Prognostic Value and Association of Sarcopenia and Systemic Inflammation for Patients with Gastric Cancer Following Radical Gastrectomy

3 months ago
AbstractObjective.The aim of this study was to investigate the prognostic value of preoperative sarcopenia and systemic inflammation for patients with resectable gastric cancer (GC) and develop a novel and powerful prognostic score based on these factors.Materials and Methods.Patients with GC who underwent radical gastrectomy between December 2009 and December 2013 were included. A multivariate Cox regression analysis was performed to identify the prognostic factors. A novel prognostic score (SLMR) was developed based on preoperative sarcopenia and the lymphocyte‐monocyte ratio (LMR), and its prognostic value was evaluated.Results.In total, 1,167 patients with resectable GC were included in the study. On multivariate analysis, preoperative sarcopenia and the LMR were shown to be independent prognostic factors (both p < .001). A low LMR was an independent predictor from sarcopenia (p < .001). Based on preoperative sarcopenia and the LMR, we established the SLMR. An elevated SLMR was associated with older age, higher ASA scores, larger tumor size, advanced stages, and vascular invasion (all p < .05). Multivariate analysis revealed that the SLMR was a significant independent predictor (p < .001). We incorporated the SLMR into a prognostic model that included tumor size and TNM stage and generated a nomogram, which accurately predicted 3‐ and 5‐year survival for GC patients.Conclusion.Preoperative systemic inflammation is significantly associated with sarcopenia. The LMR combined with sarcopenia could enhance prognostication for patients with GC who underwent radical gastrectomy.Implications for Practice.Increasing evidence shows that sarcopenia and systemic inflammation are closely associated with the prognosis of malignant tumors, and it is essential for clinicians to understand the relationship and combined prognostic effects of these factors for gastric cancer (GC). Based on a large data set, this study found that preoperative systemic inflammation was significantly associated with sarcopenia in GC, and combining these two predictors could effectively predict the prognosis and complement the prognostic value of the TNM staging system. These findings may lead to the development of new therapeutic avenues to improve cancer outcomes.
Jian-Xian Lin, Jun-Peng Lin, Jian-Wei Xie, Jia-bin Wang, Jun Lu, Qi-Yue Chen, Long-long Cao, Mi Lin, Ruhong Tu, Chao-Hui Zheng, Chang-Ming Huang, Ping Li

Personalizing Precision Oncology Clinical Trials in Latin America: An Expert Panel on Challenges and Opportunities

3 months ago
AbstractThe participation of patients in precision oncology trials needs to fulfill molecular‐based selection criteria. This strongly limits accrual, and as a consequence, screening successes have decreased, costs have increased, and fewer subjects are enrolled. To achieve narrowed targets, studies have been forced to be multicenter and multinational to reach a larger pool of candidates. However, this globalization faces many challenges, as, for example, in the case of precision oncology trials. These trials have a complex structure that is dependent upon a high‐tech infrastructure and knowledge in a dynamic environment. Given the movement of precision clinical cancer research to regions other than Europe and the U.S., it is important to evaluate the feasibility of performing such trials in lower‐middle‐ and low‐income countries. Here we critically discuss the advantages of conducting precision oncology clinical trials in Latin America and make suggestions on how to overcome the main challenges involved.Implications for Practice.Precision clinical trials in oncology are studies that require candidates to have tumors with specific molecular alterations, which are considered the target for the trial experimental therapy. Because many molecular alterations are rare, fewer patients are enrolled. This has led to trials being forced to be multicenter and multinational, including trials in Latin America. This article discusses the challenges and opportunities to conduct precision oncology trials in Latin America, aiming to help sponsors and investigators to solve complex issues that ultimately lead to more of such trials being run in the region, potentially benefiting more Latin American patients with cancer.
Roberto Jun Arai, Rodrigo Santa Cruz Guindalini, Andrea Sabina Llera, Juan Manoel O'Connor, Bettina Muller, Mauricio Lema, Helano C. Freitas, Tannia Soria, Lucia Delgado, Denis Landaverde, Paola Montenegro, Rachel P. Riechelmann

Anlotinib Versus Sunitinib as First‐Line Treatment for Metastatic Renal Cell Carcinoma: A Randomized Phase II Clinical Trial

