Extravascular red blood cells and hemoglobin promote tumor growth and therapeutic resistance as endogenous danger signals.

Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1ß release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance.

68Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study.

INTRODUCTION: Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom 68Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of 68Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration. METHODS AND ANALYSIS: In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo 68Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by 68Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of 68Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300067591.

Which is false: oxaliplatin or fluoropyrimidine? An analysis of patients with KRAS wild-type metastatic colorectal cancer treated with first-line epidermal growth factor receptor monoclonal antibody.

This meta-analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin-based chemotherapy treatment improves efficacy in KRAS wild-type metastatic colorectal cancer (mCRC), and whether infusional 5-fluorouracil (5-FU) and oxaliplatin is a preferred combination for EGFR mAbs. Oxaliplatin (including treatment), EGFR mAbs, first-line treatment, KRAS wild-type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. Time-to-event outcomes of overall survival (OS) and progression-free survival (PFS) were analyzed using HRs (hazard ratios) with fixed effect, and response rate (RR) using odd ratios (OR) with fixed effect. A total of 1767 patients who were KRAS wild-type were included in this meta-analysis, with 866 patients in the mAbs and chemotherapy combination group and 901 patients in the chemotherapy alone group. The addition of mAbs to oxaliplatin-based chemotherapy in patients with KRAS wild-type mCRC as first-line treatment resulted in significant improvements in PFS (HR = 0.88; 95% confidence interval (CI), 0.79-0.99; P = 0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14-1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR = 0.96; 95% CI, 0.85-1.08; P = 0.48). However, the differences in OS and PFS were not significant when mAbs were added to bolus 5-FU or capecitabine-based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5-FU and oxaliplatin combination (P = 0.06; PFS, HR = 0.76; 95% CI, 0.65-0.86; P = 0.0002), and even OS was marginally significant, which was consistent with the subgroup analysis of cetuximab and panitumumab. EGFR mAbs combined with oxaliplatin and an infusional 5-FU regimen was associated with significantly improved RR, PFS and OS as first-line treatment in KRAS wild-type mCRC.

Optimum duration of extended adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer: protocol for a network meta-analysis of randomised controlled trials.

INTRODUCTION: The type of extended adjuvant endocrine therapy is not clear, nor is the optimum duration of extended adjuvant endocrine therapy for patients with early breast cancer. Our study aims to satisfy the requirements for systematically identifying and synthesising the available evidence on the clinical safety and efficacy of extended adjuvant endocrine therapy for patients with hormone receptor-positive early breast cancer. METHODS AND ANALYSIS: A comprehensive electronic literature database search will be performed using three electronic databases: PubMed, Cochrane Library and Embase (Ovid interface). Our main outcomes of interest were overall survival, disease-free survival, relapse-free survival, invasive contralateral breast cancer, acceptability and grades 3 and 4 non-haematological toxicities in this study. We will assess the risk of bias and overall quality of evidence using the Cochrane Collaboration's tool and Grades of Recommendation, Assessment, Development and Evaluation, respectively. We will perform subgroup and sensitivity analyses in the selected trials. We will assess the three key assumptions of network meta-analysis: transitivity, consistency and homogeneity. ETHICS AND DISSEMINATION: The protocol was preregistered in the International Prospective Register of Systematic Reviews (PROSPERO) database. Ethics approval and patient consent are not required for the network meta-analysis. The final results of this network meta-analysis will be disseminated through national and international conferences and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021278271.

Comparison of trimodality therapy and neoadjuvant chemotherapy combined with radical cystectomy for the survival of muscle-invasive bladder cancer: a population-based analysis.

