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Cancer of Unknown Primary in Adolescents and Young Adults: Clinicopathological Features, Prognostic Factors and Survival Outcomes. - PloS one
Cancer in adolescents and young adults (AYAs) (15-39 years) is increasingly recognized as a distinct clinical and biological entity. Cancer of unknown primary (CUP), a disease traditionally presenting in older adults with a median age of 65 years, poses several challenges when diagnosed in AYA patients. This study describes clinicopathological features, outcomes and challenges in caring for AYA-CUP patients.A retrospective review of 47 AYAs diagnosed with CUP at MD Anderson Cancer Center (6/2006-6/2013) was performed. Patients with favorable CUP subsets treated as per site-specific recommendations were excluded. Demographics, imaging, pathology and treatment data was collected using a prospectively maintained CUP database. Kaplan-Meier product limit method and log-rank test were used to estimate and compare overall survival. The cox-proportional model was used for multivariate analyses.Median age was 35 years (range 19-39). All patients underwent comprehensive workup. Adenocarcinoma was the predominant histology (70%). A median of 9 immunostains (range 2-29) were performed. The most common putative primary was biliary tract based on clinicopathological parameters as well as gene profiling. Patients presented with a median of 2 metastatic sites [lymph node (60%), lung (47%), liver (38%) and bone (34%)]. Most commonly used systemic chemotherapies included gemcitabine, fluorouracil, taxanes and platinum agents. Median overall survival for the entire cohort was 10.0 (95% confidence interval (CI): 6.7-15.4) months. On multivariate analyses, elevated lactate dehydrogenase (Hazard ratio (HR) 3.66; 95%CI 1.52-8.82; P = 0.004), â‰¥3 metastatic sites (HR 5.34; 95%CI 1.19-23.9; P = 0.029), and tissue of origin not tested (HR 3.4; 95%CI 1.44-8.06; P = 0.005) were associated with poor overall survival. Culine's CUP prognostic model (lactate dehydrogenase, performance status, liver metastases) was validated in this cohort (median overall survival: good-risk 25.2 months vs. poor-risk 6.1 months).AYA-CUP is associated with a poor prognosis. In the current "-omics" era collaborative research efforts towards understanding tumor biology and therapeutic targets in AYA-CUP is an unmet need, necessary for improving outcomes in young CUP patients.
Metastatic Gastroesophageal Adenocarcinoma Patients Treated with Systemic Therapy Followed by Consolidative Local Therapy: A Nomogram Associated with Long-Term Survivors. - Oncology
Patients with metastatic gastroesophageal adenocarcinoma (MGEAC) have a poor but heterogeneous clinical course. Some patients have an unusually favorable outcome. We sought to identify clinical variables associated with more favorable outcomes.Of 246 patients with MGEAC, we identified 64 who received systemic therapy and eventually received local consolidation therapy. Univariate and multivariate Cox regression models were used, and a nomogram was developed.Of these 64 patients, 61% had received consolidation chemoradiation (CRT) with doses of 50-55 Gy and 78% did not undergo surgery. The median follow-up time of survivors was 3.9 years, and the median overall survival (OS) from CRT start was 1.5 years (95% CI, 1.2-2.2). Surgery (as local consolidation) was an independent prognosticator for longer OS in the multivariate analysis (p = 0.02). The 5-year OS rate was 25% (SE = 6%). The contributors to the nomogram were longer duration of systemic therapy before CRT and the type of local therapy.Our data suggest that a subset of patients with MGEAC have an excellent prognosis (OS >5 years). However, these patients need to be identified during their clinical course so that local consolidation (CRT, surgery, or both) may be offered.Â© 2016 S. Karger AG, Basel.
The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation. - Oncology
Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established.We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or
Initial Standardized Uptake Value of Positron Emission Tomography Influences the Prognosis of Patients with Localized Gastric Adenocarcinoma Treated Preoperatively. - Oncology
In patients with localized gastric adenocarcinoma (LGAC) who receive preoperative therapy, tools to predict response or prognosticate outcome before therapy are lacking. We used initial standardized uptake value (iSUV) of positron emission tomography (PET) to evaluate its association with overall survival (OS).We identified 60 patients with confirmed LGAC who were treated with preoperative chemoradiation and had a baseline PET in addition to other routine staging. Fisher's exact test and Wilcoxon's rank sum test were used to determine the association between iSUV and other variables, and the log-rank test and Cox proportional hazards model were used for survival analysis.The median iSUV was 6 (range, 0-28). The presence of signet ring cells in pretreatment biopsies correlated highly with low iSUV (â‰¤ 6; p = 0.0017). Patients with a high iSUV (> 6) had a longer OS compared to those with a low iSUV (â‰¤ 6; p = 0.0344). iSUV was not an independent predictor (p = 0.12); however, the risk of death was reduced for patients with an iSUV > 6 (hazard ratio = 0.26).Our novel findings show that among LGAC patients treated with preoperative chemoradiation and surgery, those with a high iSUV have longer OS than patients with a low iSUV. iSUV appears to have a predictive role in patients with LGAC when treated with preoperative chemoradiation.Â© 2015 S. Karger AG, Basel.
