Validation of a clinical score (CS) for patients (pts) with well-differentiated neuroendocrine tumors (WD NETs) under consideration for peptide receptor radionuclide therapy (PRRT) with Lu 177 dotatate.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4109-4109
Author(s):  
Satya Das ◽  
Aman Chauhan ◽  
Liping Du ◽  
Katharine Thomas ◽  
Aasems Jacob ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Proportional Hazards ◽  
Medical Center ◽  
Cox Proportional Hazards ◽  
Secondary Outcome ◽  
Unknown Primary ◽  
Cancer Center ◽  
Tumor Type ◽  
Primary Tumor Site ◽  
Point Increase

4109 Background: Questions remain regarding when to sequence PRRT and how to categorize pts being considered for the treatment (tx). We previously developed a CS (comprised of 5 categories: available non-PRRT tx for tumor type, prior systemic tx, pt symptoms, tumor burden in critical organs and peritoneal carcinomatosis presence) at Vanderbilt Ingram Cancer Center (VICC) for pts being considered for PRRT to help answer these questions and demonstrated the score to be associated with progression-free survival (PFS) in pts receiving PRRT. Herein, we present the performance of the CS in a validation cohort (VC) and combined cohort (CC). Methods: Our original cohort (OC) included pts with progressive WD NETs (N = 122) under consideration for PRRT between 3/1/2016-3/17/2020 at VICC while our VC included pts under consideration for PRRT (N = 126) between 1/25/2017-11/18/2019 at Ochsner Medical Center (OMC) (N = 51), Markey Cancer Center (MCC) (N = 51) and Rush Medical Center (RMC) (N = 24). All pts in the OC were prospectively scored while pts in the VC were scored retrospectively, with the CS-assigning investigator blinded to patient outcomes. The primary outcome PFS, was estimated by the Kaplan‐Meier method; a Cox proportional‐hazards model adjusting for primary tumor site, tumor grade and number of PRRT doses administered (0, 1-2 or 3-4) was used to analyze effect of CS. Overall survival (OS) was a key secondary outcome. Results: In our VC, on multivariable (MV) analysis, for each 2-point increase in CS, the hazard ratio (HR) for PFS was 2.58 (95% confidence interval (CI) 1.62-4.11). On MV analysis, for each 2-point increase in CS, the HR for OS was 3.89 (95% CI 1.8-4.83). We combined the OC and VC for this analysis in order to increase the predictive power of our originally developed Cox proportional-hazards models. In our CC, of the 248 total pts, median pt age, CS and number of prior tx were 63.3 years, 4 (range 0-8) and 1 (range 0-7), respectively. The most represented primary tumor sites were small intestinal (N = 136), pancreatic (N = 58), unknown primary (N = 26) and lung (N = 14). A total of 140, 82 and 26 pts received 3-4, 0 or 1-2 doses of PRRT, respectively. On MV analysis, for each 2-point increase in CS, the HR for PFS was 2.52 (95% CI 1.90-3.35). On MV analysis, for each 2-point increase in CS, the HR for OS was 3.48 (95% CI 2.33-5.18). No interaction between PRRT doses administered and CS was observed. Conclusions: Increases in CS were strongly associated with worsening PFS and OS in our VC and CC, validating findings from our OC. Although we cannot determine whether the CS specifically predicts PRRT response or is prognostic based upon these data, it is the first presented clinical metric which can categorize pts with WD NETs under consideration for PRRT and estimate anticipated benefit from PRRT for pts.

A clinical score (CS) for patients with well-differentiated neuroendocrine tumors (WD NETs) under consideration for peptide receptor radionuclide therapy (PRRT) with Lu 177-dotatate.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 363-363
Author(s):  
Satya Das ◽  
Liping Du ◽  
Aimee Schad ◽  
Shikha Jain ◽  
Aaron Jessop ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Primary Tumor ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards Model ◽  
Tumor Board ◽  
Cancer Center ◽  
Tumor Type ◽  
Primary Tumor Site ◽  
Point Increase ◽  
Systemic Treatments