BACKGROUND: Trimodality therapy (TMT) is a mature alternative to radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC) who seek to preserve their primary bladder or are inoperable due to comorbidities. To date, there has been increasing evidence of the effectiveness of TMT as an alternative to RC. In contrast, no literature has stated the effectiveness of neoadjuvant chemotherapy combined with RC (NAC + RC) compared with TMT. OBJECTIVE: We aimed to compare the prognosis between patients receiving TMT and NAC + RC. METHODS: The clinicopathological characteristics of patients with T2-4aN0M0 MIBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models and Kaplan‒Meier survival curves were used for the survival analysis. Propensity-score matching (PSM) was applied to determine the differences between the two groups. The primary outcome was cancer-specific survival (CSS), and the secondary outcome was overall survival (OS). RESULTS: In total, 1,175 patients with MIBC who underwent TMT (n = 822) or NAC + RC (n = 353) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. After 1:1 PSM, the final patient sample included 303 pairs. The prognosis of patients receiving NAC + RC was significantly better than that of patients receiving TMT in both unmatched and matched cohorts (5-year CSS: before PSM, 75.4% vs. 50.6%, P < 0.0001; after PSM, 76.3% vs. 49.5%, P < 0.0001; 5-year OS: before PSM, 71.7% vs. 37.4%, P < 0.0001; after PSM, 71.7% vs. 31.4%, P < 0.0001). The survival advantages of NAC + RC remained remarkable in the stratified analysis of most factors after PSM. Multivariate Cox regression analysis showed that being older than 68 years old, unmarried, grade III/IV, T3-4a stage, and undergoing TMT independently correlated with poor OS. CONCLUSION: Thus, in this study, patients with MIBC receiving NAC + RC presented with a better prognosis than those receiving TMT.

Effects of selenium supplementation on concurrent chemoradiotherapy in patients with cervical cancer: A randomized, double-blind, placebo-parallel controlled phase II clinical trial.

Objective: Selenium (Se) is an essential trace element and may affect cervical cancer occurrence and progression. The association between selenium supplementation and acute toxic reactions and clinical outcomes in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy remains unclear. The aim of this study was to determine the safety profile of add-on Se yeast and assess the potential of Se to ameliorate the hematologic toxicity of concurrent chemoradiotherapy in patients with cervical cancer. Methods: Patients with Federation International of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer who met all inclusion criteria were randomly assigned to either the experimental group or the control group. The experimental group received Se yeast tablets (100 µg Se, twice daily), while the control group received placebos (twice daily) for 5 weeks in total. All patients in both groups received standard treatment, including pelvic external irradiation, concurrent five cycles of chemotherapy, and brachytherapy. Measures included the incidence of myelosuppression, impairment of liver and kidney function, objective response rate (ORR), and blood Se concentrations before, during and after the treatment of the two groups. Results: A total of 104 eligible patients were enrolled in the experimental group (n = 50) or the control group (n = 54). The ORR in the experimental group and control group were 96 and 94%, respectively (p = 0.47). The baseline levels of blood Se before treatment in the experimental and control groups were similar (58.34 ± 17.63 µg/L and 60.21 ± 18.42 µg/L, p = 0.60), but the concentrations became significantly different after course completion between the two groups (76.16 ± 24.47 µg/L and 57.48 ± 14.92 µg/L, respectively, p < 0.01). Se dramatically decreased the incidence of grade 3 myelosuppression (48% vs. 63%, p = 0.034) compared to the control group. In the subgroup of patients with moderately well-differentiated cervical cancer, the incidence of thrombocytopenia induced by concurrent chemoradiotherapy was lower in the experimental group than in the control group (53.8% vs. 78.9%, p < 0.01). However, no difference was observed in liver and kidney injuries between the two groups. Conclusion: Supplementation with Se effectively increased blood Se levels in Se-inadequate cervical cancer patients. As an add-on to standard treatment, Se-yeast significantly decreased the hematologic toxicity of concurrent chemoradiotherapy.

Role of CDK4/6 inhibitors in patients with hormone receptor (HR)-positive, human epidermal receptor-2 negative (HER-2) metastatic breast cancer study protocol for a systematic review, network meta-analysis and cost-effectiveness analysis.

