Kaplan-Meier Curves For Overall Survival Research Articles

The Prognostic Significance of Surgical Treatment for Excessive Elderly Soft Tissue Sarcoma Patients over 90 Years Old: A Clinicopathological Study of 16 Cases.

The incidence of soft tissue sarcomas (STSs) among older patients is increasing. Although surgical treatment of elderly patients with STS has been reported to improve their prognosis, most of these studies included patients with STS aged <85 years. This study aimed to analyze the clinical features and prognostic factors of STS in elderly patients aged ≥90 years. We retrospectively identified patients aged ≥90 years with STS who were treated at our two hospitals between 1994 and 2022. Data on clinical information and detailed assessments were collected. We evaluated the features and factors affecting the prognosis of patients with older-extremity STS. In addition, we compared the clinical courses and results of patients treated with surgery and radiotherapy for primary tumors. Among 454 patients with STS, 16 were aged ≥90 years. Kaplan-Meier curves for overall survival showed a significantly poorer prognosis in patients who did not receive surgical treatment (p = 0.0348) and those who received radiotherapy (p = 0.0070). Moreover, we investigated the difference in prognosis between surgical treatment and radiotherapy, excluding two cases with distant metastasis at initial diagnosis and one case with no treatment. Kaplan-Meier curves for overall survival showed a significantly better prognosis in patients who underwent surgical treatment (p = 0.0161). Univariate analysis revealed that only primary tumor size was a significant predictor of poor prognosis (p = 0.0426). In patients with STS aged ≥90 years old, aggressive surgical treatment may improve the prognosis more than radiotherapy.

Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

#1883 SUrvey of renal Biopsy database and Anti-cancer dRUg therapy in Japan (SUBARU-J study)

Abstract Background and Aims The frequency of consultations for renal complications associated with anti-cancer drug therapy has greatly increased in recent years, but the actual situations remain yet to be fully understood. We aimed to investigate the clinical outcomes of anti-cancer drug therapy-associated renal complications, using the Japan Renal Biopsy Registry (J-RBR), a nationwide registry system in Japan. Method This nationwide survey was performed in 449 cases with “drug-induced” checked in J-RBR database from 2018 to 2021. In total 449 subjects, top-ranked histopathological diagnoses were as follows, TIN (49.8%), TMA (14.5), MN (10.0), MCNS (6.5), FSGS (4.4), Vasculitis (2.2) and others (12.2). Regardless of the causative agent, TIN was the most common diagnosis. Though, it was followed by TMA or MN in anti-cancer drug (n = 139)- or non-anticancer drug (n = 190)-related cases, respectively. Because there was also TMA included as 2nd highest in causative-agent unidentified cases (n = 120), we employed total 259 subjects of anti-cancer drug-related and causative-agent unidentified for this survey. Our surveillance files investigating on renal pathology, medications and cancer prognosis were distributed. Of the 224 cases with a file uploaded, a total of 135 anti-cancer drug-related cases confirmed by the information were analyzed. Patients’ clinical data collected at pre- and post-biopsy as well as histopathological diagnoses were used for epidemiological and clinicopathological analyses. Mann-Whitney U test or chi-square test was used for continuous or categorical variables. Overall survival (OS) was estimated using Kaplan–Meier method and compared by log-rank test. Results In total 135 subjects, top-ranked histopathological diagnoses were as follows: tubulointerstitial nephritis (TIN; 64 cases), thrombotic microangiopathy (TMA; 48), focal segmental glomerulosclerosis (FSGS; 5), IgA nephropathy (IgAN; 4), acute tubular necrosis (ATN; 3), minimal change nephrotic syndrome (MCNS; 3), crescentic glomerulonephritis (CrGN; 2), membranoproliferative glomerulonephritis (MPGN; 2) and others (4). 80% of TIN and 75% of TMA, the most frequent diagnoses in our survey, were associated with immune-checkpoint inhibitors (ICI) and anti-angiogenic therapy (AAG), respectively. All IgAN, MCNS and CrGN cases were ICI-related. Proton pump inhibitors and antibiotics were used concomitantly in TIN (p = 0.054) and TMA (p < 0.001), respectively. Among cases with TIN, their OS in the subgroups of targeted therapy (Tx), and the combination with Tx and conventional cytotoxic agents (Combi) seemed to be worse than that of cytotoxic agents alone (CTx); it may be due to more cases in the Tx and Combi subgroups with treatment response category of progressive disease (by RECIST criteria). In contrast, among TMA cases, OS in each of the three subgroups of Tx, CTx, and Combi seemed to be overlapped, suggesting the prognostic impact of TMA on OS. The serum LDH level was higher in TMA associated with CTx (CTx-TMA) than that with others (Fig. 1: 393.2 vs. 225.1 U/L, p = 0.06). Of note, Kaplan-Meier curves for OS in TMA cases with increased LDH (>220 U/L) showed poor prognosis in CTx-TMA than in others-TMA (Fig. 2: p = 0.018). Conclusion Our nationwide survey using J-RBR registry database with renal biopsy data provides a snapshot of kidney complications associated with anti-cancer drug therapy. Higher LDH in CTx-TMA cases may be associated with systemic TMA, probably leading to the poor prognosis. To explore the detail of anti-cancer drug-associated TMA and other complications, further research employing more sample size is warranted in the future.

