Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors

PubMed Central

O’Sullivan, Ciara C.; Moon, Dominic H.; Kohn, Elise C.; Lee, Jung-Min

2014-01-01

Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm)-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single-agents and/or combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers are critical to expanding the scope of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here, we briefly review the preclinical data and clinical development of PARPi, and discuss its future development in solid tumors beyond gBRCAm-associated breast and ovarian cancers. PMID:24616882

Radioimmunoconjugates for treating cancer: recent advances and current opportunities.

PubMed

Bourgeois, Mickaël; Bailly, Clément; Frindel, Mathieu; Guerard, François; Chérel, Michel; Faivre-Chauvet, Alain; Kraeber-Bodéré, Françoise; Bodet-Milin, Caroline

2017-07-01

Radioimmunoconjugates have been used for 30 years to diagnose and treat cancer. For many years, the use of these therapeutic tools has been limited to haematological disorders, such as non-Hodgkin's lymphoma, given that they have only had a moderate effect on solid tumours. Areas covered: Recently, several strategies have revived the potential therapeutic application for radioimmunoconjugates. In this review, the authors review the advances in immunological engineering to develop new tools like monoclonal antibodies and their derivatives. Then, the authors summarize the development of radionuclides, the use of recombinant antibodies, pretargeting approaches, and dose fractionation techniques, providing opportunities for both therapeutic and diagnostic applications. Expert opinion: Radioimmunoconjugates used in nuclear medicine have entered a new era of development. These advances give rise to a variety of opportunities in the management of various cancers, where the radiolabelled antibodies may be particularly useful in immuno-specific phenotypic imaging e.g. companion diagnostics. Concerning therapeutic applications, radioimmunoconjugates have demonstrated their efficacy in the treatment of both haematological malignancies and solid tumours. Recent procedural developments are of great interest in optimising oncological targeted therapies. In the field of cancer theranostics, we believe that radioimmunoconjugated compounds are likely to play a large part in near future.

Trial opens to evaluate experimental cancer drug against solid tumors | Center for Cancer Research

Cancer.gov

Chemotherapy drugs have long been the mainstay of treatment for advanced solid tumors, but the toxic side effects of these drugs often limit the amount that can safely be given to patients. Doctors hope that PEN-866, an experimental cancer drug, can help to overcome this difficulty. Anish Thomas, M.D., who is leading this new trial, says, “This is a first-of-its-kind approach

Decitabine in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2013-02-06

Male Breast Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Melanoma; Stage III Melanoma; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Unspecified Adult Solid Tumor, Protocol Specific

Glembatumumab Vedotin, Nivolumab, and Ipilimumab in Treating Patients With Advanced Metastatic Solid Tumors That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-06-11

Advanced Malignant Solid Neoplasm; Estrogen Receptor Negative; GPNMB Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Uveal Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

Next-generation sequencing: advances and applications in cancer diagnosis

PubMed Central

Serratì, Simona; De Summa, Simona; Pilato, Brunella; Petriella, Daniela; Lacalamita, Rosanna; Tommasi, Stefania; Pinto, Rosamaria

2016-01-01

Technological advances have led to the introduction of next-generation sequencing (NGS) platforms in cancer investigation. NGS allows massive parallel sequencing that affords maximal tumor genomic assessment. NGS approaches are different, and concern DNA and RNA analysis. DNA sequencing includes whole-genome, whole-exome, and targeted sequencing, which focuses on a selection of genes of interest for a specific disease. RNA sequencing facilitates the detection of alternative gene-spliced transcripts, posttranscriptional modifications, gene fusion, mutations/single-nucleotide polymorphisms, small and long noncoding RNAs, and changes in gene expression. Most applications are in the cancer research field, but lately NGS technology has been revolutionizing cancer molecular diagnostics, due to the many advantages it offers compared to traditional methods. There is greater knowledge on solid cancer diagnostics, and recent interest has been shown also in the field of hematologic cancer. In this review, we report the latest data on NGS diagnostic/predictive clinical applications in solid and hematologic cancers. Moreover, since the amount of NGS data produced is very large and their interpretation is very complex, we briefly discuss two bioinformatic aspects, variant-calling accuracy and copy-number variation detection, which are gaining a lot of importance in cancer-diagnostic assessment. PMID:27980425

Breast cancer: updates and advances in 2016.

PubMed

Giordano, Sara B; Gradishar, William

2017-02-01

Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment. Breast cancer is a heterogeneous disease and targeted therapy is improving the outcomes of women. The use of cyclin-dependent kinase inhibitors (CDK) 4/6 have demonstrated a substantial improvement in progression-free survival in the first line setting of metastatic hormone receptor positive breast cancer. And newer agents directed at HER2 continue to revolutionize HER2-positive breast cancer treatment. This review highlights the recent updates in breast cancer treatment, new concepts in clinical trial design and provides a current overview of cancer genetic risk assessment.

GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

ClinicalTrials.gov

2013-01-23

Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin

ClinicalTrials.gov

2018-04-23

Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; Thymoma; Unresectable Solid Neoplasm

Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer.

