/PD-L1 therapy.

Transl Lung Cancer Res 2021 Jul;10(7):3191-3202

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: The aim of this study was to evaluate the safety and survival outcomes of anti-programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) monotherapy in patients with advanced non-small cell lung cancer (NSCLC) and different hepatitis B virus (HBV) infection status.

Methods: Patients with advanced NSCLC and both chronic and/or resolved HBV infection who were treated with anti-PD-(L)1 monotherapy were retrospectively enrolled. The primary endpoint was the safety of PD-1/PD-L1 monotherapy, while the secondary endpoints included the survival outcomes.

Results: Of the 62 eligible patients, 10 (16.1%) were hepatitis B surface antigen (HBsAg) positive [chronic hepatitis B (CHB) infection] and 52 (83.9%) were HBsAg negative and HBcAb positive [resolved hepatitis B (RHB) infection]; 42 (67.7%) patients had at least 1 treatment-related adverse event (AE), with 4 patients (6.5%) developing grade 3 AEs and 6 (9.7%) developing hepatic AEs. One CHB patient experienced HBV reactivation during anti-PD-1 immunotherapy due to the interruption of antiviral prophylaxis. The objective response rate and durable clinical benefit (DCB) rate were 17.7% and 29.0%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 23.6 months [95% confidence interval (CI): 14.4-32.8] and 2.1 months (95% CI: 1.2-3.0), respectively. The DCB rate was significantly higher in the CHB group than in the RHB group (60% 23.1%; P=0.048). Patients with CHB experienced a longer PFS (8.3 2.0 months; P=0.103) and OS (35.0 18.2 months, P=0.119) than did RHB patients.

Conclusions: Anti-PD-(L)1 monotherapy was safe and effective in patients with NSCLC and HBV infection. This population should not be excluded from receiving immunotherapy in routine clinical practice or within clinical trials if HBV biomarkers are monitored and antiviral prophylaxis is properly used.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr-21-455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350074PMC
July 2021

Efficacy and safety of PD-L1 inhibitors versus PD-1 inhibitors in first-line treatment with chemotherapy for extensive-stage small-cell lung cancer.

Cancer Immunol Immunother 2022 Mar 23;71(3):637-644. Epub 2021 Jul 23.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Objectives: Programmed cell death-ligand 1 inhibitors plus chemotherapy (PD-L1 + Chemo) have achieved substantial progress in extensive-stage small-cell lung cancer (ES-SCLC). However, evidence about programmed cell death 1 inhibitors plus chemotherapy (PD-1 + Chemo) in SCLC is relatively lacking. Whether PD-1 inhibitors differ from PD-L1 inhibitors in their clinical outcomes remains controversial.

Materials And Methods: We performed a meta-analysis to compare efficacy and safety of PD-L1 + Chemo vs PD-1 + Chemo in ES-SCLC by searching PubMed, Embase, the Cochrane Library, and major oncology conferences. We examined overall survival (OS) as the primary outcome. Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs).

Results: We included four randomized trials (IMpower133, CASPIAN, KEYNOTE-604, and EA5161) with a total of 1553 patients. Direct comparison showed that PD-L1 + Chemo (PFS: hazard ratio [HR] 0.79; OS: HR 0.75) and PD-1 + Chemo (PFS: HR 0.72; OS: HR 0.77) significantly prolonged survival time compared with chemotherapy alone. But PD-L1 + Chemo (relative risk [RR]: 1.07) and PD-1 + Chemo (RR: 1.13) were not superior to chemotherapy alone in terms of ORR. Indirect comparison showed no significant difference in clinical efficacy between PD-L1 + Chemo and PD-1 + Chemo (OS: HR 0.99; PFS: HR 1.10; ORR: RR 0.95). We further stratified patients according to subgroups in terms of OS. In the subgroup of patients with brain metastasis, PD-L1 + Chemo tended to prolong OS (HR: 0.61, 0.28 to 1.32). There were no significant differences between PD-L1 + Chemo and PD-1 + Chemo regarding safety analyses. However, PD-L1 + Chemo exhibited a better safety profile in reducing the risk of treatment discontinuation due to AEs (RR: 0.43, 0.19 to 0.95) and pneumonia (pneumonia of any grade, RR: 0.59, 0.24 to 1.42; pneumonia of grade ≥ 3, RR: 0.37, 0.10 to 1.39).