INTRODUCTION: It is currently unclear which cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, combined with endocrine therapy, is the preferred treatment approach in patients with hormone receptor (HR)-positive, human epidermal receptor-2 (HER2) negative metastatic breast cancer. The aim of this study was to evaluate the existing evidence for the comparative efficacy, safety and cost-effectiveness of different CDK4/6 inhibitors for metastatic breast cancer in first-line and second-line settings. METHODS AND ANALYSIS: We will systematically conduct a literature search in Embase, PubMed and the Cochrane Library and additional searches by handsearching citations of previous systematic reviews. We will also screen major conference proceedings (American Society of Clinical Oncology, European Society of Medical Oncology and San Antonio Breast Cancer Symposium). Preliminary scoping searches were conducted in July 2021, but the search will be updated when new trials are available. The primary outcome was progression-free survival. The secondary outcomes were overall survival, objective response rates, grade 3-4 haematological and non-haematological toxicities, quality-adjusted life years and incremental cost-effectiveness ratios. The risk of bias will be assessed by Cochrane risk of bias tools, and the quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation. Subgroup analyses and sensitivity analyses will be performed to further confirm our findings. In addition, one-way sensitivity analysis and probabilistic sensitivity analyses will be conducted to determine uncertainty. ETHICS AND DISSEMINATION: This study does not require ethics approval as only secondary data will be collected. The results of our study will provide an overview of the current level of CDK4/6 inhibitors for patients with HR-positive, HER2-negative metastatic breast cancer, and undertake subgroup analyses to explore variables that might affect these effects. The results of this study will be presented at an international clinical conference and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021266597.

Cost-effectiveness analysis of ultra-hypofractionated radiotherapy and conventionally fractionated radiotherapy for intermediate- to high-risk localized prostate cancer.

Background: Radiotherapy is an effective curative treatment option for intermediate- to high-risk localized prostate cancer. According to the HYPO-RT-PC trial (ISRCTN45905321), there was no significant difference in 5 years of follow-up in terms of failure-free survival, overall survival, urinary toxicity, and bowel toxicity, while erectile function decreased between ultra-hypofractionated radiotherapy with conventionally fractionated radiotherapy, except that the incidence of urinary toxicity in ultra-hypofractionated radiotherapy was higher at 1 year of follow-up. We evaluated the cost-effectiveness of ultra-hypofractionated radiotherapy and conventionally fractionated radiotherapy for intermediate- to high-risk localized prostate cancer from the Chinese payer's perspective. Methods: We developed a Markov model with a 15-year time horizon to compare the cost and effectiveness of ultra-hypofractionated radiotherapy with those of conventionally fractionated radiotherapy for localized intermediate- to high-risk prostate cancer. The outcomes were measured in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and willingness-to-pay (WTP). Univariable and probability sensitivity analyses were performed to evaluate the robustness of the Markov model. Results: Based on the Markov model, conventionally fractionated radiotherapy yielded 2.32 QALYs compared with 2.14 QALYs in ultra-hypofractionated radiotherapy in China. The cost of ultra-hypofractionated radiotherapy was found to be decreased by about 14% folds ($4,251.04) in comparison with that of conventionally fractionated radiotherapy. The ICER of conventionally fractionated radiotherapy versus that of ultra-hypofractionated radiotherapy was $23,616.89 per QALY in China. The failure-free survival with grade 2 or worse urinary toxicity and the discount rate per annum were the most sensitive parameters utilized in ultra-hypofractionated radiotherapy. The cost-effectiveness acceptability curve showed that conventionally fractionated radiotherapy had 57.7% probability of being cost-effective under the Chinese WTP threshold. Conclusion: From the perspective of Chinese payers, ultra-hypofractionated radiotherapy was not a cost-effective strategy compared with conventionally fractionated radiotherapy for patients with localized intermediate- to high-risk prostate cancer. Nevertheless, reduction of the grade 2 or worse urinary toxicity of ultra-hypofractionated radiotherapy could alter the results.

