Efficacy and safety of low-dose apatinib plus S-1 versus regorafenib and fruquintinib for refractory metastatic colorectal cancer: a retrospective cohort study

BackgroundAt present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies.MethodsThe records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5–2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded.ResultsThe baseline clinical characteristics of the patients were broadly similar among the three groups. The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5–5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9–4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1–2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4–11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3–10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2–10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant.ConclusionsLow-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.     

VCD/IE方案联合阿帕替尼治疗化疗失败进展期尤因肉瘤的回顾性研究

目的：评估VCD/IE方案（长春新碱+环磷酰胺+多柔比星与异环磷酰胺+依托泊苷交替）联合阿帕替尼治疗化疗失败进展期尤因肉瘤的疗效与安全性。方法：回顾性研究2017年1月至2021年12月于华中科技大学同济医学院附属协和医院,接受VCD/IE方案联合阿帕替尼治疗化疗失败的进展期尤因肉瘤11例患者的临床资料。与同期接受阿帕替尼单药治疗的尤因肉瘤患者对比,评估该方案的疗效及安全性。主要观察终点为疾病无进展生存期（progression-free survival,PFS）,次要观察终点为客观缓解率（objective response rate,ORR）、疾病控制率（disease control rate,DCR）、总生存时间（overall survival,OS）和不良反应（adverse event,AE）。结果：共筛选出符合入排标准的联合治疗患者11例,阿帕替尼单药组10例。两组患者中位随访时间分别为19.5个月和14.5个月。其中男性占比分别为72.7%(8/11)和70%(7/10),平均年龄分别为18.1±6.7岁和20.8±15.7岁。VCD/IE方案联合阿帕替尼的ORR、...     

Safety and effectiveness of apatinib in elderly patients with metastatic gastric cancer: a sub-analysis from the large-scale,prospective observational study of apatinib for gastric cancer treatment in a real-world clinical setting (AHEAD-G202)

BackgroundApatinib was shown to improve the survival of Chinese patients with refractory metastatic gastric cancer (mGC). As an orally administered drug, it has been widely used in elderly patients because the dosing schedule can be adjusted flexibly. However, data on the efficacy and safety of apatinib in elderly patients is scarce. The aim of this study was to evaluate the toxicity and effectiveness of apatinib for elderly patients with mGC in a real-world setting.MethodsData from the sub-population of patients who were ≥65 years enrolled in the AHEAD-G202 trial were analyzed. Patients with mGC were prospectively registered and initially received ≤850 mg oral apatinib daily combined or not combined with chemotherapy, at the investigator’s discretion. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsA total of 117 patients were included. There were 51 (43.59%) patients in the low-dose (250 mg) group, 60 (51.28%) patients in the mid-dose (425 to 500 mg) group, and 6 (5.13%) patients in the high-dose (850 mg) group according to the initial daily doses. Hypertension (6.84%) was the only grade 3–4 adverse event (AE) with a prevalence of more than 5% and across the low-dose (11.76%), mid-dose (3.33%) and high-dose group (0%). The median OS and PFS were 7.13 months (95% CI: 5.04 to 9.22 months) and 4.27 months (95% CI: 3.24 to 5.29 months), respectively. The OS and PFS were similar among the 65–74 and ≥75 years groups (χ²=1.406, P=0.306; χ²=0.378, P=0.066, respectively). The OS and PFS were also comparable among the 3 dose groups.ConclusionsElderly patients with mGC can tolerate and benefit from apatinib therapy. A lower initial daily dosing strategy may be a suitable choice for elderly patients in clinical practice.     

Osteosarcoma of the pelvis--oncological results of 40 patients registered by The Netherlands Committee on Bone Tumours.

AIM and METHODS: We reviewed the oncological outcome in 40 consecutive patients with an osteosarcoma of the pelvic region, registered in the files of the Netherlands Committee on Bone Tumours (NCBT) between 1978 and 1995. RESULTS: Six patients had distant metastases at initial presentation (Enneking stage IIIB), 33 patients had stage IIB osteosarcoma and one patient stage IB osteosarcoma. Patients with metastases were treated with chemotherapy (four) or palliative procedures (two). Patients with non-metastatic osteosarcoma were treated with surgical procedures with (14) or without (four) neoadjuvant chemotherapy, chemotherapy without surgical resection (nine), or palliative procedures (seven). The median survival of stage IIB and IIIB osteosarcoma was 14 months (2-175) and 7.5 months (2-16), respectively. Survival in patients with stage IIB osteosarcoma treated with curative procedures was significantly better (P<0.0006) compared with stage IIB patients treated with palliative intent. Two and 5-year survival for patients with curatively treated stage IIB osteosarcoma was 35% and 26%, respectively; distant metastases had developed in 65% of these patients. On univariate analysis, positive prognostic factors for patients with stage IIB osteosarcoma were complaints of 3 months or less before initial presentation, tumour size of 8 cm or less, osteoblastic subtype, surgical resection of the primary tumour and limb salvage procedures. CONCLUSION: In conclusion, the prognosis of pelvic osteosarcoma remained poor despite modern multimodality treatment regimens, including neoadjuvant chemotherapy.     

