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// Long Ge 1, 2, 3, * , Yan Tang 4, * , Qiu-Ning Zhang 5 , Jin-Hui Tian 2, 3 , Xiao-Hu Wang 4, 5 , Dawid Pieper 6 , Bei Pan 7 , Lun Li 8 , Juan Ling 2, 3 , Zhi-Tong Bing 9 and Ke-Hu Yang 2, 3 1 First Clinical Medical College of Lanzhou University, Lanzhou 730000, P.R. China 2 Evidence-Based Medicine Center of Lanzhou University, Lanzhou 730000, P.R. China 3 Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou 730000, P.R. China 4 Second People’s Hospital of Lanzhou City, Lanzhou 730046, P.R. China 5 Gansu Provincial Academic Institute for Medical Research, Gansu Provincial Cancer Hospital, Lanzhou 730050, P.R. China 6 Institute for Research in Operative Medicine, Faculty of Health, School of Medicine, Witten/Herdecke University, 51109, Cologne, Germany 7 School of Public Health of Lanzhou University, Lanzhou 730000, P.R. China 8 Department of Breast-Thyroid Surgery, The Second Xiangya Hospital of Central South University, Changsha 410000, P.R. China 9 Institute of Modern Physics of Chinese Academy of Sciences, Lanzhou 730000, P.R. China * Co-first authors Correspondence to: Ke-Hu Yang, email: kehuyangebm2006@126.com Keywords: targeted agents, chemotherapy, triple-negative breast cancer, network meta-analysis, randomized controlled trials Received: January 31, 2017 Accepted: June 27, 2017 Published: July 08, 2017 ABSTRACT Objective: Our network meta-analysis aimed to determine the assistant efficacy of targeted therapy in combined with chemotherapy for advanced/metastatic triple-negative breast cancer (TNBC). Results: A total of 15 randomized controlled trials (RCTs), involving 2,410 patients, met our inclusion criteria. Eight targeted agents involving 11 treatment arms were included. The methodological quality of included RCTs was acceptable. The results of direct comparisons showed that progression-free survival (PFS) was significantly longer with bevacizumab+chemotherapy when compared to chemotherapy alone (hazard ratio [HR] = 0.62, 95% credible intervals [CrI]: 0.41–0.87). However, there were no statistically significant differences for all other direct comparison groups. The results of indirect comparison of different targeted agents revealed no significant differences regarding all outcomes of interest. According to ranking probabilities, all outcomes favored bevacizumab+chemotherapy and veliparib+chemotherapy. Bayesian and Frequentist network meta-analysis showed similar results, and the probability of bias of small-study effects was small. Materials and Methods: A comprehensive literature search in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (via ISI Web of Knowledge), BIOSIS Previews (via ISI Web of Knowledge), and Chemical Abstracts (CA) was conducted to identify RCTs involving targeted agents in the treatment of advanced/metastatic TNBC. Two reviewers independently extracted related data and assessed the risk of bias of included studies. Bayesian network meta-analysis was conducted using R-3.3.2 software. Conclusions: Limited evidence showed that targeted agents combined with chemotherapy for advanced/metastatic TNBC were slightly effective. Further investigation of targeted therapies for TNBC is required to improve patient outcomes. The registration number was CRD42014014299.

The present study aimed to investigate the efficacy and safety of different therapeutic regimens for brain metastases (BMs) from lung cancer (LC). A total of 13 controlled trials (1,783 cases) involving chemotherapy, tyrosine kinase inhibitors or endostatin plus radiotherapy (combination group) vs. radiotherapy alone group were identified from PubMed. Compared with the radiotherapy alone group, the combination group resulted in a significant benefit for objective response rate (ORR) [risk ratio (RR), 1.38; 95% confidence interval (CI), 1.19-1.60; P

