Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer

BACKGROUND Gemcitabine plus nab-paclitaxel(GA)and modified FOLFIRINOX(FFX)have been widely used as standard first-line treatment in pancreatic cancer.However,it is unclear which regimen is more efficacious.AIM To evaluate a retrospective analysis comparing the efficacy and safety of FFX and GA as first-line chemotherapeutic regimens in patients with metastatic pancreatic cancer.METHODS We retrospectively analyzed and compared outcomes in 101 patients who presented with pancreatic cancer and were treated with either GA(n=54)or FFX(n=47).Moreover,we performed subgroup analysis based on the neutrophil/lymphocyte ratio(NLR)and Eastern Cooperative Oncology Group(ECOG)performance status.RESULTS There were no significant differences between two groups in baseline characteristics,except for the ECOG performance status.The median progression-free survival(PFS)(6.43 mo vs 4.90 mo,P=0.058)was comparable between two groups;however,median overall survival(OS)(10.17 mo vs 6.93 mo,P=0.008)was longer in patients who received GA regimen.In patients with ECOG 0(PFS:8.93 mo vs 5.43 mo,P=0.002;OS:16.10 mo vs 6.97 mo,P=0.000)and those with NLR<3(PFS:8.10 mo vs 6.57 mo,P=0.008;OS:12.87 mo vs 9.93 mo,P=0.002),GA regimen showed higher efficacy.CONCLUSION GA regimen may be recommended to the patients with NLR<3 or ECOG 0 status although GA and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer.

Update on the treatment of metastatic renal cell carcinoma

Metastatic renal cell cancer(mRCC)management has undergone a paradigm shift in recent decades.The first revolution came with the emergence of vascular endothelial growth factor inhibitors;there was a second wave with the unprecedented success of checkpoint inhibitors,and then the latest approach,which is becoming the new care standard in mRCC,of combining these two strategies in different ways.Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival(PFS),overall survival(OS),and objective response rate(ORR)in intermediate and high-risk patients.However,several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place,and so far,the only one for nivolumab/ipilimumab is the frontline setting.The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembrolizumab/axitinib over sunitinib in favorable-risk mRCC,suggesting that it should no longer be the first line of choice in low-risk patients.Finally,the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS,OS,and ORR,providing a new first-line option among all International Metastatic RCC Database Consortium risk patients.Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib,cabozantinib/atezolizumab,and lenvatinib/pembrolizumab,providing promising grounds upon which to start phase III studies.In addition,other works are using novel therapeutic agents with different mechanisms of action,including telaglenastat(a glutaminase inhibitor),entinostat[an inhibitor of histone deacetylases(HDACs)],and olaparib and talazoparib,poly(ADP-ribose)polymerase inhibitors widely used in other tumors.However,some questions regarding mRCC management still need to be addressed,such as head-to-head comparisons between the current options,treatment sequencing,non-clear cell mRCC,and the role of biomarkers to ascertain the best treatment choice.

Practice change in the management of metastatic urothelial carcinoma after ASCO 2020

Metastatic urothelial carcinoma(mUC)is an incurable and aggressive disease.In the past decades there have been few effective treatment options that have impacted the prognosis of mUC patients.However,in the last few years,several drugs have emerged as new treatment choices that are changing the therapeutic landscape of mUC.Immune checkpoint inhibitors(ICIs)and targeted agents are useful treatment strategies that have been incorporated into our clinical practice.Nevertheless,cisplatin-based chemotherapy is still the standard of care in the first-line of metastatic disease.The results of the JAVELIN Bladder 100 phase 3 trial were presented at ASCO 2020,this trial evaluated the role of avelumab,an ICI,as maintenance therapy in patients who had not progressed after first-line platinum-based chemotherapy.The trial met its primary endpoint demonstrating an overall survival benefit with avelumab maintenance.In addition,new drugs and combinations are being evaluated to improve the outcomes of second and subsequent lines.Fibroblast growth factor receptor(FGFR)inhibitors and immunotherapy combinations were some of the strategies presented at ASCO 2020 that have shown promising results.Finally,the development of predictive biomarkers that help us in the decision-making process will be one of the most important challenges in the next years.

