Independent Prognostic Factor For Overall Survival Research Articles

46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens

Abstract Background IO-based regimens (IO + IO or IO + VEGF inhibitor) represent current standard of care systemic therapies for the management of patients with mRCC. IMDC is the current standard to assess prognosis in patients with mRCC of clear cell histology. Baseline radiological tumor burden (BRTB) is a readily available measurement to calculate using routine CT-scans. Here we describe the utility of BRTB as prognostic factor in patients with mccRCC treated with first line IO-based regimens. Methods We reviewed data of 183 patients with mccRCC treated at Dana-Farber Cancer Institute from August 2014 to October 2023 and who received ≥ 1 dose of an IO-based regimen (IO + IO or IO + VEGF inhibitor). Patients with available CT-scan reports within 1 month prior to first line treatment initiation were included in our analysis. BRTB was assessed by a single operator as the sum of all measurable lesions as listed on the RECIST v1.1 report. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and time to next therapy (TTNT). To evaluate the impact of BRTB on OS, TTF and TTNT, we used univariable and multivariable Cox regression models accounting for IMDC risk group, history of nephrectomy, and presence of either bone, liver, or brain metastases prior to first line initiation. Results A total of 150 patients satisfied the inclusion criteria and were included in our final analysis, of which 80% of patients were male (120/150). 9% (13/150) had favorable risk, 51% (77/150) had intermediate risk and 20% (30/150) had poor risk by IMDC criteria. Overall, 73% (109/150) of patients had nephrectomy prior to first line therapy initiation and 41% (61/150) had either brain, bone, or liver metastasis. Median follow-up was 44.8 months. Every 1 cm increase in BRTB was associated with a 5% increase in risk of death (HR: 1.05; 95% CI: 1.03 – 1.08; p < 0.0001). On multivariable analysis, radiological tumor burden was significantly associated with OS (HR: 1.04; 95%CI: 1.00 – 1.08; p = 0.03). After categorizing BRTB by tertiles, tertile 1 included 0 - 7.5 cm, tertile 2: 7.6– 15.3 cm and tertile 3: 15.4 – 47.7 cm. The 4-year OS estimates were 84% (95%CI: 74 – 97%), 60% (95%CI: 45 – 81%) and 43% (95%CI: 29 – 66%), respectively, for the 1st, 2nd and 3rd tertile (log-rank P < 0.0001). BRTB did not show a significant association with TTF on univariable (HR: 1.00; 95%CI: 0.99 – 1.01; p = 0.783), or multivariable analysis (HR: 0.99; 95%CI: 0.97 – 1.01; p = 0.428). As for TTNT, BRTB also did not show a significant association on univariable (HR: 1.01; 95%CI: 1.0 – 1.02; p = 0.234) or multivariable analysis (HR: 1.01; 95%CI: 0.99 – 1.03; p = 0.453). Conclusions Baseline radiological tumor burden is an independent prognostic factor for OS in patients with mccRCC treated with first line immunotherapy-based regimens. However, tumor burden is not significantly associated with TTF or TTNT. Figure: Kaplan-Meier curves representing OS based on baseline radiological tumor burden assessed by RECIST v1.1 (Tertile 1: 0 - 7.5 cm; Tertile 2: 7.6 - 15.3 cm; Tertile 3: 15.4 – 47.7 cm). P value is derived from the log-rank test.

Comprehensive assessment of postoperative recurrence and survival in patients with cervical cancer