// Tingyu Wen 1 , Hai Xiao 2 , Chao Luo 3 , Li Huang 4 and Meimei Xiong 5 1 College of Basic Medical Sciences, Gannan Medical University, Ganzhou, China 2 Department of Pathology, Gannan Medical University, Ganzhou, China 3 Department of Urology, People’s Hosptial of Pingxiang, Pingxiang, China 4 Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China 5 Department of Nephrology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China Correspondence to: Hai Xiao, email: // Keywords : renal cell carcinoma, sorafenib, sunitinib, targeted agents, meta-analysis Received : November 10, 2016 Accepted : January 09, 2017 Published : January 15, 2017 Abstract The most efficient sequence of targeted agents for metastatic renal cell carcinoma patients has yet to be identified. Whether the sequence of sorafenib and sunitinib really matters is controversial and not answered clearly until now. This meta-analysis aims to estimate the efficacy of receptor tyrosine kinase inhibitors sorafenib-sunitinib and sunitinib-sorafenib for metastatic renal cell carcinoma, on the outcome of first-line progression-free survival, second-line progression-free survival, total progression-free survival and overall survival. We searched PubMed, Embase, Cochrane Library and ClinicalTrails.gov for eligible studies. Data were analyzed using random or fixed effects model depending on the heterogeneity of the eligible studies. Heterogeneity across studies were analyzed using Q and I2 statistics. Of 902 identified studies, ten were qualified in our analysis ( N = 1732 patients). Sorafenib-sunitinib yielded no statistically significant benefit in first-line progression-free survival (fixed effects; HR = 0.95; 95%CI 0.75-1.21; p = 0.702), total progression-free survival (random effects; HR = 0.92; 95%CI 0.71-1.19; p = 0.531) and overall survival (fixed effects; HR = 0.89; 95%CI 0.72-1.09; p = 0.257), compared with sunitinib-sorafenib. Second-line progression-free survival was longer for sorafenib-sunitinib than sunitinib-sorafenib (fixed effects; HR = 0.55; 95%CI 0.44-0.68; p = 0.000). Sequential therapies with sorafenib and sunitinib is well tolerated and efficient in mRCC. However, there are no evidence supported that sorafenib–sunitinib has the superiority to sunitinib-sorafenib in sequence. The ideal sequence of targeted agents requires further elucidation.

The management of thymic malignancies is based on multidisciplinary discussion. Systemic agents may be administered as an exclusive treatment if local treatment is not achievable. Novel and innovative agents are used based on the results of next-generation sequencing that may report the activation of targetable signaling pathways both in thymomas and thymic carcinomas. Phase II trials reported the antitumor activity of PI3K/mTOR inhibitors, CDK inhibitors, and antiangiogenic agents in advanced, refractory, or metastatic thymic epithelial tumors. The use of immune checkpoint inhibitors is challenging given the frequent association of those tumors with auto-immune disorders. Meanwhile, a better understanding of systemic treatment sequences in a real-life setting is mandatory to analyze the actual indication of each agent, define the potential biomarkers for the selection of patients, and develop individualized decision-making to optimize the survival of patients.

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72−0.94) and DCR (HR 1.27, 95% CI 1.04−1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70−1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31−0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48−0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.

Introduction: Lung metastases occur in 10-20% of patients with colorectal cancer (CRC). Most of them are treated with palliative intent and have a poor prognosis. Pulmonary metastasectomy may be a curative option for carefully selected patients with 5-year survival rates ranging from 25% to 60%. However, up to 70% of patients develop recurrence after pulmonary metastasectomy. Therefore, the identification of prognostic factors is essential in CRC patients with resectable lung metastases. Areas covered: This review aims at summarizing the actual body of knowledge available on lung metastases from CRC focusing on their clinical, pathological and molecular profile. Moreover, we provide an update on experts' attitudes towards lung metastasectomy, adjuvant or perioperative chemotherapy. Expert opinion: Traditional clinical prognosticators such as the total number of pulmonary metastases, carcinoembryonic antigen (CEA) serum levels before surgery, and presence of lymph node metastases cannot provide reliable criteria to predict survival after lung metastasectomy. Indeed, research efforts have been directed in recent years toward studying the biological characteristics of lung lesions to better define prognosis and response to treatment, and ultimately shed new light on their proper local and systemic management.

