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1.
Raman Jay RR McKay L Werner MB Atkins EM Van Allen KM Olivier J Song S Signoretti DF McDermott TK Choueiri 《Urologic oncology》2017,35(3):117-118
Background
Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.Methods
This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary end point was the objective response rate (ORR). Secondary end points included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives.Results
Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had>10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with≤10% sarcomatoid histology (P = 0.04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7).Conclusions
These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation. 相似文献2.
Zaydfudim V Smoot RL Clark CJ Kendrick ML Que FG Farnell MB Nagorney DM 《Journal of gastrointestinal surgery》2012,16(8):1516-1523
Introduction
We investigated the role of operative therapy in non-cirrhotic patients who developed metastatic hepatocellular carcinoma (HCC).Methods
This retrospective cohort study included consecutive non-cirrhotic patients with metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients were stratified by operative therapy (resection, ablation, transcatheter therapy). Kaplan?CMeier analyses with log-rank comparisons tested effects of operative therapy on overall survival (OS) and progression-free survival (PFS).Results
Of 195 non-cirrhotic patients treated for HCC during the study period, 98 [median age 65, interquartile range (IQR) 53?C71; 55?% male] subsequently developed metastatic HCC (55 intrahepatic only). Median time to development of metastases after the index operation was 10?months (IQR 5?C20?months); median number of metastases was 3 (IQR 2?C7). Half of these patients (n?=?50) underwent operative treatment of metastases; 20 (40?%) underwent metastasectomy, 18 (36?%) ablation, and 12 (24?%) transcatheter therapy. Operative therapy was associated with improved OS (p?0.001). Resection or ablation was associated with improved PFS and OS compared to transcatheter therapy (all p????0.006). Nine patients (seven resection, two ablation) are disease free at a median of 50?months (IQR 24?C80?months) posttreatment.Conclusions
Resection and ablation are associated with an improved PFS and long-term OS and should be considered in select patients with metastatic HCC. 相似文献3.
Yuasa T Tsuchiya N Urakami S Horikawa Y Narita S Inoue T Saito M Yamamoto S Yonese J Fukui I Nakano K Takahashi S Hatake K Habuchi T 《BJU international》2012,109(9):1349-1354
Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment‐naïve metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves (P < 0.001), suggesting that MSKCC prognostic factors might be still valid to predict survival in metastatic RCC in the era of molecular targeted therapy.
OBJECTIVES
- ? To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice.
- ? In addition, to investigate the prognostic clinicopathological factors in these patients.
PATIENTS AND METHODS
- ? The present study consisted of native Japanese patients with metastatic RCC, comprising 29 pretreated and 34 systemic treatment‐naïve patients.
- ? Univariate and multivariate analyses were performed by the log‐rank test and the Cox proportional hazards model, respectively.
RESULTS
- ? Estimated median progression‐free survival and overall survival (OS) were 9.3 months (95% confidence interval, CI, 5.0–13.7) and 32.2 months (95% CI, 24.4–40.0), respectively.
- ? Among the patients pretreated before sunitinib, two patients were treated with initialized systemic therapy with sorafenib and the remaining 27 were initialized with interferon‐α.
- ? The OS from the initial systemic therapy of the patients in pretreated groups was 79.6 months (95% CI, 14.6–144.5).
- ? The application of the Memorial Sloan‐Kettering Cancer Center model distinctly separated the OS curves (P < 0.001).
- ? The most common grade 3 adverse events were fatigue (53%), thrombocytopaenia (48%), hand‐foot syndrome (16%), anaemia (20%), hypertension (10%) and leucopaenia (9%), although these events were manageable and reversible.
CONCLUSIONS
- ? Sunitinib has a favourable efficacy/safety profile for Japanese metastatic RCC patients in clinical practice.
- ? The estimated median OS was >2 years with acceptable tolerability.
- ? The median OS from the initial systemic therapy of the pretreated patients was >6 years.
- ? Memorial Sloan‐Kettering Cancer Center prognostic factors still appear to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.
4.
