Systemic chemotherapy

全身化疗
  • 文章类型: Case Reports
    在美国,皮肤鳞状细胞癌(cSCC)占非黑色素瘤皮肤癌病例的20%。总的来说,3%至5%的鳞状细胞癌(SCC)在出现时转移,与由于缺乏标准化治疗方案而导致的显著死亡率相关。总的来说,这些肿瘤中有95%符合最初的治疗标准,也就是手术切除.然而,其中一小部分患者需要全身治疗,因为它们要么局部进展到局部淋巴结,要么有远处转移。出现cSCC的常见部位是头皮和面部,可预测扩散到腮腺内,颈上静脉,和面周淋巴结.在我们的案例报告中,然而,我们的病人在上背部有一个大的肿块病变,一个不寻常的cSCC出现地点,左腋窝淋巴结局部晚期转移。随后,肿瘤标志物研究显示SMARCA4变异体(Switch(SWI)/蔗糖非发酵(SNF)染色质-重塑复合物的必需ATP酶亚基)阳性,在cSCC中更为罕见.此外,作为免疫检查点抑制剂(ICI)治疗的靶向治疗,SWI/SNF染色质-重塑复合物亚基的异常显示出有希望的结果.我们提出了在初次手术切除后接受放化疗和ICI全身治疗的患者中局部晚期罕见变异SMARCA4阳性cSCC的非典型表现部位。迄今为止,文献中仅发现2例SMARCA4阳性cSCC,但未提供治疗细节.我们的病例在其非典型表现部位以及对放射疗法(RT)和ICI全身治疗的部分反应方面是独特的。
    Cutaneous squamous cell carcinoma (cSCC) comprises 20% of cases of nonmelanoma skin cancers in the United States. In total, 3% to 5% of squamous cell carcinoma (SCC) are metastatic at the time of presentation, associated with significant mortality due to a lack of standardized treatment options. In total, 95% of these tumors are amenable to the initial standard of treatment, which is surgical resection. However, a small percentage of them require systemic therapy as they are either locally advanced to regional lymph nodes or have distant metastasis. The common sites of presentation of cSCC are the scalp and the face with predictable spread to the intra-parotid, upper jugular, and perifacial lymph nodes. In our case report, however, our patient had a large lump lesion on the upper back, an unusual site of presentation of cSCC, with locally advanced metastasis to the left axillary lymph nodes. Subsequently, the tumor marker study revealed a positive SMARCA4 variant (the essential ATPase subunit of the Switch (SWI)/Sucrose Nonfermenting (SNF) chromatin-remodeling complex) that is even rarer in the context of cSCC. Furthermore, abnormalities in SWI/SNF chromatin-remodeling complex subunits have shown promising results as a target therapy for immune checkpoint inhibitor (ICI) therapy. We present an atypical presentation site of locally advanced rare variant SMARCA4-positive cSCC in a patient who received treatment with chemoradiation and systemic therapy with ICI after primary surgical resection. To date, only 2 cases of SMARCA4-positive cSCC were found in the literature with no details of the treatment received. Our case is unique in its atypical site of presentation as well as showing partial response to radiotherapy (RT) and systemic therapy with ICI.
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  • 文章类型: Journal Article
    不可切除,转移性,晚期尿路上皮癌(aUC)是一种侵袭性疾病,采用含铂一线化疗治疗,其次是免疫检查点抑制剂和抗体-药物偶联物。对一线化疗的反应是序贯治疗策略中至关重要的优先事项,因为对一线化疗的更好反应与对后续治疗的更好反应相关。对于顺铂不合格的患者,通常推荐吉西他滨加卡铂化疗。这个多中心,单臂前瞻性试验将调查剂量密集的甲氨蝶呤,长春碱,阿霉素,卡铂(DD-MVACarbo)化疗在铂类药物疗效方面优于吉西他滨联合卡铂化疗,顺铂不合格的aUC患者。经过筛选和登记,共有46例患者将接受这种新型化疗方案的治疗.主要终点是客观反应率。次要终点包括疾病控制率,患者报告的结果,和不良事件。截至2024年7月,尚无这种新颖干预措施的证据。结果有望改变护理标准并改善aUC患者的管理。
    Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody-drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC.