PubMed

Bendell, J; O'Reilly, E M; Middleton, M R; Chau, I; Hochster, H; Fielding, A; Burke, W; Burris, H

2015-04-01

Olaparib (Lynparza) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that induces synthetic lethality in cancers with homologous recombination defects. In this phase I, dose-escalation trial, patients with advanced solid tumours received olaparib (50-200 mg capsules b.i.d.) continuously or intermittently (days 1-14, per 28-day cycle) plus gemcitabine [i.v. 600-800 mg/m(2); days 1, 8, 15, and 22 (cycle 1), days 1, 8, and 15 (subsequent cycles)] to establish the maximum tolerated dose. A separate dose-escalation phase evaluated olaparib in tablet formulation (100 mg o.d./b.i.d.; days 1-14) plus gemcitabine (600 mg/m(2)). In an expansion phase, patients with genetically unselected locally advanced or metastatic pancreatic cancer were randomised 2 : 1 to the tolerated olaparib capsule combination dose or gemcitabine alone (1000 mg/m(2)). Sixty-six patients were treated [dose-escalation phase, n = 44 (tablet cohort, n = 12); dose-expansion phase, n = 22 (olaparib plus gemcitabine, n = 15; gemcitabine alone, n = 7)]. In the dose-escalation phase, four patients (6%) experienced dose-limiting toxicities (raised alanine aminotransferase, n = 2; neutropenia, n = 1; febrile neutropenia, n = 1). Grade ≥3 adverse events were reported in 38/47 patients (81%) treated with olaparib capsules plus gemcitabine; most common were haematological toxicities (55%). Tolerated combinations were olaparib 100 mg b.i.d. capsule (intermittently, days 1-14) plus gemcitabine 600 mg/m(2) and olaparib 100 mg o.d. tablet (intermittently, days 1-14) plus gemcitabine 600 mg/m(2). There were no differences in efficacy observed during the dose-expansion phase. Olaparib 100 mg b.i.d. (intermittent dosing; capsules) plus gemcitabine 600 mg/m(2) is tolerated in advanced solid tumour patients, with no unmanageable/unexpected toxicities. Continuous dosing of olaparib or combination with gemcitabine at doses >600 mg/m(2) was not considered to have an acceptable tolerability profile

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

ClinicalTrials.gov

2018-06-01

Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer.

PubMed

Moehler, Markus; Mahlberg, Rolf; Heinemann, Volker; Obermannová, Radka; Kubala, Eugen; Melichar, Bohuslav; Weinmann, Arndt; Scigalla, Paul; Tesařová, Marietta; Janda, Petr; Hédouin-Biville, Fabienne; Mansoor, Wasat

2017-03-01

This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m 2 followed by oxaliplatin 130 mg/m 2 (maximum 8 cycles) and then S-1 [20 mg/m 2 (cohort 1) or 25 mg/m 2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. DLT was reported for two of the five patients in cohort 2, defining 20 mg/m 2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m 2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. The promising activity of EOS (S-1 dose level, 25 mg/m 2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

ClinicalTrials.gov

2017-11-22

Solid Neoplasm; Stage III Pancreatic Cancer; Stage IIIA Breast Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer; Sarcoma; Colorectal Cancer; Head and Neck Cancer; Cancer of Unknown Primary; Bladder Cancer; Ovarian Cancer

Advanced Materials and Solids Analysis Research Core (AMSARC)

EPA Science Inventory

The Advanced Materials and Solids Analysis Research Core (AMSARC), centered at the U.S. Environmental Protection Agency's (EPA) Andrew W. Breidenbach Environmental Research Center in Cincinnati, Ohio, is the foundation for the Agency's solids and surfaces analysis capabilities. ...

Advances in Solid State Physics

NASA Astrophysics Data System (ADS)

Kramer, Bernhard

The present volume 45 of Advances in Solid-State Physics contains the written versions of selected invited lectures from the spring meeting of the Arbeitskreis Festkörperphysik of the Deutsche Physikalische Gesellschaft in the World Year of Physics 2005, the Einstein Year, which was held from 4 - 11 March 2005 in Berlin, Germany. Many topical talks given at the numerous symposia are included. Most of these were organized collaboratively by several of the divisions of the Arbeitskreis. The book presents, to some extent, the status of the field of solid-state physics in 2005 not only in Germany but also internationally.

Solid cancers after allogeneic hematopoietic cell transplantation

PubMed Central

Curtis, Rochelle E.; Socié, Gérard; Sobocinski, Kathleen A.; Gilbert, Ethel; Landgren, Ola; Travis, Lois B.; Travis, William D.; Flowers, Mary E. D.; Friedman, Debra L.; Horowitz, Mary M.; Wingard, John R.; Deeg, H. Joachim

2009-01-01

Transplant recipients have been reported to have an increased risk of solid cancers but most studies are small and have limited ability to evaluate the interaction of host, disease, and treatment-related factors. In the largest study to date to evaluate risk factors for solid cancers, we studied a multi-institutional cohort of 28 874 allogeneic transplant recipients with 189 solid malignancies. Overall, patients developed new solid cancers at twice the rate expected based on general population rates (observed-to-expected ratio 2.1; 95% confidence interval 1.8-2.5), with the risk increasing over time (P trend < .001); the risk reached 3-fold among patients followed for 15 years or more after transplantation. New findings showed that the risk of developing a non–squamous cell carcinoma (non-SCC) following conditioning radiation was highly dependent on age at exposure. Among patients irradiated at ages under 30 years, the relative risk of non-SCC was 9 times that of nonirradiated patients, while the comparable risk for older patients was 1.1 (P interaction < .01). Chronic graft-versus-host disease and male sex were the main determinants for risk of SCC. These data indicate that allogeneic transplant survivors, particularly those irradiated at young ages, face increased risks of solid cancers, supporting strategies to promote lifelong surveillance among these patients. PMID:18971419

Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

ClinicalTrials.gov

2018-05-15

Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

Engagement of Patients With Advanced Cancer

ClinicalTrials.gov

2017-05-12

End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

Sarcoidosis Occurring After Solid Cancer: A Nonfortuitous Association

PubMed Central

Grados, Aurélie; Ebbo, Mikael; Bernit, Emmanuelle; Veit, Véronique; Mazodier, Karin; Jean, Rodolphe; Coso, Diane; Aurran-Schleinitz, Thérèse; Broussais, Florence; Bouabdallah, Reda; Gravis, Gwenaelle; Goncalves, Anthony; Giovaninni, Marc; Sève, Pascal; Chetaille, Bruno; Gavet-Bongo, Florence; Weitten, Thierry; Pavic, Michel; Harlé, Jean-Robert; Schleinitz, Nicolas

2015-01-01

Abstract The association between cancer and sarcoidosis is controversial. Some epidemiological studies show an increase of the incidence of cancer in patients with sarcoidosis but only few cases of sarcoidosis following cancer treatment have been reported. We conducted a retrospective case study from internal medicine and oncology departments for patients presenting sarcoidosis after solid cancer treatment. We also performed a literature review to search for patients who developed sarcoidosis after solid cancer. We describe the clinical, biological, and radiological characteristics and outcome of these patients. Twelve patients were included in our study. Various cancers were observed with a predominance of breast cancer. Development of sarcoidosis appeared in the 3 years following cancer and was asymptomatic in half of the patients. The disease was frequently identified after a follow-up positron emission tomography computerized tomography evaluation. Various manifestations were observed but all patients presented lymph node involvement. Half of the patients required systemic therapy. With a median follow-up of 73 months, no patient developed cancer relapse. Review of the literature identified 61 other patients for which the characteristics of both solid cancer and sarcoidosis were similar to those observed in our series. This report demonstrates that sarcoidosis must be considered in the differential diagnosis of patients with a history of malignancy who have developed lymphadenopathy or other lesions on positron emission tomography computerized tomography. Histological confirmation of cancer relapse is mandatory in order to avoid unjustified treatments. This association should be consider as a protective factor against cancer relapse. PMID:26181571

Advanced solid-state NMR spectroscopy of natural organic matter

USDA-ARS?s Scientific Manuscript database

Solid-state NMR is essential for the characterization of natural organic matter (NOM) and is gaining importance in geosciences and environmental sciences. This review is intended to highlight advanced solid-state NMR techniques, especially the systematic approach to NOM characterization, and their ...

Solid waste and pancreatic cancer: an ecologic study in Florida, USA.

PubMed

Schwartz, G G; Skinner, H G; Duncan, R

1998-10-01

Other than cigarette smoking, modifiable risk factors for pancreatic cancer have not been consistently identified. This study explored the ecologic relationship between pancreatic cancer incidence and measures of cigarette smoking, income, and solid waste collection for Florida's 67 counties. We used Florida's population-based cancer registry to compare county-specific incidence rates of pancreatic cancer among Whites to median household income, the per county prevalence of cigarette smoking, and to measures of per capita municipal solid waste collected. County-specific incidence rates for pancreatic cancer ranged from 0 to 8.1 per 100,000 per year and were significantly correlated with income (r = 0.35), cigarette smoking (r = 0.39), and solid waste (r = 0.47). The correlation between pancreatic cancer and solid waste was largely attributable to one sub-component of solid waste, yard trash (grass clippings, and tree and shrub trimmings) (r = 0.42). Using a stepwise regression procedure, only cigarette smoking and yard trash remained significant in the model. These data suggest that some factor associated with grass and tree trimmings, e.g. insecticides and herbicides, may increase the risk for pancreatic cancer. This hypothesis is consistent with several reports of pancreatic cancer and insecticide exposure in individuals and may suggest new avenues for research in pancreatic cancer.

Solid propulsion advanced concepts

NASA Technical Reports Server (NTRS)

Nakamura, Y.; Shafer, J. I.

1972-01-01

The feasibility and application of a solid propulsion powered spacecraft concept to implement high energy missions independent of multiplanetary swingby opportunities are assessed and recommendations offered for future work. An upper stage, solid propulsion launch vehicle augmentation system was selected as the baseline configuration in view of the established program goals of low cost and high reliability. Spacecraft and propulsion system data that characterize mission performance capabilities were generated to serve as the basis for subsequent tradeoff studies. A cost effectiveness model was used for the preliminary feasibility assessment to provide a meaningful comparative effectiveness measure of the various candidate designs. The results substantiated the feasibility of the powered spacecraft concept when used in conjunction with several intermediate-sized launch vehicles as well as the existence of energy margins by which to exploit the attainment of extended mission capabilities. Additionally, in growth option applications, the employment of advanced propulsion systems and alternate spacecraft approaches appear promising.

Precision medicine for advanced prostate cancer.

PubMed

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

Advances in Therapeutic Cancer Vaccines.

PubMed

Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

2016-01-01

Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. © 2016 Elsevier Inc. All rights reserved.

Radiation risk models for all solid cancers other than those types of cancer requiring individual assessments after a nuclear accident.

