Treatment patterns and survival among older adults in the United States with advanced soft-tissue sarcomas

Background

To describe patient and tumor characteristics, treatments, and survival among older adults in the United States with advanced soft-tissue sarcoma (STS), across and by categories of specifically defined histologic subtypes.

Methods

We conducted a retrospective cohort analysis using the SEER. The study population comprised patients ≥?65 years old with advanced STS (excluding osteosarcoma, Kaposi sarcoma, and gastrointestinal stromal tumors) diagnosed from January 1, 2001 to December 31, 2011.

Results

Of 4274 study patients, 2103 (49.2%) were male. Mean age was 77.8 years, and 1539 (36.0%) had distant disease at initial diagnosis. The most common histologic categories were leiomyosarcoma (922[21.6%]), undifferentiated pleomorphic sarcoma (652[15.3%]), and liposarcoma (554[13.0%]). Overall, 1227 (28.7%) patients received first-line systemic therapy. Among these patients, 325 (26.5%) received docetaxel plus gemcitabine and 231 (18.8%) received doxorubicin alone. Only 476 patients received second-line therapy (11.1%), most commonly doxorubicin alone (n?=?101). Median overall survival (95% confidence interval) from advanced STS diagnosis was 8.9 (8.3, 9.7) months.

Conclusions

Although previous studies of younger populations reported anthracycline-based therapy predominated in first line, our study of older advanced STS patients found that docetaxel plus gemcitabine was most commonly used. Despite variation by histologic category, prognosis remains poor for older adult patients with advanced STS.

     

Pancreatic and biliary tract cancers]

There are several tumor markers for pancreatic and biliary tract cancers, such as carcinoembryonal antigen, pancreatic enzyme, carbohydrate antigen and tumor associated gene. CA19-9 and SPan-1, which are type I carbohydrate antigens, are especially useful among these tumor markers. Combination assays of these tumor markers improve the positive rate for these cancers. These tumor markers are useful not only in diagnosis but also in assessing the therapeutic efficacy and early detection of recurrence after operation.     

Preoperative imaging of biliary tract cancers

Many imaging techniques are available for the evaluation of patients with malignant obstructive jaundice. Ultrasonography, in experienced hands, is valuable for evaluating the local extent of the disease, but its usefulness for staging distant metastases is limited. When used properly, CT and MR imaging can provide valuable information about the extent of local tumor involvement and distant metastases. These noninvasive techniques provide images of the bile ducts and vascular images that are comparable in quality to those obtained with more invasive procedures, such as PTC, ERCP, and angiography, and do not have the risk for complications of these invasive techniques.     

Systemic therapy for biliary tract cancers

Biliary tract cancers (BTCs) are invasive carcinomas that arise from the epithelial lining of the gallbladder and bile ducts. These include intrahepatic, perihilar, and distal biliary tree cancers as well as carcinoma arising from the gallbladder. Complete surgical resection offers the only chance for cure; however, only 10% of patients present with early-stage disease and are considered surgical candidates. Among those patients who do undergo "curative" resection, recurrence rates are high; thus, for the majority of BTC patients, systemic chemotherapy is the mainstay of their treatment plan. Patients with unresectable or metastatic BTC have a poor prognosis, with a median overall survival time of <1 year. Despite a paucity of randomized phase III data, a consensus on first-line systemic therapy is emerging. In this review, we discuss the clinical experience with systemic treatment of BTC, focusing on the rationale for a first-line regimen as well as future directions in the field.     

Multidisciplinary treatment of biliary tract cancers

Ninety-six patients referred for radiation therapy to Washington University affiliated institutions with tumors of the extrahepatic biliary tree form the basis of this report. Patients were examined with regard to demographic factors, tumor primary site, presenting symptoms, methods of diagnosis, and methods of management. The median survival of all 96 patients in this series was 11 months. There was no significant difference between patients with gallbladder cancer and patients with cancer of the biliary ductal system. There was a statistically significant improvement in survival in those patients undergoing resection as management or as a component of the management of their tumors (P = 0.02). Patients receiving >4,000 cGy of radiation therapy had an improved survival compared to those patients receiving ≤4,000 cGy of radiation therapy (P = 0.003). While surgical resection improved survival for those patients undergoing removal of all gross tumor, this effect was noted especially in patients with gallbladder cancer. © Wiley-Liss, Inc.     