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  • 文章类型: Case Reports
    目的:虽然大肠癌的化疗进展明显,长期化疗可导致多种感染。然而,如果必须停止化疗以控制感染,结直肠癌有进展的风险.颅内硬膜下积脓是一种危及生命的颅内感染。这种情况需要6-8周的抗生素治疗,患者在治疗期间必须停止化疗。我们在此介绍了转移性直肠癌长期化疗期间颅内硬膜下积脓的病例。
    方法:一名69岁女性患有不可切除的转移性直肠癌,出现惊厥性癫痫发作,入院治疗。惊厥性癫痫发作的原因被认为是直肠癌的转移性脑肿瘤。然而,在对比增强计算机断层扫描和对比增强磁共振成像的基础上,我们诊断为颅内硬膜下积脓。感染由抗生素控制,但在抗生素治疗期间,直肠癌化疗停止.因此,直肠癌进展,患者在入院65天后死亡。
    结论:化疗期间颅内硬膜下积脓很少发生。这种情况需要长期使用抗生素治疗;因此,早期详细的影像学检查和诊断可以改善预后。
    OBJECTIVE: Although chemotherapy for colorectal cancer has advanced remarkably, long-term chemotherapy can lead to a variety of infections. However, if chemotherapy must be discontinued to control infection, there is a risk of progression of colorectal cancer. Intracranial subdural empyema is a life-threatening intracranial infection. The condition requires 6-8 weeks of antibiotic therapy, and the patient must discontinue chemotherapy during treatment. We herein present a case of intracranial subdural empyema during long-term chemotherapy for metastatic rectal cancer.
    METHODS: A 69-year-old woman with unresectable metastatic rectal cancer had a convulsive seizure and was admitted to our hospital. The cause of the convulsive seizure was considered a metastatic brain tumor from rectal cancer. However, on the basis of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging, we diagnosed intracranial subdural empyema. The infection was controlled by antibiotics, but chemotherapy for rectal cancer was discontinued during antibiotic treatment. As a result, the rectal cancer progressed, and the patient died 65 days after admission to our hospital.
    CONCLUSIONS: Intracranial subdural empyema may develop rarely during chemotherapy. This condition requires long-term treatment with antibiotics; therefore, early detailed imaging and diagnosis may improve the prognosis.
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  • 文章类型: Journal Article
    并非所有患有多形性胶质母细胞瘤(GBM)的患者在预先手术和放疗后最终都有资格接受全身化疗。从监测中检索到GBM患者的信息,流行病学,和最终结果数据库。在2010年至2019年期间接受前期手术或活检和外部束放疗的患者符合全身化疗的条件。使用多变量逻辑回归和卡方检验评估可用的患者和肿瘤特征。在符合资格的16682名患者中,92.1%接受全身化疗。与最低全身化疗利用率相关的特征包括脑干/小脑肿瘤(P=0.01),前几年的诊断(P=0.001),≥80岁(P<0.001),西班牙裔,非西班牙裔亚洲人,太平洋岛民,或黑人种族(P<0.001),非合作状态(P<0.001),家庭收入中位数较低(P=0.006)。原发肿瘤部位,诊断年份,年龄,种族,伙伴地位,家庭收入中位数与成人患者GBM未进行全身化疗相关。
    Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.
