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Blood May 2024Selection of patients with NPM1-mutated acute myeloid leukemia (AML) for allogeneic transplant in first complete remission (CR1-allo) remains controversial because of a...
Selection of patients with NPM1-mutated acute myeloid leukemia (AML) for allogeneic transplant in first complete remission (CR1-allo) remains controversial because of a lack of robust data. Consequently, some centers consider baseline FLT3-internal tandem duplication (ITD) an indication for transplant, and others rely on measurable residual disease (MRD) status. Using prospective data from the United Kingdom National Cancer Research Institute AML17 and AML19 studies, we examined the impact of CR1-allo according to peripheral blood NPM1 MRD status measured by quantitative reverse transcription polymerase chain reaction after 2 courses of induction chemotherapy. Of 737 patients achieving remission, MRD was positive in 19%. CR1-allo was performed in 46% of MRD+ and 17% of MRD- patients. We observed significant heterogeneity of overall survival (OS) benefit from CR1-allo according to MRD status, with substantial OS advantage for MRD+ patients (3-year OS with CR1-allo vs without: 61% vs 24%; hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.64; P < .001) but no benefit for MRD- patients (3-year OS with CR1-allo vs without: 79% vs 82%; HR, 0.82; 95% CI, 0.50-1.33; P = .4). Restricting analysis to patients with coexisting FLT3-ITD, again CR1-allo only improved OS for MRD+ patients (3-year OS, 45% vs 18%; compared with 83% vs 76% if MRD-); no interaction with FLT3 allelic ratio was observed. Postinduction molecular MRD reliably identifies those patients who benefit from allogeneic transplant in first remission. The AML17 and AML19 trials were registered at www.isrctn.com as #ISRCTN55675535 and #ISRCTN78449203, respectively.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; fms-Like Tyrosine Kinase 3; Hematopoietic Stem Cell Transplantation; Induction Chemotherapy; Leukemia, Myeloid, Acute; Mutation; Neoplasm, Residual; Nucleophosmin; Prospective Studies; Remission Induction; Transplantation, Homologous
PubMed: 38364112
DOI: 10.1182/blood.2023023096 -
Materials Today. Bio Oct 2023Residual tumor recurrence after surgical resection of hepatocellular carcinoma (HCC) remains a considerable challenge that imperils the prognosis of patients. Notably,...
Residual tumor recurrence after surgical resection of hepatocellular carcinoma (HCC) remains a considerable challenge that imperils the prognosis of patients. Notably, intraoperative bleeding and postoperative infection are potential risk factors for tumor recurrence. However, the biomaterial strategy for the above problems has rarely been reported. Herein, a series of cryogels (coded as SQ-n) based on sodium alginate (SA) and quaternized chitosan (QC) were synthesized and selected for optimal ratios. The assays showed that SQ-50 possessed superior hemostasis, excellent antibacterial property, and great cytocompatibility. Subsequently, SQAP was constructed by loading black phosphorus nanosheets (BPNSs) and anlotinib hydrochloride (AL3818) based on SQ-50. Physicochemical experiments confirmed that near-infrared (NIR)-assisted SQAP could control the release of AL3818 in photothermal response, significantly inhibiting the proliferation and survival of HUVECs and H22 cells. Furthermore, studies indicated that the NIR-assisted SQAP prevented local recurrence of ectopic HCC after surgical resection, achieved through the synergistic effect of mPTT and molecular targeted therapy. Thus, the multifunctional SQAP provides a "one-stop" synergistic strategy for HCC postoperative recurrence, showing great potential for clinical application.
PubMed: 37564266
DOI: 10.1016/j.mtbio.2023.100746 -
Cancer Imaging : the Official... Nov 2023Neoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is...
Evaluating residual tumor after neoadjuvant chemotherapy for muscle-invasive urothelial bladder cancer: diagnostic performance and outcomes using biparametric vs. multiparametric MRI.
BACKGROUND
Neoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is important but suboptimal using CT. We assessed MRI without vs. with intravenous contrast (biparametric [BP] vs. multiparametric [MP]) for identifying residual disease on cystectomy and explored its prognostic role.
METHODS
Consecutive MIBC patients that underwent NAC, MRI, and cystectomy between January 2000-November 2022 were identified. Two radiologists reviewed BP-MRI (T2 + DWI) and MP-MRI (T2 + DWI + DCE) for residual tumor. Diagnostic performances were compared using receiver operating characteristic curve analysis. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with disease-free survival (DFS).
