Significant Predictor Of Overall Survival Research Articles

Patterns and predictors of relapse in Merkel cell carcinoma: Results from a population-based study

Background and purposeProspective data evaluating the role of adjuvant radiotherapy (RT) for Merkel Cell Carcinoma(MCC) is lacking. To better understand the efficacy of adjuvant RT, a population-based patterns of failure study was conducted. MethodsWe identified MCC patients treated from 1988 to 2018.Primary outcome measures were recurrence-free survival (RFS), overall survival (OS) and MCC-specific survival (MCC-SS). Charlson Co-morbidity Index (CCI) was also calculated. Results217 patients with mean age 79 (range: 33–96) were analyzed. The median follow-up was 40 months. Treatments were: surgery(S) alone (n = 101, 45%) or S + RT(n = 116, 55%).Local recurrence (LR) was low in stage I (n = 6, 6.5%) with clear margin of ≥1 cm, negative sentinel lymph node biopsy (SLNB) without high-risk factors, irrespective of adjuvant RT. Tumor size ≥ 2 cm (HR:2.95; p = 0.024) and immunosuppression(HR:3.98; p = 0.001) were associated with high risk of nodal failure. Adjuvant RT was associated with significant reduction in regional failure (HR:0.36; p = 0.002). Distant metastases (DM) were infrequent in stage I (4/90) and stage II (4/34), compared to stage III (32/93). Adjuvant RT improvedRFS but did not influence MCC-SS and OS. CCI was a significant predictor of OS. ConclusionsAdjuvant RT improvedRFS, withoutimpact on MCC-SS and OS. Co-morbidity rather than RT influenced OS. Adjuvant RT may be avoided instage I patients with negative SLNB and no associated high-risk factors. Prophylactic RNI could be considered in stage II with high risk features, inspite of negative SLNB. Stage III patients benefited from adjuvant RNI, but no impact on prevention of DM.

Abstract 12337: Gender Specific Phenomapping and Outcomes in Ischemic Cardiomyopathy

Background: There is limited data on gender specific remodeling and its associated risk in patients with ischemic cardiomyopathy (ICM). We conducted gender based phenomapping analysis using Cardiac MRI (CMR) variables to identify novel sex-specific phenotypes in patients with ICM. We then assessed if these phenotypes were predictive of overall survival. Methods: Patients with ICM who underwent CMR between January 2002 and January 2017, were retrospectively evaluated . Cluster analysis was performed using nearest centroid sorting with nine variables: left ventricular end systolic volume index (LVESVi), mitral regurgitation severity on CMR (MR) , left atrial volume index (LAVi), right ventricular ejection fraction (RVEF), RV end diastolic volume index (RVEDVi) , LVEF, LV mass index (LVmassi), left atrial ejection fraction (LAEF), and myocardial scar burden (Scar). For each cluster size a Cox proportional hazards model was used to test if the phenotypes were predictive of survival. Results: Data was analyzed from 407 males and 119 females. The optimal number of clusters was four, based on the ability of the phenotypes to predict overall survival. Phenotype was a statistically significant predictor of overall survival in men (p=0.002) and women (p=0.016) after adjusting for age, body mass index, renal function, hypertension, diabetes, revascularization and mitral valve intervention. (Figure 1a) These distinct phenotypes predicted survival differently in men compared to women. Of interest, there were significant differences in the contribution of each CMR variable to predict the phenotype based on sex. (Figure 1b) In females, CMR MR and RVEF were stronger contributors to the phenotype. Conclusion: Significant differences in phenotypic signatures based on gender are present in patients with ICM. These distinct phenotypes predicted survival differently in men compared to women and emphasizes the importance of sex specific risk stratification in the ICM cohort.

Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer

Simple SummaryRadical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, it is necessary to carefully predict the prognosis before surgery and to determine the surgical indication. According to the results of the retrospective analysis of our 177 RC cases, we found the Hounsfield units of the psoas muscle at the third lumbar vertebral level to be a prognostic factor. Univariate and multivariate analyses revealed that age, sex, clinical T stage, and psoas muscle Hounsfield units were significant preoperative factors for overall survival. Furthermore, risk classification using these four factors was useful for predicting the prognosis of patients with RC.Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

Clinical Characteristics and Contemporary Outcomes of Acute Myeloid Leukemia Evolving from Chronic Myelomonocytic Leukemia

Clinical Characteristics and Contemporary Outcomes of Acute Myeloid Leukemia Evolving from Chronic Myelomonocytic Leukemia

Therapy Biosimulation Using the Cellworks Computational Omics Biology Model (CBM) Is Predictive of Individual Acute Myeloid Leukemia (AML) Patient Probability of Clinical Response (CR) and Overall Survival (OS): Mycare-023