Comparing survival in trial- versus routine-care advanced urothelial cancer patients on immune checkpoint blockade.

Although recent trials involving first-line immune checkpoint inhibitors have expanded treatment options for patients with advanced urothelial carcinoma (aUC) who are ineligible for standard cisplatin-based chemotherapy, there exists limited evidence for whether trial efficacy translates into real-world effectiveness for patients seen in routine care. This retrospective cohort study compares differences in overall survival (OS) between KEYNOTE-052 trial participants and routine-care patients receiving first-line pembrolizumab monotherapy. A routine-care patient cohort was constructed from the Flatiron Health database using trial eligibility criteria and was weighted to balance EHR and trial patient characteristics using matching-adjusted indirect comparisons. The routine-care cohort was older, more likely to be female, and more often cisplatin-ineligible due to renal dysfunction. ECOG performance status was comparable between the cohorts. Median OS was 9 months (95% CI 7-16) in the weighted routine-care cohort and 11.3 months (9.7-13.1) in the trial cohort. No significant differences between the Kaplan-Meier OS curves were detected (p = 0.76). Survival probabilities were similar between the weighted routine-care and trial cohorts at 12-, 24-, and 36- months (0.45 vs. 0.47, 0.31 vs. 0.31, 0.26 vs. 0.23, respectively). Notably, routine care patients had modestly lower survival at 3 months compared to trial participants (0.69 vs. 0.83, respectively). Our results provide reassurance that cisplatin-ineligible aUC patients receiving first-line immunotherapy in routine care experience similar benefits to those observed in trial patients.

Comparison of uncut Roux-en-Y anastomosis and Billroth-II with Braun anastomosis after distal gastrectomy.

This study aimed to compare the clinical outcomes and patient benefits of uncut Roux-en-Y (URY) anastomosis and Billroth-II with Braun (BB) anastomosis after distal gastrectomy. We retrospectively reviewed the data of patients who underwent URY or BB anastomosis after distal gastrectomy between March 2015 and December 2017. Clinical characteristics, survival data, postoperative recovery data, and long-term outcomes were recorded and compared between the two groups. A total of 231 patients were included, with 167 in the URY group and 64 in the BB group. Kaplan-Meier curves for overall survival showed no differences after propensity score matching (p = 0.488). Long-term postoperative quality of life evaluation also showed no significant differences. Compared to the BB group, patients in the URY group had a significantly shorter time to start a liquid diet after propensity score matching (67.6 h vs. 46.5 h, p = 0.003), and a lower occurrence of bile reflux on follow-up gastroscopy (p < 0.001). The URY anastomosis appears to be a feasible method for digestive tract reconstruction after distal gastrectomy, resulting in less bile reflux and better postoperative recovery. However, there is no significant difference between URY and BB anastomosis in terms of overall survival and long-term quality of life.

A meta-analysis of overall survival and response in metastatic adrenocortical carcinoma: A review of 23 prospective trials of 880 patients.

4 Background: Metastatic adrenocortical carcinoma (mACC) is a rare, aggressive tumour of the adrenal gland, with historically poor survival and limited established treatment modalities. The aim of this study was to systematically search for and analyse all prospective trials for mACC to establish benchmark response and survival outcomes. The study was registered on PROSPERO CRD42023430557. Methods: A systematic review and meta-analysis of five databases was performed between June 2023- July 2023. Key outcomes extracted included patient demographics, overall survival (OS), progression-free survival (PFS) and objective response rates (ORR). ORR was calculated using a random effects model and inverse variance methods. Time-to-event outcomes including PFS and OS, were extracted digitally from available Kaplan- Meier curves using the IPDfromKM tool and individual patient data (IPD) was generated as per Guyot et al. The PFS and OS data from individual studies were then pooled using a multivariate extension of the DerSimonian–Laird method to generate summary survival curves. Results: The final 23 trials (5 Phase 1b, 16 Phase II and 3 Phase 3) encompassed 880 patients were retrieved. Pooled ORR was 9.0% overall (2.9% for targeted therapy, 12.3% for chemotherapy and 15.3% for immunotherapy). Median OS was 9.9 months (7.4 months for targeted therapy, 11.2 months for chemotherapy and 10.6 months for immunotherapy). Median PFS was 2.6 months (2.7 months for targeted therapy, 3.0 months for chemotherapy and 2.1 months for immunotherapy). Kaplan-Meier curves for OS were available for 10 treatment lines (n = 605), with a pooled median OS of 9.9 months (95% CI 7.7-11.9) and 12-month OS of 41.6% (95CI 33.1-51.2). Median OS was 7.4 months for patients receiving targeted therapy (95% CI 4.7–12.0), 11.2 months for patients receiving chemotherapy (95% CI 6.9–14.7) and 10.6 months for patients receiving immunotherapy (95% CI 4.4–13.2]. 12-month OS was 30.4% (95% CI 15.9-58.3) for patients receiving targeted therapy, 45.4% (95% CI 33.7-61.2) for patients receiving chemotherapy and 45.3% (95% CI 36.2-56.6) for patients receiving immunotherapy. Conclusions: This study found that current treatments strategies confer limited survival and response benefit in mACC and highlight the need for research into the pathogenesis and novel strategies in the disease. Immunotherapy and chemotherapy demonstrate modest benefits for patients and future trials should attempt to surpass the survival benchmarks set in this study.