Study Type – Therapy (Phase II non‐randomized trial) Level of Evidence 2b What’s known on the subject? and What does the study add? Interim result of this study had shown promising efficacy, with response rate of 14.7% and median PFS of 7.4 months, and good tolerability of sorafenib in previously‐treated Japanese patients with metastatic RCC. Final result of the study adds: (1) the median overall survival of 25.3 months, which is longer than that in the global phase III study TARGET; (2) the response rate which elevated to 19.4% because of 6 late responders achieved after 9.2 months or longer of SD period; (3) lack of either unknown adverse events nor cumulative toxicity in the long‐term use of sorafenib.
OBJECTIVE
? To explore the long‐term efficacy and safety of sorafenib in Japanese patients with metastatic renal cell carcinoma (RCC) in a phase II trial.PATIENTS AND METHODS
? In all, 131 Japanese patients with metastatic RCC who had received nephrectomy and failed at least one cytokine‐containing systemic therapy received continuous sorafenib 400 mg twice daily, and the efficacy and safety parameters were evaluated in these patients, including objective response rate, progression‐free survival and overall survival.RESULTS
? Of the total, 129 patients were valid for intention‐to‐treat analyses and 131 patients were valid for safety analyses. ? Twenty‐five patients (19.4%) had confirmed partial response and 87 patients (67.4%) had stable disease as best overall response. The 25 patients included six late‐responders who achieved response after 9.2 months or longer of stable disease. The objective response rate and disease control rate were 19.4% and 73.6%, respectively. ? The median overall survival and median progression‐free survival were 25.3 and 7.9 months, respectively. ? Safety profile was consistent with those previously reported, with hand–foot skin reaction (58.0%), lipase elevation (57.3%) and diarrhoea (42.7%) as the most frequently observed drug‐related adverse events. Neither unknown adverse event nor cumulative toxicity was observed over the long‐term use of sorafenib. ? Despite the dose discontinuation/interruption/reduction, the mean and median relative dose intensities were 86.4% and 97.4%, respectively.CONCLUSION
? The final results of this trial showed that long‐term use of sorafenib after cytokine treatment was well tolerated and provided new efficacy data, including late‐response events and favourable overall survival in Japanese patients with metastatic RCC. 相似文献5.
Aymen A. Elfiky M.D. M.A. M.P.H. Daniel C. Cho M.D. M.S. David F. McDermott M.D. Jonathan E. Rosenberg M.D. Barry Fortner Ph.D. Lucia Antràs Ph.D. Kristina Chen Ph.D. Mei Sheng Duh Ph.D. Sujata S. Jayawant Ph.D. William K. Oh M.D. Michael B. Atkins M.D. Toni K. Choueiri M.D. 《Urologic oncology》2011,29(6):756
Objective
To identify factors that can be used to identify metastatic clear cell RCC patients more likely to benefit from sequential sunitinib.Patients and methods
We identified patients who failed sorafenib or bevacizumab and subsequently received sunitinib. We looked at objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) to sunitinib in relation to baseline clinical variables.Results
Seventy-one patients received sunitinib sequential therapy. Median duration of follow-up after starting sunitinib was 9.3 months. Median PFS was 5.8 months; median OS was not reached. Significantly higher ORR was seen in patients with normal hemoglobin (25.6%) [defined as >12 gm/dl for female; >13 gm/dl for male]. In addition, a shorter PFS for patients with low hemoglobin, and patients with time from diagnosis to first treatment ≤1 year was found. There was a shorter OS for patients ≥60 years old, with brain metastasis, low hemoglobin, and time from diagnosis to treatment ≤1 year. There was no difference in ORR, PFS, or OS in patients who started sunitinib after or within a 30-day period.Conclusions
Metastatic clear-cell RCC patients with anemia have less clinical benefit from sequential sunitinib after failure of bevacizumab or sorafenib. Other factors associated with poor outcome include brain metastases, older age, and <1 year between diagnosis and first treatment. Importantly, no difference in outcomes was observed if sequential therapy was initiated within or after 30 days. External validation and prospective evaluation are needed to confirm these findings. 相似文献6.
