Recurrence Time Research Articles

Post recurrence survival in early versus late period and its prognostic factors in rectal cancer patients

To identify factors associated with post-recurrence survival (PRS), we examined our institutional recurrence patterns following definitive resection for rectal cancer. We reviewed all patients with rectal cancer diagnosed at three hospitals in the east of Iran from 2011 to 2020. The optimal cut-off value was determined by receiver operating characteristic (ROC) analysis to determine early recurrence. The effect of recurrence time was evaluated on PRS. 326 eligible patients with a mean ± SD age of 56 ± 12.8 years were included in this study. In a median (IQR: Inter-quartile range) follow-up time of 76 (62.2) months, 106 (32.5%) patients experienced at least any recurrence (locoregional or distant metastasis) following primary resection. The median (IQR) time from initial surgery to recurrence was 29.5 (31.2) months. Based on ROC analysis, early recurrence was specified at ≤ 29 months. However, for the patients who experienced only locoregional recurrence, 33 months was the cut-off to define early recurrence. Recurrence time and recurrence management were both significant variables on PRS. Moreover, TNM staging was significantly associated with early recurrence (P = 0.003). In this research, recurrence time, recurrence management and TNM staging were found to be correlated with PRS.

Improved survival outcome of curative liver resection for Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma in the era of tyrosine kinase inhibitors.

This study was undertaken to evaluate the outcome of curative liver resection, (LR) of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC) after tyrosine kinase inhibitors (TKIs) became approved as a treatment option for recurrent lesions. Sixty-seven patients with BCLC-C HCC who underwent curative LR were enrolled in this study. The patients were classified into two groups according to whether LR was performed before (n=24) or after (n=43) TKI approval ("beforeTKI" and "afterTKI" group, respectively). There was no difference in the median disease-free survival time after LR between the beforeTKI and afterTKI groups (5.6 and 7.1months, respectively; p=0.435). However, the median survival time after LR was longer in the afterTKI than beforeTKI group (42.7 and 14.9months, respectively; p=0.022). Univariate and multivariate analyses showed that the date of LR was the only independent factor affecting postresection survival. When the patients were limited to those with recurrence, there were no differences in the recurrence pattern or progression of HCC at the time of recurrence between the two groups. The only difference in the treatment distribution was the administration of TKIs (14 of 34 patients in afterTKI group and only 1 of 19 patients in beforeTKI group, p<0.001). These data suggest that TKI therapy for recurrent BCLC-C HCC is associated with improved overall survival. Thus, LR could be a promising option for BCLC-C HCC in the current era of TKI therapy.

Burst-recurrence properties revealed with Insight-HXMT and NICER for the newly discovered accreting millisecond pulsar MAXI J1816--195

We report the results of our analysis of 83 type-I bursts during the 2022 outburst of the newly discovered accreting millisecond pulsar MAXI J1816--195 based on Insight-HXMT and NICER observations. We focus on the burst-recurrence time and its correlation with persistent flux and outburst evolution. The extensive observations of Insight-HXMT and NICER confirm the presence of quasi-periodic thermonuclear bursts during this outburst, with a recurrence time in the range of 1.15 to 2 hours, which varies with the source persistent flux. The burst recurrence times are, in general, longer at comparable flux levels in the outburst rising phase than those in the fading phase, forming an apparent hysteresis phenomenon. These burst properties make MAXI J1816--195 a unique target for investigating the underlying burst-accretion mechanisms. We discuss the plausible explanations for the hysteresis phenomenon, which appears to be related to changes in the ignition condition or accretion geometry during the outburst.

Recurrence Dynamics of Pathological N2 Non-small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor.

