Predictive Factors For Overall Survival Research Articles

Venetoclax Plus Azacitidine as a Bridge Treatment to Allogeneic Stem Cell Transplantation in Unfit Patients with Acute Myeloid Leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely recommended for unfit patients with newly diagnosed acute myeloid leukemia (AML). Patient survival can improve with venetoclax plus azacitidine (VEN plus AZA). However, the long-term outcome of this treatment strategy is still unsatisfactory. The high response and low treatment toxicity rates of patients receiving VEN plus AZA can provide an opportunity for HSCT among unfit patients. Nevertheless, the outcomes and complications of VEN plus AZA, followed by HSCT, remain unclear. This single-center retrospective study aimed to compare patients with newly diagnosed AML receiving VEN plus AZA as induction therapy (n = 27) to those receiving the conventional I3A7 regimen as induction therapy (n = 34). The 1-year overall survival, relapse, and non-relapse mortality rates in the two groups were similar. The cytogenetic risks and the hematopoietic cell transplantation-specific comorbidity index are the most significant predictive factors of overall survival. In older patients unfit for intensive chemotherapy, a low-intensity regimen with VEN plus AZA is a suitable bridge therapy. Furthermore, allo-HSCT is feasible and can be a curative option.

Evaluation of the prognostic significance of clinical features of tumoral lesions in an extensive series of mycosis fungoides.

Tumors indicating the advanced stage of mycosis fungoides (MF) have a rich clinical spectrum. Although it is known that the prognosis of MF generally worsens following the development of tumors, some cases may have a relatively indolent course, and the role of clinical characteristics regarding prognosis has still not been well understood. MF patients were retrospectively evaluated regarding the development of tumors. Besides demographic characteristics, data of the subtype and stage of the disease were recorded. The clinical features of tumors, including number (<5, 5-10, 11-20, or >20), location, dimension (diameter of ≥5 cm), presence of ulceration, and surrounding inflammation, were noted. Univariate and multivariate analyses evaluated the relationship between overall survival (OS) with demographic and clinical features. Among 730 consecutive MF patients, tumors developed in 8.2% (n = 60), of whom 46.7% were diagnosed with advanced-stage MF from the beginning. The most common subtype was folliculotropic MF (53.3%). Most patients (55%) had multiple tumors, and the most frequent localization was the trunk (71.7%). Most tumors presented as smooth-surfaced, indurated papules and/or nodules (70%), while others were reddish-purple, occasionally accompanied by ulceration (50%), perilesional inflammation (23.3%), and attaining large dimensions (25%). Mortality was recorded in 51.7% of patients, and the 5-year OS rate from the diagnosis of tumors was 49%. Independent poor prognostic factors for OS in multivariate analysis included older age at the time of diagnosis, presence of tumors at the initial MF diagnosis, presence of over 20 tumors, and the existence of large tumors. Tumoral MF seen in older patients, the first diagnosis of MF in this stage, presenting with generalized and large tumors, seems to be a predictive factor for OS.

Analysis of the survival time of patients with heart failure with reduced ejection fraction: a Bayesian approach via a competing risk parametric model

PurposeHeart failure (HF) is a widespread ailment and is a primary contributor to hospital admissions. The focus of this study was to identify factors affecting the extended-term survival of patients with HF, anticipate patient outcomes through cause-of-death analysis, and identify risk elements for preventive measures.MethodsA total of 435 HF patients were enrolled from the medical records of the Rajaie Cardiovascular Medical and Research Center, covering data collected between March and August 2018. After a five-year follow-up (July 2023), patient outcomes were assessed based on the cause of death. The survival analysis was performed with the AFT method with the Bayesian approach in the presence of competing risks.ResultsBased on the results of the best model for HF-related mortality, age [time ratio = 0.98, confidence interval 95%: 0.96–0.99] and ADHF [TR = 0.11, 95% (CI): 0.01–0.44] were associated with a lower survival time. Chest pain in HF-related mortality [TR = 0.41, 95% (CI): 0.10–0.96] and in non-HF-related mortality [TR = 0.38, 95% (CI): 0.12–0.86] was associated with a lower survival time. The next significant variable in HF-related mortality was hyperlipidemia (yes): [TR = 0.34, 95% (CI): 0.13–0.64], and in non-HF-related mortality hyperlipidemia (yes): [TR = 0.60, 95% (CI): 0.37–0.90]. CAD [TR = 0.65, 95% (CI): 0.38–0.98], CKD [TR = 0.52, 95% (CI): 0.28–0.87], and AF [TR = 0.53, 95% (CI): 0.32–0.81] were other variables that were directly related to the reduction in survival time of patients with non-HF-related mortality.ConclusionThe study identified distinct predictive factors for overall survival among patients with HF-related mortality or non-HF-related mortality. This differentiated approach based on the cause of death contributes to the estimation of patient survival time and provides valuable insights for clinical decision-making.

Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis.

To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC). In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between groups were compared. Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC-PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC-PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression-free survival (median progression-free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC-PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC-PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression-free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival. The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

A Multicenter Retrospective Case-Control Study on Simple vs Extended Sleeve Lobectomies

BackgroundSleeve resection is currently the gold standard procedure for centrally located non-small cell lung cancer (NSCLC). Extended sleeve lobectomy (ESL) consists of an atypical bronchoplasty with resection of >1 lobe and carries several technical difficulties compared with simple sleeve lobectomy (SSL). Our study compared the outcomes of ESL and SSL for NSCLC. MethodsThis multicenter, retrospective, cohort study included 1314 patients who underwent ESL (155 patients) or SSL (1159 patients) between 2000 and 2018. The primary end points were 30-day and 90-day mortality, overall survival (OS), disease-free survival (DFS), and complications. ResultsNo differences were found between the 2 groups in general characteristics and surgical and survival outcomes. In particular, there were no differences in early and late complication frequency, 30- and 90-day mortality, R status, recurrence, OS (54.26 ± 33.72 months vs 56.42 ± 32.85 months, P = .444), and DFS (46.05 ± 36.14 months vs 47.20 ± 35.78 months, P = .710). Mean tumor size was larger in the ESL group (4.72 ± 2.30 cm vs 3.81 ± 1.78 cm, P < .001). Stage IIIA was the most prevalent stage in ESL group (34.8%), whereas stage IIB was the most prevalent in SSL group (34.3%; P < .001). The multivariate analyses found nodal status was the only independent predictive factor for OS. ConclusionsESL gives comparable short- and long-term outcomes to SSL. Appropriate preoperative staging and exclusion of metastases to mediastinal lymph nodes, as well as complete (R0) resection, are essential for good long-term outcomes.

The number of metastatic lymph nodes is more predictive of prognosis than location-based N stage for nonsmall cell lung cancer: a retrospective cohort study.

The eighth edition of nodal classification is defined only by the anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. The authors aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected nonsmall cell lung cancer. Patients with stage IA to IIIB resected nonsmall cell lung cancer between 1 January 2009 and 31 December 2013 were analyzed as a Chinese cohort. The optimal thresholds for the nN classification were determined by the X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the surveillance, epidemiology, and end results database was performed to test the robustness of the nN classification. Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort, which included 4432 patients, then validated in the SEER cohort ( n =28022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N 0 vs. N 1-3 , P <0.001; N 0 vs. N 3-6 , P <0.001; N 0 vs. N >6 , P <0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI: 0.049-0.132) and 5-year time-independent AUC, 0.593 (95% CI: 0.560-0.625) vs. 0.554 (95% CI: 0.520-0.588), P <0.001]. The nN classification tended to be a superior prognostic indicator than the location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of the TNM system.

CyberKnife-based stereotactic radiosurgery or fractionated stereotactic radiotherapy in older patients with brain metastases from non-small cell lung cancer.

We analyzed clinical results of CyberKnife (CK)-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in older patients (age ≥65 years) affected by brain metastases (BM) from non-small cell lung cancer (NSCLC). Forty-three older patients with 92 BM were treated with CK-based SRS/FSRT at our institution between 2009 and 2019. The end-point was overall survival (OS). Univariate and multivariate analyses were performed to identify the prognostic factors influencing OS. The in-field local control (IFLC) within the SRS/FSRT field was also assessed. During a median follow-up period of 18 months, the median OS was 32 months. NSCLC-specific graded prognostic assessment (GPA) (p = 0.027) was an independent significant factor affecting OS in the multivariate analysis. The median IFLC period was 31 months, and the total BM volume (p = 0.025) appeared to be a significant feature of IFLC. No adverse events >grade 2 were reported after SRS/FSRT. CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects. GPA, which was consisted in age, performance status, extra-cerebral metastasis, and number of BM, seemed to be predictive factors for OS.

