Do cancer patients fully understand clinical trial participation? A pilot study to assess informed consent and patient expectations

Background. Accepted practices of informed consent often result in suboptimal patient understanding of research studies.Methods. This pilot study aimed to assess trial-specific tailored materials, compared to a widely used generic booklet about clinical trials, randomly assigned to 118 candidates for cancer clinical trials. Study outcomes were: satisfaction with decision-making; satisfaction with materials; and subjective understanding of the clinical trial.Results. There were no major differences between groups. Participants rated tailored materials higher as a useful reference.Conclusions. Trial-specific materials hold utility for reference during clinical trials. Studies of informed consent are feasible, although important factors limit research.     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.     

Soft tissue sarcomas of adults: state of the translational science.

Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.     

Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225.

PURPOSE: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. PATIENTS AND METHODS: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. RESULTS: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. CONCLUSION: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.     

Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred.

PURPOSE: Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs. PATIENTS AND METHODS: Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTs and cutaneous lesions underwent physical examination, imaging studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques. RESULTS: In addition to evidence of multiple GISTs, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T --> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY-14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTs. cDNA array profiling demonstrated clustering with sporadic GISTs, and expression of GIST markers comparable to sporadic GISTs. CONCLUSION: These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTs. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes.     

GD2抗体达妥昔单抗β治疗神经母细胞瘤的临床应用专家共识（2021年版）

神经母细胞瘤(neuroblastoma,NB)是儿童最常见的颅外实体肿瘤,临床表现及预后具有高度异质性。低危患儿预后较好,高危患儿即使接受化疗、放疗、手术、造血干细胞移植等多种方法的综合治疗,长期存活率仍不足50%。探索潜在的治疗靶点对于提高高危患者的生存率具有重要意义。双唾液酸神经节苷脂抗原GD2在NB细胞高表达,达妥昔单抗β可与NB细胞膜表面过表达的GD2特定靶点结合,触发抗体依赖性细胞介导的细胞毒性作用和补体依赖的细胞毒性效应,通过双重免疫机制而发挥抗肿瘤作用。通过总结国外多项关键临床研究,并结合在海南和天津医疗先行区的上市前初步应用经验,我们对达妥昔单抗β的安全性、有效性、适用人群及使用方法进行总结和推荐,提出本共识,旨在为临床医师提供指导与帮助。     

Challenges in the development of platelet growth factors: low expectations for low counts

Thrombocytopenia remains a significant clinical problem for which only symptomatic therapy, namely platelet transfusion, is available for management of acute events. Platelet transfusions are often complicated by febrile reactions, as well as the risk of transmission of infectious agents and the likelihood of alloimmunization, which then decreases the effectiveness of additional transfusion support. The availability of a hematopoietic cytokine that could reliably stimulate platelet recovery, analogous to the effect of granulocyte colony-stimulating factor on neutrophil recovery following chemotherapy, would greatly enhance supportive care in cancer and provide an effective therapy for a variety of diseases that cause thrombocytopenia. To identify such a thrombopoietic cytokine, studies initially focused on regulatory molecules that stimulates early multipotent hematopoietic progenitors, such as interleukin-1 and interleukin-6. Unfortunately, these cytokines had poor efficacy and significant toxicity in human testing. Recombinant human interleukin-11, an early-acting cytokine, has modest efficacy and clinically challenging toxicities, but in the absence of other active drugs, it has been licensed for prevention of severe chemotherapy-induced thrombocytopenia. Recent interest has focused on analogs of thrombopoietin, the endogenous regulator of thrombopoiesis, which have the potential for much greater efficacy with minimal toxicity due to the more specific targeting of megakaryocyte-specific signaling.