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The Oncologist Dec 2023Circulating tumor DNA (ctDNA) is increasingly used as a biomarker for metastatic rectal cancer and has recently shown promising results in the early detection of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating tumor DNA (ctDNA) is increasingly used as a biomarker for metastatic rectal cancer and has recently shown promising results in the early detection of recurrence risk.
METHODS
We conducted a systematic review and meta-analysis to explore the prognostic value of ctDNA detection in LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT). We systematically searched electronic databases for observational or interventional studies that included LARC patients undergoing nCRT. Study selection according to the PRISMA guidelines and quality assessment of the REMARK tool for biomarker studies. The primary endpoint was the impact of ctDNA detection at different time points (baseline, post-nCRT, post-surgery) on relapse-free survival (RFS) and overall survival (OS). The secondary endpoint was to study the association between ctDNA detection and pathological complete response(pCR) at different time points.
RESULTS
After further review and analysis of the 625 articles initially retrieved, we finally included 10 eligible studies. We found no significant correlation between ctDNA detection at baseline and long-term survival outcomes or the probability of achieving a pCR. However, the presence of ctDNA at post-nCRT was associated with worse RFS (HR = 9.16, 95% CI, 5.48-15.32), worse OS (HR = 8.49, 95% CI, 2.20-32.72), and worse pCR results (OR = 0.40, 95%CI, 0.18-0.89). The correlation between the presence of ctDNA at post-surgery and worse RFS was more obvious (HR = 14.94; 95% CI, 7.48-9.83).
CONCLUSIONS
Our results suggest that ctDNA detection is a promising biomarker for the evaluation of response and prognosis in LARC patients undergoing nCRT, which merits further evaluation in the following prospective trials.
Topics: Humans; Prognosis; Neoadjuvant Therapy; Prospective Studies; Chemoradiotherapy; Neoplasm Recurrence, Local; Rectal Neoplasms; Biomarkers, Tumor
PubMed: 37294663
DOI: 10.1093/oncolo/oyad151 -
Frontiers in Oncology 2021Machine learning (ML) is emerging as a feasible approach to optimize patients' care path in Radiation Oncology. Applications include autosegmentation, treatment planning...
BACKGROUND AND PURPOSE
Machine learning (ML) is emerging as a feasible approach to optimize patients' care path in Radiation Oncology. Applications include autosegmentation, treatment planning optimization, and prediction of oncological and toxicity outcomes. The purpose of this clinically oriented systematic review is to illustrate the potential and limitations of the most commonly used ML models in solving everyday clinical issues in head and neck cancer (HNC) radiotherapy (RT).
MATERIALS AND METHODS
Electronic databases were screened up to May 2021. Studies dealing with ML and radiomics were considered eligible. The quality of the included studies was rated by an adapted version of the qualitative checklist originally developed by Luo et al. All statistical analyses were performed using R version 3.6.1.
RESULTS
Forty-eight studies (21 on autosegmentation, four on treatment planning, 12 on oncological outcome prediction, 10 on toxicity prediction, and one on determinants of postoperative RT) were included in the analysis. The most common imaging modality was computed tomography (CT) (40%) followed by magnetic resonance (MR) (10%). Quantitative image features were considered in nine studies (19%). No significant differences were identified in global and methodological scores when works were stratified per their task (i.e., autosegmentation).
DISCUSSION AND CONCLUSION
The range of possible applications of ML in the field of HN Radiation Oncology is wide, albeit this area of research is relatively young. Overall, if not safe yet, ML is most probably a bet worth making.
PubMed: 34869010
DOI: 10.3389/fonc.2021.772663 -
The Pharmacogenomics Journal Jun 2016Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy.... (Meta-Analysis)
Meta-Analysis Review
Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy. This review collects, evaluates and combines data on the influence of reported somatic and germline genetic variations on histological tumor regression in neoadjuvant settings of rectal and esophageal cancers. Five hundred and twenty-seven articles were identified, 204 retrieved and 61 studies included. Among 24 and 14 genetic markers reported for rectal and esophageal cancers, respectively, significant associations in meta-analyses were demonstrated for the following markers. In rectal cancer, major response was more frequent in carriers of the TYMS genotype 2 R/2 R-2 R/3 R (rs34743033), MTHFR genotype 677C/C (rs1801133), wild-type TP53 and KRAS genes. In esophageal cancer, successful therapy appeared to correlate with wild-type TP53. These results may be useful for future research directions to translate reported data into practical clinical use.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Chi-Square Distribution; Esophageal Neoplasms; Genetic Association Studies; Genotype; Germ-Line Mutation; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Neoadjuvant Therapy; Odds Ratio; Pharmacogenomic Variants; Phenotype; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Risk Factors; Thymidylate Synthase; Treatment Outcome; Tumor Suppressor Protein p53
PubMed: 26122021
DOI: 10.1038/tpj.2015.46 -
Journal of the American Academy of... Nov 2017The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from these drugs is unknown.