Therapy Biosimulation Using the Cellworks Computational Omics Biology Model (CBM) Is Predictive of Individual Acute Myeloid Leukemia (AML) Patient Probability of Clinical Response (CR) and Overall Survival (OS): Mycare-023

Spontaneous apoptosis and BCL2 gene expression as predictors of early death and short overall survival in acute leukemia patients: a prospective, case cohort study

BackgroundSpontaneous apoptosis and expression of MCL1, BCL2, and BCL-XL may be useful prognostic markers in acute leukemia patients. The purpose of this study is to examine the prognosis in adult leukemia patients based on spontaneous apoptosis and anti-apoptosis gene expressions in circulating leukocytes.ResultsEarly, late, and total apoptosis were significantly increased in peripheral blood leukocytes from patients diagnosed with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) compared to controls and in cases of ALL versus AML (P < 0.001). Total apoptosis decreased significantly in AML and ALL patients who died early (ED); P = 0.001 and P = 0.002, respectively. Anti-apoptosis genes MCL1, BCL2, and BCL-XL were upregulated in 62.4%, 64.2%, and 62.4% of the acute leukemia patients, respectively. Among the AML patients, the up-regulation of BCL2 was paradoxically associated with increased apoptosis and low rates of ED. The expression levels of MCL1 and BCL-XL had no significant prognostic values; among patients diagnosed with non-acute promyelocytic leukemia (non-APL-AML), total spontaneous apoptosis, expression of BCL2, and performance status were independent predictors of overall survival (OS).ConclusionTotal spontaneous apoptosis and BCL2 gene expression may be valuable independent markers for OS in patients with non-APL-AML. Moreover, in ALL patients decreased levels of spontaneous apoptosis were associated with ED, although this was not a significant predictor of OS.

Fitness Assessment of Elderly Patients with AML and Outcomes

Background:AML is a complex disease that encompasses a huge variation of cytogenetic and mutational backgrounds, which is often complicated by age related functional deficits (Klepin et al. 2013). Given the expanding availability of reduced-intensity treatment options, patient fitness and frailty measures have become increasingly instrumental in the decision between a wide range of treatment options. Furthermore, studies have also demonstrated potential benefits in older patients who receive intensive induction chemotherapy (Julisson 2011), creating a need for additional assessments to identify suitable induction candidates. Some frailty-associated assessments including timed-up-and-go test (TUGT) and the short physical performance battery have been linked to outcomes but are not yet in broad clinical use (Kleplin et al. 2013, Khalaf et al. 2020). To minimize the burden of implementing new patient assessments, we evaluated the utility of commonly available clinical measures of frailty-associated factors including sit-to-stand test and iADL status in predicting patient outcomes.Methods:We performed a retrospective cohort study of elderly patients newly diagnosed with AML at Juravinski Cancer Center between Jan 2019 and Dec 2020. We examined a total of 44 patients aged 65+. The primary outcome was overall survival (OS). Significant risk factors were identified using the Cox proportional hazards model.Results:43 patients had sufficient data and were included in the analysis. The median age was 70 years (range 65-89), 53% were female and 47% were male. At the time of review, 21 patients were deceased (48.8%). The median survival time was 345 days. 26 patients received full induction treatment (7+3, FLAG-IDA, or Vyxeos), and 18 received conservative treatment (LDAC, azacytidine, or supportive care). The clinical wellness of the patients at diagnosis time was assessed by baseline clinical and laboratory findings. (Table 1) The Cox regression model was used to examine these variables in predicting overall survival (Figure 1). As expected, the ELN risk group was significantly correlated with OS (HR 2.94 95%CI [1.41-6.11]), along with laboratory measures of disease burden including blood blast count (HR 1.02 [1.00-1.03]), WBC, (HR 1.02 [1.01-1.03]) and ANC (HR 1.05 [1.02-1.08]).We then assessed the influence of patient fitness factors on OS. The HCT-CI score was used as an aggregate comorbidities measure. While typically used for post-SCT prognosis, we found that HCT-CI assessed at diagnosis time was a significant predictor of OS (HR 1.22[1.04-1.45]). When added to a multivariate Cox model including ELN and age, the HCT-CI independently predicted OS (p = 0.003) and improved prediction efficiency by the Akaike information criteria (115 vs 122). This corroborates earlier findings by Sorror et al. 2017, who showed incorporation of biochemical and AML-specific variables to HCT-CI yields improved prognostic value. Within the HCT-CI, the AST and cardiac disease scores were the most associated with OS (HR 1.03[1.00-1.05] and 2.27[1.09-4.76]). While clinical and laboratory assessments were readily available, functional assessments of frailty were scarce. Previously reported frailty measures such as KPS score or TUGT were not assessed at the study center. OT/PT routinely administer sit-to-stand or standing balance tests as a part of fall risk assessment. However, this data was only available for 18 patients (41.8%). Independent sit-to-stand was not detected as a significant OS predictor (HR 0.63[0.14-2.83]), possibly related to the very limited sample size. BMI was marginally predictive (HR 1.07[0.99 - 1.08]), but unlike HCT-CI it was not an independent predictor when combined with ELN. Patient age did not significantly predict OS.Conclusion:This single center retrospective study was aimed at examining the role of existing clinical or functional measures of fitness and frailty in predicting overall survival. HCT-CI and ELN were found to be the most predictive factors amongst the variables examined, suggesting that a morbidity index such as HCT-CI could provide prognostic utility. However, functional assessments of frailty were not readily completed, limiting the ability to evaluate their usefulness. A future larger prospective study focused on optimizing and incorporating routine functional assessments of frailty is needed to address this topic. [Display omitted] DisclosuresLeber: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TaiHo: Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Khalaf: Novartis: Honoraria; Paladin: Honoraria; Pfizer: Honoraria.