Conclusions: PD-L1 + Chemo and PD-1 + Chemo provided a significant survival benefit relative to chemotherapy alone for ES-SCLC. The efficacy and safety of PD-L1 + Chemo and PD-1 + Chemo were similar based on current evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-021-03017-zDOI Listing
March 2022

Surgical resection of primary tumors improved the prognosis of patients with bone metastasis of non-small cell lung cancer: a population-based and propensity score-matched study.

Ann Transl Med 2021 May;9(9):775

Department of Thoracic Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Most patients with lung cancer are in an advanced stage at the time of diagnosis due to occult onset. Bone is one of the most common sites of hematogenous metastasis of lung cancer. This study aimed to evaluate the impact of surgical resection of primary tumors on the prognosis of patients with bone metastasis of non-small cell lung cancer, using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: A total of 9,804 patients with only bone metastasis were identified from the SEER database. Propensity score matching was used to reduce the selection bias. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with or without primary tumor resection. The Cox regression model was applied to evaluate multiple prognostic factors.

Results: After propensity score matching, 424 patients were selected for survival analysis. No statistically significant differences were found in age, sex, race, tumor location, histology, T stage, and N stage between patients with or without surgical resection of primary tumors. The prognosis of patients who underwent surgical resection of primary tumors was significantly better than that of patients who had not undergone surgery. The surgical resection of primary tumors was an independent prognostic factor. The prognosis of patients who underwent lobectomy/bilobectomy was significantly better compared to other surgical types. Regional lymph node resection during surgery also significantly improved the prognosis of the patients.

Conclusions: For patients with only bone metastasis, surgical resection of primary tumors could significantly improve prognosis. Lobectomy/bilobectomy with regional lymph node resection was the best surgical strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-21-540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246174PMC
May 2021

Baseline and early changes in circulating Serum Amyloid A (SAA) predict survival outcomes in advanced non-small cell lung cancer patients treated with Anti-PD-1/PD-L1 monotherapy.

Lung Cancer 2021 08 28;158:1-8. Epub 2021 May 28.

State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Background: Systemic inflammation plays an important role in carcinogenesis and is associated with overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). Serum Amyloid A (SAA) is an acute-phase protein and a marker of persistent inflammation. We hypothesized that circulating SAA may predict outcomes in advanced non-small cell lung (aNSCLC) patients treated with PD-1/PD-L1 ICB.

Materials And Methods: This retrospective study included 91 aNSCLC patients who received anti-PD-(L)1 monotherapy in Sun Yat-sen University Cancer Center (Guangzhou, China) between August 2016 and June 2018. We examined the impact of circulating SAA at baseline and 8 (±2) weeks later on overall survival (OS). X-tile program was used to determine the cut-off values which optimized the significance of the split between Kaplan-Meier survival curves. Kaplan-Meier methodology and Cox regression analyses were conducted for survival analyses.

Results: The optimal cut-off value of baseline SAA for OS stratification was 137.6 mg/L. In univariate analysis, both high level of baseline SAA (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.47-5.18; P = 0.002) and lack of early SAA descent (HR, 1.51; 95% CI, 1.11-2.06; P = 0.009) were significantly associated with inferior OS. In multivariate analysis, gender, smoking status, performance status, liver metastasis, neutrophil-to-lymphocyte ratio, baseline SAA and early changes in SAA independently predicted OS (all with P < 0.05). A combined baseline SAA ≥ 137.6 mg/L and without early SAA descent identified a small cohort with remarkably worse OS (median, 3.2 months).

Conclusions: Both high baseline and lack of early decline in circulating SAA are significantly associated with inferior outcomes in aNSCLC patients treated with PD-1/PD-L1 ICB. Combined these two SAA indexes provided improved risk stratification. The prognostic value of this simple, readily-available, and cost-effective biomarker warrants larger, prospective validation before definitive recommendation can be made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2021.05.030DOI Listing
August 2021

Pre-Treatment Tumor Growth Rate Predicts Clinical Outcomes of Patients With Advanced Non-Small Cell Lung Cancer Undergoing Anti-PD-1/PD-L1 Therapy.

