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European Journal of Cancer (Oxford,... Jun 2024Circulating tumor DNA (ctDNA) holds promise as a biomarker for guiding adjuvant treatment decisions in solid tumors. This review systematically assembles ongoing and... (Review)
Review
Circulating tumor DNA (ctDNA) holds promise as a biomarker for guiding adjuvant treatment decisions in solid tumors. This review systematically assembles ongoing and published trials investigating ctDNA-directed adjuvant treatment strategies. A total of 57 phase II/III trials focusing on ctDNA in minimal residual disease (MRD) detection were identified, with a notable increase in initiation over recent years. Most trials target stage II or III colon/colorectal cancer, followed by breast cancer and non-small cell lung cancer. Trial methodologies vary, with some randomizing ctDNA-positive patients between standard-of-care (SoC) treatment and intensified regimens, while others aim to de-escalate therapy in ctDNA-negative patients. Challenges in trial design include the need for randomized controlled trials to establish clinical utility for ctDNA, ensuring adherence to standard treatment in control arms, and addressing the ethical dilemma of withholding treatment in high-risk ctDNA-positive patients. Longitudinal ctDNA surveillance emerges as a strategy to improve sensitivity for recurrence, particularly in less proliferative tumor types. However, ctDNA as longitudinal marker is often not validated yet. Ultimately, designing effective ctDNA interventional trials requires careful consideration of feasibility, meaningful outcomes, and potential impact on patient care.
PubMed: 38878446
DOI: 10.1016/j.ejca.2024.114159 -
European Journal of Medical Research Jun 2024Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to...
BACKGROUND
Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to investigate whether some common thyroid diseases can cause DVT using a two-sample Mendelian randomization (MR) approach.
METHODS
This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran's Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes.
RESULTS
This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran's Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods.
CONCLUSIONS
This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.
Topics: Humans; Venous Thrombosis; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Thyroid Diseases; Genetic Predisposition to Disease; Hyperthyroidism
PubMed: 38877527
DOI: 10.1186/s40001-024-01933-1 -
Scientific Reports Jun 2024The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with...
The detection of copy number variations (CNVs) and somatic mutations in cancer is important for the selection of specific drugs for patients with cancer. In cancers with sporadic tumor cells, low tumor content prevents the accurate detection of somatic alterations using targeted sequencing. To efficiently identify CNVs, we performed tumor cell enrichment using tissue suspensions of formalin-fixed paraffin-embedded (FFPE) tissue sections with low tumor cell content. Tumor-enriched and residual fractions were separated from FFPE tissue suspensions of intestinal and diffuse-type gastric cancers containing sporadic tumor cells, and targeted sequencing was performed on 225 cancer-related genes. Sequencing of a targeted panel of cancer-related genes using tumor-enriched fractions increased the number of detectable CNVs and the copy number of amplified genes. Furthermore, CNV analysis using the normal cell-enriched residual fraction as a reference for CNV scoring allowed targeted sequencing to detect CNV characteristics of diffuse-type gastric cancer with low tumor content. Our approach improves the CNV detection rate in targeted sequencing with tumor enrichment and the accuracy of CNV detection in archival samples without paired blood.
Topics: Humans; Stomach Neoplasms; DNA Copy Number Variations; Paraffin Embedding; Male; Female; High-Throughput Nucleotide Sequencing; Aged; Mutation
PubMed: 38871991
DOI: 10.1038/s41598-024-64541-3 -
Nature Communications Jun 2024The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the...
The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
Topics: Humans; Tumor Suppressor Protein p53; Animals; Chromosomal Instability; Mice; Lung Neoplasms; ErbB Receptors; Mutation; Drug Resistance, Neoplasm; Cell Line, Tumor; Protein Kinase Inhibitors; Adenocarcinoma of Lung; Molecular Targeted Therapy; Female; DNA Copy Number Variations; Male
PubMed: 38871738
DOI: 10.1038/s41467-024-47606-9 -
Blood Cancer Journal Jun 2024The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been...
The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been investigated in several studies. However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done. Here, we performed error-corrected-NGS-MRD in 189 patients homogeneously treated in the ALFA-0702 study (NCT00932412). Persistence of non-DTA mutations (HR = 2.23 for RFS and 2.26 for OS), and DTA mutations (HR = 2.16 for OS) were associated with poorer prognosis in multivariate analysis. Persistence of at least two mutations in complete remission (CR) was associated with a higher cumulative incidence of relapse (CIR) (HR = 3.71, p < 0.0001), lower RFS (HR = 3.36, p < 0.0001) and OS (HR = 3.81, p = 0.00023) whereas persistence of only one mutation was not. In 100 analyzable patients, WT1-MRD, but not NGS-MRD, was an independent factor for RFS and OS. In the subset of 67 NPM1 mutated patients, both NPM1 mutation detection (p = 0.0059) and NGS-MRD (p = 0.035) status were associated with CIR. We conclude that detectable NGS-MRD including DTA mutations correlates with unfavorable prognosis in AML. Its integration with alternative MRD strategies in AML management warrants further investigations.