This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96-1.46) and 1.58 (1.31-1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Withaferin A protects against epilepsy by promoting LCN2-mediated astrocyte polarization to stopping neuronal ferroptosis

BackgroundEpilepsy is among the most frequent severe brain diseases, with few treatment options available. Neuronal ferroptosis is an important pathogenic mechanism in epilepsy. As a result, addressing ferroptosis appears to be a promising treatment approach for epilepsy. Withaferin A (WFA) is a C28 steroidal lactone that has a broad range of neuroprotective properties. Nonetheless, the antiepileptic action of WFA and the intrinsic mechanism by which it inhibits ferroptosis following epilepsy remain unknown. PurposeThis study aimed at investigating to the antiepileptic potential of WFA in epilepsy, as well as to propose a potential therapeutic approach for epilepsy therapy. MethodsWe conducted extensive research to examine the impacts of WFA on epilepsy and ferroptosis, using the kainic acid (KA)-treated primary astrocyte as an in vitro model and KA-induced temporal lobe epilepsy mice as an in vivo model. To analyze the neuroprotective effects of WFA on epileptic mice, electroencephalogram (EEG) recording, Nissl staining, and neurological function assessments such as the Morris water maze (MWM) test, Y-maze test, Elevated-plus maze (O-maze) test, and Open field test were used. Furthermore, the mechanism behind the neuroprotective effect of WFA in epilepsy was investigated using the transcriptomics analysis and verified on epileptic patient and epileptic mouse samples using Western blotting (WB) and immunofluorescence (IF) staining. In addition, WB, IF staining and specific antagonists/agonists were used to investigate astrocyte polarization and the regulatory signaling pathways involved. More critically, ferroptosis was assessed utilizing lipocalin-2 (LCN2) overexpression cell lines, siRNA knockdown, JC-1 staining, WB, IF staining, flow cytometry, electron microscopy (TEM), and ferroptosis-related GSH and MDA indicators. ResultsIn this study, we observed that WFA treatment reduced the number of recurrent seizures and time in seizure, and the loss of neurons in the hippocampal area in in epileptic mice, and even improved cognitive and anxiety impairment after epilepsy in a dose depend. Furthermore, WFA treatment was proven to enhance to the transformation of post-epileptic astrocytes from neurotoxic-type A1 to A2 astrocytes in both in vivo and in vitro experiments by inhibiting the phosphoinositide 3-kinase /AKT signaling pathway. At last, transcriptomics analysis in combination with functional experimental validation, it was discovered that WFA promoted astrocyte polarity transformation and then LCN2 in astrocytes, which inhibited neuronal ferroptosis to exert neuroprotective effects after epilepsy. In addition, we discovered significant astrocytic LCN2 expression in human TLE patient hippocampal samples. ConclusionsTaken together, for the first, our findings suggest that WFA has neuroprotective benefits in epilepsy by modulating astrocyte polarization, and that LCN2 may be a novel potential target for the prevention and treatment of ferroptosis after epilepsy.

Risk Factors for Rectal Cancer Recurrence after Local Excision of T1 Lesions from a Decade-Long Multicenter Retrospective Study.

Background: Local surgical excision of T1 rectal adenocarcinoma is a well-established approach. Yet, there are still open questions regarding the recurrence rates and its risk factors. Methods: A retrospective multicenter study including all patients who underwent local excision of early rectal cancer with an open or MIS approach and had a T1 lesion from 2010 to 2020 in six academic centers. Data included demographics, preoperative studies, surgical findings, postoperative outcomes, and local and systemic recurrence. A univariable and multivariable logistic regression analysis was performed to identify risk factors for recurrence. Results: Overall, 274 patients underwent local excision of rectal lesions. Of them, 97 (35.4%) patients with a T1 lesion were included in the cohort. The mean age was 69 ± 10.5 years, and 42 (43.3%) were female. The mean distance of the lesions from the anal verge was 7.8 ± 3.2 cm, and the average tumor size was 2.7 ± 1.6 cm. Eighty-two patients (85%) had a full-thickness resection. Eight patients (8%) had postoperative complications. Kikuchi classification of submucosal (SM) involvement was reported in 29 (30%) patients. Twelve patients had SM1, two SM2, and fifteen SM3. Following pathology, 24 patients (24.7%) returned for additional surgery or treatment. The overall recurrence rate was 14.4% (14 patients), with 11 patients having a local recurrence and 6 having a systemic metastatic recurrence, 3 of which had both. The mean time for recurrence was 2.78 ± 2.8 years and the overall mortality rate was 11%. On univariable and multivariable logistic regression analysis of recurrence vs. non-recurrence groups, the strongest and most significant association and possible risk factors for recurrence were larger lesions (4.3 vs. 2.5 cm, p < 0.001) with an OR of 6.67 (CI-1.82-24.36), especially for tumors larger than 3.5 cm, mucinous histology (14.3% vs. 1.2%, p = 0.004, OR of 14.02, CI-1.13-173.85), and involved margins (41.7% vs. 16.2%, p = 0.003, OR of 9.59, CI-2.14-43.07). The open transanal excision (TAE) approach was also identified as a possible significant risk factor in univariant analysis, while SM3 level penetration showed only a trend. Conclusion: Surgical local excision of T1 rectal malignancy is a safe and viable option. Still, one in four patients received additional treatment. There is an almost 15% chance for recurrence, especially in large tumors, mucinous histology, or involved margin cases. These high-risk patients might warrant additional intervention and stricter surveillance protocols.

