Five-year Progression-free Survival Research Articles

Clinical and methylomic features of spinal meningiomas.

The objective of our study was to analyze methylomic and clinical features of a cohort of spinal meningiomas (SMs) resected at our institution. This is a retrospective study of patients undergoing SM resection at our institution between 2010 and 2023. Clinical and radiographic characteristics were reviewed and analyzed with standard statistical methods. A Partitioning Around Medoids approach was used to cluster SMs with methylation data in a combined cohort from our institution and a publicly available dataset by methylation profiles. Clinical variables and pathway analyses were compared for the resulting clusters. Sixty-five SMs were resected in 53 patients with median radiographic follow-up of 34 months. Forty-six (87%) patients were female. The median age at surgery was 65 years and median tumor diameter was 1.9cm. The five-year progression-free survival rate was 90%, with subtotal resection being associated with recurrence or progression (p = .017). SMs clustered into hypermethylation, intermediate methylation, and hypomethylation subgroups. Tumors in the hypermethylated subgroup were associated with higher WHO grade (p = .046) and higher risk histological subtypes (p <.001), while tumors in the hypomethylated subgroup were least likely to present with copy-number loss in chromosome 22q (p <.0001). SMs classified as immune-enriched under a previously developed intracranial meningioma classifier did not have increased leukocyte fractions or hypomethylation of genes typically hypomethylated in immune-enriched tumors. SMs are more benign than their intracranial counterparts, and gross-total resection results in long term PFS. Methylation profiling identifies subgroups with differences in clinical variables.

Bortezomib, lenalidomide, and dexamethasone versus bortezomib, doxorubicin, and dexamethasone in newly diagnosed multiple myeloma

Bortezomib, lenalidomide, and dexamethasone (VRD), and bortezomib, doxorubicin, and dexamethasone (PAD), are commonly used in induction regimens for patients with newly diagnosed multiple myeloma (NDMM) in China. This real-world study enrolled 390 patients, 195 receiving VRD and 195 receiving PAD induction. The primary endpoint was progression-free survival (PFS) and stringent complete remission/complete remission. Across the entire cohort, VRD demonstrated significantly improved five-year overall survival (OS) (74% vs. 59%, p = 0.0024) and five-year PFS (67% vs. 37%, p = 0.0018) compared to PAD. Notably, the median OS and PFS were not reached for VRD-treated patients, while they were 77 months (60-not reached [NR]) and 46 months (36-NR), respectively, for PAD. In patients with standard-risk cytogenetics, VRD showed superior five-year OS (83% vs. 58%, p = 0.0038) and PFS (78% vs. 48%, p = 0.0091) compared to PAD. However, these differences were not statistically significant in high-risk patients. For transplanted patients, VRD was associated with superior five-year OS (91% vs. 67%, p = 0.014) and PFS (79% vs. 47%, p = 0.015) compared to PAD. In non-transplanted patients, VRD showed a trend towards improved five-year OS (p = 0.085) and PFS (p = 0.073) compared to the PAD group. In conclusion, VRD displayed superior OS and PFS outcomes in standard-risk patients and those who underwent transplantation. These findings suggest potential advantages of VRD over PAD in real-world clinical settings for NDMM treatment. However, due to the imbalance in transplantation rates between the VRD and PAD groups, limitations in testing for high-risk cytogenetic abnormalities (HRA), and the difference between the received cycles and salvage therapies, the conclusions of this study should be interpreted with caution.

The controlling nutritional status score as a new prognostic predictor in patients with cervical cancer receiving radiotherapy: a propensity score matching analysis

BackgroundAs assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score’s prognostic value and survival time in patients with FIGO stage IIB–IIIB cervical cancer treated with radiotherapy.MethodsIn this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan–Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score’s predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS).ResultsThe cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54–5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52–5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis.ConclusionThe CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.