Sorafenib in patients with progressed and refractory bone tumors

Patients with metastatic, progressive, or recurrent bone tumors have a dismal outcome. Sorafenib has been proposed as an effective salvage regimen for some malignancies. Thus, we sought to evaluate this approach for young patients with relapsed or refractory bone tumors. Twelve patients with refractory bone tumors (two with Ewing sarcoma, two with chondrosarcoma, and eight with osteosarcoma) received salvage treatment with sorafenib. All patients had standard tumor imaging and laboratory evaluation. All toxicities were documented. At the time of the beginning of sorafenib treatment median age among 12 patients was 18 years (range 4.1–27.9 years), eight were male, and eight had osteosarcoma. All received sorafenib because of relapse. Seven patients were treated parallel to other standard chemotherapy. Overall response rate was 75%. Median time to sorafenib time to progression for patients with osteosarcoma was 4 months (range 1.8–7.9 months). Four patients (33%) are alive, in that two with no evidence of disease with a median follow-up of 41 months (range 26.5–60.9 months). The estimated 5 year overall survival (OS) for the whole group was 64.49%. There were no serious toxicities. Sorafenib is well-tolerated in young patients with bone tumors, and particularly could be an option for patients with metastatic disease and refractory osteosarcoma. Sorafenib only allows to extend OS and different procedures are needed to achieve permanent remission. This regimen deserves further investigation in the upfront management of patients with high-risk bone tumors.     

A Phase II Study of Apatinib in Patients with Chemotherapy-Refractory Esophageal Squamous Cell Carcinoma (ESO-Shanghai 11)

Lessons Learned

• Apatinib has potential as an effective and safe second‐line or higher treatment for patients with chemotherapy‐refractory esophageal squamous cell carcinoma (ESCC).
• Clinical safety is of potential concern when administering apatinib to patients with uncontrolled esophageal lesions or severe invasion of trachea, bronchi, or major blood vessels.
• To the best of the authors'' knowledge, this is the first prospective phase II study to investigate apatinib for patients with chemotherapy‐refractory ESCC. Apatinib could provide an alternative option for ESCC after first‐line or higher therapy in carefully selected patients.

BackgroundThe aim of this study was to evaluate the efficacy and adverse effects of the oral vascular endothelial growth factor receptor 2 (VEGFR‐2) tyrosine kinase inhibitor apatinib in patients with chemotherapy‐refractory esophageal squamous cell carcinoma (ESCC).MethodsWe enrolled patients with chemotherapy‐refractory ESCC. All patients received continuous apatinib 500 mg once daily.ResultsBetween July 2017 and August 2018, 40 patients were recruited, of whom 5 (12.5%) had uncontrolled primary tumors. Additionally, three patients with partial response (PR) and 23 with stable disease (SD) were observed for overall response rate (ORR) of 7.5% and disease control rate (DCR) of 65.0%. Median progression‐free survival (PFS) was 3.8 months (95% confidence interval [CI], 2.2–5.4); median overall survival (OS) was 5.8 months (95% CI, 3.2–8.4). Common adverse effects were fatigue (15%), hypertension (12.5%), and palmar‐plantar erythrodysesthesia syndrome (10%). Two cases of death from massive bronchopulmonary hemorrhage were observed, and esophageal fistula occurred in another two patients. Notably, both patients with esophageal fistula and one patient with massive fatal bronchopulmonary hemorrhage were individuals with uncontrolled primary tumors (3/5, 60%). Fatal bronchopulmonary hemorrhage in a second patient was associated with major blood vessel invasion.ConclusionApatinib has potential as an effective and safe treatment for patients with chemotherapy‐refractory ESCC whose primary tumors are controlled and without severe invasion of trachea, bronchi, or major blood vessels.     