363 Background: Despite the benefit of PRRT for patients with WD NETs, questions remain regarding sequencing and optimal patient selection for the treatment. We developed a CS at Vanderbilt Ingram Cancer Center (VICC) that we hoped would predict outcomes for patients with WD NETs receiving PRRT. Methods: Patients with progressive WD NETs (N = 146) under consideration for PRRT with Lu 177-dotatate between 3/1/2016-3/17/2020 at VICC (N = 122) and Rush Medical Center (RMC) (N = 24) were scored. The CS included 5 categories: available non-PRRT treatments for tumor type, prior systemic treatments, patient symptoms, tumor burden in critical organs and peritoneal carcinomatosis presence. All categories were scored from 0-2 except the peritoneal carcinomatosis category which was scored from 0-1; scoring criteria were determined by the VICC NET tumor board. All patients at VICC were prospectively scored, while patients from RMC were scored retrospectively with the investigator blinded to patient outcomes. The primary outcome, progression-free survival (PFS) was estimated by the Kaplan‐Meier method; a Cox proportional‐hazards model adjusting primary tumor site, tumor grade and number of PRRT doses administered (none, 1-2 doses or 3-4 doses) was used to analyze effect of CS. Results: Median patient age was 62.7 while median CS was 5 (range 1-8); the most common primary tumor sites were small intestinal (N = 81) and pancreatic (N = 37). A total of 101 patients and 31 patients received 3-4 doses and no doses of PRRT, respectively. On multivariable analysis, in patients treated with 3-4 doses of PRRT, for each 2-point increase in CS, the estimated hazard ratio (HR) for PFS was 3.26 (95% confidence interval (CI) 2.05-5.19). On multivariable analysis, in patients who received no doses of PRRT, for each 2-point increase in CS, the estimated HR for PFS was 1.37 (95% CI .78-2.41). Conclusions: Among patients treated with 3-4 doses PRRT, those with lower CS had better PFS with the treatment compared to patients with higher CS. This PFS difference, based upon CS, was not observed in patients who did not receive PRRT, suggesting the predictive utility of the CS for patients with WD NETs receiving PRRT with Lu 177-dotatate. Though the CS needs to be validated, it is the first of its kind reported.

Predictors of overall survival (OS) in patients (pts) with melanoma brain metastasis (MBM) in the modern era.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9540-9540
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Alicia Bea Davies ◽  
Elizabeth Sirmans ◽  
Chantal M Saberian ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Proportional Hazards ◽  
Statistical Tests ◽  
Univariate Analysis ◽  
Elevated Serum ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Significance Level

9540 Background: The management and OS of pts with metastatic melanoma have improved due to new systemic therapies. However, relatively little is known about the use of these treatments (tx) and their association with OS in pts with MBMs. We reviewed a large cohort of MBM pts to assess how pt demographics, disease characteristics, and MBM tx impact OS in the current era. Methods: Under an institutional review board-approved protocol, retrospective data were curated and analyzed from pts diagnosed with, and received tx for, MBM from 2014 to 2018 at the MD Anderson Cancer Center (MDA). Pts diagnosed with uveal or mucosal melanoma or other cancers were excluded. Pt demographics; timing and features of initial melanoma dx; timing and features of initial MBM dx; prior, initial and subsequent tx; and OS were collected. OS was determined from MBM dx to last clinical follow-up (FU). Pts alive at last FU were censored. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable (MV) associations of OS with variables of interest were investigated with Cox proportional hazards models. Initial treatment of MBM was assessed as a time-varying covariate. All statistical tests used a significance level of 5%. Results: A total of 401 MBM pts were identified. The median age at MBM dx was 61; 67% were male and 46% had a BRAF V600 mutation. At MBM diagnosis dx, most (70%) pts were asymptomatic; 70% had concurrent uncontrolled extracranial disease; 36% had elevated serum LDH. Prior tx included immunotherapy (IMT) for 39% and targeted therapy (TTX) for 17%. The median number of MBMs was 2; 31% had > 3 MBMs. Median largest MBM diameter was 1.0 cm, 9% had MBM > 3.0 cm, and 5% had concurrent leptomeningeal disease (LMD). Tx received after MBM dx included stereotactic radiosurgery (SRS; 53% as initial tx for MBM, 67% at any time after MBM dx), whole brain radiation therapy (WBRT; 16%, 35%), craniotomy (12%, 19%), IMT (37%, 74%), and/or TTX (22%, 40%). 31% received steroids during initial MBM tx. At a median FU of 13.4 (0.0 - 82.8) months (mos), the median OS was 15.1 mos, and 1- and 2-year OS rates were 56% and 40%. Notably, gender, time to MBM dx, and BRAF status were not associated with OS (univariate analysis). On MV analysis, clinical features associated with worse OS included increased age, increased primary tumor thickness, elevated LDH, > 3 MBMs, +LMD, +symptoms, and prior tx with IMT. Among tx used at any time after MBM dx, WBRT (HR 1.9, 95% CI 1.5-2.5) was associated with worse OS; SRS (HR 0.7, 95% CI 0.5-0.8) and IMT (HR 0.6, 95% CI 0.5-0.8) were associated with improved OS. Conclusions: In one of the largest cohorts of MBM pts described to date, OS has improved in MBM pts in the current era. Prognostic factors for OS include pt age, primary tumor and MBM features, prior tx, and tx for MBM. Additional analyses to assess the interaction of tx, disease features, and OS will be presented.

