Median Survival Time Research Articles

Safety and efficacy of airway stent placement following bronchial artery embolization: A retrospective study at a single institute

BackgroundAirway stenting is an established procedure for treating oncological emergencies in patients with airway disorders. In patients with airway hemorrhage, respiratory conditions may worsen during stenting. Bronchial artery embolization (BAE) is useful to prevent bleeding from the bronchus. We aimed to evaluate the efficacy and safety of airway stenting after BAE in patients with malignant airway disorders. MethodsThe medical records of all patients who underwent airway stenting following BAE at the National Hospital Organization Okayama Medical Center between 2016 and 2023 were retrospectively reviewed. ResultsThirteen procedures (11 silicone Y stents, one hybrid stent, and one self-expandable metallic stent) were performed. The median duration from BAE to airway stenting was one day (range: 1–5 days). Nine patients experienced tumor shrinkage, and none experienced severe bleeding after BAE during the stent procedure. No other major complications were associated with the stent placement. The median survival time after stenting was 169 days (range; 24–1086). No serious complications caused by BAE, such as spinal cord infarction, were observed. ConclusionsAirway stent placement was safely performed after BAE without severe bleeding or acute respiratory failure. BAE, followed by airway stenting, is useful.

Clinicopathologic characteristics and survival analysis of primary large B-cell lymphoma of the central nervous system

Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer.

The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were re-evaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

Scoring system to predict positive peritoneal cytology in patients with resectable and borderline resectable pancreatic cancer.

The aim of this study was to evaluate factors to predict positive peritoneal cytology, whcih would determine the indication for staging laparoscopy in pancreatic cancer. A total of 430 patients that underwent pancreatectomy for resectable and borderline resectable pancreatic cancer were retrospectively reviewed. Among 430 patients, 36 had positive cytology (8.4%). Median survival time in negative cytology was 24.7 months, compared with 15.1 months in positive cytology (p = .004). Factors to predict positive cytology in pancreatic cancer according to multivariate analysis were tumor location (body, tail; OR 2.66; 95% CI: 1.21-5.85; p = .015), tumor size ≥30 mm (OR 2.95; 95% CI: 1.35-6.47; p = .007) and radiographic other-organ invasion (HR 2.79; 95% CI: 1.01-7.67; p = .047). Patients were scored 0 to 3 corresponding with these factors. Rates of positive cytology increases in each score were: score 0: 2.9%, score 1: 6.7%, score 2: 18.3%, score 3: 36.8%. Tumor location (body or tail), tumor size ≥30 mm, and radiographic other-organ invasions were risk factors for positive cytology in pancreatic cancer. This scoring system might be a useful indicator to perform staging laparoscopy to diagnose positive cytology.

Trends in the survival of patients with trisomy 13 from 1995 to 2021: A population study in Japan.

It remains unclear whether recent changes in the prognosis and management of patients with trisomy 13 impact patient survival. We investigated changes in survival of patients with trisomy 13 in Japan. Data from the Vital Statistics Database in Japan was retrieved to examine the association of sex, surgical history, and years of birth and death with changes in survival patterns in 1164 patients with trisomy 13 between 1995 and 2021. The rates of deaths due to trisomy 13 increased from 9.8% to 23.1% in those over 1 year of age and from 7.3% to 19.2% in those within 24 h of birth between 1995 and 2021. The median survival time was longer in 2009-2021 than in 1996-2008 (40 vs. 84 days, p < 0.001). The median survival time and the rate of patients with surgical history increased from 91 days and 16.0% in 1996-2008 to 179 days and 28.0% in 2009-2021, respectively. Median survival time among patients with trisomy 13 has increased over the last 26 years, with almost 1 in 3 patients currently surviving for more than 1 year. The increased surgical intervention rate might have contributed to this improvement.

Effectiveness of edoxaban in portal vein thrombosis associated with liver cirrhosis