Prognostic Role of Multiparameter Flow Cytometry-Based Measurable Residual Disease Assessment in Acute Myeloid Leukemia Patients with FMS3-like Tyrosine Kinase-3 Internal Tandem Duplication (FLT3-ITD)

Introduction Measurable residual disease (MRD) monitoring is predictive in acute myeloid leukemia (AML). Assessment of FMS3-like tyrosine kinase-3 in-frame internal tandem duplications (FLT3-ITD) is usually performed at diagnosis by polymerase chain reaction (PCR). Due to its relative lower sensitivity of 2%, FLT3-ITD PCR is not routinely used during response assessment. Next-generation sequencing is similarly limited by technical difficulties in capturing tandem duplications using the short base pair-based sequencing method. Long base pair-based sequencing has been reported, but its use is limited by financial restrictions. Multiparameter flow cytometry (MFC) can be a useful tool for MRD monitoring in this AML subtype until such time that molecular techniques for detecting FLT3-ITD MRD are optimized. Patients and methods The study evaluated the outcomes of FLT3-ITD mutated AML patients diagnosed and treated from 2018 to 2022 at Princess Margaret Cancer Centre. We compared outcomes according to MFC-MRD post-induction and FLT3-ITD allele frequency (AF) status at diagnosis. MRD cut-off was 0.1%. Data were locked as of June 30, 2023. Clinical outcomes evaluated include overall survival (OS) and relapse-free survival (RFS). The cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated considering competing risk. The Kaplan-Meier method using a log-rank test and a multivariate Cox proportional hazard model was used for analyses, while the Gray test and Fine-Grey model were used for uni- and multivariate analysis for CIR and NRM. Results A total of 111 patients with a mean age of 63.5 years were included, of whom 90 received treatment. Secondary AML accounted for 12.7% of patients. Risk stratification according to European LeukemiaNet (ELN) 2022 was favorable in 2 (1.8%), intermediate in 67 (60.4%), and adverse in 42 patients (37.8%). Nucleophosmin 1 (NPM1) co-mutation was observed in 55 patients (49.5%). Seventy-nine patients (87.8%) could be assessed for overall response, including 69 (76.7%) who achieved complete remission (CR) or CR with incomplete count recovery (CRi). Of these, 54 achieved first CR/CRi (CR1) with 1 induction cycle. MFC-MRD data were available in 61 patients, of whom 44 (72.1%) were MRD negative, while 17 (27.9%) were MRD positive. With a median follow-up of 437 days, 50 patients (45%) were still alive. Median OS and RFS were 3.42 years and 1.05 years, respectively. Among patients who achieved CR1, post-induction MFC-MRD positivity correlated with an inferior OS (HR 2.35 [1.06-5.26], p=0.037) and a trend for a shorter RFS (HR 2.08 [0.99-4.35], p=0.052). We examined the impact of FLT3-ITD AF at diagnosis on long-term outcomes. By applying a binary recursive partitioning method, the cut-off of FLT3-ITD AF with the best risk stratification power for RFS, was defined at 54.6%. The group with a higher FLT3-ITD AF showed inferior OS (HR 1.86 [1.01-3.44], p=0.047) and RFS (HR 1.91 [1.09-3.33], p=0.023). Taking together FLT3-ITD AF at diagnosis and MFC-MRD status at CR1, patients with low FLT3-ITD AF and negative MRD had the highest OS rate of 86.2% at 12 months (p=0.023), and the highest RFS at 72.4% (p=0.096), while the corresponding values for low FLT3-ITD AF/positive MRD patients were 87.5% and 50%, respectively. In contrast, those with high FLT3-ITD AF/negative MRD had an OS of 72.7% and a RFS of 45.5%, while those with high FLT3-ITD AF/positive MRD showed the lowest OS (16.7%) and the shortest RFS (16.7%). There was no statistical difference in CIR and NRM among groups. Multivariate analysis with stepwise selection was performed, considering age at diagnosis, ELN 2022 risk, MFC-MRD at CR1, FLT3-ITD AF at diagnosis, cytogenetics, and NPM1 co-mutation. Predictive factors for OS were MFC-MRD post-induction (HR 2.49 [1.11-5.61], p=0.027) and FLT3-ITD AF (HR 2.29 [1.03-5.11], p=0.043). For RFS, age at diagnosis (HR 1.03 [1.00-1.06], p=0.038) and FLT3-ITD AF (HR 2.40 [1.15-5.01], p=0.019) were predictive, while MFC-MRD was not significant (HR 1.59 [0.72-3.53], p=0.25). Conclusion Our data demonstrate that MFC-based MRD assessment is feasible in AML with FLT3-ITD. Although better outcomes are expected in patients with a lower FLT3-ITD AF, patients who failed to achieve MRD negativity at CR1 showed inferior outcomes. The presence of both poor risk factors, a high AF of FLT3-ITD at diagnosis and MRD positivity at CR1, correlated with the worst treatment outcomes.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