Front Oncol 2020 19;10:621329. Epub 2021 Jan 19.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Tumor growth rate (TGR; percent size change per month [%/m]) is postulated as an early radio-graphic predictor of response to anti-cancer treatment to overcome limitations of RECIST. We aimed to evaluate the predictive value of pre-treatment TGR (TGR) for outcomes of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1/PD-L1 monotherapy. We retrospectively screened all aNSCLC patients who received PD-1 axis inhibitors in Sun Yat-Sen University Cancer Center between August 2016 and June 2018. TGR was calculated as the percentage change in tumor size per month (%/m) derived from two computed tomography (CT) scans during a "wash-out" period before the initiation of PD-1 axis inhibition. Final follow-up date was August 28, 2019. The X-tile program was used to identify the cut-off value of TGR based on maximum progression-free survival (PFS) stratification. Patients were divided into two groups per the selected TGR cut-off. The primary outcome was the difference of PFS between the two groups. The Kaplan-Meier methods and Cox regression models were performed for survival analysis. A total of 80 eligible patients were included (54 [67.5%] male; median [range] age, 55 [30-74] years). Median (range) TGR was 21.1 (-33.7-246.0)%/m. The optimal cut-off value of TGR was 25.3%/m. Patients with high TGR had shorter median PFS (1.8 months; 95% CI, 1.6 - 2.1 months) than those with low TGR (2.7 months; 95% CI, 0.5 - 4.9 months) ( = 0.005). Multivariate Cox regression analysis revealed that higher TGR independently predicted inferior PFS (hazard ratio [HR] 1.97; 95% CI, 1.08-3.60; = 0.026). Higher TGR was also significantly associated with less durable clinical benefit rate (34.8% vs. 8.8%, = 0.007). High pre-treatment TGR was a reliable predictor of inferior PFS and clinical benefit in aNSCLC patients undergoing anti-PD-1/PD-L1 monotherapy. The findings highlight the role of TGR as an early biomarker to predict benefit from immunotherapy and could allow tailoring patient's follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.621329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863973PMC
January 2021

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma.

Signal Transduct Target Ther 2020 12 30;5(1):289. Epub 2020 Dec 30.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.

Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m (day 1), gemcitabine 1 g/m (days 1 and 8) and oxaliplatin 130 mg/m (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-020-00331-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772337PMC
December 2020

Survival Trends in Patients Under Age 65 Years With Mantle Cell Lymphoma, 1995-2016: A SEER-Based Analysis.

Front Oncol 2020 20;10:588314. Epub 2020 Oct 20.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

The treatment paradigm for mantle cell lymphoma (MCL), a B-cell malignancy, has shifted considerably during the past decades. This study aimed to evaluate time trends in overall survival (OS) and disease-specific mortality (DSM) of younger (age ≤ 65 years) patients with MCL from 1995 to 2016. We used the Surveillance, Epidemiology, and End Results database. Year of diagnosis was divided into three eras: the chemotherapy-alone era (1995-2000), intensified-immunochemotherapy era (2001-2012), and targeted-therapy era (2013-2016). We used the Kaplan-Meier method, log-rank test, and subdistribution proportional hazard regression in the analysis. A total 4,892 patients were identified. Median OS increased from 67 months in the chemotherapy-alone era to 107 months in the intensified-immunochemotherapy era ( < 0.001). The DSM rate decreased significantly from 1995 to 2016 ( < 0.001); the adjusted hazard ratios of MCL-specific death were 0.589 ( < 0.001) for the intensified-immunochemotherapy era and 0.459 ( < 0.001) for targeted-therapy era, as compared with the chemotherapy-alone era. Patients with advanced-stage MCL exhibited lowering risk of death across the three eras ( < 0.001). During 1995-2016, survival in younger patients with MCL increased significantly, especially those with advanced-stage disease, potentially reflecting the impact of advancement in treatment modalities on MCL outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.588314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606943PMC
October 2020

Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma by Targeting the Epidermal Growth Factor Receptor Combined with Gemcitabine Plus Platinum.

Cancer Manag Res 2020 20;12:10353-10360. Epub 2020 Oct 20.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.

Purpose: The purpose of this study was to evaluate the anti-tumor activity and safety of anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with gemcitabine plus platinum (GP) as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC).

