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JAMA Network Open Nov 2022A considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of... (Meta-Analysis)
Meta-Analysis
Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer: A Systematic Review and Meta-analysis.
IMPORTANCE
A considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking.
OBJECTIVE
To provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer.
DATA SOURCES
PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022.
STUDY SELECTION
Published phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic >50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022.
MAIN OUTCOMES AND MEASURES
Pathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types.
RESULTS
A total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma.
CONCLUSIONS AND RELEVANCE
This study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.
Topics: Humans; Neoadjuvant Therapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Immunotherapy; Adenocarcinoma
PubMed: 36322089
DOI: 10.1001/jamanetworkopen.2022.39778 -
Supportive Care in Cancer : Official... Jun 2022To provide evidence-based recommendations on the management of malignant bowel obstruction (MBO) for patients with advanced cancer.
PURPOSE
To provide evidence-based recommendations on the management of malignant bowel obstruction (MBO) for patients with advanced cancer.
METHODS
The Multinational Association for Supportive Care in Cancer (MASCC) MBO study group conducted a systematic review of databases (inception to March 2021) to identify studies about patients with advanced cancer and MBO that reported on the following outcomes: symptom management, bowel obstruction resolution, prognosis, overall survival, and quality of life. The review was restricted to studies published in English, but no restrictions were placed on publication year, country, and study type. As per the MASCC Guidelines Policy, the findings were synthesized to determine the levels of evidence to support each MBO intervention and, ultimately, the graded recommendations and suggestions.
RESULTS
The systematic review identified 17,656 published studies and 397 selected for the guidelines. The MASCC study group developed a total of 25 evidence-based suggestions and recommendations about the management of MBO-related nausea and vomiting, bowel movements, pain, inflammation, bowel decompression, and nutrition. Expert consensus-based guidance about advanced care planning and psychosocial support is also provided.
CONCLUSION
This MASCC Guideline provides comprehensive, evidence-based recommendations about MBO management for patients with advanced cancer.
Topics: Humans; Intestinal Obstruction; Nausea; Neoplasms; Palliative Care; Quality of Life
PubMed: 35274188
DOI: 10.1007/s00520-022-06889-8 -
European Journal of Cancer Prevention :... May 2023The risk of developing breast cancer in transgender individuals [male-to-female (MtF) or female-to-male (FtM)] is still inadequately quantified. We aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The risk of developing breast cancer in transgender individuals [male-to-female (MtF) or female-to-male (FtM)] is still inadequately quantified. We aimed to evaluate the impact of breast cancer in this population.
METHODS
We conducted a systematic literature search and review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines through the PUBMED and SCOPUS databases. We identified six cohort studies (for both populations) plus 35 case reports. Incidence and breast cancer risk quantification were the main outcomes considered.
RESULTS
FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender women (SIR = 0.42; 95% CI, 0.07-2.41). Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender women (SIR = 0.30; 95% CI, 0.22-0.42).
CONCLUSION
In this systematic study and meta-analysis, we identified that FtM and MtF individuals are at substantially higher risk of developing breast cancer in comparison to cisgender men, though at lower risk than cisgender women. These individuals, in the absence of defined guidelines for breast cancer prevention, should periodically undergo breast or chest examinations.
Topics: Humans; Male; Female; Transgender Persons; Breast Neoplasms; Incidence; Risk; Cohort Studies
PubMed: 36789830
DOI: 10.1097/CEJ.0000000000000784 -
Cancer Jan 2023Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance.
METHODS
In a systematic review and meta-analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random-effects model with logit transformation and evaluated the heterogeneity between studies using I statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all-grade and grade ≥3 treatment-related adverse events and differences between different drugs, molecular structures, and cancer types.
RESULTS
In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment-related adverse events was 91.2% (95% CI, 90.7%-91.7%; I = 95.9%) for all-grade adverse events and 46.1% (95% CI, 45.2%-47.0%; I = 96.3%) for grade ≥3 adverse events. The most common all-grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%-57.3%), nausea (44.1%; 95% CI, 43.2%-44.9%), neutropenia (43.7%; 95% CI, 42.6%-44.9%), blurred vision (40.5%; 95% CI, 37.4%-43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%-41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%-32.3%), hypoesthesia (23.3%; 95% CI, 10.6%-35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%-23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%-23.1%), and lymphopenia (21.0%; 95% CI, 18.2%-23.7%).
