Relapse-free Survival Research Articles

The Dilemma for Early-Stage Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: To Treat or Not to Treat?

Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALToma) is typically treated with radiotherapy. Some studies suggested a "wait and watch" approach due to the adverse effects of radiotherapy. However, the benefits of observation for localized conjunctival MALToma remain unclear. Therefore, we aimed to explore the clinical course of early-stage conjunctival MALToma, distinguish heterogeneity between T1 and T2 patients, and identify prognostic factors. This retrospective study involved patients with stage T1-T2 conjunctival MALToma and lasted >6 months. Clinical characteristics were compared between T1 and T2 subjects. Prognostic factors were examined with Cox regression. The research comprised 32 subjects with early-stage conjunctival MALToma, of whom 25% underwent observation. No individuals expired regardless of choosing observation or radiotherapy. The T1 patients were younger (p = 0.002) and more inclined towards observation only (p = 0.035) than the T2 subjects. Despite more of the T1 patients undergoing watchful waiting than the T2 subjects, the T1 patients seemed to have longer systemic relapse-free survival than the T2 subjects (17 vs. 13 years, p = 0.343). CD43 may imply poor prognosis (p = 0.049). Careful observation may be suggested for early-stage conjunctival MALToma. While more of the T1 individuals were younger and chose observation than the T2 patients, survival seemed longer in the T1 subjects without significance. CD43 may indicate shorter survival in early-stage cases.

Effect analysis of 847 nasopharyngeal carcinoma cases treated with intensity modulated radiation: Experience and suggestions

ObjectivesTo identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. MethodsData on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. ResultsThe 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. ConclusionNPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local–regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.

CAST Regimen for GvHD Prophylaxis: A CIBMTR Propensity Score-Matched Analysis

Previously, we reported excellent results with the combination of post-transplant cyclophosphamide (PTCy), abatacept, and a short course of tacrolimus (CAST) for the prevention of graft-versus-host disease (GvHD) following peripheral blood haploidentical transplantation. To further substantiate these results, we performed a propensity score-matched analysis. Patients enrolled in the CAST trial were matched with patients from a contemporaneous cohort from the Center for International Blood and Marrow Transplant Research database who received PTCy, tacrolimus, and mycophenolate mofetil, using nearest neighbor propensity score matching. An excellent balance between pairs was achieved as measured by the density distribution and standardized differences of covariates (median 0.09). The rates of acute GvHD grades II to IV at day +120 and 1-year GvHD- and relapse-free survival were 16.7% and 66.7% in the CAST cohort versus 28.6% and 47.6% in the control group, respectively. This trend did not reach statistical significance (P = .14 and .07), possibly due to the small numbers of patients and events. On the other hand, CAST was associated with a statistically significant reduction in the incidence of relapse (9.5% versus 26.2%, P = .045) with improved disease-free survival (85.7% versus 61.9%, P = .01). Our data provides a strong impetus to examine CAST in a randomized clinical trial.

Relationship between morphologic remission with or without hematologic recovery and outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia.

Outcomes of adults with AML after allografting vary widely. While numerous covariates have been associated with relapse, non-relapse mortality (NRM), and/or shorter survival, the impact of incomplete blood count recovery before transplantation has remained unclear. To address this uncertainty, we examined all adults with AML or MDS/AML who received an allograft in first or second remission between 2006 and 2023 at a single institution. Of 1264 patients, 891 (70%) met criteria for CR, whereas 291 (23%), 24 (2%), and 58 (5%) were classified as CRh, CRi, and morphologic leukemia-free state (MLFS), respectively. CR, CRh, CRi, and MLFS patients differed significantly regarding demographics, disease biology, pre-transplant measurable residual disease, and types of transplants. After multivariable adjustment, outcomes for CRh and CRi patients were not significantly different from each other or from those of CR patients. In contrast, outcomes of MLFS patients were substantially worse than those of CR and CRh patients, with significantly higher risk of NRM and relapse, and significantly shorter relapse-free and overall survival. Similar results were obtained in several distinct subsets. Together, our analysis provides empiric evidence for the importance of distinguishing MLFS from CR and CRh patients for optimized risk assessment and, possibly, individualized treatment decision making.