Patients And Methods: This retrospective study analyzed RM-NPC patients at Sun Yat-sen University Cancer Center who received anti-EGFR antibody plus GP as a first-line treatment between July 2007 and November 2018. Survival analyses were performed using the Kaplan-Meier method with Log rank test. Cox proportional hazards model was used for the multivariate analysis.

Results: A total of 84 patients were enrolled. The median progression-free survival (PFS) was 10.3 months (95% CI, 6.9-13.6 months), and the median overall survival (OS) was 42.8 months (95% CI, 24.6-60.9 months). The objective response rate and disease control rate were 67.9% and 92.9%, respectively. The multivariate analysis identified a higher baseline EBV DNA level as a risk factor for both PFS (P=0.025) and OS (P=0.013). Additionally, age≥44 years (P =0.003), non-cisplatin (P= 0.009), and poor KPS (≤80) (P =0.034) were other risk factors for OS. The most common adverse events were leukopenia (n=73, 86.9%). The most common grade 3-4 AEs were leukopenia (n=30, 35.7%) and thrombocytopenia (n=22, 26.2%).

Conclusion: Anti-EGFR monoclonal antibody plus GP achieved promising antitumor activity with a tolerable toxicity profile in RM-NPC as a first-line treatment. Randomized clinical trials are warranted to compare the efficacy of GP with or without anti-EGFR antibody in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S275947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585779PMC
October 2020

Systemic chemotherapy and sequential locoregional radiotherapy in initially metastatic nasopharyngeal carcinoma: Retrospective analysis with 821 cases.

Head Neck 2020 08 10;42(8):1970-1980. Epub 2020 Mar 10.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: We designed this retrospective study to explore the best treatment modality for patients with initially metastatic nasopharyngeal carcinoma (NPC).

Methods: From 2008 to 2017, 821 patients were enrolled. Treatment modalities and prognostic factors were analyzed.

Results: Compared with chemotherapy alone and radiotherapy-based treatment, systemic chemotherapy-sequential locoregional radiotherapy to the nasopharyngeal primary tumor site were associated with a significantly increased 3-year overall survival (OS) rate (40.3%, 11.7%, and 22.9%, P < .001). The overall response rate of the paclitaxel combined with platinum and fluorouracil (TPF) regimen as first-line chemotherapy was higher than that of the paclitaxel plus platinum (TP) regimen (78.2% vs 70.0%, P = .038). A better OS was achieved in the TPF group compared to doublet drug regimens (3-year OS, 35.7% vs 25.3%, P < .001).

Conclusions: Systemic chemotherapy-sequential locoregional radiotherapy may prolong OS and progression-free survival for selected patients with initially metastatic NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26130DOI Listing
August 2020

Anti-epidermal growth factor receptor monoclonal antibody plus palliative chemotherapy as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma.

Cancer Med 2020 03 19;9(5):1721-1732. Epub 2020 Jan 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Platinum-based chemotherapy is the standard of care as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC); however, the prognosis of patients with RM-NPC remains poor. The aim of this study was to evaluate the role of anti-epidermal growth factor receptor (anti-EGFR) antibody plus chemotherapy for RM-NPC.

Methods: RM-NPC patients who received first-line chemotherapy plus an anti-EGFR antibody were recruited from Sun Yat-Sen University Cancer Center between July 2007 and November 2017. Survival analyses were performed using the Kaplan-Meier method with a log-rank test. A Cox proportional hazards model was used for the multivariate analyses.

Results: A total of 203 patients were enrolled in the present study. The median follow-up time was 34.3 months (interquartile range: 19.7-66.5 months). The median progression-free survival (PFS) was 8.9 months (95% CI: 7.7-10.0 months) and the median overall survival (OS) was 29.1 months (95% CI: 23.5-34.6 months). The 1-, 3-, and 5-year PFS and OS rates were 35.5% and 79.6%, 15.2% and 42.5%, and 11.6% and 23.6%, respectively. The objective response rate (ORR) was 67.5% and the disease control rate (DCR) was 91.1%. The multivariate analysis identified the following prognostic factors for PFS: anti-EGFR agent (P = .010), recurrence/metastasis sequence (P = .016), KPS (P = .017), and combined chemotherapy regimen (P = .015). Independent risk factors for OS included age >43 years (P = .002), Karnofsky performance score ≤80 (P < .001), and higher level of baseline Epstein-Barr virus (EBV) DNA (P = .008). Leukopenia was the most common adverse event (AE) in this cohort (any grade, 84.2%; grades 3-4, 43.4%).