BackgroundThe prediction of postoperative recurrence and survival in cervical cancer patients has been a major clinical challenge. The combination of clinical parameters, inflammatory markers, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and MRI-derived radiomics is expected to support the prediction of recurrence-free survival (RFS), disease-free survival (DFS), tumor-specific survival (CSS), and overall survival (OS) of cervical cancer patients after surgery. MethodsA retrospective analysis of 181 cervical cancer patients with continuous follow-up was completed. The parameters of IVIM-DWI and radiomics were measured, analyzed, and screened. The LASSO regularization was used to calculate the radiomics score (Rad-score). Multivariate Cox regression analysis was used to construct nomogram models for predicting postoperative RFS, DFS, CSS, and OS in cervical cancer patients, with internal and external validation. ResultsClinical stage, parametrial infiltration, internal irradiation, D-value, and Rad-score were independent prognostic factors for RFS; Squamous cell carcinoma antigen, internal irradiation, D-value, f-value and Rad-score were independent prognostic factors for DFS; Maximum tumor diameter, lymph node metastasis, platelets, D-value and Rad-score were independent prognostic factors for CSS; Lymph node metastasis, systemic inflammation response index, D-value and Rad-score were independent prognostic factors for OS. The AUCs of each model predicting RFS, DFS, CSS, and OS at 1, 3, and 5 years were 0.985, 0.929, 0.910 and 0.833, 0.818, 0.816 and 0.832, 0.863, 0.891 and 0.804, 0.812, 0.870, respectively. ConclusionsNomograms based on clinical and imaging parameters showed high clinical value in predicting postoperative RFS, DFS, CSS, and OS of cervical cancer patients and can be used as prognostic markers.

Evaluation of the prognosis in patients with small-cell lung cancer treated by chemotherapy using tumor shrinkage rate-based radiomics

BackgroundSmall-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown.MethodsWe performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC.ResultsThe TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR < –6.6% than in the group with a TSR ≥ − 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < − 6.6% than when it was > − 6.6%. Brain metastasis-free survival was better in the group with a TSR < − 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS.ConclusionsThe TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.

Clinical Effectiveness and Safety of Transarterial Chemoembolization: Hepatic Artery Infusion Chemotherapy Plus Tyrosine Kinase Inhibitors With or Without Programmed Cell Death Protein-1 Inhibitors for Unresectable Hepatocellular Carcinoma-A Retrospective Study.

Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC. From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC+TKI+PD-1 (THKP group) and 34 patients who received TACE-HAIC+TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs). A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25months, 95% confidence interval (CI) 24.0-26.0 vs 18months, 95% CI 16.1-19.9; p=0.000278], median PFS [16months, 95% CI 14.1-17.9 vs 12months 95% CI 9.6-14.4; p=0.004] and higher ORR (38.6% vs 23.5%, p=0. 156) and DCR (88.6% vs 64.7%, p=0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups. The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.

Establishment of nomogram to predict overall survival and cancer-specific survival of local tumor resection in patients with colorectal cancer liver metastasis with unresectable metastases: a large population-based analysis

Background and PurposeThe tumour-node metastasis (TNM) classification is a common model for evaluating the prognostic value of tumour patients. However, few models have been used to predict the survival outcomes of patients with colorectal cancer liver metastasis (CRLM) with unresectable metastases who received the primary local surgery. Thus, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to establish novel nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of these patients.MethodsExtracted primary data on CRLM patients by local surgery from SEER database. All prognostic factors of OS and CSS were determined by Cox regression analysis. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were used to further evaluate the accuracy and discrimination of these nomograms. Decision curve analysis (DCA) was executed to evaluate the nomograms for the clinical net benefit. Risk stratification analysis (RSA) was used to evaluate the reliability of them in clinical.Results3622 eligible patients were screened and assigned to training cohort (1812) or validation cohort (1810). The age, chemotherapy, tumour grade, primary tumour site, tumour size, lymph node positive rate (LNR), marital status, and carcinoembryonic antigen (CEA) were independent prognostic factors of OS. Additionally, the age, chemotherapy, tumour grade, primary tumour site, tumour size, LNR, and CEA were independent prognostic factors of CSS. The results of C-indexes and ROC curves indicated that the established nomograms exhibited better discrimination power than TNM classification. The calibration curves demonstrated excellent agreement between the predicted and actual survival rates for 1-, 3-, and 5 year OS and CSS. Meanwhile, the validation cohort demonstrated similar results. Background the clinic context, the DCA showed that these nomograms have higher net benefits, and the RSA showed that patients were further divided into low risk, medium risk, and high risk groups according to the predicted scores from nomograms. And, the Kaplan–Meier curve and log-rank test showed that the survival differences among the three groups are statistically significant.ConclusionsThe prognostic nomograms showed very high accuracy, identifiability, and clinical practicality in predicting the OS and CSS of CRLM patients with unresectable metastases treated by local surgery at 1-, 3-, and 5 years, which might improve individualized predictions of survival risks and help clinicians formulate treatment plans.