Portal vein thrombosis (PVT) worsens the long-term prognosis of patients with cirrhosis; however, the optimal treatment remains to be determined. Reports on the efficacy of direct oral anticoagulants are increasing, and further evidence is needed. Therefore, we investigated the effectiveness of treatment with edoxaban in patients with PVT. We retrospectively reviewed the outcomes of edoxaban and warfarin as antithrombotic therapies for PVT. The median overall survival time was 4.2 years in patients with PVT, with a 1-year survival rate of 70.7% and a 5-year survival rate of 47.9%. The leading cause of death was hepatocellular carcinoma. The overall response rate for thrombolysis in the edoxaban group was 76.7% compared to 29.4% in the warfarin group, and edoxaban significantly improved PVT compared to warfarin. In addition, edoxaban provided long-term improvement of PVT. Warfarin, on the other hand, was temporarily effective but did not provide long-term benefits. The Child–Pugh and albumin-bilirubin scores did not change after edoxaban or warfarin use. No deaths occurred due to adverse events associated with edoxaban or warfarin. Edoxaban as a single agent can achieve long-term recanalization without compromising the hepatic reserves. Edoxaban is easy to initiate, even in an outpatient setting, and could become a major therapeutic agent for the treatment of PVT.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients’ median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study

BackgroundExtracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF.MethodsExtracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed.ResultsmtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p < 0.001) and ≥ 11,194.3 copies/µL at the time of AE (MST: 2.6 vs. 20.0 months, p = 0.03) were associated with shorter survival after BALF collection, even after adjusting for other known prognostic factors. On the other hand, BALF-nucDNA showed different trends in correlation with other clinical variables and did not show any significant association with survival time.ConclusionsElevated BALF-mtDNA was associated with a poor prognosis in both IPF and AE-IPF. Of note, at the time of AE, it sharply distinguished survivors from non-survivors. Given the trends shown by analyses for BALF-nucDNA, the elevation of BALF-mtDNA might not simply reflect the impact of cell collapse. Further studies are required to explore the underlying mechanisms and clinical applications of BALF-mtDNA in IPF.

Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.

Treatment outcome of elderly patients (≥ 78 years) with head and neck squamous cell carcinoma: A single center experience.

Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.

Development and Validation of a Novel Machine Learning Model to Predict the Survival of Patients with Gastrointestinal Neuroendocrine Neoplasms

Introduction: Well-calibrated models for personalized prognostication of patients with gastrointestinal neuroendocrine neoplasms (GINENs) are limited. This study aimed to develop and validate a machine-learning model to predict the survival of patients with GINENs. Methods: Oblique random survival forest (ORSF) model, Cox proportional hazard risk model, Cox model with least absolute shrinkage and selection operator penalization, CoxBoost, Survival Gradient Boosting Machine, Extreme Gradient Boosting survival regression, DeepHit, DeepSurv, DNNSurv, logistic-hazard model, and PC-hazard model were compared. We further tuned hyperparameters and selected variables for the best-performing ORSF. Then, the final ORSF model was validated. Results: A total of 43,444 patients with GINENs were included. The median (interquartile range) survival time was 53 (19–102) months. The ORSF model performed best, in which age, histology, M stage, tumor size, primary tumor site, sex, tumor number, surgery, lymph nodes removed, N stage, race, and grade were ranked as important variables. However, chemotherapy and radiotherapy were not necessary for the ORSF model. The ORSF model had an overall C index of 0.86 (95% confidence interval, 0.85–0.87). The area under the receiver operation curves at 1, 3, 5, and 10 years were 0.91, 0.89, 0.87, and 0.80, respectively. The decision curve analysis showed superior clinical usefulness of the ORSF model than the American Joint Committee on Cancer Stage. A nomogram and an online tool were given. Conclusion: The machine learning ORSF model could precisely predict the survival of patients with GINENs, with the ability to identify patients at high risk for death and probably guide clinical practice.

Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single-center experience.

Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. The most common primary site was the testis (n=10), followed by the ovaries (n=7), mediastinum (n=4), retroperitoneum (n=3), pineal gland (n=2), and sacrum/coccyx (n=1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy

Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy’s effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25–8.8). Median survival time was 9.9 months (95% CI 9.2–10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889–9.328; 60 days, HR: 2.351, 95% CI 1.104–5.009; 90 days, HR: 2.416, 95% CI 1.232–4.739; and 120 days, HR: 2.521, 95% CI 1.357–4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.

Postoperative Lymph Node Recurrence in Esophageal Cancer After Surgery and Prognosis of Chemoradiotherapy.

