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Biomedicines Aug 2022Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated... (Review)
Review
Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient's preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost-benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.
PubMed: 36009592
DOI: 10.3390/biomedicines10082045 -
JCO Clinical Cancer Informatics Aug 2023Selection of appropriate adjuvant therapy to ultimately reduce the risk of breast cancer (BC) recurrence is a challenge for medical oncologists. Several automated risk... (Review)
Review
PURPOSE
Selection of appropriate adjuvant therapy to ultimately reduce the risk of breast cancer (BC) recurrence is a challenge for medical oncologists. Several automated risk prediction models have been developed using retrospective clinical data and have evolved significantly over the years in terms of predictors of recurrence, data usage, and predictive techniques (statistical/machine learning [ML]).
METHODS
Following PRISMA guidelines, we performed a systematic literature review of the aforementioned statistical and ML models published between January 2008 and December 2022 through searching five digital databases-PubMed, ScienceDirect, Scopus, Cochrane, and Web of Science. The comprehensive search yielded a total of 163 papers and after a screening process focusing on papers that dealt exclusively with statistical/ML methods, only 23 papers were deemed appropriate for further analysis. We benchmarked the studies on the basis of development, evaluation metrics, and validation strategy with an added emphasis on racial diversity of patients included in the studies.
RESULTS
In total, 30.4% of the included studies use statistical techniques, while 69.6% are ML-based. Among these, traditional ML models (support vector machines, decision tree, logistic regression, and naïve Bayes) are the most frequently used (26.1%) along with deep learning (26.1%). Deep learning and ensemble learning provide the most accurate predictions (AUC = 0.94 each).
CONCLUSION
ML-based prediction models exhibit outstanding performance, yet their practical applicability might be hindered by limited interpretability and reduced generalization. Moreover, predictive models for BC recurrence often focus on limited variables related to tumor, treatment, molecular, and clinical features. Imbalanced classes and the lack of open-source data sets impede model development and validation. Furthermore, existing models predominantly overlook African and Middle Eastern populations, as they are trained and validated mainly on Caucasian and Asian patients.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Bayes Theorem; Neoplasm Recurrence, Local; Machine Learning
PubMed: 37566789
DOI: 10.1200/CCI.23.00049 -
Respiration; International Review of... 2022Immune checkpoint inhibitors (ICIs) can lead to one of the common and quite serious immune-related adverse events (irAEs) in a real-world setting, namely, checkpoint... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune checkpoint inhibitors (ICIs) can lead to one of the common and quite serious immune-related adverse events (irAEs) in a real-world setting, namely, checkpoint inhibitor pneumonitis (CIP).
OBJECTIVE
We aimed to investigate the potential risk factors for CIP in cancer patients treated by ICIs and quantify the association.
METHODS
We conducted a systematic literature review in PubMed, EMBASE, and Web of Science from January 1, 2000, to March 20, 2022, with no study design restrictions. Studies evaluating the risk factors for CIP in cancer patients treated with ICIs-containing regimes were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for risk factors of CIP by using random-effect model. Heterogeneity was assessed by sensitivity analysis and subgroup analysis regarding CIP severity, geographical regions, cancer types, treatment regimes, and ICI types.
RESULTS
A total of 35 studies comprising 142,703 patients were eventually included. The incidence of grade I-V and grade III-V CIP in cancer patients was 0.16 (95% CI: 0.14-0.18) and 0.06 (95% CI: 0.05-0.08), respectively. When combining the adjusted ORs, the following risk factors were significantly associated with the development of CIP: squamous cell carcinoma (OR: 1.31, 95% CI: 1.18-1.45), previous thoracic radiotherapy (OR: 2.07, 95% CI: 1.34-3.19), preexisting radiation-induced pneumonitis (OR: 3.62, 95% CI: 1.53-8.58), preexisting respiratory disease (OR: 2.43, 95% CI: 1.45-4.07), preexisting interstitial lung disease (OR: 5.78, 95% CI: 3.08-10.85), preexisting ground glass attenuation (OR: 11.48, 95% CI: 1.13-116.74), preexisting honeycombing (OR: 6.11, 95% CI: 2.37-15.79), preexisting pulmonary emphysema (OR: 2.72, 95% CI: 1.00-7.36), use of pembrolizumab (OR: 2.89, 95% CI: 1.56-5.35, I2 = 0%), high PD-L1 expression (OR: 3.59, 95% CI: 1.23-10.50), and hypoalbuminemia (OR: 0.3, 95% CI: 0.14-0.64). When including the crude ORs, smoking history (OR: 1.39, 95% CI: 1.14-1.71), neutrophil-lymphocyte ratio (OR: 1.04, 95% CI: 1.01-1.08), and c-reactive protein (OR: 1.08, 95% CI: 1.01-1.16) were also risk factors for CIP.