Proton pencil beam scanning radiotherapy in the postoperative treatment of p16 positive squamous cell tonsillar cancer – evaluation of toxicity and effectivity

PurposePatients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT).MethodsBetween September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2–74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients.ResultsMedian follow-up time was 4.2 (0.15–9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent.ConclusionIMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity.

PAK4 Is Involved in the Stabilization of PD-L1 and the Resistance to Doxorubicin in Osteosarcoma and Predicts the Survival of Diagnosed Patients.

PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation.

Characterizing the Mutational Landscape of Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Mexican Patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy worldwide. Molecular classifications have tried to improve cure rates. We prospectively examined and correlated the mutational landscape with the clinical features and outcomes of 185 Mexican patients (median age 59.3 years, 50% women) with newly diagnosed DLBCL. A customized panel of 79 genes was designed, based on previous international series. Most patients had ECOG performance status (PS) < 2 (69.2%), advanced-stage disease (72.4%), germinal-center phenotype (68.1%), and double-hit lymphomas (14.1%). One hundred and ten (59.5%) patients had at least one gene with driver mutations. The most common mutated genes were as follows: TP53, EZH2, CREBBP, NOTCH1, and KMT2D. The median follow-up was 42 months, and the 5-year relapse-free survival (RFS) and overall survival (OS) rates were 70% and 72%, respectively. In the multivariate analysis, both age > 50 years and ECOG PS > 2 were significantly associated with a worse OS. Our investigation did not reveal any discernible correlation between the presence of a specific mutation and survival. In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies.

Identification of candidate biomarkers and prognostic analysis of recurrence in colorectal cancer.

Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, which has a high mortality rate especially for patients with CRC recurrence. However, the pathological mechanism of recurrence of CRC is unclear. In this study, we integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in recurrence of CRC. As results, 628 DEGs were identified from GSE33113 and GSE2630 datasets and their function and pathway were analyzed. 14 hub genes related to CRC recurrence were screened from and their influence on survival were analyzed. Two key genes (IL1B and DDAH1) regarded as prognostic factors were further screened. Relapse-free survival results indicated the interaction between IL1B and DDAH1 genes and B cells was the most obvious and correlated with survival, with statistical significance (P< 0.05). Specially, cox regression analysis suggested that patients with T1 and N0 stages had a higher risk of recurrence than patients with T2 and N1. This work would provide potential value for prognosis, and would promote molecular targeting therapy for CRC recurrence.

Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation

IntroductionAllogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes. ObjectiveTo compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT. MethodsThis is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups. ResultsWe identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8 %) patients had molecular profiling done among whom 57 (45.2 %) patients carried a spliceosome mutation. 84.9 % of patients had MDS and 55.6 % underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12–77).78.6 % and 73.7 % received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5 % (95 %CI 0.55–0.75) with a day 100 NRM of 7.1 % and 2-year cumulative incidence of relapse of 20 %. Grade II-IV acute GVHD at day 100 was 36.3 % (95 % CI 0.27–0.44) and any chronic GVHD at 2-years was 48.4 % (95 % CI 0.37–0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8 % vs 55.9 % in the non-spliceosome group (P=0.002) and a better PFS of 73.7 % vs 50.0 % (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9 % vs 18.5 % (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4 % vs 31.5 % (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups. ConclusionsAmong patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the intermediate MDS prognostic risk groups.

Volumetric Modulated Arc Therapy for High-Risk and Very High-Risk Locoregional Prostate Cancer in the Modern Era: Real-World Experience from an Asian Cohort.