3 months ago
AbstractBackground.Anlotinib is a tyrosine kinase inhibitor inhibiting angiogenesis. This multicenter, randomized phase II trial aimed to investigate the efficacy and safety of anlotinib in comparison with sunitinib as first‐line treatment for patients with metastatic renal cell carcinoma (mRCC).Materials and Methods.Patients with mRCC from 13 clinical centers were randomly assigned in a 2:1 ratio to receive anlotinib (n = 90) or sunitinib (n = 43). Anlotinib was given orally at a dose of 12 mg once daily (2 weeks on/1 week off), and sunitinib was given orally at 50 mg once daily (4 weeks on/2 weeks off). The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.Results.The median PFS was similar with anlotinib and sunitinib (17.5 vs. 16.6 months, p > .05). The median OS (30.9 vs. 30.5 months, p > .05), ORR (30.3% vs. 27.9%), and 6‐week DCR (97.8% vs. 93.0%) were similar in the two groups. Adverse events (AEs) of grade 3 or 4 were significantly less frequent with anlotinib than with sunitinib (28.9% vs. 55.8%, p < .01), especially in terms of thrombocytopenia and neutropenia. AEs occurring at a lower frequency with anlotinib were hand‐foot syndrome, eyelid edema, hair depigmentation, skin yellowing, neutropenia, thrombocytopenia, and anemia. The incidence of serious AEs was lower with anlotinib than with sunitinib.Conclusion.The clinical efficacy of anlotinib was similar to that of sunitinib as the first‐line treatment for mRCC, but with a more favorable safety profile.Implications for Practice.This study evaluated the efficacy and safety of anlotinib for the first‐line treatment of metastatic renal cell carcinoma. Anlotinib, which was developed independently in China, is a new tyrosine kinase inhibitor inhibiting multiple kinases involved in angiogenesis and tumor proliferation. Results indicated that the efficacy of anlotinib is comparable to and the safety is better than that of sunitinib.
Ai-Ping Zhou, Yuxian Bai, Yan Song, Hong Luo, Xiu-Bao Ren, Xiuwen Wang, Benkang Shi, Cheng Fu, Ying Cheng, Jiyan Liu, Shukui Qin, Jun Li, Hanzhong Li, Xianzhong Bai, Dingwei Ye, Jinwan Wang, Jianhui Ma

Genomic Signature of Driver Genes Identified by Target Next‐Generation Sequencing in Chinese Non‐Small Cell Lung Cancer

3 months ago
AbstractBackground.Non‐small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer‐related death. Over the past few decades, genomic alterations of cancer driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next‐generation sequencing (NGS) assay.Materials and Methods.A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26–89), and 83% cases were adenocarcinoma. NGS‐based genomic profiling of major lung cancer‐related genes was performed on formalin‐fixed paraffin‐embedded tumor samples and matched blood.Results.Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor (EGFR), ALK, ERBB2, MET, BRAF, RET, and ROS1. Twenty‐seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty‐six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR‐mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. In patients <40 years of age, the ALK‐positive percentage was up to 28.2%. Moreover, 3.2% of ALK‐positive patients harbored multi ALK rearrangements, and seven new partner genes were identified.Conclusion.More unique features of cancer driver genes in Chinese NSCLC were identified by next‐generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC.Implications for Practice.Molecular targeted therapy is now the standard first‐line treatment for patients with advanced non‐small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next‐generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR‐mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK‐positive patients harbored multi ALK rearrangement, and seven new partner genes were identified.
Shiwang Wen, Lei Dai, Lei Wang, Wen&#x0237;ian Wang, Duoguang Wu, Kefeng Wang, Zhanghai He, Aodi Wang, Hui Chen, Peng Zhang, Xiaowei Dong, Yu-An Dong, Kai Wang, Ming Yao, Minghui Wang

Diagnosis and Management of Immune Checkpoint Inhibitor‐Associated Renal Toxicity: Illustrative Case and Review