CONCLUSION
Histological characteristics, specific previous lung diseases and treatment history, treatment regimen, PD-L1 expression level, and serological biomarkers are all closely associated with the development of CIP. These findings would be useful for oncologists to optimize the appropriate options of ICIs and close monitoring during immunotherapy treatments, particularly for patients identified as having a higher risk for CIP.
Topics: Humans; Antineoplastic Agents, Immunological; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Pneumonia; Risk Factors
PubMed: 36108598
DOI: 10.1159/000526141 -
Pediatric Blood & Cancer Sep 2022Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm, which occurs in children and adults, with a peak incidence in young adults. For the... (Review)
Review
Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm, which occurs in children and adults, with a peak incidence in young adults. For the majority of the patients, DTF is a chronic and symptomatic disease, which affects health-related quality of life. Systemic treatment regimens tend to differ for patients treated by pediatric oncologists compared to medical oncologists. This systematic review identified 14 clinical trials in children and adults with DTF. Tumor response and progression-free survival rates varied widely between studies and study populations. Treatment choices for patients with DTF are based on a paucity of (randomized) trials. Treatment principles of DTF are similar in pediatric and adult oncology, but the treatment itself is different. This seems mostly driven by a lack of tyrosine kinase inhibitor (TKI) accessibility in pediatric oncology. An insufficient number of studies examined patient-reported outcomes, which are extremely important for patients with a chronic disease like DTF.
Topics: Child; Fibromatosis, Aggressive; Humans; Progression-Free Survival; Quality of Life; Soft Tissue Neoplasms; Young Adult
PubMed: 35714333
DOI: 10.1002/pbc.29831 -
The Oncologist Jul 2021Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics,...
Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics, and treatment, disparities exist among Black men in this country. The primary objective of this systematic review is to describe the reported disparities in screening, diagnostics, and treatments as well as efforts to alleviate these disparities through community and educational outreach efforts. Critical review took place of retrospective, prospective, and socially descriptive data of English language publications in the PubMed database. Despite more advanced presentation, lower rates of screening and diagnostic procedures, and low rates of trial inclusion, subanalyses have shown that various modalities of therapy are quite effective in Black populations. Moreover, patients treated on prospective clinical trials and within equal-access care environments have shown similar outcomes regardless of race. Additional prospective studies and enhanced participation in screening, diagnostic and genetic testing, clinical trials, and community-based educational endeavors are important to ensure equitable progress in prostate cancer for all patients. IMPLICATIONS FOR PRACTICE: Notable progress has been made with therapeutic advances for prostate cancer, but racial disparities continue to exist. Differing rates in screening and utility in diagnostic procedures play a role in these disparities. Black patients often present with more advanced disease, higher prostate-specific antigen, and other adverse factors, but outcomes can be attenuated in trials or in equal-access care environments. Recent data have shown that multiple modalities of therapy are quite effective in Black populations. Novel and bold hypotheses to increase inclusion in clinical trial, enhance decentralized trial efforts, and enact successful models of patient navigation and community partnership are vital to ensure continued progress in prostate cancer disparities.
Topics: Black or African American; Early Detection of Cancer; Humans; Male; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; United States
PubMed: 33683758
DOI: 10.1002/onco.13749 -
The Oncologist Feb 2020The Institute of Medicine recommends that survivorship care plans (SCPs) be included in cancer survivorship care. Our meta-analysis compares patient-reported outcomes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Institute of Medicine recommends that survivorship care plans (SCPs) be included in cancer survivorship care. Our meta-analysis compares patient-reported outcomes between SCP and no SCP (control) conditions for cancer survivors. Our systematic review examines the feasibility of implementing SCPs from survivors' and health care professionals' perspectives and the impact of SCPs on health care professionals' knowledge and survivorship care provision.
METHODS
We searched seven online databases (inception to April 22, 2018) for articles assessing SCP feasibility and health care professional outcomes. Randomized controlled trials comparing patient-reported outcomes for SCP recipients versus controls were eligible for the meta-analysis. We performed random-effects meta-analyses using pooled standardized mean differences for each patient-reported outcome.