PubMed

Walsh, Linda; Zhang, Wei

2016-03-01

In the assessment of health risks after nuclear accidents, some health consequences require special attention. For example, in their 2013 report on health risk assessment after the Fukushima nuclear accident, the World Health Organisation (WHO) panel of experts considered risks of breast cancer, thyroid cancer and leukaemia. For these specific cancer types, use was made of already published excess relative risk (ERR) and excess absolute risk (EAR) models for radiation-related cancer incidence fitted to the epidemiological data from the Japanese A-bomb Life Span Study (LSS). However, it was also considered important to assess all other types of solid cancer together and the WHO, in their above-mentioned report, stated "No model to calculate the risk for all other solid cancer excluding breast and thyroid cancer risks is available from the LSS data". Applying the LSS models for all solid cancers along with the models for the specific sites means that some cancers have an overlap in the risk evaluations. Thus, calculating the total solid cancer risk plus the breast cancer risk plus the thyroid cancer risk can overestimate the total risk by several per cent. Therefore, the purpose of this paper was to publish the required models for all other solid cancers, i.e. all solid cancers other than those types of cancer requiring special attention after a nuclear accident. The new models presented here have been fitted to the same LSS data set from which the risks provided by the WHO were derived. Although it is known already that the EAR and ERR effect modifications by sex are statistically significant for the outcome "all solid cancer", it is shown here that sex modification is not statistically significant for the outcome "all solid cancer other than thyroid and breast cancer". It is also shown here that the sex-averaged solid cancer risks with and without the sex modification are very similar once breast and thyroid cancers are factored out. Some other notable model

PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-16

Advanced Malignant Solid Neoplasm; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Castration-Resistant Prostate Carcinoma; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Metastatic Prostate Carcinoma; PIK3CB Gene Mutation; Progesterone Receptor Negative; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; PTEN Gene Mutation; PTEN Loss; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

Pembrolizumab and Ziv-aflibercept in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-03-08

Adult Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Colorectal Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Scientific Advances in Lung Cancer 2015.

PubMed

Tsao, Anne S; Scagliotti, Giorgio V; Bunn, Paul A; Carbone, David P; Warren, Graham W; Bai, Chunxue; de Koning, Harry J; Yousaf-Khan, A Uraujh; McWilliams, Annette; Tsao, Ming Sound; Adusumilli, Prasad S; Rami-Porta, Ramón; Asamura, Hisao; Van Schil, Paul E; Darling, Gail E; Ramalingam, Suresh S; Gomez, Daniel R; Rosenzweig, Kenneth E; Zimmermann, Stefan; Peters, Solange; Ignatius Ou, Sai-Hong; Reungwetwattana, Thanyanan; Jänne, Pasi A; Mok, Tony S; Wakelee, Heather A; Pirker, Robert; Mazières, Julien; Brahmer, Julie R; Zhou, Yang; Herbst, Roy S; Papadimitrakopoulou, Vassiliki A; Redman, Mary W; Wynes, Murry W; Gandara, David R; Kelly, Ronan J; Hirsch, Fred R; Pass, Harvey I

2016-05-01

Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Precision medicine for advanced prostate cancer

PubMed Central

Mullane, Stephanie A.; Van Allen, Eliezer M.

2016-01-01

Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

Planning for Advanced Cancer

Cancer.gov

Find out what issues need to be addressed when dealing with an advanced or metastatic cancer diagnosis. Completing advance directives, looking at health insurance, organizing records and documents, and looking at the meanings in your life are some of the things to think about.

Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer

ClinicalTrials.gov

2018-03-22

Breast Adenocarcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Metastatic Malignant Solid Neoplasm; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Unresectable Solid Neoplasm

Advanced Solid Rocket Motor case design status

NASA Technical Reports Server (NTRS)

Palmer, G. L.; Cash, S. F.; Beck, J. P.

1993-01-01

The Advanced Solid Rocket Motor (ASRM) case design aimed at achieving a safer and more reliable solid rocket motor for the Space Shuttle system is considered. The ASRM case has a 150.0 inch diameter, three equal length segment, and 9Ni-4CO-0.3C steel alloy. The major design features include bolted casebolted case joints which close during pressurization, plasma arc welded factory joints, integral stiffener for splash down and recovery, and integral External Tank attachment rings. Each mechanical joint has redundant and verifiable o-ring seals.

MACC1 - a novel target for solid cancers.

PubMed

Stein, Ulrike

2013-09-01

The metastatic dissemination of primary tumors is directly linked to patient survival in many tumor entities. The previously undescribed gene metastasis-associated in colon cancer 1 (MACC1) was discovered by genome-wide analyses in colorectal cancer (CRC) tissues. MACC1 is a tumor stage-independent predictor for CRC metastasis linked to metastasis-free survival. In this review, the discovery of MACC1 is briefly presented. In the following, the overwhelming confirmation of these data is provided supporting MACC1 as a new remarkable biomarker for disease prognosis and prediction of therapy response for CRC and also for a variety of additional forms of solid cancers. Lastly, the potential clinical utility of MACC1 as a target for prevention or restriction of tumor progression and metastasis is envisioned. MACC1 has been identified as a prognostic biomarker in a variety of solid cancers. MACC1 correlated with tumor formation and progression, development of metastases and patient survival representing a decisive driver for tumorigenesis and metastasis. MACC1 was also demonstrated to be of predictive value for therapy response. MACC1 is a promising therapeutic target for anti-tumor and anti-metastatic intervention strategies of solid cancers. Its clinical utility, however, must be demonstrated in clinical trials.