Construction of prognostic markers for gastric cancer and comprehensive analysis of pyroptosis-related long non-coding RNAs.

China's most frequent malignancy is gastric cancer (GC), which has a very poor survival rate, and the survival rate for patients with advanced GC is dismal. Pyroptosis has been connected to the genesis and development of cancer. The function of pyroptosis-related long non-coding RNAs (PRLs) in GC, on the other hand, remains uncertain. To explore the construction and comprehensive analysis of the prognostic characteristics of long non-coding RNA (lncRNA) related to pyroptosis in GC patients. The TCGA database provided us with 352 stomach adenocarcinoma samples, and we obtained 28 pyroptotic genes from the Reactome database. We examined the correlation between lncRNAs and pyroptosis using the Pearson correlation coefficient. Prognosis-related PRLs were identified through univariate Cox analysis. A predictive signature was constructed using stepwise Cox regression analysis, and its reliability and independence were assessed. To facilitate clinical application, a nomogram was created based on this signature. we analyzed differences in immune cell infiltration, immune function, and checkpoints between the high-risk group (HRG) and low-risk group (LRG). Five hundred and twenty-three PRLs were screened from all lncRNAs (absolute correlation coefficient > 0.4, P < 0.05). Nine PRLs were included in the risk prediction signature that was created through stepwise Cox regression analysis. We determined the risk score for GC patients and employed the median value as the dividing line between HRG and LRG. The ability of the risk signature to predict the overall survival (OS) of GC is demonstrated by the Kaplan-Meier analysis, risk curve, receiver operating characteristic curve, and decision curve analysis curve. The risk signature was shown to be an independent prognostic factor for OS in both univariate and multivariate Cox regression analyses. HRG showed a more efficient local immune response or modulation compared to LRG, as indicated by the predicted signal pathway analysis and examination of immune cell infiltration, function, and checkpoints (P < 0.05). In general, we have created a brand-new prognostic signature using PRLs, which may provide ideas for immunotherapy in patients with GC.

No survival benefit of primary tumor resection for non-small cell lung cancer patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Non-small cell lung cancer (NSCLC) patients with pleural dissemination are generally contraindicated for surgery. This study aimed to investigate the survival benefits of primary tumor resection for NSCLC patients with unexpectedly detected pleural disseminated nodules during thoracotomy in the era of targeted therapy. Of the 4984 patients with NSCLC who underwent surgery without induction therapy between 2000 and 2021, we retrospectively evaluated 90 (1.8%) patients with unexpectedly detected pleural disseminated nodule. Survival analyses were performed with Kaplan-Meier methods and Cox proportional hazards regression. Among the evaluated patients, 58 were male, the median age was 67, and 77 (86%) were diagnosed with adenocarcinoma. Exploratory thoracotomy was performed in 21 (23%), and primary tumor resection was performed in 69 (77%) patients, including pneumonectomy in four, lobectomy in 39, and sublobar resection in 26. Epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement were detected in 33 (37%) and 4 (4%) cases, respectively. Among them, 31 patients received targeted therapy. The overall survival (OS) was not significantly different between patients with primary tumor resection and exploratory thoracotomy (5-year OS rate: 30.2% vs. 27.8%, p = 0.81). Multivariable analysis revealed that sex (p = 0.02) and targeted therapy (p < 0.01) were independent prognostic factors for OS. Survival outcomes in patients who received targeted therapy were significantly better regardless of primary tumor resection. Primary tumor resection might not affect the survival in NSCLC patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Construction of a Cancer Stem Cell Marker Genes-Related 22-Gene Signature for Overall Survival Prediction in High-Risk Wilms’ Tumor