RESULTS
Eight articles were eligible for the meta-analysis (n = 1,286 survivors) and 50 for the systematic review (n = 18,949 survivors; n = 3,739 health care professionals). There were no significant differences between SCP recipients and controls at 6 months postintervention on self-reported cancer and survivorship knowledge, physical functioning, satisfaction with information provision, or self-efficacy or at 12 months on anxiety, cancer-specific distress, depression, or satisfaction with follow-up care. SCPs appear to be acceptable and potentially improve survivors' adherence to medical recommendations and health care professionals' knowledge of survivorship care and late effects.
CONCLUSION
SCPs appear feasible but do not improve survivors' patient-reported outcomes. Research should ascertain whether this is due to SCP ineffectiveness, implementation issues, or inappropriate research design of comparative effectiveness studies.
IMPLICATIONS FOR PRACTICE
Several organizations recommend that cancer survivors receive a survivorship care plan (SCP) after their cancer treatment; however, the impact of SCPs on cancer survivors and health care professionals is unclear. This systematic review suggests that although SCPs appear to be feasible and may improve health care professionals' knowledge of late effects and survivorship care, there is no evidence that SCPs affect cancer survivors' patient-reported outcomes. In order to justify the ongoing implementation of SCPs, additional research should evaluate SCP implementation and the research design of comparative effectiveness studies. Discussion may also be needed regarding the possibility that SCPs are fundamentally ineffective.
Topics: Cancer Survivors; Humans; Neoplasms; Patient Care Planning; Survivors; Survivorship
PubMed: 32043786
DOI: 10.1634/theoncologist.2019-0184 -
JAMA Network Open May 2024Unlike other surgical specialties, obstetrics and gynecology (OB-GYN) has been predominantly female for the last decade. The association of this with gender bias and...
IMPORTANCE
Unlike other surgical specialties, obstetrics and gynecology (OB-GYN) has been predominantly female for the last decade. The association of this with gender bias and sexual harassment is not known.
OBJECTIVE
To systematically review the prevalence of sexual harassment, bullying, abuse, and discrimination among OB-GYN clinicians and trainees and interventions aimed at reducing harassment in OB-GYN and other surgical specialties.
EVIDENCE REVIEW
A systematic search of PubMed, Embase, and ClinicalTrials.gov was conducted to identify studies published from inception through June 13, 2023.: For the prevalence of harassment, OB-GYN clinicians and trainees on OB-GYN rotations in all subspecialties in the US or Canada were included. Personal experiences of harassment (sexual harassment, bullying, abuse, and discrimination) by other health care personnel, event reporting, burnout and exit from medicine, fear of retaliation, and related outcomes were included. Interventions across all surgical specialties in any country to decrease incidence of harassment were also evaluated. Abstracts and potentially relevant full-text articles were double screened.: Eligible studies were extracted into standard forms. Risk of bias and certainty of evidence of included research were assessed. A meta-analysis was not performed owing to heterogeneity of outcomes.
FINDINGS
A total of 10 eligible studies among 5852 participants addressed prevalence and 12 eligible studies among 2906 participants addressed interventions. The prevalence of sexual harassment (range, 250 of 907 physicians [27.6%] to 181 of 255 female gynecologic oncologists [70.9%]), workplace discrimination (range, 142 of 249 gynecologic oncologists [57.0%] to 354 of 527 gynecologic oncologists [67.2%] among women; 138 of 358 gynecologic oncologists among males [38.5%]), and bullying (131 of 248 female gynecologic oncologists [52.8%]) was frequent among OB-GYN respondents. OB-GYN trainees commonly experienced sexual harassment (253 of 366 respondents [69.1%]), which included gender harassment, unwanted sexual attention, and sexual coercion. The proportion of OB-GYN clinicians who reported their sexual harassment to anyone ranged from 21 of 250 AAGL (formerly, the American Association of Gynecologic Laparoscopists) members (8.4%) to 32 of 256 gynecologic oncologists (12.5%) compared with 32.6% of OB-GYN trainees. Mistreatment during their OB-GYN rotation was indicated by 168 of 668 medical students surveyed (25.1%). Perpetrators of harassment included physicians (30.1%), other trainees (13.1%), and operating room staff (7.7%). Various interventions were used and studied, which were associated with improved recognition of bias and reporting (eg, implementation of a video- and discussion-based mistreatment program during a surgery clerkship was associated with a decrease in medical student mistreatment reports from 14 reports in previous year to 9 reports in the first year and 4 in the second year after implementation). However, no significant decrease in the frequency of sexual harassment was found with any intervention.
CONCLUSIONS AND RELEVANCE
This study found high rates of harassment behaviors within OB-GYN. Interventions to limit these behaviors were not adequately studied, were limited mostly to medical students, and typically did not specifically address sexual or other forms of harassment.
