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Theranostics 2023Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression... (Review)
Review
Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.
Topics: Humans; Tumor Microenvironment; Lipid Metabolism; Immunotherapy; Cell Death; Lipids; Neoplasms
PubMed: 37064872
DOI: 10.7150/thno.82920 -
The Cochrane Database of Systematic... Jun 2017Incurable cancer, which often constitutes an enormous challenge for patients, their families, and medical professionals, profoundly affects the patient's physical and... (Review)
Review
BACKGROUND
Incurable cancer, which often constitutes an enormous challenge for patients, their families, and medical professionals, profoundly affects the patient's physical and psychosocial well-being. In standard cancer care, palliative measures generally are initiated when it is evident that disease-modifying treatments have been unsuccessful, no treatments can be offered, or death is anticipated. In contrast, early palliative care is initiated much earlier in the disease trajectory and closer to the diagnosis of incurable cancer.
OBJECTIVES
To compare effects of early palliative care interventions versus treatment as usual/standard cancer care on health-related quality of life, depression, symptom intensity, and survival among adults with a diagnosis of advanced cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, OpenGrey (a database for grey literature), and three clinical trial registers to October 2016. We checked reference lists, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and cluster-randomised controlled trials (cRCTs) on professional palliative care services that provided or co-ordinated comprehensive care for adults at early advanced stages of cancer.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane. We assessed risk of bias, extracted data, and collected information on adverse events. For quantitative synthesis, we combined respective results on our primary outcomes of health-related quality of life, survival (death hazard ratio), depression, and symptom intensity across studies in meta-analyses using an inverse variance random-effects model. We expressed pooled effects as standardised mean differences (SMDs, or Hedges' adjusted g). We assessed certainty of evidence at the outcome level using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) and created a 'Summary of findings' table.
MAIN RESULTS
We included seven randomised and cluster-randomised controlled trials that together recruited 1614 participants. Four studies evaluated interventions delivered by specialised palliative care teams, and the remaining studies assessed models of co-ordinated care. Overall, risk of bias at the study level was mostly low, apart from possible selection bias in three studies and attrition bias in one study, along with insufficient information on blinding of participants and outcome assessment in six studies.Compared with usual/standard cancer care alone, early palliative care significantly improved health-related quality of life at a small effect size (SMD 0.27, 95% confidence interval (CI) 0.15 to 0.38; participants analysed at post treatment = 1028; evidence of low certainty). As re-expressed in natural units (absolute change in Functional Assessment of Cancer Therapy-General (FACT-G) score), health-related quality of life scores increased on average by 4.59 (95% CI 2.55 to 6.46) points more among participants given early palliative care than among control participants. Data on survival, available from four studies enrolling a total of 800 participants, did not indicate differences in efficacy (death hazard ratio 0.85, 95% CI 0.56 to 1.28; evidence of very low certainty). Levels of depressive symptoms among those receiving early palliative care did not differ significantly from levels among those receiving usual/standard cancer care (five studies; SMD -0.11, 95% CI -0.26 to 0.03; participants analysed at post treatment = 762; evidence of very low certainty). Results from seven studies that analysed 1054 participants post treatment suggest a small effect for significantly lower symptom intensity in early palliative care compared with the control condition (SMD -0.23, 95% CI -0.35 to -0.10; evidence of low certainty). The type of model used to provide early palliative care did not affect study results. One RCT reported potential adverse events of early palliative care, such as a higher percentage of participants with severe scores for pain and poor appetite; the remaining six studies did not report adverse events in study publications. For these six studies, principal investigators stated upon request that they had not observed any adverse events.