Background: This study aimed to investigate the comprehensive expression profile of cancer stem cell (CSC)-related genes and construct a prognostic signature for overall survival (OS) prediction in high-risk Wilms’ tumor (WT). Materials and methods: Gene expression and survival data from 120 high-risk WT cases in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-WT were used. Results: In total, 229 CSC-related genes were found to be significantly dysregulated in WT compared to tumor-adjacent normal tissues, among which 34 were associated with OS. Using LASSO regression, a 22-gene signature was developed, which exhibited excellent performance in 3-, 5-, and 10-year OS predictions (AUC > 0.86). The high-risk score group showed markedly poorer OS compared to the low-risk score group (median separation, HR = 6.41, 95% CI: 3.18–12.92, p = 3.2e − 9). The 22-gene signature was an independent prognostic factor for OS (HR = 5.086, 95% CI: 3.019–8.568, p < 0.001). Conclusion: This study identified a robust prognostic signature that can effectively support OS prediction.

Developing and validating a Modified Cachexia Index to predict the outcomes for colorectal cancer after radical surgery.

It was reported that the cachexia index (CXI: ) was an essential index for predicting the prognosis of tumor patients. However, since for SMI needs to be measured by CT imaging methods and its calculation was inconvenient. Thus, we developed a modified cachexia index (mCXI: ). The purpose of this study was to evaluate the association between mCXI and prognosis in patients with colorectal cancer. An analysis of 215 patients with newly diagnosed colorectal cancer was carried out retrospectively. An optimal cut-off value of mCXI was established by the receiver operating characteristic (ROC) curves for predicting prognosis. Prognostic implications of mCXI were investigated using Kaplan-Meier curves and Cox regression analysis. A comparative assessment of the predictive capacity between mCXI and the CXI was performed using time-dependent receiver operating characteristic analysis. Patients were classified into two groups based on the cut-off value of mCXI: the LOW mCXI group (n = 60) and the HIGH mCXI group (n = 155). The 3-year Overall survival (OS) (76.6% vs 96.7%, p < 0.01) and 3-year Recurrence-free survival (RFS) (68.3% vs 94.1%, p < 0.01) were significantly worse in the LOW mCXI group in contrast to that in the HIGH mCXI group. In Cox multivariate regression analysis, mCXI was an independent prognostic factor for OS (HR = 8.951, 95%CI: 3.105-25.807, <0.01). Moreover, compared with CXI (AUC = 0.723), mCXI (AUC = 0.801) has better predictive efficacy, indicating that mCXI is more suitable for prognostic assessment. The mCXI significantly correlated with survival outcomes for colorectal cancer patients after radical surgery.

Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.

PSA doubling time 4.65 months as an optimal cut-off of Japanese nonmetastatic castration-resistant prostate cancer

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.

Prognostic Significance of 18F-FDG PET/CT Radiomics in Patients With Resectable Pancreatic Ductal Adenocarcinoma Undergoing Curative Surgery.

This study aimed to investigate the prognostic significance of PET/CT radiomics to predict overall survival (OS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). We enrolled 627 patients with resectable PDAC who underwent preoperative 18F-FDG PET/CT and subsequent curative surgery. Radiomics analysis of the PET/CT images for the primary tumor was performed using the Chang-Gung Image Texture Analysis toolbox. Radiomics features were subjected to least absolute shrinkage and selection operator (LASSO) regression to select the most valuable imaging features of OS. The prognostic significance was evaluated by Cox proportional hazards regression analysis. Conventional PET parameters and LASSO score were assessed as predictive factors for OS by time-dependent receiver operating characteristic curve analysis. During a mean follow-up of 28.8 months, 378 patients (60.3%) died. In the multivariable Cox regression analysis, tumor differentiation, resection margin status, tumor stage, and LASSO score were independent prognostic factors for OS (HR, 1.753, 1.669, 2.655, and 2.946; all P < 0.001, respectively). The time-dependent receiver operating characteristic curve analysis showed that the LASSO score had better predictive performance for OS than conventional PET parameters. The LASSO score using the 18F-FDG PET/CT radiomics of the primary tumor was the independent prognostic factor for predicting OS in patients with resectable PDAC and may be helpful in determining therapeutic and follow-up plans for these patients.