Study on the mechanism of"Sangu Decoction"in the treatment of bone metastatic carcinoma

Objective:To study the mechanism of"Sangu Decoction"in the treatment of bone metastatic carcinoma by network pharmacology.Methods:TCMSP,TCMID and TCM Database@Taiwan databases and literature search were used to screen the main effective components of drugs.Swiss Target and TCMSP databases were used to search the potential therapeutic targets of"Sangu Decoction".DisGeNet and Drugbank databases were used to search the genes of bone metastatic carcinoma.Drug action targets and disease genes were mapped.Cytoscape 3.8.1 software was used to visualize and screen out the core genes.GO and KEGG pathway analysis was performed on potential therapeutic targets.Results:There were 29 main active ingredients in"Sangu Decoction",which contained 413 target proteins.There are 773 disease targets of bone metastatic carcinoma,of which 112 are potential targets of"Sangu Decoction"for the treatment of bone metastatic carcinoma.Through GO and KEGG pathway analysis,it was found that"Sangu Decoction"exerted anti-cancer,inhibiting bone metastasis and immune regulation mechanism through TNF,ErbB,FoxO,PI3K-Akt,Toll-like Receptor,NOD-like Receptor,Rap1 and other signaling pathways in the treatment of bone metastatic carcinoma.The key genes of"Sangu Decoction"in treating bone metastatic carcinoma are VEGFA,AKT1,IL6,TP53,MAPK3,SRC,EGFR and CASP3 and so on.Conclusion:In this study,we constructed a a multi-level interaction"traditional Chinese medicine-compound-target-pathway"network through network pharmacology,and found that the mechanism of"Sangu Decoction"in the treatment of bone metastasis cancer involves multiple targets and pathways,which may be related to anti-cancer,inhibition of bone metastasis,regulation of immunity and so on.

Progress in targeted therapy for metastatic renal cell carcinoma

In recent years, with the deepening of research on the pathogenesis of renal cell carcinoma, anti-VEGF receptor inhibitors and mTOR inhibitors have been produced, making metastatic renal cell carcinoma into the era of targeted therapy. This article analyzes the latest research results at home and abroad. For patients with metastatic renal cell carcinoma, sunitinib and pizopanib are the first choice for targeted drugs. The drug dose starts from the standard dose, and the disease can be increased as appropriate when the disease progresses;When responding, it should be treated or reduced in time. When using an anti-VEGF inhibitor, the patient's blood pressure should be closely monitored. When the patient has high blood sugar or diabetes, anti-VEGF inhibitors should be preferred.

Metastatic Lobular Carcinoma of the Breast Presenting with Small Bowel Metastases:Case Report and Literature Review