A short decision time for transcatheter embolization can better associate mortality in patients with pelvic fracture: a retrospective study.

Early use of hemostasis strategies, transcatheter arterial embolization (TAE) is critical in cases of pelvic injury because of the risk of hemorrhagic shock and other fatal injuries. We investigated the influence of delays in TAE administration on mortality. Patients admitted to the Advanced Critical Care Center at Gifu University with pelvic injury between January 2008 and December 2019, and who underwent acute TAE, were retrospectively enrolled. The time from when the doctor decided to administer TAE to the start of TAE (needling time) was defined as "decision-TAE time." We included 158 patients, of whom 23 patients died. The median decision-TAE time was 59.5 min. Kaplan-Meier curves for overall survival were compared between patients with decision-TAE time above and below the median cutoff value; survival was significantly better for patients with values below the median cutoff value (p = 0.020). Multivariable Cox proportional hazards regression analysis revealed that the longer the decision-TAE time, the higher the risk of mortality (p = 0.031). TAE duration modified the association between decision-TAE time and overall survival (p = 0.109), as shorter TAE duration (procedure time) was associated with the best survival rate (p for interaction = 0.109). Decision-TAE time may play a key role in establishing resuscitation procedures in patients with pelvic fracture, and efforts to shorten this time should be pursued.

Rates of Occult Invasive Disease in Patients With Biopsy-Proven Oral Cavity Squamous Cell Carcinoma in Situ

The likelihood that an oral cavity lesion harbors occult invasive disease after biopsy demonstrating carcinoma in situ (CIS) is unknown. While de-escalated treatment strategies may be appealing in the setting of CIS, knowing whether occult invasive disease may be present and its association with survival outcomes would lead to more informed management decisions. To evaluate rate of occult invasive disease and clinical outcomes in patients with oral cavity CIS. This was a retrospective population-based cohort study using the National Cancer Database and included adults with biopsy-proven oral cavity CIS as the first diagnosis of cancer between 2004 and 2020. Data were analyzed from October 10, 2022, to June 25, 2023. Surgical resection vs no surgery. Analyses calculated the rate of occult invasive disease identified on resection of a biopsy-proven CIS lesion. Univariate and multivariate logistic regression with odds ratios and 95% CIs were used to identify significant demographic and clinical characteristics associated with risk of occult invasion (age, year of diagnosis, sex, race and ethnicity, oral cavity subsite, and comorbidity status). Kaplan-Meier curves for overall survival (OS) were calculated for both unresected and resected cohorts (stratified by presence of occult invasive disease). A total of 1856 patients with oral cavity CIS were identified, with 122 who did not undergo surgery (median [range] age, 65 [26-90] years; 48 female individuals [39.3%] and 74 male individuals [60.7%]) and 1458 who underwent surgical resection and had documented pathology (median [range] age, 62 [21-90] years; 490 female individuals [33.6%] and 968 male individuals [66.4%]). Of the 1580 patients overall, 52 (3.3%) were Black; 39 (2.5%), Hispanic; 1365 (86.4%), White; and 124 (7.8%), other, not specified. Among those who proceeded with surgery with documented pathology, 408 patients (28.0%) were found to have occult invasive disease. Higher-risk features were present in 45 patients (11.0%) for final margin positivity, 16 patients (3.9%) for lymphovascular invasion, 13 patients (3.2%) for high-grade invasive disease, and 14 patients (3.4%) for nodal involvement. For those patients with occult disease, staging according to the American Joint Committee on Cancer's AJCC Cancer Staging Manual, eighth edition, was pT1 in 341 patients (83.6%), pT2 in 41 (10.0%), and pT3 or pT4 disease in 26 (6.4%). Factors associated with greater odds of occult invasive disease at resection were female sex, Black race, and alveolar ridge, vestibule, and retromolar subsite. With median 66-month follow-up, 5-year OS was 85.9% in patients who proceeded with surgical resection vs 59.7% in patients who did not undergo surgery (difference, 26.2%; 95% CI, 19.0%-33.4%). This cohort study assessed the risk of concurrent occult invasion with biopsy-proven CIS of the oral cavity, demonstrating that 28.0% had invasive disease at resection. Reassuringly, even in the setting of occult invasion, high-risk disease features were rare, and 5-year OS was nearly 80% with resection. The findings support the practice of definitive resection if feasible following biopsy demonstrating oral cavity CIS.