Ogata Y Tokunaga S Emi Y Oki E Saeki H Shirabe K Hasegawa H Sadanaga N Samura H Fujita F Tanaka T Kitazono M Yamamoto M Morikita T Inomata M Kakeji Y Shirouzu K Maehara Y;Kyushu Study Group of Clinical Cancer 《Surgery today》2011,41(1):84-90
Purpose
This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer.Methods
A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment.Results
Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%?C35.0%). The median PFS was 5.6 months (95% CI, 4.1?C7.0 months) and the median OS was 19.6 months (95% CI, 11.4?C24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable.Conclusion
The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population. 相似文献7.
目的:比较酪氨酸激酶抑制剂(TKI)治疗转移性肾细胞癌伴横纹肌样分化(mRCC-R)与伴肉瘤样分化(mRCC-S)的疗效。方法:回顾性分析天津医科大学肿瘤医院2016年2月至2018年12月采用TKI治疗的5例mRCC-R和9例mRCC-S患者的临床资料。mRCC-R患者5例,男3例,女2例;年龄(60.2±7.1)岁... 相似文献
8.
Seong Joon Park MD Min-Hee Ryu MD PhD Baek-Yeol Ryoo MD PhD Young Soo Park MD PhD Byeong Seok Sohn MD PhD Hwa Jung Kim MD PhD Chan Wook Kim MD PhD Ki-Hun Kim MD PhD Chang Sik Yu MD PhD Jeong Hwan Yook MD PhD Byung Sik Kim MD PhD Yoon-Koo Kang MD PhD 《Annals of surgical oncology》2014,21(13):4211-4217
Background
Although benefits of surgical resection of residual gastrointestinal stromal tumors (GISTs) after imatinib therapy have been suggested, those benefits over imatinib alone have not been proven. We compared the clinical outcomes of surgical resection of residual lesions after imatinib treatment (S group) with imatinib treatment alone (NS group) in patients with recurrent or metastatic GISTs.Methods
A total of 134 patients (42 in the S group, 92 in the NS group) with recurrent or metastatic GIST who had stable disease for more than 6 months after responding to imatinib were included.Results
There were no statistically significant differences in the baseline characteristics of the S and NS groups except for age and number of peritoneal metastases. The median follow-up period was 58.9 months. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the S group compared with the NS group (median PFS: 87.7 vs. 42.8 months, p = 0.001; median OS: not reached vs. 88.8 months, p = 0.001). Multivariate analysis revealed that S group, female sex, KIT exon 11 mutations, and low initial tumor burden were associated with longer PFS, and S group and low initial tumor burden were associated with a longer OS. Even after applying inverse probability of treatment weighting adjustment, the S group demonstrated significantly better outcomes in terms of PFS (HR 2.326; 95 % confidence interval [CI] 1.034–5.236; p = 0.0412) and OS (HR 5.464; 95 % CI 1.460–20.408; p = 0.0117).Conclusion
Surgical resection of residual lesions after disease control with imatinib is likely to be beneficial to patients with recurrent or metastatic GISTs. 相似文献9.
Italiano A Cioffi A Coco P Maki RG Schöffski P Rutkowski P Le Cesne A Duffaud F Adenis A Isambert N Bompas E Blay JY Casali P Keohan ML Toulmonde M Antonescu CR Debiec-Rychter M Coindre JM Bui B 《Annals of surgical oncology》2012,19(5):1551-1559
Background
Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited.Methods
Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed.Results
The three most frequent drugs used in the 3rd-line setting were: nilotinib n?=?67 (29.5%), sorafenib n?=?55 (24.5%), and imatinib n?=?40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd-line treatment were 3.6?months [95% confidence interval (95% CI), 3.1?C4.1] and 9.2?months (95% CI, 7.5?C10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC.Conclusion
In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib. 相似文献10.