Introduction: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, representing 5% to 15% of invasive tumors. ILC tends to spread to bones, lungs, central nervous system, reproductive organs, and the gastrointestinal tract (GI tract). The most commonly affected organs in the GI tract are the stomach, small intestine, followed by colon and rectum. Case presentation: A 78-year-old woman who was referred to our institution after having a bowel obstruction that required a diagnostic laparoscopy where they identified an obstructing ulcerative lesion in the distal ileum that was managed with a segmental bowel resection. Pathology report showed an invasive lobular breast carcinoma that occluded 90% of the bowel lumen. A PET/CT scan revealed a left breast tumor with increased metabolism. The patient was staged as a clinical cT4b, cN0, cM1 left breast invasive lobular carcinoma (ER/PgR positive, HER-2 negative). She was managed with endocrine therapy with Letrozole (an eight-week course). A follow-up PET/CT showed a peritoneal hypermetabolic nodule adjacent to the previous ileal anastomosis. The lesion decreased in size and metabolic activity. In a multidisciplinary fashion, the endocrine therapy was extended for another three months. Another follow-up PET/CT scan was performed three months after the identification of the peritoneal implant that showed that the nodule increased in size and in metabolism. The lesion continued to decrease significantly in size and became metabolically inactivity. Due to the good breast response and the possibility that the ileal nodule could be a granuloma, she underwent an exploratory laparoscopy with excision of the peritoneal nodule, and a modified left radical mastectomy with immediate breast reconstruction (complex wound closure). The final pathology report of the nodule was negative for malignancy. She continued on endocrine therapy and underwent whole breast irradiation four weeks after the operation. Currently, she is free of disease with no evidence of local, regional, or distant recurrence, and she is still on endocrine therapy. Discussion: The time interval between primary breast cancer and gastrointestinal involvement may range from synchronous presentation to as long as 30 years. The clinical manifestations in GI lobular breast cancer metastasis may range from non-specific complaints to acute GI symptoms, such as a bowel obstruction. There are multiple controversies in the management of ILC. Systemic treatment should be initiated as soon as possible. Indications for postmastectomy radiotherapy are also controversial, given the propensity for multifocal/multicentric tumors and late recurrences, sometimes in atypical locations. Five years of postoperative adjuvant hormonal therapy is an option for women with poor prognosis. Remissions are observed in 32% to 53% of patients. Conclusion: Metastatic lobular carcinoma of the breast has a wide range of clinical presentations. Patients with a history of breast cancer who present with new GI tumors should have these lesions evaluated for evidence of metastasis through histopathologic and immunohistochemical analysis, this will allow for appropriate management. Currently, breast cancer management involves a multidisciplinary approach including surgery, radiotherapy, and systemic medical therapy, and the treatment must be tailored to the patient’s needs.

Solitary thyroid gland metastasis from rectal cancer:A case report and review of the literature

BACKGROUND Metastatic carcinoma of the thyroid gland is a rare encounter in clinical practice, but autopsy series showed that it is not so rare. Thyroid metastasis from colorectal cancer(CRC) is rare and has a poor prognosis. We herein report a rare case of solitary thyroid metastasis from rectal cancer combined with needle tract implantation after fine-needle aspiration(FNA) of the thyroid nodule and review the relevant literature.CASE SUMMARY A 54-year-old woman with a history of TNM stage Ⅲ CRC presented a 1.3 cm × 1.0 cm mass in the left thyroid gland. FNA and histological examination of the left thyroid lobe surgical specimen confirmed the diagnosis of isolated metastatic adenocarcinoma from the rectum. Needle tract implantation was observed in the neck 11 mo after the FNA examination. The 2.5-cm seeding lesion was successfully removed by surgery, and the patient recovered well. The literature relevant to this clinical condition, the diagnostic workup, spread pathway, and surgical management of these rare lesions is reviewed.CONCLUSION For a patient with a thyroid mass and a history of CRC, metastatic thyroid carcinoma should be considered even if the patient has no evidence of other organ metastasis from CRC. FNA cytological examination of the thyroid mass is useful in the differential diagnosis between primary thyroid disease and metastatic thyroid carcinoma. Thyroid lobectomy of the gland containing the metastatic tumor is suggested in patients with metastatic carcinoma of the thyroid.

Cryoablation combined with radiotherapy for hepatic malignancy:Five case reports

BACKGROUND The survival of patients treated with monotherapy for hepatic malignancies is not ideal.A comprehensive program of cryoablation combined with radiotherapy for the treatment of hepatic malignancies results in less trauma to the patients.It may provide an option for the treatment of patients with advanced hepatic malignancies.CASE SUMMARY We reported 5 cases of advanced-stage hepatic malignancies treated in our hospital from 2017-2018,including 3 cases of primary hepatocellular carcinoma and 2 cases of metastatic hepatic carcinoma.They first received cryoablation therapy on their liver lesions.The procedure consisted of 2 freeze-thaw cycles,and for each session,the duration of freezing was 13-15 min,and the natural rewarming period was 2-8 min.Depending on the tumor size,the appropriate cryoprobes were selected to achieve complete tumor ablation to the greatest extent possible.After cryoablation surgery,intensity-modulated radiotherapy(IMRT)for liver lesions was performed,and the radiotherapy regimen was 5400 cGy/18f and 300 cGy/f.None of the 5 patients had adverse events above grade II,and their quality of life was significantly improved.Among them,4 patients were free of disease progression in the liver lesions under local control,and their survival was prolonged;3 patients are still alive.CONCLUSION Our clinical practice demonstrated that cryoablation combined with IMRT could be implemented safely.The definitive efficacy for hepatic malignancies needs to be confirmed in larger-size sample prospective studies.