OBJECTIVE
To conduct a systematic review and meta-analysis of published clinical trials and determine the incidence and risk of development of targeted therapy-induced pigmentary changes.
METHODS
A comprehensive search was conducted to identify studies reporting targeted therapy-induced pigmentary changes. The incidence and relative risk were calculated. Case reports and series were reviewed to understand clinical characteristics.
RESULTS
A total of 8052 patients from 36 clinical trials were included. The calculated overall incidences of targeted cancer therapy-induced all-grade pigmentary changes in the skin and hair were 17.7% (95% confidence interval [CI], 11.9-25.4) and 21.5% (95% CI, 14.9-30.1), respectively. The relative risk of all-grade pigmentary changes of skin and hair were 93.7 (95% CI, 5.86-1497.164) and 20.1 (95% CI, 8.35-48.248). Across 53 case reports/series (N = 75 patients), epidermal growth factor receptor and breakpoint cluster region-abelson inhibitors were the most common offending agents.
LIMITATIONS
Potential under-reporting and variability in oncologists reporting these events.
CONCLUSION
There is a significant risk of development of pigmentary changes during treatment with targeted anticancer therapies. Appropriate counseling and management are critical to minimize psychosocial impairment and deterioration in quality of life.
Topics: Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Molecular Targeted Therapy; Neoplasms; Pigmentation Disorders; Prevalence; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 28918974
DOI: 10.1016/j.jaad.2017.06.044 -
Asia-Pacific Journal of Clinical... Aug 2023Over the past decade, the number of cancer cases has continued to rise, placing a heavy burden on patients' families and healthcare systems. Although innovative... (Review)
Review
Over the past decade, the number of cancer cases has continued to rise, placing a heavy burden on patients' families and healthcare systems. Although innovative treatments and drugs have improved patient outcomes, the financial toxicity (FT) of treatment is a growing concern among oncologists. Previous research have examined the impacts of FT on the HRQOL of cancer patients. However, the extent of the association is unclear, given that previous studies vary in the enrolled population, adjustment of confounding factors, and usage of FT assessment tools. To address this gap, the main purpose of this systematic review is to examine the relationship between FT and HRQOL of cancer survivors, and explore any potential factors that may affect this relationship.
Topics: Humans; Quality of Life; Cost of Illness; Cancer Survivors; Financial Stress; Neoplasms
PubMed: 36457166
DOI: 10.1111/ajco.13901 -
The Journal of Sexual Medicine Jul 2020Greater understanding of patient-reported barriers and facilitators to seeking and accessing sexual health services will help formulate strategies to assist gynecologic... (Meta-Analysis)
Meta-Analysis
Patient-Reported Barriers and Facilitators to Seeking and Accessing Support in Gynecologic and Breast Cancer Survivors With Sexual Problems: A Systematic Review of Qualitative and Quantitative Studies.
BACKGROUND
Greater understanding of patient-reported barriers and facilitators to seeking and accessing sexual health services will help formulate strategies to assist gynecologic and breast cancer patients to overcome obstacles to accessing sexual health support because they typically do not seek sexual education and/or treatment when confronted with sexual concerns.
AIM
The objectives of this systematic review were to (i) explore the patient-reported barriers to seeking and accessing support for sexual problems in gynecologic and breast cancer survivors, and (ii) identify strategies used to successfully overcome the barriers to accessing sexual health information and/or treatment.
MAIN OUTCOME MEASURES
The main outcome measures included factors that prevent and/or facilitate gynecologic and breast cancer patients with sexual concerns seeking and accessing sexual health-related services.