AUTHORS' CONCLUSIONS
This systematic review of a small number of trials indicates that early palliative care interventions may have more beneficial effects on quality of life and symptom intensity among patients with advanced cancer than among those given usual/standard cancer care alone. Although we found only small effect sizes, these may be clinically relevant at an advanced disease stage with limited prognosis, at which time further decline in quality of life is very common. At this point, effects on mortality and depression are uncertain. We have to interpret current results with caution owing to very low to low certainty of current evidence and between-study differences regarding participant populations, interventions, and methods. Additional research now under way will present a clearer picture of the effect and specific indication of early palliative care. Upcoming results from several ongoing studies (N = 20) and studies awaiting assessment (N = 10) may increase the certainty of study results and may lead to improved decision making. In perspective, early palliative care is a newly emerging field, and well-conducted studies are needed to explicitly describe the components of early palliative care and control treatments, after blinding of participants and outcome assessors, and to report on possible adverse events.
Topics: Communication; Humans; Neoplasms; Palliative Care; Physician-Patient Relations; Quality of Life
PubMed: 28603881
DOI: 10.1002/14651858.CD011129.pub2 -
International Journal of Molecular... Sep 2022Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of... (Review)
Review
Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
Topics: Antineoplastic Agents, Immunological; Apoptosis Regulatory Proteins; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Ligands; Liver Neoplasms; Lung Neoplasms; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 36142866
DOI: 10.3390/ijms231810948 -
The Cochrane Database of Systematic... Nov 2012Cancer-related fatigue is recognised as an important symptom associated with cancer and its treatment. A number of studies have investigated the effects of physical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related fatigue is recognised as an important symptom associated with cancer and its treatment. A number of studies have investigated the effects of physical activity in reducing cancer-related fatigue. This is an updated version of the original Cochrane review published in The Cochrane Library (2008, Issue 1). The original review identified some benefits of physical activity on fatigue in cancer both during and after adjuvant treatment. We identified a number of limitations in the evidence, providing clear justification for an updated review.
OBJECTIVES
To evaluate the effect of exercise on cancer-related fatigue both during and after cancer treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL (1982 to March 2011), British Nursing Index (January 1984 to March 2011), AMED (1985 to March 2011), SIGLE (1980 to March 2011) and Dissertation Abstracts International (1861 to March 2011) using key words. We also searched reference lists off all studies identified for inclusion and relevant reviews. In addition, we handsearched relevant journals and contacted experts in the field of cancer-related fatigue.
SELECTION CRITERIA
We sought and included randomised controlled trials (RCTs) that investigated the effect of exercise on cancer-related fatigue in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the risk of bias of studies and extracted data based upon predefined criteria. Where data were available we performed meta-analyses for fatigue using a random-effects model.
MAIN RESULTS
For this update we identified a total of 56 studies (4068 participants) for inclusion (28 from the original search and 28 from the updated search), with the majority carried out in participants with breast cancer (28 studies). A meta-analysis of all fatigue data, incorporating 38 comparisons, provided data for 1461 participants who received an exercise intervention and 1187 control participants. At the end of the intervention period exercise was seen to be statistically more effective than the control intervention (standardised mean difference (SMD) -0.27, 95% confidence interval (CI) -0.37 to -0.17). Benefits of exercise on fatigue were observed for interventions delivered during or post-adjuvant cancer therapy. In relation to diagnosis, we identified benefits of exercise on fatigue for breast and prostate cancer but not for those with haematological malignancies. Finally, aerobic exercise significantly reduced fatigue but resistance training and alternative forms of exercise failed to reach significance.
AUTHORS' CONCLUSIONS
The findings of the updated review have enabled a more precise conclusion to be made in that aerobic exercise can be regarded as beneficial for individuals with cancer-related fatigue during and post-cancer therapy, specifically those with solid tumours. Further research is required to determine the optimal type, intensity and timing of an exercise intervention.
Topics: Adult; Exercise; Fatigue; Female; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 23152233
DOI: 10.1002/14651858.CD006145.pub3 -
JAMA Dermatology Apr 2016To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
To date, the magnitude of association and the quality of evidence for cutaneous squamous cell carcinoma (cSCC) and risk factors for outcomes have not been reviewed and analyzed systematically.
OBJECTIVE
To systematically analyze all published data on risk factors for recurrence, metastasis, and disease-specific death (DSD) of cSCC.
DATA SOURCES
Comprehensive search of Ovid MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, from each database's inception to May 14, 2015.
