Cyclin E is frequently encoded by CCNE1 gene amplification in various malignancies. We reviewed the medical records of patients with solid tumors displaying CCNE1 amplification to determine the ...effect of this amplification for future therapeutic development. We reviewed the medical records of patients with advanced solid tumors harboring CCNE1 amplification who were seen at the phase I clinic between September 1, 2012, and December 31, 2019. Among 79 patients with solid tumors harboring CCNE1 amplification, 56 (71%) received phase 1 clinical trial therapy, 39 (49%) had 3 or more concurrent genomic aberrances, and 52 (66%) had a concurrent TP53 mutation. The median overall survival (OS) after patients' initial phase I visit was 8.9 months and after their initial metastasis diagnosis was 41.4 months. We identified four factors associated with poor risk: age < 45 years, body mass index ≥ 25 kg/m
, presence of the TP53 mutation, and elevated LDH > upper limit of normal. In patients treated with gene aberration-related therapy, anti-angiogenic therapy led to significantly longer OS after their initial phase I trial therapy than those who did not: 26 months versus 7.4 months, respectively (P = 0.04). This study provided preliminary evidence that CCNE1 amplification was associated with frequent TP53 mutation and aggressive clinical outcomes. Survival benefit was observed in patients who received antiangiogenic therapy and gene aberration-related treatment, supporting the future development of a personalized approach to combine gene aberration-related therapy with antiangiogenesis for the treatment of advanced malignancies harboring CCNE1 amplification.
Eating disorders and schizophrenia are both moderately to highly heritable and share significant genetic risk despite distinct diagnostic criteria. Large-scale family studies on the co-aggregation of ...these disorders are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of these disorders within the entire Swedish and Danish population. The proband cohort consisted of individuals born in Sweden (1977-2003) and Denmark (1984-2006) and still residing in their respective country at age six (N
= 2,535,191, N
= 1,382,367). Probands were linked to their biological parents, siblings, grandparents, uncles/aunts, and cousins. Diagnoses for anorexia nervosa (AN) and other eating disorders (OED: bulimia nervosa, binge-eating disorder, and eating disorder not otherwise specified) for probands and schizophrenia diagnoses for both probands and relatives were obtained. The likelihood of having schizophrenia in those with AN or OED and their relatives was compared with individuals without eating disorder diagnoses and their relatives. Probands with AN or OED were more likely to have schizophrenia than probands without these disorders. All relatives of probands with AN or OED (except parents and uncles/aunts of probands with AN) were at increased risk of schizophrenia. In general, the magnitude of odds ratios attenuated with decreasing genetic relatedness. These results suggest familial liability contributes to the association between eating disorders and schizophrenia. Clinicians should be mindful of this comorbid and co-aggregation pattern as it may influence case conceptualization and treatment decisions.
Lung adenocarcinoma which invades ovaries is very rare. However, with the increase of long-survival female lung cancer, more patients will suffer ovarian metastasis. On grounds of the paucity of ...reported cases, the clinicopathological features and treatment strategies remain unknown.
This patient was stage IV lung adenocarcinoma at first diagnosis. Following multiple-line systemic treatments, she experienced extensive pelvic metastasis. After debulking surgery and reevaluation about the drive genes, she was administered by targeted therapy. Up to now, the patient has shown no evidence of progression for 8 years after the initial diagnosis of primary lung cancer and 46 months after her ovarian metastasis.
The comprehensive treatment modality for the bilateral ovarian metastasis is effective in clinical course.
Background
IBM Watson for Oncology (WFO) provides physicians with evidence‐based treatment options. This study was designed to explore the concordance of the suggested therapeutic regimen for ...advanced non‐small cell lung (NSCLC) cancer patients between the updated version of WFO and physicians in our department, in order to reflect the differences of cancer treatment between China and the United States.
Methods
Retrospective data from 165 patients with advanced NSCLC from September 2014 to March 2018 were entered manually into WFO. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with the real treatment. Potential influenced factors were also analyzed.
Results
Overall, the treatment recommendations were concordant in 73.3% (121/165) of cases. When two alternative drugs such as icotinib and nedaplatin were included as “for consideration,” the total consistency could be elevated from 73.3% to 90.3%(149/165). The logistic regression analysis showed that gender (P = 0.096), ECOG (P = 0.0.502), smoking (P = 0.455), and pathology (P = 0.633) had no effect on consistency, but stages (P = 0.019), including stage ≤III (77.8%, 21/27) and stage IV (93.5%, 129/138) had significant effects on consistency.
Conclusions
In China, most of the treatment recommendations of WFO are consistent with the real world treatment. Factors such as patient preferences, prices, drug approval and medical insurance are also taken into consideration, and they ultimately affect the inconsistency. To be comprehensively and rapidly applied in China, localization needs to be accelerated by WFO.