METHODS
Systematic searches of major electronic databases (Ovid MEDLINE, PsycINFO, CINAHL, ProQuest, and Chinese database CNKI) from January 2009 to July 2019 were used to identify the barriers and facilitators to seeking sexual education/treatment from the perspective of gynecologic and breast cancer survivors. A narrative synthesis was conducted.
RESULTS
20 studies met the inclusion criteria including 12 qualitative, 6 quantitative, and 2 mixed methods studies. 4 interconnected themes were derived from 13 subthemes relating to the barriers/facilitators to seeking and accessing sexual health support. The most common barriers were embarrassment/discomfort in discussing sexual concerns, perceived discomfort of healthcare providers in discussing sexual issues, limitations of the healthcare system to address sexual problems, and the multidimensional nature of sexuality. Help-seeking for sexual health concerns was facilitated by: (i) oncology health professionals initiating and conducting open, honest discussions around sexual concerns with patients; (ii) the availability of information in multiple forms; and (iii) appropriate timing of information provision according to women's preferences.
CLINICAL IMPLICATIONS
Oncology health professionals need to develop an open, honest, accepting communication style and be accessible to women with cancer and their partners within healthcare systems.
STRENGTHS & LIMITATIONS
The systematic review was conducted in accordance with guidelines. Variability in the primary aims and outcomes of the included studies precluded a meta-analysis.
CONCLUSIONS
Training programs for providers of oncology care should enhance their knowledge of sexual issues in gynecologic and/or breast cancer, enhance their communication skills with patients, and improve their ability to consult or refer patients to psycho-oncologists or other mental health professionals. Dai Y, Cook OY, Yeganeh L, et al. Patient-Reported Barriers and Facilitators to Seeking and Accessing Support in Gynecologic and Breast Cancer Survivors With Sexual Problems: A Systematic Review of Qualitative and Quantitative Studies. J Sex Med 2020;17:1326-1358.
Topics: Breast Neoplasms; Cancer Survivors; Female; Humans; Patient Reported Outcome Measures; Qualitative Research; Sexual Behavior
PubMed: 32331967
DOI: 10.1016/j.jsxm.2020.03.004 -
The Oncologist Dec 2019Advanced stage presentation of patients with is common in low- and middle-income countries (LMICs). A comprehensive analysis of existing delays and barriers in LMICs has...
BACKGROUND
Advanced stage presentation of patients with is common in low- and middle-income countries (LMICs). A comprehensive analysis of existing delays and barriers in LMICs has not been previously reported. We conducted a systematic literature review to comprehensively outline delays and barriers to identify targets for future interventions and provide recommendations for future research in this field.
MATERIALS AND METHODS
Multiple electronic databases were searched using a standardized search strategy. Eligible articles were of any language, from LMICs, and published between January 1, 2002, and November 27, 2017. Included studies reported cancer care intervals or barriers encountered. Intervals and associated barriers were summarized by cancer type and geographical region.
RESULTS
This review included 316 study populations from 57 LMICs: 142 (44.9%) studies addressed time intervals, whereas 214 (67.7%) studies described barriers to cancer diagnosis. The median intervals were similar in the following three stages of early diagnosis: (a) access (1.2 months), (b) diagnostic (0.9 months), and (c) treatment (0.8 months). Studies from low-income countries had significantly longer access intervals (median, 6.5 months) compared with other country income groups. Patients with breast cancer had longer delay intervals than patients with childhood cancer. No significant variation existed between geographic regions. Low health literacy was reported most frequently in studies describing barriers to cancer diagnosis and was associated with lower education level, no formal employment, lower income, and rural residence.
CONCLUSION
Early diagnosis strategies should address barriers during all three intervals contributing to late presentation in LMICs. Standardization in studying and reporting delay intervals in LMICs is needed to monitor progress and facilitate comparisons across settings.
IMPLICATIONS FOR PRACTICE
This review draws the attention of cancer implementation scientists globally. The findings highlight the significant delays that occur throughout the cancer care continuum in low- and middle-income countries and describe common barriers that cause them. This review will help shape the global research agenda by proposing metrics and implementation studies. By demonstrating the importance of standardized reporting metrics, this report sets forth additional research and evidence needed to inform cancer control policies.