Immune checkpoint inhibitors in head and neck squamous cell carcinoma:A systematic review of phase-3 clinical trials

BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.

Revisiting mechanisms of resistance to immunotherapies in metastatic clear-cell renal-cell carcinoma

Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term control.Mechanisms of resistance have been explored in a variety of solid tumors,including RCC.Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in combination.Nevertheless,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease.In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.

Metastatic high-grade neuroendocrine tumor of mandible

Neuroendocrine tumors of the oral cavity and jaws are exceedingly rare.They include paragangliomas,a melanotic neuroectodermal tumor of infants,small cell carcinomas,and Merckel cell carcinomas.Most have been non-functional in nature.Breast,lung,liver,colon,and prostate are the most common reported primary malignancies which can metastasize to the oral cavity.In most cases,oral metastases involve maxilla and mandible rather than soft tissues.The premolar-molar region is the most common localization.The purpose of this article is to describe a rare case of a high grade neuroendocrine tumor of the mandible which metastasized from the cervix.

Individualized therapy for metastatic renal cell carcinoma

Metastatic Renal Cell Carcinoma(mRCC)is a highly heterogeneous disease that is notoriously difficult to treat successfully.However,the discovery of novel,targeted therapies over the last decade has revolutionized its management.As the therapeutic options continue to evolve,developing a more individualized treatment strategy is of paramount importance.The International mRCC Database Consortium(IMDC)is a prognostic model that is commonly used in trials and clinical settings to risk stratify patients.This allows for optimal therapy selection on a more individual basis.However,the distinct lack of validated predictive biomarkers in mRCC renders it difficult to assess therapy response.An improved understanding of tumor biology and genetics has prompted a shift from cytokine therapy to the use of vascular endothelial growth factor(VEGF)inhibitors,tyrosine kinase Inhibitors,immune checkpoint inhibitors or combination strategies.Studies have identified some putative markers and genetic mutations as potential predictors of therapy response.Early results are promising,and there are many ongoing trials further assessing their suitability for clinical use.This review will evaluate the current treatment landscape and molecular biology of mRCC,with a specific focus on the prognostic and predictive markers available to guide treatment options and further improve patient outcomes.

The contemporary role of metastasectomy in the management of metastatic RCC

Metastasectomy was initially described in the 1970s as a therapeutic strategy for patients with metastatic renal cell carcinoma.Since that time,systemic therapy options have grown exponentially,most recently with the introduction of immunotherapy.We aimed to review the contemporary literature regarding the role of metastasectomy in the era of targeted therapy and immunotherapy.Historically,metastasectomy has benefited patients with small volume,single-organ metastases,with favorable outcomes amongst younger,healthier patients with metastases to specific sites.The interplay between the employment of metastasectomy and systemic therapy has been limited to small,retrospective series with significant patient selection bias.More recently,investigators have conducted randomized controlled trials exploring the use of targeted therapies in the adjuvant setting after metastasectomy.Initial randomized data suggested no benefit in using sorafenib in this setting,and a subsequent study demonstrated possible harm in using pazopanib after metastasectomy.However,the role of other novel systemic therapies,including immunotherapy,nor the timing of use,have been meaningfully explored.Metastasectomy appears to be a valuable therapeutic option in the properly selected patient,requiring a multi-disciplinary management strategy and,pending future trials,a multimodal treatment approach.