Topics: Humans; Sexual Harassment; Gynecology; Female; Obstetrics; Male; Sexism; Bullying; Prevalence; Canada; United States
PubMed: 38717770
DOI: 10.1001/jamanetworkopen.2024.10706 -
Biomedicines Jan 2022Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined... (Review)
Review
BACKGROUND
Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined chemoradiotherapy can induce treatment-related changes mimicking tumor progression on medical imaging, such as pseudoprogression (PsP). Differentiating PsP from true progression (TP) remains a challenge for radiologists and oncologists, who need to promptly start a second-line treatment in the case of TP. Advanced magnetic resonance imaging (MRI) techniques such as diffusion-weighted imaging, perfusion MRI, and proton magnetic resonance spectroscopic imaging are more efficient than conventional MRI in differentiating PsP from TP. None of these techniques are fully effective, but current advances in computer science and the advent of artificial intelligence are opening up new possibilities in the imaging field with radiomics (i.e., extraction of a large number of quantitative MRI features describing tumor density, texture, and geometry). These features are used to build predictive models for diagnosis, prognosis, and therapeutic response.
METHOD
Out of 7350 records for MR spectroscopy, GBM, glioma, recurrence, diffusion, perfusion, pseudoprogression, radiomics, and advanced imaging, we screened 574 papers. A total of 228 were eligible, and we analyzed 72 of them, in order to establish the role of each imaging modality and the usefulness and limitations of radiomics analysis.
PubMed: 35203493
DOI: 10.3390/biomedicines10020285 -
The Oncologist Jun 2023T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.
METHODS
We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.
RESULTS
From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).
CONCLUSION
TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
Topics: Male; Humans; Melanoma; Skin Neoplasms; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Melanoma, Cutaneous Malignant
PubMed: 37036865
DOI: 10.1093/oncolo/oyad078 -
Ophthalmology May 2024To develop guidelines for ocular surveillance and early intervention for individuals with von Hippel-Lindau (VHL) disease.
PURPOSE
To develop guidelines for ocular surveillance and early intervention for individuals with von Hippel-Lindau (VHL) disease.
DESIGN
Systematic review of the literature.
PARTICIPANTS
Expert panel of retina specialists and ocular oncologists.
METHODS
A consortium of experts on clinical management of all-organ aspects of VHL disease was convened. Working groups with expertise in organ-specific features of VHL disease were tasked with development of evidence-based guidelines for each organ system. The ophthalmology subcommittee formulated questions for consideration and performed a systematic literature review. Evidence was graded for topic quality and relevance and the strength of each recommendation, and guideline recommendations were developed.
RESULTS
The quality of evidence was limited, and no controlled clinical trial data were available. Consensus guidelines included: (1) individuals with known or suspected VHL disease should undergo periodic ocular screening (evidence type, III; evidence strength, C; degree of consensus, 2A); (2) patients at risk of VHL disease, including first-degree relatives of patients with known VHL disease, or any patient with single or multifocal retinal hemangioblastomas (RHs), should undergo genetic testing for pathologic VHL disease gene variants as part of an appropriate medical evaluation (III/C/2A); (3) ocular screening should begin within 12 months after birth and continue throughout life (III/C/2A); (4) ocular screening should occur approximately every 6 to 12 months until 30 years of age and then at least yearly thereafter (III/C-D/2A); (5) ocular screening should be performed before a planned pregnancy and every 6 to 12 months during pregnancy (IV/D/2A); (6) ultra-widefield color fundus photography may be helpful in certain circumstances to monitor RHs, and ultra-widefield fluorescein angiography may be helpful in certain circumstances to detect small RHs (IV/D/2A); (7) patients should be managed, whenever possible, by those with subspecialty training, with experience with VHL disease or RHs, or with both and ideally within the context of a multidisciplinary center capable of providing multiorgan surveillance and access to genetic testing (IV/D/2A); (8) extramacular or extrapapillary RHs should be treated promptly (III/C/2A).
CONCLUSIONS
Based on available evidence from observational studies, broad agreement was reached for a strategy of lifelong surveillance and early treatment for ocular VHL disease. These guidelines were endorsed by the VHL Alliance and the International Society of Ocular Oncology and were approved by the American Academy of Ophthalmology Board of Trustees.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Fluorescein Angiography; Genetic Testing; Hemangioblastoma; Retina; Retinal Neoplasms; von Hippel-Lindau Disease; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 38092079
DOI: 10.1016/j.ophtha.2023.12.014