Analysis of neoadjuvant chemotherapy for breast cancer: a 20-year retrospective analysis of patients of a single institution

BackgroundNeoadjuvant chemotherapy (NAC) has been widely applied in operable breast cancer patients. This study aim to identify the predictive factors of overall survival(OS) and recurrence free survival (RFS) in breast cancer patients who received NAC from a single Chinese institution.Patients and MethodsThere were 646 patients recruited in this study. All the patients were treated at department of Surgical Oncology, Sir Run Run Shaw Hospital between February 25, 1999 and August 22, 2018. The relevant clinicopathological and follow-up data were collected retrospectively. RFS and OS were assessed using the Kaplan-Meier method. Multivariate Cox proportional hazards model was also employed. Multi-variate logistic regression model was simulated to predict pathologic complete response (pCR).ResultsIn total, 118 patients (18.2%) achieved pCR during NAC. The 5-year OS was 94.6% versus 78.1% in patients with and without pCR, respectively (P < 0.001). The 5-year RFS was 95.3% and 72.7%, respectively (P < 0.001). No difference was detected among molecular subtypes of 5-year RFS in patients obtained pCR. Factors independently predicting RFS were HER2-positive subtype (hazard ratio(HR), 1.906; P = 0.004), triple-negative breast cancer (TNBC) (HR,2.079; P = 0.003), lymph node positive after NAC(HR,2.939; P < 0.001), pCR (HR, 0.396;P = 0.010), and clinical stage III (HR,2.950; P = 0.016). Multi-variate logistic regression model was simulated to predict the pCR rate after NAC, according to clinical stage, molecular subtype, ki-67, LVSI, treatment period and histology. In the ROC curve analysis, the AUC of the nomogram was 0.734 (95%CI,0.867–12.867).ConclusionsFollowing NAC, we found that pCR positively correlated with prognosis and the molecular subtype was a prognostic factor.

Exploring the implications of modified advanced lung cancer inflammation index on outcomes in patients with advanced non-small cell lung cancer

Aim: Sarcopenia and skeletal muscle density (SMD) have been shown to be both predictive and prognostic marker in oncology. Advanced lung cancer inflammation index (ALI) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). Computed tomography (CT) enables skeletal muscle to be quantified, whereas body mass index (BMI) cannot accurately reflect body composition. The purpose was to evaluate the prognostic value of modified ALI (mALI) using CT-determined third lumbar vertebra (L3) muscle index beyond original ALI and see the interaction between sarcopenia, SMD, neutrophil-lymphocyte ratio (NLR), ALI and mALI at baseline and post 4 cycles of chemotherapy and their effects on OS and progress free survival (PFS) in patients with advanced non-SCLC (NSCLC). Methods: This retrospective study consisted of a total of 285 advanced NSCLC patients. The morphometric parameters such as SMD, skeletal muscle index (SMI) and fat-free mass (FFM) were measured by CT at the L3 vertebra. ALI was defined as BMI × serum albumin/NLR and mALI was defined as SMI × serum albumin/NLR. Results: Sarcopenia was observed in over 70% of patients across all BMI categories. Patients having sarcopenia suffered from a higher incidence of chemotherapeutic drug toxicities but this was not found to be statistically significant. Concordance was seen between ALI and mALI in the pre-treatment setting and this was statistically significant. A significant proportion of patients with poor ALI (90.9%), poor pre-chemotherapy mALI (91.3%) and poor post-chemotherapy mALI (89%) had poor NLR and each of them was statistically significant. Conclusions: In both univariate and multivariate analyses, this study demonstrated the statistical significance of sarcopenia, SMD, and mALI as predictive factors for OS. Additionally, sarcopenia and SMD were also found to be statistically significant factors in predicting PFS. These biomarkers could potentially help triage patients for active nutritional intervention for better outcomes.

