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ESMO Open Mar 2024The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC.
MATERIALS AND METHODS
A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed.
RESULTS
Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months).
CONCLUSIONS
ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse.
Topics: Humans; Female; Circulating Tumor DNA; Breast Neoplasms; Neoplasm Recurrence, Local; Prognosis; Disease-Free Survival
PubMed: 38460249
DOI: 10.1016/j.esmoop.2024.102390 -
The Oncologist May 2024We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil...
We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer (mCRC). We conducted a systematic search on May 29, 2021, for studies reporting one or more efficacy or safety outcome with FTD/TPI-containing combinations. Our search yielded 1378 publications, with 38 records meeting selection criteria: 35 studies of FTD/TPI-containing combinations in mCRC (31 studies second line or later) and 3 studies in other tumor types. FTD/TPI plus bevacizumab was extensively studied, including 19 studies in chemorefractory mCRC. Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory mCRC. Based on one randomized and several retrospective studies, FTD/TPI plus bevacizumab was associated with improved outcomes compared with FTD/TPI monotherapy. FTD/TPI combinations with chemotherapy or other targeted agents were reported in small early-phase studies; preliminary data indicated higher antitumor activity for certain combinations. Overall, no safety concerns existed with FTD/TPI combinations; most common grade ≥ 3 adverse event was neutropenia, ranging 5%-100% across all studies. In studies comparing FTD/TPI combinations with monotherapy, grade ≥ 3 neutropenia appeared more frequently with combinations (29%-67%) vs. monotherapy (5%-41%). Discontinuation rates due to adverse events ranged 0%-11% for FTD/TPI plus bevacizumab and 0%-17% with other combinations. This systematic review supports feasibility and safety of FTD/TPI plus bevacizumab in refractory mCRC. Data on non-bevacizumab FTD/TPI combinations remain preliminary and need further validation.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Pyrrolidines; Thymine; Trifluridine
PubMed: 38366864
DOI: 10.1093/oncolo/oyae007 -
Clinical Colorectal Cancer Jun 2024A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic...
BACKGROUND
A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT).
MATERIALS AND METHODS
An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions.
RESULTS
Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT.
CONCLUSIONS
Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.
Topics: Humans; Colorectal Neoplasms; Surveys and Questionnaires; Oncologists; Liver Neoplasms; Neoplasm Metastasis; Male; Female; Practice Patterns, Physicians'; Lung Neoplasms; Radiation Oncologists; Clinical Decision-Making; Middle Aged
PubMed: 38365567
DOI: 10.1016/j.clcc.2024.01.004 -
Multiple Sclerosis and Related Disorders Apr 2024It is uncommon for individuals with demyelinating disease, notably multiple sclerosis (MS), to be diagnosed with intracranial gliomas. It has been debated whether or not... (Review)
Review
BACKGROUND
It is uncommon for individuals with demyelinating disease, notably multiple sclerosis (MS), to be diagnosed with intracranial gliomas. It has been debated whether or not the concurrence of these two disorders is accidental. Clinically, it may be challenging to diagnose someone who has MS and an intracranial tumor simultaneously. We conducted this systematic review to evaluate the glioma patients following MS.
METHODS
We collected 63 studies from 1672 databases from January 1990 to February 2023, and our inclusion criteria involved peer-reviewed case reports/series studies reporting concurrent MS and glioma in patients, considering various types of gliomas.
RESULTS
We included 145 cases, 51% were women and 49 % were men, with an average age of 47.4 years. Common symptoms of glioma at admission included seizures (31.2 %), hemiparesis (15.6 %), and headache (14.3 %). 75 % of patients had primarily with relapsing-remitting MS (RRMS). MS treatments included interferon(IFN)-ß (44.6 %), glatiramer acetate (GA) (21.4 %), fingolimod (19.6 %), and natalizumab (19.6 %). The average time between MS and glioma diagnosis was 12.1 years, with various timeframes. Among the 59 reported cases, 45.8 % led to patient fatalities, while the remaining 54.2 % managed to survive.
CONCLUSION
This co-occurrence, though rare, suggests potential underlying shared mechanisms or vulnerabilities, possibly at a genetic or environmental level. An interdisciplinary approach, combining the expertise of neurologists, oncologists, radiologists, and pathologists, is vital to ensure accurate diagnosis and optimal management of affected individuals. Nonetheless, there is still a significant lack of information regarding this phenomenon, necessitating large-scale population-based studies and experimental research.
Topics: Male; Humans; Female; Middle Aged; Glatiramer Acetate; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Fingolimod Hydrochloride; Glioma; Multiple Sclerosis; Immunosuppressive Agents
PubMed: 38330723
DOI: 10.1016/j.msard.2024.105455 -
The Oncologist May 2024The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like...
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.