Comparative efficacy and safety of neoadjuvant radiotherapy for patients with borderline resectable, and locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis protocol.

INTRODUCTION: The optimal dose and treatment modality of neoadjuvant radiotherapy applied for treating borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC) have been debated topics in oncology. The objective of the present network meta-analysis (NMA) is to study and compare the efficacy and safety of neoadjuvant radiotherapy comprehensively using different doses in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS: Four electronic databases, including PubMed, EMBASE, Cochrane library and Web of science, will be searched thoroughly to identify relevant studies published from 2006 to October 2020. Electronic searching by titles using neoadjuvant treatments for PDAC will be performed in the annual meetings of European Society of Medical Oncology and American Society of Clinical Oncology (2018-2020). CLINICALTRIALS: gov will also be searched for grey literature. Two reviewers will perform search strategies and extract data independently. R0 resection rate and local control rate are defined as primary outcomes. Secondary outcomes include overall survival, disease-free survival and acute and late grade 3 and grade 4 toxicities. For randomised control trials, the risk of bias will be assessed using the Cochrane Risk of Bias Tool, while the risk of bias for non-randomised, observational studies will be evaluated using the Risk Of Bias In Non-randomised Studies-of Interventions. The quality of evidence will be evaluated using the version of Cochrane tool and Grades of Recommendation, Assessment, Development and Evaluation. Subgroup analysis and sensitivity analysis will be conducted in the present NMA. ETHICS AND DISSEMINATION: This study will synthesise the evidence regarding dose schedule of neoadjuvant radiotherapy in patients with BRPC and LAPC. We hope the findings from this NMA will help clinicians and patients select the optimal modality and dose schedule of neoadjuvant radiotherapy with respect to patient-reported outcomes. As no primary data collection will be undertaken, no ethics approval is required. The results will be disseminated through peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020222408.

Efficacy of chemotherapy combined with toripalimab in PD-L1-positive and high tumor mutation burden pancreatic acinar cell carcinoma: case report.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare tumor, accounting for about 1% of all pancreatic exocrine cancers. Consensus on the management of metastatic PACC remains unclear. CASE PRESENTATION: Starting from April 2019, a patient first received chemotherapy with two cycles of gemcitabine and nab-paclitaxel and two cycles of SOX regimen. After progression of disease evaluated based on RECIST 1.1, toripalimab and SOX regimen was administered because of PD-L1-positive expression, high tumor mutation burden (TMB), and somatic FANCA deletion in the tumor. Both the primary and metastatic tumor mass shrank significantly after two courses. The patient exhibited sustained partial response for at least six courses with well-controlled toxic effects. Then the treatment had to be stopped for 2 months because of the coronavirus disease 2019 pandemic. Computed tomography scan in March 2020 showed disease progression. Time from initiating treatment to tumor progression on toripalimab and SOX regimen treatment took up to at least 8 months. CONCLUSIONS: We present the first case report where a PD-L1 positive, high TMB, and FANCA-deleted pancreatic acinar cell carcinoma was treated using chemotherapy combined with immunotherapy, in which the patient exhibited satisfactory response and tolerance.

Optimum adjuvant trastuzumab duration for human epidermal growth factor receptor-2 positive breast cancer: a network meta-analysis of randomized trials.