This study aimed to evaluate the long-term prognosis of definitive chemoradiotherapy and clinical features of postoperative lymph node (LN) recurrence after curative resection of thoracic esophageal squamous cell cancer (ESCC). A total of 586 patients who underwent radical resection of ESCC at the Hiroshima University Hospital from January 2000 to December 2019 were reviewed retrospectively. This study analyzed the clinical characteristics of 54 patients who developed recurrence in a solitary LN by comparing them to 182 patients who experienced total recurrence. Additionally, we analyzed the prognostic factors of 50 patients who received chemo-radiotherapy (CRT). The results revealed a tendency for a higher incidence of solitary LN recurrence in cases of early esophageal cancer and upper thoracic esophageal cancer among all recurrence cases. The 3-, 5-, and 7-year overall survival (OS) rates were 40.5%, 37.8% and 34.6%, respectively, with a median survival time of 27.9 months. Univariate analysis of OS factors, such as age, depth of the primary tumor at the initial surgery, time to LN recurrence after surgery, site of LN recurrence, and the number of the regional LNs with recurrence showed no significant impact on OS. Approximately 35% of patients with ESCC who experienced LN recurrence after curative resection achieved long-term survival through CRT. Despite the absence of identifiable prognostic factors, CRT proves to be a valuable initial treatment option for LN recurrence.

A real-world experience of venetoclax combined with hypomethylating agents vs. monotherapy hypomethylating agents in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia patients.

Current clinical research has reported the effectiveness and safety of venetoclax in combination with hypomethylating agents (VEN-HMA) in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Thus, this study aimed to examine the effectiveness and safety of VEN-HMA therapy in patients with MDS and CMML and compared its short-term and long-term therapeutic effects with HMA monotherapy. We analyzed data from our center, comprising 19 patients with MDS and CMML who received VEN-HMA therapy, compared to 32 patients treated with HMA monotherapy. The overall response rate (ORR) in the VEN-HMA group was 73.7%, compared to 59.4% in the HMA group. The survival analysis revealed that the median overall survival (mOS) time in the VEN-HMA group was 16 months, with a median progression-free survival (mPFS) time of 9 months, both of which were longer than those observed in the HMA group (p < 0.05). Key adverse events (AEs) included grade 3-4 neutropenia (89.5% in VEN-HMA group vs. 87.5% in HMA group), grade 3-4 thrombocytopenia (73.7% vs. 71.9%), and anemia (73.7% vs. 90.6%). Infection of grade 3 or higher occurred in 63.2% of patients in the VEN-HMA group and 65.6% of patients in the HMA group. Our study has confirmed the effectiveness and safety of the combined treatment of HMAs and venetoclax, which offers significant advantages to patients due to the relatively high and rapid response rates.

Abstract PO5-18-12: Can we cure de novo oligometastatic stage IV HER2+ breast cancer with multimodality therapy? (CHLOE)

Abstract Background: The current standard of care is to treat all patients with metastatic breast cancer with palliative intent, regardless of extent of disease. However, in real world practice patients with oligometastatic disease are sometimes treated with surgery and/or radiation/ablation in combination with systemic therapy to render them as having no evidence of disease. Previous randomized clinical trials have not shown a benefit to adding surgery or radiation in metastatic breast cancer, however, these trials had a small number of HER2+ patients. HER2+ patients are uniquely responsive to combination of chemotherapy and targeted HER2 therapy and therefore may have different outcomes with a multimodality approach. The goal of this project is to use a novel, user friendly, on-line clinical study platform that registers patients and enables follow-up data collection to test the hypothesis that de novo stage IV oligometastatic HER2+ patients treated with multimodality therapy may result in improved long-term distant metastasis free survival and overall survival. Trial design: This is a prospective, nationwide registry study that will enroll newly diagnosed (de novo) oligometastatic (operationally defined by local tumor boards as disease where all metastatic lesions can be ablated) HER2+ breast cancer. A secure online portal has been created by the Yale IT team in accordance with HIPPA and cybersecurity guidelines. Data will be directly entered into the online portal by participating investigators and information regarding what treatment the patient received, if they completed treatment, and survival data will be collected. All treatment decisions will be at the discretion of the treating provider. Eligibility criteria: Patients with de novo oligometastatic HER2+ breast cancer in whom local treatment of all metastatic sites by either surgery, radiation, or ablative techniques is feasible as determined by multidisciplinary discussion or local tumor board. Specific aims: Primary: To estimate the 3 year distant metastasis free survival in patients with de novo oligometastatic HER2+ breast cancer treated with a multi-modality treatment plan. Secondary: To estimate 3 year overall survival and to monitor QOL. Statistical methods: The major analysis will occur after at least 3 years following the last subject’s enrollment in a cohort, to ensure that the objective of distant metastasis free survival at 3 years will be analyzed. It will include: tabulation of all cases entered, number and location of metastases, if treatment plan was implemented, compliance rate of treatment delivery, observed results with respect to the primary endpoint. Kaplan-Meier estimates will be presented for the analysis of survival endpoints together with a summary of associated statistics (median survival time if reached, landmark survival rate estimates and estimates for every 6 months thereafter if applicable), including the corresponding two-sided 95% confidence intervals. The 95% exact Clopper Pearson confidence intervals will be presented for binary endpoints. Paired t-test or Wilcoxon signed rank test will be used to assess the difference of continuous variables measured at different time points. The secondary clinical outcome is overall survival at 3 years, defined as the percentage of patients without an event at the 3-year follow-up time point measured from the study registration date. An event is considered death from any cause. OS time will be measured from the date of randomization to the date of first OS failure or last follow-up. OS will be estimated by the Kaplan-Meier method with OS failure defined as: death from any cause. Present accrual and target accrual: 4/42 patients Contact information for people with a specific interest in the trial: Mariya.Rozenblit@yale.edu https://chloe.yalepathaws.org Citation Format: Mariya Rozenblit, Nathalie Wiesendanger, Kelly Shanahan, Christine Hodgdon, Peter Gershkovich, Mehra Golshan, Meena Moran, Maryam Lustberg, Lajos Pusztai. Can we cure de novo oligometastatic stage IV HER2+ breast cancer with multimodality therapy? (CHLOE) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-12.