Understanding Treatment Patterns and Outcomes among Patients with De Novo Unresectable Locally Advanced or Metastatic Urothelial Cancer: A Population-Level Retrospective Analysis from Alberta,Canada

Despite a high disease burden, real-world data on treatment patterns in patients with unresectable locally advanced or metastatic urothelial carcinoma (la/mUC) in Canada are limited. This retrospective, longitudinal cohort study describes treatment patterns and survival in a population of patients with de novo unresectable la/mUC from Alberta, Canada, diagnosed between 1 January 2015 and 31 December 2019, followed until mid-2020. The outcomes of interest were systemic therapy treatment patterns and overall survival (OS). Of 206 patients, most (65.0%, n = 134) did not receive any systemic therapies. Of 72 patients (35.0%) who received first-line systemic therapy, the median duration of treatment was 2.8 months (IQR 3.3). Thirty-five patients (48.6% of those who received first-line therapy) received subsequent second-line therapy, for a median of 3.0 months (IQR 3.3). In all patients (n = 206), the median OS from diagnosis was 5.3 months (95% CI, 4.5–7.0). In patients who received treatment, the median OS from the initiation of first-line and second-line systemic therapy was 9.1 (6.4–11.6) and 4.6 months (3.9–19.2), respectively. The majority of patients did not receive first-line systemic therapy, and, in those who did, survival outcomes were poor. This study highlights the significant unmet need for safe and efficacious therapies for patients with la/mUC in Canada.     

阿帕替尼联合依托泊苷治疗三阴性乳腺癌的疗效及不良反应

目的探讨甲磺酸阿帕替尼联合依托泊苷治疗晚期、复发、难治性三阴性乳腺癌的疗效及不良反应。方法收集10例晚期复发难治性三阴性乳腺癌患者的临床资料,均接受甲磺酸阿帕替尼联合依托泊苷治疗,观察用药后疾病控制率(DCR)、客观缓解率(ORR)、无进展生存期(PFS)并记录不良反应。结果10例患者均接受了至少2个周期的治疗,无完全缓解病例,部分缓解4例,疾病稳定5例,疾病进展1例,ORR为40%(4/10),DCR为90%(9/10),中位PFS为4.0个月(95%CI:1.15~6.85)。阿帕替尼联合依托泊苷作为二线治疗方案治疗晚期复发难治性三阴性乳腺癌患者的中位PFS为4.0个月,与作为二线以上治疗方案的3.0个月比较,差异无统计学意义(P﹥0.05)。阿帕替尼联合依托泊苷治疗2个部位转移三阴性乳腺癌患者的中位PFS为4.0个月,与治疗2个以上部位转移患者的7.0个月比较,差异无统计学意义(P﹥0.05)。10例三阴性乳腺癌患者最常见治疗相关不良反应为中性粒细胞减少,发生率为50.0%,不良反应以1~2级为主,仅发生1例3~4级不良反应,经对症治疗后好转,无治疗相关死亡。结论甲磺酸阿帕替尼联合口服依托泊苷化疗对晚期复发难治性三阴性乳腺癌有一定疗效,不良反应可控。     

Association between progression-free survival and metal stent patency in patients with advanced pancreatic cancer

BackgroundChemotherapy reportedly affects the patency of self-expandable metal stents (SEMSs) in patients with cancer. However, knowledge regarding the association between SEMS patency and progression-free survival (PFS) remains limited. This study aimed to assess PFS and SEMS patency in patients with advanced pancreatic cancer.MethodsBetween January 2012 and June 2021, 74 patients with locally advanced or metastatic pancreatic cancer (MPC) were enrolled in the study. Patients received gemcitabine plus nab-paclitaxel (GnP) or fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) as initial chemotherapy and SEMS within 1 month before or after the initial chemotherapy. Longer PFS was defined as PFS ≥7 months.ResultsThis study enrolled 38 male patients (51.4%); the mean age was 66.2 [95% confidence interval (CI), 63.7–68.6] years. Of the patients, 46 (62.2%) had MPC and 58 (78.4%) received FOLFIRINOX as the initial chemotherapy. Of the patients, 61 (82.4%) underwent endoscopic SEMS insertion. The median stent patency and PFS were 6.9 [interquartile range (IQR), 4.5–12.9] and 6.4 (IQR, 4.2–12.5) months, respectively; the median overall survival (OS) was 10.5 (IQR, 6.7–16.5) months. Of the clinical parameters assessed using multivariate analysis, shorter PFS [PFS <7 months; hazard ratio (HR), 2.117; 95% CI, 1.020–4.393; P=0.044] and metastatic cancer (HR, 2.414; 95% CI, 1.159–5.018; P=0.019) were found to be associated with shorter SEMS patency. The median SEMS patency in patients with longer PFS and those with shorter PFS was 14.3 and 7.0 months (P=0.012), respectively, and that in patients with locally advanced cancer and those with metastatic cancer was 16.7 and 7.0 months (P=0.006), respectively. The coefficient of determination between stent patency and PFS was 0.624.ConclusionsSEMS patency may be associated with PFS in patients with advanced pancreatic cancer who receive GnP or FOLFIRINOX.     