3 months ago
AbstractImmune checkpoint inhibitors (ICIs) are monoclonal antibodies directed at negative regulatory components on T cells, such as cytotoxic T lymphocyte‐associated antigen 4, programmed cell death‐1 (PD‐1), and its ligand, programmed cell death ligand‐1. ICIs initate antitumor immunity; however, these agents are associated with immune‐related adverse events (irAEs) that may affect a variety of organs. Renal irAEs most commonly present with asymptomatic acute kidney injury (AKI), which is often detected by routine laboratory testing. The severity of AKI associated with irAEs ranges from mild (grade 1–2) to severe (grade 3–4). It is often challenging to diagnose because this group of patients often have multiple reasons to have AKI (dehydration, sepsis, or nephrotoxic medication exposure). We present an illustrative case of a 60‐year‐old man with metastatic melanoma who presented with AKI during treatment with nivolumab and review the literature to address frequently asked questions concerning the diagnosis and management of renal irAEs in patients with advanced cancer. Importantly, most patients will recover completely, and some may tolerate a rechallenge of ICI therapy, with prompt and effective treatment.Key Points. Renal immune‐related adverse events (irAEs) are less frequently reported than other irAEs; however, it is possible that available data underestimate their true incidence because of missed diagnoses and under‐reporting. Although severe renal irAEs are more easily detected, smaller rises in creatinine may not be appreciated or may be attributed to other causes, because the differential diagnosis of acute kidney injury (AKI) in patients with cancer is broad.Baseline creatinine should be established prior to beginning immune checkpoint inhibitorss (ICIs), and it should be monitored with every cycle. If a patient develops AKI, the ICI should be held while the evaluation is pursued. A thorough workup of suspected renal irAEs must exclude other potential causes of AKI such as infection, dehydration, urinary tract obstruction, and nephrotoxin exposure.Acute kidney injury after ICI therapy does not appear to be more common in patients with baseline estimated glomerular filtration rate <60 mL per min per 1.73 m. One particular concern, however, is that those with baseline renal disease have less “renal reserve,” and repeated AKI events may push a patient closer to end‐stage renal disease. Thus, clinicians must exert caution when rechallenging patients with pre‐existing renal disease with ICI therapy in the event of a prior AKI from ICI‐related allergic interstitial nephritis.
Meghan E. Sise, Harish Seethapathy, Kerry L. Reynolds

Cutaneous Toxicity after Chemoradiotherapy and PD‐L1 Inhibition in Two Patients with Esophageal Adenocarcinoma: More than Meets the Eye

3 months ago
AbstractDermatological adverse events have frequently been reported after immune checkpoint inhibition. When an adverse event occurs during combination of immune checkpoint inhibition with chemotherapy, the question arises which agent is responsible. Unnecessary withdrawal of either chemotherapy or immunotherapy could lead to suboptimal treatment outcomes. Here we report on two patients who developed a cutaneous drug reaction with fever during treatment with paclitaxel, carboplatin, radiotherapy, and PD‐L1 inhibition (atezolizumab) for resectable esophageal adenocarcinoma. In the first case atezolizumab was suspected, and in the second paclitaxel. We discuss the clinical manifestation, treatment, and pathophysiology underlying both cases.
Tom van den Ende, Stef P. Menting, Carmen A. Ambarus, Martijn G.H. van Oijen, Hanneke W.M. van Laarhoven

Accelerated Risk of Premature Ischemic Stroke in 5‐Year Survivors of Nasopharyngeal Carcinoma

3 months ago
AbstractBackground.Research on cancer survivorship associated with nasopharyngeal carcinoma (NPC) is rare. We aimed to elucidate the risk of ischemic stroke in 5‐year survivors of NPC following radiotherapy (RT) or concurrent chemoradiation therapy (CCRT).Subjects, Materials, and Methods.NPC survivors, defined as those who survived longer than 5 years after diagnosis, were identified and matched at a 1:5 ratio with normal controls from the Longitudinal Health Insurance Database 2005 of Taiwan. The stratified Cox regression models were used to access the risk of ischemic stroke, with adjustment for age, treatment modality, comorbidities, and socioeconomic characteristics.Results.From 2000 to 2005, a total of 3,016 NPC survivors who had received RT (n = 959) or CCRT (n = 2,057) and 15,080 controls were matched for age, sex, income, and urbanization level. The risk of ischemic stroke was significantly higher in the NPC survivor cohort than in the control cohort. Stroke was positively related to death. Moreover, the age onset of stroke for NPC survivors was 10 years earlier than that for the general population.Conclusion.Not only was the stroke risk in NPC survivors higher than that in the general population, but the onset age was also 10 years earlier. Future survivorship care should include ischemic stroke as a late complication, for its proper prevention and management.Implications for Practice.Nasopharyngeal carcinoma (NPC) is endemic in Taiwan, and its 5‐year survival is 65.2%. With the increased 5‐year cancer survivors, survivorship has become an important issue. However, research on NPC survivorship is very rare. To the authors’ knowledge, this is the first population‐based study on long‐term NPC survivors. This study's results indicated that not only was the risk of ischemic stroke in NPC survivors at least triple that of the general population, but the onset age was also 10 years earlier. These results may provide solid evidence that survivorship care guidelines should include stroke as a late complication in 5‐year NPC survivors, for its proper prevention and management.
Min-Chi Chen, Feng-Che Kuan, Shiang-Fu Huang, Chang-Hsien Lu, Ping-Tsung Chen, Cih-En Huang, Ting-Yao Wang, Chih-Cheng Chen, Kuan-Der Lee