Achieving SVR in patients with hepatitis C-related HCC is associated with an improvement in overall survival: real word data

Aims: The optimal timing for DAA therapy initiation in patients with chronic hepatitis C (CHC) and HCC is still debated. The aim of our study was to provide real-world data on virological response and overall survival in patients with hepatitis C-related HCC. Methods: Retrospectively, we included patients with HCV-related HCC between 2015 and 2020. The primary outcome was to compare the SVR rate in the patients with active or historical HCC who were treated with DAA therapy. The secondary outcome was to measure the overall survival of those patients. Results: 98 patients were included, and the majority were cirrhotic with compensated liver disease. 71.4% received DAA therapy at the time of initial HCC diagnosis and 11.2% received HCV treatment at the time of HCC recurrence (Active HCC cohort). 17.3% had previously received HCC treatment, but there was no evidence of recurrence at the time of DAA (Historical HCC Cohort). The SVR rate was 81.6%, but decreased to 75.7% in patients with active HCC. The presence of active HCC and the number of HCC nodules were the only factors associated with not achieving SVR in the multivariate analysis. The median survival was higher in those who achieved SVR. Active HCC and failure to achieve SVR were the main factors associated with mortality. Conclusions: Treating hepatitis C in patients with HCC is feasible with significant rates of SVR, even if SVR rates decrease in patients with active HCC and these patients require more than one DAA therapy. Failure to achieve SVR is one of the main factors associated with mortality.

Pattern of LRR in Endometrial Cancer and Identification of Predictive Factors

Background: Tailored adjuvant treatment is key to managing endometrial cancer effectively. Understanding prognostic factors of loco-regional failure and the impact of adjuvant treatment can help in treatment de-escalation without compromising survival outcomes. The aim of this study was to assess the pattern of failure in endometrial cancer patients and to determine predicting Loco-Regional Recurrence (LRR) factors. Patients and methods: Data were collected from 214 patients treated for endometrial cancer between 2005 and 2012 in Salah Azaiez Institute in Tunisia. All patients underwent upfront surgery followed by adjuvant brachytherapy with or without external beam radiation. The median follow-up period was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors for LRR. Results: The 5-year overall survival rate was 78.1%, and the 5-year progression-free survival rate was 80.1%. LRR occurred in 25 patients (11.6%), with a median recurrence time of 29 months (range 4 months - 46 months). Pelvic relapse was the most common site, occurring in 10 patients. Vaginal relapses were observed in 9 patients, and retro-peritoneal relapses were observed in 6 cases. FIGO stage, tumor grade, histologic type, Lympho-Vascular Space Invasion (LVSI), and delays in adjuvant treatment were significant predictors of LRR. Conclusion: Identifying prognostic factors for LRR in endometrial cancer is crucial for optimizing adjuvant treatment strategies. Higher FIGO stages and the presence of LVSI were independent predictive factors for LRR. Tailored adjuvant treatment, taking these prognostic factors into account, is essential to improve patient outcomes and minimize unnecessary treatment-related toxicity.

