Current Treatment Options in Oncology最新文献

{"title":"PSMA-based Therapies and Novel Therapies in Advanced Prostate Cancer: The Now and the Future.","authors":"Ann Ayzman, Russell K Pachynski, Melissa A Reimers","doi":"10.1007/s11864-025-01317-5","DOIUrl":"https://doi.org/10.1007/s11864-025-01317-5","url":null,"abstract":"<p><strong>Opinion statement: </strong>The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) is rapidly evolving with the advent of PSMA-targeted radioligand therapies (RLTs) and bispecific T-cell engagers (BiTEs). These novel approaches provide new hope for patients who have progressed on standard therapies. However, their full clinical potential will be realized only by addressing key challenges, including tumor heterogeneity, resistance mechanisms, immune-related toxicities, and the immunosuppressive tumor microenvironment. Additionally, the optimal sequencing of these therapies at different stages of disease remains an open question. While most of these interventions are currently introduced in late-stage, heavily pretreated patients, ongoing clinical trials are exploring their role in earlier disease settings, where they may be more effective in altering the natural history of disease. PSMA-based RLTs, such as 177Lu-PSMA- 617, have demonstrated promising efficacy, particularly in patients with high PSMA expression. However, the presence of PSMA-negative or heterogeneous tumors necessitates the development of additional biomarkers and combination strategies. The ongoing PSMAddition trial may establish RLTs as an earlier-line treatment in hormone-sensitive metastatic prostate cancer, potentially shifting the standard of care. Moreover, mitigating toxicities through radioprotective agents may aid in expanding their clinical utility. BiTE therapies offer a different but complementary mechanism of action, leveraging T-cell engagement to drive tumor cell destruction. While cytokine release syndrome (CRS) and immunogenicity remain significant hurdles, modifications such as low-affinity CD3 binding and optimized dosing regimens are showing promise. The potential synergy of BiTEs with immune checkpoint inhibitors and tumor microenvironment-modulating agents should be further explored to enhance therapeutic efficacy. Given these advancements, the future of mCRPC treatment likely lies in a personalized, multimodal approach that integrates PSMA-based RLTs, BiTEs, and complementary therapies at earlier disease stages. Strategic biomarker-driven patient selection and combination regimens will be essential in optimizing outcomes while minimizing resistance and toxicity.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"26 5","pages":"375-384"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Geriatric Assessment in Hematopoietic Stem Cell Transplant and Cellular Therapies.","authors":"Lawrence Cheng Kiat Ng, Rachel Qiao Ming Ng, Joseph DiTursi, Kah Poh Loh","doi":"10.1007/s11864-025-01316-6","DOIUrl":"https://doi.org/10.1007/s11864-025-01316-6","url":null,"abstract":"<p><strong>Opinion statement: </strong>Hematological malignancies are common among older adults, a group that faces unique challenges in treatment. While hematopoietic stem cell transplantation and CAR-T therapy offer promising, potentially curative and durable treatment options for older adults with high-risk diseases, their effectiveness can be limited by the individual's overall health and ability to tolerate intensive treatments. Conventional fitness assessments in this population often fall short in addressing the complexities of aging. Conversely, geriatric assessment provides a more comprehensive evaluation of an older adult's health across multiple domains, including physical health, cognitive function, mental health, nutrition, comorbidities, polypharmacy, and social support. This holistic approach helps to better understand the patient's resilience and facilitate timely adjustments to interventions, potentially improving both survival outcomes and quality of life. This review aims to explore the current evidence on integrating geriatric assessments into the optimization of older patients for hematopoietic stem cell transplantation and CAR-T therapy, along with various care models, their potential, and future directions.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"26 5","pages":"348-359"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook.","authors":"Giovanni Luca Ceresoli, Letizia Gianoncelli","doi":"10.1007/s11864-025-01320-w","DOIUrl":"https://doi.org/10.1007/s11864-025-01320-w","url":null,"abstract":"<p><strong>Opinion statement: </strong>Pleural mesothelioma is an incurable cancer with unmet diagnostic and therapeutic needs. Due to its pattern of local spread, few patients are candidates for multimodality treatment and thus most patients only receive systemic therapy. Chemotherapy (pemetrexed plus platinum) was standard of care until the recent addition of immunotherapy (nivolumab plus ipilimumab, or pembrolizumab plus chemotherapy) as further first-line option. Physicians treating pleural mesothelioma should be aware of another option with Tumor Treating Fields (TTFields) therapy, a