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  • 文章类型: Case Reports
    多形性癌(PC)是一种罕见的高级乳腺癌形式,其特征是存在独特的多形性巨大肿瘤细胞,表现出奇异的核和非典型的有丝分裂。在这项研究中,我们报告了3例患者,他们在显微镜下出现了由大型多形性细胞增生组成的病变,其中多核巨细胞占优势。免疫组织化学分析显示,在各个恶性成分中具有不同的免疫学特征。值得注意的是,这份报告旨在提供有价值的见解,增加了对这种罕见肿瘤的理解,伴随着文献综述。尽管它很罕见,由于其独特的形态学和病理学特征,乳腺中的PC仍然具有临床相关性。这些独特的属性需要在临床表现和管理方面进行具体考虑。
    Pleomorphic carcinoma (PC) is an uncommon and high-grade form of breast carcinoma characterized by the presence of distinctive pleomorphic giant tumor cells exhibiting bizarre nuclei and atypical mitosis. In this study, we report three patients who presented with lesions composed of a proliferation of large pleomorphic cells with a predominance of multinucleated giant cells on a microscope. Immunohistochemical analysis revealed distinct immunologic profiles within the respective malignant components. Notably, this report aims to contribute valuable insights, adding to the understanding of this uncommon tumor, accompanied by a literature review. Despite its rarity, PC in the breast remains clinically relevant due to its distinctive morphological and pathological features. These unique attributes require specific considerations in both clinical presentation and management.
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  • 文章类型: Journal Article
    先前的细胞减灭术(CRS)和腹腔热化疗(HIPEC)后复发性结直肠腹膜转移的二次治疗研究甚少。
    评估继发性(重复)CRS+HIPEC与姑息治疗在复发性腹膜疾病中的总体生存结果。
    使用CRS+HIPEC指数治疗的结直肠腹膜转移患者,随后患有复发性腹膜疾病,从瑞典国家前瞻性HIPEC注册中确定。将患者分为介入组(继发性CRS+HIPEC)或姑息组。多变量逻辑回归,倾向得分匹配,并计算生存结局.
    在2010年至2021年期间接受完全CRS的575例患者中,有208例(36%)被诊断为随后的复发性腹膜疾病。42名患者(20%)接受了二级CRS+HIPEC。在88%(n=37)的女性中,继发性介入病例与姑息性病例的倾向评分匹配成功,索引手术时腹膜癌指数较低,更长的无病间隔,无腹膜外转移被确定为最相关的匹配协变量。介入治疗组自复发之日起的中位OS为38个月(95CI30-58),姑息治疗组为19个月(95CI:15-24)(HR0.3595CI:0.20-0.63,p=0.0004)。敏感性分析证实了结果。作为参考,整个结直肠登记处(n=575)的CRS+HIPEC指数的中位OS为41个月(95CI:38~45).
    匹配相关因素后,在为复发性腹膜疾病提供二次CRS+HIPEC手术的患者中,死亡风险比显著降低.选择偏见是固有的,但生存结局与初次手术后的生存结局相当.
    UNASSIGNED: Secondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated.
    UNASSIGNED: To evaluate the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease.
    UNASSIGNED: Patients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated.
    UNASSIGNED: Among 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % (n = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30-58) in the interventional group and 19 months (95%CI: 15-24) in the palliative group (HR 0.35 95%CI: 0.20-0.63, p = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry (n = 575) was 41 months (95%CI: 38-45).
    UNASSIGNED: After matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure.
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  • 文章类型: Journal Article
    目的:不可切除肝内胆管癌(ICC)的治疗方案有限,以全身化疗(SC)为主要方法。本研究旨在评估一线肝动脉灌注化疗(HAIC)联合lenvatinib和PD-(L)1抑制剂(HLP)与SC联合PD-(L)1抑制剂(SCP)或SC单独治疗不可切除的ICC的有效性。
    方法:接受HLP一线治疗的不可切除ICC患者,对2016年1月至2022年12月的SCP或SC进行回顾性分析。该研究评估并比较了三个治疗组的疗效和安全性结果。
    结果:该研究包括42、49和50名HLP患者,SCP,和SC组,分别。HLP的中位无进展生存期(PFS)时间分别为30.0、10.2和6.5个月,SCP,SC组。虽然SC组的中位总生存期(OS)为21.8个月,HLP和SCP组尚未达到中位OS。与其他组相比,HLP组显示出明显优于PFS(p<0.001)和OS(p=0.014)。此外,HLP组客观缓解率(ORR)最高,为50.0%,疾病控制率最高,为88.1%,超越SC组(ORR,6.0%;DCR,52.0%)和SCP组(ORR,18.4%;DCR,73.5%)(p<0.05)。一般来说,与其他组相比,HLP组报告的3-4级不良事件(AE)较少.