Five-year outcomes with first-line nivolumab plus ipilimumab with 2 cycles of chemotherapy versus 4 cycles of chemotherapy alone in patients with metastatic non-small cell lung cancer in the randomized CheckMate 9LA trial

BackgroundWe report 5-year efficacy and safety outcomes from CheckMate 9LA in patients with metastatic non-small cell lung cancer (mNSCLC) and exploratory analyses in key patient subgroups. MethodsAdults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to receive nivolumab plus ipilimumab with chemotherapy (n = 361) or chemotherapy (n = 358). Outcomes were assessed in all randomized patients and subgroups. ResultsWith 57.3 months’ minimum follow-up, patients continued to derive overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy over chemotherapy (HR, 0.73; 95% CI, 0.62–0.85; 5-year OS rates, 18% vs. 11%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 < 1%, 22% vs. 8%; PD-L1 ≥ 1%, 18% vs. 11%), histology (squamous, 18% vs. 7%; non-squamous, 19% vs. 12%), or presence of baseline brain metastases (20% vs. 6%). Five-year duration of response (DOR) rates were 19% versus 8% with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, with consistent benefit across subgroups. Patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events had a 5-year OS rate of 37%. Five-year progression-free survival and DOR rates in 5-year survivors were 55% versus 38% and 59% versus 46%, respectively. No new safety signals were observed in 5-year survivors, regardless of the number of ipilimumab doses received. ConclusionThis 5-year update supports the long-term, durable OS benefit and improved 5-year survivorship with nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with mNSCLC, regardless of tumor PD-L1 expression or histology. ClinicalTrials.gov registrationNCT03215706

Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation

The effect of primary cytoreductive surgery versus interval cytoreductive surgery on FIGO IV ovarian cancer outcomes remains uncertain, and may vary depending on the stage and the extraperitoneal metastasis location. Emulating target trials through causal assessment combined with propensity score adjustment has become a leading method for evaluating interventions using observational data. To assess the effect of primary versus interval cytoreductive surgery on progression-free and overall survival in patients with FIGO IV ovarian cancer using target trial emulation. Utilizing the comprehensive French national health insurance database, we emulated a target trial to explore primary versus interval cytoreductive surgery causal impacts on FIGO IV ovarian cancer prognosis (Surgery for Ovarian cancer FIGO 4: SOFI-4). The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and balance baseline characteristics between the groups. Subgroup analyses were conducted based on FIGO stages and extraperitoneal metastasis locations. The study included patients under 75 years of age, in good health condition, diagnosed with FIGO IV ovarian cancer between January 1, 2014, and December 31, 2022. The primary and secondary outcomes were respectively five-year progression-free survival and seven-year overall survival. Among the 2,772 patients included in the study, 948 (34.2%) were classified as FIGO IVA and 1,824 (65.8%) as FIGO IVB at inclusion. Primary cytoreductive surgery was performed on 1,182 patients (42.6%), while interval cytoreductive surgery was conducted on 1,590 patients (57.4%). The median progression survival for primary cytoreductive surgery was 19.7 months (interquartile range [IQR]: 19.3-20.1), compared to 15.7 months (IQR: 15.7-16.1) for those who underwent interval cytoreductive surgery. The median overall survival was 63.1 months [IQR: 61.7-65.4] for primary cytoreductive surgery, in comparison to 55.6 months [IQR: 53.8-56.3] for interval cytoreductive surgery. The findings of our study indicate that primary cytoreductive surgery is associated with a 5.0-month increase in five-year progression-free survival (95% Confidence Intervals [CI]: 3.8-6.2) and a 3.9-month increase in seven-year overall survival (95% CI: 1.9-6.2). These survival benefits of primary over interval cytoreductive surgery were observed in both the FIGO IVA and IVB subgroups. Primary cytoreductive surgery demonstrated improved progression-free survival and overall survival in patients with pleural, supra-diaphragmatic, or extra-abdominal lymph node metastasis. SOFI-4 advocates for the benefits of primary cytoreductive surgery over interval cytoreductive surgery for patients with FIGO IV ovarian cancer, suggesting extraperitoneal metastases like supra-diaphragmatic or extra-abdominal lymph nodes should not automatically preclude primary cytoreductive surgery consideration in suitable patients.