Development and Validation of a Novel Prognostic Model for Endometrial Cancer Based on Clinical Characteristics.

ObjectiveExisting prognostic models for endometrial cancer are short of facility and effective validation. In this study, we aim to develop and validate a novel prognostic model for endometrial cancer based on clinical characteristics.MethodsThe clinical data such as age, BMI (body mass index), FIGO stage, surgical approach, myometrial invasion, grade, lymph node metastasis, pathology and menopause status were collected for constructing and validating the prognostic model from The Cancer Genome Atlas (TCGA) and Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, respectively. COX regression and the least absolute shrinkage and selection operator (LASSO) COX were applied to identify the significant predictors of overall survival (OS) and construct the prognostic model. The discrimination, calibration, and clinical usefulness of the model were evaluated in both cohorts.ResultsThree hundred and sixty-seven and 286 EC patients were collected for training and validation cohort, respectively. A clinical prognostic model integrating six clinical variables including age, BMI, FIGO stage, surgical approach, myometrial invasion and grade was established. K-M analysis shows a significant difference between the low- and high-risk groups. The area under the receiver operating characteristic curve (AUC-ROC) was 0.775 (95% CI, 0.708 to 0.843) and 0.870 (95% CI, 0.758 to 0.982) for the training and validation cohorts which indicating reliable discrimination. The calibration curve revealed excellent predictive accuracy and the Hosmer–Lemeshow test also verified this. Decision curve analysis (DCA) for the prognostic model indicated that it would add more benefits than either the detect-all-patients scheme or the detect-none scheme. In addition, our model has a superior AUC comparing with any single factor as predicting OS.ConclusionOur predictive model offers a convenient and accurate tool for clinicians to estimate the prognosis of EC patients.

Sub-Acute Post-Treatment Dysphagia and Shortness of Breath Symptoms Associate With Worse Survival in Oropharyngeal Cancer

Post-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness of breath may empirically guide earlier detection of disease recurrence, their association with patient outcomes is less well studied, especially for HPV-positive disease. This study aimed to investigate the association between patient reported dysphagia and shortness of breath at 3-to-6 months following radiotherapy (RT) and overall survival (OS).Data were collected from oropharyngeal cancer patients that received RT with curative intent from 2015-2019. Included patients had self-reported scores for shortness of breath, choking/coughing ("choke"), and difficulty swallowing/chewing ("swallow"), which were surveyed via the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) questionnaire at 3-to-6 months after RT. Symptom severity was scored from 0-10. Significant predictors of OS were analyzed via Cox regression. Symptom scores were also discretized for Kaplan-Meier (KM) analysis, with more severe symptoms being 6+ for "swallow" and "choke" and 2+ for shortness of breath.Symptom scores were collected at 3-to-6 months from 470 patients. The majority (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable Cox regression (Table 1) showed significant associations between OS and MDASI scores for shortness of breath, "choke," and "swallow." Furthermore, a composite variable integrating scores of all three symptoms had the best predictive value for OS (c-index = 0.748). Symptom severity stratified patients based on OS for all three symptoms, with more severe symptoms predicting worse OS on KM analysis (P < 0.001 for all symptoms). On subset analysis more severe symptoms remained significantly associated with worse OS among HPV-positive patients (P < 0.01 for all symptoms).Quantitative early patient-reported measures of dysphagia and shortness of breath are significant predictors of OS in head and neck cancer, in particular for HPV-positive disease. Integrating quantitative symptom surveys into post-treatment surveillance may be beneficial for individualizing follow-up strategies.