    结论:与使用或不使用PD-(L)1抑制剂的全身化疗相比,结合HAIC的三联疗法,lenvatinib,和PD-(L)1抑制剂对不可切除的ICC显示出良好的生存获益和可控制的不良事件。
    OBJECTIVE: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC.
    METHODS: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups.
    RESULTS: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn\'t reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others.
    CONCLUSIONS: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.
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  • 文章类型: Case Reports
    睾丸髓样肉瘤(TMS)是一种具有挑战性的病理学,通常由于肿瘤细胞在最初表现时的低分化性质而造成诊断困难。诊断延迟会显著影响患者的预期寿命,强调需要及时识别和开始治疗。在某些情况下,Fms样酪氨酸激酶(FLT3)突变的存在增加了疾病的复杂性,需要量身定制的治疗方法。在这份报告中,我们介绍了1例具有FLT3酪氨酸激酶结构域(TKD)突变的双侧TMS的独特病例.患者表现出积极的临床过程,在初步评估期间最初误诊为睾丸炎。随后在第二个中心重新评估睾丸活检导致了准确的诊断,强调在具有挑战性的情况下进行彻底检查的重要性。鉴于FLT3突变在骨髓肉瘤中的重要性,对所有FLT3变异体进行全面检测对于确定合适的治疗方式至关重要.这一案例强调了医疗保健专业人员对TMS相关的诊断细微差别和潜在遗传变异的认识。此外,包括酪氨酸激酶抑制剂,如midostaurin或gilteritinib,特别是在存在FLT3突变的情况下,可能会显著影响治疗结果。该报告为越来越多的TMS文献做出了贡献,并强调了在诊断和治疗决策过程中考虑FLT3突变以改善患者护理的重要性。
    Testicular myeloid sarcoma (TMS) is a challenging pathology often posing diagnostic difficulties due to the poorly differentiated nature of tumor cells at the initial presentation. The delay in diagnosis significantly impacts patient life expectancy, emphasizing the need for prompt identification and treatment initiation. In certain cases, the presence of the Fms-like tyrosine kinase (FLT3) mutation adds complexity to the disease, requiring tailored therapeutic approaches. In this report, we present a unique case of bilateral TMS with FLT3 tyrosine kinase domain (TKD) mutation. The patient exhibited an aggressive clinical course, initially misdiagnosed with orchitis during the initial evaluation. Subsequent reevaluation of the testicular biopsy at a second center led to an accurate diagnosis, highlighting the importance of thorough examination in challenging cases. Given the emerging significance of FLT3 mutations in myeloid sarcomas, comprehensive testing for all FLT3 variants is crucial to determine the appropriate treatment modality. This case underscores the need for increased awareness among healthcare professionals regarding the diagnostic nuances and potential genetic variations associated with TMS. Furthermore, the inclusion of tyrosine kinase inhibitors, such as midostaurin or gilteritinib, especially in the presence of FLT3 mutations, may significantly impact treatment outcomes. This report contributes to the growing body of literature on TMS and highlights the importance of considering FLT3 mutations in the diagnostic and therapeutic decision-making process for improved patient care.