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-01-12

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Advanced Prostate Cancer

MedlinePlus

... to learn about these types of treatments. This article is for men with metastatic and castrate-resistant ... Related Resources Urology 101 Fact Sheet UrologyHealth extra® Articles What is Advanced Prostate Cancer? Keeping Your Bones ...

Advances in chemical pharmacotherapy to manage advanced breast cancer.

PubMed

Gombos, Andrea; Awada, Ahmad

2017-01-01

Advanced breast cancer is still incurable. However, patients diagnosed with this fatal disease live longer. The selection of systemic therapy is mainly based on molecular subtype. The aim of management in these patients is to not only improve outcome, but also to maintain quality of life. Areas covered: In this paper we focus on available treatments and drugs under late development in the three main subtypes of breast cancer: luminal (hormone receptor positive), HER2 positive and triple negative disease. Main advances during the last years have been made in the treatment of HER2 positive breast cancer with the approval of several new targeted agents. Luminal breast cancer is also a field of active clinical research. So far triple negative breast cancer remains the subtype with the worse prognosis, even though new discoveries have been made to better understand the huge heterogeneity of this type of breast cancer. Expert opinion: Several new treatment options have recently been established in metastatic breast cancer. Side effects are sometimes cumbersome for the patient and are difficult to manage easily. Thus, identification of patients who derive the most benefit is needed. In addition, collaborative efforts should integrate the genotypic fragmentation in the management and future clinical research strategies of metastatic breast cancer patients.

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-03-29

Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm

Advances in cancer immunology and cancer immunotherapy.

PubMed

Voena, Claudia; Chiarle, Roberto

2016-02-01

After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.

Uncaria tomentosa (cat's claw) improves quality of life in patients with advanced solid tumors.

PubMed

de Paula, Larissa Carvalho Lopes; Fonseca, Fernando; Perazzo, Fabio; Cruz, Felipe Melo; Cubero, Daniel; Trufelli, Damila Cristina; Martins, Suelen Patrícia Dos Santos; Santi, Patrícia Xavier; da Silva, Eliana Araújo; Del Giglio, Auro

2015-01-01

Cat's claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients. This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy - Fatigue questionnaires were used to assess the participants' quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients' overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however, the disease stabilized for more than 8 months in four participants. The medication was well tolerated by most patients. Use of cat's claw might be beneficial in patients with advanced cancer by improving their quality of life and reducing fatigue. The mechanism of action does not seem to be related to the anti

Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

PubMed

Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

2018-07-01

Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

Head and neck cancer: proteomic advances and biomarker achievements.

PubMed

Rezende, Taia Maria Berto; de Souza Freire, Mirna; Franco, Octávio Luiz

2010-11-01

Tumors of the head and neck comprise an important neoplasia group, the incidence of which is increasing in many parts of the world. Recent advances in diagnostic and therapeutic techniques for these lesions have yielded novel molecular targets, uncovered signal pathway dominance, and advanced early cancer detection. Proteomics is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the analysis of different types of samples. The proteomic profiles of different types of cancer have been studied, and this has provided remarkable advances in cancer understanding. This review covers recent advances for head and neck cancer; it encompasses the risk factors, pathogenesis, proteomic tools that can help in understanding cancer, and new proteomic findings in this type of cancer. Copyright © 2010 American Cancer Society.

Novel agents for advanced pancreatic cancer

PubMed Central

Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

2015-01-01

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

The Advanced Solid Rocket Motor

NASA Technical Reports Server (NTRS)

Mitchell, Royce E.

1992-01-01

The Advanced Solid Rocket Motor will utilize improved design features and automated manufacturing methods to produce an inherently safer propulsive system for the Space Shuttle and future launch systems. This second-generation motor will also provide an additional 12,000 pounds of payload to orbit, enhancing the utility and efficiency of the Shuttle system. The new plant will feature strip-wound, asbestos-free insulation; propellant continuous mixing and casting; and extensive robotic systems. Following a series of static tests at the Stennis Space Center, MS flights are targeted to begin in early 1997.

Advances in cancer pain from bone metastasis.

PubMed

Zhu, Xiao-Cui; Zhang, Jia-Li; Ge, Chen-Tao; Yu, Yuan-Yang; Wang, Pan; Yuan, Ti-Fei; Fu, Cai-Yun

2015-01-01

With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models.

Advanced solid-state NMR spectroscopy of natural organic matter.

PubMed

Mao, Jingdong; Cao, Xiaoyan; Olk, Dan C; Chu, Wenying; Schmidt-Rohr, Klaus

2017-05-01

Solid-state NMR is essential for the characterization of natural organic matter (NOM) and is gaining importance in geosciences and environmental sciences. This review is intended to highlight advanced solid-state NMR techniques, especially a systematic approach to NOM characterization, and their applications to the study of NOM. We discuss some basics of how to acquire high-quality and quantitative solid-state 13 C NMR spectra, and address some common technical mistakes that lead to unreliable spectra of NOM. The identification of specific functional groups in NOM, primarily based on 13 C spectral-editing techniques, is described and the theoretical background of some recently-developed spectral-editing techniques is provided. Applications of solid-state NMR to investigating nitrogen (N) in NOM are described, focusing on limitations of the widely used 15 N CP/MAS experiment and the potential of improved advanced NMR techniques for characterizing N forms in NOM. Then techniques used for identifying proximities, heterogeneities and domains are reviewed, and some examples provided. In addition, NMR techniques for studying segmental dynamics in NOM are reviewed. We also briefly discuss applications of solid-state NMR to NOM from various sources, including soil organic matter, aquatic organic matter, organic matter in atmospheric particulate matter, carbonaceous meteoritic organic matter, and fossil fuels. Finally, examples of NMR-based structural models and an outlook are provided. Copyright © 2016 Elsevier B.V. All rights reserved.