Single Institute Experience Treating Uterine Carcinosarcoma: Outcome Analysis

Uterine carcinosarcoma (UCS) is rare with a poor prognosis. We report over 10 years' experience, reporting prognostic and predictive factors for overall survival (OS) and disease-free survival (DFS). Patient, tumor, treatment and relapse characteristics of 168 women with stages I-IVB UCS treated at our institute between 2010 and 2020 were analyzed. OS and DFS at 2 and 5 years were the primary outcomes, estimated with Kaplan-Meier. The benefit of adjuvant chemotherapy and radiotherapy in the curative cohort was estimated using the log rank test. Median follow up was 23 months (range 1-137 months). 34% had FIGO stage IA disease, 10% IB, 8% II. 16% IIIA-IIIC1, and 10% IIIC2 and 22% IVB. The overall 2-year OS was 52% and 5-year OS 30%. 2-year OS by FIGO stage were: IA 66%; IB 63%; II 54%; IIIA-IIIC1 54%; IIIC2 45%; IVB 26%. Within the curative cohort who were surgically staged, 2-year DFS was 47% and 5-year was 30%. 2-year DFS were 61% in IA disease, 53% IB, 12% II, 51% IIIA-IIIC1, and 45% IIIC2 and 4% IVB. A greater risk of death was conferred by lack of adjuvant treatment (lack of chemo > lack of radiotherapy). The most common chemotherapy regimen used was Carboplatin Paclitaxel and pelvic radiotherapy 45Gy 25F over 5 weeks. The combination of surgery and chemotherapy +/- radiotherapy significantly improved OS compared to surgery +/- radiotherapy (HR 0.5 with CI 0.3 - 0.9) p<0.05. Radiotherapy improved OS compared to surgery only (HR 0.4 with CI 0.2 - 1.1) p<0.05. Relapse rate in all patients following curative treatment is 72% within year 1 and 86% within year 2 from diagnosis. In 52 patients with stage 1A disease treated with surgery +/- radiotherapy only, 42.4% relapsed, median time to relapse was 8 months from diagnosis. Relapse occurred despite 69.2 % stage 1A patients receiving adjuvant pelvic EBRT and in these patients relapse within the pelvis occurred in 50%. This study constitutes the largest retrospective analyses of long-term mortality outcomes in UCS and confirms poor outcomes despite curative surgery and adjuvant therapy. Most patients relapse within the first year following curative treatment. The use of adjuvant chemotherapy improves OS in all stages. In stage 1A disease 42 % patients relapse locally and distantly. This is an area of controversy and this data would strongly suggest that the addition of adjuvant paclitaxel-carboplatin or cisplatin-doxorubicin chemotherapy to EBRT should be considered in all patients including earliest stage disease.

Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens.

Pembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear. This study included 66 patients with R/M HNSCC who received a pemblolizumab-containing regimen as a first-line therapy at Tohoku University Hospital, Sendai, Japan. The patients' characteristics, combined positive score, baseline tumor size, tumor response, DpR, overall survival (OS), progression-free survival (PFS), PFS2, and adverse events were reviewed. The associations between DpR and survival outcomes were analyzed. The 1 year-OS and 1 year-PFS rates of pembrolizumab-containing regimens were 69.4% and 24.4%, respectively. The response rate was 28.8%. The mean and median values of tumor change from baseline were 5.1% and -9.0%. In the correlation analysis, a significant negative correlation was observed between tumor change rate from baseline and survival outcomes (OS: r= -0.41, p=0.0017; PFS: r=-0.49, p<0.001). In the multivariate analysis, DpR with tumor change of ≤-45 was associated with better OS and PFS. DpR induced by pembrolizumab-containing regimens may be a predictive factor for OS and PFS in patients with R/M HNSCC.