Associations between R.E.N.A.L. nephrometry score and survival outcomes in renal tumours.

The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P <0.001; recurrence-free survival , P <0.001), E (exophytic/endophytic) (overall survival, P =0.003; recurrence-free survival, P <0.001), N (nearness) (overall survival, P =0.063; recurrence-free survival, P <0.001), A (anterior/posterior) (overall survival, P <0.001; recurrence-free survival, P =0.005), L (location) (overall survival, P =0.008; recurrence-free survival, P <0.001) and suffix 'h' (overall survival, P =0.237; recurrence-free survival, P =0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P <0.001; recurrence-free survival, P <0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P =0.027, hazard ratio (95% confidence interval)=1.151 (1.016-1.303)] and recurrence-free survival [P <0.001, hazard ratio (95% confidence interval)=1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.

Risk assessment according to the presence of left heart disease phenotype in pulmonary arterial hypertension patients: a multicenter cohort study

Abstract Introduction Subclinical left heart disease (LHD) may impact the management of pulmonary arterial hypertension (PAH) [1]. Purpose To evaluate the influence of a LHD phenotype on PAH risk stratification. Methods We retrospectively reviewed the data of consecutive PAH patients followed at 7 tertiary centers from 2001 to 2021, and selected those with all parameters available to determine risk of death by means of the COMPERA and COMPERA 2.0 scores, both at baseline and at the first disease reassessment including right heart catheterization. These subjects were classified as no-LHD or LHD according to the AMBITION trial criteria, i.e. absence or presence, respectively, of ≥ 3 among body mass index ≥ 30 kg/m2, systemic hypertension, diabetes mellitus, and coronary artery disease; and/or pulmonary vascular resistance between 3 and 3.75 WU or between 3.75 and 6.25 WU together with pulmonary artery wedge pressure (PAWP) between 13 and 15 mmHg [2,3]. The characteristics between the 2 groups were compared by chi-square test, T-test, or Mann-Whitney test, and Kaplan-Meier curves for overall survival by log-rank test. Results Of 286 patients included in the analysis, 57 (20%) had a LHD phenotype. The first complete reassessment was performed 7 ± 5 months after baseline. Compared with no-LHD, subjects with LHD were older, had more often cardiovascular comorbidities, and had higher E/e’ ratio, left atrial area and PAWP, but had lower brain natriuretic peptide concentrations and better right ventricular function and pulmonary hemodynamics (Figure 1). They were also less commonly treated with phosphodiesterase inhibitors or riociguat (54% vs 70%, P=0.03) and dual oral therapy (26% vs 43%, P=0.03), while they used more beta-blockers (47% vs 16%, P&amp;lt;0.001) and ACE inhibitors or angiotensin receptor blockers (40% vs 21%, P=0.004). At baseline, the proportion of patients with low vs high risk was greater in LHD than in no-LHD with COMPERA, but not with COMPERA 2.0. Moreover, risk profile significantly improved during follow-up only in no-LHD with COMPERA, but in both groups with COMPERA 2.0 (Figure 1). While all-cause mortality was significantly different across baseline COMPERA and COMPERA 2.0 risk strata in no-LHD, either approach for risk stratification failed to discriminate LHD subgroups with different prognosis (Figure 2). However, both COMPERA and COMPERA 2.0 risk categories differentiated mortality in LHD at the first disease reassessment (log-rank P &amp;lt;0.001, not shown). Conclusions This study suggests that the performance of risk stratification scores COMPERA and COMPERA 2.0 in PAH subjects with a LHD phenotype is limited, although the former may retain value during follow-up. Alternative tools may be needed for prognostication in this patient subset.