目的总结在靶向药物治疗基础上单中心转移性肾癌的多学科诊疗经验。方法回顾性分析2007年12月至2019年2月中山大学肿瘤防治中心经多学科诊疗团队(multi-disciplinary team,MDT)诊治的168例转移性肾癌(metastatic renal cell,mRCC)患者的临床数据。根据治疗方式将患者分为3组。单纯靶向药物治疗(A组)76例,男55例,女21例;年龄52(17~73)岁;透明细胞癌60例,非透明细胞癌16例;国际转移性肾细胞癌联合数据库(International Metastatic Renal Cell Carcinoma Database consortium,IMDC)预后评分低危11例,中危48例,高危17例;初诊时即有转移44例;行原发灶切除术63例。靶向药物治疗+局部治疗(B组)66例,男55例,女11例;年龄54(21~86)岁;透明细胞癌49例,非透明细胞癌17例;IMDC预后评分低危13例,中危39例,高危14例;初诊时即有转移32例;行原发灶切除术56例。靶向药物治疗+局部治疗+免疫治疗(C组)26例,男19例,女7例;年龄52(23~83)岁;透明细胞癌15例,非透明细胞癌11例;IMDC预后评分低危9例,中危13例,高危4例;初诊时即有转移9例;行原发灶切除术26例。3组患者一般资料比较差异均无统计学意义(P>0.05)。一线靶向治疗药物为舒尼替尼、索拉非尼、阿昔替尼。舒尼替尼50 mg,每日1次,用药4周停2周;索拉非尼400 mg,每日2次;阿昔替尼5 mg,每日2次。接受舒尼替尼、索拉非尼、阿昔替尼一线治疗者分别为103、18、39例。靶向药物治疗时间均>6个月。免疫治疗采用派姆单抗(Pembrolizumab)2 mg/kg静脉应用,每3周1次,或低剂量(20 mg)派姆单抗孵育经体外扩增后的自体外周血树突状细胞细胞因子诱导杀伤细胞(dendritic cells cytokine induced killer,DC.CIK),每周1次,4次后改为每2周1次。18例采用DC.CIK,8例采用派姆单抗。局部治疗方式包括立体定向放疗(stereotactic body radiation therapy,SBRT)和外科治疗(手术切除或能量消融治疗)。根据靶向药物治疗效果,转移灶部位、数量、与周围器官关系,以及患者的意愿,经MDT专家讨论后决定局部治疗方式。92例接受局部治疗,其中单纯外科治疗34例,单纯SBRT 37例,外科治疗+SBRT 21例。比较3组的疗效和不良反应情况,分析不同治疗方法与患者总生存时间(overall survival,OS)的关系。结果168例中位随访23个月(6~117个月)。中位无进展生存时间(progression free-survival,PFS)为18.3个月,中位OS为33.5个月;2年生存率为66%,5年生存率为35%。A、B、C组的中位OS分别为29.8个月、44.6个月和未达,2年生存率分别为58%、67%和89%,5年生存率分别为12%、46%和57%。在靶向药物治疗的基础上接受联合治疗者的预后均优于单纯靶向药物治疗者,5年总OS分别为51%和11%。C组的中高危mRCC患者预后明显优于A、B组。在接受免疫治疗的患者中,靶向药物治疗联合DC.CIK与联合派姆单抗的中位OS分别为49.1个月和53.1个月,差异无统计学意义(P=0.541)。单因素分析结果显示,OS与IMDC评分、原发灶切除、治疗模式相关(P<0.05)。多因素分析结果显示,OS与治疗模式、原发灶切除显著相关(P<0.05),靶向药物治疗+免疫治疗+局部治疗可使mRCC患者死亡风险下降约60%(HR=0.39,95%CI 0.17~0.89,P=0.026)。78例使用靶向药物治疗发生3~4级不良反应,12例因无法耐受一线靶向药物治疗不良反应而停药或换药。16例采用靶向药物联合免疫治疗发生3~4级药物不良反应,主要为疲乏8例次、白细胞降低4例次、血小板降低3例次、转氨酶和胆红素升高3例次。靶向药物治疗联合DC.CIK治疗的严重不良反应发生例数少于联合派姆单抗治疗(6例与12例),特别是显著降低了血液学毒性(2例与5例)和肝毒性(0例与3例),差异均有统计学意义(P<0.05)。外科治疗后出现ClavienⅢ~Ⅳ级并发症16例次,主要为感染和切口延期愈合6例次、不全肠梗阻4例次,围手术期输血15例次。SBRT治疗后6例出现美国放射肿瘤协作组评分(Radiotherapy Oncology Group,RTOG)3级不良反应,其中骨髓抑制4例,皮肤反应和放射性神经炎2例,未观察到≥4级不良反应。结论在靶向药物治疗基础上联合免疫治疗和局部治疗的mRCC患者预后明显优于采用单纯靶向药物治疗的患者。经MDT诊疗的综合治疗可使mRCC患者生存获益。 相似文献
11.