2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer: oncologic outcomes based on involvement of adnexa, serosa, or both

ObjectiveTo assess clinicopathologic features and survival outcomes of patients with endometrial carcinoma involving adnexal, full-thickness serosal, or combined involvement.MethodsThis international, multi-institutional, retrospective study examined patients with 2009 International Federation of...

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study

BackgroundThe 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4...

Molecular and clinical characterization of atypical central neurocytomas: implications for diagnosis and treatment strategies

ObjectivesThis study aimed to investigate the histological and molecular characteristics of atypical central neurocytomas (CNs) and evaluate their clinical treatment outcomes, with the aim of identifying reliable biomarkers for differentiation and optimal treatment strategies.MethodsWe conducted a retrospective study including 61 patients diagnosed with CNs. Clinical data, neuroimaging, and pathological findings were analyzed. RNA sequencing was performed on tumor tissues to identify differentially expressed genes.ResultsHistological atypia and the Ki-67 index showed no significant impact on progression-free survival (PFS) or overall survival (OS). RNA sequencing identified significant genetic alterations in pathways such as neuroactive ligand–receptor interaction, cAMP, MAPK, and Ras signaling. Differently expressed genes included AMOTL1, PIK3R3, TGFBR1, SMO, COL4A6, MGP, SOX4, IGF2, SLIT1, and CKS2. The five-year OS rate (p = 0.015) and PFS rate (p = 2.00 × 10−6) were significantly higher in the complete resection (CR) group compared to the incomplete resection (IR) group. Postoperative radiotherapy did not affect OS or PFS in the CR group. The five-year PFS rate (p = 3.80 × 10−5) was significantly longer in patients in the CR group who did not receive radiotherapy compared to those in the IR group who did receive radiotherapy. The extent of surgical resection and operative approaches were found to be irrelevant to perioperative complications and dysfunctions at the last follow-up.ConclusionCR is crucial for a better prognosis in patients with atypical CNs. Additional radiotherapy after CR offers little benefit. Histological atypia and the Ki-67 index are not effective in distinguishing between atypical and typical CNs. Identified genetic alterations provide insights into the aggressive behavior of atypical CNs, suggesting potential therapeutic targets and underscoring the need for further research to optimize treatment strategies.

Pathologic Response and Survival after Neoadjuvant Chemotherapy with Bevacizumab Followed by Surgery for Clinical Stage II/IIIA Nonsquamous Non-Small-Cell Lung Cancer: Results from a Phase II Feasibility Study (NAVAL).

The objective of this study was to evaluate the relationship between pathologic response and survival in patients with clinical stage II/IIIA nonsquamous non-small-cell lung cancer (NSCLC) who intended to undergo neoadjuvant chemotherapy with bevacizumab, followed by surgery. In this phase II NAVAL study evaluating the feasibility of neoadjuvant chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg), followed by surgery, progression-free survival (PFS) and overall survival (OS) were assessed as the secondary endpoints. Patients were categorized based on the proportion of residual viable primary tumor in the resected specimen after neoadjuvant chemotherapy: those with residual tumor in less than one-third were classified as pathologic responders, the rest as nonresponders. Of the 30 patients, 25 underwent surgical resection after three cycles of neoadjuvant chemotherapy with bevacizumab; 5 did not undergo surgery. Among all 30 patients, the rates of 2- and 5-year PFS were 41.5% and 34.6%, respectively, and the rates of 2- and 5-year OS were 70.0% and 60.0%, respectively. A total of 6 patients (20%) were classified as pathologic responders; the other 24 (80%), as nonresponders. The five-year PFS differed significantly between pathologic responders (100%) and nonresponders (17.5%; p = 0.002). The five-year OS also differed significantly between pathologic responders (100%) and nonresponders (43.5%; p = 0.006). Pathologic response seems to be a predictor of survival. Long-term survival after surgery is expected for pathologic responders, whereas additional therapy is needed for nonresponders.

BeEAM vs. BEAM: evaluating conditioning regimens for autologous stem cell transplantation in patients with relapsed or refractory DLBCL.

To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups. The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804). As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.

The Effectiveness of Denosumab in Middle Eastern Patients With Giant Cell Tumor of the Bone: A Single-Center, Retrospective Study.