Anemia and Transfusion Dependency Are Important Prognostic Factors for Overall Survival in Patients with Myelofibrosis: Results of a Real-World Analysis of Medicare Patients

Introduction: Anemia is a hallmark feature of myelofibrosis (MF) and causes many patients (pts) to require red blood cell transfusions. Both anemia and transfusion dependency have been associated with decreased survival in pts with MF. The purpose of this study was to assess the relationship between anemia severity and transfusion dependency on overall survival (OS) among pts with MF in the Medicare population. Methods: This retrospective cohort study used the Medicare fee-for-service database to identify pts with a diagnosis of MF between January 1, 2012, and December 31, 2020. Study inclusion criteria were as follows: (1) ≥1 inpatient or ≥2 outpatient claims for MF (on separate dates &amp;lt;90 days apart; the earliest appearance of MF was set as the MF diagnostic index date [MFDID]); (2) 12 months of continuous enrollment preceding (baseline) and 6 months of continuous enrollment following (follow-up) the MFDID; (3) absence of Janus kinase inhibitor therapy during the 12-month baseline period; (4) absence of polycythemia vera, essential thrombocythemia, or another primary cancer other than basal and squamous cell skin carcinoma during the baseline period; and (5) absence of participation in a clinical trial. Transfusions were assessed over a 180-day landmark period following anemia index date (AID; set to the earliest evidence of anemia, unless it occurred during the 100 days prior to the MFDID, in which the AID was set to the MFDID), and pts were stratified into 3 subcohorts: transfusion independent (TI; no transfusions), transfusion dependent (TD; ≥6 transfusion claims on 6 separate days over any 12-week window), or transfusion requiring (TR; received transfusion claims but did not meet TD criteria). A subset of pts were identified as having anemia based on medical claims from the Medicare fee-for-service database or laboratory test results from the Prognos Biomarker and Laboratory Database ≤100 days before and any time after the MFDID, with severity subcohorts graded based on hemoglobin levels: mild (10 to &amp;lt;12 g/dL), moderate (8 to &amp;lt;10 g/dL), or severe (&amp;lt;8 g/dL) disease. OS from the MFDID was assessed for all pts using Kaplan-Meier analyses, with log-rank tests used to determine statistically significant differences among the transfusion dependency and anemia severity subcohorts. Results: A total of 1749 pts qualified for the transfusion cohorts: 980 were TI, 559 were TR, and 210 were TD. Mean age was 74.8 years, 47.9% were male, and 81.7% were White. Results of Kaplan-Meier analyses showed a median OS of 44.1 months (95% CI, 39.8-48.5 months) for the overall transfusion sample and 62.6 months (95% CI, 57.8-68.2 months) for the TI cohort, 29.0 months (95% CI, 25.9-32.9 months) for the TR cohort, and 22.6 months (95% CI, 20.1-28.1 months) for the TD cohort ( P&amp;lt;.001) (Figure A). A total of 265 pts with corresponding laboratory testing data qualified for the anemia cohorts: 128 were mild, 99 were moderate, and 38 were severe. Mean age was 73.6 years, 47.5% were male, and 79.6% were White. Results of Kaplan-Meier analyses showed a median OS of 64.3 months (95% CI, 56.5-76.9 months) for the overall anemia sample and 89.8 months (95% CI, 72.9 months-not calculable) for the mild cohort, 58.9 months (95% CI, 40.8-69.1 months) for the moderate cohort, and 20.6 months (95% CI, 15.9-49.4 months) for the severe cohort ( P&amp;lt;.001) (Figure B). Conclusions: These results demonstrate that dependency on transfusions, increasing transfusion requirements, and greater anemia severity are each negative prognostic factors for OS among Medicare fee-for-service pts with diagnosed MF. Therapies that reduce transfusion dependency and anemia severity may aid in improving health outcomes and prolong survival in pts with MF. Figure. Kaplan-Meier Curves of Overall Survival in Transfusion (A) and Anemia (B) Subcohorts, Calculated from the Myelofibrosis Diagnostic Index Date

SLC22A3 that encodes organic cation transporter-3 is associated with prognosis and immunogenicity of human lung squamous cell carcinoma.

SLC22A3, the gene which encodes organic cation transporter (OCT)-3, has been linked to the prognosis of several types of cancer. However, its role in lung squamous cell carcinoma (LSCC) has not been addressed elsewhere. We analyzed gene expression, DNA methylation, and clinicopathological data from The Cancer Genome Atlas - Lung Squamous Cell Carcinoma (TCGA-LUSC) (n=501), a publicly available database exclusively consisting of LSCC patients. Using a 5 FPKM (fragments per kilobase of exon per million mapped fragments) cut-off, we divided LSCC patients into two groups: patients with tumors possessing high and low SLC22A3 expression (SLC22A3-high and SLC22A3-low, respectively). Prognostic significance was determined through Cox analyses and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). Differential methylation position (DMP), differentially gene expression, and pathway analyses were performed. Validation was carried out in GSE74777 (n=107), GSE37745 (n=66), GSE162520 (n=45) and GSE161537 (n=17). SLC22A3-high LSCC patients had lower OS and DFS rates than SLC22A3-low LSCC patients. The different expression levels of SLC22A3 in LSCC were correlated with the methylation status of the SLC22A3 gene. Pathway analysis indicated that SLC22A3 expression levels were positively correlated with immune-related pathways such as inflammatory response and abundance of infiltrating immune cells in the tumor microenvironment (TME). Notably, in the SLC22A3-high group, many genes encoding immunological checkpoint inhibitory molecules were upregulated. In addition, SLC22A3 expression positively correlated with the Hot Oral Tumor (HOT) score, indicating high tumor immunogenicity. These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.