Most chronic lymphocytic leukemia patients experience a relapse or become refractory to treatment with conventional chemotherapeutic agents. The network meta-analysis assesses the relative efficacy of novel targeted agents for the treatment of a relapse or refractory chronic lymphocytic leukemia. A systematic literature search included seven phase III randomized controlled trials, including a total of 2512 patients treated with nine regimens. Data were extracted and evidence synthesized using network meta-analysis. All novel targeted therapies were significantly more effective than ofatumumab and demonstrated promising prolongation of progression free survival (PFS), with a hazard ratio (HR) ranging from 0.10 to 0.52. Two novel targeted agent regimens, venetoclax plus rituximab and ibrutinib monotherapy, resulted in greater overall survival (HR, 0.335 and 0.361, respectively). Venetoclax plus rituximab and ibrutinib monotherapy were most favorable based on (1) HR for PFS compared with ofatumumab (Ibrutinib: HR, 0.10, 95% CI, 0.07&ndash, 0.14, Venetoclax plus rituximab: HR, 0.10, 95% CI, 0.05&ndash, 0.21) and SUCRA value (probability of being best) (Ibrutinib SUCRA, 0.92, Venetoclax rituximab SUCRA, 0.90) (2) HR for overall survival compared with ofatumumab (Ibrutinib: HR, 0.361, 95% CI, 0.208&ndash, 0.627, Venetoclax rituximab: HR, 0.335, 95% CI, 0.112&ndash, 0.997) and SUCRA value (Ibrutinib SUCRA, 0.84, Venetoclax rituximab SUCRA, 0.85) Both treatments reduced the risk of progression or death by 90% versus conventional ofatumumab. Both ibrutinib monotherapy and venetoclax rituximab have a high probability of being the most effective treatments for a relapse or refractory chronic lymphocytic leukemia with respect to long-term progression-free survival and overall survival.

The emergence of various targeted anticancer agents has led us to uncharted territory secondary to their cardiotoxic potential with many burning questions, which in turn has led to the evolution of the cardio-oncology field. These targeted agents differ in their cardiovascular complication (CVC) potential even within the same class and it is very difficult to design screening tests that can predict CVCs. Moreover, there is a need for more research to answer many crucial questions, since these toxicities are unanticipated and can lead to poor overall survival of cancer patients. We still do not clearly understand the mechanism for such toxicity, risk factors, and natural history. A better understanding of the underlying risk factors and identification of biomarkers would help us develop protocols for appropriate monitoring strategies which in turn would help capture these toxicities at early stages. In this succinct review, we try to focus on CVC definition, summarize some published research, and point to areas of unmet need in this new field.

The therapeutic paradigm for treatment of acute myeloid leukemia (AML) is rapidly changing with the advent of a new generation of drugs targeting diverse aspects of leukemogenesis. Whereas standard treatment for AML until recently consisted of a classic chemotherapy backbone, the incorporation of novel agents targeting pathogenic mutations, myeloid surface markers, and apoptosis-related proteins may become a reality in the next few years. In this review, we outline the therapeutic landscape of recently approved novel agents for AML, including FLT3 inhibitors, isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors, Bcl-2 antagonists, hedgehog signaling inhibitors, and immunotherapy-based approaches. Some of the future challenges in the field would be to delineate which specific patient subsets derive the most clinical benefit from a given novel agent and, furthermore, which drug combinations will yield the maximal antileukemia effect without increased toxicity. To this end, it is expected that advances in genomic and epigenomic classification of AML will facilitate a rational and optimal choice of these novel agents for AML patients.