This study retrospectively evaluates the clinical outcomes of definitive volumetric modulated arc therapy (VMAT) for high-risk or very high-risk locoregional prostate cancer patients from an Asian institution. Consecutive patients who received VMAT (76 Gy in 38 fractions) between January 2017 and June 2022 were included. Whole pelvic radiotherapy (WPRT) (46 Gy in 23 fractions) was employed for clinically node-negative disease (cN0) and a Roach estimated risk of ≥15%, as well as simultaneous integrated boost (SIB) of 55-57.5 Gy to node-positive (cN1) disease. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints included radiographic relapse-free survival (RRFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS). A total of 209 patients were identified. After a median follow-up of 47.5 months, the 4-year actuarial BRFS, RRFS, MFS and PCSS were 85.2%, 96.8%, 96.8% and 100%, respectively. The incidence of late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 15.8% and 11.0%, respectively. No significant difference in cancer outcomes or toxicity was observed between WPRT and prostate-only radiotherapy for cN0 patients. SIB to the involved nodes did not result in increased toxicity. International Society of Urological Pathology (ISUP) group 5 and cN1 stage were associated with worse RRFS (p < 0.05). PSMA PET-CT compared to conventional imaging staging was associated with better BRFS in patients with ISUP grade group 5 (p = 0.039). Five-year local experience demonstrates excellent clinical outcomes. PSMA PET-CT staging for high-grade disease and tailored pelvic irradiation based on nodal risk should be considered to maximize clinical benefit.

Induction plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy in elderly patients with locoregionally advanced nasopharyngeal carcinoma

BackgroundThe effectiveness and safety of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in elderly patients with locoregionally advanced nasopharyngeal carcinomas (LANPCs) remain subjects of debate. This study evaluated the efficacy of IC+CCRT compared to CCRT alone in elderly LANPC patients. Materials and methodsThis retrospective, single-center study analyzed 335 elderly patients diagnosed with stage III or IVa NPC who received CCRT with or without IC between 2010 and 2016. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival rates. Multivariate analysis using Cox proportional hazards regression model was conducted to assess prognostic risk factors. Toxicities were compared using the χ2 test. ResultsThe median follow-up duration was 69.3 months (interquartile range: 42.7–72.6). Baseline clinical characteristics were well-balanced between groups. No significant differences were observed between IC+CCRT and CCRT for any survival-related endpoints, including overall survival (hazard ratio [HR] = 1.26, 95 % confidence interval [CI]: 0.89–1.77, p = 0.188), locoregional relapse-free survival (HR=1.03, 95 % CI: 0.56–1.91, p = 0.913), distant metastasis-free survival (HR=1.39, 95 % CI: 0.90–2.16, p = 0.139), and failure-free survival (HR = 1.25, 95 % CI: 0.85–1.83, p = 0.255). However, the incidence and severity of acute and late toxicities were significantly higher in the IC+CCRT group compared to the CCRT group. ConclusionIn elderly LANPC patients, the addition of IC to CCRT did not improve survival outcomes, but was associated with significant toxicities.

Survival (Time-To-Event) Curve Names and Endpoints

In oncology, “survival curves” frequently appear in journal articles and meeting presentations. The most common labels on survival curves are overall survival, relapse-free survival, progression-free survival, distant metastasis-free survival, and local and/or regional control. Unfortunately, consistency in the definition of an event differs between authors for the same prescribed survival analyses. Furthermore, the quality of survival curves can be greatly impacted by the methodology used for endpoint selection. This paper will briefly explain widely used names and event endpoints for survival analyses in a way that will help radiation oncologists consistently present and interpret experimental findings that influence clinical practice decisions.

PD-L1 expression and tumor-infiltrating lymphocytes: Correlations and prognostic values in Chinese triple-negative breast cancer patients with different molecular subtyping