scholarly journals A novel nomogram to predict the overall survival in esthesinoeroblastoma

2020 ◽  
Author(s):  
Lijie Jiang ◽  
Tengjiao Lin ◽  
Yu Zhang ◽  
Wenxiang Gao ◽  
Jie Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Validation Cohort ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
P Value ◽  
Training Cohort

Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

scholarly journals Nephrectomy Delay of More than 10 Weeks from Diagnosis Is Associated with Decreased Overall Survival in pT3 RCC

2021 ◽  
Vol 8 (2) ◽  
pp. 27-33
Author(s):  
Jiping Zeng ◽  
Ken Batai ◽  
Benjamin Lee
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Logistic Regression ◽  
Proportional Hazards ◽  
Surgical Margin ◽  
Cox Proportional Hazards ◽  
Cancer Center ◽  
Integrated Network ◽  
Factors Associated ◽  
The Impact

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary out-come was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson–Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15–1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson–Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04–1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.

Epidemiology, Risk Factors, and Outcomes After Early Posttransplant Clostridiodes difficile Infection in Renal Transplant Recipients

2019 ◽  
Vol 53 (10) ◽  
pp. 1020-1025
Author(s):  
Margaret R. Jorgenson ◽  
Jillian L. Descourouez ◽  
Dou-Yan Yang ◽  
Glen E. Leverson ◽  
Christopher M. Saddler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Transplant ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Female Gender ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Secondary Outcome ◽  
Induction Agent ◽  
Renal Transplant Recipients

Background: Modifiable risk-factors associated with Clostridioides difficile infection (CDI) in renal-transplant (RTX) have not been clearly established and peri-transplant risk has not been described. Objective: Evaluate epidemiology, risk-factors and outcomes after CDI occurring in the first 90 days after RTX (CDI-90).Methods: Observational cohort study/survival analysis of adult RTX recipients from 1/1/2012-12/31/2015. Primary outcome was CDI-90 incidence/risk-factors. Secondary outcome was evaluation of post-90 day transplant outcomes. Results: 982 patients met inclusion criteria; 46 with CDI-90 and 936 without (comparator). CDI incidence in the total population was 4.7% at 90 days, 6.3% at 1 year, and 6.4% at 3 years. Incidence of CDI-90 was 5%; time to diagnosis was 19.4±25 days (median 7). Risk-factors for CDI-90 were alemtuzumab induction (Hazard ratio [HR] 1.5, 95% CI(1.1-2.0), p = 0.005) and age at transplant (HR 1.007/year, 95% CI (1.002-1.012), p= 0.007). However, risk-factors for CDI at any time were different; donation-after-circulatory-death (DCD) donor (HR 2.5 95% CI (1.3-4.9), p = 0.008) and female gender (HR 1.6 95% CI (1.0-2.7), p = 0.049). On Kaplan-Meier, CDI-90 appeared to have an impact on patient/graft survival, however when analyzed in a multivariable stepwise Cox proportional hazards model, only age was significantly associated with survival ( p = 0.002). Conclusion and Relevance: Incidence of CDI-90 is low, mostly occurring in the first post-operative month. Risk-factors vary temporally based on time from transplant. In the early post-op period induction agent and age at transplant are significant, but not after. Associations between CDI and negative graft outcomes appear to be largely driven by age. Future studies validating these risk-factors as well as targeted prophylaxis strategies and their effect on long term graft outcomes and the host microbiome are needed.