Topics: Humans; Immune Checkpoint Inhibitors; Colorectal Neoplasms; Microsatellite Instability
PubMed: 38309719
DOI: 10.1093/oncolo/oyae013 -
Anticancer Research Feb 2024Intraventricular cerebral metastases (IVCM) are a rare but clinically significant subset of brain metastases. This systematic review aimed to provide a comprehensive... (Review)
Review
BACKGROUND/AIM
Intraventricular cerebral metastases (IVCM) are a rare but clinically significant subset of brain metastases. This systematic review aimed to provide a comprehensive analysis of IVCM by synthesizing current literature on epidemiology, clinical presentation, imaging features, pathophysiology, and treatment options.
MATERIALS AND METHODS
A systematic literature search was conducted, identifying 11 relevant studies encompassing 11 studies encompassing 842 IVCM cases. Data regarding primary tumor origins, patient demographics, presenting symptoms, treatment modalities, and survival outcomes were analyzed.
RESULTS
IVCM cases displayed a diverse range of primary tumor origins, with the kidney (27.4%), thyroid (21.6%), lung (19.8%), colon (11.7%), melanoma (8.4%), and breast ductal carcinoma (7.9%) being common sources. Patients presented with a wide spectrum of symptoms, including headaches (42.3%), nausea (31.5%), altered mental status (25.7%), neurological deficits (18.2%), and others. Treatment approaches varied, encompassing surgical resection (41.2%), radiation therapy (32.5%), chemotherapy (15.3%), and immunotherapy (7.9%). Overall survival was generally limited, with a mean duration of approximately 10.3 months (±8.7 months). The time to recurrence after treatment exhibited considerable variability.
CONCLUSION
IVCM represents a challenging and underexplored metastatic disease. This systematic review underscores the need for further research to enhance our understanding of IVCM's pathophysiology and develop tailored diagnostic and treatment approaches. Such efforts are crucial to improving outcomes and the overall quality of life for patients facing this complex condition. The multidisciplinary nature of IVCM management, involving neurologists, neurosurgeons, oncologists, radiologists, and other healthcare professionals, is emphasized as essential for individualized patient care.
Topics: Humans; Quality of Life; Melanoma; Brain Neoplasms
PubMed: 38307552
DOI: 10.21873/anticanres.16833 -
Asian Pacific Journal of Cancer... Jan 2024Breast cancer surgery related complications are a complex condition influenced by interactions among nerve pathways and the physiological responses to breast surgery.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breast cancer surgery related complications are a complex condition influenced by interactions among nerve pathways and the physiological responses to breast surgery. The intensity of this complications displays substantial heterogeneity, dependent on individual patient characteristics, the extent of the surgical procedure performed, and various contributing factors.
METHODS
A comprehensive search of electronic databases was conducted to identify relevant randomized controlled trials (RCTs) investigating interventions for post-mastectomy pain syndrome (PMPS). A network meta-analysis was performed to integrate direct and indirect evidence, enabling comparisons of multiple interventions across different outcome measures.
RESULTS
The systematic search yielded a total of 26 RCTs investigating 4 groups of different interventions for PMPS. The interventions included pharmacological agents, nerve blocks, physical therapy, and anesthesia regimens. Nerve blocks (OR: 0.34; 95% CrI: 0.24-0.46) and anesthesia (OR: 0.39; 95% CrI: 0.26-0.56) demonstrated improvements in functional outcomes and quality of life.
CONCLUSION
This systematic review and network meta-analysis provide a comprehensive evaluation of interventions for PMPS, highlighting their varying efficacy in alleviating pain and improving functional outcomes and quality of life. However, further research with large-scale, well-designed RCTs is warranted to strengthen the evidence base and validate the effectiveness of these interventions in managing PMPS effectively.
Topics: Humans; Female; Network Meta-Analysis; Breast Neoplasms; Nerve Block; Mastectomy; Pain
PubMed: 38285764
DOI: 10.31557/APJCP.2024.25.1.9 -
Current Problems in Cardiology Mar 2024Sodium-glucose cotransporter 2-inhibitors (SGLT2i) improve cardiovascular outcomes including reduction in risk of first hospitalisation for heart failure (HF), worsening... (Review)
Review
BACKGROUND
Sodium-glucose cotransporter 2-inhibitors (SGLT2i) improve cardiovascular outcomes including reduction in risk of first hospitalisation for heart failure (HF), worsening HF and cardiovascular death regardless of HF or diabetes mellitus (DM) status. It is not known whether SGLT2i can prevent the development of incident HF or reduce the risk of HF in patients receiving trastuzumab with or without other concurrent anti-HER2 agent or sequential anthracycline for treatment of HER2 positive breast cancer. Patients with active malignancy or recent history of malignancy were excluded from participating in the main cardiovascular outcome trials involving SGLT2i.
AIM
A systematic review was performed to objectively assess published literature on the cardioprotective effects of SGLT2i in breast cancer treatment-related cardiotoxicity.
METHODS
Systematic searches of Embase, Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were performed. Titles and abstracts were screened separately by two cardio-oncologists (JHC, WTC). Full texts of potentially eligible records were then assessed separately by JHC and WTC before inclusion into review upon joint agreement.