ObjectiveTo investigate the correlation between programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) and evaluate the prognostic value of PD-L1 and TILs in Chinese triple-negative breast cancer (TNBC) patients with different molecular subtype MethodsThis retrospective study was conducted at 2020. Specifically, the pre-chemotherapy clinical data and non-stained tissue blocks of 465 TNBC patients visited the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014 were collected, with their blocks sliced and stained using PD-L1(SP142), and the outcome of subsequent chemotherapy obtained in 2020. The relapse-free survival (RFS) of the study population was calculated. The baseline PD-L1 expression status correlations with TILs and molecular subtypes were assessed using Spearman’s rank correlation analysis and the Kruskal-Wallis test. Kaplan-Meier survival analyses were undertaken to evaluate the prognosis value of TILs and PD-L1 expression. ResultsPD-L1 expression status on IC was moderately and positively correlated with stromal tumor-infiltrating lymphocytes (sTILs) (rs = 0.502, P <0.001) and iTILs (rs = 0.410, P < 0.001), respectively. PD-L1 expression status and TILs showed significant differences among molecular subtypes (P < 0.001), with the highest proportion of PD-L1+ and high TILs patients observed in the immunomodulatory (IM) subtype. TILs were significantly associated with RFS. Moreover, sTILs could act as an independent predictor of RFS (RR 0.953, 95 % CI 0.920 ∼ 0.987, P = 0.007), while PD-L1 expression status did not show the same prognostic significance. ConclusionsThe incorporation of pre-treatment TILs and PD-L1 expression status as valuable tools for optimizing patient selection for immunotherapy and managing the risks associated with chemotherapy in Chinese TNBC patients. Data availabilityThe data sets generated and analyzed during the current study are available from the corresponding author.

Health-related quality of life with gilteritinib vs placebo posttransplant for FLT3-ITD+ acute myeloid leukemia

AbstractThe Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being “bothered by side effects of treatment” did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202.

Graft Versus Host Disease Prophylaxis in Matched Donor Stem Cell Transplantation: Post-transplantation Cyclophosphamide Combinations Versus Methotrexate/Tacrolimus

BackgroundThe use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft versus host disease (GVHD) for haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is limited data on the role of PTCy as GVHD prophylaxis in matched-sibling and fully matched-unrelated donor (MSD/MUD) allo-HSCT. MethodsOur single-center retrospective study aims to compare outcomes of PTCy alone or in combination with mycophenolate mofetil and tacrolimus (PTCy/MMF/TAC) relative to methotrexate and tacrolimus (MTX/TAC). The primary endpoint of our study was GVHD-free, relapse free survival (GRFS). Secondary endpoints were overall survival (OS), disease free survival (DFS), and incidence of severe acute and chronic GVHD. We identified 74 adult patients who underwent MSD/MUD allo-HSCT at our institution from 2015 to 2023. ResultsWithin our cohort, 33.8% (n = 25) received MTX/TAC, while 54.0% (n = 40) received PTCy/MMF/TAC, and 12.2% (n = 9) received PTCy alone. Patients receiving PTCY had the longest time to neutrophil engraftment relative to MTX/TAC (15 days vs. 12 days, P = .010). PTCy/MMF/TAC was associated with improved GRFS relative to MTX/TAC (hazard ratio [HR] = HR 0.42, 95% CI 0.19-0.93, P = .031), which persisted when controlling for age. Incidence of chronic GVHD was lower in the PTCy/MMF/TAC group compared to MTX/TAC (1-year 9.0% vs. 30.1%, HR 0.19, 95% CI 0.06-0.59, P = .005). However, OS and DFS were comparable across all groups. ConclusionsOur results demonstrate decreased rates of severe chronic GVHD resulting in improved GRFS when using PTCy/TAC/MTX as GVHD prophylaxis compared to MTX/TAC in MSD/MUD.

Fluctuations in serum lipid levels during neoadjuvant treatment as novel predictive and prognostic biomarkers for locally advanced breast cancer: a retrospective analysis based on a prospective cohort