Prognostic factors of patients with human epidermal growth factor receptor 2-positive breast cancer following neoadjuvant therapy: Development and validation of a predictive nomogram

ObjectiveHuman epidermal growth factor receptor 2 (HER2)–positive breast cancer exhibits an aggressive phenotype and poor prognosis. The application of neoadjuvant therapy (NAT) in patients with breast cancer can significantly reduce the risks of disease recurrence and improve survival. By integrating different clinicopathological factors, nomograms are valuable tools for prognosis prediction. This study aimed to assess the prognostic value of clinicopathological factors in patients with HER2-positive breast cancer and construct a nomogram for outcome prediction. MethodsWe retrospectively analyzed the clinicopathological data from 374 patients with breast cancer admitted to the Fourth Hospital of Hebei Medical University between January 2009 and December 2017, who were diagnosed with invasive breast cancer through preoperative core needle biopsy pathology, underwent surgical resection after NAT, and were HER2-positive. Patients were randomly divided into a training and validation set at a ratio of 7:3. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox proportional hazards regression models. Results of the multivariate analysis were used to create nomograms predicting 3-, 5-, and 8-year overall survival (OS) rates. Calibration curves were plotted to test concordance between the predicted and actual risks. Harrell C-index and time-dependent receiver operating characteristic (ROC) curves were used to evaluate the discriminability of the nomogram prediction model. ResultsAll included patients were women, with a mean age of 50 ± 10.4 years (range: 26–72 years). In the training set, both univariate and multivariate analyses identified residual cancer burden (RCB) class, tumor-infiltrating lymphocytes(TILs), and clinical stage as independent prognostic factors for OS, and these factors were combined to construct a nomogram. The calibration curves demonstrated good concordance between the predicted and actual risks, and the C-index of the nomogram was 0.882 (95% CI 0.863–0.901). The 3-, 5-, and 8-year areas under the ROC curve (AUCs) were 0.909, 0.893, and 0.918, respectively, indicating good accuracy of the nomogram. The calibration curves also demonstrated good concordance in the validation set, with a C-index of 0.850 (95% CI 0.804–0.896) and 3-, 5-, and 8-year AUCs of 0.909, 0.815, and 0.834, respectively, which also indicated good accuracy. ConclusionThe nomogram prediction model accurately predicted the prognostic status of post-NAT patients with breast cancer and was more accurate than clinical stage and RCB class. Therefore, it can serve as a reliable guide for selecting clinical treatment measures for breast cancer.

Prognostic value of sarcopenia and myosteatosis alterations on survival outcomes for esophageal squamous cell carcinoma before and after radiotherapy