Stephen Boorjian 《Urologic oncology》2014,32(4):514-515
ObjectivesTo evaluate the role of cytoreductive radiofrequency ablation (cRFA) in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with immuno- or targeted therapy. To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumours.Patients and methodsThree parallel single-arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumour <5 cm; good or intermediate prognosis according to the Memorial Sloan-Kettering Cancer Center model; and no previous therapy. Study 1: Patients were treated with percutaneous cRFA under computed tomography guidance followed by interferon (IFN)-α, 9 MIU, s.c., three times per week. Study 2: Patients received cRFA followed by sunitinib in repeated 6-week cycles of 50 mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression-free survival (PFS).ResultsBaseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumour size) were similar in all three studies. Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively. Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P<0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 months (P = 0.02). The median (95% CI) objective survival (OS) times were greater in study 2 (cRFA/sunitinib) and study 3 (sunitinib-alone) than in study 1 (IFN-α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the cRFA/sunitinib group compared with the sunitinib-alone group (HR = 0.71; P = 0.04). There were no unexpected toxicities of medical treatment or complications of cRFA.ConclusionscRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy. The cRFA technique did not improve PFS in patients treated with sunitinib; cRFA probably has impact on OS in these patients. This needs to be tested in a larger trial. Sunitinib was effective in patients with metastatic RCC with unresected small primary tumours. 相似文献
12.
Mark Warren Peter M. Venner Scott North Tina Cheng Chris Venner Sunita Ghosh Allison A. Venner Daygen Finch 《Canadian Urological Association journal》2009,3(4):281-289
Background
We performed a retrospective population-based study to assess the impact of tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients treated for metastatic renal cell carcinoma (mRCC) in Alberta, Canada and to assess the impact of nephrectomy on OS in patients treated with TKIs.Methods
We identified 134 patients who began taking a TKI between December 2003 and June 2007 for mRCC in Alberta. We compared survival in this group to that in an earlier cohort of 141 patients treated with interferon-α (IFN-α) between May 1995 and March 2003. We used the Kaplan–Meier method to determine OS, and we used a Cox proportional hazards model to determine hazard ratios (HRs) and confidence intervals (CIs). We performed multivariate analysis to assess the impact of neprhectomy on OS.Results
Of the 134 patients treated with TKIs, 81 received treatment in the first-line setting, whereas 53 received treatment after prior IFN-α therapy. All 141 patients from the IFN-α cohort received treatment in the first-line setting. Patients treated with TKIs had an improved OS compared with the IFN-α cohort (HR 0.61, 95% CI 0.45–0.83, p = 0.001). The median OS was 18 months in the TKI group and 10 months in the IFN-α group. The benefit of TKIs was confined to favourable and intermediate risk groups according to the Memorial Sloan-Kettering Cancer Center prognostic model. Prior nephrectomy was associated with improved OS in the TKI cohort, independent of other prognostic factors.Conclusion
Tyrosine kinase inhibitors improve OS compared with IFN-α in mRCC. In patients treated with TKIs, prior nephrectomy is associated with improved survival independent of other prognostic variables. 相似文献13.