Skeletal Muscle Metastasis from Renal Cell Carcinoma: 21 cases and review of the literature. - Sultan Qaboos University medical journal
This study aimed to raise radiologists' awareness of skeletal muscle metastases (SMM) in renal cell carcinoma (RCC) cases and to clarify their imaging appearance.A retrospective analysis was undertaken of 21 patients between 44-75 years old with 72 SMM treated from January 1990 to May 2009 at the MD Anderson Cancer Center in Houston, Texas, USA. Additionally, 37 patients with 44 SMM from a literature review were analysed.Among the 21 patients, the majority of SMM were asymptomatic and detected via computed tomography (CT). Mean metastasis size was 18.3 mm and the most common site was the trunk muscles (83.3%). The interval between discovery of the primary tumour and metastasis detection ranged up to 234 months. Peripheral enhancement (47.1%) was the most common post-contrast CT pattern and non-contrasted CT lesions were often isodense. Magnetic resonance imaging (MRI) characteristics were varied. Five lesions with available T1-weighted pre-contrast images were hyperintense to the surrounding muscle. Other organ metastases were present in 20 patients. Of the 44 SMM reported in the literature, the majority were symptomatic. Average metastasis size was 53.4 mm and only 20.5% of SMM were in trunk muscles. The average interval between tumour discovery and metastasis detection was 101 months. Other organ metastases were recorded in 17 out of 29 patients.SMM should always be considered in patients with RCC, even well after primary treatment. SMM from RCC may be invisible on CT without intravenous contrast; contrast-enhanced studies are therefore recommended. SMM are often hyperintense to the surrounding muscle on T1-weighted MRI scans.
Early versus Delayed Therapy of Advanced Gastric Cancer Patients--Does It Make a Difference? - Oncology
Nearly 50% of gastric cancer patients are diagnosed with advanced gastric cancer (AGC). Therapy is palliative but results in ill effects. The median overall survival (OS) of AGC patients is often <12 months. It is unclear if the early initiation of therapy in all AGC patients is beneficial.A retrospective analysis of AGC patients in our database was carried out. The patients were divided into two groups: asymptomatic or symptomatic. We sought to assess whether the delay of systemic therapy was harmful in asymptomatic patients.A total of 135 patients were analyzed. Most patients were symptomatic (68%), males (67%), and had low ECOG scores (0-1; 85%). In univariate analyses, ECOG performance status 0 (p = 0.005), delayed initiation of therapy (p = 0.03), and lack of symptoms (p = 0.03) were associated with a longer OS. The multivariate model for OS identified only ECOG performance status as an independent prognosticator of longer OS (p = 0.02). Asymptomatic patients who had delayed (â‰¥ 4 weeks) systemic therapy had an OS rate of 77% at 1 year compared to 58% for patients treated within 4 weeks (p = 0.47).Symptomatic AGC patients had a poor outcome compared to asymptomatic AGC patients. Treatment delay in asymptomatic patients had no detrimental effect on OS, suggesting that the timing of therapy can be based on patient selection.Â© 2015 S. Karger AG, Basel.
Postoperative Morbidity and Mortality Rates are Not Increased for Patients with Gastric and Gastroesophageal Cancer Who Undergo Preoperative Chemoradiation Therapy. - Annals of surgical oncology
This study aimed to determine whether postoperative morbidity and mortality rates increased after preoperative chemoradiation in patients who underwent gastrectomy.The medical records of 7404 patients with gastric or gastroesophageal cancer seen from January 1995 to August 2012 were reviewed to identify patients who underwent gastrectomy. Ï‡ (2) and logistic regression analysis were used to determine differences in the 90-day postoperative morbidity and mortality rates of patients who underwent upfront surgery (SURG), preoperative chemotherapy (CHEMO), or preoperative chemoradiation (CHEMOXRT).Of the 500 patients included in this study, 200 underwent SURG, 65 had CHEMO, and 235 had CHEMOXRT. Respectively, 33, 43, and 58 % of these patients underwent total gastrectomy (p < 0.01). Resection of other organs was performed respectively in 19, 26, and 23 % of the patients (p = 0.37). Minor complications within 90 days (Clavien-Dindo 1 or 2) occurred for 41 % of the SURG patients, 43 % of the CHEMO patients, and 45 % of the CHEMOXRT patients (p = 0.68). Major complications or death within 90 days (Clavien-Dindo 3, 4, or 5) occurred for 21, 28, and 29 % of the patients, respectively (p = 0.15). The 90-day mortality (Clavien-Dindo 5) rates were 2 % for the SURG patients, 6 % for the CHEMO patients, and 3 % for the CHEMOXRT patients (p = 0.25). The median hospital stays were respectively 12, 12, and 13 days (p = 0.09). In the multivariate analysis, male sex, gastroesophageal junction cancer, total gastrectomy, and resection of other organs were associated with increased major morbidity and mortality rates, whereas preoperative therapy was not.The CHEMOXRT patients had postoperative morbidity and mortality rates similar to those for the SURG and CHEMO patients.