Giant cell tumor of the bone (GCTB) is an aggressive benign tumor, which constitutes 5% of all primary bone tumors. Denosumab, a receptor activator of nuclear factor κB ligand monoclonal antibody, inhibits osteoclast-induced bone destruction and has demonstrated promising results in patients with GCTB. However, the long-term efficacy of the drug has not been extensively studied, especially in the Middle East. In this study, we retrospectively analyzed the five-year progression-free survival (PFS) in patients with GCTB at a single Saudi center. PFS was defined as the time from diagnosis until disease progression, relapse, or death. Events were censored after five years from diagnosis. Sixty-two patients with GCTB were included in the study. The median age at diagnosis was 31.16 years, and 38 (61.3%) patients were female. Twenty-nine patients (46.8%) received denosumab during the study period. The median duration of denosumab treatment was 5.06 months, and the median number of cycles was 6. The median PFS was not reached, and the five-year PFS rate was 60.3%. Age, gender, body mass index, performance status at presentation, and tumor location had no impact on five-year PFS. Denosumab treatment prolonged PFS; however, this was not statistically significant compared to non-denosumab patients (P= 0.603). Denosumab does not seem to provide superior long-term outcomes compared to surgery alone. Although our findings are generally consistent with other studies in the literature, larger long-term studies are needed to confirm our findings.

Abstract 7319: Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis

Abstract Background: Clinical diabetic traits have been reported to be associated with increased colorectal cancer risk (CRC) in observational studies. Using the Mendelian randomization (MR) analysis method, we examined the causal association between glycemic traits, such as fasting glucose (FG), fasting insulin (FI), and glycosylated hemoglobin A1c (HbA1c), and survival in a cohort of CRC patients. Methods: We conducted a two-sample MR analysis among a cohort of patients with locally advanced CRC at Seoul National University Hospital. Single-nucleotide polymorphisms robustly associated (P&amp;lt;5 × 10−8) with the three glycemic traits were obtained from the Meta-Analyses of Glucose and Insulin-related traits Consortium, Asian Genetic Epidemiology Network, and Korea Biobank Array. Three-year and five-year overall survival (OS) and progression-free survival (PFS) were used as outcomes. Survival analysis was conducted using subgroup analysis by cancer stage and subsite in a multivariate Cox proportional hazards model adjusted for age and sex to examine whether glycemic traits affected survival. Results: A total of 509 patients were included in our final analysis. MR analysis showed that HbA1c levels were associated with poor three-year OS (β=4.20, P=0.02). Sensitivity analyses did not show evidence of any violations of the MR assumptions. In the cancer subgroup analysis of the Cox proportional hazards model, pooled hazard ratios for FG were significantly associated with poor three-year OS and PFS regardless of cancer stage. FI was not significantly associated with any three-year survival endpoints. Among stage III patients, three glycemic traits were significantly associated with both five-year OS and PFS. Location-specific subgroup analysis showed a significant association between three glycemic traits and five-year PFS in patients with left-sided colon cancer. FG was associated with poor three-year survival for colon cancer but not rectal cancer. Conclusions: Our results suggest that FG and HbA1c could be used to predict prognosis in CRC patients. Lifestyle and/or pharmacological interventions targeting glycemic traits could help improve survival for CRC patients. Citation Format: So Yon Jun, Sooyoung Cho, Min Jung Kim, Ji Won Park, Seung Yong Jeong, Aesun Shin. Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7319.

Efficacy and tolerability of bacillus Calmette-Guérin strain Russia for the treatment of non-muscle-invasive bladder cancer Analysis of a prospective registry.

