T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitors and the synthetic cytotoxic retinoid fenretinide have achieved durable clinical responses in T-cell lymphomas as single agents, and patients who failed prior HDAC inhibitor treatment have responded to fenretinide. We have previously shown fenretinide synergized with the class I HDAC inhibitor romidepsin in preclinical models of TCLMs. There exist some key differences between...
Breast cancer is one of the most common cancers endangering women’s health. SRY-related high-mobility-group box 6 (SOX6) is associated with many cancers, though its role has not been reported in breast cancer. Here, we aimed to explore the expression and function of SOX6 in breast cancer. On the basis of the analysis of SOX6 in The Cancer Genome Atlas, Cancer Cell Line Encyclopedia and Genotype-Tissue Expression databases, we revealed that SOX6 was downregulated in breast cancer, and we verified...
Approximately 50% of melanomas are characterized by BRAF mutation (V600E in 90% of cases), that predicts more aggressive behaviour. This mutation is the target of dabrafenib, an anti-BRAF tyrosine-kinase inhibitor (TKI), that together with trametinib, anti-MEK TKI, is approved for first-line treatment of metastatic melanoma due to significant benefit in overall and progression-free survival. Most common treatment-related adverse events are pyrexia, chills, fatigue, rash, nausea, vomiting, and diarrhoea....
The epidermal growth factor receptor (EGFR) signaling is frequently activated in lung cancer. In our previous study, a new class of compounds containing pyrido[3,4-d]pyrimidine scaffold with an acrylamide moiety was designed as irreversible EGFR-tyrosine kinase inhibitors to overcome acquired EGFR-T790M resistance. In this study, we selected the most promising compound Z25h to further investigate its effects and the underlying mechanism against non-small cell lung adenocarcinoma cells in vitro. Four...
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Abstract Background TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination...
Abstract Background This prospective study investigated the feasibility, toxicity, and oncologic outcomes of definitive radiotherapy (RT) consisting of whole pelvic radiotherapy with no central shielding (noCS-WPRT) and CT-based intracavitary brachytherapy (ICBT) in Japanese patients with cervical cancer. Methods Patients with cervical...
Abstract Background The indications for neoadjuvant chemotherapy (NAC) in resectable colorectal liver metastases (CRLMs) remain unclear. Tumor burden score (TBS) is a prognostic tool based on tumor size and number of tumors. However, its utility in the NAC setting for initially resectable CRLM has never been investigated. Methods TBS is a distance...
Abstract Background Local recurrence is the most difficult postoperative challenge and the leading cause of death in patients with retroperitoneal liposarcoma (RLPS). We aimed to establish a postoperative nomogram exclusively focused on RLPS for predicting local recurrence-free survival (LRFS). Methods A cohort of 124 patients after surgical resection...
Abstract Background Worldwide, there has been a growing interest in oncofertility issues. In 2017, the Japanese Society of Clinical Oncology published clinical practice guidelines for fertility preservation (FP) in cancer patients. We conducted a questionnaire survey to explore the FP practices among hematologists before the publication of this guideline. Methods ...
Abstract Background Constipation is a common side effect of opioid therapy. An observational study of opioid-induced constipation (OIC) in Japanese patients with cancer (OIC-J) included 212 patients with various tumor types. This post hoc analysis of OIC-J evaluated a subgroup of patients with gastrointestinal (GI) cancer. Methods Patients were aged ≥ 20 years,...
Abstract Background This study compared real-world outcomes of metastatic renal-cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors or nivolumab plus ipilimumab. Methods Using the International mRCC Database Consortium (IMDC), we retrospectively evaluated intermediate- and poor-risk mRCC patients who were treated with nivolumab plus...
Abstract Background Individuals with advanced gastric cancer (AGC) who present with severe peritoneal metastasis (SPM) have poor prognosis. This study aimed to evaluate efficacy and safety of second-line treatment for patients with such condition. Methods This retrospective study included patients receiving taxane-based second-line chemotherapy at...
Abstract Background It is important to recognize regional and racial differences in drug efficacy and safety when performing multi-regional clinical trials (MRCTs). To understand regional differences, we compared the efficacy results in Japanese patients and the overall population in the MRCTs of anticancer drugs. Methods All new approvals of oncology...