Molecular biomarkers in gastric cancer. - Journal of the National Comprehensive Cancer Network : JNCCN
Gastric cancer (GC) represents a serious health problem on a global scale. Despite some recent advances in the field, the prognosis in metastatic GC remains poor. Even in localized disease the adjunctive therapies improve overall survival (OS) by only approximately 10%. A better understanding of molecular biology, which would lead to improved treatment options, is needed and is the basis for this review. Many potential biomarkers of prognostic significance have been identified, including ALDH, SHH, Sox9, HER2, EGFR, VEGF, Hippo/YAP, and MET. However, inhibition of only HER2 protein has led to a modest survival benefit. A new approach to GC treatment, which is a disease influenced by inflammation, is the exploitation of the immune system to fight disease. Two interesting targets/prognostic markers that bear further investigation in GC are PD1 and PDL, particularly given their success in the treatment of other inflammation/immune-associated malignancies.
Predictors of Survival in Patients with Resectable Gastric Cancer Treated with Preoperative Chemoradiation Therapy and Gastrectomy. - Journal of the American College of Surgeons
The purpose of this study was to determine the overall survival (OS) of patients with resectable gastric cancer treated with preoperative chemoradiation therapy and gastrectomy.The medical records of patients with gastric adenocarcinoma presenting to our institution (January 1995 to August 2012) were reviewed to identify patients who underwent diagnostic laparoscopy, preoperative chemoradiation, and gastrectomy. Associations between various clinicopathologic factors and OS were examined with Cox proportional hazards models.Of 192 patients who met inclusion criteria, 103 (54%) required total gastrectomy. One hundred sixty-eight patients (88%) had an extended lymph node dissection, 26 (14%) had resection of adjacent organs, and 178 (93%) had an R0 resection. Median follow-up time for surviving patients was 4.2 years. Median OS for all patients was 5.8 years, and 5-year OS rate was 56%. Multivariable Cox regression model results identified variables associated with diminished OS including age â‰¥ 65 years (hazard ratio [HR] 1.62; 95% CI 1.05 to 2.51), male sex (HR 1.76; 95% CI 1.13 to 2.74), adjacent organ resection (HR 1.97; 95% CI 1.16 to 3.35), R1 status (HR 2.29; 95% CI 1.17 to 4.48), pathologic N1 stage (HR 1.92; 95% CI 1.24 to 2.98), N2 stage (HR 2.58; 95% CI 1.01 to 6.58), and N3 stage (HR 6.54; 95% CI 2.69 to 15.93). Five-year OS rates for patients with pathologic N0, N1, N2, and N3 disease were 67%, 42%, 43%, and 0%, respectively.Patients with gastric cancer who undergo diagnostic laparoscopy, preoperative chemoradiation, and gastrectomy have a high frequency of obtaining an R0 resection and excellent OS rates. Nodal status after surgery remains an important determinant of OS.Copyright Â© 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Long-term survival in patients with metastatic gastric and gastroesophageal cancer treated with surgery. - Journal of surgical oncology
The purpose of this study was to determine the survival of patients with metastatic gastric cancer treated with surgery.We reviewed the medical records of 7,404 patients with gastric or gastroesophageal cancer seen from January 1995 to August 2012 at MD Anderson Cancer Center and identified patients with stage IV disease treated with surgery. Kaplan-Meier curves were created to compare overall survival (OS) between groups.Of the 82 patients who met inclusion criteria, sites of metastatic disease included peritoneum (Nâ€‰=â€‰34, 42%), positive cytology only (Nâ€‰=â€‰17, 21%), distant lymph nodes (Nâ€‰=â€‰12, 15%), and distant organs (Nâ€‰=â€‰19, 23%). The median time from initial cancer diagnosis to surgery for metastatic disease was 10 months (range, 0-70). Surgery included exploratory surgery only (Nâ€‰=â€‰16, 20%), primary tumor resection with or without resection of distant disease (Nâ€‰=â€‰50, 61%), and distant disease resection only (Nâ€‰=â€‰16, 20%). Median follow-up for living patients was 3 years (range, 0.1-14). Median survival for all patients was 1.5 years (range, 0.1-14). Five year OS for patients with peritoneal metastases, positive cytology only, distant lymph nodes, and distant organ involvement was 13, 42, 20, and 34%, respectively.Surgery in the setting of metastatic disease is an uncommon clinical scenario and has a considerable risk of exploration without resection, although long-term survival is possible.Â© 2015 Wiley Periodicals, Inc.
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