Abstract PO2-04-04: Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)

Abstract Background: ROSET-BM (UMIN000044995) was a multicenter, retrospective chart review study of patients (pts) who received trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic breast cancer (MBC) with brain metastases (BM) and/or leptomeningeal carcinomatosis (LMC). Primary results (data cutoff, October 31, 2021) were presented at SABCS2022 (median progression-free survival [PFS], 16.1 months; 1-year overall survival [OS] rate, 74.9%; and median follow-up duration, 11.2 months). To confirm the long-term effectiveness of T-DXd in HER2+ MBC pts with BM and/or LMC, we conducted an updated analysis using additional 1-year follow-up data. Methods: Pts who started T-DXd treatment between May 25, 2020, and April 30, 2021, were registered for ROSET-BM. For this updated OS analysis, the extended observation period ended on October 31, 2022. OS, PFS, and time to treatment failure (TTF) were evaluated. Median survival times and 95% CIs were calculated using the Kaplan–Meier method. In addition, prespecified and exploratory subgroup analyses were performed based on patient background characteristics. Univariate and multivariate Cox proportional hazards regression models were used to evaluate baseline prognostic factors for OS. Results: 104 pts from 62 institutions were included in this updated OS analysis. Median duration of follow-up was 20.4 months. Median number of prior lines of therapy was 4 (range, 1–15). Median time from first diagnosis of MBC to first administration of T-DXd was 37.5 months. Median time from first diagnosis of BM to first administration of T-DXd was 18.9 months. The prevalence of active BM, stable BM, LMC, and unclassified (image not evaluated) was 64.4% (n=67), 11.5% (n=12), 18.3% (n=19), and 5.8% (n=6), respectively. Median OS was not reached (NR) among all pts (1-year OS rate, 74.8%; 2-year OS rate, 56.0%). Subgroup analyses showed that median OS in pts with active BM was 27.0 months (95% CI, 16.4 to NR) and that median OS was NR in pts with stable BM or LMC (2-year OS rate for pts with stable BM, 71.6%; 2-year OS rate for pts with LMC, 61.6%). The results of univariate and multivariate analyses for OS showed no relevant baseline prognostic factors. Among all pts, median PFS was 14.6 months (95% CI, 10.6–20.8). Subgroup analyses showed that in pts with active BM, stable BM, and LMC, median PFS was 13.2 months (95% CI, 10.0–20.3), NR (95% CI, 5.3 to NR), and 17.5 months (95% CI, 8.3–22.1), respectively. Among all pts, median TTF was 9.3 months (95% CI, 6.3–11.8). The most common event and adverse event leading to discontinuation of T-DXd was progressive disease (37 pts, 35.6%) and interstitial lung disease (ILD; 24 pts, 23.1%), respectively. Median time to onset of an ILD event was 5.3 months (range, 0.7–20.0). ILD was grade 1 in 14 pts (13.5%), grade 2 in 3 pts (2.9%), grade 3 in 5 pts (4.8%), grade 4 in 2 pts (1.9%), and grade 5 in 0 pts. The Table summarizes the primary and updated results of ROSET-BM. Conclusion: The updated OS results of this retrospective chart review show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. This study was funded by Daiichi Sankyo Co., Ltd. Primary and updated results from the ROSET-BM study The updated results show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC. Citation Format: Takashi Yamanaka, Naoki Niikura, Takahiro Nakayama, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Hironori Nomura, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Shuji Sakai, Daisuke Takiguchi, Takehiko Takata, Armin Bastanfard, Kazuhito Shiosakai, Junji Tsurutani. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-04.