Hospital-Based Registry Analysis of Staging Efficacy and Proposed Substaging for HPV Positive Oropharynx Cancers

The American Joint Committee on Cancer (AJCC) introduced the 8th edition staging for cancer in 2017, which provided separate staging for HPV+ oropharyngeal cancer (OPC). This update simplified staging with the intent of restoring prognostic discrimination between stages with regard to disease-specific survival. However, it also altered implications for treatment as many patients formerly classified as group stage I-IVA in the 7th edition, treated with either single or multimodality therapy including chemoradiation, were now classified as stage I. We used the National Cancer Database (NCDB) to study the efficacy of AJCC staging in a modern cohort of HPV+ OPC in the years prior to the introduction of AJCC 8th edition, and explore substaging of the AJCC 8th edition in order to provide better guidance for treatment.We queried the NCDB for patients with HPV+ OPC as their first primary cancer diagnosis, with known radiotherapy, surgery, and chemotherapy treatment status and without mortality within 90 days of surgery. Clinical T, N, and M stages per AJCC 7th edition were converted to AJCC 8th edition staging. Kaplan-Meier estimates were generated for overall survival (OS) at 5 years and compared using log-rank testing. Cox-proportional hazards models were generated to test for significant predictors of overall survival which were then used to generate substages for AJCC 8th edition stage I patients.A total of 8249 patients diagnosed from 2010-2016 met search criteria. Median age was 57 years (22-90). By AJCC 7th edition, 6% (470) of patients were group stage I, 10% (839) stage II, 23% (1913) stage III, 58% (4755) stage IVA, and 3% (272) stage IVB/C. A Cox-proportional hazards model including AJCC 7th edition T and N stage as covariates was generated using 5933 patients with clinical T1-2N0-2b staging, showing significant association of cT2 and cN2b status with OS (P = < 0.001, HR of 1.7 [95% CI 1.4-2.1] and 1.4 [95% CI 1.2-1.8] respectively). These results were used for substaging of AJCC 8th edition group stage I: cT1N0-2a were designated stage IA, cT2N0-2a and cT1N2b as stage IB, and cT2N2b as stage IIA. Using this substaging, log-rank testing between substages showed significant differences between the respective curves for OS at 5 years (P < 0.01 for all comparisons).Substaging of AJCC 8th edition group staging for HPV+ OPC provided significant hazard stratification for patients currently classified as group stage I, with subclassification by cT2 and cN2b (7th ed stage) showing significant association with OS at 5 years. Substaging by these factors not only maintains prognostic risk stratification, but also may provide better guidance in treatment decision making. For example, stage IA patients could be treated with either with surgery or radiation alone, stage IB with either single or multimodality therapy, and stage IIA and above would be treated with multimodality therapy. Further validation of this staging is warranted.

Assessment of Treatment Response and Re-Bleeding After Palliative Radiation Therapy for Bleeding Gastric Cancer: A Longitudinal Multicenter Prospective Observational Study

In the largest prospective study to date, we examined the effectiveness of palliative radiation therapy for bleeding gastric cancer, and the association of the biologically effective dose (BED) with survival, bleeding response, or re-bleeding.We recruited patients with incurable gastric cancer for whom palliative radiation therapy was planned. Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) response rate at four weeks. Response entailed all of the following criteria: 1) hemoglobin levels ≥ 8.0 g/dL, 2) seven consecutive days from enrollment to blood sampling without blood transfusion, and 3) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or reirradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. Response was assessed at 2, 4, and 8 weeks after enrollment; re-bleeding was assessed monthly during the 6-month follow-up. Sample size was designed with the probability of obtaining a 90% confidence interval (CI) ≤ ± 15% being set at 0.8, assuming a per-protocol (PP) response rate of 70% at 4 weeks.We enrolled 55 patients from 15 institutions. A median total radiation dose of 20 Gy (range, 8-45 Gy) was delivered in a median of five fractions. Of the 55 patients, 38 responded to treatment; of the 38 responders, 19 (50%) died and 12 (32%) experienced re-bleeding. The ITT response rates were 47%, 53% (95% CI, 39%-66%), and 49% at 2, 4, and 8 weeks, respectively. The PP response rates were 55%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Restricted mean response and re-bleeding time up to 8 months were 2.3 months and 0.8 months, respectively. The median overall survival was 3.8 months (median follow-up, 12.1 months). The multivariable Cox model showed that neither response (a time-dependent covariate) (hazard ratio [HR], 1.04; 95% CI, 0.44-2.48) nor BED (alpha/beta = 10) (HR, 0.98; 95% CI, 0.95-1.02) were significant predictors of overall survival. The multivariable Fine-Gray model showed that BED was not a significant predictor of response (subdistribution HR, 1.02; 95% CI, 0.99-1.06). The univariable Cox model on transition hazard from response to re-bleeding showed that BED was not significantly associated with re-bleeding (HR, 0.98; 95% CI, 0.92-1.04). Grade 1, 2, 3, and ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively.The PP bleeding response rate increased to 90% during the 8-week follow-up period. The frequent occurrence of death from shortly after enrollment lowered the ITT response rate and shortened the duration of response. BED was not significantly associated with survival, bleeding response, or re-bleeding.