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  • 文章类型: Journal Article
    原发性骨平滑肌肉瘤(LMSoB)极为罕见,仅包含<0.7%的原发性恶性骨肿瘤,因此被认为是一种非常罕见的肿瘤。目前,对于治疗策略是否应基于软组织平滑肌肉瘤的生物学特征或原发性肿瘤在骨骼中的定位,目前尚无共识。围手术期化疗的使用及其在这种罕见肿瘤实体中的有效性尚不清楚。我们旨在评估不同治疗方法在多中心环境中的影响,共纳入35例患者。5年总生存率(OS)为74%。与未接受手术治疗的患者相比,接受手术的局限性疾病患者的5年OS明显更高(82%vs.0%,p=0.0015)。轴向肿瘤定位与更差的无事件生存率(EFS)概率(p<0.001)和OS(p=0.0082)相关。我们的患者中有很大一部分发生了继发性转移。此外,应用于我们患者的围手术期化疗方案与EFS或OS改善无关.因此,LMSoB围手术期化疗的益处需要进一步研究,而代理人的选择仍需明确。
    Primary leiomyosarcoma of bone (LMSoB) is extremely rare, comprising only <0.7% of primary malignant bone tumors, and is therefore considered an ultra-rare tumor entity. There is currently no consensus as to whether therapeutic strategies should be based on the biological characteristics of soft tissue leiomyosarcoma or on primary tumor localization in the bone. The use of perioperative chemotherapy and its effectiveness in this rare tumor entity remains unclear. We aimed to evaluate the impact of different treatment approaches in a multicenter setting with a total of 35 patients included. The 5-year overall survival (OS) was 74%. Patients with localized disease undergoing surgery had a significantly higher 5-year OS compared to patients who did not undergo surgical treatment (82% vs. 0%, p = 0.0015). Axial tumor localization was associated with worse event-free survival (EFS) probability (p < 0.001) and OS (p = 0.0082). A high proportion of our patients developed secondary metastases. Furthermore, the perioperative chemotherapy protocols applied to our patients were not associated with an improved EFS or OS. Therefore, the benefit of perioperative chemotherapy in LMSoB needs to be further investigated, and the choice of agents still needs to be clarified.
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  • 文章类型: Systematic Review
    胰腺癌是一种对化疗反应有限的高度侵袭性恶性肿瘤。这项研究旨在比较区域性动脉内化疗(RIAC)与常规全身化疗治疗晚期胰腺癌的有效性和安全性。
    使用PubMed,Embase,WebofScience,还有Cochrane图书馆.包括评估RIAC和全身化疗的比较结果的研究。数据提取和质量评价由两名研究人员独立进行。采用STATA16软件进行统计学分析,计算赔率比(OR),风险差异(RD),和95%置信区间(CI)。
    11项研究,共有627名患者,纳入荟萃分析。结果显示,与接受全身化疗的患者相比,接受RIAC的患者部分缓解率(PR)明显更高(OR=2.23,95%CI:1.57,3.15,I2=0%)。此外,RIAC组的并发症发生率较低(OR=0.45,95%CI:0.33,0.63,I2=0%).此外,接受RIAC治疗的患者中位生存时间明显更长.
    这项研究的结果表明,RIAC与较高的部分缓解率有关,改善临床效益,在晚期胰腺癌的治疗中,与全身化疗相比,并发症更少。这些研究结果表明,对于晚期胰腺癌患者,RIAC可能是一种更有效,更安全的治疗选择。
    https://www.crd.约克。AC.英国/普华永道/,标识符CRD42023404637。
    UNASSIGNED: Pancreatic cancer is a highly aggressive malignancy with limited response to chemotherapy. This research aims to compare the effectiveness and safety of regional intra-arterial chemotherapy (RIAC) with conventional systemic chemotherapy in treating advanced stages of pancreatic cancer.
    UNASSIGNED: A comprehensive literature review was conducted using databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Studies assessing the comparative outcomes of RIAC and systemic chemotherapy were included. Data extraction and quality evaluation were performed independently by two researchers. Statistical analysis was conducted using STATA16 software, calculating odds ratios (OR), risk differences (RD), and 95% confidence intervals (CI).
    UNASSIGNED: Eleven studies, comprising a total of 627 patients, were included in the meta-analysis. The findings showed that patients undergoing RIAC had significantly higher rates of partial remission (PR) compared to those receiving systemic chemotherapy (OR = 2.23, 95% CI: 1.57, 3.15, I2= 0%). Additionally, the rate of complications was lower in the RIAC group (OR = 0.45, 95% CI: 0.33, 0.63, I2= 0%). Moreover, patients treated with RIAC had notably longer median survival times.
    UNASSIGNED: The results of this research indicate that RIAC is associated with a higher rate of partial remission, improved clinical benefits, and fewer complications compared to systemic chemotherapy in the management of advanced pancreatic cancer. These findings suggest that RIAC may be a more effective and safer treatment option for patients with advanced stages of pancreatic cancer.
    UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023404637.
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