Organ-specific variations in tumor marker dynamics in postoperative pancreatic cancer recurrence: Trends in lung and liver recurrence highlighting biological heterogeneity

Background/ObjectivesAlthough tumor recurrence after surgical resection in pancreatic cancer (PC) is generally considered incurable, it is well-accepted that clinical presentations and outcomes vary according to the recurrent sites (e.g., liver vs. lung recurrence), suggesting a possible biological inhomogeneity of PC recurrence. Understanding the behavior of biological factors, specifically tumor markers (TMs), at different recurrence sites may contribute to individualized treatment strategies. Therefore, this study aimed to compare the dynamics of pre-recurrence TMs at liver and lung recurrence sites. MethodsPatients with isolated postoperative liver or lung recurrence as their first recurrence were enrolled. Starting from the recurrence date confirmed by imaging examinations, the values of TMs (carbohydrate antigen 19-9: CA19-9; carcinoembryonic antigen: CEA) were retrospectively evaluated 6 and 3 months before recurrence and at the time of recurrence. ResultsPatients with liver recurrence displayed a significant increase in CA19-9 and CEA levels from as early as 6 months before recurrence. Contrastingly, patients with lung recurrence demonstrated a significant elevation of CA19-9 levels starting from 3 months before recurrence, with no increase in CEA levels, even at the time of recurrence. The relative change in CA19-9 and CEA levels during each period were significantly lower in patients with lung recurrence. ConclusionsBoth TMs exhibited organ-specific variations in patients with postoperative PC recurrence. This disparity may reflect the biological heterogeneity of PC between recurrence patterns, thereby highlighting the importance of conducting postoperative follow-up with consideration of this fact.

Lymph Node Yield is Associated with Improved Overall Survival and Increased Time to Recurrence in Node-Negative Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy.

To determine if lymph node yield (LNY) is associated with improved overall survival (OS) and time to recurrence (TTR) in patients with node-negative pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant therapy (NAT). Lymph node yield has been associated with survival in solid gastrointestinal cancers, including PDAC. Patients with pathological T stage I-III, node-negative (N0), PDAC treated with NAT followed by pancreatoduodenectomy were identified in the Massachusetts General Hospital (MGH) pancreatectomy database and the National Cancer Database (NCDB). A cutoff point of 22 nodes was identified in the NCDB using the point with the optimal (log-rank test) split. Overall survival and TTR were evaluated using univariate and multivariable analyses. In the MGH cohort, 233 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (59 months vs. 25 months, P<0.001) and prolonged TTR (32 months vs. 14 months, P=0.019). On multivariable analysis, LNY was an independent predictor of survival (HR 0.97, 95% CI 0.95-0.99, P=0.034) per sampled node. In the NCDB, 2,029 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (49 months vs. 33 months, P<0.001). On multivariable analysis, LNY was an independent predictor of survival (HR 0.99, 95% CI 0.98-0.99, P<0.001) per sampled node. Lymph node yield was associated with improved oncologic outcomes in patients treated with NAT followed by pancreatoduodenectomy in two independent datasets. Responsible mechanisms by which LNY impacts the outcomes of node-negative patients following NAT warrant further exploration.

Analyzing Racial Disparities in Pediatric Atopic Comorbidity Emergency Department Visitation Using Electronic Health Records

BackgroundAlthough atopic diseases and associated co-morbidities are prevalent in children, little is known about racial differences in emergency department (ED) visitation. ObjectiveWe sought to examine racial differences in ED visitation among children with allergic comorbidities. MethodsWe conducted a retrospective study of patients (<21 years) who visited the ED at a large pediatric hospital for atopic dermatitis (AD), food allergy (FA), asthma, allergic rhinitis (AR), and eosinophilic esophagitis (EoE) from 2015 to 2019. We determined the probability of ED encounter-free using hazard ratios (HR) and time to recurrence (TTR) of ED encounter for patients identified as Black/African American (AA) and White/European American (EA). We assessed potentially underlying allergic, demographic, and place-based factors, and potential interactions between factors. ResultsA total of 30,894 patients (38% AA, 62% EA) had 83,078 ED encounters (38,378 first ED encounters, and 44,700 recurrent ED encounters) during the study period. Asthma and AR showed the highest rate of comorbidity in ED encounters in both AA and EA children. AA children exhibited higher HR for encounter following index AD and asthma encounters. We found an interaction between the type of insurance and race in ED encounters for AD, FA, AR, and EoE. In AA children, those insured by Medicaid demonstrated a higher HR for any encounter compared to those with commercial insurance. Conversely, in EA children, those with Medicaid insurance showed a lower HR compared to their commercially insured peers. Regardless of race, allergic comorbidity increased the HR of ED encounter (1.12-1.62) for all allergic diseases. At 5-years follow up, mean differences in TTR were shorter in AA children compared to EA children in AD, FA, and asthma. ConclusionIdentification of disease-specific racial disparities in ED visitation related to atopic diseases is a necessary first step toward the design and implementation of interventions capable of equitably reducing emergency care in atopic comorbid children.