ObjectiveWe assessed the impact and prognostic significance of alterations in muscle quality and quantity (myosteatosis and sarcopenia, respectively) in patients with esophageal cancer treated with radiotherapy (RT). MethodsWe retrospectively pooled 258 patients with esophageal squamouscell cancer who underwent RT. Myosteatosis and sarcopenia were determined based on the skeletal muscle index derived from the muscle area and attenuation at the L3 level from computed tomography images. Subgroups were formed as: 2 subgroups of non-sarcopenia/myosteatosis and sarcopenia/myosteatosis(with or without other muscle status) at either timepoint of RT, 3 subgroups of only-sarcopenia, only-myosteatosis(without other muscle status), and the co-presence of sarcopenia and myosteatosis at either timepoint of RT, as well as 4 subgroups of continuous sarcopenia/myosteatosis, developed sarcopenia/myosteatosis, reduced sarcopenia/myosteatosis and non-sarcopenia/myosteatosis according to alterations of muscle status at both timepoints of RT. Overall survival (OS) was compared. Univariate and multivariate analyses based on Cox regression identified independent risk factors for prognosis. ResultsEither pre- or post-RT, patients with sarcopenia and myosteatosis(with or without other muscle status) had poor OS. Patients with only-myosteatosis(without other muscle status) showed the best OS (1352 days pre-RT vs. 1648 days post-RT), while patients with concurrent myosteatosis and sarcopenia had the worst OS (907 days pre-RT vs. 706 days post-RT). The ascending order of OS for sarcopenia alterations was as follows: continuous sarcopenia (1093 days), non-sarcopenia (1740 days), developed sarcopenia (2187 days), and reduced sarcopenia (2208 days)(p=0.002). The ascending order of OS for myosteatosis alterations was ranked as follows: continuous myosteatosis (1165 days), reduced myosteatosis (1275 days), developed myosteatosis (1783 days), and non-myosteatosis (1942 days)(p=0.061). Univariate and multivariate Cox regression analyses revealed that increased age, longer tumor length, developed myosteatosis, and continuous myosteatosis were independent prognostic factors for OS. ConclusionMuscle mass status at presentation and alterations in patients with esophageal cancer before and after RT should be considered prognostic indicators.

A novel inflammatory nutrient index for predicting survival outcomes in patients with non-small cell lung cancer.

Lung cancer is one of the most common contributors to cancer-related deaths worldwide. This study aimed to develop a new blood index on the basis of the patient's systemic inflammation and nutritional status, which can be used to predict the prognosis of patients with non-small cell lung cancer (NSCLC). Pre-treatment blood markers were analyzed in 556 NSCLC patients from 2010 to 2019. A least absolute shrinkage and selection operator (LASSO) method was used to select indicators to establish a new integrated biomarker (PNAGR). Kaplan-Meier survival curves were used to assess the prognostic impact of platelet-to-lymphocyte ratio (PLR), albumin (ALB), and the PNAGR. The prognostic value was verified using univariate and multivariate Cox analyses. We used four biomarkers including PLR, ALB, 1/albumin-to-globulin ratio (1/AGR), and neutrophil/albumin-to-globulin ratio (N/AGR) were used to screen for the PNAGR using LASSO. Patients with high PNAGR demonstrated lower overall survival (OS) compared to those with low PNAGR. In both univariate and multivariate analyses, PNAGR was revealed as an independent prognostic factor for OS. The predictive power of PNAGR [area under the curve (AUC): 0.753] was higher than that of the metrics alone. PNAGR is a novel and effective clinical prognostic tool with good clinical predictive value for NSCLC patients.

Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy.

Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain. To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians. A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors. The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS. Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered.

Fibrinogen-to-albumin ratio (FAR) is the best biomarker for the overall survival of patients with non-small-cell lung cancer.

The inflammatory response and the nutritional status are associated with overall survival (OS) in patients with non-small cell lung cancer (NSCLC), but it is unclear which biomarkers are better suited to predict prognosis. This study sought to determine which of the commonly existing inflammatory and nutritional indicators best predicted the OS. This study included 15 compound indicators based on inflammation or nutrition, with cutoff points obtained through the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional risk models were used to evaluate the relationship between these predictors and OS. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used to compare differences between groups. The C-index was calculated to evaluate the predictive ability of the different indicators. The study included 899 patients with NSCLC. In the univariate analysis, all 15 measures were significantly associated with the OS of patients (all p < 0.05). The results of the C-index analysis showed that the fibrinogen-to-albumin ratio (FAR), the systemic immune-inflammation index (SII), and the albumin-to-alkaline phosphatase ratio (AAPR) were the three indices with the best predictive performance. Among them, FAR (C-index = 0.639) had the best predictive power for OS in patients with NSCLC. In the different subgroups, FAR had the highest C-index in male, non-smoking, adenocarcinoma, and stage II patients. The C-index of the platelet-to-lymphocyte ratio (PLR) in female patients was the highest. SII was the highest in smokers, in those aged <65 and ≥65 years, and in stage III patients. The C-index of AAPR was the highest in non-adenocarcinomas. The C-index of the pan-immune-inflammation value (PIV) was the highest in stage I patients. In the multivariate Cox regression analysis, among FAR, SII, and AAPR, only FAR was an independent predictor of OS in patients with NSCLC. A high FAR was associated with a higher risk of death in patients with NSCLC (HR = 1.601, 95% CI = 1.028-2.495). In order to further evaluate the potential prognostic value of FAR, SII, and AAPR in patients with different stages, Cox regression analysis was performed for those with stage I-II and stage III NSCLC. The results showed that FAR was an independent prognostic factor for OS in patients with stage I-II NSCLC. For all patients with NSCLC, the prognostic power of FAR was superior to that of other inflammatory and nutritional indicators.