Radical Cystectomy Versus Bladder-Preserving Therapy in Muscle-Invasive Bladder Cancer Patients After Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Analysis

Purpose: Although radical cystectomy (RC) and concurrent chemoradiotherapy (CCRT) are curative options for muscle-invasive bladder cancer (MIBC), the optimal treatment strategy for MIBC patients with a history of nephroureterectomy for upper tract urothelial carcinoma (UTUC) remains unclear. This retrospective analysis was conducted to compare survival rates and evaluate prognostic factors related to treatment outcomes.Materials and Methods: We conducted a multi-institutional retrospective study of patients with MIBC after nephroureterectomy for UTUC between 2005 to 2023. Out of 75 patients, 30 underwent bladder-preserving therapy (BPT), including 22 patients who underwent radiation therapy (RT) and 8 patients who underwent CCRT, while 45 patients underwent RC. The overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) after BPT and RC were evaluated using Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with OS, CSS, and PFS. Posttreatment changes in renal function were compared.Results: At 3 years, the OS, CSS, and PFS rates in the BPT group were 52.4%, 71.7%, and 31.3%, respectively, with no significant difference compared to RC. In multivariate analysis, bladder cancer T stage was the only predictive factor for OS, CSS, and PFS. Similar results were also observed in the RT group compared to RC. A significant decrease in renal function was detected among patients in the RC group, while patients in the BPT group maintained preserved renal function. Patients in the BPT group experienced a lower grade of toxicity after treatment compared to those in the RC group, and the rates of survival with functional bladder at 1 year, 3 years, and 5 years were 87.0%, 69.9%, and 69.9%, respectively.Conclusions: Bladder-preserving therapy, including RT alone, may be a viable treatment option for patients with MIBC who have undergone nephroureterectomy, as it can achieve comparable oncologic outcomes to RC, while potentially preserving bladder and renal function.

Predicting Survival of Patients with Nonmetastatic Breast Cancer Based on Fibrinogen-to-Albumin Ratio and Lymphocyte-to-Monocyte Ratio: A Nomogram-Based Assessment

Background: Parameters of systemic inflammation have received attention as prognostic surrogates in various malignant tumors. Fibrinogen-to-albumin ratio (FAR) and lymphocyte-to-monocyte ratio (LMR) correlate with tumor growth and dissemination. We aimed to bring the combination of FAR and LMR (FAR-LMR) together to establish novel nomograms for survival and recurrence in nonmetastatic breast cancer patients. Methods: We retrospectively recruited 461 female patients with nonmetastatic breast cancer from January 2011 to December 2013 in our hospital and randomly assigned them into the training cohort (N = 318) and the validation cohort (N = 143). The potential predictive factors for overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Cox proportional hazards models and log-rank test. Results: Elevated FAR was associated with poor OS (p < 0.001) and DMFS (p = 0.02), whereas increased LMR was associated with satisfactory OS (p = 0.01) and LRFS (p = 0.01). High FAR combined with low LMR was associated with less favorable OS (p = 0.001), LRFS (p = 0.005), and DMFS (p = 0.003) Based on multivariate analysis, FAR-LMR, tumor size, lymph node metastasis, age, and pathologic status contributed to prognostic nomograms of OS, DMFS, and LRFS. Nomograms presented exceptional performance for 3-, 5-, and 8-year OS, DMFS, and LRFS prediction compared with clinical TNM stage. The C-index was significantly higher than that of TNM stage, either of FAR or LMR (3-year: 0.709 vs. 0.621 vs. 0.544 vs. 0.641, 5-year: 0.761 vs. 0.597 vs. 0.605 vs. 0.677, 8-year: 0.84 vs. 0.62 vs. 0.539 vs. 0.623). Conclusions: We developed and validated a convenient predictive model for the survival outcomes of patients with nonmetastatic breast cancer. The nomograms can be utilized as auxiliary tools to provide prognostic information.

The efficacy of fat-free mass index and appendicular skeletal muscle mass index in cancer malnutrition: a propensity score match analysis.