Immune checkpoint inhibitor (ICI) has been proven to be a major breakthrough in patients with advanced non-small cell lung cancer. Up to now, neoadjuvant therapy using ICI are rare. However, in the ...context of cancer immunotherapy, neoadjuvant treatment may offer an extra advantage. In this review, we will disscuss the existing preclinical data and emerging clinical findings in the neoadjuvant setting and its potential mechanism of action. We will also highlight the potential damage and the questions that are required to be answered.
Hyperprogressive disease (HPD) is a novel pattern of progression caused by immune checkpoint inhibitors (ICIs). It is characterized by a dramatic tumor surge and is associated with poor clinical ...outcomes. Up to now, the definition of HPD is still controversial across various studies. Although it has been indicated that HPD has related to multiple clinicopathological features and genetic alterations, it is lack of biomarker to predict its occurrence, and the potential mechanism remains unknown. This review is to summarize current data on HPD specialized in the field of non-small cell lung cancer. And we expect to provide helpful clinical strategies for oncologists using ICIs. .
Vaccines have been used to fight and protect against infectious diseases for centuries. With the emergence of immunotherapy in cancer treatment, researchers began investigating vaccines that could be ...used against cancer, especially against tumors that are resistant to conservative chemotherapy, surgery, and radiotherapy. The Wilms' tumor 1 (WT1) protein is immunogenic, has been detected in almost all types of malignancies, and has played a significant role in prognosis and disease monitoring. In this article, we review recent developments in the treatment of various types of cancers with the WT1 cancer vaccine; we also discuss theoretic considerations of various therapeutic approaches, which were based on preclinical and clinical data.
已经证实免疫检查点抑制剂（immune checkpoint inhibitor, ICI）使多种肿瘤的治疗有了翻天覆地的变化。尽管治疗的有效性让人欣慰，但是这些治疗也造成了多样化的免疫治疗相关的不良反应（immune-related adverse events, irAEs）。重症肌无力（myasthenia gravis, ...MG）就是一种罕见且危及生命的irAE，通常在ICI治疗后急性发病并迅速进展。早期诊断和积极的治疗非常重要。在此，我们对近几年的相关文献进行了复习和整理，针对ICI-MG诊断和治疗相关的常见问题提供参考意见。 Immune checkpoint inhibitor (ICI) has been proven to be a major breakthrough in the treatment of various tumor types. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Myasthenia gravis (MG) is one of rare but life-threatening irAEs, with acute onset and rapid progression after ICI initiation. Early diagnosis and active treatment are crucial. Herein, we review recent literatures to provide guidance to frequently asked questions concerning the diagnosis and management of ICI-MG.
Background
Arginine depletion interferes with pyrimidine metabolism and DNA damage repair pathways. Preclinical data demonstrated that depletion of arginine by PEGylated arginine deiminase (ADI‐PEG ...20) enhanced liposomal doxorubicin (PLD) cytotoxicity in cancer cells with argininosuccinate synthase 1 (ASS1) deficiency. The objective of this study was to assess safety and tolerability of ADI‐PEG 20 and PLD in patients with metastatic solid tumors.
Methods
Patients with advanced ASS1‐deficient solid tumors were enrolled in this phase 1 trial of ADI‐PEG 20 and PLD following a 3 + 3 design. Eligible patients were given intravenous PLD biweekly and intramuscular (IM) ADI‐PEG 20 weekly. Toxicity and efficacy were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0) and Response Evaluation Criteria in Solid Tumors (version 1.1), respectively.
Results
Of 15 enrolled patients, 9 had metastatic HER2‐negative breast carcinoma. We observed no dose‐limiting toxicities or treatment‐related deaths. One patient safely received 880 mg/m2 PLD in this study and 240 mg/m2 doxorubicin previously. Treatment led to stable disease in 9 patients and was associated with a median progression‐free survival time of 3.95 months in 15 patients. Throughout the duration of treatment, decreased arginine and increased citrulline levels in peripheral blood remained significant in a majority of patients. We detected no induction of anti‐ADI‐PEG 20 antibodies by week 8 in one third of patients.
Conclusion
Concurrent IM injection of ADI‐PEG 20 at 36 mg/m2 weekly and intravenous infusion of PLD at 20 mg/m2 biweekly had an acceptable safety profile in patients with advanced ASS1‐deficient solid tumors. Further evaluation of this combination is under discussion.
This combination therapy with ADI‐PEG 20 and Doxil had a reversible and manageable toxicity profile, and patients tolerated the treatment. Tumor shrinkage and prolonged duration of therapy were observed in several patients.
PDF