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Targeting of poly(ADP-ribose)polymerase (PARP) enzymes has emerged as an effective therapeutic strategy to selectively target cancer cells with deficiencies in homologous recombination (HR) signaling. Currently used to treat BRCA-mutated cancers, PARP inhibitors (PARPi) have demonstrated improved outcome in various cancer types as single agents. Ongoing efforts have seen the exploitation of PARPi combination therapies, boosting patient responses as a result of drug synergisms. Despite great successes...
Purpose: The RET proto-oncogene encodes a receptor tyrosine kinase which is activated by gene fusion in 1-2% of non-small cell lung cancers (NSCLC) and rarely in other cancer types. Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating RET gene fusions and mutations. Molecular mechanisms of acquired resistance to selpercatinib are poorly understood. Patients and Methods: We studied patients treated on the first-in-human...
Background: Despite the expansion of immune checkpoint inhibitor (ICI) indications, the relationship between ICI dose and toxicity or response is not well established. To understand this correlation, we performed a meta-analysis of ICI trials that used dose-escalation. Methods: We searched PubMed and abstracts presented at (inter)national meetings for trials using FDA-approved ICIs. The reported rates of grade 3-5 adverse events (G3-5AEs), immune-related adverse events (irAEs), and response were...
Purpose: Women with hormone-receptor-positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late recurrence risk. Experimental Design: In a secondary analysis of Study of Letrozole Extension (SOLE) trial, a case-cohort-like sampling selected 598 primary breast cancer for targeted next-generation sequencing (NGS) analysis of gene mutations and copy number gains (CNG). Correlations...
Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematological malignancies. Experimental Design: We describe the natural history of NBS, including cancer incidence, risk of death and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency. Results: Among two hundred forty-one (n=241) patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were...
Purpose: To evaluate somatic mutations, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in the PDAC patients with pathological complete response (pCR) to neoadjuvant therapy (NAT) and find their associations with outcome. Design: Thirty-six PDAC patients with pCR were identified from 2009 to 2017. Macro-dissection was performed on resected specimens to isolate DNA from 332 regions of interest including fibrosis, normal duct, normal parenchyma, and undefined ductal cells (UDCs). Cell-free...
T cell-engagers are a rapidly evolving novel group of treatments that have in common the concurrent engagement of a T cell-surface molecule and a tumoral cell antigen. Bispecific antibodies and genetically engineered adoptive cell therapies, as chimeric antigen receptor or T cell receptor T cells, have similarities and differences among their mechanisms of action, toxicity profiles, and resistance pathways. Nevertheless, the success observed in the hematological field has not been obtained with solid...
Purpose: Stabilization of the transcription factor NRF2 through genomic alterations in KEAP1 and NFE2L2 occurs in a quarter of lung adenocarcinoma (LUAD) and a third of lung squamous (LUSC) patients. In LUAD, KEAP1 loss often co-occurs with STK11 loss and KRAS activating alterations. Despite its prevalence, the impact of NRF activation on tumor progression and patient outcomes is not fully defined. Experimental Design: We model NRF2 activation, STK11 loss and KRAS activation in vivo using novel genetically...
Chronic graft-versus-host disease (GVHD) following hematopoietic cell transplantation is associated with reduced relapse incidence in patients with leukemias. This impact has been investigated in myelodysplastic syndrome, showing a beneficial impact of limited chronic GVHD on transplant outcomes in a cohort of more than 3,000 patients.
Purpose:We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment.Experimental Design:Plasma circulating tumor DNA (ctDNA) was quantified in 125 samples collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- (n = 32) or second-line (n = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy (n = 66). An external validation...
Purpose: Recent data has shown that single fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiation therapy (RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses. Experimental design: Therefore, we aimed at simultaneously investigating the anti-tumor efficacy...
Uveal melanoma (UM) is a rare cancer in adults but its treatment is one of the clinical unmet needs in the melanoma field. Metastatic disease develops in approximately 50% of patients and is associated with poor survival due to the lack of effective treatment options. It provides a paradigm for cancers that show evidence of aberrant G-protein coupled receptor signaling, tumor dormancy, liver-selective metastatic tropism and are associated with the loss of the BAP1 tumor suppressor. At the Melanoma...
On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. This was the first new molecular entity evaluated under Project Orbis, an FDA Oncology Center of Excellence initiative which supports concurrent review of oncology drugs by multiple...
