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Journal of Clinical Oncology : Official... Dec 2023Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in...
Intraoperative MRI-Guided Resection Is Not Superior to 5-Aminolevulinic Acid Guidance in Newly Diagnosed Glioblastoma: A Prospective Controlled Multicenter Clinical Trial.
PURPOSE
Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in glioblastoma surgery. We investigated this hypothesis in a prospective clinical trial and correlated residual disease volumes with clinical outcome in newly diagnosed glioblastoma.
METHODS
This is a prospective controlled multicenter parallel-group trial with two center-specific treatment arms (5-ALA and iMRI) and blinded evaluation. The primary end point was complete resection of contrast enhancement on early postoperative MRI. We assessed resectability and extent of resection by an independent blinded centralized review of preoperative and postoperative MRI with 1-mm slices. Secondary end points included progression-free survival (PFS) and overall survival (OS), patient-reported quality of life, and clinical parameters.
RESULTS
We recruited 314 patients with newly diagnosed glioblastomas at 11 German centers. A total of 127 patients in the 5-ALA and 150 in the iMRI arm were analyzed in the as-treated analysis. Complete resections, defined as a residual tumor ≤0.175 cm³, were achieved in 90 patients (78%) in the 5-ALA and 115 (81%) in the iMRI arm ( = .79). Incision-suture times ( < .001) were significantly longer in the iMRI arm (316 215 [5-ALA] minutes). Median PFS and OS were comparable in both arms. The lack of any residual contrast enhancing tumor (0 cm³) was a significant favorable prognostic factor for PFS ( < .001) and OS ( = .048), especially in methylguanine-DNA-methyltransferase unmethylated tumors ( = .006).
CONCLUSION
We could not confirm superiority of iMRI over 5-ALA for achieving complete resections. Neurosurgical interventions in newly diagnosed glioblastoma shall aim for safe complete resections with 0 cm³ contrast-enhancing residual disease, as any other residual tumor volume is a negative predictor for PFS and OS.
Topics: Humans; Glioblastoma; Aminolevulinic Acid; Brain Neoplasms; Prospective Studies; Neoplasm, Residual; Quality of Life; Magnetic Resonance Imaging
PubMed: 37335962
DOI: 10.1200/JCO.22.01862 -
Virchows Archiv : An International... Feb 2018Neoadjuvant therapy has been successfully introduced in the treatment of locally advanced gastrointestinal malignancies, particularly esophageal, gastric, and rectal... (Review)
Review
Neoadjuvant therapy has been successfully introduced in the treatment of locally advanced gastrointestinal malignancies, particularly esophageal, gastric, and rectal cancers. The effects of preoperative chemo- or radiochemotherapy can be determined by histopathological investigation of the resection specimen following this treatment. Frequent histological findings after neoadjuvant therapy include various amounts of residual tumor, inflammation, resorptive changes with infiltrates of foamy histiocytes, foreign body reactions, and scarry fibrosis. Several tumor regression grading (TRG) systems, which aim to categorize the amount of regressive changes after cytotoxic treatment in primary tumor sites, have been proposed for gastroesophageal and rectal carcinomas. These systems primarily refer to the amount of therapy-induced fibrosis in relation to the residual tumor (e.g., the Mandard, Dworak, or AJCC systems) or the estimated percentage of residual tumor in relation to the previous tumor site (e.g., the Becker, Rödel, or Rectal Cancer Regression Grading systems). TRGs provide valuable prognostic information, as in most cases, complete or subtotal tumor regression after neoadjuvant treatment is associated with better patient outcomes. This review describes the typical histopathological findings after neoadjuvant treatment, discusses the most commonly used TRG systems for gastroesophageal and rectal carcinomas, addresses the limitations and critical issues of tumor regression grading in these tumors, and describes the clinical impact of TRG.
Topics: Gastrointestinal Neoplasms; Humans; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm, Residual; Treatment Outcome
PubMed: 28918544
DOI: 10.1007/s00428-017-2232-x -
Jornal Brasileiro de Pneumologia :... Sep 2021
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Neoplasm, Residual; Neoplasms, Second Primary
PubMed: 34495181
DOI: 10.36416/1806-3756/e20210275 -
British Journal of Haematology Jun 2019In the modern era, clinicians and pathologists increasingly make challenging diagnoses in patients with suspected lymphoma using minimal amounts of diagnostic material.... (Review)
Review
In the modern era, clinicians and pathologists increasingly make challenging diagnoses in patients with suspected lymphoma using minimal amounts of diagnostic material. The increase in utilization of minimally invasive procedures, such as fine needle aspiration or needle core biopsies, lead to challenges in our ability to make accurate histopathological assessments of disease, including the integration of new diagnostic and prognostic testing, with smaller amounts of material. The trend towards minimally invasive diagnostics is also often in conflicting interest with researchers seeking to study tissue specimens to better understand the biology and genetics of these diseases to move the field forward. Thankfully, there are emerging fields which seek to extract large amounts of diagnostic and prognostic data out of material that is circulating in the blood of patients with lymphoma. Here we will review recent exciting data regarding the use of circulating tumour cells, circulating tumour DNA, and the detection and utility of circulating exosomes and how it can assist in diagnosis, prognosis and therapeutic monitoring. These advances hold the promise to enable continued safe patient care while also advancing discovery, translational and clinical research.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Disease Management; Exosomes; Humans; Lymphoma; Neoplasm, Residual; Neoplastic Cells, Circulating
PubMed: 30784044
DOI: 10.1111/bjh.15788 -
The Oncologist Mar 2018This editorial highlights evidence to date on the question of whether chemotherapy promotes cancer metastases.