BACKGROUND: Adjuvant trastuzumab treatment for 12 months is the standard-of-care for early HER2-positive breast cancer; however, the optimal duration is unclear. We performed a network meta-analysis (NMA) to determine the optimal treatment duration. METHODS: We identified 16 randomized controlled trials involving 29,837 patients that assessed trastuzumab treatment in HER2-positive early breast cancer. Our NMA compared six trastuzumab durations: observation, T-9 weeks, T-12 weeks, T-6 months, T-12 months, and T-24 months. We assessed overall survival (OS), disease-free survival (DFS), acceptability, and cardiotoxicities and grade 3-4 nonhematologic toxicities, and ranked the durations in terms of efficacy and safety by surface under the cumulative ranking (SUCRA). RESULTS: Pairwise meta-analysis showed that while T-6 months was associated with a significant reduction in DFS compared to T-12 months. In our NMA, increasing or decreasing durations showed a significant benefit in DFS compared to observation; however, decreasing durations was not associated with a significant reduction in DFS compared with T-12 months, regardless of the lymph node and hormone receptor statuses. SUCRA ordered the optimum durations of trastuzumab treatment based on PFS as T-12 months (95.6%), T-24 months (69.6%), T-6 months (53.2%), T-9 weeks (41.2%), T-12 weeks (34.3%) and observation (6.1%). CONCLUSIONS: Escalating trastuzumab treatment beyond T-12 months confers no additional survival benefit but increased risk of cardiotoxicities. Furthermore, de-escalating treatment confers no improvement on OS compared to T-12 months. These data suggest that T-12 months is the most appropriate treatment schedule for HER2-positive early breast cancer.

Apatinib treatment for unresectable gastrointestinal stromal tumor with synchronous gastric cancer.

Nearly one-fifth of patients diagnosed with gastrointestinal stromal tumors (GISTs) simultaneously experience a second primary tumor. In particular, coexistence of gastric GISTs and gastric cancer is relatively more common. However, the optimal treatment for advanced GIST with gastric cancer is largely unknown. We report a case of simultaneous occurrence of gastric GIST and gastric cancer that benefited from apatinib. After first-line imatinib and S-1 treatment for 6 months, the GIST and the gastric cancer both progressed. The patient was then treated with apatinib, exhibiting a partial response (PR) both in the GIST and the gastric cancer at 7 months, and continuous PR so far with well-controlled toxic effects of hypertension. Progression-free survival reached 10 months. In view of the relatively high incidence of advanced GIST with synchronous gastric cancer, therapy to simultaneously treat the two kinds of tumors is urgently needed. Apatinib provides promising and well-tolerated therapy for GISTs with synchronous gastric cancer refractory to chemotherapy combined with imatinib.

Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials.

INTRODUCTION: Controversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers. METHODS AND ANALYSIS: Electronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration's tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA. ETHICS AND DISSEMINATION: Ethics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports. TRIAL REGISTRATION NUMBER: CRD42019139109.

Optimal dose-fractionation schedule of palliative radiotherapy for patients with bone metastases: a protocol for systematic review and network meta-analysis.

INTRODUCTION: The optimal dose-fractionation schedule of palliative radiotherapy has been debated in patients with bone metastases. Our objective is to comprehensively compare multiple fraction schedules with single fraction radiotherapy in terms of efficacy and toxicities by performing a systematic review and network meta-analysis. METHODS AND ANALYSIS: Electronic searches of titles/abstracts of palliative radiotherapy for bone metastases will be performed, using PubMed, Cochrane Library, Embase, clinical trials, American Society for Therapeutic Radiology and Oncology and European Society of Radiotherapy and Oncology. The primary outcome of interest is the incidence of skeletal-related event following palliative radiotherapy for bone metastases in prospective studies. The risk of bias and quality of evidence will be evaluated based on Cochrane Collaboration's tool and Grades of Recommendation, Assessment, Development and Evaluation in the network meta-analysis. We will conduct subgroup analysis and sensitivity analysis regardless of heterogeneity estimates. ETHICS AND DISSEMINATION: This study will synthesise the evidence regarding dose-fractionation schedule of palliative radiotherapy in patients with bone metastases. We hope the findings from this study will help clinicians and patients select optimum palliative radiotherapy by identifying the optimal dose-fractionation schedule of palliative radiotherapy with the most value in terms of patient-important outcomes. The evidence obtained from network meta-analysis will help to guide head-to-head research in the future. The results will be disseminated through international conference reports and peer-reviewed manuscripts. Ethics review board is not required for this network meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42019135195.