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia

3 months ago
AbstractOn February 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product gemtuzumab ozogamicin (Mylotarg; Pfizer, New York City, NY), intended for the treatment of acute myeloid leukemia. Mylotarg was designated as an orphan medicinal product on October 18, 2000. The applicant for this medicinal product was Pfizer Limited (marketing authorization now held by Pfizer Europe MA EEIG).The demonstrated benefit with Mylotarg is improvement in event‐free survival. This has been shown in the pivotal ALFA‐0701 (MF‐3) study. In addition, an individual patient data meta‐analysis from five randomized controlled trials (3,325 patients) showed that the addition of Mylotarg significantly reduced the risk of relapse (odds ratio [OR] 0.81; 95% CI: 0.73–0.90; p = .0001), and improved overall survival at 5 years (OR 0.90; 95% CI: 0.82–0.98; p = .01) [Lancet Oncol 2014;15:986–996]. The most common (>30%) side effects of Mylotarg when used together with daunorubicin and cytarabine are hemorrhage and infection.The full indication is as follows: “Mylotarg is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33‐positive acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL).”The objective of this article is to summarize the scientific review done by the CHMP of the application leading to regulatory approval in the European Union. The full scientific assessment report and product information, including the Summary of Product Characteristics, are available on the European Medicines Agency website (www.ema.europa.eu).Implications for Practice.This article reflects the scientific assessment of Mylotarg (gemtuzumab ozogamicin; Pfizer, New York City, NY) use for the treatment of acute myeloid leukemia based on important contributions from the rapporteur and co‐rapporteur assessment teams, Committee for Medicinal Products for Human Use members, and additional experts following the application for a marketing authorization from the company. It's a unique opportunity to look at the data from a regulatory point of view and the importance of assessing the benefit‐risk.
Sahra Ali, Helen-Marie Dunmore, Dominik Karres, Justin L. Hay, Tomas Salmonsson, Christian Gisselbrecht, Sinan B. Sarac, Ole W. B&#x0237;errum, Doris Hovgaard, Yolanda Barbachano, Nithyanandan Nagercoil, Francesco Pignatti

Managing Pulmonary Toxicities Associated with Immunotherapy: A Case Discussion

3 months ago
AbstractImmunotherapy has changed the field of oncology around the world with the approval of immune checkpoint inhibitors for a number of tumor types over the last 5 years. However, immune‐mediated adverse events can be challenging and difficult to treat, with one of the most dire consequences being immune‐mediated pneumonitis.Key Points. Rapid intervention and aggressive management for grade 3 or greater pneumonitisSlow taper of steroids and also recommend pneumocystis carinii pneumonia prophylaxisMonitor carefully for a pneumonitis flare with steroid taper, which can occur in the absence of resuming anti‐programmed cell death protein 1 (PD‐1) [1], and do not resume anti‐PD‐1 therapy until completely off steroids and no clinical or radiologic evidence of recurrenceConsider observation without anti‐PD‐1 resumption—in this case, durable response was maintained even without resuming anti‐PD‐1 therapy.
Vanessa A. Reed, Naiyer Rizvi

Mismatch Repair Status of Gastric Cancer and Its Association with the Local and Systemic Immune Response

