Higher On Overall Survival Research Articles

Modeling Overall Survival in Patients With Pancreatic Cancer From a Pooled Analysis of Phase II Trials.

We evaluated the validity of surrogacy of progression-free survival (PFS) or time-to-progression (TTP) and overall response rate (ORR) in phase II trials of pancreatic ductal adenocarcinoma (PDAC). In addition, we explored the impact of predictive variables on overall survival (OS) and developed an optimal OS model. We analyzed 1867 clinical endpoint from 619 phase II PDAC trials with a systematic search from PubMed. Endpoint correlations were determined by Spearman's rank correlation. The assessed predictive factors included PFS/TTP, treatment size, therapy type, stage, and previous treatment. The relationship between predictors and OS was explored by a gamma generalized linear model (GLM) with a log-link function and compared with linear models. The Spearman rank correlation coefficient between PFS/TTP and OS was 0.88 (95% confidence interval [CI] 0.85-0.89; p < 0.0001; n = 610) and between ORR and OS was 0.58 (0.52-0.64; p < 0.0001; n = 514). Model comparison favored the GLM model over the linear model, offering more accurate predictions for higher OS values. Consequently, PFS/TTP was the strongest predictor (pseudo-R2 = 0.75), with 1 added median PFS/TTP month associated with 13% (95% CI 13%-14%) increase in median OS. Subgroup analysis revealed that chemotherapy conferred significantly longer OS compared to targeted therapy in 1-Agent and 2-Agent trials, exhibiting a "very large" and "medium" effect size, respectively (rank biserial, rrb = 0.40 [95% CI 0.22-0.56] and rrb = 0.29 [0.16-0.41], both p < 0.0001), although inconsistent efficacy in 3-Agent trials (rrb = 0.12 [-0.07-0.30], p = 0.21). PFS/TTP is a more reliable surrogate than ORR and a strong predictor of OS in phase II trials of pancreatic cancer. Moreover, gamma GLM (log-link function) is a robust tool for modeling positively skewed survival data with non-constant variance, thus can be applied to other cancers' OS data of such nature.

Impact of Facility Volume on Overall Survival in Patients With Head and Neck Cancer Undergoing Palliative Treatment.

Treatment at high-volume facilities (HVF) has been associated with improved prognosis of HNC patients undergoing curative treatment. Whether this systemic factor influences survival outcomes of patients with HNC undergoing palliative treatment is unknown. To investigate the impact of palliative treatment facility volume on overall survival (OS) in patients with head and neck cancer (HNC). The 2004 to 2018 National Cancer Database was queried retrospectively for patients with HNC undergoing palliative treatment. Patients were stratified based on treatment facility volume percentile. Multivariable binary logistic and Cox proportional hazards regression models were implemented. Of 8682 patients included, 1661 (19.1%) underwent palliative therapy at facilities with volume ≥80th percentile. Among 972 facilities included, 643 (66.2%), 182 (18.7%), 85 (8.8%), 44 (4.5%), and 18 (1.9%) had volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentiles, respectively. 5-year OS rates of patients undergoing palliative therapy at facilities with volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentile was 11%, 13%, 11%, 14%, and 23%, respectively (P < .001). Facility volume ≥80th percentile was associated with higher 5-year OS on multivariable Cox regression (aHR 0.34, 95% CI 0.16-0.69, P < .001). Surgical treatment (aOR 1.34, 95% CI 1.07-1.68, P = .012) was associated with undergoing treatment at facilities with volume ≥80th percentile. Undergoing palliative treatment at HVFs is associated with higher OS in HNC. The survival benefit derived from high facility volume should be carefully considered in the context of other patient and facility characteristics in end-of-life management, with specific emphasis on patient-directed goals of care.

Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.

88 Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. Clinical trial information: NCT06106568 . [Table: see text]

Impact of Targeted Systemic Therapy and Radiotherapy on Patients Undergoing Spine Surgery for Metastatic Renal Cell Carcinoma.