Conclusions: Anti-EGFR antibody plus chemotherapy achieved promising antitumor activity with a tolerable toxicity profile in RM-NPC. Thus, randomized clinical trials are warranted to compare the efficacy of chemotherapy with or without anti-EGFR antibody in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.2838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050081PMC
March 2020

Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition.

J Immunother Cancer 2019 11 21;7(1):322. Epub 2019 Nov 21.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: Hepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy.

Methods: This retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation.

Results: In total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16-76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3-35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 10 IU/mL (range, 1.80 × 10-6.00 × 10 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 [95% CI, 1.95-157.07], P = .004).

Conclusions: HBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40425-019-0808-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873745PMC
November 2019

First-line platinum-based chemotherapy and survival outcomes in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma.

Lung Cancer 2019 11 12;137:100-107. Epub 2019 Sep 12.

State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Objectives: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of primary lung cancer. Due to the lack of prospective studies, the optimal first-line chemotherapy regimens and survival outcomes remain unclear.

Materials And Methods: This real-world, retrospective study enrolled consecutive patients with unresectable pulmonary LELC. The survival outcomes, prognosis, and comparative efficacy of different chemotherapy regimens were investigated.

Results: In total, 127 patients were included in the analyses. The first-line chemotherapy regimens included gemcitabine plus platinum (GP, n = 19 [15.0%]), taxanes plus platinum (TP, n = 70 [55.1%]) and pemetrexed plus platinum (AP, n = 38 [30.0%]). 25 (19.7%) patients underwent palliative thoracic radiotherapy. 60 (47.2%) patients had detectable baseline Epstein-Barr virus (EBV) DNA. For the entire cohort, objective response was obtained in 41 patients (32.3%). Median progression-free survival (PFS) and overall survival (OS) were 7.7 months (95% CI, 6.6-8.8) and 36.7 months (95% CI, 30.9-42.5), respectively. Among the three chemotherapy regimens, GP achieved the highest response rate (GP, 63.2% vs. TP, 30.0% vs. AP, 21.1%; p = 0.005). Median PFS in the GP group (8.8 months) was also significantly longer than that in the TP group (7.9 months) and AP group (6.4 months) (p = 0.031). In the multivariate model, cycles of first-line chemotherapy (p < 0.001), palliative thoracic radiotherapy (p < 0.001), and chemotherapy regimens (p = 0.031) remained independent prognostic factors for PFS; while cycles of first-line chemotherapy (p = 0.002), baseline EBV DNA (p = 0.033) and palliative thoracic radiotherapy (p = 0.041) were significantly associated with OS.

Conclusion: Gemcitabine-based chemotherapy and palliative thoracic radiotherapy are active in pulmonary LELC. These data provide added evidence for the similarity between pulmonary LELC and nasopharyngeal carcinoma in endemic area. Randomized controlled studies are needed to further define the standard-of-care for patients with advanced pulmonary LELC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2019.09.007DOI Listing
November 2019

First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy.

J Immunother Cancer 2019 05 3;7(1):120. Epub 2019 May 3.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at least 50%. However, little is known about the value of adding chemotherapy to pembrolizumab in this setting. Therefore, we performed an indirect comparison for pembrolizumab plus chemotherapy versus pembrolizumab, using the frequentist methods. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Data were retrieved from randomized trials comparing pembrolizumab plus chemotherapy or pembrolizumab monotherapy against chemotherapy. Five trials involving 1289 patients were included. Direct meta-analysis showed that both pembrolizumab plus chemotherapy (ORR: relative risk (RR) 2.16; PFS: hazard ratio (HR) 0.36; OS: HR 0.51) and pembrolizumab alone (ORR: RR 1.33; PFS: HR, 0.65; OS: HR 0.67) improved clinical outcomes compared with chemotherapy. Indirect comparison showed that pembrolizumab plus chemotherapy was superior to pembrolizumab alone, in terms of ORR (RR 1.62, 1.18-2.23) and PFS (HR 0.55, 0.32-0.97). A trend towards improved OS was also observed (HR 0.76, 0.51-1.14). In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40425-019-0600-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500047PMC
May 2019

Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis.

J Immunother Cancer 2018 12 22;6(1):155. Epub 2018 Dec 22.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: Immune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors.