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Purpose of reviewThis review provides guidance in the rapidly changing scenario of chronic lymphocytic leukemia (CLL) treatment. New studies as well as updates of other seminal ones have been recently presented and are likely to change the management of patients with CLL in everyday clinical practice.Recent findingsKinase inhibitors (e.g. ibrutinib and idelalisib) have transformed the treatment paradigm in CLL in both front-line and relapsed/refractory patients. Longer follow-up data are now available supporting the safety of ibrutinib and the continuous administration required per current label. Novel studies show the superiority of the drug alone or in combination with monoclonal antibodies compared with standard chemoimmunotherapy. The combination of venetoclax and obinutuzumab (treatment-naïve, only in United States) or rituximab (relapsed/refractory) has granted approval from the regulatory authorities in United States and Europe, based on phase 3 randomized studies. These novel chemo-free combinations allow for fixed-duration treatment and undetectable minimal residual disease. Novel targeted strategies including second and third generation BTK and PI3K inhibitors are currently under investigation and promise to further improve the CLL treatment armamentarium. The chimeric-antigen receptor (CAR) T cells are coming to the stage with promising efficacy and new challenges.SummaryA bright chemo-free era for CLL patients is just around the corner. A deep knowledge of currently available evidences is key to tailor treatment choice and optimize long-term tolerability and disease control. Fixed-duration combinations are investigated to allow treatment holidays and avoid the emergence of resistant clones under the selective pressure of continuous treatment.

The introduction of anti-EGFR (cetuximab and panitumumab) and antiangiogenic (bevacizumab, regorafeninb, ramucirumab, and aflibercept) agents in the therapeutic armamentarium of the metastatic Colorectal Cancer (CRC) has significantly improved the therapeutic efficacy and patients survival. However, despite the great improvements achieved in the patients life expectation, the high inter-individual heterogeneity in the response to the targeted agents still represent an issue for the management of advanced CRC patients. Even if the role of tumor genetic mutations as predictive markers of drug efficacy has been well-established, the contribution of the host genetic markers is still controversial. Promising results regard the germ-line immune-profile, inflammation and tumor microenvironment. Inherent variations in KRAS 3’UTR region as well as EGF/ EGFR genes were investigated as markers of cetuximab effectiveness. More recently interesting data in the field of anti- EGFR agents were generated also for germ-line variants in genes involved in inflammation (e.g. COX-2, LIFR, IGF1 signaling), immune system (e.g., FCGRs, IL-1RA), and other players of the RAS signaling, including the Hippo pathway related genes (e.g. Rassf, YAP, TAZ). Host genetic variants in VEGF-dependent (i.e., EGF, IGF-1, HIF1α, eNOS, iNOS) and -independent (i.e., EMT cascade, EGFL7) pathways, with specific attention on inflammation and immune system-related factors (e.g., IL-8, CXCR-1/2, CXCR4-CXCL12 axis, TLRs, GADD34, PPP1R15A, ANXA11, MKNK1), were investigated as predictive markers of bevacizumab outcome, generating some promising results. In this review, we aimed to summarize the most recent literature data regarding the potential role of common and rare inhered variants in predicting which CRC patients will benefit more from a specifically targeted drug administration.

The survival rates of patients with metastatic colorectal cancer (mCRC) have improved in recent years. We analysed the survival of mCRC patients followed at a single institution over the last 17 years. We retrospectively collected data from 899 mCRC patients treated from 2001 to 2016. Patients were divided into two groups based on the year of diagnosis: Cohort A (2001&ndash, 2006) and Cohort B (2007&ndash, 2014). A total of 788 patients were analysed. The median survival of the whole population was 32.0 months with a significant difference between Cohort A and B (29.2 vs. 33.5 months, p = 0.041). Surgical procedures significantly increased in Cohort B, however, no significant changes in survival were observed in patients undergoing surgery (58.9 months Cohort A vs. 58.2 months Cohort B, p = 0.822). Similarly, we did not demonstrate survival improvement in patients treated with systemic therapy alone (18.9 months Cohort A vs. 20.7 months Cohort B, p = 0.948). At the multivariate analysis, right-sided primary and synchronous metastatic tumour were found to be independent unfavorable prognostic factors. Improvements of mCRC patient survival might relate to integrated approach, with more patients undergoing extra-hepatic surgery. The medical approach seems to have had a more favourable impact on subgroups characterized by a worse prognosis.