Topics: Developing Countries; Humans; Neoplasms
PubMed: 31387949
DOI: 10.1634/theoncologist.2019-0057 -
Breast Cancer Research and Treatment Aug 2019Oncologists, clinical trialists, and guideline developers need tools that enable them to efficiently review the settings and results of previous studies testing... (Meta-Analysis)
Meta-Analysis
PURPOSE
Oncologists, clinical trialists, and guideline developers need tools that enable them to efficiently review the settings and results of previous studies testing metastatic breast cancer (MBC) drug therapies.
METHODS
We searched the literature to identify clinical trials testing MBC drug therapies. Key eligibility criteria included at least 90% of patients enrolled in the trial having MBC, therapeutic clinical trials, and Phase II-III studies. Studies were stratified based on patients' tumor receptor statuses and prior exposure to therapy. Survival and toxicity of each drug therapy were estimated from randomized controlled trials using network meta-analysis and from all studies using meta-analysis. These results, along with estimated drug costs, are presented in a web-based visualization tool.
RESULTS
We included 1865 studies containing 2676 treatment arms and 184,563 patients in the tool ( http://www.cancertrials.info ). Meta-analysis-based efficacy and toxicity estimates are available for 85 HER-2-directed therapies, 84 hormonal therapies, and 442 undirected therapies. Network meta-analysis-based estimates are available for 16 HER-2-directed therapies, 26 hormonal therapies, and 131 undirected therapies.
CONCLUSIONS
In this era of increasing choices of MBC therapeutic agents and no superior approach to choosing a treatment regimen, the ability to compare multiple therapies based on survival, toxicity and cost would enable treating physicians to optimize therapeutic choices for patients. For investigators, it can point them in research directions that were previously non-obvious and for guideline designers, enable them to efficiently review the MBC clinical trial literature and visualize how regimens compare in the key dimensions of clinical benefit, toxicity, and cost.
Topics: Breast Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Female; Health Care Costs; Humans; Neoplasm Metastasis; Neoplasm Staging; Outcome Assessment, Health Care
PubMed: 31089928
DOI: 10.1007/s10549-019-05208-w -
Gynecologic Oncology Feb 2009Ovarian cancer outcome varies among different institutions, regions, and countries. This systematic review summarizes the available data evaluating the impact of... (Review)
Review
OBJECTIVE
Ovarian cancer outcome varies among different institutions, regions, and countries. This systematic review summarizes the available data evaluating the impact of different physician and hospital characteristics on outcome in ovarian cancer patients.
METHODS
A MEDLINE database search for pertinent publications was conducted and reference lists of each relevant article were screened. Experts in the field were contacted. Selected studies assessed the relationship between physician and/or hospital specialty or volume and at least one of the outcomes of interest. The primary outcome was survival. Additional parameters included surgical outcome (debulking), completeness of staging, and quality of chemotherapy. The authors independently reviewed each article and applied the inclusion/exclusion criteria. The quality of each study was assessed by focusing on strategies to control for important prognostic factors.
RESULTS
Forty-four articles met inclusion criteria. Discipline and sub-specialization of the primary treating physician were identified as the most important variable associated with superior outcome. Evidence showing a beneficial impact of institutional factors was weaker, but followed the same trend. Hospital volume was hardly related to any outcome parameter.
CONCLUSIONS
The limited evidence available showed considerable heterogeneity and has to be interpreted cautiously. Better utilization of knowledge about institutional factors and well-established board certifications may improve outcome in ovarian cancer. Patients and primary-care physicians should select gynecologic oncologists for primary treatment in countries with established sub-specialty training. Policymakers, insurance companies, and lay organizations should support development of respective programs.
Topics: Female; Gynecology; Hospitals; Humans; Medical Oncology; Medicine; Neoplasm Staging; Ovarian Neoplasms; Specialization
PubMed: 18990435
DOI: 10.1016/j.ygyno.2008.09.036 -
Health Technology Assessment... 2001The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about... (Review)
Review
BACKGROUND
The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion.
OBJECTIVES
This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed.
METHODS
This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE ANALYSIS: Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on cost-effectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen.
CONCLUSIONS
The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE NEWER DRUGS: One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH: Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Deoxycytidine; Docetaxel; England; Humans; Lung Neoplasms; Paclitaxel; Quality of Life; Survival Rate; Taxoids; Vinblastine; Vinorelbine; Wales; Gemcitabine
PubMed: 12065068
DOI: 10.3310/hta5320