Clinical outcomes of colorectal neoplasm with positive resection margin after endoscopic submucosal dissection.

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Prognosis and influencing factors of ER-positive, HER2-low breast cancer patients with residual disease after neoadjuvant chemotherapy: a retrospective study.

Previously, we found that patients with estrogen receptor (ER)-positive, HER2-low breast cancer are resistant to neoadjuvant chemotherapy (NACT) and have worse outcomes than those who achieve pathological complete response (pCR) after NACT. This study aimed to investigate the prognosis and influencing factors in these patients. A total of 618 patients with ER-positive breast cancer who received standard thrice-weekly NACT were enrolled, including 411 patients with ER-positive, HER2-low breast cancer. Data on the clinicopathological features of these patients before and after NACT were collected. Univariate and multivariate Cox regression analyses were used to identify the independent factors affecting 5-year disease-free survival (DFS). Among the ER-positive, HER2-low patients, 49 (11.9%) achieved a pCR after NACT. A significant difference in survival was observed between patients with and without residual disease after NACT. Additionally, changes in immunohistochemical markers and tumor stages before and after NACT were found to be significant. According to univariate and multivariate analyses, cN_stage (P = 0.002), ER (P = 0.002) and Ki67 (P = 0.023) expression before NACT were significantly associated with 5-year DFS, while pT_stage (P = 0.015), pN_stage (P = 0.029), ER (P = 0.020) and Ki67 (P < 0.001) levels after NACT were related to 5-year DFS in ER-positive, HER2-low patients with residual disease. Our study suggested that high proliferation, low ER expression and advanced stage before and after NACT are associated with a poor prognosis, providing useful information for developing long-term treatment strategies for ER-positive, HER2-low breast cancer in patients with residual disease in the future.

Measuring response to therapy in AML: Difference from normal flow cytometry vs RQ-PCR.

Multiple technologies have been used to monitor response to therapy in acute myeloid leukemia (AML) to improve detection of leukemia over the standard of practice, morphologic counting of blasts. The two techniques most frequently used in a routine clinical setting, flow cytometry and RQ-PCR, differ in their targets, sensitivity, and ability to detect residual disease. Both flow cytometry and RQ-PCR detect the expression of abnormal gene products, at the protein level or RNA level, respectively. Flow cytometry can be applied to a broad range of AML cases while RQ-PCR is limited to specific genetic abnormalities identified in subsets of AML. This article compares the results when both techniques were used in a reference laboratory to monitor AML over the course of treatment, comparing quantitative and qualitative results.

[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma.

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

[Malignant lymphomas - quo vadis? - What developments await us in diagnostics and therapy?] / Maligne Lymphome ­ Quo vadis?

The diagnosis and treatment of malignant lymphoma is rapidly advancing, offering hope but also highlighting inherent limitations. Technological breakthroughs in sequencing technologies enable more precise subtyping and risk stratification. For example, in diffuse large B-cell lymphoma (DLBCL), exome sequencing revealed molecular subtypes. Understanding these subtypes sheds light on lymphomagenesis and prognosis, and may provide targets for tailored therapies. Additionally, tumor-derived cell-free DNA (ctDNA) detected in blood plasma allows for genotyping, risk stratification, and measurement of minimal residual disease (MRD). Current studies often examine drug effectiveness through "all-comer" approaches or in transcriptionally defined subtypes. Molecular agnostic studies increasingly focus on clinically defined high-risk patients (e.g., using the IPI) to better demonstrate the statistical significance of therapy effects. Improved patient selection can enhance the cost-effectiveness of modern, often expensive, therapies.

Intracranial residual lesions following early intensification in a patient with T-cell acute lymphoblastic leukemia: a case report.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) tends to involve central nervous system (CNS) infiltration at diagnosis. However, cases of residual CNS lesions detected at the end of induction and post early intensification have not been recorded in patients with T-ALL. Also, the ratio and prognosis of patients with residual intracranial lesions have not been defined. CASE PRESENTATION: A 9-year-old boy with T-ALL had multiple intracranial tumors, which were still detected post early intensification. To investigate residual CNS lesions, we used 11C-methionine (MET)-positron emission tomography. Negative MET uptake in CNS lesions and excellent MRD status in bone marrow allowed continuing therapies without hematopoietic cell transplantation. CONCLUSIONS: In cases with residual lesions on imaging studies, treatment strategies should be considered by the systemic response, direct assessment of spinal fluid, along with further development of noninvasive imaging methods in CNS. Further retrospective or prospective studies are required to determine the prognosis and frequency of cases with residual intracranial lesions after induction therapy.

Effect of sustained measurable residue disease negativity and post-remission treatment selection on the prognosis of acute lymphoblastic leukemia in adults.

BACKGROUND: To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia (B-ALL) in adults. METHODS: Between September 2010 and January 2022, adult patients with B-ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions. RESULTS: One hundred and forty-three B-ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo-HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo-HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo-HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo-HSCT and chemotherapy groups with negative MRD after consolidation therapy. CONCLUSIONS: B-ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long-term outcomes even without allo-HSCT. Allo-HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.