scholarly journals Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew T. Carr ◽  
Camille J. Hochheimer ◽  
Andrew K. Rock ◽  
Alper Dincer ◽  
Lakshmi Ravindra ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Medical Center ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Individual Characteristic ◽  
Prior History ◽  
Central Nervous System Tumor ◽  
Medical Conditions ◽  
Characteristic Analysis ◽  
History Of

AbstractGlioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24–5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09–3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95–5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02–4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11–3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses.

scholarly journals Sodium Fluctuations and Mortality in a General Hospitalized Population

2019 ◽  
Vol 44 (4) ◽  
pp. 604-614 ◽  
Author(s):  
Gianmarco Lombardi ◽  
Pietro Manuel Ferraro ◽  
Luca Calvaruso ◽  
Alessandro Naticchia ◽  
Silvia D’Alonzo ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Hospital Admission ◽  
Hospital Stay ◽  
Proportional Hazards ◽  
Medical Center ◽  
Cerebrovascular Diseases ◽  
Linear Increase ◽  
Cox Proportional Hazards ◽  
Hospital Death ◽  
Cox Proportional Hazards Models

Background/Aims: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. Methods: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. Results: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend <0.001) irrespective of severity of dysnatremia (HR 2.34, 95% CI 1.55, 3.54, p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). Conclusions: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.

scholarly journals Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rachel Howard ◽  
Peter A. Kanetsky ◽  
Kathleen M. Egan
Keyword(s):  
Prognostic Value ◽  
Clinical Characteristics ◽  
Proportional Hazards ◽  
Area Under The Curve ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cancer Center ◽  
Lymphocyte Ratio ◽  
Patient Subgroups

AbstractIn cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple “high-risk” demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.

Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide.

1997 ◽  
Vol 15 (6) ◽  
pp. 2385-2393 ◽  
Author(s):  
J D Hainsworth ◽  
J B Erland ◽  
L A Kalman ◽  
M T Schreeder ◽  
F A Greco
Keyword(s):  
Primary Tumor ◽  
Site Response ◽  
Response Rates ◽  
Unknown Primary ◽  
Tumor Site ◽  
Unknown Primary Tumor ◽  
Primary Tumor Site ◽  
Carcinoma Of Unknown Primary ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated

PURPOSE To evaluate the efficacy and toxicity of a novel chemotherapy combination that includes paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of patients with carcinoma of unknown primary tumor site. PATIENTS AND METHODS Fifty-five patients with carcinoma of unknown primary tumor site were treated with the following regimen, administered every 21 days: paclitaxel 200 mg/m2 by 1-hour intravenous (I.V.) infusion on day 1, carboplatin at an estimated area under the concentration-time curve (AUC) of 6.0 on day 1, and etoposide 50 mg alternated with 100 mg orally on days 1 through 10. Responding patients received a total of four courses of treatment. The following histologies were included: adenocarcinoma, 30 patients; poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA), 21; poorly differentiated neuroendocrine carcinoma, three; and squamous carcinoma, one. RESULTS Twenty-five of 53 assessable patients (47%; 95% confidence interval [CI], 33% to 61%) had major objective responses to treatment (seven complete responses). Response rates were similar in patients with adenocarcinoma versus PDC (45% and 48%, respectively). The actuarial median survival time for the entire group was 13.4 months. The regimen was well tolerated, with only seven hospitalizations for treatment of neutropenia and fever (4% of courses) and no treatment-related deaths. CONCLUSION The combination of paclitaxel, carboplatin, and extended-schedule etoposide is highly active and well tolerated in patients with carcinoma of unknown primary tumor site. Response rates and survival in this multicenter community-based trial compare favorably with all previously studied empiric regimens. In addition, this regimen is substantially less toxic and easier to administer than the cisplatin-based regimens previously used in this setting. If this level of efficacy is confirmed, this treatment should be considered standard first-line therapy in patients with carcinoma of unknown primary tumor site.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center

2014 ◽  
Vol 14 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Dima Suki ◽  
Rami Khoury Abdulla ◽  
Minming Ding ◽  
Soumen Khatua ◽  
Raymond Sawaya
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Tumor Type ◽  
Primary Cancer ◽  
Extracranial Metastases ◽  
The Brain

Object Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Methods Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Results Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months). Conclusions The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

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