90-Day Hospitalization as a Surrogate for Overall Survival in Hepatocellular Carcinoma (HCC) Patients Treated With Magnetic Resonance-Guided Liver Stereotactic Body Radiation Therapy: Results of a Single-Center Retrospective Study

With the increased utilization of stereotactic body radiation therapy (SBRT) for the management of hepatocellular carcinoma (HCC), it is important to have accurate prognostic factors for survival to guide treatment management decisions. Here, we examine 90-day hospitalization as a prognostic factor in addition to established staging systems including the albumin-bilirubin (ALBI) grade, Child-Pugh score, and Barcelona Clinic Liver Cancer (BCLC) stage.This retrospective single-institution study analyzed 95 patients with HCC treated with SBRT from August 2017 to September 2020. Overall survival (OS) rates were retrospectively analyzed from treatment completion date to death date or last follow-up. Patients were censored from further analysis if subsequent SBRT courses were administered. Patient characteristics, 90-day hospitalization, ALBI grade, Child-Pugh score, and BCLC liver stage were analyzed with the Cox proportional hazard model and log-rank test; any significant factors on univariate analysis were subsequently analyzed in the multivariate analysis.Median overall survival among the entire cohort was 67 months (range 0-38 months). Univariate predictors of overall survival included patient sex (P = 0.02), performance status (P = 0.03), Child-Pugh score (P = 0.003), ALBI grade (P < 0.0001), as well as 90-day hospitalization (P < 0.0001). However, 90-day hospitalization itself was associated with patient male gender (26.9% vs 7.1%; P = 0.03), performance status (P < 0.0001), Child-Pugh score (P = 0.003), ALBI grade (P = 0.003), and BCLC stage (P = 0.002). In the multivariate analysis, patient male sex (P = 0.02), ALBI grade 3 (P = 0.05), and 90-day hospitalization (P = 0.03) remained significant.90-day hospitalization is a significant predictor of overall survival among patients treated with SBRT for HCC. 90-day hospitalization could be used as an early endpoint in trials evaluating liver SBRT.

Biologically Active Volume of Disease (BaVD) Predicts for Survival in Metastatic Non-Small Cell Lung Cancer

Multiple randomized trials incorporating locally ablative therapy in oligometastatic non-small cell lung cancer (NSCLC) have used number of metastatic sites to identify which patient populations benefit from aggressive local therapy. In this study, we measure the amount of fluorodeoxyglucose (FDG) activity on positron emission tomography/computerized tomography (PET/CT) scans to quantify the biologically active volume of disease (BaVD) at diagnosis. We hypothesize that BaVD is a significant predictor of overall survival (OS) for NSCLC.We reviewed consecutive charts of metastatic NSCLC patients treated at our institution. All patients included had a PET/CT scan prior to starting any therapy. An oncology imaging informatics system was utilized to auto-contour individual PET/CT scans. A threshold SUV of 3 was selected a priori to auto-contour all FDG avid areas on each patient's pre-treatment PET/CT. SUV activity was measured in cubic centimeters (cc). Normal physiologic activity in expected organs including brain, heart, liver, spleen, genitourinary track, and gastrointestinal track was removed through auto-contouring and adjusted manually if needed. All plans were reviewed by a radiation oncologist to confirm FDG avid areas contoured only included areas of gross disease. Kaplan-Meier analysis evaluated overall survival (OS) based on volume of metastatic disease at diagnosis. Multivariate Cox regression (MVA) was performed accounting for age, histology, gender, race, smoking status, molecular mutations, presence of brain metastasis at diagnosis, number of metastatic sites (1-3, 4-5, > 5 sites), and type of systemic treatment received.A total of 43 patients were included. Median volume of disease using an SUV cutoff of ≥3 was 317 cc (range, 23-2476 cc). Median survival was worse for patients with ≥ 317 cc of disease compared to those < 317 cc, 17 mo vs 22 mo (P = 0.010). Volume of disease was found to be significant under univariate analysis (UVA) both when analyzed as a continuous (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.00-1.02, P < 0.001) and categorical variable with a cutoff of 317 cc (HR 3.27, 95% CI, 1.26-8.48, P = 0.013). On MVA, volume of disease remained a significant predictor of OS (HR 5.19, 95% CI 1.17-22.99, P = 0.030). Additional variables associated with OS included older age (HR 6.26, 95% CI 1.65-23.76, P = 0.007) and receipt of chemotherapy/immunotherapy (HR 20.51, 95% CI 1.98-212.09, P = 0.011) vs targeted therapy. While number of metastatic sites was significant under UVA (HR 8.45, 95% CI 1.10-64.72, P = 0.040), it was not significant under MVA (HR 5.23, 95% CI 0.56-49.91, P = 0.164) CONCLUSION: To our knowledge, this is one of the first studies to demonstrate the significance of BaVD as an important predictive factor of OS in metastatic NSCLC. Our results also suggest BaVD may be a stronger correlate to OS compared to number of metastatic sites. Further work is needed to better understand the impact BaVD on OS.