Bernhard Ralla Barbara Erber Irena Goranova Luise von der Aue Anne Floercken Stefan Hinz Carsten Kempkensteffen Ahmed Magheli Kurt Miller Jonas Busch 《World journal of urology》2016,34(8):1147-1154
Introduction
Evidence for sequencing targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) beyond third line is limited. Treatment decisions for these sequence options are largely based on individual preferences and experience. The aim of this study was to describe the efficacy and toxicity of fourth-line TT.Materials and methods
We retrospectively reviewed patients treated with fourth-line TT for mRCC after failure of previous treatment lines at a German academic high-volume center. Out of 406 patients treated in first line, 56 patients (14.8 %) were identified with more than three lines of TT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Cox proportional hazards models were applied to explore predictors of PFS and OS in uni- and multivariable analysis.Results
For the fourth-line treatment, disease control rate was 35.7 %. Median OS from beginning of first-line therapy was 47.4 months (IQR 31.0–76.5). Primary resistance at first-line TT, metastatic disease at initial diagnosis and an intermediate MSKCC score were independent predictors of shorter OS from start of first-line TT. Median OS from the time of initiation of fourth-line therapy was 10.5 months (IQR 5.6–22.6). The corresponding median PFS for fourth-line TT was 3.2 months (IQR 1.6–8.0) and was not correlated with treatment response in first-line TT. The rate of toxicity-induced treatment termination was 16.1 %. Limitations are the retrospective and unicentric design with a limited number of patients.Conclusions
Patients might benefit from subsequent treatment lines independently from treatment response in first line.14.
索拉非尼治疗具有肉瘤样分化的转移性肾癌的疗效观察 总被引:1,自引:1,他引:0
目的 分析索拉非尼治疗具有肉瘤样分化的转移性肾癌的疗效.方法 已行肾脏原发肿瘤切除的转移性肾细胞癌患者14例,病理证实原发肿瘤中含有肉瘤样分化成分.平均年龄61(45~77)岁.肾透明细胞癌伴肉瘤样分化8例,乳头状癌伴肉瘤样分化2例,单纯肉瘤样癌4例,肾原发病灶中肉瘤样成分比例为20%~100%.肿瘤转移部位分别为肺、淋巴结、肾上腺、肝或骨.采用索拉非尼400 mg或600 mg,2次/d治疗.采用Kendall相关检验和Pearson相关检验分别检测肉瘤样成分比例与治疗客观反应及中位无疾病进展时间(PFS)的相关性.中位治疗时间8(3~19)个月.结果 部分缓解(PR)2例,其转移病灶均位于腹膜后及纵隔淋巴结,肉瘤样成分比例分别为100%和20%;疾病稳定(SD)7例,转移部位包括肺、淋巴结、肾上腺、骨和肝;疾病进展(PD)5例,总疾病控制率为64%.随访至2009年7月,出现PD 9例,PFS 6(0~19)个月.肉瘤样成分比例与治疗的客观反应及PFS均无相关性(P=0.247,P=0.554).结论 索拉非尼常规剂量治疗具有肉瘤样分化的转移性肾细胞癌有一定疗效,但客观有效率及PFS与肉瘤样成分的比例无明显相关性. 相似文献
15.
Sara Massironi Davide Campana Stefano Partelli Francesco Panzuto Roberta Elisa Rossi Antongiulio Faggiano Nicole Brighi Massimo Falconi Maria Rinzivillo Gianfranco Delle Fave Anna Maria Colao Dario Conte 《Annals of surgical oncology》2018,25(11):3200-3206
Background
The optimal management of duodenal neuroendocrine neoplasms (dNENs) is unclear, and endoscopic resection is increasingly performed instead of surgery.Methods
This is a retrospective analysis of patients with histologically confirmed diagnosis of dNENs, managed at five Italian tertiary referral Centers in Italy.Results
From 2000 to 2017, 108 patients (69 males, 39 females, median age 59.5 years) were included in this study. Seventy-one patients had G1, 21 G2, 4 G3 dNENs (12 Ki-67 not available). Fifty-four patients showed metastases at diagnosis, and 20 patients developed metachronous metastases. Thirty patients had a functioning dNEN (14 metastatic). Fifty-seven patients had the dNEN surgically resected, 16 endoscopically, 23 metastatic, received medical therapy?+?surgery or endoscopy. Seven patients underwent liver-directed therapies, and one patient had PRRT. Median OS was 187 months. During a median follow-up of 76 months, 20 patients died (19 of disease-related causes). At Cox’s multivariate proportional hazard regression, grading and age were the only variables independently related to OS. Median PFS was 170 months. Grading and staging at the initial diagnosis were independently related to PFS. No differences in terms of OS and PFS were observed between patients treated surgically or endoscopically.Conclusions
dNENs prognosis may be highly variable. These tumors can be metastatic in up to 50% of cases at the time of first diagnosis and can develop metastases thereafter. Functioning neoplasms express high metastatic potential. Nuclear imaging should be performed to exclude distant metastases in all dNENs. Endoscopy and surgery play a primary role in the management of the disease. Further prospective studies are needed.16.