Development of a novel staging classification for Siewert II adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy.

Stage classification for Siewert II adenocarcinoma of the esophagogastric junction (AEG) treated with neoadjuvant chemotherapy (NAC) has not been established. To investigate the optimal stage classification for Siewert II AEG with NAC. A nomogram was established based on Cox regression model that analyzed variables associated with overall survival (OS) and disease-specific survival (DSS). The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test, Akaike information criterion, Harrell concordance index, time-receiver operating characteristic curve, and decision curve analysis. Data from 725 patients with Siewert type II AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses revealed that sex, marital status, race, ypT stage, and ypN stage were independent prognostic factors of OS, whereas sex, race, ypT stage, and ypN stage were independent prognostic factors for DSS. These factors were incorporated into the OS and DSS nomograms. Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer. Finally, a user-friendly web application was developed for clinical use. The nomogram established specifically for patients with Siewert type II AEG receiving NAC demonstrated good prognostic performance. Validation using external data is warranted before its widespread clinical application.

Prognosis of locoregional recurrence after early breast cancer with immediate breast reconstruction.

e12595 Background: Several studies have shown no difference in the prognosis of breast cancer patients who underwent total mastectomy (MT) with or without immediate breast reconstruction (IBR), which is now a standard surgical technique in the treatment of breast cancer. While some studies have reported a poor prognosis for locoregional recurrence (LRR) following breast cancer surgery, the prognosis of LRR without simultaneous distant metastasis after IBR is not known. We conducted a multi-facility retrospective observational study to investigate the prognosis of breast cancer patients with LRR after IBR. Methods: Of the 4,726 primary breast cancer patients for whom IBR was performed at 12 Japanese medical facilities between January 1, 2008, and December 31, 2016, MT or skin-sparing mastectomy (SSM) was performed in 3,295 patients. LRR was observed in 87 of these patients, 17 of whom had distant metastasis (n=13) or metastasis to the supraclavicular or internal mammary lymph nodes (n=4) before LRR was excluded. The measured outcomes were IBR-LRR-related prognostic factors, five-year distant metastasis-free survival (DMFS), and five-year overall survival (OS). The statistical analyses employed Kaplan–Meier curves and a Cox proportional hazards model. Results: The median observation period was 39.3 months and the median age at which IBR was performed was 44 years. There were 61 cases (87.1%) of invasive cancer. Sixty-one cases (87.1%) were ER-positive, 54 (77.1%) were PR-positive, and 13 (19.7%) were HER2-positive. Fifteen cases (21.4%) had pathological lymph node metastasis (pN), 60 cases (85.7%) underwent implant reconstruction, 33 cases (47.1%) had a disease-free interval ≤ 36 months, 9 cases (12.9%) had regional lymph node recurrence (RR), and 65 cases (92.9%) underwent surgical resection to treat LRR. The five-year DMFS after LRR was 92.4%, and the five-year OS was 91.2%. The relationship between DMFS and clinical pathology factors was analyzed using a Cox proportional hazards model. Univariate analysis revealed significant differences for pN (HR 10.634, 95% CI 1.102–102.616, P=0.041) and RR (HR 9.960, 95% CI 1.400–70.862, P=0.022), and multivariate analysis indicated that RR was the only independent prognostic factor for DMFS (HR 7.834, 95% CI 1.085–56.587, P=0.041) (Table 1). Univariate analysis revealed significant differences for post-mastectomy radiation therapy (PMRT) (HR 130.676, 95% CI 1.552–412.278, P=0.023) and RR (HR 8.181, 95% CI 1.106–60.503, P=0.043), and multivariate analysis indicated that both PMRT (HR 61.281, 95% CI 2.540–1478.426, P=0.010) and RR (HR 15.687, 95% CI 1.354–181.772, P=0.028) were independent prognostic factors for OS. Conclusions: This is the first study to report the prognosis of breast cancer patients with LRR after IBR. Although these patients have a favorable prognosis overall, our results indicate that RR may be a significant factor for poor prognosis.