Purpose:Preclinical and early clinical data suggested that combining histone deacetylase (HDAC) and mTOR inhibitors can synergistically inhibit Hodgkin lymphoma.Patients and Methods:During the dose-escalation study (ClinicalTrials.gov number: NCT01087554) with the HDAC inhibitor vorinostat and the mTOR inhibitor sirolimus (V+S), a patient with Hodgkin lymphoma refractory to nine prior therapies demonstrated a partial response (PR) lasting for 18.5 months, which promoted additional enrollment of patients...
Purpose.Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). Experimental Design. Here, we developed a novel digital droplet PCR (ddPCR) assay, that incorporates features to...
Background RNA-sequencing-based subtyping of pancreatic ductal adenocarcinoma (PDAC) has been reported by multiple research groups, each using different methodologies and patient cohorts. 'Classical' and 'basal-like' PDAC subtypes are associated with survival differences, with basal-like tumors associated with worse prognosis. We amalgamated various PDAC subtyping tools to evaluate the potential of such tools to be reliable in clinical practice. Methods Sequencing data for 574 PDAC tumors was...
The recent impressive clinical responses to antibody-based immunotherapy have prompted the identification of clinically relevant tumor antigens that can serve as targets in solid tumors. Among them, B7-H3, a member of the B7 ligand family, represents an attractive target for antibody-based immunotherapy: it is overexpressed on differentiated malignant cells and cancer initiating cells, with limited heterogeneity, and high frequency (60% of 25,000 tumor samples) in many different cancer types, but...
Purpose: Approximately 30% of patients with chronic lymphocytic leukemia (CLL) can be grouped into subsets with stereotyped B cell receptor immunoglobulin (BcR IG) displaying remarkable similarity in the heavy complementarity-determining region 3 (VH CDR3). Here, we investigated whether the consensus VH CDR3 sequences from CLL stereotyped subsets can be exploited for immunotherapy approaches. Experimental Design: Immunogenic epitopes from the consensus VH CDR3 sequence of the clinically aggressive...
Coronavirus disease 2019 (COVID-19) is a novel infectious disease that has spread world-wide. In the United States, COVID-19 disproportionately affects racial and ethnic minorities, particularly African Americans, with an observed two-fold higher rate for hospitalization and greater than two-fold higher rate for death as compared to White Americans. The disparity seen with COVID-19 is consistent with patterns of disparities observed for cancer; it is well-documented that 5-year survival rates for...
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Abstract Objective For patients presenting with recurrent, inoperable, or metastatic sarcoma, treatment options are limited. The inherent low radiosensitivity of many sarcoma histologies can limit effectiveness of palliative radiation for these patients. Stereotactic radiation (SBRT) allows escalation of biologically effective dose while limiting dose to normal tissues, which is particularly important in previously irradiated tissues....
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Background The recent mobile technology advancements, such as the development of applications (apps) for mobile phones and tablets, can assist in the development of low-cost platforms to monitor therapeutic adherence or complications, providing easily accessible information or guidelines in self-care focused on the care recipient. Objective The aim of this study was to gather scientific evidence about the efficacy of the use of mobile apps during chemotherapy treatments. Methods A systematic...
Background Flushing and locking of totally implantable venous access devices (TIVADs) is recommended to maintain their patency when not in use. Although manufacturers’ recommendations indicate monthly access for TIVAD maintenance, there is a tendency in real life to prolong this interval. Objectives To assess the effectiveness of prolonged versus short flushing and locking intervals to prevent TIVAD occlusions in adults with cancer. Methods A systematic search was carried out in MEDLINE,...
Background Religious and spiritual beliefs including forgiveness are an important aspect of cancer survivorship; however, the relationship between forgiveness and health is not well understood. Objective The aim of this study was to conduct a scoping review that examines and maps the current research regarding relationships between forgiveness and health outcomes in individuals with cancer. Methods We searched 5 electronic databases using key search terms related to forgiveness and cancer....
Background Mindfulness-based interventions (MBIs) have demonstrated benefits for adults with chronic illness and are becoming increasingly popular among children and young people. Mindfulness-based interventions could have benefits for young people with cancer throughout the treatment journey, through to survivorship. Objective The aim was to review intervention studies about MBI used with young people with cancer between the ages of 10 and 29 years. Methods Six electronic databases...