In patients undergoing spine surgery for renal cell carcinoma (RCC), we sought to: (1) describe patterns of postoperative targeted systemic therapy and radiotherapy (RT), (2) compare perioperative outcomes among those treated with targeted systemic therapy to those without, and (3) evaluate the impact of targeted systemic therapy and/or RT on overall survival (OS) and local recurrence (LR). A single-institution, retrospective cohort study of patients undergoing spine surgery for metastatic RCC from 2010 to 2021 was undertaken. Treatment groups were RT alone, targeted systemic therapy alone, dual therapy consisting of RT and targeted systemic therapy, and neither therapy. Multivariable Cox regression controlled for age, race, sex, insurance, and preoperative targeted systemic therapy. Forty-nine patients underwent spine surgery for RCC. Postoperatively, 4 patients (8%) received RT alone, 19 (38.8%) targeted systemic therapy alone, 12 (24.5%) dual therapy, and 13 (28.6%) neither. All groups were similar in demographics, preoperative Karnofsky Performance Score (P = 0.372), tumor size (P = 0.413), readmissions (P = 0.884), complications (P = 0.272), Karnofsky Performance Score (P = 0.466), and Modified McCormick Scale (P = 0.980) at last follow-up. Higher 1-year survival was found in dual therapy (83.3%) compared with other therapies. OS was significantly longer in patients with dual therapy compared with other therapies (log-rank; P = 0.010). Multivariate Cox regression (HR = 0.08, 95% CI = 0.02-0.31, P < 0.001) showed longer OS in dual therapy compared with other therapies. Seven patients (14.3%) experienced LR, and a similar time to LR was found between groups (log-rank; P = 0.190). In patients undergoing metastatic spine surgery for RCC, postoperative dual therapy demonstrated significantly higher 1-year survival and OS compared with other therapies. Multidisciplinary management of metastatic RCC is necessary to ensure timely implementation of targeted systemic therapy and RT to improve outcomes.

Impact of surgical types on overall survival in patients with ductal carcinoma in situ: an analysis based on the SEER database.

Breast cancer, as one of the most common malignancies among women globally, presents a concerning incidence rate, underscoring the importance of addressing the treatment of its precursor lesion, ductal carcinoma in situ (DCIS). Treatment decisions for DCIS, involving the balance between breast-conserving surgery (BCS) and mastectomy, remain an area requiring further investigation. This study aimed to compare influence of different surgical types on overall survival (OS) of patients with DCIS and identify specific subgroups with improved OS to develop an effective survival nomogram for patients. Patient data from the Surveillance, Epidemiology, and End Results (SEER) database for DCIS cohort from 2010 to 2020 were retrieved. Kaplan-Meier (K-M) survival curves were utilized to compare prognostic OS of patients with different surgical methods. Cox regression analysis was employed to determine prognostic factors and establish a nomogram to predict 3-, 5-, and 10-year survival rates. The model was confirmed by Concordance Index (C-index), calibration curves, and receiver operating characteristic (ROC) curves. A total of 71,675 patients with DCIS were included. Patients who underwent subcutaneous mastectomy (SM) demonstrated the best OS compared to other surgical types. Additionally, adjuvant radiotherapy or chemotherapy in combination with surgery significantly improved OS compared to surgery alone. Among DCIS patients aged ≤74 years, those who underwent SM benefited the most in terms of OS, while in the age group of 63-74 years, patients who underwent BCS had significantly higher OS than those who underwent total (simple) mastectomy (TM)/modified radical mastectomy (MRM). Multiple factors were associated with improved OS in DCIS patients, and these factors were integrated into the nomogram to establish OS predictions. The C-index, calibration curves, and ROC curves indicated that the nomogram was suitable for assessing patient prognosis. This study demonstrated that SM treatment yielded the best survival rates for DCIS patients, providing important guidance for future surgical decision-making. Moreover, identifying multiple independent factors related to survival and establishing reliable survival nomograms can assist physicians in developing personalized treatment plans and prolonging patient survival.

Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.

e16298 Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. [Table: see text]

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Blinatumomab Therapy Is Associated with Favorable Outcomes after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with B Cell Acute Lymphoblastic Leukemia

Blinatumomab, a bispecific T cell engager that binds CD19 in leukemic cells and CD3 in cytotoxic T cells and leads to leukemic blast lysis, is often used in pediatric patients with relapsed/refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL) prior to allogeneic hematopoietic cell transplantation (allo-HCT). Concerns about the potential risk of blinatumomab-related immune-mediated toxicities after allo-HCT have not been adequately addressed. These include graft-versus-host disease (GVHD), delayed engraftment, and graft failure or rejection. Pediatric-specific data reporting post-HCT outcomes of patients treated with blinatumomab are scarce and limited to small cohorts. We sought to investigate the clinical outcomes of pediatric patients with R/R B-ALL who received blinatumomab therapy pre-HCT, focusing on overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM), as well as the incidence of immune-mediated post-HCT complications including GVHD, delayed neutrophil or platelet engraftment, graft failure, and graft rejection. We also investigated blinatumomab's effects on B cell reconstitution based on achievement of i.v. immunoglobulin (IVIG) independence post-HCT. This single-center, retrospective study included patients with B-ALL receiving blinatumomab therapy before undergoing allo-HCT, with transplantation performed between 2016 and 2021 at our institution. Patients receiving blinatumomab for relapse after allo-HCT were excluded. Patients receiving chemotherapy alone before allo-HCT during the same period composed the control group. Seventy-two patients were included, 31 of whom received blinatumomab before allo-HCT. Survival estimates were obtained using the Kaplan-Meier method, and the log-rank test was used to analyze differences between groups. Categorical variables were compared between groups using the chi-square test or Fisher exact test, and continuous variables were compared using the Wilcoxon rank-sum test. Cumulative incidences were estimated using the competing risks method, and Gray's test was used to analyze differences between groups. A Cox proportional hazards regression model was used for univariate and multivariable analyses for OS. Landmark analysis was performed at the set time points of 30 days and 100 days post-allo-HCT. Most patients in the study cohort had high-risk relapsed B-ALL. Blinatumomab therapy induced minimal residual disease (MRD)-negative remissions in all patients, whereas 5 patients (12.2%) receiving chemotherapy alone had persistent MRD pre-allo-HCT. Time from the start of therapy to the date of allo-HCT was shorter for patients who received blinatumomab compared with those who received chemotherapy (P < .0001). Blinatumomab therapy was associated with greater LFS compared to chemotherapy alone (P = .049), but when limited to 1 year, LFS was not significantly different from control (P = .066). There appeared to be higher OS, lower CIR, and lower NRM in patients receiving blinatumomab compared to the control group; however, the differences were not significant. None of the variables assessed in multivariable analysis was associated with differences in OS. When compared to the controls, blinatumomab therapy did not result in a higher incidence of acute or chronic GVHD, delayed neutrophil or platelet engraftment, or graft failure or rejection. The time to IVIG infusion independence post-allo-HCT was similar in the 2 groups. This study supports the use of blinatumomab salvage therapy for R/R B-ALL before allo-HCT given its efficacy in inducing MRD-negative remissions and optimizing LFS, as well as its lack of association with an increased incidence of post-allo-HCT adverse immune-mediated toxicities. Larger, prospective studies are needed to confirm these findings and to investigate blinatumomab's effects in long-term post-allo-HCT events.