RESULTS
479 records were identified from 3 databases (MEDLINE=51, EMBASE=408, CENTRAL=13) and 1 registry (Clinicaltrials.gov=7). 460 records were excluded based on title and abstract (including duplicates). 19 full text reports were assessed for eligibility and included in review (basic science/animal study paper 2, Clinicaltrials.gov randomised controlled trial submission 1 (currently recruiting), basic science/animal study conference abstract 5, case report 2, review 3, editorial comment 2, clinical guidelines 1, retrospective/registry-based conference abstract 3).
CONCLUSION
Cardiotoxicity is the most common dose-limiting toxicity associated with trastuzumab. Discontinuation of trastuzumab however, can lead to worse cancer outcomes. There have been case reports, registry-based, retrospective cohort-based and mechanistic studies suggesting the cardioprotective potential of SGLT2i in cancer therapy-related cardiac dysfunction (CTRCD). Based on these, there is now a call for randomised controlled trials to be performed in this patient cohort to advise guideline-directed therapy for CTRCD, which will in turn also provide detailed safety information and improve cancer and cardiovascular outcomes.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Cardiotoxicity; Heart Failure; Trastuzumab; Glucose; Sodium; Diabetes Mellitus, Type 2
PubMed: 38281354
DOI: 10.1016/j.cpcardiol.2024.102372 -
Current Cancer Drug Targets Jan 2024Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast...
BACKGROUND
Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast cancer cells. However, there is a need to summarize the evidence to provide conclusive advice on the benefit of PI3K inhibitors in breast cancer patients. Therefore, this review assessed the effectiveness and safety of the PI3K inhibitors amongst breast cancer patients.
METHODS
Searches were made in PubMed Central, EMBASE, MEDLINE, SCOPUS, CENTRAL, WHO trial registry and Clinicaltrials.gov up to December 2022. Meta-analysis was executed using the random-effects model. Pooled hazard ratio (HR)/risk ratio (RR) was reported with 95% confidence intervals (CIs).
RESULTS
In total, 13 studies were included in the analysis. Most were multi-country studies and had a higher risk of bias. Regarding the efficacy parameters, pooled HR for progression-free survival was 0.79 (95%CI: 0.67-0.92), pooled RR for complete response was 1.54 [95%CI: 1.14 to 2.09], partial response was 1.18 [95%CI: 0.87-1.61], overall response was 1.20 [95%CI: 0.93-1.56], stable disease was 1.09 [95%CI: 0.78-1.53], progressive disease was 0.80 [95%CI: 0.74 to 0.87], and clinical benefit was 1.08 [95%CI: 0.80-1.49]. For safety parameters, pooled RR for hyperglycemia was 4.57 [95%CI: 3.15-6.62], and gastrointestinal toxicity was 1.82 [95%CI: 1.56 to 2.14].
CONCLUSION
PI3K inhibitors had better efficacy than the present standard of concern for patients with breast cancer, especially among patients with PIK3CA mutations. Hence, clinicians and oncologists can provide this drug for the target population with extra caution for diabetes patients.
PubMed: 38275057
DOI: 10.2174/0115680096266181231207110048 -
The Oncologist Apr 2024Rural residents have a higher prevalence of colorectal cancer (CRC) mortality compared to urban individuals. Policies have been aimed at improving access to CRC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rural residents have a higher prevalence of colorectal cancer (CRC) mortality compared to urban individuals. Policies have been aimed at improving access to CRC screening to reduce these outcomes. However, little attention has been paid to other determinants of CRC-related outcomes, such as stage at diagnosis, treatment, or survivorship care. The main objective of this analysis was to evaluate literature describing differences in CRC screening, stage at diagnosis, treatment, and survivorship care between rural and urban individuals.
MATERIALS AND METHODS
We conducted a systematic review of electronic databases using a combination of MeSH and free-text search terms related to CRC screening, stage at diagnosis, treatment, survivorship care, and rurality. We identified 921 studies, of which 39 were included. We assessed methodological quality using the ROBINS-E tool and summarized findings descriptively. A meta-analysis was performed of studies evaluating CRC screening using a random-effects model.
RESULTS
Seventeen studies reported disparities between urban and rural populations in CRC screening, 12 on treatment disparities, and 8 on staging disparities. We found that rural individuals were significantly less likely to report any type of screening at any time period (pooled odds ratio = 0.81, 95% CI, 0.76-0.86). Results were inconclusive for disparities in staging at diagnosis and treatment. One study reported a lower likelihood of use of CRC survivorship care for rural individuals compared to urban individuals.
CONCLUSION
There remains an urgent need to evaluate and address CRC disparities in rural areas. Investigators should focus future work on assessing the quality of staging at diagnosis, treatment, and survivorship care in rural areas.
Topics: Humans; Survivorship; Rural Population; Early Detection of Cancer; Colorectal Neoplasms; Mass Screening
PubMed: 38243853
DOI: 10.1093/oncolo/oyad347