Sublobar resection versus lobectomy for stage IA non-small-cell lung cancer ≤ 2cm: a systematic review and patient-level meta-analysis.

Despite lobectomy being the standard of care for early-stage non-small-cell lung cancer (NSCLC), sublobar resection (segmentectomy or wedge resection) has recently been suggested to achieve similar outcomes. An electronic literature search was conducted to retrieve randomized controlled trials (RCTs) or propensity score-matched studies (PSMs) comparing lobectomy to sublobar resection in stage IA NSCLC ≤ 2cm in size, with provision of Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). A graphical reconstructive algorithm was used to obtain OS and DFS of individual patients, which was then pooled under random-effects individual patient data meta-analysis using Cox models to determine hazard ratios (HRs). Sensitivity analyses for OS and DFS were also performed, restricting to results from RCTs only. Seven studies (2528 patients) were retrieved. There were no significant differences in OS (shared-frailty HR = 0.92, 95% CI = 0.77-1.11, p = 0.378) or DFS (shared-frailty HR = 1.06, 95% CI = 0.90-1.24, p = 0.476) between lobectomy and sublobar resection. This comparison remained non-significant even when restricted to RCTs only. Pooled Kaplan-Meier curves of OS appeared to diverge over time, in favor of sublobar resection. This was confirmed on analysis of restricted mean survival time curves. This patient-level meta-analysis of high-quality studies demonstrates that sublobar resection is equivalent to lobectomy in patients with small stage IA NSCLC. Sublobar resection offers greater down-the-road benefits in patients who experience recurrence or a second primary tumor since the lung-sparing index surgery allows patients to receive further treatment safely. This heralds sublobar resection as the new standard of care in carefully selected early-stage patients.Trial registration: PROSPERO CRD42023385358.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p=.09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic.

The FLAURA trial demonstrated improved overall survival (OS) with first-line osimertinib for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). We studied the efficacy and safety of osimertinib in a cohort treated during the coronavirus disease 2019 (COVID-19) pandemic. Patients diagnosed with EGFR-mutated advanced NSCLC between 11 March 2020 to 31 December 2021 who received first-line osimertinib in British Columbia, Canada were identified retrospectively. Kaplan-Meier curves of OS and progression-free survival (PFS) from the start of osimertinib were plotted. The associations of baseline characteristics with PFS, and development of pneumonitis or dose reductions due to toxicity with OS were evaluated with hazard ratios estimated using univariable and multivariable Cox models. The cohort comprised 231 individuals. 58.7% of patients with de novo advanced NSCLC were initially diagnosed after presentation to the Emergency Room. At osimertinib initiation, 31.6% were aged ≥75 years and 45.5% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Median PFS and OS were 18.0 months [95% confidence interval (CI): 16.1-26.2] and 25.4 months (95% CI: 20.3-not reached), respectively. On multivariable analysis, age ≥75 years (vs. <75), ECOG PS 2/3 (vs. 0/1), ECOG PS 4 (vs. 0/1), current smokers (vs. never smokers), programmed death ligand 1 (PD-L1) expression ≥50% (vs. <1%), and L858R mutation (vs. exon 19 deletion) were associated with shorter PFS. Among 110 patients who progressed, 33.6% received subsequent therapy. A proportion of 16.5% of the cohort developed grade ≥3 adverse events. Pneumonitis from osimertinib (3.9% incidence) was weakly associated with shorter OS (hazard ratio: 2.59, 95% CI: 0.94-7.12, P=0.066); dose reductions were not associated with worse OS. 10.8% of patients developed COVID-19. In a cohort receiving first-line osimertinib during the COVID-19 pandemic, ECOG PS ≥2 was observed in nearly half of patients at treatment initiation contributing to a median OS shorter than in FLAURA. The incidence of severe adverse events was low and dose reduction for drug toxicity did not impact OS. Identifying and reducing barriers to the diagnosis of NSCLC during the COVID-19 pandemic are required.