Influence of contralateral prophylactic mastectomy on textbook outcome attainment at time of mastectomy

IntroductionThe objective of this study was to determine the incidence of textbook oncologic outcome (TOO) and its impact on overall survival (OS) among patients with invasive ductal carcinoma (IDC) following modified radical mastectomy (MRM) versus MRM with contralateral prophylactic mastectomy (MRM ​+ ​CPM). MethodsThe 2004–2017 National Cancer Database was queried for patients with IDC who underwent MRM and MRM ​+ ​CPM. TOO was defined as: resection with negative margins, adequate lymphadenectomy, length of stay ≤50th percentile, and no 30-day readmission or mortality. Results87,573 patients were identified, of which 14.3% underwent MRM ​+ ​CPM. Logistic regression models revealed that MRM ​+ ​CPM is independently associated with a reduced likelihood of achieving TOO (AOR ​= ​0.71; P ​< ​0.001). MRM patients who achieved TOO had a higher median OS compared to those who did not (164.6 vs.142.2 months, P ​< ​0.001). ConclusionsMRM ​+ ​CPM is associated with a lower incidence of TOO attainment compared to MRM.

Timing of Postoperative Radiation Therapy for Early-Stage Endometrial Carcinoma: A 20-Year Single-Center Retrospective Cohort Experience in China

To investigate the appropriate timing of radiotherapy (RT) after hysterectomy for women with early-stage endometrial carcinoma (EC). Between 1999 and 2020, 1080 patients with I and II endometrial cancer received postoperative RT at our hospital. All patients underwent hysterectomy followed by RT. The optimal cut-off values for the surgery-RT interval (SRI) based on overall survival (OS) were determined using the R software. The disease-free survival (DFS), OS, locoregional recurrence free survival (LRFS), and distant metastasis free survival (DMFS) rates were estimated using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Median follow-up time was 52 months. Median SRI were 46 days. The optimal cut-off value for the surgery-RT interval (SRI) based on overall survival (OS) is 40 days. The group initiated RT within 40 days following surgery has higher OS (P = 0.004), higher LRFS (P = 0.002) and higher DMFS (P = 0.039). An SRI of ≤ 40 days was independently associated with higher OS (HR 0.454, 95% CI:0.261-0.788), higher LRFS (HR 0.487, 95% CI:0.304-0.779), and higher DMFS (HR 0.643, 95% CI:0.421-0.982) than SRI of >40 days. However, SRI had no significant effect on DFS. The surgery-RT interval affects the patients' survival endpoints. Based on this analysis, the timing of the initiation of RT after hysterectomy is crucial for patients with early-stage endometrial carcinoma (EC). The postoperative radiation therapy for endometrial cancer should be initiated within 40 days following surgery.

The Association of Time Interval between Surgery and Neoadjuvant Chemoradiation Therapy with pCR and Overall Survival for Locally Advanced Rectal Adenocarcinoma

To determine the best time interval between neoadjuvant radiation therapy (RT) and surgery that is associated with the highest rate of complete pathological response (pCR) and evaluate its impact on overall survival (OS) for locally advanced rectal adenocarcinoma. We hypothesize that the longer interval the higher pCR and a higher pCR is associated with a higher OS. The National Cancer Database (NCDB) was used to extract data on patients diagnosed with stage II and III adenocarcinoma of the anus, rectum, or rectosigmoid between 2004-2019 and who had ≤ 24 weeks' time interval between neoadjuvant RT and surgery. Multivariable logistic regression analysis was used to determine factors associated with achieving pCR and odds ratios (OR) were reported as a measure of association between the covariates of interest and the outcome of achieving pCR. Multivariable Cox regression analysis was conducted to estimate hazard ratios (HR) and their associated 95% confidence intervals. The multivariable analyses were adjusted for age at diagnosis, sex, race, income, education, facility type, insurance status, comorbidity score, place of living, chemotherapy's sequence with surgery and RT, and year of diagnosis. Among 28,656 patients, 4,455 (15.6%) achieved pCR. In the multivariable logistic regression analysis, patients who received surgery between 5-8 weeks, 9-12 weeks, 13-16 weeks, 17-20 weeks, or 21-24 weeks after the completion of RT were more likely to achieve pCR compared to < = 4 weeks (ORs: 1.63, 2.16, 1.82, 1.73, 1.75, respectively, p<0.001 for all) with OR being the highest for the 9-12 weeks interval. In the multivariable Cox regression analysis, patients who achieved pCR had comparable OS regardless of when the surgery took place between < = 4 to 24 weeks after completing RT compared to < = 4 weeks after RT. Among patients who did not achieve pCR, OS was only similar if surgery was received between 5-8 weeks or 9-12 weeks after RT compared to < = 4 weeks after RT (HR: 0.90, p = 0.19 and HR: 1.02, p = 0.78 respectively). However, surgery between 13-16 weeks after RT, 71-20 weeks or 21-24 weeks after RT was associated with worse OS compared to < = 4 weeks after RT (HRs: 1.30, 1.67, 1.79, respectively, p<0.01). In the current study, we found that among patients who achieve pCR, OS does not depend on the time interval between the completion of RT and receipt of surgery, while among patients who do not achieve pCR, delaying surgery >12 weeks is associated with reduced OS. An interval of 9-12 weeks was the best optimal time as it was associated with the highest OR of achieving pCR and better OS compared to other interval times.

Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer.

Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.

Social determinants of health burden among adolescent and young adult cancer patients and impact on overall survival.

12017 Background: The 5-year survival rates for adolescents and young adults (AYA) with cancer have steadily improved, yet disparities by race/ethnicity persist. The drivers of these disparities remain unclear. Neighborhood socioeconomic deprivation has been linked to adverse health outcomes independent of the effects of individual-level measures of social determinants of health (SDOH). We evaluated the impact of neighborhood SDOH on overall survival (OS) in a diverse AYA cancer patient population treated in a single academic setting. Methods: This study utilized a multi-ethnic cohort of AYA cancer survivors (N=10,261) diagnosed between ages 15-39 seen at MD Anderson Cancer Center between 2000 and 2016. Patient demographics, zip code at presentation, cancer characteristics, and follow-up were obtained from our institutional tumor registry. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI representing worse SDOH. Results: The cohort included 6,361 (62%) non-Hispanic White, 1,112 (10.8%) non-Hispanic Black, and 2,133 (20.8%) Hispanic AYA cancer patients, with 655 (6.4%) of other ethnicities or missing information. The mean ADI value was significantly higher (p&lt;0.05) for Black (61.7) and Hispanic (65.3) patients, compared to White (51.2) patients. Analysis of ADI by cancer type showed significant differences, mainly driven by the significantly higher ADI in patients with cervical cancer (62.3) than other cancer types. In contrast, AYA patients diagnosed with breast cancer (53.0) and CNS tumors (52.9) resided in neighborhoods with the lowest ADI values. ADI was a significant predictor of OS overall. In multivariable models that included gender, age at diagnosis, cancer diagnosis, and race/ethnicity, risk of death for AYA cancer patients residing in neighborhoods with ADI in the highest quartile was greater than that for patients in the lowest quartile (HR: 1.09, 95% CI: 1.00-1.19, p=0.043). Conclusions: Our results in this large multi-ethnic cohort indicate that non-White AYA patients with cancer more commonly live in neighborhoods associated with higher ADI compared to their White counterparts. Even when treated in the same academic setting, AYA cancer patients with higher ADI experienced worse OS across cancers. Although the magnitude of the effect was moderate, the presence of this effect within a tertiary cancer center with existing barriers to care suggests that ADI is a meaningful risk factor impacting survival. Further analysis is warranted to determine the generalizability of these findings to the patient population more broadly. However, the results provide intriguing evidence for potential interventions aimed at supporting AYA cancer patients from disadvantaged backgrounds.

The negative influence of baseline cell-free DNA on long-term survival in DLBCL depends on frontline treatment intensity.

In this study, we address the question of the effect of first-line treatment intensity in de novo DLBCL on the impact of baseline cfDNA on long-term survival. The GOELAMS 075 randomized clinical trial compared R-CHOP with high-dose R-chemotherapy plus autologous stem cell transplantation (R-HDT) for patients aged ≤60. An interim PET assessment was used to refer patients for salvage therapy. With a median follow-up of more than 5.8 years, we analyzed the effects of the treatment arm, salvage therapy, and cfDNA level at diagnosis on overall survival (OS). In a representative group of 123 patients, a high cfDNA concentration (>55ng/ml) at diagnosis was associated with poor clinical prognostic factors and constituted a prognostic marker, independently of the age-adjusted International Prognostic Index. A cfDNA level above a threshold value of 55 ng/ml at diagnosis was associated with significantly worse OS. In an intention-to-treat analysis, high-cfDNA R-CHOP patients (but not high-cfDNA R-HDT patients) had worse OS (hazard ratio [95% confidence interval]: 3.99 [1.98-10.74], P=0.006). In patients with high cfDNA levels, salvage therapy and transplantation were associated with a significantly higher OS rate. Among 50 patients with complete response 6 months after the end of treatment, for 11 out of 24 R-CHOP patients, the cfDNA did not fall back to normal values. In this randomized clinical trial, intensive regimens mitigated the negative influence of high cfDNA levels in de novo DLBCL, relative to R-CHOP.

PD24-03 BEST TREATMENT FOR OLIGOMETASTATIC RENAL CANCER: A QUASI-INDIVIDUAL PATIENT DATA ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023PD24-03 BEST TREATMENT FOR OLIGOMETASTATIC RENAL CANCER: A QUASI-INDIVIDUAL PATIENT DATA ANALYSIS Giuseppe Fallara, Giuseppe Rosiello, Alberto Martini, Giacomo Musso, Francesco Cei, Chiara Re, Federico Belladelli, Andrea Necchi, Daniele Raggi, Laura Marandino, Roberto Bertini, Pierre I. Karakiewicz, Alexandre Mottrie, Alberto Briganti, Andrea Salonia, Francesco Montorsi, Alessandro Larcher, and Umberto Capitanio Giuseppe FallaraGiuseppe Fallara More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Alberto MartiniAlberto Martini More articles by this author , Giacomo MussoGiacomo Musso More articles by this author , Francesco CeiFrancesco Cei More articles by this author , Chiara ReChiara Re More articles by this author , Federico BelladelliFederico Belladelli More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Daniele RaggiDaniele Raggi More articles by this author , Laura MarandinoLaura Marandino More articles by this author , Roberto BertiniRoberto Bertini More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Alexandre MottrieAlexandre Mottrie More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , and Umberto CapitanioUmberto Capitanio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003302.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Oligometastatic renal cell carcinoma is a frequent diagnosis for which very few randomized control studies (RCTs) have been conducted and still represent a challenge for clinicians. Over the past few years, the results of two Phase I/II trials on this issue, the RESORT (Sorafenib+SBRT) and the RAPPORT (Pembrolizumab+SBRT) have been published. In addition, at ASCO23 the Kaplan Meier curves regarding the M1-NED group of the KEYNOTE-564 (surgery on metastases+Pembro) has been presented. In this hypothesis generating work, we aimed to assess which of these approaches has the best outcomes. METHODS: A comprehensive search for all published trials which included survival data on treatment for oligometastatic RCC was conducted in PubMed, EMBASE, Web of Science, and Scopus databases up to 10/2022. We reconstructed the survival data from published Kaplan-Meier curves on overall survival (OS) meta-analyzed Pembrolizumab+SBRT versus Sorafenib+SBRT versus surgery Pembro. The outcomes of interest were assessed using differences in restricted mean survival time (ΔRMST) at different time points and Cox regression. RESULTS: Three studies were included in the final analysis (RESORT, RAPPORT and KEYNOTE-564). Overall, 91 patients were included in the meta-analysis. In all the trials, patients had histologically confirmed clear cell RCC (nephrectomy in all the patients out of 3/30 in the RAPPORT) with ECOG≤2 and a number of one to five sites of metastatic disease at the time of enrollment. The small number of patients and the incomplete reporting of data did not allow statistical meaningful comparison among the studies. Pembrolizumab+NED obtained the higher OS benefit (Figure 1) (HR: 0.37 compared to Sorafenib+SBRT and 0.33 compared to Pembro+SBRT, all p<0.05), with ΔRMST at 24 months of 1.4 months (1.0-1.8) compared with Sorafenib+SBRT and of 1.2 months (0.9-1.3) compared to Pembro+SBRT. CONCLUSIONS: Despite lack of baseline differences, lack of power and presence of confounding, this hypothesis generating meta-analysis support the use of the combination of surgery+Pembro for oligometastatic ccRCC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e722 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giuseppe Fallara More articles by this author Giuseppe Rosiello More articles by this author Alberto Martini More articles by this author Giacomo Musso More articles by this author Francesco Cei More articles by this author Chiara Re More articles by this author Federico Belladelli More articles by this author Andrea Necchi More articles by this author Daniele Raggi More articles by this author Laura Marandino More articles by this author Roberto Bertini More articles by this author Pierre I. Karakiewicz More articles by this author Alexandre Mottrie More articles by this author Alberto Briganti More articles by this author Andrea Salonia More articles by this author Francesco Montorsi More articles by this author Alessandro Larcher More articles by this author Umberto Capitanio More articles by this author Expand All Advertisement PDF downloadLoading ...

The Association Between Cytoreductive Nephrectomy and Overall Survival in Metastatic Renal Cell Carcinoma with Primary Tumor Size ≤4 cm

BackgroundIt is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size ≤4 cm. ObjectiveTo test the association between CN on overall survival (OS) of mRCC patients with primary tumor size ≤4 cm. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2006–2018), all mRCC patients with primary tumor size ≤4 cm were identified. Outcome measurements and statistical analysisPropensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus naïve, clear-cell (ccmRCC) versus non–clear-cell (non-ccmRCC) mRCC histology, historical (2006–2012) versus contemporary (2013–2018), and young (≤65 yr) versus old (>65 yr) patients. Results and limitationsOf 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Δ = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy naïve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001). ConclusionsThe current study validates the association between CN and higher OS in patients with primary tumor size ≤4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age. Patient summaryIn the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics.

Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib

ObjectivesTo evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. Patients and MethodsA total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). ResultsThe ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88–4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16–1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02–0.55; p=0.035) were associated with poorer ORR. ConclusionOur findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

Survival benefit of primary tumor resection for gastric cancer with liver metastasis: A propensity score-matched, population-based study.

Gastric cancer with liver metastasis (GCLM) is highly aggressive and has a poor prognosis. This study aims to evaluate the survival benefit of primary tumor resection (PTR) for gastric cancer with liver metastasis. Data on patients with GCLM was extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015.A 1:1 propensity score matching (PSM) analysis was performed to minimize the heterogeneity between the PTR and no-PTR groups. The Kaplan-Meier method and Cox regression analysis were used to assess the impact of primary tumor resection (PTR) on overall survival (OS) and cause-specific survival (CSS). A total of 3,001 patients with GCLM were included, with 328 patients treated with primary tumor resection (PTR), whereas the other 2,673 patients were not. Patients with PTR had a significantly higher OS and CSS rate than those without PTR in unmatched and PSM cohorts. In an unmatched cohort, the median OS was 12.0 months (95% CI, 10 months to 14 months) for those who underwent PTR and 4 months (95% CI, 4 months to 5 months) for those without PTR; the median CSS for those who underwent PTR was 12.0 months (95% CI, 10 months to14 months) and 4 months (95% CI, 4 months to 5 months) for those without PTR, respectively. After PMS, the median OS was 12.0 months (95% CI, 10 months to 17 months) for those who underwent PTR and 7 months (95% CI, 5 months to 10 months) for those without PTR, respectively; the median CSS for those who underwent PTR was 12.0 months (95% CI, 11 months to 17 months) and 7 months (95% CI, 5 months to 8 months) for those without PTR, respectively. In addition, multivariate Cox analysis in the PSM cohort showed that PTR, age, degree of tumor differentiation, and chemotherapy were independent prognostic factors for OS and CSS in GCLM. Specifically, PTR was a significant protective factor for OS (HR: 0.427; 95% CI, 0.325 to 0.561, P <0.001) and CSS (HR: 0.419; 95% CI, 0.313 to 0.561, P <0.001). Primary tumor resection improves the survival of gastric cancer patients with liver metastasis.

Guideline concordant therapy improves survival in high-grade endometrial cancer patients

PurposeData from randomized controlled trials in high-grade endometrial cancer are scarce due to its low prevalence. Therefore, guideline recommendations in this cancer subtype rely on relatively few randomized trials and data from retrospective studies. The aim of this study was to evaluate the benefits from guideline-concordant therapy in high-grade endometrial cancer in a real-world patient group.MethodsThe effect of treatment according to German S3 guidelines and the former S2k guideline on overall survival (OS) and recurrence-free survival (RFS) was evaluated in a cohort of 293 high-grade endometrial cancer patients.ResultsTreatment concordant with the S3 guideline significantly improved OS (HR 0.623, CI 0.420–0.923, p = 0.018) and RFS (HR 0.578, CI 0.387–0.863, p = 0.007). Treatment concordant with the S2k guideline did not result in a significantly higher OS (HR 0.783, CI 0.465–1.316, p = 0.335) or RFS (HR 0.741, CI 0.347–1.740, p = 0.242).ConclusionTherapy according to the German S3 guideline improved OS and RFS in univariate as well as multivariate analysis in this cohort of high-grade endometrial cancer patients.

Socioeconomic deprivation and survival outcomes in primary central nervous system lymphomas

ObjectiveTo our knowledge, the impact of area-level socioeconomic status (SES) has not yet been described in primary central nervous system lymphomas (PCNSLs). Current study sought to explore the association of socioeconomic deprivation, measured using the Area Deprivation Index (ADI), with PCNSL outcomes.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCNSL patients diagnosed between 2006 and 2015 for our analyses. The impact of ADI on overall survival (OS) and cancer-specific survival (CSS) were investigated. Survival analyses were conducted using Kaplan-Meier method with log-rank tests. The Inverse Probability Weighting (IPW) analysis and multivariate cox proportional hazards regression analysis were employed to make covariate adjustments. Multiple mediation analysis (MMA) was performed to estimate the mediating effects.ResultsA total of 3159 PCNSL patients classified into low and high ADI subgroups according to the median ADI score were studied. The Kaplan-Meier analyses showed that low ADI was significantly associated with higher OS rates (HR 1.15, 95%CI 1.06-1.26, P<0.01) and CSS rates (HR 1.15, 95%CI 1.05-1.27, P<0.01). Similar results were observed in analyses adjusted via IPW and multivariate cox methods. Subgroup analyses revealed that ADI could remain a prognostic indictor among different subsets. MMA revealed that several factors including chemotherapy and HIV status making up about 40% of the overall effect, mediated PCNSL survival disparities related to the ADI. Finally, multivariable logistic regression analysis showed that ADI as well as several other factors were independently related to receipt of chemotherapy.ConclusionsOur study highlights the role of area-level SES in prognosis of PCNSLs. And several factors including chemotherapy and HIV status of PCNSL patents contributed to the CSS disparities between ADI subgroups were uncovered by MMA. Such relationships would highlight the importance of policies development to enhance healthcare delivery and promote awareness of HIV prevention and treatment in low-resource neighborhoods.