Bounds for the distribution and moments of the forward and backward recurrence times in a renewal process

We obtain a variety of lower and upper bounds for the bivariate tail of the joint distribution between the (forward and backward) recurrence times in a renewal process. Some of these bounds are valid generally, some others in the case where the interarrival distribution F exhibits monotone aging. We also give various bounds for the moments of the recurrence times. Our results improve upon existing bounds for these quantities in the literature. We also discuss the case where the aging of F is non-monotonic. Finally, we present numerical examples to illustrate the performance of the new bounds.

Paroxysmal Atrial Fibrillation History is Associated with Earlier Recurrence After First Cardioversion Compared to Primary Persistent Atrial Fibrillation

BackgroundParoxysmal atrial fibrillation (pAF) may progress through cardiac remodeling to persistent atrial fibrillation (psAF). However, some may present in psAF without a preceding history of pAF. A preceding history of pAF may affect recurrence following direct current cardioversion (DCCV). ObjectiveTo determine if a preceding history of pAF is associated with a difference in recurrence rates after DCCV compared to patients without a preceding history of pAF. MethodsA prospective procedural database at a Veterans Affairs center identified 565 patients who underwent their first DCCV for psAF. Initial rhythm history was separated by prior pAF and those with none were considered primary psAF. ECG follow-up was standardized at 1- and 3- months post cardioversion. ResultsPatients who underwent their first DCCV for psAF were more likely to have presented with primary psAF (81.6%). Those with pAF had a similar left atrial size, but were more likely to have chronic kidney disease, sleep apnea, previous stroke, and utilizing antiarrhythmic drugs at the time of cardioversion. Patients with pAF had earlier recurrence and shorter median AF survival time, 1.6 months compared to 5 months (Kaplan-Meier plot p=0.0101). This difference persisted when controlling for AAD use. Recurrence type was mostly persistent AF, similar in both groups. ConclusionPatients with primary psAF may have a more sustained response to DCCV when compared to those with a preceding history of pAF. Thus, those patients with pAF may benefit from a more aggressive, early rhythm control strategy due to higher likelihood of recurrence with DCCV.

Treatment options for patients with pilonidal sinus disease: PITSTOP, a mixed-methods evaluation.