Association Between Radiation Heart Dose and Overall Survival in Lung Stereotactic Body Radiation Therapy

<h3>Purpose/Objective(s)</h3> To determine if heart radiation dose and location affects overall survival (OS) in patients treated with Stereotactic Body Radiation Therapy (SBRT) to the lung. <h3>Materials/Methods</h3> Patients treated with SBRT to the lung at a single institution were identified. Pertinent information regarding patient characteristics, treatment delivered, and patient outcomes were obtained from a prospectively maintained cancer registry and the medical record. Radiation treatment information was obtained from the treatment planning system. Radiation dose in each voxel was extracted from the treatment planning system, mapped on anatomical organs, and converted to 2 Gy equivalent dose using linear quadratic model. The V% dosimetric variable, a percentage of volume receiving the dose ‘D' or greater, was used in the statistical analysis. Multivariate Cox regression analysis with Akaike Information Criterion (AIC) was used to determine which patient specific variables were predictive for OS. All predictive variables were further used in the Cox model with an addition of dosimetric variables for the heart. We examined V%_D variables for the whole heart, heart digitally subdivided into four segments (right-superior, left-superior, right-inferior, left-inferior), and heart digitally subdivided into 64 segments. <h3>Results</h3> 197 patients treated for lung lesions with SBRT were selected for this study. 135 patients were treated for primary lung cancer (117 stage I, 18 stage II) and 42 patients were treated for lung metastasis from other primary sites. There were 79 patients with lung adenocarcinoma, 38 with lung squamous cell carcinoma (SCC), and 62 patients with other histologies. Dose prescriptions were 50 Gy in 5 fractions (35%) and 48 Gy in 4 fractions (65%). The reference patient was 72.2 years old, with stage I, primary lung adenocarcinoma. Mean OS was 76.8 months and mean follow up was 40 months (2 – 230). Patient age (HR = 1.08/year, <i>P</i> < 0.01), histology (HR = 2.8 for SCC, <i>P</i> < 0.01) and stage (HR = 3.5 for stage II primary lung cancer, <i>P</i> < 0.01) were predictive for OS. Patients with right lung disease had longer OS than patients with left lung disease (HR = 0.6, <i>P</i> = 0.03). Whole heart DVH analysis did not reveal statistically significant predictors for OS. A DVH analysis of the heart divided into four segments suggested that low doses in the inferior segments of the heart decreased OS (V%_2 Gy, HR = 1.007/1%, <i>P</i> = 0.02). Maximum dose in the right-inferior portion of the heart was also predictive for OS (HR = 1.02/Gy, <i>P</i> = 0.02). A more detailed analysis of 3D dose distributions in the heart, using a digital subdivision of the heart into 64 segments, confirmed that low doses to the inferior part of the heart decreased OS (<i>P</i> = 0.01). <h3>Conclusion</h3> Low doses to the inferior portion of the heart may be associated with reduced OS in patients treated with SBRT to the lung. Age, histology and stage were associated with OS.

Radiation Plus Anti-PD-1 Therapy for NSCLC Brain Metastases: A Retrospective Study.