Molecular pathology of biliary tract cancers

The molecular mechanisms underlying the development, growth and metastatic diffusion of biliary tract cancers are still undefined. The increase in worldwide incidence and mortality of cholangiocarcinoma justifies the impellent need to clarify the intracellular mechanisms triggering the malignant transformation of the biliary epithelium and growth of biliary malignancies. A more complete characterization of the molecular pathology of bile duct cancers could lead to the identification of valid targets for the diagnosis and therapy of these devastating malignancies. This review describes the scientific progress made over the past decades with regard to the understanding of the molecular processes of cholangiocarcinogenesis.     

胆系肿瘤化疗及其分子靶向治疗

 胆系肿瘤是一种起源于胆管上皮的恶性肿瘤。多数患者发病时已达局部晚期或已发生远处转移。尽管系统化疗方案层出不穷,但是无法行手术切除的患者预后极差。吉西他滨与顺铂联合方案化疗可显著延长患者的生存期,是目前局部晚期或转移性胆系肿瘤化疗的标准方案。应用分子靶向药物治疗进展期胆系肿瘤是临床研究的新趋势。     

Treatment of advanced biliary tract cancers: from chemotherapy to targeted agents

Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage and have a dismal prognosis. The treatment of advanced disease is mainly based on system...     

Cellular and molecular biology of biliary tract cancers

Cancer of the biliary tract has been associated with point mutations of K-ras and beta-catenin proto-oncogenes; alterations of p53, p16, APC, and DPC4 tumor suppressor genes by a combination of chromosomal deletion, mutation, or methylation; and infrequently microsatellite instability. The frequencies of these alterations vary by location and race of the patient, tumor subsite, histology, and associated disease. Advances in the understanding of the genetics of this disease will help in diagnosing biliary tract cancer, screening at-risk patients, and developing therapies.     

Treatment of upper aerodigestive tract cancers in England and its effect on survival.

The evidence base for head and neck cancers is low with relatively few randomized controlled trials of the two main treatments, surgery and radiotherapy. The aim of the study was to investigate the patterns of surgery and radiotherapy treatment for head and neck cancers in three large areas of England and to investigate their effects on survival. This was a retrospective study of 13510 cases of head and neck cancers (ICD10: C00-C14, C30-C32) diagnosed and treated from 1984 to 1992 in England. We undertook multivariate analyses of survival using a step-wise Cox proportional hazard model and Kaplan-Meier analysis. There were regional variations in the treatments given to patients. Four in ten patients did not receive currently recommended treatments. In multivariate analyses treatment content and timing had an independent effect on survival. Better survival was associated with surgery for mouth cancers, radiotherapy for laryngeal cancers and combined treatment for pharyngeal cancers independent of tumour and demographic factors. Further research is needed to investigate the findings of this study through large randomized controlled trials and multi-centre audits.     

Inflammatory markers and overall survival in older adults with cancer

Background

Our aim was to evaluate the prognostic impact of three inflammatory markers - neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) - on overall survival (OS) in older adults with cancer.