Background Poor sleep, nausea, psychological distress, and a lowered quality of life are common during radiotherapy for cancer. There is a lack of studies on the relationship between radiotherapy-induced nausea and sleep. This longitudinal study analyzes data from 196 patients who underwent pelvic-abdominal radiotherapy for cancer. Objective The aim of this study was to investigate sleep parameters weekly before, during, and after radiotherapy in relation to nausea and other patient characteristics,...
Background Cervical and uterine cancers are common in women. Diagnosis and treatment of these cancers can lead to significant issues with body image, sexuality, and sexual functioning. A comprehensive review can improve understanding of these 3 concepts, in turn enhancing identification and management. Objectives To (1) present the qualitative, descriptive, and correlational research literature surrounding body image, sexuality, and sexual functioning in women with uterine and cervical cancer;...
Background Lung cancer (LC) is the most common cause of death in cancer patients. The influence of cardiorespiratory fitness (CF) and physical activity (PA) on LC mortality has not previously been investigated. Objective The aim of this study was to investigate through a meta-analysis the associations among CF, PA, walking speed, or leisure activity, and LC mortality and all-cause mortality. Methods MEDLINE and EMBASE were used to select relevant studies from January 2000 to August 2019....
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Background Approximately 60% of the more than 3.8 million breast cancer survivors (BCSs) living in the United States are 60 years or older. Breast cancer survivors experience many symptoms including cognitive dysfunction; however, little is known regarding how age affects these symptoms. Objective This integrative review was conducted to synthesize the literature on cognitive dysfunction in older BCSs. The purpose was to (1) describe the prevalence of objective and subjective cognitive dysfunctions...
Background Early diagnosis of lung cancer is key to improving the long-term prognosis for many individuals. Still, utilization rates of lung cancer screening (LCS) remain low. Objective To investigate the association between worry about future health issues of smoking and intention to undergo recommended LCS with low-dose computed tomography (LDCT) within the next 3 months. Methods A cross-sectional online survey was conducted using the Qualtrics Panel to recruit adult smokers between...
Background Chemotherapy-induced alopecia (CIA) is a common adverse effect among patients undergoing chemotherapy. Patients experiencing CIA suffer psychological distress and even refuse or discontinue chemotherapy. A variety of interventions have been applied to prevent CIA. However, the best intervention option remains unknown. Objective To evaluate and determine the comparative effects of all available interventions for preventing CIA. Methods A comprehensive literature search of four...
Background Colorectal cancer is one of the most common cancers worldwide. Although colostomies are necessary for disease treatment, they unavoidably affect patient quality of life (QOL), especially in the early postoperative stage. Objective The aim of this study was to investigate the dynamic changes and factors influencing QOL among Chinese patients with permanent colostomy. Methods We investigated 74 patients before discharge and at 1 and 3 months after discharge. Instruments included...
Background A culture of serious overwork in South Korea, more than other developed countries, may impact symptoms and quality of life (QOL) experienced by Korean breast cancer survivors (BCS). Objectives The aim of this study was to examine health-related QOL and influencing factors in BCS in Seoul, Korea, who have recovered from treatment for at least 1 year and returned to normal life and work. Methods In a cross-sectional study, 199 BCS completed a self-administered questionnaire...
Background Mothers parenting children with leukemia face innumerable challenges in meeting their own personal needs, as well as the needs of their ill child. Objective To explore the lived experiences of Omani mothers who are parenting children with leukemia, using interpretative phenomenological analysis design. Methods Data were collected from 10 mothers who were parenting children with leukemia who shared their experiences through a face-to-face recorded interview. Data were analyzed...
Background Trans and gender-diverse people with a cervix experience difficulties accessing cervical cancer screening because of structural, interpersonal, and individual barriers. Objective The aim of this study was to explore issues with cervical cancer screening participation, awareness, and healthcare provider recommendation for trans and gender-diverse people. Methods A national Australian survey was conducted in 2018 to 2019. Participants included 196 trans and gender-diverse people...
Background Patients undergoing hematopoietic stem cell transplantation (HSCT) require extensive care, and their caregivers were previously found to experience high levels of caregiver’s burden. However, the current status of HSCT patient caregiver burden in Suzhou, China, is still unknown. Objective To investigate the current status of caregiver burden among family caregivers of HSCT patients from Suzhou, China, and explore the related factors of caregiver burden. Methods This cross-sectional...