Methods: We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.

Results: Six trials involving 3144 patients were included. PD-1/PD-L1 inhibitor plus chemotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.62; 95% CI 0.57-0.67; P < .001), OS (HR, 0.68; 95% CI 0.53-0.87; P = .002) and ORR (relative ratio [RR], 1.56; 95% CI 1.29-1.89; P < .001), irrespective of PD-L1 expression level. The significant predictor(s) for treatment benefit with combination therapy versus chemotherapy alone were PD-L1 expression level for PFS (P < .001); types of checkpoint inhibitor for ORR (P < .001); histology (P = .025), age (P = .038), gender (P < .001), and types of checkpoint inhibitor (P < .001) for OS. In safety analyses, PD-1/PD-L1 inhibitor plus chemotherapy had significantly higher incidence of adverse events (AEs) of grade 3 or higher (RR, 1.14; P = .007), AEs leading to treatment discontinuation (RR, 1.29; P = .022), serious AEs (RR 1.70; P = .006), immune mediated AEs of any grade (RR, 2.37; P < .001), and immune mediated AEs of grade 3 or higher (RR, 3.71; P < .001).

Conclusions: PD-1/PD-L1 inhibitor plus chemotherapy, compared with chemotherapy, is associated with significantly improved PFS, ORR, and OS in first-line therapy in NSCLC, at the expense of increased treatment-related AEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40425-018-0477-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303974PMC
December 2018

Clinical characteristics and outcomes of Castleman disease: A multicenter study of 185 Chinese patients.

Cancer Sci 2018 Jan 28;109(1):199-206. Epub 2017 Dec 28.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. One hundred and twenty-one patients (65.4%) were classified as unicentric CD (UCD) and 64 patients (34.6%) were classified as multicentric CD (MCD). The histology subtype was hyaline-vascular for 132 patients (71.4%), plasma cell for 50 patients (27%), and mixed type for 3 patients (1.6%). The 5-year overall survival (OS) of 185 CD cases was 80.3%. All UCD patients underwent surgical excision, whereas the treatment strategies of MCD patients were heterogeneous. The outcome for UCD patients was better than MCD patients, with 5-year OS rates of 93.6% and 51.2%, respectively. In further analysis of the MCD subgroup, a multivariate analysis using a Cox regression model revealed that age, splenomegaly and pretreatment serum albumin level were independent prognostic factors for OS. This multicenter study comprising the largest sample size to date suggested that MCD is a distinct entity from UCD with a significantly worse outcome. Older age (≥40 years), splenomegaly, and hypoalbuminemia were risk factors for poorer MCD prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.13439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765290PMC
January 2018

Clinical characterization and outcome of primary bone lymphoma: a retrospective study of 61 Chinese patients.

Sci Rep 2016 06 30;6:28834. Epub 2016 Jun 30.

Department of Lymphoma, Peking University Cancer Hospital &Institute, 52 Fucheng Road, Beijing 100142, China.

Primary bone lymphoma(PBL) is a rare disease. To assess the clinical characteristics, outcome, and prognostic factors of this entity in Chinese population, we retrospectively analyzed 61 PBL patients initially treated in our institution between 1997 and 2014. The median age was 45 years. The most common histological subtype was diffuse large B-cell lymphoma (DLBCL) (55.7%), followed by T-cell lymphoma (18.0%). All patients underwent systemic chemotherapy as initial treatment while 24 patients (39.3%) were additionally treated with radiotherapy. The 5-year overall survival (OS) and the 5-year progression-free survival (PFS) rates of 57 cases with completed follow-up were 52.3% and 40.1%, respectively. In further analysis of the primary bone DLBCL (PB-DLBCL) subgroup, the 5-year OS and PFS rates were 53.0% and 47.0%, and a multivariable analysis revealed that baseline Eastern Cooperative Oncology Group (ECOG) score and response to initial treatment (complete remission versus no complete remission) were independent prognostic factors for both OS and PFS. The proportion of T-cell lymphoma is higher in China than in western populations. High baseline ECOG scores (≥2) and unachieved CR in initial therapy were factors for poor PB-DLBCL prognosis. The role of radiotherapy and rituximab in PLB therapy remains to be confirmed in further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep28834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928085PMC
June 2016
-->