3 months ago
AbstractBackground.Microsatellite instability (MSI)‐high (MSI‐H) colorectal cancer is known to be associated with increased tumor‐infiltrating lymphocytes (TILs), elevated host systemic immune response, and a favorable prognosis. In gastric cancer, however, MSI status has rarely been evaluated in the context of TILs and systemic immune response.Materials and Methods.We evaluated data for 345 patients with gastric cancer who underwent gastrectomy with MSI typing. The numbers of TILs were counted after immunohistochemical staining with anti‐CD3, CD4, CD8, forkhead box P3 (Foxp3), and granzyme B to quantify the subsets of TILs. To evaluate the systemic immune response, the differential white blood cell count and prognostic nutritional index (PNI) were obtained.Results.Of the 345 patients, 57 demonstrated MSI‐H tumors and 288 demonstrated non‐MSI‐H tumors. MSI‐H tumors carried significantly higher densities of CD8+ T cells, Foxp3+ T cells, and granzyme B+ T cells and a higher ratio of Foxp3/CD4 and granzyme B/CD8. The prognostic impact of TILs differed between patients with MSI‐H tumors and those with non‐MSI‐H tumors. The TIL subsets were not found to be significant prognostic factors for recurrence‐free survival (RFS) or overall survival (OS) in the MSI‐H tumor group. In the non‐MSI‐H tumor group, multivariate analysis showed that stage, PNI, and CD4+ T cells were independent prognostic factors for RFS, and stage, PNI, and the Foxp3/CD4 ratio were independent prognostic factors for OS.Conclusions.The association between systemic/local immune response and prognosis differed according to MSI status. Different tumor characteristics and prognoses according to MSI status could be associated with the immunogenicity caused by microsatellite instability and subsequent host immune response.Implications for Practice.This study demonstrates that the density of each subset of tumor‐infiltrating lymphocytes (TILs) differed between microsatellite instability (MSI)‐high and non‐MSI‐high tumors. Moreover, the prognostic effect of the preoperative systemic immune response status and TILs differed between the MSI‐high (MSI‐H) and non‐MSI‐H tumor groups. The present study may help to identify the mechanisms of cancer progression and develop treatment strategies for MSI‐high gastric cancer.
Su-Jin Shin, Sang Yong Kim, Yoon Young Choi, Taeil Son, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Chung-Gyu Park, Hyoung-Il Kim

Adapalene Gel 0.1% Versus Placebo as Prophylaxis for Anti‐Epidermal Growth Factor Receptor‐Induced Acne‐Like Rash: A Randomized Left‐Right Comparative Evaluation (APPEARANCE)

3 months ago
AbstractLessons Learned. The results of the APPEARANCE trial indicate that adapalene does not prevent acne‐like rash over placebo when added to topical moisturizer and oral minocycline but instead may have a detrimental effect. Therefore, adapalene is not recommended as prophylaxis against acne‐like rash induced by anti‐epidermal growth factor receptor therapies.Given that acne‐like rash was completely controlled with placebo in approximately half of patients, predictive measures to identify patients needing intensive prophylaxis are required.Background.Anti‐epidermal growth factor receptor (EGFR) therapies are frequently associated with acne‐like rash. To evaluate the prophylactic efficacy of adapalene, a topical retinoid used as first‐line therapy for acne vulgaris, we conducted a randomized, placebo‐controlled, evaluator‐blinded, left‐right comparative trial.Methods.Patients with non‐small cell lung, colorectal, or head and neck cancer scheduled to receive anti‐EGFR therapies were randomly assigned to once‐daily adapalene application on one side of the face, with placebo on the other side. All patients had topical moisturizer coapplied to both sides of the face, and received oral minocycline. The primary endpoint was the difference in total facial lesion count of acne‐like rash at 4 weeks. Secondary endpoints included complete control rate (CCR) of acne‐like rash (≤5 facial lesions) and global skin assessment (Investigator's Global Assessment [IGA] scale, grade 0–4) at 4 weeks. Two blinded dermatologists independently evaluated the endpoints from photographs.Results.A total of 36 patients were enrolled, of whom 26 were evaluable. Adapalene treatment was associated with a greater lesion count than placebo at 4 weeks, although the difference was not statistically significant (mean, 12.6 vs. 9.8, p = .12). All four patients with a difference >10 in lesion count between face sides had a greater count on the adapalene‐treated side. No significant differences were observed in CCR of acne‐like rash (54% vs. 50%) or IGA scale (mean grade, 1.9 vs. 1.7) between the adapalene and placebo sides.Conclusion.Adapalene is not recommended as prophylaxis against acne‐like rash induced by anti‐EGFR therapies.
Naoko Chayahara, Toru Mukohara, Motoko Tachihara, Yoshimi Fujishima, Atsushi Fukunaga, Ken Washio, Masatsugu Yamamoto, Kyosuke Nakata, Kazuyuki Kobayashi, Kei Takenaka, Masanori Toyoda, Naomi Kiyota, Kazutoshi Tobimatsu, Hisayo Doi, Naomi Mizuta, Naho…

Inequalities in Financial Distress, Symptoms, and Quality of Life Among Patients with Advanced Cancer in France and the U.S.