BackgroundRadiation therapy (RT) is the mainstay of brain metastases (BMs), and anti-PD-1 blockade has led to intracranial responses in non-small cell lung carcinoma (NSCLC) patients with BMs.ObjectiveThis study aimed to evaluate the efficacy and safety of adding anti-PD-1 blockade to RT in the management of NSCLC patients with BM in terms of survival outcome.Materials and MethodsWe retrospectively reviewed 70 NSCLC patients with BMs who were treated with whole brain radiation therapy (WBRT) between January 2016 and January 2021. Of the 70 patients, 29 additionally received anti-PD-1 therapy within 30 days of WBRT initiation. Baseline characteristics of the patients and efficacy outcomes such as progression-free survival (PFS) and overall survival (OS) were statistically compared using SPSS v26. Results were obtained using the Chi-square test/Fisher exact test, t-test, Kaplan-Meier, and Cox regression survival analyses.ResultsThe median survival for the entire cohort was 24 months (95% CI, 19.5–28.5). The median survival times for WBRT alone and WBRT plus anti-PD-1 therapy cohorts were 20 months (95% CI, 11.6–28.3) and 27 months (95% CI, 19.5–28.5), respectively (p=0.035). There was no statistical difference in PFS for the treatment cohorts (median PFS for WBRT alone: 7 months vs. 12 months for WBRT plus anti-PD-1, p=0.247). In EGFR wild-type subgroup (n=31), both PFS (p=0.037) and OS (p=0.012) were significantly improved. Only the treatment group (WBRT plus anti-PD-1) was a significant predictor of OS on univariate and multivariate analyses (p=0.040). There were no significant differences in adverse events among the treatment groups.ConclusionsNSCLC patients with BM receiving additional anti-PD-1 therapy may derive better OS than WBRT alone without any increase in adverse events. Prospective well-designed studies are warranted to validate and elucidate the additive effects of the two modalities in this group of patients.

A systematic review of the current management approaches in leiomyosarcoma of inferior vena cava-Results from analysis of 118 cases.

Primary intravenous leiomyosarcomas are rare vascular tumors with aggressive disease biology. The diagnosis and management have been challenging as little data exist from large databases. A literature search was done to identify all cases of primary leiomyosarcomas in the last five years. Clinicopathological features and management strategies were evaluated. The median age was 53 years, predominantly females (2.5:1), presenting as metastases in up to 12.1% cases. Most tumors were locally advanced with a median size of 10cm. Inferior vena cava involvement from renal veins to infrahepatic veins remains the most frequent site (57.1%cases) while nearly half (52.8%) proceeded for surgery without histological proof. Most patients could undergo upfront resection (88.0%) with few patients receiving neoadjuvant chemotherapy (4.3%) or neoadjuvant radiotherapy (2.2%). Significant multivisceral resections included right nephrectomy (41.3%), liver resection (25.7%) and left nephrectomy (2.2%). Most patients (91.8%) needed an inferior vena cava graft placement with remarkable microscopically negative margins (85.5% cases). Doxorubicin and ifosfamide were the most frequently used combination chemotherapy regimens in both pre and postoperative settings with partial responses. The median overall and disease free survival among operated patients was 60 months and 28 months respectively. In multivariate analysis large tumor, extensive inferior vena cava involvement, and need for adjuvant chemotherapy appeared significant predictors for overall survival. Aggressive upfront surgical resection with clear margin remains the key for long-term survival. Doxorubicin-based regimens were preferred as neoadjuvant chemotherapy while adjuvant treatment with chemotherapy, radiotherapy, or both may be considered in high-risk patients.

Metabolic active tumour volume quantified on [18F]FDG PET/CT further stratifies TNM stage IV non-small cell lung cancer patients.

This study aimed to assess whether the whole body metabolic active tumour volume (MTVWB), quantified on staging [18F]FDG PET/CT, could further stratify stage IV non-small cell lung cancer (NSCLC) patients. A group of 160 stage IV NSCLC patients, submitted to staging [18F]FDG PET/CT between July 2010 and May 2020, were retrospectively evaluated. MTVWB was quantified. Univariate and multivariate Cox regressions were carried out to assess correlation with overall survival (OS). C-statistic was used to test predictive power. Kaplan-Meier survival curves with Log-Rank tests were performed to compute statistical differences between strata from dichotomized variables and to calculate the estimated mean survival times (EMST). Survival rates at 1 and 5 years were calculated. MTVWB was a statistically significant predictor of OS on univariate (p < 0.0001) and multivariate analyses (p < 0.0001). The multivariate model with MTVWB (Cindex ± SE = 0.657 ± 0.024) worked significantly better as an OS predictor than the cTNM model (Cindex ± SE = 0.544 ± 0.028) (p = 0.003). An EMST of 29.207 ± 3.627(95% CI 22.099-36.316) months and an EMST of 10.904 ± 1.171(95% CI 8.609-13.199) months (Log-Rank p < 0.0001) were determined for patients with MTVWB < 104.3 and MTVWB ≥ 104.3, respectively. In subsamples of stage IVA (cut-off point = 114.5) and IVB patients (cut-off point = 191.1), statistically significant differences between EMST were also reported, with p-values of 0.0001 and 0.0002, respectively. In both substages and in the entire cohort, patients with MTVWB ≥ cut-off points had lower EMST and survival rates. Baseline MTVWB, measured on staging [18F]FDG PET/CT, further stratifies stage IV NSCLC patients. This parameter is an independent predictor of OS and provides valuable prognostic information over the 8th edition of cTNM staging.