Abstract PO2-10-07: Patterns of presentation, treatment and survival for older patients with metastatic breast cancer (MBC): results from a large prospective registry

Abstract Background: The median age of breast cancer diagnosis in the U.S. is 62 years; however, older pts with breast cancer are consistently underrepresented in clinical research. In population-based studies, older pts, particularly those aged 70+, do worse than their younger counterparts at every stage of disease, including stage IV. However, our understanding of patterns of recurrence, treatment patterns, and outcomes for older pts with MBC is limited by a lack of available data. Methods: We identified pts age &amp;gt;60 years seen at least once at a single, NCI-designated cancer center for a diagnosis of MBC between 1999-2022 with 1+ years of follow-up from the time of their metastatic diagnosis. We categorized pts into 5-year age groups (60-65; 66-70; 71-75; 76-80; &amp;gt;80) and two groups of 60-70 and &amp;gt;70. Clinicopathologic characteristics, treatment patterns, reason for treatment discontinuation, and the proportion enrolling on clinical trials were compared by tumor subtype and age group using Chi-Square testing. Median overall survival using Kaplan-Meier method was calculated from the date of initial MBC diagnosis to date of death or last follow-up, examined by tumor subtype and age. Results: The final analytic cohort included 1,115 patients diagnosed with MBC with median follow-up of 2.9 years (1.0-18.5). Median age at MBC diagnosis was 66.3 years (60.0-95.4) and 10% were non-White; disease subtype distribution was the following: 70.7% HR+HER2-, 11.9% HER2+, 17.4% TN. Overall, 22.2 presented with de novo MBC. Presentation of MBC did not vary by ages 60-70 vs. 70+, with no differences in disease characteristics such as grade and disease sites at MBC diagnosis (except for bone). However, the proportion of pts with HR+HER2- disease increased with age, from 69% of MBC in ages 60-70 and 76% in ages &amp;gt;70 (p=.02). In pts with this subtype receiving first-line (1L) therapy (n=783), use of endocrine therapy as 1L (with or without a CDK4/6 inhibitor) increased by age (77.8% in ages 60-65 v. 94.7% in ages &amp;gt;80); use of 1L chemotherapy also varied by age (22.2% in ages 60-65 v. 5.3% in &amp;gt;80). Among pts with HER2+ BC, 89% received a trastuzumab-containing regimen in the 1L setting; in pts with TN MBC, 94% received at least 1L line of chemotherapy. Overall, most pts discontinued 1L therapy for progression, not toxicity, and there was no variation in rates of discontinuation due to toxicity by age with 10.4% noted in both age groups, 60-70 and &amp;gt;70. The proportion of patients receiving 3+ lines of chemotherapy across disease subtype decreased with increasing age (e.g., 54% in ages 60-65 v. 25% in ages &amp;gt;80 among HR+HER2-; 69% in ages 60-65 and 33% in ages &amp;gt;80 among TN MBC). Overall, enrollment on a clinical trial in the MBC setting steadily decreased with older age from 40% in ages 60-65 to 13% in ages &amp;gt;80 (p=.0004). Overall median overall survival differed with increasing age from 4.4 yrs in ages 60-65 to 2.7 yrs in ages &amp;gt;80 (p&amp;lt; 0.005). In descriptive analyses, the proportion of pts alive at 2 yrs was variable. For those ages 60-65, 37.8%, 17.1%, and 42.9% of pts with HR+HER2, TN, and HR-HER2+, respectively were alive at 2 yrs. For those ages &amp;gt;80, 23.7%, 0%, and 0% of pts with HR+HER2-, TN, and, HR-HER2+ disease were alive at 2 yrs. Median survival times were &amp;lt; 2 years for pts with TN regardless of age. Conclusions. In a unique, large prospective cohort of older pts with MBC, we examined detailed information on disease presentation, treatments, and outcomes, lending new information on patterns of care and experiences for older pts with MBC in a modern real-world experience. Limitations include a single center experience and small numbers of older pts with HER2+ and TN disease. Although the oldest pts with MBC had similar disease characteristics as younger pts in our dataset, survival outcomes were poor, particularly for those ages 80+. Therapeutic approaches, likely including improved supportive care, are urgently needed to optimize outcomes in the oldest pts with MBC. Table 1. Outcomes for older pts with MBC Citation Format: Melissa Hughes, Alyssa Patterson, Alexandra Newman, Amanda Higgins, Gregory Kirkner, Janet Files, Molly Skeffington, McKenna Moore, Sarah Strauss, Nicole Kuhnly, Lindsey Crowley, Sara Tolaney, Nancy Lin, Rachel Freedman. Patterns of presentation, treatment and survival for older patients with metastatic breast cancer (MBC): results from a large prospective registry [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-07.