Complex treatment of residual metastatic germ cell cancer: A single center experience.

BACKGROUND: Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1 cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease. OBJECTIVE: To assess patient outcomes and complications considering different treatment regimens and clinical characteristics. MATERIALS AND METHODS: In a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed. RESULTS: Standard 3-4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5-6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases. CONCLUSIONS: The study suggests no significant benefit from exceeding 3-4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical.

Prognostic relevance of radiological findings on early postoperative MRI for 187 consecutive glioblastoma patients receiving standard therapy.

Several prognostic factors are known to influence survival for patients treated with IDH-wildtype glioblastoma, but unknown factors may remain. We aimed to investigate the prognostic implications of early postoperative MRI findings. A total of 187 glioblastoma patients treated with standard therapy were consecutively included. Patients either underwent a biopsy or surgery followed by an early postoperative MRI. Progression-free survival (PFS) and overall survival (OS) were analysed for known prognostic factors and MRI-derived candidate factors: resection status as defined by the response assessment in neuro-oncology (RANO)-working group (no contrast-enhancing residual tumour, non-measurable contrast-enhancing residual tumour, or measurable contrast-enhancing residual tumour) with biopsy as reference, contrast enhancement patterns (no enhancement, thin linear, thick linear, diffuse, nodular), and the presence of distant tumours. In the multivariate analysis, patients with no contrast-enhancing residual tumour or non-measurable contrast-enhancing residual tumour on the early postoperative MRI displayed a significantly improved progression-free survival compared with patients receiving only a biopsy. Only patients with non-measurable contrast-enhancing residual tumour showed improved overall survival in the multivariate analysis. Contrast enhancement patterns were not associated with survival. The presence of distant tumours was significantly associated with both poor progression-free survival and overall survival and should be considered incorporated into prognostic models.

Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.

BACKGROUND: Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL. METHODS: The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). RESULTS: Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles. CONCLUSION: Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.

The Evolving Landscape of Flowcytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia.

Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based on aberrant expression of markers (antigens) during malignant B-cell maturation. Recent advances highlight the significance of novel markers (e.g., CD58, CD81, CD304, CD73, CD66c, and CD123), improving MRD identification. Second and next-generation flow cytometry, such as the EuroFlow consortium's eight-color protocol, can achieve sensitivities down to 10-5 (comparable with the PCR-based method) if sufficient cells are acquired. The introduction of targeted therapies (especially those targeting CD19, such as blinatumomab or CAR-T19) introduces several challenges for flow cytometric MRD analysis, such as the occurrence of CD19-negative relapses. Therefore, innovative flow cytometry panels, including alternative B-cell markers (e.g., CD22 and CD24), have been designed. (Semi-)automated MRD assessment, employing machine learning algorithms and clustering tools, shows promise but does not yet allow robust and sensitive automated analysis of MRD. Future directions involve integrating artificial intelligence, further automation, and exploring multicolor spectral flow cytometry to standardize MRD assessment and enhance diagnostic and prognostic robustness of MRD diagnostics in BCP-ALL.

Efficacy and safety of salvage endoscopy in the treatment of residual or recurrent colorectal neoplasia after endoscopic resection: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of salvage endoscopy for residual or recurrence of colorectal tumors after endoscopic resection. METHODS: Multiple databases including PubMed, EMBASE and the Cochrane Library were searched to screen for eligible studies and perform data extraction and pooled analysis. RESULTS: Sixteen studies on salvage endoscopy for residual or recurrent colorectal cancer after endoscopic resection were included, covering approximately 994 patients. The results of the meta-analysis demonstrated that salvage endoscopic therapy for residual or recurrent colorectal tumors following endoscopic resection achieved an en bloc resection rate of 92% (95% CI 0.85-0.97; I2 = 91%) and an R0 resection rate of 82% (95% CI 0.75-0.87; I2 = 78%). The rates of intraoperative or postoperative bleeding and perforation were 10%/1% and 5%/2%, and the recurrence rate was 2%. CONCLUSIONS: Salvage endoscopic resection is an effective and safe treatment strategy for residual or recurrent colorectal tumors after endoscopic resection.

Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant.

We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10-5 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT® system and liquid chromatography-mass spectrometry (LC-MS). Forty-two patients entered the treatment phase; forty were evaluable for the primary endpoint. The rate of sCR and/or MRD < 10-5 following C8 was 30/40 (75%), meeting the statistical threshold for efficacy. The 10-6 MRD negative rate improved with treatment beyond C8. Agreement between EXENT® and NGS was high and increased over time; agreement between LC-MS and NGS was lower. The estimated 3-year progression-free survival progression-free survival was 85%, and 3-year overall survival was 95%. Upper respiratory infections occurred in 67% (7% grade 3-4). There were no treatment-related deaths. Extended frontline Dara-KRd induced a high rate of sCR and/or MRD negativity; the rate and depth of MRD negativity improved beyond C8.