Nivolumab combined with high dose multisite radiotherapy in previously untreated advanced melanoma (NIRVANA): A non-randomised, open-label, multicenter, phase 2 trial.

e21505 Background: Outcome of advanced melanoma remains poor for the majority of patients (pts) and new treatment strategies are needed. Preclinical and clinical data suggest a potential increase of the immunotherapy efficacy when combined with hypofractionated multisite radiotherapy (HMR). Objective: To assess the impact of HMR combined with nivolumab in advanced melanoma. Methods: This is a non-randomised, open-label, multicentre phase 2 trial(NCT02799901). Pts must have locally advanced or metastatic melanoma (AJCC7), previously untreated. Pts with mucosal or uveal melanoma, those with brain metastasis and LDH ≥ 1.5 the upper limit were not included. Pts received (until progression or unacceptable toxicity) nivolumab (fixed dose 240 mg/15 days) plus radiotherapy (day 15) delivered 3 x 6 Gy every second day, at every metastatic organ, if feasible.At progression, second irradiation was authorized while pursuing nivolumab (rechallenging strategy).The primary endpoint was 1-year overall survival (OS) (hypothetic improvement of 1-year OS from 71%1). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Subgroups and multivariate analyses were performed. Results: A total of 64 pts were included, from 03/2017 to 07/2019. Median follow-up was 23.5 months [IQR 2.3-43.8]. Median age was 64 years [35-95], majority of pts were male (67%), had an ECOG-PS 0 (75%), a stage IV-M1C disease (47%) and were BRAF-wild-type (67%).] The 1-year OS and PFS rates were 79% and 56% respectively (p = 0.12 and p = 0.0.3 in comparison with the 1-year OS and PFS of 71% and 43% of Robert et al’study1). 39 pts were irradiated at 1 target, 25 at ≥2 targets (total of 92 tumor targets). The 2-years OS rates were 83% and 52% for pts who were irradiated on several sites and one site respectively (p = 0.03). The ORR in the whole cohort was 53% [95% CI, 40.23; 65.72], 33% [95% CI, 14.59; 56 .97] and 62% [95% CI, 45.64; 76.43] in BRAF mutated and BRAF-wild type respectively. Among BRAF status, gender, PS, stage, age, LDH level and number of irradiated sites (1 vs ≥ 1), the independent prognostic factors for OS in multivariate analysis were number of irradiated sites (HR = 0.26, p = 0.03) and ECOG-PS (HR = 6.2, p = 0.001). Rechallenging was performed in 11 pts, among them; 3 were progression-free at last follow-up, 10 were reirradiated once and 1 was reirradiated 3 times. ICI was stopped due to toxicities for 6 pts. Drug-related adverse events of grade 3-4 occurred in 8.3% of the patients (no grade 5). Conclusions: Combined nivolumab and HMR did not improve significantly OS compare to nivolumab alone but improve significantly PFS1. However, this strategy has an acceptable safety and could be a treatment option for some patients. Multisite irradation and rechallenging strategies deserve to be considered. 1 Robert et al, J Clin Oncol 2020. Clinical trial information: NCT02799901 .