3 months 1 week ago
AbstractBackground.Financial distress (FD) is common among patients with advanced cancer. Our purpose was to compare the frequency and intensity of FD and its associations with symptom distress and quality of life (QOL) in these patients in France and the U.S.Materials and Methods.In this secondary analysis of two cross‐sectional studies, we assessed data on 292 patients who received cancer care at a public hospital or a comprehensive cancer center in France (143 patients) or the U.S. (149 patients). Outpatients and hospitalized patients over 18 years of age with advanced lung or breast or colorectal or prostate cancer were included. Diagnosed cognitive disorder was considered a noninclusion criterion. Advanced cancer included relapse or metastasis or locally advanced cancer or at least a second‐line chemotherapy regimen. Patients self‐rated FD and assessed symptoms, psychosocial distress, and QOL on validated questionnaires.Results.The average patient age was 59 years, and 144 (49%) were female. FD and high intensity were reported more frequently in U.S. patients than in French (respectively 129 [88%] vs. 74 [52%], p < .001; 100 [98%] vs. 48 [34%], p < .001,). QOL was rated higher by the U.S. patients than by the French (69 [SD, 18] vs. 63 [SD, 18], p = .003). French patients had more psychological symptoms such as anxiety (8 [SD, 4] vs. 6 [SD, 5], p = .008). Associations were found between FD and U.S. residence, FD and single status (0.907, p = .023), and FD and metastasis (1.538, p = .036). In contrast, negative associations were found between FD and older age (−0.052, p = .003) and FD and France residence (−3.376, p = .001).Conclusion.Regardless of health care system, FD is frequent in patients with advanced cancer. U.S. patients were more likely to have FD than French patients but reported better QOL. Further research should focus on factors contributing to FD and opportunities for remediation.Implications for Practice.Suffering is experienced in any component of the lives of patients with a life‐threatening illness. Financial distress (FD) is one of the least explored cancer‐related symptoms, and there are limited studies describing its impact on this frail population. This study highlights the high frequency and severity of FD in patients with advanced cancer in the U.S. and France as well as its impact on their physical and emotional symptoms and their quality of life in these different health care systems. It is necessary for all health care providers to explore and evaluate the presence of FD in patients living with life‐threatening illnesses.
Cecile Barbaret, Marvin O. Delgado-Guay, Stephane Sanchez, Christelle Brosse, Murielle Ruer, Lea Monsarrat, Patrick Michaud, Anne Marie Schott, Eduardo Bruera, Marilene Filbet

A Single‐Arm, Phase II Study of Apatinib in Refractory Metastatic Colorectal Cancer

3 months 1 week ago
AbstractLessons Learned.Patients with metastatic colorectal cancer with good performance status or no liver metastasis could benefit from apatinib.Circulating tumor DNA abundance may be a predictor in serial monitoring of tumor load.Background.Apatinib, an oral vascular endothelial growth factor (VEGF) receptor‐2 inhibitor, has been approved as third‐line treatment for metastatic gastric cancer in China. The aim of this study was to evaluate the efficacy and safety of apatinib, in the treatment of patients with refractory metastatic colorectal cancer after failure of two or more lines of chemotherapy.Methods.In this open‐label, single‐arm, phase II study, patients with histological documentation of adenocarcinoma of the colon or rectum were eligible if they had received at least two prior regimens of standard therapies including fluoropyrimidine, oxaliplatin, and irinotecan. These patients were treated with apatinib in a daily dose of 500 mg, p.o., in the third‐line or higher setting. Capture sequencing was dynamically performed to identify somatic variants in circulating tumor DNA (ctDNA) with a panel of 1,021 cancer‐related genes. The primary endpoint was progression‐free survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Interim analysis was applied as predefined.Results.From June 1, 2016 to December 31, 2017, 26 patients were enrolled. The median PFS of the whole group was 3.9 months (95% confidence interval [CI]: 2.1–5.9). The median overall survival (OS) was 7.9 months (95% CI: 4.6–10.1+). Patients with performance status (PS) 0–1 had longer PFS than those with PS 2 (4.17 months vs. 1.93 months, p = .0014). Patients without liver metastasis also had longer PFS than those who had live metastasis (5.87 months vs. 3.33 months, p = .0274). The common side effects of apatinib were hypertension, hand‐foot syndrome, proteinuria, and diarrhea. The incidence of grade 3–4 hypertension, hand‐foot syndrome, proteinuria, and diarrhea was 76.92%, 11.54%, 73.08%, and 23.08%, respectively. All of the patients received dose reduction because of adverse effect. Results of capture sequencing showed APC, TP53, and KRAS were most frequently mutant genes. ctDNA abundance increased before the radiographic assessment in ten patients.Conclusion.Apatinib monotherapy showed promising efficiency for patients with refractory colorectal cancer, especially in patients with PS 0–1 or no liver metastasis. ctDNA abundance may be a predictor in serial monitoring of tumor load.
Xiaofeng Chen, Tianzhu Qiu, Yingwei Zhu, Jing Sun, Ping Li, Biao Wang, Peinan Lin, Xiaomin Cai, Xiao Han, Fengjiao Zhao, Yongqian Shu, Lianpeng Chang, Hua Jiang, Yanhong Gu