RESULTS
61 patients (36 men and 25 women; median age 65 years, interquartile range 59-72) were included. After NAC, no residual disease was detected on pathology in 19 (31.1%) patients. BP-MRI was more accurate than MP-MRI for detecting residual disease after NAC: area under the curve = 0.75 (95% confidence interval (CI), 0.62-0.85) vs. 0.58 (95% CI, 0.45-0.70; p = 0.043). Sensitivity were identical (65.1%; 95% CI, 49.1-79.0) but specificity was higher in BP-MRI compared with MP-MRI for determining residual disease: 77.8% (95% CI, 52.4-93.6) vs. 38.9% (95% CI, 17.3-64.3), respectively. Positive BP-MRI and residual disease on pathology were both associated with worse DFS: hazard ratio (HR) = 4.01 (95% CI, 1.70-9.46; p = 0.002) and HR = 5.13 (95% CI, 2.66-17.13; p = 0.008), respectively. Concordance between MRI and pathology results was significantly associated with DFS. Concordant positive (MRI+/pathology+) patients showed worse DFS than concordant negative (MRI-/pathology-) patients (HR = 8.75, 95% CI, 2.02-37.82; p = 0.004) and compared to the discordant group (MRI+/pathology- or MRI-/pathology+) with HR = 3.48 (95% CI, 1.39-8.71; p = 0.014).
CONCLUSION
BP-MRI was more accurate than MP-MRI for identifying residual disease after NAC. A negative BP-MRI was associated with better outcomes, providing complementary information to pathological assessment of cystectomy specimens.
Topics: Male; Humans; Female; Aged; Multiparametric Magnetic Resonance Imaging; Neoadjuvant Therapy; Neoplasm, Residual; Urinary Bladder Neoplasms; Muscles; Retrospective Studies
PubMed: 37964386
DOI: 10.1186/s40644-023-00632-0 -
Journal of Clinical Oncology : Official... Feb 2024We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial.
PATIENTS AND METHODS
Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis.
RESULTS
MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% 88.9%; = .013) and at EOI (93.1% 86.7%; = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% 16.0% in those receiving CHOP; < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% G-CHOP, 7.0%; R-CVP, 21.7% G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse.
CONCLUSION
MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; Gallium; Lymphoma, Follicular; Neoplasm, Residual; Prednisone; Rituximab; Vincristine
PubMed: 38096461
DOI: 10.1200/JCO.23.00838 -
Clinical Cancer Research : An Official... Sep 2023We aim to evaluate the prognostic significance of tumor-infiltrating lymphocyte on residual disease (RD-TIL) in HER2+ patients with breast cancer who failed to achieve...
PURPOSE
We aim to evaluate the prognostic significance of tumor-infiltrating lymphocyte on residual disease (RD-TIL) in HER2+ patients with breast cancer who failed to achieve pathologic complete response (pCR) after anti-HER2+ chemotherapy (CT)-based neoadjuvant treatment (NAT). We assessed the feasibility of combining the prognostic information provided by residual cancer burden (RCB) and RD-TILs into a composite score (RCB+TIL).
EXPERIMENTAL DESIGN
HER2+ patients with breast cancer treated with CT+anti-HER2-based NAT at three institutions were retrospectively included. RCB and TIL levels were evaluated on hematoxylin and eosin-stained slides from surgical samples according to available recommendations. Overall survival (OS) was used as an outcome measure.
RESULTS
A total of 295 patients were included, of whom 195 had RD. RCB was significantly associated with OS. Higher RD-TILs were significantly associated with poorer OS as compared with lower RD-TILs (15% cutoff). In multivariate analysis, both RCB and RD-TIL maintained their independent prognostic value. A combined score, RCB+TIL, was calculated from the estimated coefficient of RD-TILs and the RCB index in a bivariate logistic model for OS. The RCB+TIL score was significantly associated with OS. The C-index for OS of the RCB+TIL score was numerically higher than that of RCB and significantly higher than that of RD-TILs.