STUDY SELECTION
Inclusion criteria were studies of at least 10 patients, comparative data for at least 1 cSCC risk factor, and an outcome of interest. Exclusion criteria were noncutaneous squamous cell carcinoma (SCC), anogenital SCC, inability to extract cSCC data from other malignancy data, SCC in situ, Marjolin ulcer, and genetic disorders predisposing to cSCC.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale.
MAIN OUTCOMES AND MEASURES
A priori outcomes were recurrence, metastasis, and DSD.
RESULTS
Thirty-six studies (17 248 patients with 23 421 cSCCs) were included. Significant risk factors for recurrence were the following: Breslow thickness exceeding 2 mm (risk ratio [RR], 9.64; 95% CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95% CI, 4.17-13.88), Breslow thickness exceeding 6 mm (RR, 7.13; 95% CI, 3.04-16.72), perineural invasion (RR, 4.30; 95% CI, 2.80-6.60), diameter exceeding 20 mm (RR, 3.22; 95% CI, 1.91-5.45), location on the temple (RR, 3.20; 95% CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95% CI, 1.72-4.14). Significant risk factors for metastasis were: invasion beyond subcutaneous fat (RR, 11.21; 95% CI, 3.59-34.97), Breslow thickness exceeding 2 mm (RR, 10.76; 95% CI, 2.55-45.31), Breslow thickness exceeding 6 mm (RR, 6.93; 95% CI, 4.02-11.94), diameter exceeding 20 mm (RR, 6.15; 95% CI, 3.56-10.65), poor differentiation (RR, 4.98; 95% CI, 3.30-7.49), perineural invasion (RR, 2.95; 95% CI, 2.31-3.75), immunosuppression (RR, 1.59; 95% CI, 1.07-2.37), and location on the temple (RR, 2.82; 95% CI, 1.72-4.63), ear (RR, 2.33; 95% CI, 1.67-3.23), or lip (RR, 2.28; 95% CI, 1.54-3.37). Significant risk factors for DSD were: diameter exceeding 20 mm (RR, 19.10; 95% CI, 5.80-62.95), poor differentiation (RR, 5.65; 95% CI, 1.76-18.20), location on the ear (RR, 4.67; 95% CI, 1.28-17.12) or lip (RR, 4.55; 95% CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95% CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95% CI, 3.10-5.32). Evidence quality was considered low to moderate.
CONCLUSIONS AND RELEVANCE
Tumor depth is associated with the highest RR of local recurrence and metastasis of cSCC, and tumor diameter exceeding 20 mm is associated with the highest RR of DSD. Unified, consistent collection and reporting of risk factors in a prospective, multicentered effort are needed to further understand the increasing incidence of cSCC.
Topics: Carcinoma, Squamous Cell; Genetic Predisposition to Disease; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Risk Factors; Skin Neoplasms
PubMed: 26762219
DOI: 10.1001/jamadermatol.2015.4994 -
Annals of Oncology : Official Journal... Feb 2020Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical... (Meta-Analysis)
Meta-Analysis
Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.
BACKGROUND
Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population.
MATERIALS AND METHODS
Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment.
DATA SYNTHESIS
Summary effects were estimated using random-effects models.
OUTCOMES
Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population.
RESULTS
Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073).
CONCLUSIONS
Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.
Topics: Alphapapillomavirus; Female; Humans; Incidence; Middle Aged; Papillomavirus Infections; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 31959338
DOI: 10.1016/j.annonc.2019.11.004 -
Frontiers in Public Health 2022Artificial intelligence has far surpassed previous related technologies in image recognition and is increasingly used in medical image analysis. We aimed to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Artificial intelligence has far surpassed previous related technologies in image recognition and is increasingly used in medical image analysis. We aimed to explore the diagnostic accuracy of the models based on deep learning or radiomics for lung cancer staging.