CONCLUSIONS
Different ADCs appear to affect various treatment-related adverse events and provide comprehensive data on treatment-related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.
LAY SUMMARY
Unique anticancer drugs called antibody-drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Neoplasms; Neutropenia; Lymphopenia
PubMed: 36408673
DOI: 10.1002/cncr.34507 -
Clinical & Translational Oncology :... Sep 2023Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of...
Breast cancer is the leading cause of cancer in women in Spain and its annual incidence is rapidly increasing. Thanks to the screening programs in place, nearly 90% of breast cancer cases are detected in early and potentially curable stages, despite the COVID-19 pandemic possibly having impacted these numbers (not yet quantified). In recent years, locoregional and systemic therapies are increasingly being directed by new diagnostic tools that have improved the balance between toxicity and clinical benefit. New therapeutic strategies, such as immunotherapy, targeted drugs, and antibody-drug conjugates have also improved outcomes in some patient subgroups. This clinical practice guideline is based on a systematic review of relevant studies and on the consensus of experts from GEICAM, SOLTI, and SEOM.
Topics: Female; Humans; Breast Neoplasms; Pandemics; COVID-19; Consensus; Drug Delivery Systems
PubMed: 37326826
DOI: 10.1007/s12094-023-03215-4 -
JAMA Oncology Oct 2022Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has... (Meta-Analysis)
Meta-Analysis
Association of PD-L1 Expression and Other Variables With Benefit From Immune Checkpoint Inhibition in Advanced Gastroesophageal Cancer: Systematic Review and Meta-analysis of 17 Phase 3 Randomized Clinical Trials.
IMPORTANCE
Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.
OBJECTIVE
To systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.
DATA SOURCES
MEDLINE, Embase, Scopus, Web of Science, Cochrane Central Register (2000-2022).
STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS
Randomized clinical trials (RCTs) were included of adults with aGEC (adenocarcinoma [AC] or squamous cell carcinoma [SCC]) randomized to anti-PD-1 or PD-L1-containing treatment vs standard of care (SOC). Study screening, data abstraction, and bias assessment were completed independently by 2 reviewers. Of 5752 records screened, 26 were assessed for eligibility; 17 trials were included in the analysis.
MAIN OUTCOMES AND MEASURES
The prespecified primary end point was overall survival. The mean hazard ratio (HR) for ICI vs SOC was calculated (random-effects model). Predictive values were quantified by calculating the ratio of mean HRs between 2 levels of each variable.
RESULTS
In all, 17 RCTs (9 first line, 8 after first line) at low risk of bias and 14 predictive variables were included, totaling 11 166 participants (5067 with SCC, 6099 with ACC; 77.6% were male and 22.4% were female; 59.5% of patients were younger than 65 years, 40.5% were 65 years or older). Among patients with SCCs, PD-L1 tumor proportion score (TPS) was the strongest predictor of ICI benefit (HR, 0.60 [95% CI, 0.53-0.68] for high TPS; and HR, 0.84 [95% CI, 0.75-0.95] for low TPS), yielding a predictive value of 41.0% favoring high TPS (vs ≤16.0% for other variables). Among patients with AC, PD-L1 combined positive score (CPS) was the strongest predictor (after microsatellite instability high status) of ICI benefit (HR, 0.73 [95% CI, 0.66-0.81] for high CPS; and HR, 0.95 [95% CI, 0.84-1.07] for low CPS), yielding a predictive value of 29.4% favoring CPS-high (vs ≤12.9% for other variables). Head-to-head analyses of trials containing both levels of a variable and/or having similar design generally yielded consistent results.
CONCLUSIONS AND RELEVANCE
Tissue-based PD-L1 expression, more than any variable other than microsatellite instability-high, identified varying degrees of benefit from ICI-containing therapy vs SOC among patients with aGEC in 17 RCTs.
Topics: Adult; Female; Humans; Male; Adenocarcinoma; B7-H1 Antigen; Clinical Trials, Phase III as Topic; Esophageal Neoplasms; Immune Checkpoint Inhibitors; Microsatellite Instability; Randomized Controlled Trials as Topic; Stomach Neoplasms; United States
PubMed: 36006624
DOI: 10.1001/jamaoncol.2022.3707 -
The European Respiratory Journal Jun 2020The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for...
The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including and () for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
Topics: Humans; Medical Oncology; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Surgeons
PubMed: 32451346
DOI: 10.1183/13993003.00953-2019 -
Journal of Pain and Symptom Management May 2021Children with cancer and their families have complex needs related to symptoms, decision-making, care planning, and psychosocial impact extending across the illness...