Background: Lung cancer is the leading cause of cancer death worldwide. More effective treatments are needed to increase durable responses and prolong patient survival. Standard of care treatment for patients with non-operable stage III-IV NSCLC is concurrent chemotherapy and radiation. An activated NOTCH signaling pathway is associated with poor outcome and treatment resistance in non-small cell lung cancer (NSCLC). NOTCH/gamma-secretase inhibitors have been effective in controlling tumor growth in preclinical models but the therapeutic benefit of these inhibitors as monotherapy in patients has been limited so far. Because NOTCH signaling has been implicated in treatment resistance, we hypothesized that by combining NOTCH inhibitors with chemotherapy and radiotherapy this could result in an increased therapeutic effect. A direct comparison of the effects of NOTCH inhibition when combined with current treatment combinations for NSCLC is lacking.Methods: Using monolayer growth assays, we screened 101 FDA-approved drugs from the Cancer Therapy Evaluation Program alone, or combined with radiation, in the H1299 and H460 NSCLC cell lines to identify potent treatment interactions. Subsequently, using multicellular three-dimensional tumor spheroid assays, we tested a selection of drugs used in clinical practice for NSCLC patients, and combined these with a small molecule inhibitor, currently being tested in clinical trials, of the NOTCH pathway (BMS906024) alone, or in combination with radiation, and measured specific spheroid growth delay (SSGD). Statistical significance was determined by one-way ANOVA with post-hoc Bonferroni correction, and synergism was assessed using two-way ANOVA.Results: Monolayer assays in H1299 and H460 suggest that 21 vs. 5% were synergistic, and 17 vs. 11% were additive chemoradiation interactions, respectively. In H1299 tumor spheroids, significant SSGD was obtained for cisplatin, etoposide, and crizotinib, which increased significantly after the addition of the NOTCH inhibitor BMS-906024 (but not for paclitaxel and pemetrexed), and especially in triple combination with radiation. Synergistic interactions were observed when BMS-906024 was combined with chemoradiation (cisplatin, paclitaxel, docetaxel, and crizotinib). Similar results were observed for H460 spheroids using paclitaxel or crizotinib in dual combination treatment with NOTCH inhibition and triple with radiation.Conclusions: Our findings point to novel synergistic combinations of NOTCH inhibition and chemoradiation that should be tested in NSCLC in vivo models for their ability to achieve an improved therapeutic ratio.

Jianqing Chen, Jianbo Chen, Xiaoan Wu, Tao Shi, Meiling Kang Department of Medical Oncology, TheAffiliated Chenggong Hospital, Xiamen University, Xiamen, Fujian Province, People’s Republic of China Purpose: The efficacy of targeted agents (TAs) in the treatment of elderly patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. We aimed to assess the efficacy of TAs in the treatment of advanced NSCLC in this setting. Materials and methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials assessing chemotherapies with or without TAs in elderly patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS) in elderly patients with advanced NSCLC. Results: A total of 4,093 elderly patients from 17 randomized controlled trials were included for analysis. The addition of TAs to chemotherapy significantly improved PFS (hazard ratio [HR] 0.85, 95% confidence interval [CI]: 0.75–0.96, P=0.01) when compared to chemotherapy alone. There was also a tendency to improve OS in the combination groups (HR 0.92, 95% CI: 0.85–1.01, P=0.064). Subgroup analysis based on treatment line indicated that TAs plus chemotherapy as first-line chemotherapy in elderly patients with advanced NSCLC significantly improved PFS (HR 0.80, 95% CI: 0.68–0.95, P=0.01) and OS (HR 0.91, 95% CI: 0.83–0.99, P=0.037), while the use of TA-containing regimens as second-line therapy in these patients did not significantly improve PFS (HR0.91, 95% CI: 0.75–1.10, P=0.33) and OS (HR 1.04, 95% CI: 0.81–1.33, P=0.77) in comparison with chemotherapy alone. No publication bias was detected by Begg’s and Egger’s tests for OS. Conclusion: The findings of this study suggest that the addition of TAs to first-line chemotherapy in elderly patients with advanced NSCLC offers an improved PFS and OS. Further trials are recommended to clearly investigate the efficacy of adding specific TAs to first-line chemotherapy for advanced NSCLC in this setting. Keywords: non-small-cell lung cancer, elderly, targeted agents, randomized controlled trials, meta-analysis