locoregionally-applied therapy utilizing electric fields generated by a portable medical device, and delivered to the tumor by skin-placed arrays. TTFields therapy delivered to the thorax using the NovoTTF- 100L device concomitant with pemetrexed and platinum agent is approved for unresectable pleural mesothelioma in the US, and received Conformité Européenne certification in Europe, based on results from the phase 2 STELLAR study (EF- 23; NCT02397928), where TTFields-related toxicity was limited to mild-to-moderate reversible skin reactions. Overall survival in the STELLAR study with TTFields therapy was 18.2 months, with further post-hoc analysis showing extended survival in patients with epithelioid histology. Within the evolving landscape of systemic treatments, TTFields therapy represents a novel and clinically versatile therapeutic option in the battle against pleural mesothelioma without introducing additional toxicities other than mild-to-moderate skin irritation. While promising, additional research is needed to optimize clinical application of TTFields therapy in patients with pleural mesothelioma, such as identifying the molecular determinants of therapy efficacy, and further investigation into the safe and effective delivery of TTFields therapy together with systemic agents, including immunotherapies.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"26 5","pages":"398-414"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Challenges in the Management of Serous Endometrial Intraepithelial Carcinoma (SEIC).","authors":"Emily Hicks, Akash Shah, Robert V Higgins","doi":"10.1007/s11864-025-01314-8","DOIUrl":"10.1007/s11864-025-01314-8","url":null,"abstract":"<p><strong>Opinion statement: </strong>Serous endometrial intraepithelial carcinoma (SEIC) is an aggressive precursor and a similar biology to uterine serous carcinoma (USC). Patients diagnosed with SEIC should undergo surgical staging that includes total hysterectomy with bilateral salpingo-oophorectomy, lymph node sampling, and omentectomy. With trends in lymph node evaluation shifting towards sentinel lymph node sampling, we recommend bilateral sentinel lymph node sampling as a reasonable alternative to full pelvic and para-aortic lymphadenectomy. There is limited data to support the use of adjuvant chemotherapy, however, it is apparent that those with extrauterine disease have a higher likelihood of recurrence and decreased overall survival. Those with stage IVB SEIC have similar rates of survival to those with stage IVB USC and may be a population that could benefit from newer regimens for advanced stage endometrial cancer including immunotherapy and maintenance therapy. Unfortunately, strong data to support this will continue to be a challenge given the rare incidence of isolated SEIC without concurrent USC. The utility of adjuvant radiotherapy remains unclear and given its noninvasive nature and propensity for distant recurrence, may be of little utility. Regardless of the adjuvant therapies selected, routine surveillance like that of USC should be followed as recurrences are often noted greater than one year after initial surgery. Unlike other precursor lesions, SEIC behaves similarly to invasive carcinoma and ultimately should be treated as such for optimal disease control and outcomes.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"341-347"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Advances in the Molecular Landscape of Penile Cancer and Their Implications for Precision Medicine.","authors":"Laura Elst, Kaat Vandermaesen, Maarten Albersen","doi":"10.1007/s11864-025-01319-3","DOIUrl":"https://doi.org/10.1007/s11864-025-01319-3","url":null,"abstract":"<p><strong>Opinion statement: </strong>Penile cancer is a rare but aggressive malignancy, characterized by early lymphatic spread which is the most critical prognostic factor. Treatment options for patients with locally advanced and metastatic disease are limited, primarily relying on cisplatin-based chemotherapy, which is characterized by high toxicity and early resistance. In recent years, there has been a growing interest on translational research exploring the tumor microenvironment, enabling the identification of novel potential therapeutic targets. Emerging preclinical evidence supports the use of immune checkpoint inhibitors, antibody-drug conjugates and novel exploratory therapies targeting myeloid-derived suppressor cells and tumor associated macrophages, as well as their combinations. However, robust phase III trials investigating such therapies are currently lacking. A deeper understanding of the penile cancer immune landscape and the role of specific mutations in carcinogenesis, might lead to the development of novel combination strategies to overcome cisplatin resistance and disease progression, and to a better selection of patients for inclusion in future clinical trials.