Symptom clusters in advanced cancer.

PubMed

Jiménez, Ana; Madero, Rosario; Alonso, Alberto; Martínez-Marín, Virginia; Vilches, Yolanda; Martínez, Beatriz; Feliu, Marta; Díaz, Leyre; Espinosa, Enrique; Feliu, Jaime

2011-07-01

Patients with advanced cancer often experience multiple concurrent symptoms. Few studies have explored symptom clusters (SCs) in this population. The aim of the present study was to explore SCs in advanced cancer, evaluate the characteristics associated with various clusters, and determine their relationship to survival. This study included patients in the palliative care program of the Hospital Universitario La Paz from 2003 to 2005. The Edmonton Symptom Assessment System and a supplement including 13 other symptoms were used to detect symptoms. Principal component analysis was performed to determine symptom relationships and compare SCs with associated parameters. In total, 406 patients were included, 61% men and 39% women. The median age was 66.4 (range 18-95). The most common primaries were gastrointestinal (35%), lung (25%), genitourinary (8%), breast (5%), and head and neck (5%) carcinomas. The following clusters were identified: confusion (cognitive impairment, agitation, urinary incontinence), neuropsychological (anxiety, depression, and insomnia), anorexia-cachexia (anorexia, weight loss, and tiredness), and gastrointestinal (nausea and vomiting). The presence of these SCs was influenced by primary cancer site, gender, age, and performance status. Survival was related to the number of SCs present in a given patient: zero SC, 52 days; one SC, 38 days; two SCs, 23 days; and three to four SCs, 19 days; P < 0.001. Different SCs can be identified in patients with advanced cancer. These SCs are influenced by primary cancer site, gender, age, and Eastern Cooperative Oncology Group performance status, and they can have prognostic value. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Taking Care of Yourself - Advanced Cancer and Caregivers

Cancer.gov

Caring for someone with advanced cancer brings new challenges and concerns. It's important to take care of yourself and reach out for help. Find tips specific to caregivers of patients with advanced cancer.

Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

ClinicalTrials.gov

2015-09-30

Breast Cancer; Chronic Myeloproliferative Disorders; Colorectal Cancer; Head and Neck Cancer; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic/Myeloproliferative Diseases; Prostate Cancer; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Pragmatic medicine in solid cancer: a translational alternative to precision medicine

PubMed Central

Brábek, Jan; Rosel, Daniel; Fernandes, Michael

2016-01-01

The precision medicine (PM) initiative is a response to the dismal outlook in solid cancer. Despite heterogeneity, common mechanistic denominators may exist across the spectrum of solid cancer. A shift from conventional research and development (R&D) toward PM will require conceptual and structural change. As individuals and as a society, we welcome innovation, but question change. We ask: In solid cancer, does PM identify and address the causes of prior failures, and, if so, are the proposed solutions feasible? And, when may we expect safer, more effective and affordable drugs in the clinic? Considerations that prompt a pragmatic rethink include a failure analysis of translational R&D in solid cancer suggesting that trials and regulations need to be aligned with the natural history of the disease. In successful therapeutic interventions in chronic, complex disease, surrogate markers and endpoints should be consistent with the Prentice’s criteria. In solid cancer, drug induced tumor shrinkage, is a drug effect and not a disease response; tumor shrinkage does not reflect nor predict interruption of the disease. Overall, we support a pragmatic, multidisciplinary, and collaborative R&D, and suggest that direction be set by clinical need and utility, and by questions, not answers. PM will prove worthwhile if it could improve clinical outcomes. The lag in therapeutics relative to diagnostics is a cause for confusion. Overdiagnosis adds to fear and harm, especially in the absence of effective interventions. A revised initiative that prioritizes metastasis research could replicate the successful HIV/AIDS model in solid cancer. A pragmatic approach may further translational efforts toward meaningfully effective, generally available, and affordable solutions. PMID:27103822

Creation of an optically tunable, solid tissue phantom for use in cancer detection

NASA Astrophysics Data System (ADS)

Tucker, Matthew B.; Wallace, Catherine; Mantena, Sreekar; Cornwell, Neil; Ross, Weston; Odion, Ren; Vo-Dinh, Tuan; Codd, Patrick

2018-02-01

An optically tunable, solid tissue phantom was developed in order to aid in the verification and validation of non-destructive cancer detection technologies based on fluorescence spectroscopy. The solid tissue phantom contained agarose, hemoglobin, Intralipid, NADH, and FAD. The redox ratio of the solid phantoms were shown to be tunable; thus, indicating that these phantoms could be used to tailor specific optical conditions that mimic cancerous and healthy tissues. Therefore, this solid tissue phantom can serve as a suitable test bed to evaluate fluorescence spectroscopy based cancer detection devices.

Advances in cryoablation for pancreatic cancer.

PubMed

Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

2016-01-14

Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer.

A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors.