Inhibition of Serotonin Synthesis May Have Antitumor Activity? Long‐Term Efficacy in a Patient with Gastrointestinal Neuroendocrine Tumor

3 months 1 week ago
AbstractIn this article, we propose, based on a clinical case, the potential antitumor effect related to the inhibition of serotonin in neuroendocrine tumors (NETs). Currently, the only drug that exists for the symptomatic treatment of carcinoid syndrome refractory to somatostatin analogues is telotristat, based on its pivotal study, the TELESTAR trial. Based on the existing preclinical rationale, it seems that the inhibition of serotonin may have an antitumoral role in NETs. Briefly, serotonin may act as an autocrine growth factor of NETs, and it may also play an immunomodulatory role by enhancing macrophage polarization to an immunotolerant M2 phenotype. To our knowledge, this rationale for the possible antitumor effect of serotonin in NETs has not yet been published in the literature.
Javier Molina-Cerrillo, Enrique Grande, Teresa Alonso-Gordoa

What Is Important When Making Treatment Decisions in Metastatic Breast Cancer? A Qualitative Analysis of Decision‐Making in Patients and Oncologists

3 months 1 week ago
AbstractBackground.Metastatic breast cancer (MBC) is an ideal environment for shared decision‐making because of the large number of guideline‐based treatment options with similar efficacy but different toxicity profiles. This qualitative analysis describes patient and provider factors that influence decision‐making in treatment of MBC.Materials and Methods.Patients and community oncologists completed in‐person interviews. Academic medical oncologists participated in focus groups. Interviews and focus groups were audio‐recorded, transcribed, and analyzed using NVivo. Using an a priori model based on the Ottawa Framework, two independent coders analyzed transcripts using a constant comparative method. Major themes and exemplary quotes were extracted.Results.Participants included 20 patients with MBC, 6 community oncologists, and 5 academic oncologists. Analysis of patient interviews revealed a decision‐making process characterized by the following themes: decision‐making style, contextual factors, and preferences. Patient preference subthemes include treatment efficacy, physical side effects of treatment, emotional side effects of treatment, cognitive side effects of treatment, cost and financial toxicity, salience of cutting‐edge treatment options (clinical trial or newly approved medication), treatment logistics and convenience, personal and family responsibilities, treatment impact on daily activities, participation in self‐defining endeavors, attending important events, and pursuing important goals. Physician decisions emphasized drug‐specific characteristics (treatment efficacy, side effects, cost) rather than patient preferences, which might impact treatment choice.Conclusion.Although both patients with MBC and oncologists considered treatment characteristics when making decisions, patients’ considerations were broader than oncologists’, incorporating contextual factors such as the innovative value of the treatment and life responsibilities. Differences in perspectives between patients and oncologists suggests the value of tools to facilitate systematic communication of preferences in the setting of MBC.Implications for Practice.Both patients with metastatic breast cancer (MBC) and oncologists emphasized importance of efficacy and physical side effects when making treatment decisions. However, other patient considerations for making treatment decisions were broader, incorporating contextual factors such as the logistics of treatments, personal and family responsibilities, and ability to attend important events. Furthermore, individual patients varied substantially in priorities that they want considered in treatment decisions. Differences in perspectives between patients and oncologists suggest the value of tools to facilitate systematic elicitation of preferences and communication of those preferences to oncologists for integration into decision‐making in MBC.
Gabrielle B. Rocque, Aysha Rasool, Beverly R. Williams, Audrey S. Wallace, Soumya J. Niran&#x0237;an, Karina I. Halilova, Yasemin E. Turkman, Stacey A. Ingram, Courtney P. Williams, Andres Forero-Torres, Tom Smith, Smita Bhatia, Sara J. Knight

Mutation Profile of Resected EGFR‐Mutated Lung Adenocarcinoma by Next‐Generation Sequencing