Epidemiology of biliary tract cancers: an update

Background: Biliary tract cancer (BTC) is a rare cancer in Europeand North America, characterized by wide geographic variation,with high incidence in some areas of Latin America and Asia. Materials and methods: BTC mortality and incidence have beenupdated according to recent data, using joinpoint regressionanalysis. Results: Since the 1980s, decreasing trends in BTC mortalityrates (age-standardized, world standard population) were observedin the European Union as a whole, in Australia, Canada, HongKong, Israel, New Zealand, and the United States, and high-riskcountries such as Japan and Venezuela. Joinpoint regressionanalysis indicates that decreasing trends were more favorableover recent calendar periods. High-mortality rates are, however,still evident in central and eastern Europe (4–5/100 000women), Japan (4/100 000 women), and Chile (16.6/100 000 women).Incidence rates identified other high-risk areas in India (8.5/100000 women), Korea (5.6/100 000 women), and Shanghai, China (5.2/100000 women). Conclusions: The decreasing BTC mortality trends essentiallyreflect more widespread and earlier adoption of cholecystectomyin several countries, since gallstones are the major risk factorfor BTC. There are, however, high-risk areas, mainly from SouthAmerica and India, where access to gall-bladder surgery remainsinadequate. Key words: biliary tract cancer, epidemiology, gall-bladder cancer, incidence, mortality, risk factors Received for publication April 24, 2008. Revision received June 24, 2008. Accepted for publication June 26, 2008.     

Predictors of survival among older adults with ependymoma

The biological process of aging encompasses a multitude of complex physiological and lifestyle changes that may alter the way typical prognostic factors affect survival among older ependymoma patients. Because very little is known about the clinical significance of traditional prognostic factors and the magnitude of their effects among older individuals, the purpose of this study was to evaluate the associations between survival and demographic and tumor characteristics among patients with ependymoma who were 60 years of age or older. Using the 1973–2007 dataset from the Surveillance, Epidemiology and End Results (SEER) program, we evaluated the impact of several factors on both overall and ependymoma-specific survival, utilizing multivariable Cox proportional hazards regression. We identified 367 ependymoma cases who were 60 years of age or older at diagnosis and had complete data from SEER. Of these, 19 (5.2%) had anaplastic tumors; all others were low-grade tumors. Age, tumor site, extent of surgery, and tumor histology were found to be significant predictors of ependymoma prognosis. The strongest predictor of poor outcome was supratentorial tumor location (adjusted HR: 6.94, 95% CI: 3.19–15.08, compared to spinal cord tumors). Our study suggests that tumor location, tumor histology, and surgical margin may be key predictors of survival among older ependymoma patients. We believe our study is one of the first to assess the prognostic value of these factors for ependymoma survival exclusively in an older patient population.     

Increased multimodality treatment options has improved survival for Hepatocellular carcinoma but poor survival for biliary tract cancers remains unchanged

BackgroundPrimary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre.MethodPatients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data.ResultsA total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time.ConclusionHCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.     

Preoperative biliary drainage-related inflammation is associated with shorter survival in biliary tract cancer patients

Background

An association between inflammation and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the influence of preoperative biliary drainage-related inflammation in patients with biliary tract cancer.

Methods

The clinical data of 97 patients who underwent surgery for extrahepatic bile duct cancer between February 2002 and September 2014 were analyzed, and the prognostic significance of tube-obstructive cholangitis after preoperative biliary drainage and pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) was evaluated.

Results

Eighty-four (86.6 %) of the 97 patients underwent ERCP and preoperative biliary drainage. Tube-obstructive cholangitis occurred in 25 cases and post-ERCP pancreatitis in 8 cases. Collectively, 30 patients experienced preoperative biliary drainage-related inflammation consisting of tube-obstructive cholangitis and/or post-ERCP pancreatitis. Drainage-related inflammation was significant risk factor of postoperative complications (P = 0.006), and significant poor predictors of shorter progression-free survival (P = 0.003) and overall survival (OS; P = 0.006) after surgery. In multivariate analysis, drainage-related inflammation was an independent predictor of shorter OS (hazard ratio, 1.924; P = 0.037) after surgery.

Conclusion

Preoperative biliary drainage-related inflammation was an independent prognostic factor for shorter OS in biliary tract cancer patients.

     

Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma.

PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival. RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% +/- 9% and 56% +/- 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% +/- 10%). CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.     

Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract

Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer.