5-year Survival Benefit Research Articles

Obesity paradox: is a high body mass index positively influencing survival outcomes in gynecological cancers? A systematic review and meta-analysis

ObjectiveObesity represents an exponentially growing preventable disease leading to different health complications, particularly when associated with cancer. In recent years, however, an ‘obesity paradox’ has been hypothesized where obese individuals...

Five-year follow-up of neoadjuvant PD-1 inhibitor (sintilimab) in non-small cell lung cancer

BackgroundNeoadjuvant anti-programmed cell death protein-1 (PD-1) therapy exhibits potential in treating resectable non-small cell lung cancer (NSCLC). Previously, we have reported the 3-year clinical outcomes of this trial, implying the...

Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non–Small Cell Lung Cancer

Outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy. To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC. This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023. Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy. The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points. A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events. These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes. ClinicalTrials.gov Identifier: NCT03102242.

Comparison of D2 vs D3 lymph node dissection for RIght COloN cancer (RICON): study protocol for an international multicenter open-label randomized controlled trial

BackgroundColon cancer is a global health concern, ranking fifth in both new diagnoses and deaths among tumors worldwide. Surgical intervention remains the primary treatment for localized cases, with a historical evolution marked by a focus on short-term outcomes. While Japan pioneered radical tumor removal with a systematic categorization of lymph nodes (D1, D2, D3), the dissemination of Japanese practices to the West was delayed until 90th of last century. Discrepancies between Japanese D3 dissection and the CME with CVL principle persist, with variations in longitudinal margins and recommended procedures. Non-randomized trials indicate the superiority of D3 over D2, but a consensus is lacking.MethodsThis prospective, international, multicenter, randomized controlled trial employs a two-arm, parallel-group, open-label design to rigorously compare the 5-year overall survival outcomes between D2 and D3 lymph node dissection in stage II-III right colon cancer. Building on prior studies, the trial aims to address existing knowledge gaps and provide a comprehensive evaluation of the outcomes associated with D3 dissection. The study population comprises patients with right colon cancer, ensuring a focused investigation into the specific context of this disease. The trial design emphasizes its global scope and collaboration across multiple centers, enhancing the generalizability of the findings.DiscussionThis study’s primary objective is to elucidate the potential superiority in 5-year overall survival benefits of D3 lymph node dissection compared to the conventional D2 approach in patients with stage II-III right colon cancer. By examining this specific subset of patients, the research aims to contribute valuable insights into optimizing surgical strategies for improved long-term outcomes. The trial’s international and multicenter nature enhances its applicability across diverse populations. The outcomes of this study may inform future guidelines and contribute to the ongoing discourse surrounding the standardization of colon cancer surgery, particularly in the context of right colon cancer.Trial registrationClinicalTrials.gov NCT03200834. Registered on June 27, 2017.

Waiting list mortality and 5-year transplant survival benefit of patients with MASLD: An Italian liver transplant registry study

BackgroundInternational consensus has recently introduced a new definition of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of MASLD and non-MASLD patients waiting for liver transplantation (LT) in Italy. Materials and methodsUtilising the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT due to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was employed to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and MELD-sodium values. ResultsA total sample of 1,941 MASLD and 11,201 non-MASLD was considered. A significant increase in the prevalence of MASLD as an indication for liver transplantation was observed from 2012 to 2022, both for HCC (from 17.7 to 30%) and non-HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, while it was lower in non-HCC patients without MASLD. ConclusionsNon-HCC MASLD patients had an increased waitlist mortality and 5-year transplant survival benefit compared to other candidates.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study

ABSTRACT The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Genome-matched treatments and patient outcomes in the Maine Cancer Genomics Initiative (MCGI)

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52–0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials.

Prediction of 5-year overall survival of diffuse large B-cell lymphoma on the pola-R-CHP regimen based on 2-year event-free survival and progression-free survival.

This study aimed to predict the 5-year overall survival (OS) benefit of pola-R-CHP versus R-CHOP in the POLARIX trial based on the 2-year event-free survival (EFS) and progression-free survival (PFS) rates in diffuse large B-cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS) or PFS (HRPFS) and the HR for OS (HROS) was estimated at the trial-level. Correlation analysis was performed between 2-year PFS or EFS and 5-year OS rates at the treatment arm-level. Linear regression models were used to calculate the 5-year OS of pola-R-CHP and R-CHOP. In the included 20 RCTs, a linear correlation between HREFS (r = 0.765) or HRPFS (r = 0.534) and HROS was observed at the trial- level. Two-year EFS (r = 0.918) or 2-year PFS (r = 0.865) correlated linearly with 5-year OS. Linear regression analysis between 2-year EFS/PFS and 5-year OS gave estimated 5-year OS rates between pola-R-CHP and R-CHOP of 6.4% and 6.3%, respectively. Two-year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The pola-R-CHP regimen is expected to improve 5-year OS.

Prognostic impact of percutaneous coronary intervention in chronic dialysis patients with acute myocardial infarction

Abstract Background Patients on chronic dialysis are less likely to receive percutaneous coronary intervention (PCI) for treatment of acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Thus, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue. Purpose We analyzed data of patients on chronic dialysis hospitalized with AMI (both ST-elevation myocardial infarction [STEMI] and non-ST-elevation myocardial infarction [NSTEMI]) from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they were treated or not with PCI during hospitalization. The primary outcome was in-hospital mortality while 1-year mortality was the secondary endpoint. Results During the study period, 265,048 patients were hospitalized with AMI in Lombardy. Of them, 3,206 (1.2%) were on chronic dialysis (age 71±11; 72% males). Among dialysis patients, 44% were treated with PCI, while 54% underwent PCI among non-dialysis patients (P&amp;lt;0.0001). Dialysis was an independent predictor of conservative treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%. It was significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; P&amp;lt;0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; P&amp;lt;0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients treated with PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Similar results were found in STEMI and NSTEMI patients considered separately. Conclusions Our real-world data showed that in patients with AMI on chronic dialysis, PCI use is associated with a significant in-hospital and 1-year survival benefit.

Analysis of survival outcomes following robotic hepatectomy for malignant liver diseases

BackgroundDespite increased adoption of the robotic platform for complex hepatobiliary resections for malignant disease, little is known about long-term survival outcomes. This is the first study to evaluate the postoperative outcomes, and short- and long-term survival rates after a robotic hepatectomy for five major malignant disease processes. MethodsA prospectively collected database of patients who underwent a robotic hepatectomy for malignant disease was reviewed. Pathologies included colorectal liver metastases (CLM), hepatocellular carcinoma (HCC), Klatskin tumor, intrahepatic cholangiocarcinoma (IHCC), and gallbladder cancer (GC). Data are presented as median (mean ​± ​standard deviation) for illustrative purposes. ResultsOf the 210 consecutive patients who underwent robotic hepatectomy for malignant disease, 75 (35 ​%) had CLM, 69 (33 ​%) had HCC, 27 (13 ​%) had Klatskin tumor, 20 (10 ​%) had IHCC, and 19 (9 ​%) had GC. Patients were 66 (65 ​± ​12.4) years old with a BMI of 29 (29 ​± ​6.5) kg/m2. R0 resection was achieved in 91 ​%, and 65 ​% underwent a major hepatectomy. Postoperative major complication rate was 6 ​%, length of stay was four (5 ​± ​4.3) days, and 30-day readmission rate was 17 ​%. Survival at 1, 3, and 5-years were 93 ​%/75 ​%/72 ​% for CLM, 84 ​%/71 ​%/64 ​% for HCC, 73 ​%/55 ​%/55 ​% for Klatskin tumor, 80 ​%/69 ​%/69 ​% for IHCC, 79 ​%/65 ​%/65 ​% for GC. ConclusionThis study suggests a favorable 5-year overall survival benefit with use of the robotic platform in hepatic resection for colorectal metastases, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, Klatskin tumor, and gallbladder cancer. The robotic platform facilitates fine dissection in complex hepatobiliary operations, with a high rate of R0 resections and excellent perioperative clinical outcomes.

Survival benefit from liver transplantation for patients with and without hepatocellular carcinoma

In the USA, inequal liver transplantation (LT) access exists between patients with and without hepatocellular carcinoma (HCC). Survival benefit considers survival without and with LT and could equalise LT access. We calculated bias-corrected LT survival benefit for patients with(out) HCC who underwent a transplant, based on longitudinal data in a recent United States cohort. Adult LT candidates with(out) HCC between 2010 and 2019 were included. Waitlist survival over time was contrasted to post-transplant survival, to estimate 5-year survival benefit from the moment of LT. Waitlist survival was modelled with a bias-corrected Cox regression, and post-transplant survival was estimated through Cox proportional hazards regression. Mean HCC survival without LT was always lower than non-HCC waitlist survival. Below model for end-stage liver disease (sodium) (MELD(-Na)) 30, patients with HCC gained more life-years from LT than patients without HCC at the same MELD(-Na) score. Only patients without HCC below MELD(-Na) 9 had negative benefit. Most patients with HCC underwent a transplant below MELD(-Na) 14, and most patients without HCC underwent a transplant above MELD(-Na) 26. Liver function [MELD(-Na), albumin] was the main predictor of 5-year benefit. Therefore, during 5 years, most patients with HCC gained 0.12 to 1.96 years from LT, whereas most patients without HCC gained 2.48 to 3.45 years. On an individual level, performing a transplant in patients with HCC resulted in survival benefit. However, on a population level, benefit was indirectly decreased, as patients without HCC were likely to gain more survival owing to decreased liver function. For patients who underwent a transplant, a constructed online calculator estimates 5-year survival benefit given specific patient characteristics. Survival benefit scores could serve to equalise LT access. Benefit is a comparison of the survival with and without liver transplantation, and it is important when deciding who should undergo a transplant. Liver function is most important when predicting possible benefit from transplantation. Patients with liver cancer die sooner on the waiting list than similar patients without liver cancer. However, patients with liver cancer more often have better liver function. Most patients without liver cancer derive more benefit from transplantation than patients with liver cancer.

Liver transplantation for refractory hepatic hydrothorax is associated with a greater survival benefit compared to other complications of cirrhosis.

Hepatic hydrothorax (HH) is a significant complication of cirrhosis associated with increased mortality. Liver transplantation (LT) remains the best treatment modality. We aim to assess predictors of mortality and the survival benefit of LT in patients with HH. A prospectively maintained cohort of adult patients with cirrhosis, being evaluated for LT at our institution, was retrospectively reviewed from 2015 to 2020. The primary outcome was death or LT. Cox proportional hazard regression identified associations between covariates and death. We calculated the years saved due to LT by comparing patients who were on the waiting list with patients who received an LT. This was done by calculating the area under the Kaplan-Meier curve. Censoring occurred at the time of the last follow-up or death. Patients with refractory HH had the lowest median survival of only 0.26 years. Within the HH group, having a refractory HH group was significantly associated with an increased risk of mortality (HR 1.73; 95% CI 1.06-2.81; p -value 0.03). Refractory HH was also significantly associated with mortality when evaluated in the entire cohort and after adjusting for other covariates (HR 1.48, 95% CI 1.03-2.11; p -value 0.03). Patients with refractory HH had the highest 1-year survival benefit with LT (0.48y), followed by patients with non-refractory HH (0.28y), then patients with other complications of cirrhosis (0.19y). In this large study evaluating the prognostic impact of HH on patients with cirrhosis, refractory HH was an independent predictor of mortality. LT provides an additional survival benefit to patients with HH compared with those without HH.

#5733 NIERKEUZE.NL: A WEB-BASED APPLICATION TO SUPPORT THE SHARED DECISION PROCESS FOR KIDNEY REPLACEMENT THERAPY BASED ON OUTCOME DATA IN THE NETHERLANDS

Abstract Background and Aims Access to individualized, evidence-based prognostics is needed to facilitate shared decision making about the clinical implications of whether to opt for kidney transplantation or long-term dialysis. We aim to implement a data-driven support tool (Nierkeuze.nl) that incorporates basic patient characteristics and treatment options. Method Consecutive patients (N = 14.275) above 18 years of age with end-stage-renal-disease (ESRD) who were eligible candidates for their first kidney transplantation and started renal replacement therapy between 2000 and 2019 were included from the national registries RENINE and NOTR. SF-12 quality of life data was obtained from RENINE and a local transplant database. Several algorithms were developed to predict waiting time, short- and long-term patient survival, graft survival, and quality of life according to factors that are known at ESRD. Probabilities of 3- and 5-year mortality were calculated using two-stage distinct Cox regression: 1) waitlist-mortality according to median time on the waiting list, 2) mortality after transplantation in remaining follow-up. Product and complement rules defined the final probabilities. No mortality on the waiting list was assumed for living donor transplants. Missing data were imputed. Model performance was evaluated by internally validated C-statistics and calibration plots. Results We included 4.889 deceased donor transplants, of which 990 were within the Eurotransplant Senior allocation Program (ESP), and 6.251 living donor transplants. Discrimination varied for patient survival models (C-stats: 0.68 deceased-ETKAS-TX; 0.58 for deceased-ESP-TX; 0.74 for living-TX; 0.64 for waitlisted-candidates). Survival models achieved good calibration by visual inspection across the range of predicted probabilities. Figure 1 illustrates a clear 5-year survival benefit of transplantation (living and deceased donor groups) compared with wait-listed candidates for a 65-year-old male with glomerulonephritis. Other developed algorithms of the support tool will be presented with an overview of the first experiences in the kidney failure clinic. Conclusion Nierkeuze.nl depicts the influence of anticipated waiting time, patient characteristics, kidney allocation program, and donor type on survival outcome of the different treatment options. Incorporating this individualized quantitative outcome information may provide valuable support for an informed choice by patients and potential living donors.

Underutilization or appropriate care? Assessing adjuvant chemotherapy use and survival in 3 heterogenous subpopulations with stage II/III colorectal cancer within a large integrated health system.

BACKGROUND: Clinical guidelines have recommended adjuvant chemotherapy (ACT) for patients with high-risk stage II colon cancer, although the survival benefit is unclear. ACT is also recommended for patients with stage III colon cancer to reduce the risk of recurrence and mortality. For stage II/III rectal cancer, however, the role of perioperative chemotherapy (PCT, adjuvant or neoadjuvant) remains controversial, resulting in substantial variation in its use in clinical practice. OBJECTIVES: To understand real-world use and predictors of ACT or PCT use and survival outcomes in 3 heterogeneous patient groups with colorectal cancer (CRC), and to inform the evidence gap between guideline-based care and clinical practice. METHODS: This retrospective cohort study included patients with an initial stage II/III CRC diagnosis between 2008 and 2013 identified from Kaiser Permanente Southern California electronic health record databases. Patients were eligible if they were aged 18-74 years at diagnosis and received primary curative surgery. We fitted mixed effects logistic regression models to evaluate predictors of ACT receipt and Cox proportional hazards models on propensity score-matched (PS-matched) samples to assess the association between ACT/PCT receipt and survival. RESULTS: We included 1,690 patients with colon cancer (stage II: 820 and stage III: 870) and 587 patients with rectal cancer (stage II: 241 and stage III: 346). We found that 65% of patients with high-risk stage II colon cancer, 15% of those with stage III colon, and 15% of those with stage II/III rectal cancer did not receive ACT/PCT. Patients with stage II colon cancer with T4 stage (odds ratio [OR] = 5.79, 95% CI = 3.33 - 10.06) and a lower comorbidity score were more likely to receive ACT (high vs low Charlson score: OR = 0.69, 95% CI = 0.55 - 0.87). Patients with stage III rectal cancer were more likely to receive PCT than those with stage II disease (OR = 7.85, 95% CI = 2.07 - 29.74). Patients with another cancer diagnosis prior to CRC diagnosis were less likely to receive PCT (OR = 0.37, 95% CI = 0.16 - 0.85). ACT/PCT use was associated with improved overall survival among patients with high-risk stage II colon cancer (PS-matched hazard ratio [HR] = 0.42, 95% CI = 0.25 - 0.70) and those with stage III CRC (stage III colon: PS-matched HR = 0.3, 95% CI = 0.25 - 0.36; stage III rectal: PS-matched HR = 0.2, 95% CI = 0.13 - 0.31). CONCLUSIONS: We found potential underuse of appropriate chemotherapy treatment in patients with high-risk stage II colon cancer and stage III CRC. Clinicians' and providers' decisions on ACT administration may not be fully guided by the risk of recurrence and 5-year survival benefits in stage II colon cancer. DISCLOSURES: This research was supported by the National Cancer Institute of the National Institutes of Health (NIH) (under R37-CA218413). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Validation of recurrence prediction using circulating tumor DNA in patients with curatively treated early stage non-small cell lung cancer.

8535 Background: Stage II-III non-small cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard-of-care treatment, despite an absolute 5-year disease free survival benefit of only 5.8%. Stage I patients do not receive adjuvant treatment but may benefit. Identification of residual disease by circulating tumor DNA (ctDNA) after curative intent therapy may allow more accurate decisions. Methods: Tumor tissue and serial plasma samples were collected from stage I-III NSCLC patients enrolled in the LEMA trial (NCT02894853). Somatic mutations identified by tumor exome sequencing were used to design patient-specific RaDaR assays, targeting up to 48 variants per patient, to analyze ctDNA in serial plasma samples. Results were compared and combined with an independent dataset (LUCID; Gale et al, Annals Oncol 2022). Results: In LEMA, 129 patients (53% stage I, 18% stage II and 29% stage III) were treated with curative intent by surgery (n=117), chemoradiation (n=8) or stereotactic radiotherapy (n=4) and followed for a median of 3.4 years. The LUCID dataset included 88 patients (49%/28%/23% in stage I/II/III). Results in the two cohorts were highly concordant (Table) and were assessed in the combined dataset of 808 serial plasma samples. Before treatment, ctDNA was detected in 22%, 72% and 90% of patients with stage I, II and III disease. ctDNA was detected post-treatment (at least one positive samples ≥14 days after the end of therapy) in 41/65 (63%) of patients who developed radiographic recurrence of their primary cancer, and preceded recurrence by a median of 204 days. For recurrence prediction by ctDNA detection post-treatment, the sensitivity, specificity, positive and negative predictive value (PPV and NPV) in stage I patients were 53%, 99%, 91% and 90%. In stage II-III patients, sensitivity was higher but specificity and NPV were lower (67%, 93%, 91% and 74%, respectively). ctDNA detection after treatment was associated with shorter recurrence-free survival (hazard ratio (HR) 11.5, P=1.8x10-32) and overall survival (HR 8.1, P=1.2x10-17). Conclusions: ctDNA detection by RaDaR assays predicted recurrence in two independent cohorts, confirming the potential to identify patients for adjuvant treatment. In stage I patients with positive ctDNA, adjuvant treatment could be offered with confidence due to high specificity of 99% and PPV of 91%. In stage II-III patients, the primary cancer recurred in a quarter of patients with no ctDNA detected post-treatment (NPV 74%). Our results help identify the potential role for ctDNA analysis as a decision support tool for adjuvant therapy in NSCLC. [Table: see text]

Patient-reported symptom monitoring linked to an alert algorithm: Effects on progression-free and overall survival in the SYMPRO-Lung trial.

12099 Background: Physician-initiated (active) monitoring of patient-reported outcomes (PROs) improves health-related quality of life (HRQOL) and overall survival (OS) in comparison to care as usual. We recently reported data from the SYMPRO-Lung trial showing for the first time that patient-initiated (reactive) PRO monitoring is equally effective as physician-initiated (active) monitoring in improving HRQOL. Here we investigate whether online PRO symptom monitoring via the active and reactive approach is also associated with improvements in 1-year progression-free survival (PFS) and OS compared to care as usual in lung cancer patients. Methods: SYMPRO-Lung is a Dutch multicenter randomized trial using a stepped wedge design. Inclusion criteria were (non-)small cell lung cancer stage I-IV, starting treatment. Patients in the intervention groups reported PRO symptoms weekly up to 1 year follow-up using the PRO-CTCAE lung cancer subset. If symptoms exceeded a pre-determined threshold, an alert was sent to a physician/nurse (active intervention group) or to the patient themselves (reactive intervention group). Survival was defined as time from start of treatment until progression (PFS), death (OS) or loss to follow-up. Follow-up time of all groups was calculated using the reverse Kaplan-Meier method. Cox proportional hazard analyses were performed to estimate the effect of PRO symptom monitoring on PFS and OS, adjusting for potential confounding (i.e. clinical characteristics and baseline EORTC QLQ-C30 domain scores). Results: 515 patients were included in the study (266 control, 249 intervention). The most pronounced uneven distribution in baseline characteristics was that the active intervention group had significantly more stage IV patients compared to the control group and the reactive intervention group (63% vs. 44% vs. 44%, p = 0.001). The median follow-up duration was 12 months for all groups. Age, sex, cancer staging, ECOG performance status and some baseline EORTC domain scores affected the association and were included as covariates in the analyses. Although not significant, we observed a tendency towards a PFS benefit for the active intervention group compared to care as usual (HR .78, 95%CI: .58 – 1.04) and an OS benefit for both of the intervention groups compared to care as usual (active: HR .80, 95% CI: .55 – 1.15; reactive: HR .69, 95% CI: .42 – 1.15). Conclusions: Although not significant, weekly PRO symptom monitoring linked to an alert algorithm showed a tendency towards a small 1-year survival benefit in lung cancer patients. Since we did not power the trial to demonstrate a survival benefit, the non-significant association might be due to a limited sample size. However, the positive results of symptom monitoring in improving HRQOL within our trial still provide sufficient evidence for implementation of PROMs in standard (lung) cancer care. Clinical trial information: NL7897 .

Reevaluating the role of adjuvant chemotherapy in early-stage, resectable NSCLC with high-risk clinical and pathologic features.

8572 Background: The preferred treatment for early-stage non-small cell lung cancer remains surgical resection with the consideration of adjuvant chemotherapy for tumors with certain high-risk features. It is commonly cited that such treatments confer a meager 5% 5-year survival benefit compared to observation alone. We sought to reassess the benefit of adjuvant chemotherapy using modern, real-world datasets. Methods: We performed a retrospective cohort study using a dataset from the National Cancer Database. All patients with early-stage stage NSCLC (3-5cm, node-negative) who would be eligible for adjuvant chemotherapy based on National Comprehensive Cancer Network guidelines were included (i.e., presence of at least 1 high-risk feature). High-risk clinical and pathologic features were defined as poor differentiation, tumor size (≥4cm), non-anatomic wedge resection, inadequate lymph node evaluation, vascular invasion, and visceral pleural involvement. We employed average treatment effect on the treated (ATT) weighting to match patients with similar demographic, tumor, and treatment-related variables to compare outcomes between chemotherapy versus observation groups. The primary outcome was overall survival. These findings were further validated in an independent cohort from the US Veteran Health Administration (VHA). Results: The study included 10,812 patients with early-stage NSCLC who had at least 1 high-risk feature. The frequencies of high-risk features were as follows: tumor size ≥4cm (n = 3,271, 30.3%), poor differentiation (n = 9,454, 87.4%), visceral-pleural invasion (n = 2,542, 23.5%), vascular invasion (n = 1,742, 16.11%), non-anatomic wedge resection (n = 781, 7.2%), and inadequate nodal sampling (n = 6,306, 58.3%). Despite the presence of high-risk features, only 1,427 (13.2%) patients received adjuvant chemotherapy. In the ATT weighted analysis, 1,261 (49.7%) patients received adjuvant chemotherapy and 1,278 (50.3%) patients received observation. The 5-year overall survival was 70.0% (95% CI 67.1-72.7) in the chemotherapy group versus 62.0% (95% CI 60.2-63.7%) in the observation group (absolute 5-year survival difference 8.0%). In the VHA cohort, 11.3% of patients received adjuvant chemotherapy. Similarly, the 5-year overall survival was 64.0% (95% CI 51.4-74.2) in the chemotherapy group versus 56.2% (95% CI 48.3-63.4) in the observation group (absolute 5-year survival difference 7.8%). Conclusions: These data suggest a notably larger benefit of adjuvant chemotherapy in eligible patients with high-risk clinical pathologic features compared to commonly cited statistics. With the addition of more robust treatment options in early-stage disease, adherence to adjuvant and neoadjuvant treatment guidelines may disproportionately improve early-stage NSCLC outcomes following curative-intent resection.

Prognostic Impact of Percutaneous Coronary Intervention in Chronic Dialysis Patients with Acute Myocardial Infarction: Findings from the Lombardy Health Database.

Patients on chronic dialysis are less likely to be treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Therefore, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue. We analyzed data of patients on chronic dialysis hospitalized with AMI from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they underwent or not PCI during index hospitalization. The primary outcome was in-hospital mortality, 1-year mortality was the secondary endpoint. During the study period, 265,048 patients were hospitalized with AMI. Of them, 3206 (1.2%) were on chronic dialysis (age 71 11; 72% males). Among dialysis patients, 44% underwent PCI, while 54% underwent PCI among non-dialysis patients (p 0.0001). Dialysis was an independent predictor of treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%, significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; p 0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; p 0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients undergoing PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. This study showed that in AMI patients on chronic dialysis, PCI is associated with a significant in-hospital and 1-year survival benefit. Yet, they underwent PCI less frequently than patients with preserved renal function.

Association of survival with adjuvant radiotherapy for pN0 esophageal cancer

Introduction: This study was conducted to elucidate the link between adjuvant radiotherapy and survival in pathologic node-negative (pN0) esophageal cancer patients with upfront esophagectomy. Methods: From 2000 to 2016, patients with pN0 esophageal cancer who underwent upfront esophagectomy were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The association of high-risk covariates with survival after adjuvant radiotherapy was evaluated using propensity score matching and multivariate analysis. Results: We identified 3197 patients, 321 (10.0%) underwent postoperative radiotherapy and 2876 (90.0%) underwent esophagectomy alone. In the unmatched cohort, postoperative radiotherapy was associated with a statistically significant but modest absolute decrease in survival outcomes (P < 0.001). In the matched cohort, the survival differences disappeared. Additionally, adjuvant radiotherapy was linked to a 5-year overall survival (OS) benefit for patients with the pT3-4N0 disease (34.8% vs. 27.7%; P = 0.008). Adjuvant radiotherapy for pT3-4N0 disease with tumor length ≥3 cm, adenocarcinoma, and evaluated lymph node count <12 was shown to independently function as a risk factor for improved OS, as per a multivariate analysis (P < 0.01). Conclusions: This population-based trial showed that high-risk patients with pT3-4N0 esophageal cancer had better OS following upfront esophagectomy followed by radiotherapy therapy. This discovery may have major significance in the use of adjuvant radiotherapy following upfront esophagectomy in patients with pN0 esophageal cancer.

Simultaneous heart-kidney transplant in patients with borderline estimated glomerular filtration rate without dialysis dependency.

Appropriate patient selection for simultaneous heart-kidney transplantation (sHK) in patients with moderate renal dysfunction remains challenging. From the United Network for Organ Sharing database (2003-2020), we identified 5678 adults with an estimated pre-transplant glomerular filtration rate (eGFR) between 30 and 45mL/min/1.73m2 and no pre-transplant dialysis. Patients undergoing sHK (n=293) were compared with those undergoing heart transplantation alone (n=5385) using 1:3 propensity score matching. The sHK utilization rate increased from 1.8% in 2003 to 12.2% in 2020 (p<.001). After matching, 1 and 5-year survival was 87.7% (95% confidence interval [CI] 83.3-91.0) and 80.0% (95% CI 74.2-84.6) after sHK, and 87.3% (95% CI 85.2-89.1) and 71.8% (95% CI 68.4-74.9) after heart transplant alone (p=.04). In the subgroup analysis, sHK was associated with a 5-year survival benefit only in patients with 30<eGFR≤35mL/min/1.73m2 (p=.05) but not in those with 35<eGFR<45mL/min/1.73m2 (p=.45). Patients who underwent heart transplants alone also had a higher incidence of becoming chronic dialysis-dependent after transplant within 5-year follow-up (10.2%, 95% CI 8.0-12.6 vs. 3.8%, 95% CI 1.7-7.1, p=.004). The 5-year incidence of subsequent kidney waitlisting and transplants after heart transplants alone was 5.6% and 1.9%, respectively. Among propensity-matched patients without pre-transplant dialysis, compared to heart transplants alone, sHK had improved 5-year survival in those with 30<eGFR≤35 but not in those with 35<eGFR<45mL/min/1.73m2 . One-year survival was similar irrespective of eGFR. Receiving a kidney after a heart transplant alone is rare under the current allocation system.