METHODS
Studies were systematically reviewed using literature searches from PubMed, EMBASE, Web of Science, and Wanfang Database, according to PRISMA guidelines. Studies about the diagnostic accuracy of radiomics and deep learning, including the identifications of lung cancer, tumor types, malignant lung nodules and lymph node metastase, were included. After identifying the articles, the methodological quality was assessed using the QUADAS-2 checklist. We extracted the characteristic of each study; the sensitivity, specificity, and AUROC for lung cancer diagnosis were summarized for subgroup analysis.
RESULTS
The systematic review identified 19 eligible studies, of which 14 used radiomics models and 5 used deep learning models. The pooled AUROC of 7 studies to determine whether patients had lung cancer was 0.83 (95% CI 0.78-0.88). The pooled AUROC of 9 studies to determine whether patients had NSCLC was 0.78 (95% CI 0.73-0.83). The pooled AUROC of the 6 studies that determined patients had malignant lung nodules was 0.79 (95% CI 0.77-0.82). The pooled AUROC of the other 6 studies that determined whether patients had lymph node metastases was 0.74 (95% CI 0.66-0.82).
CONCLUSION
The models based on deep learning or radiomics have the potential to improve diagnostic accuracy for lung cancer staging.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2022-3-0167/, identifier: INPLASY202230167.
Topics: Artificial Intelligence; Deep Learning; Humans; Lung; Lung Neoplasms; Neoplasm Staging
PubMed: 35923964
DOI: 10.3389/fpubh.2022.938113 -
The Cochrane Database of Systematic... Jan 2019Although people with haematological malignancies have to endure long phases of therapy and immobility, which is known to diminish their physical performance level, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although people with haematological malignancies have to endure long phases of therapy and immobility, which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy.
OBJECTIVES
In this update of the original review (published in 2014) our main objective was to re-evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies considering the current state of knowledge.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 7) and MEDLINE (1950 to July 2018) trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing an aerobic physical exercise intervention, intending to improve the oxygen system, in addition to standard care with standard care only for adults suffering from haematological malignancies. We also included studies that evaluated aerobic exercise in addition to strength training. We excluded studies that investigated the effect of training programmes that were composed of yoga, tai chi chuan, qigong or similar types of exercise. We also excluded studies exploring the influence of strength training without additive aerobic exercise as well as studies assessing outcomes without any clinical impact.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events, mortality and 100-day survival, standardised mean differences (SMD) for quality of life (QoL), fatigue, and physical performance, and mean differences (MD) for anthropometric measurements.
MAIN RESULTS
In this update, nine trials could be added to the nine trials of the first version of the review, thus we included eighteen RCTs involving 1892 participants. Two of these studies (65 participants) did not provide data for our key outcomes (they analysed laboratory values only) and one study (40 patients) could not be included in the meta-analyses, as results were presented as changes scores only and not as endpoint scores. One trial (17 patients) did not report standard errors and could also not be included in meta-analyses. The overall potential risk of bias in the included trials is unclear, due to poor reporting.The majority of participants suffered from acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), malignant lymphoma and multiple myeloma, and eight trials randomised people receiving stem cell transplantation. Mostly, the exercise intervention consisted of various walking intervention programmes with different duration and intensity levels.Our primary endpoint overall survival (OS) was only reported in one of these studies. The study authors found no evidence for a difference between both arms (RR = 0.67; P = 0.112). Six trials (one trial with four arms, analysed as two sub-studies) reported numbers of deceased participants during the course of the study or during the first 100 to 180 days. For the outcome mortality, there is no evidence for a difference between participants exercising and those in the control group (RR 1.10; 95% CI 0.79 to 1.52; P = 0.59; 1172 participants, low-certainty evidence).For the following outcomes, higher numbers indicate better outcomes, with 1 being the best result for the standardised mean differences. Eight studies analysed the influence of exercise intervention on QoL. It remains unclear, whether physical exercise improves QoL (SMD 0.11; 95% CI -0.03 to 0.24; 1259 participants, low-certainty evidence). There is also no evidence for a difference for the subscales physical functioning (SMD 0.15; 95% CI -0.01 to 0.32; 8 trials, 1329 participants, low-certainty evidence) and anxiety (SMD 0.03; 95% CI -0.30 to 0.36; 6 trials, 445 participants, very low-certainty evidence). Depression might slightly be improved by exercising (SMD 0.19; 95% CI 0.0 to 0.38; 6 trials, 445 participants, low-certainty evidence). There is moderate-certainty evidence that exercise probably improves fatigue (SMD 0.31; 95% CI 0.13 to 0.48; 9 trials, 826 patients).Six trials (435 participants) investigated serious adverse events. We are very uncertain, whether additional exercise leads to more serious adverse events (RR 1.39; 95% CI 0.94 to 2.06), based on very low-certainty evidence.In addition, we are aware of four ongoing trials. However, none of these trials stated, how many patients they will recruit and when the studies will be completed, thus, potential influence of these trials for the current analyses remains unclear.