There is no consensus on optimal management of pilonidal disease. Surgical practice is varied, and existing literature is mainly single-centre cohort studies of varied disease severity, interventions and outcome assessments. A prospective cohort study to determine: • disease severity and intervention relationship • most valued outcomes and treatment preference by patients • recommendations for policy and future research. Observational cohort study with nested mixed-methods case study. Discrete choice experiment. Clinician survey. Three-stage Delphi survey for patients and clinicians. Inter-rater reliability of classification system. Thirty-one National Health Service trusts. Patients aged > 16 years referred for elective surgical treatment of pilonidal disease. Surgery. Pain postoperative days 1 and 7, time to healing and return to normal activities, complications, recurrence. Outcomes compared between major and minor procedures using regression modelling, propensity score-based approaches and augmented inverse probability weighting to account for measured potential confounding features. Clinician survey: There was significant heterogeneity in surgeon practice preference. Limited training opportunities may impede efforts to improve practice. Cohort study: Over half of patients (60%; N = 667) had a major procedure. For these procedures, pain was greater on day 1 and day 7 (mean difference day 1 pain 1.58 points, 95% confidence interval 1.14 to 2.01 points, n = 536; mean difference day 7 pain 1.53 points, 95% confidence interval 1.12 to 1.95 points, n = 512). There were higher complication rates (adjusted risk difference 17.5%, 95% confidence interval 9.1 to 25.9%, n = 579), lower recurrence (adjusted risk difference -10.1%, 95% confidence interval -18.1 to -2.1%, n = 575), and longer time to healing (>34 days estimated difference) and time to return to normal activities (difference 25.9 days, 95% confidence interval 18.4 to 33.4 days). Mixed-methods analysis: Patient decision-making was influenced by prior experience of disease and anticipated recovery time. The burden involved in wound care and the gap between expected and actual time for recovery were the principal reasons given for decision regret. Discrete choice experiment: The strongest predictors of patient treatment choice were risk of infection/persistence (attribute importance 70%), and shorter recovery time (attribute importance 30%). Patients were willing to trade off these attributes. Those aged over 30 years had a higher risk tolerance (22.35-34.67%) for treatment failure if they could experience rapid recovery. There was no strong evidence that younger patients were willing to accept higher risk of treatment failure in exchange for a faster recovery. Patients were uniform in rejecting excision-and-leave-open because of the protracted nursing care it entailed. Wysocki classification analysis: There was acceptable inter-rater agreement (κ = 0.52, 95% confidence interval 0.42 to 0.61). Consensus exercise: Five research and practice priorities were identified. The top research priority was that a comparative trial should broadly group interventions. The top practice priority was that any interventions should be less disruptive than the disease itself. Incomplete recruitment and follow-up data were an issue, particularly given the multiple interventions. Assumptions were made regarding risk adjustment. Results suggest the burden of pilonidal surgery is greater than reported previously. This can be mitigated with better selection of intervention according to disease type and patient desired goals. Results indicate a framework for future higher-quality trials that stratify disease and utilise broad groupings of common interventions with development of a patient-centred core outcome set. This trial is registered as ISRCTN95551898. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/17/02) and is published in full in Health Technology Assessment; Vol. 28, No. 33. See the NIHR Funding and Awards website for further award information.

Prognostic Factors for Progression-free Survival and Overall Survival After Recurrence of Glioblastoma.

Many patients with glioblastoma experience an intracerebral recurrence and require a personalized treatment. This study aimed to facilitate this approach by identifying prognostic factors for progression-free survival (PFS) and overall survival (OS). In 102 patients with recurrent glioblastoma following primary treatment with resection or biopsy plus adjuvant chemoradiation, 11 characteristics were retrospectively investigated regarding PFS and OS. In the multivariate analyses, Karnofsky performance score (KPS) 90-100 at the time of recurrence (p=0.032), maximum cumulative diameter of recurrent lesions ≤40 mm (p=0.002), resection of recurrent glioblastoma (p=0.025), and systemic therapy for recurrent glioblastoma (p=0.025) were significantly associated with improved PFS. In addition, KPS 90-100 (p=0.024), maximum cumulative diameter ≤40 mm (p=0.033), and systemic therapy (p=0.006) were significantly associated with better OS. Our study identified high Karnofsky Performance Status (KPS 90-100), maximum cumulative diameter of recurrent glioblastoma lesions ≤40 mm, and systemic therapy for recurrent glioblastoma as independent predictors of overall survival (OS) and progression-free survival (PFS). These independent prognostic factors may help select the most suitable treatment for individual patients with recurrent glioblastoma, potentially improving patient outcomes.

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases

ObjectiveThis study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility.MethodsOur study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3–4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy.ResultsOverall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages.ConclusionGnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design

BackgroundDisease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial.MethodsThis randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the “Trials within Cohorts” (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19–9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment.DiscussionThe RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients’ quality of life will be obtained.Trial registrationClinicaltrials.gov, NCT04875325. Registered on May 6, 2021.

Von Willebrand Factor Antigen Improves Risk Stratification for Patients with a Diagnosis of Resectable Hepatocellular Carcinoma.

Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS). The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection. In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated. For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.