Lymph Node Dissections for T3T4 Stage Penile Cancer Patients Without Preoperatively Detectable Lymph Node Metastasis Bring More Survival Benefits: A Propensity Matching Analysis.

Background and AimsThe current guidelines for the treatment of penile cancer patients with clinically non-invasive normal inguinal lymph nodes are still broad, so the purpose of this study is to determine which patients are suitable for lymph node dissection (LND).MethodsHistologically confirmed penile cancer patients (primary site labeled as C60.9-Penis) from 2004 to 2016 in the Surveillance, Epidemiology, and Results database were included in this analysis. Univariate and multivariate Cox regression analyses were applied to determine an overall estimate of LND on overall survival and cancer-specific survival. A 1:1 propensity matching analysis (PSM) was applied to enroll balanced baseline cohort, and further Kaplan–Meier (KM) survival analysis was used to get more reliable results.ResultsOut of 4,458 histologically confirmed penile cancer patients with complete follow-up information, 1,052 patients were finally enrolled in this analysis. Age, pathological grade, T stage, and LND were identified as significant predictors for overall survival (OS) in the univariate Cox analysis. In the multivariate Cox regression, age, pathological grade, T stage, and LND were found significant. The same results were also found in the univariate and multivariate Cox regression analyses for cancer-specific survival (CSS). After the successful PSM, further KM analysis revealed that LND could bring significant OS and CSS benefits for T3T4 patients without lymph node metastasis.ConclusionLymph node dissection may bring survival benefits for penile cancer patients without preoperatively detectable lymph node metastasis, especially for T3T4 stage patients. Further randomized control trial is needed.

Prognostic Significance of Prognostic Nutritional Index in Esophageal Squamous Cell Carcinoma Patients Undergoing Radical Radiotherapy: A Propensity Score Matching Analysis

Background The preoperative prognostic nutritional index (PNI) is associated with postoperative complications and long-term survival of various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting survival in ESCC patients undergoing radical radiotherapy. Methods We retrospectively reviewed 354 ESCC patients undergoing radical radiotherapy. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value. The association between PNI and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching was applied to balance the baseline characteristics. Results PNI was positively correlated with hemoglobin (P < 0.001) and prealbumin (P < 0.001). The optimal cutoff value of PNI was set at 50.5. The 5-year overall survival (OS) in low PNI group and high PNI group were 20.8% and 34.0%, respectively (P < 0.001). The 5-year progression free survival in patients with low PNI and high PNI were 15.2% and 28.5%, respectively (P = 0.001). Multivariate analysis showed that PNI was a significant predictor for OS (P = 0.038). In the PSM analysis, PNI still remained an independent predictor for OS (P = 0.015). Conclusions The PNI is a significant and independent predictor for OS of ESCC patients undergoing radical radiotherapy.

Significance of intra/post-operative prognostic scoring system in hepatectomy for colorectal liver metastases.

AimThe prognostic impact of postoperative systemic inflammatory response using an intra/post‐operative prognostic scoring system in patients with colorectal liver metastases (CRLM) after hepatic resection had never been investigated previously.MethodsIn total, 149 patients who underwent hepatic resection for CRLM were analyzed retrospectively. Intra/post‐operative prognostic scoring was performed using the postoperative modified Glasgow Prognostic Score (mGPS) at the first visit, after discharge, or a month after surgery during hospitalization. We investigated the association between clinicopathologic variables and disease‐free survival or overall survival by univariate and multivariate analyses.ResultsThe median evaluation period of postoperative mGPS was 30 (26‐36) days after hepatectomy. Seventy‐one patients (48%) were classified as postoperative day 30 mGPS 1 or 2. In multivariate analysis, an extrahepatic lesion (P = .02), multiple tumors (P = .05), and postoperative day 30 mGPS 1 or 2 (P < .01) were independent and significant predictors of disease‐free survival. Moreover, extrahepatic lesion (P = .04), and postoperative day 30 mGPS 1 or 2 (P = .02) were independent and significant predictors for overall survival. Patients with postoperative day 30 mGPS 1 or 2 had significantly more advanced tumors, more invasive surgery, and more chances of infectious postoperative complications than those with postoperative day 30 mGPS 0.ConclusionPostoperative systemic inflammatory response, as evidenced by intra/post‐operative prognostic scoring system using postoperative day 30 mGPS, was a strong predictor for outcomes in patients who underwent liver resection for CRLM.