Background: Concurrent chemoradiotherapy (CRT) is the preferred treatment strategy for inoperable esophageal cancer (EC). However, the effect of CRT needs to be improved., Methods: This study comprehensively analyzed targeted agents combined with CRT for the treatment of EC by a network meta-analysis. The search was performed in public databases from incipient to 5 August 2021. Randomized controlled trials comparing the effect of targeted agents combined with CRT and CRT alone on EC patients were included., Results: Ten studies were included. For progression-free survival (PFS), nivolumab (67.4%) and erlotinib (64.6%) had advantages based on Cox analysis. Regarding the frequency of PFS, cetuximab (OR: 1.39; 95% CI: 1.01, 1.91; p=0.042) and nivolumab (OR: 1.81; 95% CI: 1.34, 2.44; p<0.01) were significantly superior to the control. For overall survival (OS), nivolumab (71.6%) in Cox analysis and nimotuzumab (69.7%) in frequency analysis were found to have relative advantages. Nimotuzumab combined with CRT was significantly better than the control with regard to endoscopic and the pathologic complete response (epCR; OR: 2.81; 95% CI: 1.28, 6.14; p=0.011) and objective response rate (ORR; 4.71; 95% CI: 1.45, 15.29; p=0.008). The targeted drugs were not associated with significant SEA risk., Conclusion: In conclusion, compared to CRT alone, cetuximab and nivolumab combined with CRT were found to significantly improve the PFS rate only based on the frequency results. However, there was no benefit in terms of OS. For epCR and ORR, nimotuzumab was better than the blank control. Considering the limitations in this study, more well-designed RCTs are needed in the future to validate the results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Wang, Peng, Zhang, Li, Zeng, Li and Zhou.)

Background: Targeted agents were introduced over past years because of better understanding of oncogenetic mechanisms in metastatic renal cell carcinoma (mRCC). These agents include tyrosine kinase inhibitors (TKIs) such as sorafenib, sunitinib, pazopanib and axitinib. Methods: Review of recorded data from patients’ files with mRCC were analysed during the period from August 2008 to December 2014. Those patients were treated by sunitinib as first-line therapy. The data included patients characteristics such as age, sex, ECOG performance status (ECOG PS), number and sites of metastasis and pathological type. Also, we reviewed response to sunitinib therapy, its adverse events and progression-free survival (PFS). Results: This study included 26 patients; median age was 56 years with male predominance (76.9%) and 61.5% of patients were of ECOG PS0. Lymph nodes were the most common site of metastasis (38.5%) and 46.2% presented with ≥3 sites of disease. Clear cell pathology was reported in 96.2%. No grade IV adverse events to sunitinib reactions were observed. Thrombocytopenia was the most predominant haematological reaction (46%) followed by neutropenia (38.6%), whilst fatigue was the most reported non-haematological one (50%) followed by diarrhoea (42.3%). Partial response (PR) was found in 30.8% and stable disease (SD) in 46.2%. One-year PFS was 57.7% with median PFS time of 12 months. Conclusion: This study proved effectiveness and safety of sunitinib as first-line treatment for mRCC. However, this is a retrospective study and relatively small numbers of patients were included, so prospective studies with larger number of patients are needed for further evaluation.

Lymphoma is the most common hematologic malignancy, and its incidence increases year by year. It is estimated that there are over 80 000 new cases of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) in 2015 and more than 20 000 deaths. In recent years, the 5-year survival rate of patients with lymphoma has been over 50% as molecular targeted agents come out, and combination of novel specific targeted agents and traditional cytotoxic drugs brings about a revolution in the treatment of cancers. This review mainly discussed the novel targeted agents in the treatment of lymphoma from the following three aspects, including receptors and antigens acting on cell surface, signaling pathways and proteins acting on cells as well as tumor micro-environment.