Reactor-based boron neutron capture therapy for 44 cases of recurrent and refractory high-grade meningiomas with long-term follow-up

BackgroundHigh-grade meningioma (HGM) is difficult to treat, and recurrent HGM after radiotherapy has an especially poor prognosis. We retrospectively analyzed the cases of 44 consecutive patients with recurrent and refractory HGM who were treated by reactor-based boron neutron capture therapy (BNCT).MethodsIn 2005–2019, we treated 44 recurrent and refractory HGMs by reactor-based BNCT. We analyzed the patients’ tumor shrinkage, overall survival (OS) after initial diagnosis, OS after BNCT, progression-free survival (PFS) post-BNCT, and treatment failure patterns.ResultsThe median OS (mOS) after BNCT and mOS after initial diagnosis were 29.6 (95% CI: 16.1–40.4) and 98.4 (95% CI: 68.7–169.4) months, respectively. The median follow-up after BNCT was 26 (6.4–103) months. The grade 2 (20 cases) and 3 (24 cases) post-BNCT mOS values were 44.4 (95% CI: 27.4–not determined) and 21.55 (10.6–30.6) months, respectively (P = .0009). Follow-up images were obtained from 36 cases at >3 months post-BNCT; 35 showed tumor shrinkage during the observation period. The post-BNCT median PFS (mPFS) of 36 cases was 13.7 (95% CI: 8.3–28.6) months. The post-BNCT mPFS values in patients with grade 2 and 3 disease were 24.3 (95% CI: 9.8–not determined) and 9.4 (6.3–14.4) months, respectively (P = .0024). Local recurrence was observed in only 22.2% of cases. These results showed good local tumor control and prolonged survival for recurrent HGM cases.ConclusionsMost of these cases had relatively large tumor volumes. The proportion of grade 3 patients was extremely high. Our patients thus seemed to have poor prognoses. Nevertheless, reactor-based BNCT exerted relatively good local control and favorable survival for recurrent and refractory HGMs.     

阿帕替尼治疗难治性鼻咽癌的疗效和生存分析

  目的  评价阿帕替尼治疗难治性鼻咽癌的疗效及安全性并探索预后不良因素。  方法  回顾性分析2016年9月至2019年4月郑州大学第一附属医院接受阿帕替尼治疗66例难治性鼻咽癌患者资料,采用Kaplan-Meier法及Cox模型分析疗效及影响生存的相关因素。  结果  阿帕替尼治疗难治性鼻咽癌的客观缓解率为33.33%,疾病控制率为54.55%。中位无进展生存时间（progres?sion-free survival time,PFS）为7个月（95%CI:2.816~11.184）,中位总生存时间（overall survival,OS）为20个月（95%CI:11.496~28.504）。评价66例患者不良反应,最常见的不良反应为蛋白尿40.90%（27/66）、高血压45.45%（30/66）、手足综合征37.88%（25/66）,无4级不良反应发生;Cox单因素分析显示乳酸脱氢酶水平是PFS的影响因素,WHO病理类型是OS的影响因素。  结论  难治性鼻咽癌应用阿帕替尼治疗可能具有一定疗效,不良反应可控制,对于依从性好、无其他有效治疗方案的难治性鼻咽癌患者可考虑选择,但仍需大样本前瞻性研究证实。      