Little is known about the efficacy and tolerability of intravesical bacillus Calmette-Guérin (BCG) strain Russia for treatment of non-muscle-invasive bladder cancer (NMIBC) in a middle-European population. A prospective collection of outcomes of 101 BCG-naive patients with urothelial bladder carcinoma was carried out between January 2013 and October 2023 at the University Hospital Basel, Basel, Switzerland. Patients underwent BCG (ONCO-BCG-SIIL, Serum Institute of India, Pune, India) induction and a maximum of three maintenance cycles within one year. Adverse events were classified according to the World Health Organization rating scale. One-, three-, and five-year recurrence-free survival (RFS) was 75.9%, 65.6%, and 61.6%, respectively. Tumor recurrence was seen in 31.7% of patients. One-, three-, and five-year progression-free survival (PFS) was 100%, 93.4%, and 93.4%, respectively. Cystectomy rate was 8.9%, with progression to muscle-invasive disease seen in two patients. Adverse events occurred in 72.3% of patients, with adverse events >class II seen in 8.9%. No BCG-related deaths occurred. Early cessation due to side effects resulting in non-adequate BCG therapy was seen in 3% of patients during induction and in 1% during maintenance therapy. BCG Russia was well-tolerated and resulted in comparable RFS and PFS to historical results of prospective clinical trials with other BCG strains. The use of BCG Russia for adjuvant treatment of papillary NMIBC and therapy of carcinoma in situ of the urinary bladder could help alleviate the BCG shortage.

Time trends in real-world treatment patterns and survival in patients diagnosed with de novo HER2+ metastatic breast cancer: an analysis of the SONABRE registry

PurposeThe aim was to determine whether the real-world first-line progression-free survival (PFS) of patients diagnosed with de novo human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer (ABC) has improved since the introduction of pertuzumab in 2013. In addition to PFS, we aimed to determine differences in overall survival (OS) and the use of systemic and locoregional therapies.MethodsIncluded were patients systemically treated for de novo HER2+ ABC in ten hospitals in 2008–2017 from the SONABRE Registry (NCT-03577197). First-line PFS and OS in 2013–2017 versus 2008–2012 was determined using Kaplan–Meier analyses and multivariable Cox proportional hazards modelling. First-given systemic therapy and the use of locoregional therapy within the first year following diagnosis were determined per period of diagnosis.ResultsMedian and five-year PFS were 26.6 months and 24% in 2013–2017 (n = 85) versus 14.5 months and 10% in 2008–2012 (n = 81) (adjusted HR = 0.65, 95%CI:0.45–0.94). Median and five-year OS were 61.2 months and 51% in 2013–2017 versus 26.1 months and 28% in 2008–2012 (adjusted HR = 0.55, 95%CI:0.37–0.81). Of patients diagnosed in 2013–2017 versus 2008–2012, 84% versus 60% received HER2-targeted therapy and 59% versus 0% pertuzumab-based therapy as first-given therapy. Respectively, 27% and 23% of patients underwent locoregional breast surgery, and 6% and 7% surgery of a metastatic site during the first year following diagnosis.ConclusionThe prognosis of patients with de novo HER2 + ABC has improved considerably. Since 2013 one in four patients were alive and free from progression on first-given therapy for at least five years.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Children: A Retrospective Cohort Study at a Pediatric Oncology Center.

Background and objective Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+) is quite rare among pediatric patients. Its management has undergone significant changes in the past few years, leading to some variability in how it is approached. At the Portuguese Oncology Institute of Porto (IPOP),a tertiary oncological center, the standard of carehas been aligned with the guidelines proposed by the European intergroup study of post-induction treatment of ALL Ph+ (EsPhALL). In this study, we aimed to examine the experience and outcomes related tothe treatment of pediatric patients with ALL Ph+ at IPOP. Methods This retrospective cohort study involvedpediatric patients diagnosed with ALL Ph+ at IPOP between January 2008 and December 2022 and analyzed their outcomes. Results A total of 14 patients were included. IKFZ1 was altered in five patients (out of nine in whom it was searched). Five patients were treated according to EsPhALL 2004, which involved starting imatinib later in a discontinuous manner [resulting in both five-year overall survival (OS) and progression-free survival (PFS) of 60%]. The EsPhALL 2010 (preconizing a continuous imatinib regimen instead) was employed in three patients, with a five-year OS and PFS of 66.7%. Allchildren mentioned above received cranial irradiationtherapy (CRT). Finally, six were treated according to the EsPhALL 2015, which stopped including CRT in its backbone. The five-year OS was 100%, whereas every patient progressed with an increase in BCR::ABL1 levels greater than 1-log. Moreover, until 2015, all patients had been recommended to undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). However, since 2015, alloHSCT has been exclusively reserved for relapsed/refractory (R/R) disease or poor responders with positive measurable residual disease (MRD). In total, alloHSCT was performed in nine patients. Conclusions Although initially associated with a poor prognosis, the ALL Ph+ paradigm is drastically shifting. Further studies will hopefully clarify the outcomes in this population and help understand the role of central nervous system (CNS) prophylaxis, alloHSCT, and MRD quantification.

Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features

AbstractPrimary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare lymphoma with a variable prognosis and a unique relapse/dissemination pattern involving the central nervous system and skin. The underlying molecular mechanisms leading to this heterogeneity and progression pattern remain uncharted, hampering patient-tailored treatment. To investigate associated mechanisms, we analyzed clinical data and used immunohistochemistry, gene-expression profiling, cytogenetics, and next-generation sequencing in a cohort of 117 patients with PSDLBCL. The distribution in cell-of-origin (COO) was 68 (58%) activated B-cell (ABC), 44 (38%) germinal center B-cell (GCB), and 5 (4%) unclassifiable. COO was significantly associated with progression-free survival (PFS) and lymphoma-specific mortality (LSM) in both the overall cohort (5-year PFS: ABC, 43% vs GCB, 73%; LSM: ABC, 45% vs GCB, 14%) and in the subgroup of patients receiving immunochemotherapy (5-year PFS: ABC, 55% vs GCB, 85%; LSM: ABC, 28% vs GCB, 0%). ABC lymphomas were mainly MCD class, showing a high prevalence of MYD88 (74%) and CD79B (35%) mutations compared with GCB lymphomas (MYD88 23%; CD79B 10%) (P < .01). The ABC subtype frequently displayed cMYC/BCL2 coexpression (76% vs 18% GCB; P < .001) and HLA-II loss (48% vs 10% GCB; P < .001). PD-L1 expression and copy-number alterations were rare. All lymphomas were Epstein-Barr virus-negative. Our data suggest molecular profiling as a potent tool for detecting prognostic subgroups in PSDLBCL, exposing links to known relapse/dissemination sites. The ABC subgroup’s MCD genetic features, shared with lymphomas at other nonprofessional lymphoid sites, make them potential candidates for targeted B-cell and toll-like receptor signaling therapy.

Radiotherapy for Advanced Hodgkin Lymphoma with Initial Bulk: A Combined Analysis of Two Randomized Trials

PurposeThe role of consolidative radiotherapy (RT) in patients with advanced Hodgkin lymphoma (HL) with initial bulk is unclear. GITIL/FIL HD0607 and FIL HD0801, two randomized controlled trials with similar design and methodologies, did not identify a benefit to consolidative RT after a metabolic complete response (CR) to 6 cycles of ABVD. However, their limited sample sizes reduced statistical power to detect a small but clinically meaningful benefit to RT. Materials and MethodsIn a secondary analysis of these two phase 3 trials, reconstructed patient data were used to compare outcomes for early and complete responders randomized to no RT or RT to the site(s) of initial bulk. Estimates of progression-free survival (PFS) in the intent-to-treat (ITT) and per-protocol (PP) analyses were generated using the combined data and compared between groups using the log-rank test. ResultsA total of 412 patients were included in the ITT analysis and 373 patients were included in the PP analysis. Median age was 30-32, 42% of patients were stage IIB, and 73% of bulky sites were located in the mediastinum. For the no RT versus RT groups, 5-year ITT PFS estimates were 90.1% versus 90.1% (p=0.81). Five-year PP PFS rates were 90.9% versus 92.9% (p=0.31), respectively. There was no observed difference between no RT and RT groups in subgroups according to size of bulky disease: 5-7 cm (p=0.78), 7-10 cm (p=0.25), and >10 cm (p=0.69). ConclusionIn this combined analysis of two randomized phase 3 clinical trials, consolidative RT to initial sites of bulky nodal involvement was not associated with a PFS benefit in patients with advanced HL in metabolic CR after 2 and 6 cycles of ABVD.