Background Black women face cervical cancer disparities with higher rates of morbidity and mortality compared with White women. Identifying predictors of Papanicolaou (Pap) testing is a first step to decrease morbidity and mortality from cervical cancer, with barriers and self-efficacy being constructs that should be related to Pap testing adherence. Although barriers and self-efficacy scales have been developed, they have not been validated in Black women for Pap testing. Objective The purpose...
Background Numerous women with breast cancer (BC) exhibit early menopausal symptoms after undergoing cancer treatments. Medications that control menopausal symptoms can cause severe side effects and are contraindicated for patients with BC. Therefore, complementary and alternative medicines should be used. This study investigates the use of cognitive-behavioral therapy (CBT) for patients with menopausal symptoms after BC treatment. Objective A systematic review was conducted to determine...
Background Patients with breast cancer usually experience depression, anxiety, stress, fatigue, pain, poor sleep quality, and low quality of life after their cancer treatment. Some studies used mindfulness-based stress reduction (MBSR) interventions for reducing these symptoms; however, the results are conflicting. Objective This study evaluated the clinical efficacy of MBSR interventions in the short term. Methods Five databases were searched from their inception to April 2020. We included...
Background Patients with colorectal cancer (CRC) experience multiple symptoms. Resilience is a positive health outcome that can assist patients to face and adapt to their disease. Objective The purpose of this study was to evaluate a proposed resilience model for patients with CRC. Methods Patients (n = 416), who were given a diagnosis of stage Ι to III CRC within the past 5 years, were recruited from 2 medical centers in Northern Taiwan. Symptom Severity Scale, Fatigue Symptom Inventory,...
Background Evidence suggests that digital health interventions are feasible and acceptable in pediatric cancer survivors. Efforts to synthesize user experiences, however, are limited. Objective The aim of this study was to systematically identify, appraise, and synthesize qualitative evidence on the user experiences of pediatric cancer survivors participating in digital health interventions. Methods We searched 4 databases to identify studies with qualitative data of the digital health...
Background Dyadic coping may play an important role in promoting marital adjustment in couples with breast cancer. However, few studies have explored dyadic coping and its predictors in couples with breast cancer. Objective To assess the dyadic coping level of Chinese couples with breast cancer and identify its predictors and explore the actor and partner effects of marital adjustment on dyadic coping. Methods Chinese couples (n = 114) with breast cancer participated in a cross-sectional...
Background Physical activity (PA) has been shown to improve total mortality and colorectal-specific mortality risk; however, colorectal cancer (CRC) survivors have lower rates of PA compared with survivors with other types of cancers. Objective To examine the effect of PA interventions on CRC survivors. Methods A systematic review and meta-analysis were conducted to identify randomized controlled trials that met the inclusion criteria, which included an intervention designed to increase...
Background Little research has examined the moderating influence of posttraumatic growth (PTG) on the relationship between social support and quality of life. Objectives This study examined the relationship between social support and quality of life by the level of PTG in colorectal cancer patients with ostomies. Methods Using a cross-sectional design, colorectal cancer patients with ostomies (n = 140) were recruited using convenience sampling. The City of Hope Quality of Life–Ostomy,...
Background Fatigue and sleep disturbance are common co-occurring symptoms in patients receiving chemotherapy. While the results from meta-analyses support the use of exercise to decrease the severity of these symptoms, information is needed on patients’ “real world experiences” with the use of exercise. Objective The aims of this study were to determine distribution of patients who did and did not exercise on a regular basis and evaluate for differences in demographic and clinical characteristics,...
Background Adolescents and young adults (AYAs) experience treatment nonadherence rates as high as 60%, which can increase the risk of cancer relapse. Involvement of AYAs in treatment decisions might support adherence to medical treatment. Objective The aim of this study was to explore the involvement of AYAs, aged 15 to 20 years, in cancer treatment decision making (TDM). Methods Using interpretive focused ethnography, we conducted interviews with 16 AYAs (total of 31 interviews) receiving...
Background Lung cancer patients with advanced disease and no active treatment options currently face frequent follow-up visits to outpatient clinics, associated with significant anxiety, time commitment, and costs. Visits also place considerable strain on the health system. Evidence from other cancers and chronic health conditions suggests virtual or remote follow-up can lead to higher patient satisfaction without negatively impacting health outcomes such as survival time. Objective The aim...
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