Network meta-analysis comparing neoadjuvant chemoradiation, neoadjuvant chemotherapy and upfront surgery in patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma.

PURPOSE: Neoadjuvant chemoradiation or chemotherapy has improved the treatment efficacy of patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma (PDAC). Due to the optimal regimen remains inconclusive, we aimed to compare these treatments in terms of margin negative (R0) resection rate and overall survival (OS) with Bayesian analysis. PATIENTS AND METHODS: We reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiation, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology and ClinicalTrials.gov database from 2009 to 2018 to estimate relative odds ratios (ORs) for margin negative (R0) resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials. RESULTS: A total of 14 literatures with 1056 patients were enrolled in this Bayesian analysis. In the pairwise meta-analysis from limited head-to-head studies, compared with neoadjuvant chemotherapy, neoadjuvant chemoradiation showed superior OS significantly (HR 0.8, 95% CI 0.60-0.99, p < 0.001) and there was no significant difference in R0 resection rate (OR 1.02, 95%CI 0.45-2.33, I2 = 34.6%). However, in the network meta-analysis from all enrolled clinical trials, neoadjuvant chemoradiation showed significantly higher R0 resection rate over upfront surgery (HR 0.15, 95% CrI 0.02-0.56), whereas neoadjuvant chemotherapy did not provide better efficacy in R0 resection over upfront surgery (HR 0.42, 95% CrI 0.02-4.41). For R0 resection rate, neoadjuvant chemoradiation has the highest probability of ranking one compared with neoadjuvant chemotherapy or upfront surgery (79% vs 21% vs 0%). For OS, neoadjuvant chemotherapy has the highest probability of ranking one compared with neoadjuvant chemoradiation or upfront surgery (98% vs 0% vs 2%). Neoadjuvant chemotherapy was associated with higher rates of postoperative complications (rank worst: 84%), followed by neoadjuvant chemoradiotherapy (13%) and upfront surgery (3%). CONCLUSIONS: Different neoadjuvant treatment was selected based on various purposes, whether increasing R0 resection rate or not. Future clinical trials comparing neoadjuvant chemoradiation with neoadjuvant chemotherapy are warranted to confirm our results.

Which is the optimal adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma?: A protocol for a network meta-analysis of randomized controlled trials.

BACKGROUND: Although adjuvant chemotherapy has been shown to reduce relapse and prolong survival after surgery, it is still unclear which adjuvant chemotherapy regimen will be favorable over the all adjuvant treatments evaluated for patients with resected pancreatic ductal adenocarcinoma. METHODS: PubMed, Embase (Ovid version), Cochrane Library, the American Society of Clinical Oncology, and ClinicalTrials.gov database will be searched from their inception to January 19, 2019. We will include studies that contain adjuvant chemotherapy following surgery in patients with pancreatic ductal adenocarcinoma. The outcomes are overall survival, disease-free survival, and grade 3-4 hematological and nonhematological toxicity. The risk of bias for each randomized controlled trial will be assessed as low, moderate, or high using Cochrane Collaboration's tool independently. Pairwise and network meta-analysis will be performed using STATA 13.0, GeMTC, and WinBUGS, respectively. The competing adjuvant chemotherapy regimens will be ranked by an advantage index. RESULTS: The study is ongoing and the results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This network meta-analysis will systematically provide suggestions to select optimum adjuvant treatment for clinical practice in the future.PROSPERO registration number: CRD42019123907 (https://www.crd.york.ac.uk/PROSPERO/#searchadvanced).

Resection of primary lesion for patients with metastatic breast cancer: where are we now?