Look Hong NJ Pandalai PK Hornick JL Shekar PS Harmon DC Chen YL Butrynski JE Baldini EH Raut CP 《Annals of surgical oncology》2012,19(8):2707-2715
Purpose
To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS).Methods
This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival.Results
Data from 18 patients (78?% male) were reviewed. Sixteen patients (89?%) had AS originating in the right atrium. At diagnosis, eight patients (44?%) had localized/locally advanced disease and ten patients (56?%) had metastatic disease. Initial treatment strategies included resection (44?%), chemotherapy (39?%), and radiotherapy (11?%). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12?months. Median overall survival (OS) was 13?months for the entire cohort; median OS was 19.5?months for those presenting with localized/locally advanced AS and 6?months for those with metastatic disease at presentation (p?=?0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5?months, p?=?0.01).Conclusions
Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression. 相似文献17.
BackgroundFor human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies.Patients and methodsWomen with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA.ResultsEighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55–1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26–1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX.ConclusionIn women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX.Trial registration numberUMIN000005219. 相似文献
18.
《Urologic oncology》2020,38(9):739.e9-739.e15
BackgroundTyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN).ObjectiveTo assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting.MethodsOverall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS).ResultsOverall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis.ConclusionThe role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC. 相似文献
19.
Costa WH Rocha RM Cunha IW Fonseca FP Guimaraes GC Zequi Sde C 《World journal of urology》2012,30(4):553-558
Purpose
To evaluate the prognostic impact of the histological expression of CD133 in renal cell carcinoma (RCC).Methods
From 1992 to 2009, 142 consecutive patients underwent radical nephrectomy or partial nephrectomy for RCC. All cases were reviewed by a single pathologist and then subjected to analysis of the immunohistochemical expression of CD133 using tissue microarray. Several clinical and pathological variables were also evaluated.Results
The median postoperative follow-up was 44?months. Of the 142 immunostained RCC specimens, 77 (54%) showed low and 65 (46%) high expression of CD133. Expression of CD133 was associated with clinical stage (P?=?0.05), lymph node involvement (P?=?0.03), metastatic disease (P?=?0.02) and MVI (P?=?0.03). Among other variables, clinical stage, necrosis and metastasis were associated with disease-specific survival (DSS) and progression-free survival (PFS) on univariate analysis. The 5-year PFS rates in patients who provided specimens with high and low expression of CD133 were 83 and 66%, respectively (P?=?0.01). It was observed that the 5-year DSS for patients who provided specimens with high and low expression of CD133 was 90 and 71%, respectively (P?=?0.003). Multivariate survival analysis showed that patients in the CD133 low-expression group had a higher probability of disease progression (HR 3.4, P?=?0.02) and a higher probability of death from cancer (HR 2.4, P?=?0.01).Conclusions
Immunohistochemical expression of CD133 had an impact on survival in patients with RCC, which shows that CD133 might be a useful tool for risk stratification. Low expression of this marker remained as an independent predictor of poor DSS and PFS. 相似文献20.
Liancheng Fan Baijun Dong Chenfei Chi Yanqing Wang Yiming Gong Jianjun Sha Jiahua Pan Xun Shangguan Yiran Huang Lixin Zhou Wei Xue 《BMC urology》2018,18(1):110