Surgical management of Rathke cleft cysts in pediatric patients: a single institution experience

ObjectiveRathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs.MethodsWe performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022.ResultsOverall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up.ConclusionDue to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.

Five-year follow-up of a phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial therapy in CLL

AbstractWe previously reported high rates of undetectable minimal residual disease <10−4 (uMRD4) with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) followed by 2-year ibrutinib maintenance (I-M) in treatment-naïve chronic lymphocytic leukemia (CLL). Here, we report updated data from this phase 2 study with a median follow-up of 63 months. Of 85 patients enrolled, including 5 (6%) with deletion 17p or TP53 mutation, 91% completed iFCR and 2-year I-M. Five-year progression-free survival (PFS) and overall survival were 94% (95% confidence interval [CI], 89%-100%) and 99% (95% CI, 96%-100%), respectively. No additional deaths have occurred with this extended follow-up. No difference in PFS was observed by immunoglobulin heavy-chain variable region gene status or duration of I-M. High rates of peripheral blood (PB) uMRD4 were maintained (72% at the end of iFCR, 66% at the end of 2-year I-M, and 44% at 4.5 years from treatment initiation). Thirteen patients developed MRD conversion without clinical progression, mostly (77%) after stopping ibrutinib. None had Bruton tyrosine kinase (BTK) mutations. One patient had PLCG2 mutation. Six of these patients underwent ibrutinib retreatment per protocol. Median time on ibrutinib retreatment was 34 months. The cumulative incidence of atrial fibrillation was 8%. Second malignancy or nonmalignant hematologic disease occurred in 13%, mostly nonmelanoma skin cancer. Overall, iFCR with 2-year I-M achieved durably deep responses in patients with diverse CLL genetic markers. Re-emergent clones lacked BTK mutation and retained sensitivity to ibrutinib upon retreatment. This trial is registered at www.clinicaltrials.gov as #NCT02251548.

Impact of prognostic nutritional index change on prognosis after colorectal cancer surgery under propofol or sevoflurane anesthesia

BackgroundThe alteration of the prognostic nutritional index (PNI) or the utilization of distinct anesthesia strategies has been linked to the prognosis of various cancer types, but the existing evidence is limited and inconclusive, particularly for colorectal cancer (CRC). Our objective was to evaluate the association between PNI change and progression free survival (PFS) and overall survival (OS) in patients treated with CRC surgery after propofol-based or sevoflurane-based anesthesia.MethodsWe conducted a retrospective analysis of 414 patients with CRC who underwent surgical resection. Among them, 165 patients received propofol-based total intravenous anesthesia (TIVA-P), while 249 patients received sevoflurane-based inhalation anesthesia (IA-S). The PNI change (ΔPNI) was calculated by subtracting the pre-surgery PNI from the post-surgery PNI, and patients were categorized into high (≥ -2.25) and low (< -2.25) ΔPNI groups. Univariate and multivariate analyses were employed to evaluate the effects of the two anesthesia methods, ΔPNI, and their potential interaction on PFS and OS.ResultsThe median duration of follow-up was 35.9 months (interquartile range: 18–60 months). The five-year OS rates were 63.0% in the TIVA-P group and 59.8% in the IA-S group (hazard ratio [HR]: 0.96; 95% confidence interval [CI]: 0.70–1.35; p = 0.864), while the five-year PFS rates were 55.8% and 51.0% (HR: 0.92; 95% CI: 0.68–1.26; p = 0.614), respectively. In comparison to patients in the low ΔPNI group, those in the high ΔPNI group exhibited a favorable association with both OS (HR: 0.57; 95% CI: 0.40–0.76; p < 0.001) and PFS (HR: 0.58; 95% CI: 0.43–0.79; p < 0.001). Stratified analysis based on ΔPNI revealed significant protective effects in the propofol-treated participants within the high ΔPNI group, whereas such effects were not observed in the low ΔPNI group, for both OS (p for interaction = 0.004) and PFS (p for interaction = 0.024).ConclusionsOur data revealed that among patients who underwent CRC surgery, those treated with TIVA-P exhibited superior survival outcomes compared to those who received IA-S, particularly among individuals with a high degree of PNI change.