Rationale: The prognosis of patients with aggressive relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) remains poor. Both immunomodulatory drugs and histone deacetylase inhibitors have demonstrated activity against R/R NHL; yet, the combination of these 2 targeted therapies has rarely been explored. Patient concerns: Here, we report 3 cases. Case 1 was a 68-year-old woman who presented to our hospital with dyspnea. Case 2 was a 75-year-old man with massive upper gastrointestinal bleeding. Case 3 was a 62-year-old woman with cough, dyspnea, and lymphadenopathy. Diagnosis: The biopsy results revealed diffuse large B cell lymphoma (DLBCL), DLBCL, and angioimmunoblastic T-cell lymphoma, for Case 1, 2, and 3 respectively. Intervention: All 3 patients experienced relapse after first-line therapy and multiple lines of salvage therapy. Finally, they all received lenalidomide combined with chidamide. Outcomes: All 3 patients achieved complete and durable remission. Case 1 relapsed again after 3 months, while the other 2 cases remained in complete remission. Lessons: To our knowledge, this is the first report of lenalidomide combined with chidamide for the treatment of R/R NHL. Our findings warrant further evaluation of this novel chemo-free therapy in future prospective clinical trials.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare and aggressive non-Hodgkin’s lymphomas. Clinical staging, prognostic scoring, and initial treatment strategies have historically been based on paradigms developed in B-cell lymphomas. Despite primary treatment protocols that are typically anthracycline-based and frequently involve consolidative autologous stem cell transplantation in first remission, many patients develop disease progression. There remains a high unmet medical need for improved treatment strategies in the relapsed or refractory setting. Salvage chemotherapy and stem cell transplantation in those who are suitable has traditionally been the accepted approach, but this remains a minority of the total patient population. As increasing knowledge is gleaned regarding the biological heterogeneity within the various PTCL subtypes, newer targeted agents have been developed, studied, and approved in this small, heterogeneous population of relapsed or refractory disease. Given its success and tolerability in this pretreated population, brentuximab vedotin, an anti-CD30 antibody drug conjugate, was brought earlier in the disease course and is a model for advances in the targeted treatment of PTCL. As others undergo further development in the relapsed setting and successes are brought earlier in the disease course, the outcome for PTCL patients is likely to improve. However, innovative clinical trial designs are crucial for the assessment of targeted agents in this highly heterogeneous population. This review explores the current treatment environment for patients with relapsed and refractory PTCL, including newer strategies such as targeted agents and immunotherapy.

Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) bears a dismal prognosis due to the limited activity of systemic chemotherapy. In our platform for precision medicine, we aim to offer molecular-guided treatments to patients without further standard therapy options. Methods: In this single center, real-world retrospective analysis of our platform, we describe the molecular-based therapy approaches used in all 50 patients diagnosed with therapy-refractory mPDAC. A molecular portrait of the tumor specimens was created by next-generation sequencing, immunohistochemistry (IHC), microsatellite instability (MSI) testing, and fluorescence in situ hybridization. Results: In total, we detected 123 mutations in 50 patients. The five most frequent mutations were KRAS ( n = 40; 80%), TP53 ( n = 29; 58%), CDKN2A ( n = 8; 16%), SMAD4 ( n = 4; 8%), and NOTCH1 ( n = 4; 8%), which together accounted for 40.2% of all mutations. Two patients had gene fusions, namely, TBL1XR1–PIK3CA and EIF3E–RSPO2. IHC detected expression of EGFR, phosphorylated mTOR, and PTEN in 36 (72%), 33 (66%), and 17 patients (34%), respectively. For 14 (28%) of the 50 patients, a targeted therapy was suggested based on the identified molecular targets. The recommended treatments included the mTOR inhibitor everolimus ( n = 3), pembrolizumab ( n = 3), palbociclib ( n = 2), nintedanib ( n = 2), and cetuximab, crizotinib, tamoxifen, and the combination of lapatinib and trastuzumab, in one patient each. Finally, five patients received the recommended therapy. Four patients died due to disease progression before radiological assessment. One patient was treated with nintedanib and achieved stable disease for 6 months. Conclusion: Based on our observations, precision medicine approaches are feasible and implementable in clinical routine and may provide molecular-based therapy recommendations for mPDAC.