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"26 5","pages":"367-374"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locoregional Non-Surgical Treatments for Unresectable or Oligometastatic Sarcomas: A Literature Review.","authors":"Annarita Peddio, Antonio Pizzolorusso, Ottavia Clemente, Lucia Cannella, Flavia Balzamo, Giuseppina Della Vittoria Scarpati, Federica Papa, Fernanda Picozzi, Carmela Garosi, Debora De Bartolo, Francesco Fiore, Salvatore Tafuto","doi":"10.1007/s11864-025-01313-9","DOIUrl":"https://doi.org/10.1007/s11864-025-01313-9","url":null,"abstract":"<p><strong>Opinion statement: </strong>Sarcomas are rare neoplasms, whose complex management is a consequence of their heterogeneity. Due to their variegate histology and characteristics, prospective trials are challenging to design. Thus, diagnostic and therapeutic guidelines are often based on limited evidence available, and only few and dated systemic treatment regimens are included in our current practice. For all these reasons, we believe that implementing therapeutic options, including local approach, is mandatory to guarantee the best management possible to patients. We explored evidence about locoregional treatments, assuming they could represent a fundamental part of an integrated oncological approach. The goal is to maximize local control of oligometastatic or oligoprogressive diseases, saving systemic treatment options for later stages, as well as to avoid demolitive surgery in patients affected by locally advanced sarcomas. Although several retrospective and prospective series have been conducted, evidence available is still poor in our opinion. Research should focus on evaluating predictive factors and individualized follow up strategies to identify ideal patients' features and more sensitive histological subtypes.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"26 5","pages":"415-429"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Budesonide in Oncology: A Novel Approach to Managing Gastrointestinal Immune-Related Adverse Events.","authors":"Piotr T Wysocki, Jarosław Reguła","doi":"10.1007/s11864-025-01318-4","DOIUrl":"https://doi.org/10.1007/s11864-025-01318-4","url":null,"abstract":"<p><strong>Opinion statement: </strong>Budesonide is a potent topical glucocorticosteroid with limited systemic activity owing to its extensive hepatic first-pass metabolism following oral administration. Its efficacy and safety have been well-established in gastroenterology, particularly for inducing and maintaining remission in patients with inflammatory bowel diseases: mild-to-moderate ulcerative colitis, Crohn's disease and microscopic colitis. However, the potential role of oral budesonide in oncology has only recently been recognized, particularly for managing various types of gastrointestinal immune-related adverse events, which are among the most common toxicities observed in cancer patients treated with immune checkpoint inhibitors. Potential applications of oral budesonide in this context include the treatment of immunotherapy-induced microscopic and non-microscopic colitis, enteritis, upper gastrointestinal involvement, and, to a lesser extent, hepatitis. In these cases, oral budesonide may serve as a primary treatment to induce remission, replacing systemic steroids, or as a bridging therapy transitioning from systemic steroids, facilitating a quicker resumption of immunotherapy following its temporary discontinuation due to toxicity. Oral budesonide represents a particularly attractive treatment option in oncology due to its minimal systemic activity, low risk of steroid-related side effects, and very limited potential to cause immune suppression - offering a marked contrast to systemic steroids. In this article, we summarize the current evidence on the potential applications of oral budesonide in oncology, highlighting its promise as a targeted and well-tolerated treatment option for managing gastrointestinal immune-related toxicities that preserves the anti-cancer efficacy of immunotherapy.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":"26 5","pages":"360-366"},"PeriodicalIF":3.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Estrogen Receptor - Targeted Therapies in Hormone-Receptor Positive Breast Cancer.","authors":"Nina E Neill, Lauren A Mauro, Angela Pennisi","doi":"10.1007/s11864-025-01310-y","DOIUrl":"10.1007/s11864-025-01310-y","url":null,"abstract":"<p><strong>Opinion statement: </strong>Endocrine therapy is the backbone of treatment for HR + /HER2- MBC. The introduction of novel endocrine-based therapies has changed the landscape of metastatic breast cancer care, with even more promising agents on the horizon. Given the consistent success in prolonging PFS and OS, CDK4/6 inhibitors should be used as first-line treatment. Once secondary resistance eventually develops after use of a CDK4/6 inhibitor, use of monotherapy with either AI or fulvestrant has shown poor outcome. For example, in the control group of the EMERALD trial, in which all the patients were required to have previously received a CDK4/6 inhibitor, median progression-free survival with endocrine therapy was only 1.9 months. Based on the emerging evidence, molecular profiling of tissue or liquid biopsy at progression of disease is crucial to select future therapy. For patients whose tumors harbor ESR1 mutations, oral SERDs are the preferred option. For those with PIK3CA or AKT1 mutation