3 months 1 week ago
AbstractBackground.The efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co‐mutations in resected epidermal growth factor receptor (EGFR)‐mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment.Materials and Methods.Mutation profiling of 416 cancer‐relevant genes was conducted for 139 resected stage I–IIIa lung ADCs with EGFR mutations using targeted next‐generation sequencing. Co‐mutation profiles were systematically analyzed.Results.Rare EGFR alterations other than exon 19 deletion and L858R, such as L861Q (∼3%) and G719A (∼2%), were identified at low frequencies. Approximately 10% of patients had mutations in EGFR exon 20 that could confer resistance to first‐generation TKIs. Ninety‐one percent of patients harbored at least one co‐mutation in addition to the major EGFR mutation. TP53 was the top mutated gene and was found more frequently mutated at later stage. Markedly, NF1 mutations were found only in stage II–III ADCs. Conversely, RB1 mutations were more frequent in stage I ADCs, whereas APC mutations were observed exclusively in this group. Thirty‐four percent of patients with EGFR TKI‐sensitizing mutations had genetic alterations involving EGFR downstream effectors or bypass pathways that could affect the response to EGFR TKIs, such as PIK3CA, BRCA1, and NOTCH1.Conclusion.Operable lung ADCs with EGFR TKI‐sensitizing mutations are associated with a high proportion of co‐mutations. Mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy.Implications for Practice.The efficacy of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer harboring EGFR mutation after surgical resection is still under debate. Next‐generation sequencing of 416 cancer‐relevant genes in 139 resected lung cancers revealed the co‐mutational landscape with background EGFR mutation. Notably, the study identified potential EGFR TKI‐resistant mutations in 34.71% of patients with a drug‐sensitizing EGFR mutation and who were naive in terms of targeted therapy. A comprehensive mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy for these patients.
Ze-Rui Zhao, Yao-Bin Lin, Calvin S.H. Ng, Rong Zhang, Xue Wu, Qiuxiang Ou, Wendan Chen, Wen-Jie Zhou, Yong-Bin Lin, Xiao-Dong Su, Yang W. Shao, Hao Long

Pretreatment Hemoglobin as an Independent Prognostic Factor in Primary Central Nervous System Lymphomas

3 months 1 week ago
AbstractBackground.Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma. Despite established clinical prognostic scoring such as that of the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Extranodal Lymphoma Study Group, outcome prediction needs to be improved. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in PCNSL. We sought to assess the association between hematological parameters and overall survival (OS) in patients with PCNSL.Methods.Pretreatment blood tests were analyzed in patients with newly diagnosed PCNSL (n = 182), and we divided the analysis into two cohorts (A and B, both n = 91). OS was evaluated using the Cox proportional hazards models and log‐rank test. Furthermore, the accuracy of the different multivariate models was assessed by Harrell's concordance index (C‐index).Results.Using prechemotherapy blood tests, anemia was found in 38 patients (41.8%) in cohort A and 34 patients (37.4%) in cohort B. In univariate analysis, anemia (<12 g/dL in women and <13 g/dL in men) was significantly associated with OS. None of the other blood tests parameters (neutrophils, lymphocyte, or platelets counts) or their ratios (neutrophil‐to‐lymphocyte ratio and neutrophil‐to‐platelets ratio) were associated with OS. In multivariate analysis, after adjusting by MSKCC score, anemia remained an independent prognostic factor. Interestingly, the prediction accuracy of OS using Harrell's C‐index was similar using anemia or MSKCC (mean C‐index, 0.6) and was increased to 0.67 when combining anemia and MSKCC.Conclusion.The presence of anemia was associated with poor prognosis in both cohorts of PCNSL. Validation of these results and biologic role of hemoglobin levels in PCNSL requires further investigation.Implications for Practice.The prediction of the outcome of primary central nervous system lymphoma (PCNSL) using the most frequently used scores (i.e., Memorial Sloan Kettering Cancer Center [MSKCC] or International Extranodal Lymphoma Study Group) needs to be improved. We analyzed a large cohort of PCNSL to dissect the potential prognostic value of blood tests in this rare entity. We found anemia as an independent predictor for overall survival in PCNSL. Interestingly, the accuracy to predict PCNSL outcome was improved using hemoglobin level. This improvement was additional to the currently used clinical score (i.e., MSKCC). Finally, none of the other blood tests parameters or their ratios had a prognostic impact in this study.
My Le, Ytel Garcilazo, Maria-Jose Ibanez-Julia, Nadia Younan, Louis Royer-Perron, Marion Benazra, Karima Mokhtari, Caroline Houillier, Khe Hoang-Xuan, Agusti Alentorn
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