联合应用阿帕替尼在不可切除晚期胃癌转化治疗中的研究

  目的   探讨在不可切除晚期胃癌转化治疗中服用阿帕替尼的安全性及有效性。   方法   回顾性分析2017年3月至2018年6月天津医科大学肿瘤医院收治的33例晚期胃癌服用阿帕替尼转化治疗病例。合并腹膜转移或卵巢转移组，予以阿帕替尼+紫杉醇+S1方案（紫杉醇:50 mg/m2 iv，20 mg/m2 ip，d1，d8，q3w；S1:60 mg，bid，d1~d14；阿帕替尼:500 mg，qd），非腹膜转移或卵巢转移组，予以阿帕替尼+SOX方案化疗（奥沙利铂130 mg/m2；S1:60 mg，bid，d1~d14；阿帕替尼:500 mg，qd），经多学科联合会诊（multiple disciplinary team，MDT）后评估为可根治手术的患者停用1个周期阿帕替尼后行手术治疗。   结果   经转化治疗后，33例患者中部分缓解（partial response，PR）21例，疾病进展（progressive disease，PD）8例，客观缓解率（objective response rate，ORR）为75.7%。22例患者转化后行手术治疗，R0手术切除率63.6%，术中清扫淋巴结（57.0±15.6）枚，手术时间（212.0±44.8）min，术中出血（164±46）mL，术后住院时间（13.0±2.7）d。手术组中位无进展生存期（median progression free survival，mPFS）为10.5个月，中位总生存期（median overall survival，mOS）为16.5个月，未手术组mPFS为2.5个月，mOS为5.5个月。   结论   晚期胃癌转化治疗中联合抗血管生成药物阿帕替尼可以获得较高的R0切除率，且安全可靠。      

Quaternary cytoreductive surgery in ovarian cancer: does surgical effort still matter?

Background:

To evaluate surgical outcome and survival benefit after quaternary cytoreduction (QC) in epithelial ovarian cancer (EOC) relapse.

Methods:

We systematically evaluated all consecutive patients undergoing QC in our institution over a 12-year period (October 2000–January 2012). All relevant surgical and clinical outcome parameters were systematically assessed.

Results:

Forty-nine EOC patients (median age: 57; range: 28–76) underwent QC; in a median of 16 months (range:2–142) after previous chemotherapy. The majority of the patients had an initial FIGO stage III (67.3%), peritoneal carcinomatosis (77.6%) and no ascites (67.3%). At QC, patients presented following tumour pattern: lower abdomen 85.7% middle abdomen 79.6% and upper abdomen 42.9%. Median duration of surgery was 292 min (range: a total macroscopic tumour clearance could be achieved. Rates of major operative morbidity and 30-day mortality were 28.6% and 2%, respectively.Mean follow-up from QC was 18.41 months (95% confidence interval (CI):12.64–24.18) and mean overall survival (OS) 23.05 months (95% CI: 15.5–30.6). Mean OS for patients without vs any tumour residuals was 43 months (95% CI: 26.4–59.5) vs 13.4 months (95% CI: 7.42–19.4); P=0.001. Mean OS for patients who received postoperative chemotherapy (n=18; 36.7%) vs those who did not was 40.5 months (95% CI: 27.4–53.6) vs 12.03 months (95% CI: 5.9–18.18); P<0.001.Multivariate analysis indentified multifocal tumour dissemination to be of predictive significance for incomplete tumour resection, higher operative morbidity and lower survival, while systemic chemotherapy subsequent to QC had a protective significant impact on OS. No prognostic impact had ascites, platinum resistance, high grading and advanced age.

Conclusion:

Even in this highly advanced setting of the third EOC relapse, maximal therapeutic effort combining optimal surgery and chemotherapy appear to significantly prolong survival in a selected patients ‘group''.     

Safety and Efficacy of Drug-eluting Microspheres Chemoembolization under Cone Beam Computed Tomography Control in Patients with Early and Intermediate Stage Hepatocellular Carcinoma

BackgroundDrug-eluting microsphere transarterial chemoembolization (DEM-TACE) is the standard of care in patients with intermediate-stage hepatocellular carcinoma and ensures targeted and controlled cytotoxic and ischemic effects. Proper patient selection and optimized treatment techniques are associated with longer median survival. The aim of this single-institution retrospective study was to evaluate safety and efficacy of DEM-TACE under cone beam computed tomography (CBCT) control in patients with early and intermediate stage hepatocellular carcinoma.Patients and methodsA total of 144 patients (mean age 67.9 ± 8.0 years, 127 males and 17 females) between February 2010 and December 2018 were studied. Microparticles of different dimensions according to two manufacturers (diameter of 70–150 μm, 100–300 μm or 300–500 μm and 40-μm, 75-μm or 100-μm) were used and loaded with 50–150 mg of doxorubicin. The objective tumour response according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), the time to progression, adverse events and overall survival were (OS) evaluated.ResultsIn total, 452 procedures were performed (median, 3 per patient). Four (0.9% of all procedures) major complications were noted. Postembolization syndrome occurred after 35% of procedures. At the first imaging follow-up 2–3 months after first treatment, 91% of patients achieved an objective response. The median time to progression was 10.2 months (95% CI: 8.3-12.1 months). OS rates at 1, 2, 3, 4, and 5 years were 85%, 53%, 33%, 20% and 14%, respectively. The median survival time was 25.8 months (95% CI: 22.1–29.5 months).ConclusionsDEM-TACE under CBCT control in patients with early and intermediate stage hepatocellular carcinoma is a safe and effective method of treatment with high objective tumour response and survival rates.Key words: hepatocellular carcinoma, drug-eluting microspheres, doxorubicin, transarterial chemoembolization, cone beam computed tomography, safety, efficacy     