CONCLUSIONS
We have reported an independent prognostic impact of RD-TILs after anti-HER2+CT NAT, which might underlie an imbalance of the RD microenvironment towards immunosuppressive features. We provided a new composite prognostic score based on RCB+TIL, which was significantly associated with OS and proved to be more informative than the isolated evaluation of RCB and RD-TILs.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Lymphocytes, Tumor-Infiltrating; Neoplasm, Residual; Neoadjuvant Therapy; Retrospective Studies; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 37417941
DOI: 10.1158/1078-0432.CCR-23-0480 -
Hematology/oncology Clinics of North... Apr 2024Measurable (minimal) residual disease (MRD) has already proven to be one of the most important prognostic factors in multiple myeloma (MM). Each improvement in the depth... (Review)
Review
Measurable (minimal) residual disease (MRD) has already proven to be one of the most important prognostic factors in multiple myeloma (MM). Each improvement in the depth of MRD testing has led to superior discrimination of outcomes, and sustained MRD negativity seems to be paramount to durable responses. Peripheral blood assays to assess for MRD are still under investigation but hold promise as complementary tools to bone marrow MRD assays such as next-generation sequencing and flow cytometry. Herein, the authors explore the evidence and potential benefits and drawbacks of MRD-adapted clinical decision-making in MM.
Topics: Humans; Multiple Myeloma; Bone Marrow; Neoplasm, Residual; Flow Cytometry; High-Throughput Nucleotide Sequencing
PubMed: 38184470
DOI: 10.1016/j.hoc.2023.12.009 -
Blood Dec 2023
Topics: Child; Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Neoplasm, Residual; Phenotype
PubMed: 38095922
DOI: 10.1182/blood.2023022072 -
Annals of Oncology : Official Journal... Oct 2023We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative...
BACKGROUND
We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy.
PATIENTS AND METHODS
We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence.
RESULTS
Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10 (range 7.9 × 10-4.9 × 10). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12.
CONCLUSIONS
Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.
Topics: Humans; Female; Circulating Tumor DNA; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Neoplasm, Residual; Prospective Studies; Breast Neoplasms; Neoplasm Recurrence, Local
PubMed: 37597579
DOI: 10.1016/j.annonc.2023.08.004 -
Blood Feb 2024The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the...
The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the setting of MRD may improve outcomes. Patients with ALL in first complete remission (CR1) or beyond (CR2+) with MRD ≥ 1 × 10-4 were enrolled in this phase 2 trial. Inotuzumab was administered at 0.6 mg/m2 on day 1 and 0.3 mg/m2 on day 8 of cycle 1, then at 0.3 mg/m2 on days 1 and 8 of cycles 2-6. Twenty-six consecutive patients with a median age of 46 years (range, 19-70 years) were treated. Nineteen (73%) were in CR1 and seven (27%) in CR2+; 16 (62%) had Philadelphia chromosome-positive ALL. Fifteen (58%) had baseline MRD ≥ 1 × 10-3. A median of 3 cycles (range, 1-6) were administered. Eighteen (69%) patients responded and achieved MRD negativity. After a median follow-up of 24 months (range, 9-43), the 2-year relapse-free survival rate was 54% and the 2-year overall survival rate was 60% in the entire cohort. Most adverse events were low grade; sinusoidal obstruction syndrome was noted in 2 patients (8%). In summary, inotuzumab ozogamicin resulted in favorable survival, MRD negativity rates, and safety profiles for patients with ALL and MRD-positive status. This study was registered at www.ClinicalTrials.gov as #NCT03441061.
Topics: Humans; Young Adult; Adult; Middle Aged; Aged; Inotuzumab Ozogamicin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Hepatic Veno-Occlusive Disease; Neoplasm, Residual
PubMed: 37879077
DOI: 10.1182/blood.2023022330 -
NEJM Evidence Jul 2023The development of fluorescence imaging in oncology led to the possibility of using intraoperative devices to improve the precision of surgical techniques. In this issue...
The development of fluorescence imaging in oncology led to the possibility of using intraoperative devices to improve the precision of surgical techniques. In this issue of Smith et al. report results from a prospective multicenter trial evaluating the ability of intravenous pegulicianine with an optical head device and software to intraoperatively identify lumpectomy margins with residual cancer and excise them immediately. Identifying these margins intraoperatively avoids the need for a second surgery, which is required when margins are positive on the final pathology.
Topics: Humans; Mastectomy, Segmental; Neoplasm, Residual; Optical Imaging; Prospective Studies
PubMed: 38320169
DOI: 10.1056/EVIDe2300114