Clinical outcomes of soft tissue sarcoma in the Philippines: A single-center experience.

e23549 Background: Soft-tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that account for less than 1 percent of all adult malignant tumors. Data are scarce in the Asia-Pacific region, especially in the Philippines. This study aims to evaluate the epidemiology and clinical outcomes of STS from a private tertiary hospital in the Philippines. Methods: All adult patients treated at St. Luke’s Medical Center (SLMC), Quezon City and Global City, between January 2010 and December 2020 were reviewed. Continuous variables are described in median and categorical variables are described in count and percentage. Kaplan-Meier curves for overall survival (OS) and recurrence-free survival (RFS) were compared by the Log-Rank test. Results: One hundred eighty-seven patients diagnosed with STS were eligible for the study. The median age at diagnosis was 53 years old; the majority were male (54.55%). The most common histologic subtypes were liposarcoma (19.79%), pleomorphic sarcoma, undifferentiated (16.58%), and leiomyosarcoma (11.76%). Most were diagnosed with localized disease (90.9%), with the lower extremities (44.39%) as the most common primary site. The median tumor size was 10.3 cm, primarily high grade (46.52%). Nodal involvement on diagnosis was 4.28%. Twelve patients (6.42%) presented with de novo metastasis; lung (45%) was the most common site. The majority had surgery (81.82%) on the primary tumor, with 56.86% achieving R0. Eighty patients (42.78%) had radiotherapy; the majority were given post-operatively (N = 60). Sixty-three patients (33.68%) received systemic therapy. Out of 170 patients with localized disease, 70 (40%) had disease recurrence, mostly local recurrence (57.14%). The 3-year OS and RFS were 58.67% and 55.20%, respectively, for the entire cohort; for localized disease was 95.06%. There was a statistical difference in OS between distant vs local recurrence (23.28% vs 49.11%)(p &lt; 0.001), nodal involvement (p = 0.041), surgery (p &lt; 0.001), and radiotherapy (p = 0.001). Conclusions: Most STS seen and diagnosed in SLMC is mostly localized disease but with lower rates of resection than in other countries in the Asia-Pacific region. The clinicopathologic features, treatment modalities received, histological subtype, and primary anatomical site are similar to other data. The low survival rate may be attributed to the site of recurrence, nodal involvement, and treatment pattern received.

Evaluating novel imaging-based mathematical modeling prediction of immunotherapy response by individual melanoma brain metastasis and patient prognosis.

e14013 Background: Ipilimumab/Nivolumab (Ipi/Nivo) significantly transformed outcomes for patients with melanoma brain metastases (MBM), however inter- and intra-patient responses can vary widely. The purpose of this study is to develop and calibrate an imaging-based mathematical model to predict lesion-specific immune response to Ipi/Nivo in patients with MBM to guide early local treatments such as radiotherapy and evaluate the prognostic value of identifying treatment resistant lesions. Methods: Baseline and follow-up 3D T1-W contrast MRIs of patients who solely received Ipi/Nivo after diagnosis with MBM were used to segment individual brain metastases and track serial volumetric data for each lesion to develop a mechanistic model (eq 1). After applying appropriate assumptions to our model, tumor burden ( ρ), intrinsic lesion growth rate ( α 0), Ipi/Nivo-induced kill rate ( μ) and immune response strength ( Λ) were quantified for each lesion. Growth rate shortly after the start of treatment ( α 1 ) was calculated using the short-term model solution (eq 2). dρ/dt= (α0- μ+μ.Λ).ρ - μ.Λ.ρ2 (eq 1) ρ(t)≈eα1.t (eq 2) Change in BM volume between baseline and last follow-up was used to classify each lesion as either ‘responder’ or ‘non-responder’; these were compared with the Wilcoxon-rank-sum test. The highest α1 value for any one BM within a patient tumor was evaluated for its potential to sort patient overall survival (OS). Because the median survival was not reached for this cohort, we determined the α1 threshold of 0.005 to sort patients using an optimization routine that generates the maximum AUC to separate the cohort into 2 groups on an ROC curve. Kaplan-Meier (KM) curves were compared between these 2 groups. Results: In 23 patients, we evaluated 61 lesions. At the lesion level, model parameters representing μ and Λ were significantly different between responder and non-responder lesions (p-values &lt;0.0001 and 0.0004, respectively). The highest α1value for any one BM within a patient tumor was used to sort patient overall survival (OS) into prognostically ‘favorable’ or ‘unfavorable’ groups based on patient survival to ±1,200 days. In this limited cohort, OS KM curves by most aggressive lesion for favorable (α1 &lt; 0.005) vs. unfavorable (α1 &gt; 0.005) were not significant by log-rank test (p = 0.3263). Conclusions: In this limited cohort, we demonstrate feasibility to leverage serial conventional imaging and tumor volumetric data to calibrate a mechanistic model to predict per-lesion treatment response of MBM to Ipi/Nivo. Although the p-value between groups was found to be insignificant when predicting survival using α1, this is likely because of the small number of patients included in this study (n=23). Furthermore, when taken together with the notable AUC (=0.7917) observed in the ROC curve, this promising result supports further investigation in a larger cohort.

Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era.