BackgroundWith increasing attention given to host-specific lipid metabolism status, it is of urgent need to identify lipid metabolism indices with predictive or prognostic value in locally advanced breast cancer patients treated with neoadjuvant chemotherapy (NAC), and to evaluate the performance improvement by incorporating them into the existing Neo-Bioscore staging system.MethodsPatients from a prospectively maintained database of locally advanced breast cancer patients who received radical surgery after NAC between January 2014 to December 2020 were enrolled in this study. The enrolled patients were randomly divided into a training set and a test set at a ratio of 6:4. The random forest algorithm was applied to rank the importance of prognostic factors, top-ranked lipid metabolism indices of which were then incorporated into Neo-Bioscore to construct an updated prognostic model. The performances of these two models were compared in both training set and test set from multiple perspectives. Study outcomes included disease-free survival (DFS), relapse-free survival (RFS), distance-recurrence-free survival (DRFS), locoregional-recurrence-free survival (LRFS) and overall survival (OS).ResultsA total of 200 eligible patients were included in this study. After a median follow-up of 4.73 years, it was demonstrated that the relative increase in total cholesterol (TC; DFS: HR = 4.782, 95%CI 1.410 ~ 16.217, P = 0.012) and low-density lipoprotein (LDL; DFS: HR = 4.622, 95%CI 1.517 ~ 14.088, P = 0.007) during NAC led to poorer survival outcomes. Patients with either a higher body mass index (BMI) or elevated LDL during NAC had a worse prognosis (DFS: HR = 6.351, 95%CI 1.938 ~ 20.809, P = 0.002; OS, HR = 6.919, 95%CI 1.296 ~ 36.932, P = 0.024). Incorporating BMI and LDL fluctuations during NAC into Neo-Bioscore improved the prognostic stratification, especially in terms of LRFS (P = 0.046 vs. P = 0.65) and OS (P = 0.013 vs. P = 0.61). Multidimensional evaluation confirmed the improvement in model fit and clinical use for the updated model in both training set and test set.ConclusionsThis is the first study to illustrate the relative elevation of LDL and TC levels during NAC as independent prognosticators for locally advanced breast cancer. This is also the first attempt to incorporate lipid metabolism indices into the original Neo-Bioscore staging system, which further improves the prognostic stratification of patients receiving NAC.

Oncological similarities between large type 3 and type 4 tumors in patients with resectable gastric cancer: a propensity score-matched analysis of a multi-institutional dataset

BackgroundLarge type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue.MethodsIn this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences.ResultsOf patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14–2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73–2.25) and relapse-free survival (HR 1.34; 95% CI 0.80–2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15).ConclusionsLarge type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials.

Patterns and Predictors of Recurrence After Curative Resection of Colorectal Liver Metastasis (CRLM).

Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection. A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables. The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38months (30-54) and 13months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences. The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers.

Prognostic significance of CRLF2 in patients with acute lymphoblastic leukemia: a meta-analysis and systematic review.

The association between cytokine receptor-like factor 2 (CRLF2) and clinical outcomes in acute lymphoblastic leukemia (ALL) has been a topic of ongoing debate, with divergent findings. This article intended to investigate the influence of CRLF2 alterations on ALL prognosis. Following the PRISMA 2020 guidelines, this meta-analysis was conducted. Hazard ratio (HR) values and confidence intervals (CIs) were the primary statistical measures used. Data heterogeneity was judged using the chi-square test and I2 statistic. Publication bias was appraised with funnel plots, Begg's test, and Egger's test. 16 studies with 6771 patients were finally screened out. CRLF2 over-expression (CRLF2 OE) was associated with poorer event-free survival (EFS) (HR = 1.70, 95% CI = 1.18-2.44, P = 0.004) and relapse-free survival (RFS) (HR = 1.70, 95% CI = 1.28-2.24, P = 0.000) in pediatric ALL. Patients with CRLF2-deregulation (CRLF2-d), also known as CRLF2 rearrangement, exhibited shorter overall survival (OS) (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.93, 95% CI = 1.43-2.60, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) compared to those without CRLF2-d. Subgroup analysis of multivariate HRs and corresponding CIs indicated that childhood with CRLF2 OE had a shorter RFS (HR = 1.70, 95% CI = 1.28-2.24, P = 0.006), and CRLF2-d was identified as an independent prognostic biomarker for OS (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.95, 95% CI = 1.44-2.64, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) in pediatric ALL patients. Both CRLF2 OE and CRLF2-d are associated with poor prognosis in ALL patients.

Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.