CONTEXT
Children with cancer and their families have complex needs related to symptoms, decision-making, care planning, and psychosocial impact extending across the illness trajectory, which for some includes end of life. Whether specialty pediatric palliative care (SPPC) is associated with improved outcomes for children with cancer and their families is unknown.
OBJECTIVE
We conducted a systematic review following PRISMA guidelines to investigate outcomes associated with SPPC in pediatric oncology with a focus on intervention delivery, collaboration, and alignment with National Quality Forum domains.
METHODS
We searched PubMed, Embase, Scopus, Web of Science, and CINAHL databases from inception until April 2020 and reviewed references manually. Eligible articles were published in English, involved pediatric patients aged 0-18 years with cancer, and contained original data regarding patient and family illness and end-of-life experiences, including symptom management, communication, decision-making, quality of life, satisfaction, and healthcare utilization.
RESULTS
We screened 6682 article abstracts and 82 full-text articles; 32 studies met inclusion criteria, representing 15,635 unique children with cancer and 342 parents. Generally, children with cancer who received SPPC had improved symptom burden, pain control, and quality of life with decreased intensive procedures, increased completion of advance care planning and resuscitation status documentation, and fewer end-of-life intensive care stays with higher likelihood of dying at home. Family impact included satisfaction with SPPC and perception of improved communication.
CONCLUSION
SPPC may improve illness experiences for children with cancer and their families. Multisite studies utilizing comparative effectiveness approaches and validated metrics may support further advancement of the field.
Topics: Child; Hospice and Palliative Care Nursing; Humans; Neoplasms; Palliative Care; Quality of Life; Terminal Care
PubMed: 33348034
DOI: 10.1016/j.jpainsymman.2020.12.003 -
International Journal of Molecular... Jun 2023Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown... (Meta-Analysis)
Meta-Analysis Review
Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.
Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.
Topics: Humans; Circulating Tumor DNA; Neoplasm, Residual; Chemotherapy, Adjuvant; Colorectal Neoplasms; Biomarkers, Tumor; Neoplasm Recurrence, Local
PubMed: 37373376
DOI: 10.3390/ijms241210230 -
PloS One 2022Mindfulness-based interventions (MBIs) are increasingly being integrated into oncological treatment to mitigate psychological distress and promote emotional and physical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Mindfulness-based interventions (MBIs) are increasingly being integrated into oncological treatment to mitigate psychological distress and promote emotional and physical well-being. This review aims to provide the most recent evaluation of Mindfulness-Based Stress Reduction (MBSR), Mindfulness-Based Cognitive Therapy (MBCT), and Mindfulness-Based Cancer Recovery (MBCR) treatments, in reducing symptoms of depression, anxiety and CRF in oncology populations.
METHODS
A search using the following search terms was conducted: (mindful* OR mindfulness* OR mindfulness-based* OR MBI* OR MBCT OR MBSR OR MBCR) AND (Oncol* OR cancer OR neoplasm OR lymphoma OR carcinoma OR sarcoma) to obtain relevant publications from five databases: PsycINFO, PubMed, Embase, and MEDLINE by EC, and ProQuest Dissertations & Theses Global from January 2000 to February 2022. 36 independent studies (n = 1677) were evaluated for their overall effect sizes (using random-effects models), subgroup analyses, and quality appraisals. Evaluations were performed separately for non-randomized (K = 20, n = 784) and randomized controlled trials (K = 16, n = 893).
RESULTS
The results showed that MBIs have significant medium effects in reducing symptoms of depression (Hedges' g = 0.43), anxiety (Hedges' g = 0.55) and CRF (Hedges' g = 0.43), which were maintained at least three months post-intervention. MBIs were also superior in reducing symptoms of anxiety (Hedges' g = 0.56), depression (Hedges' g = 0.43), and CRF (Hedges' g = 0.42) in oncology samples relative to control groups. The superiority of MBIs to control groups was also maintained at least three months post-intervention for anxiety and CRF symptoms, but not for depressive symptoms. The risk of bias of the included studies were low to moderate.
CONCLUSIONS
This review found that MBIs reduced symptoms of depression, anxiety and CRF in oncology populations.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO: International Prospective Register of Systematic Reviews: CRD42020143286.
Topics: Anxiety; Depression; Fatigue; Humans; Mindfulness; Neoplasms
PubMed: 35834503
DOI: 10.1371/journal.pone.0269519