This editorial highlights evidence to date on the question of whether chemotherapy promotes cancer metastases.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Humans; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm, Residual; Pyrazoles; Pyridines; Quinolines; Taxoids; Tumor Microenvironment
PubMed: 29523674
DOI: 10.1634/theoncologist.2017-0648 -
Annals of Oncology : Official Journal... Mar 2019Circulating cell-free DNA (cfDNA) is one of the fastest growing and most exciting areas in oncology in recent years. Its potential clinical uses cover now each phase of... (Review)
Review
Circulating cell-free DNA (cfDNA) is one of the fastest growing and most exciting areas in oncology in recent years. Its potential clinical uses cover now each phase of cancer patient management care (predictive information, detection of the minimal residual disease, early detection of resistance, treatment monitoring, recurrence surveillance, and cancer early detection/screening). This review relates the recent advances in the application of circulating DNA or RNA in oncology building on unpublished or initial findings/work presented at the 10th international symposium on circulating nucleic acids in plasma and serum held in Montpellier from the 20th to the 22nd of September 2017. This year, presenters revealed their latest data and crucial observations notably in relation to (i) the circulating cell-free (cfDNA) structure and implications regarding their optimal detection; (ii) their role in the metastatic or immunological processes; (iii) evaluation of miRNA panels for cancer patient follow up; (iv) the detection of the minimal residual disease; (v) the evaluation of a screening tests for cancer using cfDNA analysis; and (vi) elements of preanalytical guidelines. This work reviews the recent progresses in the field brought to light in the meeting, as well as in the most important reports from the literature, past and present. It proposes a broader picture of the basic research and its potential, and of the implementation and current challenges in the use of circulating nucleic acids in oncology.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Early Detection of Cancer; Humans; Liquid Biopsy; MicroRNAs; Neoplasm Recurrence, Local; Neoplasm, Residual; Neoplasms
PubMed: 30753271
DOI: 10.1093/annonc/mdz031 -
Journal of Nanobiotechnology Oct 2023Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This...
Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.
Topics: Humans; Liver Neoplasms; Neoplasm, Residual; Cell Line, Tumor; Immunogenic Cell Death; B7-H1 Antigen; Nanoparticles; Immunotherapy; Autophagy; Tumor Microenvironment
PubMed: 37789342
DOI: 10.1186/s12951-023-02067-y -
Cytometry. Part B, Clinical Cytometry Sep 2021
Topics: Flow Cytometry; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasm, Residual
PubMed: 34536066
DOI: 10.1002/cyto.b.22031 -
Acta Obstetricia Et Gynecologica... Mar 2022It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking...
INTRODUCTION
It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer.
MATERIAL AND METHODS
We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses.
RESULTS
In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS.
CONCLUSIONS
Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.
Topics: Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Female; Humans; Neoadjuvant Therapy; Neoplasm, Residual; Ovarian Neoplasms; Pleural Effusion, Malignant; Retrospective Studies
PubMed: 35187660
DOI: 10.1111/aogs.14319 -
Best Practice & Research. Clinical... Dec 2022Quantification of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) is a well-established clinical tool used to risk stratify patients during the... (Review)
Review
Quantification of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) is a well-established clinical tool used to risk stratify patients during the course of chemotherapy, immunotherapy, and/or transplant therapy. As technologies evolve, the sensitivity for quantifying exceptionally low disease burden using either next generation sequencing (NGS) or next generation flow cytometry (NGF) has improved. It is now possible to detect MRD and quantify it precisely in patients who would previously have been deemed MRD negative by older, lower sensitivity methods. Persistence or recurrence of ALL disease burden above 10 (0.01%) is accepted as the minimum threshold for making clinical decisions, but with NGS and NGF, clinicians now confront decision-making with disease burdens sometimes quantified to as low as 10 (0.0001%, or one leukemia cell in a million leukocytes). Emerging data suggest these higher sensitivity methods are superior for identifying patients at lowest risk for relapse, but it remains controversial whether to institute therapies such as blinatumomab or chimeric antigen receptor (CAR)-T cells or move patients to allogeneic hematopoietic cell transplant (alloHCT) when they have quantifiable disease burden less than 10. With additional evidence to facilitate integration of highly sensitive MRD quantification into clinical care and to contextualize MRD within the genotype of individual patients, it will likely be increasingly possible to identify patients able to avoid alloHCT and potentially even de-escalate therapy.
Topics: Humans; Hematopoietic Stem Cell Transplantation; High-Throughput Nucleotide Sequencing; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36517126
DOI: 10.1016/j.beha.2022.101407