Topics: Humans; Neoplasm, Residual; Leukemia, Myeloid, Acute; Female; Male; Middle Aged; Nucleophosmin; Adult; Aged; Mutation; High-Throughput Nucleotide Sequencing; Young Adult; Prognosis; DNA Methyltransferase 3A; Aged, 80 and over; DNA (Cytosine-5-)-Methyltransferases; Adolescent; Repressor Proteins; DNA Mutational Analysis
PubMed: 38871702
DOI: 10.1038/s41408-024-01078-8 -
BMC Endocrine Disorders Jun 2024Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of...
BACKGROUND
Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky.
CASE PRESENTATION
A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery.
CONCLUSION
Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.
Topics: Humans; Female; Aged; Lymphatic Metastasis; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Carcinoma, Anaplastic; Prognosis; Fatal Outcome; Neck; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 38867258
DOI: 10.1186/s12902-024-01617-1 -
Surgical Case Reports Jun 2024Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal...
BACKGROUND
Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants.
CASE PRESENTATION
The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively.
CONCLUSIONS
If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.
PubMed: 38867137
DOI: 10.1186/s40792-024-01936-4 -
Nature Communications Jun 2024Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT...
Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT's adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.
Topics: Humans; Leukemia, Myeloid, Acute; INDEL Mutation; CRISPR-Cas Systems; Nucleophosmin; Neoplasm, Residual; Nuclear Proteins; Proto-Oncogene Proteins B-raf; Genetic Testing; ErbB Receptors; Bacterial Proteins; Endodeoxyribonucleases; CRISPR-Associated Proteins
PubMed: 38866774
DOI: 10.1038/s41467-024-49414-7 -
International Journal of Surgery Case... Jul 2024Cystic lesions in long bones are the radiological presentation of various bone pathologies, they can easily be misdiagnosed and thus mistreated; treatment varies from...
INTRODUCTION
Cystic lesions in long bones are the radiological presentation of various bone pathologies, they can easily be misdiagnosed and thus mistreated; treatment varies from observation to aggressive surgical interventions based on the nature and characteristics of the lesion.
CASE PRESENTATION
A 25-year-old male had a twisting injury to his ankle and his radiographs showed a cystic lesion in the distal tibia that was asymptomatic until he injured his ankle. he had persistent pain since then. and after conservative methods failure, a two-stage surgical intervention was done; first, we curetted the lesion and filled it with antibiotics cement; then the cement was removed with autologous bone grafting. The patient eventually healed and returned to his normal activity level.
DISCUSSION
Brodie's abscess has a similar radiological appearance to other bone neoplasms and tumor-like lesions. Clinically, it is minimally symptomatic, and often initially misdiagnosed; surgical treatment is very effective, but it depends on the size, location, and aggressiveness of the lesion; the goal is to eliminate the infection, refill the residual gap, and restore the normal function, especially in weight-bearing bones.
CONCLUSION
Brodie's abscess is a hideous lesion that is hard to diagnose. It could mimic other tumor-like lesions. However, applying bone cement and a second stage of bone grafting might help maximize the treatment efficiency.
PubMed: 38865946
DOI: 10.1016/j.ijscr.2024.109865 -
Supportive Care in Cancer : Official... Jun 2024We conducted a systematic review to describe health-related quality of life (HRQOL) in rural cancer survivors (RCS), and compare HRQOL between RCS and urban cancer... (Comparative Study)
Comparative Study Review
PURPOSE
We conducted a systematic review to describe health-related quality of life (HRQOL) in rural cancer survivors (RCS), and compare HRQOL between RCS and urban cancer survivors (UCS).
METHOD
We searched Medline, Embase, CINAHL Plus, and PsycINFO for studies with HRQOL in adult cancer survivors living in rural, regional, remote, and urban areas, who had completed definitive primary cancer treatment, without evidence of residual disease. Where available, we used normative and clinically important values to ascribe meaning to HRQOL data.
FINDINGS
Fifteen studies (16 papers) were included. Most were from the US (n = 8) and reported on breast cancer survivors (n = 9). Six HRQOL instruments, collecting data across 16 domains, were used. Three instruments were specific to the survivorship phase. Normative and clinical data were available for 12 studies. Compared with normative populations, RCS had clinically worse physical HRQOL (6/12 studies), better social/family (5/7), and functional (3/6) HRQOL, and there were no differences in emotional or/mental HRQOL (9/12). In six studies with rural-urban comparator groups and normative and clinically important data, RCS and UCS had clinically worse physical (3/6 and 2/6, respectively) and better social/family (3/4 and 2/4 studies, respectively) HRQOL than normative populations. Functional HRQOL was better in RCS (2/4 studies) than UCS and normative populations. In 3/6 studies, there were no clinical differences in emotional or/mental HRQOL between RCS, UCS, and normative populations.
CONCLUSION
Overall, HRQOL is not clearly better or worse in RCS than UCS. Future research should include different tumor types, rural residents, and survivorship-specific HRQOL instruments.
Topics: Humans; Quality of Life; Cancer Survivors; Rural Population; Urban Population; Neoplasms
PubMed: 38864894
DOI: 10.1007/s00520-024-08618-9