AUTHORS' CONCLUSIONS
Eighteen, mostly small RCTs did not identify evidence for a difference in terms of mortality. Physical exercise added to standard care might improve fatigue and depression. Currently, there is inconclusive evidence regarding QoL, physical functioning, anxiety and SAEs .We need further trials with more participants and longer follow-up periods to evaluate the effects of exercise intervention for people suffering from haematological malignancies. To enhance comparability of study data, development and implementation of core sets of measuring devices would be helpful.
Topics: Adult; Exercise; Exercise Tolerance; Feasibility Studies; Female; Hematologic Neoplasms; Humans; Male; Physical Conditioning, Human; Qigong; Quality of Life; Randomized Controlled Trials as Topic; Resistance Training; Tai Ji; Yoga
PubMed: 30702150
DOI: 10.1002/14651858.CD009075.pub3 -
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 -
Annals of Oncology : Official Journal... Dec 2019Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a... (Meta-Analysis)
Meta-Analysis
Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a systematic review and meta-analysis to assess its efficacy on previously treated advanced metastatic cutaneous melanoma. The PubMed electronic database was searched from inception to 17 December 2018 to identify studies administering TIL-ACT and recombinant interleukin-2 (IL-2) following non-myeloablative chemotherapy in previously treated metastatic melanoma patients. Objective response rate (ORR) was the primary end point. Secondary end points were complete response rate (CRR), overall survival (OS), duration of response (DOR) and toxicity. Pooled estimates were derived from fixed or random effect models, depending on the amount of heterogeneity detected. Analysis was carried out separately for high dose (HD) and low dose (LD) IL-2. Sensitivity analyses were carried out. Among 1211 records screened, 13 studies (published 1988 - 2016) were eligible for meta-analysis. Among 410 heavily pretreated patients (some with brain metastasis), 332 received HD-IL-2 and 78 LD-IL-2. The pooled overall ORR estimate was 41% [95% confidence interval (CI) 35% to 48%], and the overall CRR was 12% (95% CI 7% to 16%). For the HD-IL-2 group, the ORR was 43% (95% CI 36% to 50%), while for the LD-IL-2 it was 35% (95% CI 25% to 45%). Corresponding pooled estimates for CRR were 14% (95% CI 7% to 20%) and 7% (95% CI 1% to 12%). The majority of HD-IL-2 complete responders (27/28) remained in remission during the extent of follow-up after CR (median 40 months). Sensitivity analyses yielded similar results. Higher number of infused cells was associated with a favorable response. The ORR for HD-IL-2 compared favorably with the nivolumab/ipilimumab combination following anti-PD-1 failure. TIL-ACT therapy, especially when combined with HD-IL-2, achieves durable clinical benefit and warrants further investigation. We discuss the current position of TIL-ACT in the therapy of advanced melanoma, particularly in the era of immune checkpoint blockade therapy, and review future opportunities for improvement of this approach.
Topics: Combined Modality Therapy; Disease-Free Survival; Dose-Response Relationship, Drug; Humans; Interleukin-2; Lymphocytes, Tumor-Infiltrating; Melanoma; Recombinant Proteins; Remission Induction; Skin Neoplasms; Transplantation, Autologous; Melanoma, Cutaneous Malignant
PubMed: 31566658
DOI: 10.1093/annonc/mdz398