It is largely unclear that whether or not surgical resection of the primary tumors could confer survival benefit among patients with metastatic breast cancer at initial presentation. We thoroughly reviewed the up-to-date evidence on surgical resection of the primary lesion in metastatic breast cancer, including comparative studies (of particular interest in risk modifiers, the type, and timing of surgical procedures), Chinese and international guidelines, as well as the progress of clinical trials. Partial modified radical mastectomy and breast-conserving surgery are by far the most common choices for patients with metastatic breast cancer. Patients with certain characteristics, for example, younger than 45 years of age or with oligo-metastasis, might benefit from the surgery. The type and timing of surgical procedures are still in debate according to the guidelines from different countries. Forthcoming evidence from the ongoing clinical trials might help close the knowledge gaps in surgical treatment for patients with metastatic breast cancer and aid the decision-making in clinical practice.

Application status of tamoxifen in endocrine therapy for early breast cancer.

The aim of the present study was to investigate the application status of tamoxifen as an adjuvant treatment for early-stage breast cancer. Data for patients with early breast cancer were collected from an information management system for breast cancer in a single hospital between 1989 and 2012. The inclusion criteria included no distant metastasis during diagnosis with breast cancer, and a diagnosis of estrogen and/or progesterone receptor-positive breast cancer, or an unclear hormonal receptor status with tamoxifen used as the preferred drug. A total of 2,738 patients were selected, with 99.4% female and 0.6% male patients. Within females, 75.7% were premenopausal when diagnosed with early breast cancer, 24.3% were postmenopausal, and the median age of menopause was 47 years. The percentage of tamoxifen preference in adjuvant therapy was 97.3% prior to 2000, which decreased to 60.4% in 2011. Tamoxifen preference among premenopausal patients reduced from 97.3% prior to 2000 to 89.5% in 2011, while in postmenopausal patients tamoxifen preference declined from 97.4% prior to 2000 to 22.7% in 2011. One-year duration of tamoxifen treatment accounted for 79.4% of cases, while five-year duration accounted for 24.7%. The rate of one-year disease-free survival (DFS) was 98.5% and of five-year DFS was 89.1%. Patients with early breast cancer had a one-year overall survival (OS) rate of 99.2% and a five-year OS rate of 95.6%. The gradually decreased usage and shortened duration of tamixofen treatment, as well as reduced DFS and OS rates were observed in a 'real world' clinical setting. Improved treatment compliance in patients is recommended.

Trends and present treatment patterns of early breast cancer in Southwest China.

To analyze the changing patterns of treatment and to explore the current treatment approaches for breast cancer in Southwest China, we conducted a population-based retrospective cohort study of early breast cancer cases. The data of patients who registered in the information management system for breast cancer in Huaxi Hospital, Sichuan University from 1989 to 2012 were extracted. Nearly all patients underwent surgery, among whom radical mastectomy was the predominant option. Chemotherapy (88.7%) was the most predominant adjuvant therapy approach. The percentage of patients receiving radiation therapy displayed fluctuant increase, which was 37.1 % in 2001 and reached up to 67.6% in 2011. Besides, the endocrinetherapy became more and more popular in the hormone-receptor positive patients and the percentage of endocrinetherapy was increased from 54.1 at 2001 to 85.6% at 2011. However, more than 10% of hormone-receptor positive patients still did not receive endocrinetherapy annually. The hormone-receptor positive patients who received endocrinetherapy had better 5-year disease free survival (DFS) and overall survival (OS) compared to those without endocrinetherapy (5-y DFS: 88.4% vs. 75.1 %, P < 0.001; 5-y OS: 95.7% vs. 88.4%, P < 0.001). N stage appeared to have greater impact on the 5-year DFS and OS than molecular subtyping. The treatment for breast cancer in China has been significantly improved but more attentions should be paid to radiotherapy and endocrine therapy. In addition, the value of N stage in the prognosis of breast cancer should not be ignored when the molecular typing draws more and more attentions.

Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in a Chinese population.

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently available results are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680 female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the three VEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46, 95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) had a protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikely to be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumor aggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47, 95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed that the VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Han patients.