MDB-103. THE SIGNIFICANCE OF CEREBROSPINAL FLUID CYTOLOGY IN SURVEILLANCE FOR RECURRENT MEDULLOBLASTOMA

Abstract BACKGROUND Surveillance of patients with medulloblastoma includes magnetic resonance imaging of the brain and spine and cerebrospinal fluid (CSF) cytology evaluation. Certain protocols require frequent CSF cytology evaluations off-therapy while others perform CSF cytology only at the time of radiographic relapse. We wanted to determine the incidence of isolated CSF positivity at the time of recurrence and the outcome of these patients. METHODS We performed a retrospective analysis of patients with relapsed medulloblastoma treated at Texas Children’s Hospital between 1997 and 2023. RESULTS Out of 223 patients with medulloblastoma, 45 patients developed recurrences. Twenty-five (55.5%) patients underwent lumbar puncture for CSF cytology at the time of relapse. The radiographic distribution of recurrences was focal (n=7), focal and disseminated (n=6), disseminated (n=11), and negative imaging (n=1). Seven out of the 25 (28%) patients had positive CSF cytology for malignant cells at initial relapse. All seven patients succumbed secondary to disease progression. Among 18 patients who had negative CSF cytology at recurrence, three infant patients at initial diagnosis were disease-free following craniospinal radiation at recurrence. Only one among 25 patients had positive CSF cytology without radiographic evidence of relapse. Among ten patients with focal disease at the time of relapse, seven had negative CSF cytology for malignant cells, and three did not have CSF cytology evaluated at the time of relapse. DISCUSSION Frequent evaluation of CSF cytology to detect recurrence may not be necessary in addition to imaging studies. In our study, it did not influence the outcome of patients with recurrence. Prospective studies are necessary to support periodic CSF surveillance to detect ctDNA, which may allow for early interventions that may influence outcomes in patients with recurrent medulloblastoma who have poor outcomes.

MDB-82. TRANSFUSION-RELATED IRON OVERLOAD MIMICKING METASTATIC DISEASE IN A PEDIATRIC PATIENT WITH MEDULLOBLASTOMA ON A RADIATION-DELAYING CHEMOTHERAPY REGIMEN

Abstract BACKGROUND Transfusion-related iron overload (TRIO) is a known complication of administering numerous packed red blood cell (pRBC) transfusions in pediatric oncology patients undergoing myelosuppressive therapy. Infant medulloblastoma regimens attempt to avoid or delay radiation and its adverse effects in this population, with intensive myelosuppressive chemotherapy. We report a case of TRIO first suspected as hepatic metastatic disease at time of CNS recurrence in a young patient with medulloblastoma after completion of a high-dose chemotherapy protocol. METHODS Case Report RESULTS A five-year-old male presented with four months of headaches, dizziness, imbalance, and emesis. MRI revealed a posterior fossa mass with near total resection of the mass confirming classic medulloblastoma, non-WNT, non-SHH. The patient received five cycles of induction chemotherapy. This was followed by a single cycle of high-dose chemotherapy (HDCSCR) with autologous stem cell rescue. During therapy, he received 26 pRBC transfusions to correct severe anemia. CNS recurrence occurred 19 months after therapy. Abdominal imaging revealed enlarging hepatic lesions concerning for metastases. Ferritin was 1,268 ng/mL (normal: 7-142 ng/mL) and MRI of liver revealed severe iron load with LIC of 11 mg Fe/g dry weight (dw) (normal: 0.4-2.2 mg Fe/g dw). Ultimately, hepatic lesions were thought to be non-cancerous, and he proceeded with craniospinal irradiation. He was diagnosed with TRIO. He underwent phlebotomy for 33 months with ferritin and MRI liver LIC within normal limits. CONCLUSION This case illustrates an occurrence of TRIO presenting as hepatic lesions concerning for metastatic disease during CNS recurrence in a patient who underwent an infant medulloblastoma regimen with HDCSCR. Our patient required phlebotomy for nearly 3 years to return ferritin and LIC to normal limits. Further investigation on the prevalence of TRIO in medulloblastoma survivors treated with radiation delaying/sparing protocols is necessary to improve outcomes and avoid end organ damage due to iron overload.