or PTEN inactivation, combination therapy with the AKT pathway inhibitor capivasertib is recommended. Alpelisib, the first AKT1 inhibitor approved in combination therapy with fulvestrant in PIK3CA mutated tumors only, is now less in favor given its challenging side effect profile. When mutations are not present, options include combination therapy with the mTOR inhibitor everolimus or changing endocrine therapy and continuing a CDK 4/6 inhibitor. In patients with short response to CDK4/6 inhibitors suggesting endocrine resistant disease, chemotherapy or antibody-drug conjugates should be considered. With better understanding of the mechanisms of resistance to CDK4/6 inhibitors, additional mutations could be identified and potentially targeted in order to provide individualized treatment options. Optimal sequencing of treatment options depends on several factors: (1) the presence of specific molecular aberrations; (2) previous treatment history, duration of response and patient's performance status; (3) balance between maximizing survival benefits with quality of life/toxicities; (4) disease burden. In the upcoming years, we anticipate FDA approvals for more of the SERD molecules both in monotherapy and in combination therapy which will continue to expand the options available for HR + /HER2- MBC patients.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"302-312"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in PSMA-Targeted Radionuclide Therapeutics.","authors":"Samuel Ruder, Andres Ricaurte-Fajardo, Michael Sun, Sandra Huicochea Castellanos, Joseph R Osborne, Scott T Tagawa","doi":"10.1007/s11864-025-01296-7","DOIUrl":"10.1007/s11864-025-01296-7","url":null,"abstract":"<p><strong>Opinion statement: </strong>Prostate-specific membrane antigen targeted radionuclide therapies (PSMA-TRT) such as 177Lu-PSMA-617 hold great promise in improving clinical outcomes at various stages of prostate cancer. The FDA approval of 177Lu-PSMA-617 represents a significant advancement in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The VISION trial demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) with 177Lu-PSMA-617 in patients with mCRPC who had already receive androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy. Exploration of 177Lu-PSMA-617 in earlier stages of prostate cancer, such as in the PSMAfore trial for patients who have not received chemotherapy, holds great promise for improving long-term outcomes and delaying exposure to chemotherapy. Combining 177Lu-PSMA-617 with other therapies, including chemotherapy, PARP inhibitors, and immunotherapy, is an area of active investigation. This review will also discuss alternative radionuclides (such as actininum-225 and terbium-161) and delivery vehicles (such as PSMA-I&T), which we find promising. Predictive biomarkers and dosimetry will be crucial for identifying patients most likely to benefit from PSMA-TRT. Continued research and refinement of these therapies will lead to PSMA-targeted treatments becoming an integral part of prostate cancer management.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"291-301"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Therapeutic Potential of Natural Polyphenols in Esophageal Cancer.","authors":"Chengu Niu, Jing Zhang, Patrick I Okolo","doi":"10.1007/s11864-025-01308-6","DOIUrl":"10.1007/s11864-025-01308-6","url":null,"abstract":"<p><strong>Opinion statement: </strong>Esophageal cancer (EC), one highly malignant upper gastrointestinal cancer, is the eighth most commonly occurring cancer and the sixth leading cause of cancer-related deaths worldwide. Clinically, this malignancy is considered to be one of the most difficult-to-treat cancers, owing to its resistance to common therapies like chemotherapy and radiotherapy, and few targeted therapies are available. There is currently an unmet need for treatment of EC. Polyphenols are naturally occurring plant secondary metabolites in response to environmental threats and injury. Epidemiological evidence suggests that long-term consumption of a polyphenol-rich diet is inversely associated with the risk of cancer. Currently, natural polyphenols have received increased attention for their potential therapeutic effects on EC. In this review, we summarize and discuss recent progress in the therapeutic potential of natural polyphenols in EC, as well as their sources, oral bioavailability, and pharmacokinetics. We review natural polyphenols combined with approved chemotherapy and radiotherapy to overcome challenges faced by either monotherapy. We also discuss the current challenges and future directions to accelerate the clinical application of natural polyphenols in EC. We concluded that natural polyphenols represent promising candidates for the management of EC. Well-designed randomized controlled studies are warranted to verify the efficacy and safety of natural polyphenols for EC. Knowledge gained from this review will outline possible future research directions and should help to develop new therapeutics for this disease.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"278-290"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}