Risk stratification in multiple myeloma – A review and update

Multiple myeloma (MM) is a hematological malignancy of plasma cell origin with a prevalence rate of 1% and 10% of all cancers and hematopoietic malignancies, respectively. Though the median survival time has improved dramatically in the patients diagnosed with MM with the administration of novel therapeutic agents, the disease, by and large, remains incurable with frequent progression and relapses. In the recent past, an increased understanding of MM pathogenesis has opened facets for improved diagnosis, prognosis, and response assessment in patients diagnosed with MM. This review focuses on the various laboratory and clinical features used to stratify the MM patients into high vs. low-risk groups. Furthermore, it also highlights the role of artificial intelligence-based innovative research tools for risk stratification and prognostication in MM patients.

Abstract PS06-06: Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer

Abstract Background: The detection of ctDNA in patients with early-stage breast cancer after completion of adjuvant therapy is associated with a high risk of recurrence. Current clinical guidelines do not recommend routine screening for metastatic disease unless there are clinical signs and symptoms in patients who completed adjuvant therapy. However, ctDNA may serve as an early biomarker of recurrence which may allow effective identification of patients with asymptomatic distant metastases or molecular relapse only, who could benefit from early treatment intervention. Herein, we utilized a tissue-free, multiomic assay for the sensitive and specific detection of MRD in patients with early-stage breast cancer. Methods: Plasma samples were collected from patients with stage I-III breast cancer who were enrolled in the SUCCESS-A phase 3 clinical trial (NCT02181101) between 2006 and 2007. All patients received adjuvant chemotherapy +/- endocrine therapy and/or anti-HER2 therapy. Samples were collected approximately two years after completion of adjuvant chemotherapy, and plasma samples selected for analysis were from patients without evidence of disease recurrence prior to sample collection. Presence of MRD was assessed using Guardant Reveal powered by Infinity, which evaluates the epigenomic signals associated with cancer versus normal DNA for the detection of ctDNA. Samples with the presence of ctDNA are characterized for somatic alterations with common sources of interference such as clonal hematopoiesis excluded. An analytically validated bioinformatics pipeline was used for the detection of breast cancer ctDNA. Samples were analyzed blinded to the clinical data. Median survival times were estimated using the Kaplan-Meier method and hazard ratios were calculated based on univariable cox regression models. Results: A total of 311 plasma samples from 311 patients were evaluable. ctDNA was detected in 34% (13/38) of patients who subsequently developed distant recurrence and in none (0/7) of the patients who had local or contralateral breast cancer recurrence. ctDNA was detected in 60% (9/15) of samples that were collected within one year before recurrence. In the ctDNA detected samples from patients who had disease recurrence, the median time from sample collection to recurrence was 7.9 months (range, 1.4-28.6 months). ctDNA was detected in 6 patients who did not have a documented disease recurrence, resulting in a specificity of 97.7% (260/266). In the overall cohort, ctDNA detection was prognostic for recurrence-free survival (RFS; HR 11.0, 95% CI 2.28-53.6; p&amp;lt; 0.0001), distant recurrence-free survival (D-RFS; HR 13.7, 95% CI 2.52-74.9; p&amp;lt; 0.0001), and overall survival (OS; HR 17.4, 95% CI 1.33-227; p&amp;lt; 0.0001). Conclusion: Detection of ctDNA after adjuvant chemotherapy was highly prognostic and demonstrated high specificity in an early-stage breast cancer cohort. Larger, prospective studies are needed to confirm the prognostic value of ctDNA in the post-treatment setting and assess the clinical utility of MRD detection in this population. Citation Format: Wolfgang Janni, Thomas Friedl, Brigitte Rack, Peter A. Fasching, Andreas Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Müller, Andreas Schneeweiss, Matthias Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai. Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS06-06.