Reduced muscle mass (RMM) is a phenotypic criterion for malnutrition; the appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI) are both applicable indicators in the global leadership initiative on malnutrition (GLIM) guideline. However, their sensitivity and prognostic effect remain unclear. Clinical data of 2,477 patients with malignant tumors were collected. Multi-frequency bioelectrical impedance analysis was used to obtain ASMI and FFMI. RMM was confirmed by ASMI (< 7.0 kg/m2 for men and < 5.7 kg/m2 for women) or FFMI (< 17 kg/m2 for men and < 15 kg/m2 for women). Propensity score match analysis and logistic regression analysis were used to evaluate the efficacy of FFMI and ASMI in diagnosing severe malnutrition and multivariate Cox regression analysis to determine the efficacy of RMM in predicting survival. In total, 546 (22.0%) and 659 (26.6%) participants were diagnosed with RMM by ASMI (RMM.ASMI group) and FFMI (RMM.FFMI group); 375 cases overlapped. Body mass index (BMI), midarm circumference, triceps skinfold thickness, and maximum calf circumference were all significantly larger in the RMM.FFMI group for both sexes (P < 0.05). A 1:1 matched dataset constructed by propensity score match contained 810 cases. RMM.FFMI was an influential factor of severe malnutrition with HR = 3.033 (95% CI 2.068-4.449, P < 0.001), and RMM.ASMI was a predictive factor of overall survival (HR = 1.318, 95% CI 1.060-1.639, P = 0.013 in the RMM.ASMI subgroup, HR = 1.315, 95% CI 1.077-1.607, P = 0.007 in the RMM.FFMI subgroup). In general, RMM indicates negative clinical outcomes; when defined by FFMI, it predicts nutritional status, and when defined by ASMI, it is related to poor survival in cancer patients.

Tumor attachment to Major intrahepatic vascular for Colorectal liver metastases

BackgroundColorectal liver metastases attached major intrahepatic vessels has been considered to be a risk factor for survival outcome after liver resection. The present study aimed to clarify the outcomes of R1 surgery (margin < 1 mm) in CRLM patients, distinguishing parenchymal margin R1 and attached to major intrahepatic vessels R1.MethodsIn present study, 283 CRLM patients who were evaluated to be attached to major intrahepatic vessels initially and underwent liver resection following preoperative chemotherapy. They were assigned to two following groups: R0 (n = 167), R1 parenchymal (n = 58) and R1 vascular (n = 58). The survival outcomes and local recurrence rates were analyzed in each group.ResultsOverall, 3- and 5-year overall survival rates after liver resection were 53.0% and 38.2% (median overall survival 37 months). Five-year overall survival was higher in patients with R0 than parenchymal R1 (44.9%% vs. 26.3%, p = 0.009), whereas there was no significant difference from patients with vascular R1 (34.3%, p = 0.752). In the multivariable analysis, preoperative chemotherapy > 4 cycles, clinical risk score 3–5, RAS mutation, parenchymal R1 and CA199 > 100 IU/ml were identified as independent predictive factors of overall survival (p < 0.05). There was no significant difference for local recurrence among three groups.ConclusionParenchymal R1 resection was independent risk factor for CRLM. Vascular R1 surgery achieved survival outcomes equivalent to R0 resection. Non-anatomic liver resection for CRLM attached to intrahepatic vessels might be pursued to increase patient resectability by preoperative chemotherapy.

Clinical characteristics of late-onset interstitial pneumonia after allogeneic hematopoietic stem cell transplantation.

Non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT) remain fatal. In particular, information regarding late-onset interstitial lung disease predominantly including organizing pneumonia and interstitial pneumonia (IP) is limited. A retrospective nationwide survey was conducted using data collected from the Japanese transplant outcome registry database from 2005 to 2010. This study focused on patients (n = 73) with IP diagnosed after day 90 post-HSCT. A total of 69 (94.5%) patients were treated with systemic steroids, and 34 (46.6%) experienced improvement. The presence of chronic graft-versus-host disease at the onset of IP was significantly associated with non-improvement of symptoms (odds ratio [OR] 0.35). At the time of last follow-up (median, 1471days), 26 patients were alive. Of the 47 deaths, 32 (68%) were due to IP. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates were 38.8% and 51.8%, respectively. In the multivariate analysis, the predictive factors for OS were comorbidities at IP onset (hazard ratio [HR]: 2.19) and performance status (PS) score of 2-4 (HR 2.77). Furthermore, cytomegalovirus reactivation requiring early intervention (HR 2.04), PS score of 2-4 (HR 2.63), and comorbidities at IP onset (HR 2.90) were also significantly associated with increased risk of NRM.

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases

PurposeDespite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery. Patients and methodsFrom January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13–22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3. ResultsThe 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41–98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8–13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11–NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05). ConclusionA long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.