8595 Background: The role of consolidative thoracic and prophylactic brain radiation in extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether Radiation has a benefit to overall survival (OS) in the total patient group and whether this benefit is the same if Chemotherapy (CT) only is used, or chemo-immunotherapy (CT-IO) is used. Methods: The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, were treated 2 to 6 months from diagnosis, and if treated to the brain received 25Gy in 10 fractions only. Multi-variate analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. Results: The total number of patients receiving RT or systemic therapy alone as well as their median follow-ups(months(mn) were (981, 33.02mn) and (8909, 30.59mn). The median time to the start of STX and RT were 22days and 135 days respectively. MVA noted that RT had a greater effect on OS (Thoracic, Brain, Both – HRs = 0.78, 0.75, and 0.68) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.07). Selection for radiation depended significantly upon factors affecting OS(HR) including liver metastases (0.59), females (1.21), age/10yr(0.78) and Charlson co-morbidity index of &gt; 3(0.66), but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity score matched OS curves noted the same effects of RT on OS whether CT or CT-IO was given. The lowest HRs were noted when both thoracic and brain RT were given (see table). Conclusions: The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy. [Table: see text]

Cost-effectiveness of Nivolumab Plus Cabozantinib Versus Cabozantinib as First-Line Treatment of Metastatic Renal Cell Carcinoma

ObjectivesWe first evaluated the cost-effectiveness of nivolumab plus cabozantinib compared with cabozantinib alone as a first-line treatment of metastatic renal cell carcinoma (mRCC) from a US healthcare payer perspective. In the present study, we found that nivolumab plus cabozantinib was not cost-effective compared with cabozantinib alone for first-line treatment of mRCC. MethodsThis economic evaluation study used a 3-state partitioned survival model to assess the cost-effectiveness of nivolumab plus cabozantinib versus cabozantinib alone. The observed Kaplan-Meier curves for overall survival and PFS were digitized from the CheckMate 9ER and CABOSUN trials and the long-term survivals (over a lifetime horizon) beyond the end of the trial were extrapolated using the Log-Logistic model. The cost and health preference data were collected from published literature before. ResultsThe estimated cost for nivolumab plus cabozantinib group was 654 851.32 USD, which was higher than 312 360.47 USD estimated for cabozantinib alone group, resulting in an incremental cost (IC) of 342 490.85 USD. Compared with cabozantinib alone group, nivolumab plus cabozantinib group gains 1.19 QALYs, resulting the ICER was 288 443.23 USD per QALY. One-way sensitivity analysis suggested the cost of nivolumab, the discount rate, and the cost of cabozantinib had a great impact on the ICER. The cost-effectiveness acceptability curves showed the probability of nivolumab plus cabozantinib being cost-effective was 9.9% at a threshold of 150,000 USD per QALY. ConclusionThe findings of this economic evaluation suggest nivolumab plus cabozantinib is unlikely to be cost-effective compared with cabozantinib alone as first-line treatment for mRCC at WTP thresholds of 150,000 USD per QALY from the perspective of US payers. A substantial price reduction for nivolumab would be needed to achieve favorable cost-effectiveness.

Epigenetic and Tumor Microenvironment for Prognosis of Patients with Gastric Cancer.

Epigenetics studies heritable or inheritable mechanisms that regulate gene expression rather than altering the DNA sequence. However, no research has investigated the link between TME-related genes (TRGs) and epigenetic-related genes (ERGs) in GC. A complete review of genomic data was performed to investigate the relationship between the epigenesis tumor microenvironment (TME) and machine learning algorithms in GC. Firstly, TME-related differential expression of genes (DEGs) performed non-negative matrix factorization (NMF) clustering analysis and determined two clusters (C1 and C2). Then, Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) rates suggested that cluster C1 predicted a poorer prognosis. The Cox-LASSO regression analysis identified eight hub genes (SRMS, MET, OLFML2B, KIF24, CLDN9, RNF43, NETO2, and PRSS21) to build the TRG prognostic model and nine hub genes (TMPO, SLC25A15, SCRG1, ISL1, SOD3, GAD1, LOXL4, AKR1C2, and MAGEA3) to build the ERG prognostic model. Additionally, the signature's area under curve (AUC) values, survival rates, C-index scores, and mean squared error (RMS) curves were evaluated against those of previously published signatures, which revealed that the signature identified in this study performed comparably. Meanwhile, based on the IMvigor210 cohort, a statistically significant difference in OS between immunotherapy and risk scores was observed. It was followed by LASSO regression analysis which identified 17 key DEGs and a support vector machine (SVM) model identified 40 significant DEGs, and based on the Venn diagram, eight co-expression genes (ENPP6, VMP1, LY6E, SHISA6, TMEM158, SYT4, IL11, and KLK8) were discovered. The study identified some hub genes that could be useful in predicting prognosis and management in GC.