A Pilot Study of Apatinib as Third-Line Treatment in Patients With Heavily Treated Metastatic Colorectal Cancer

Background

Antiangiogenic therapy has shown improved clinical outcome in metastatic colorectal cancer (mCRC). After the failure of standard treatments, regorafenib and TAS-102 would be recommended for patients with mCRC, however, they have not been approved in China during this study period.

The Rethinking Clinical Trials (REaCT) Program. A Canadian-Led Pragmatic Trials Program: Strategies for Integrating Knowledge Users into Trial Design

We reviewed patient and health care provider (HCP) surveys performed through the REaCT program. The REaCT team has performed 15 patient surveys (2298 respondents) and 13 HCP surveys (1033 respondents) that have addressed a broad range of topics in breast cancer management. Over time, the proportion of surveys distributed by paper/regular mail has fallen, with electronic distribution now the norm. For the patient surveys, the median duration of the surveys was 3 months (IQR 2.5–7 months) and the median response rate was 84% (IQR 80–91.7%). For the HCP surveys, the median survey duration was 3 months (IQR 1.75–4 months), and the median response rate, where available, was 28% (IQR 21.2–49%). The survey data have so far led to: 10 systematic reviews, 6 peer-reviewed grant applications and 19 clinical trials. Knowledge users should be an essential component of clinical research. The REaCT program has integrated surveys as a standard step of their trials process. The COVID-19 pandemic and reduced face-to-face interactions with patients in the clinic as well as the continued importance of social media highlight the need for alternative means of distributing and responding to surveys.     

Pseudoprogression after high-dose busulfan-thiotepa with autologous stem cell transplantation and radiation therapy in children with brain tumors: Impact on survival

Children with a brain tumor treated with high-dose busulfan-thiotepa with autologous stem cell transplantation (ASCT) and radiation therapy (RT) often experience radiographic changes during follow-up. The purpose of the study was to identify the incidence, time course, risk factors, and clinical outcome of this complication. From May 1988 through May 2007, 110 patients (median age, 3.6 years; range, 1 month to 15.3 years) with a brain tumor had received 1 course of high-dose busulfan-thiotepa with stem cell rescue, followed or preceded by RT as part of their treatment. All MRI follow-up examinations were systematically reviewed. Twenty-three patients (21%) developed neuroradiological abnormalities at a median time of 9.2 months (range, 5.6–17.3 months) after ASCT. All contrast-enhancing lesions appeared in patients who had received RT after ASCT and were localized inside the 50–55Gy isodoses. They disappeared in 14 of 23 patients after a median time of 8 months (range, 3–17 months), leaving microcalcifications in some cases. The presence of MRI abnormalities was an independent prognostic factor for overall survival in the multivariate analysis (hazard ratio, 0.12; 95% confidence interval [CI], 0.04–0.33), with a 5-year overall survival rate of 84% among patients with MRI abnormalities (95% CI, 62–94), compared with 27% (95% CI, 19–37) among those without lesions. MRI-detectable pseudoprogression is a common early finding in children treated with high-dose busulfan-thiotepa followed by radiation therapy and is correlated with a better outcome.     

Efficacy and tolerability of bendamustine,bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study

Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with ⩽4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1–2 prior therapies and 33% were refractory to the last treatment. The response rate⩾partial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.     

The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis

BackgroundPatients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population.MethodsArticles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2−) MBC; pooled overall estimates for incidence were calculated using random effects models.Results937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2− MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0–34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5–40.6), and 15% among patients with HR+/HER2− MBC (median follow-up: 33.0 months, IQR: 31.9–36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10–0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09–0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03–0.08) for patients with HR+/HER2− MBC.ConclusionThere is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.