PubMed

LoRusso, Patricia M; Infante, Jeffrey R; Kim, Kevin B; Burris, Howard A; Curt, Gregory; Emeribe, Ugochi; Clemett, Delyth; Tomkinson, Helen K; Cohen, Roger B

2017-03-06

The RAS/RAF/MEK/ERK pathway is constitutively activated in many cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric MEK1/2 inhibitor with a short half-life that has shown clinical activity as monotherapy in phase I and II studies of advanced cancer. Preclinical data suggest that selumetinib may enhance the activity of chemotherapeutic agents. We assessed the safety, tolerability, and pharmacokinetics (PK) of selumetinib (AZD6244, ARRY-142886) in combination with docetaxel or dacarbazine in patients with advanced solid tumors. This study was a phase I, open-label, multicenter study in patients aged ≥18 years with advanced solid tumors who were candidates for docetaxel or dacarbazine treatment. Part A of the study (dose escalation) evaluated safety, tolerability, PK, and maximum tolerated dose (MTD) of selumetinib twice daily (BID) with docetaxel 75 mg/m 2 or dacarbazine 1000 mg/m 2 administered every 21 days. Patients receiving docetaxel could be administered primary prophylactic granulocyte-colony stimulating factor according to standard guidelines. Part B of the study (dose expansion) further evaluated safety, tolerability, and PK in 12 additional patients at the MTD combinations determined in part A. A total of 35 patients received selumetinib plus docetaxel, and 25 received selumetinib plus dacarbazine. The MTD of selumetinib was 75 mg BID in combination with either docetaxel (two dose-limiting toxicity [DLT] events: neutropenia with fever, and thrombocytopenia) or dacarbazine (one DLT event: thrombocytopenia). Common adverse events occurring with each treatment combination were diarrhea, peripheral/periorbital edema, fatigue, and nausea. PK parameters for selumetinib and docetaxel or dacarbazine were similar when administered alone or in combination. Partial responses were reported in 6/35 patients receiving selumetinib plus docetaxel and 4/25 patients receiving selumetinib plus dacarbazine. The combinations of

Cardiac autonomic modulation impairments in advanced breast cancer patients.

PubMed

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Advance directives: cancer patients' preferences and family-based decision making.

PubMed

Xing, Yan-Fang; Lin, Jin-Xiang; Li, Xing; Lin, Qu; Ma, Xiao-Kun; Chen, Jie; Wu, Dong-Hao; Wei, Li; Yin, Liang-Hong; Wu, Xiang-Yuan

2017-07-11

Advance directives are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, and these decisions might violate patients' personal will. This study aimed to examine the acceptance of advance directives among Chinese cancer patients and their families and patient participation in this procedure and, finally, to analyze the moral risk involved. While 246 patients and their family members refused official discussion of an advance directive, the remaining 166 patients and their families accepted the concept of an advance directive and signed a document agreeing to give up invasive treatment when the anti-cancer treatment was terminated. Of these, only 24 patients participated in the decision making. For 101 patients, anti-cancer therapy was ended prematurely with as many as 37 patients not told about their potential loss of health interests. Participants were 412 adult cancer patients from 9 leading hospitals across China. An advance directive was introduced to the main decision makers for each patient; if they wished to sign it, the advance directive would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients' awareness of their disease, and participation in an advance directive. Advance directives were not widely accepted among Chinese cancer patients unless anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an advance directive.

Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Ozols, Robert F; Herbst, Roy S; Colson, Yolonda L; Gralow, Julie; Bonner, James; Curran, Walter J; Eisenberg, Burton L; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schilsky, Richard L; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Winn, Rodger J

2007-01-01

A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries

Recent advances in radiation cancer therapy

NASA Astrophysics Data System (ADS)

Ma, C.-M. Charlie

2007-03-01

This paper presents the recent advances in radiation therapy techniques for the treatment of cancer. Significant improvement has been made in imaging techniques such as CT, MRI, MRS, PET, ultrasound, etc. that have brought marked advances in tumor target and critical structure delineation for treatment planning and patient setup and target localization for accurate dose delivery in radiation therapy of cancer. Recent developments of novel treatment modalities including intensity-modulated x-ray therapy (IMXT), energy- and intensity modulated electron therapy (MERT) and intensity modulated proton therapy (IMPT) together with the use of advanced image guidance have enabled precise dose delivery for dose escalation and hypofractionation studies that may result in better local control and quality of life. Particle acceleration using laser-induced plasmas has great potential for new cost-effective radiation sources that may have a great impact on the management of cancer using radiation therapy.

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

PubMed

Suki, Dima; Khoury Abdulla, Rami; Ding, Minming; Khatua, Soumen; Sawaya, Raymond

2014-10-01

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. 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. 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

Advanced heart failure due to cancer therapy.

PubMed

Shah, Sachin; Nohria, Anju

2015-01-01

Certain chemotherapeutic agents and mediastinal irradiation can be cardiotoxic and place cancer survivors at risk for developing advanced heart failure (HF). Anthracyclines are the prototypical agents associated with left ventricular (LV) dysfunction. Newer agents including trastuzumab and certain tyrosine kinase inhibitors such as sunitinib can also cause cardiomyopathy. Cancer survivors with advanced HF refractory to standard medical management should be considered for advanced therapies, including mechanical circulatory support (MCS) and transplantation. While overall outcomes after MCS and transplantation are similar in cancer survivors compared to other etiologies of HF, patients with radiation-induced restrictive cardiomyopathy have a significantly worse prognosis after transplantation. The increased need for right ventricular (RV) support after MCS in cancer survivors necessitates a careful evaluation for pre-operative RV dysfunction. Special consideration must also be given to the risk for recurrent malignancy, neurocognitive dysfunction, and increased psychological needs in this patient population.

Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

PubMed Central

Kandel, Pujan; Wallace, Michael B.

2018-01-01

Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer. PMID:29463004

Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors.

PubMed

Strauss, Julius; Heery, Christopher R; Schlom, Jeffrey; Madan, Ravi A; Cao, Liang; Kang, Zhigang; Lamping, Elizabeth; Marté, Jennifer L; Donahue, Renee N; Grenga, Italia; Cordes, Lisa; Christensen, Olaf; Mahnke, Lisa; Helwig, Christoph; Gulley, James L

2018-03-15

Purpose: M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused to a TGFβ "trap." Experimental Design: In the 3+3 dose-escalation component of this phase I study (NCT02517398), eligible patients with advanced solid tumors received M7824 at 1, 3, 10, or 20 mg/kg once every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal; in addition, a cohort received an initial 0.3 mg/kg dose to evaluate pharmacokinetics/pharmacodynamics, followed by 10 mg/kg dosing. The primary objective is to determine the safety and maximum tolerated dose (MTD); secondary objectives include pharmacokinetics, immunogenicity, and best overall response. Results: Nineteen heavily pretreated patients with ECOG 0-1 have received M7824. Grade ≥3 treatment-related adverse events occurred in four patients (skin infection secondary to localized bullous pemphigoid, asymptomatic lipase increase, colitis with associated anemia, and gastroparesis with hypokalemia). The MTD was not reached. M7824 saturated peripheral PD-L1 and sequestered any released plasma TGFβ1, -β2, and -β3 throughout the dosing period at >1 mg/kg. There were signs of efficacy across all dose levels, including one ongoing confirmed complete response (cervical cancer), two durable confirmed partial responses (PR; pancreatic cancer; anal cancer), one near-PR (cervical cancer), and two cases of prolonged stable disease in patients with growing disease at study entry (pancreatic cancer; carcinoid). Conclusions: M7824 has a manageable safety profile in patients with heavily pretreated advanced solid tumors. Early signs of efficacy are encouraging, and multiple expansion cohorts are ongoing in a range of tumors. Clin Cancer Res; 24(6); 1287-95. ©2018 AACR . ©2018 American Association for Cancer Research.

Genetically Engineered Immunotherapy for Advanced Cancer

Cancer.gov

In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

Advanced Solid State Lighting for Human Evaluation Project

NASA Technical Reports Server (NTRS)

Zeitlin, Nancy; Holbert, Eirik

2015-01-01

Lighting intensity and color have a significant impact on human circadian rhythms. Advanced solid state lighting was developed for the Advanced Exploration System (AES) Deep Space Habitat(DSH) concept demonstrator. The latest generation of assemblies using the latest commercially available LED lights were designed for use in the Bigelow Aerospace Environmental Control and Life Support System (ECLSS) simulator and the University of Hawaii's Hawaii Space Exploration Analog and Simulation (Hi-SEAS) habitat. Agreements with both these organizations will allow the government to receive feedback on the lights and lighting algorithms from long term human interaction.

Current management of advanced and castration resistant prostate cancer.

PubMed

Gomella, Leonard G; Petrylak, Daniel P; Shayegan, Bobby

2014-04-01

Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11 C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related to androgen deprivation therapy are also gaining attention as men are being treated with longer courses of androgen deprivation. Understanding the theory behind these new agents and management approaches while focusing on the practical clinical considerations are essential to improve outcomes in advanced prostate cancer. A review of the current state of the art in the management of advanced and castration resistant prostate cancer presented in this Canadian Journal of Urology International supplement was performed. Key findings are summarized and presented along with critical updates based on recent publications and meeting presentations. Key concepts identified in the management of advanced prostate cancer included the new understanding of prostate cancer based on translational discoveries, applications of various hormonally based strategies in advanced disease including traditional and recently approved agents. The use of new imaging modalities to identify metastatic disease, immunotherapy approaches and discussions of sequencing and which new agents are likely to be available in the future in the management of CRPC were identified. Bone targeted strategies are also addressed in the setting of androgen deprivation and metastatic disease. The management of men with advanced prostate cancer has

Solid Cancer Incidence in the Techa River Incidence Cohort: 1956-2007.

PubMed

Davis, F G; Yu, K L; Preston, D; Epifanova, S; Degteva, M; Akleyev, A V

2015-07-01

Previously reported studies of the Techa River Cohort have established associations between radiation dose and the occurrence of solid cancers and leukemia (non-CLL) that appear to be linear in dose response. These analyses include 17,435 cohort members alive and not known to have had cancer prior to January 1, 1956 who lived in areas near the river or Chelyabinsk City at some time between 1956 and the end of 2007, utilized individualized dose estimates computed using the Techa River Dosimetry System 2009 and included five more years of follow-up. The median and mean dose estimates based on these doses are consistently higher than those based on earlier Techa River Dosimetry System 2000 dose estimates. This article includes new site-specific cancer risk estimates and risk estimates adjusted for available information on smoking. There is a statistically significant (P = 0.02) linear trend in the smoking-adjusted all-solid cancer incidence risks with an excess relative risk (ERR) after exposure to 100 mGy of 0.077 with a 95% confidence interval of 0.013-0.15. Examination of site-specific risks revealed statistically significant radiation dose effects only for cancers of the esophagus and uterus with an ERR per 100 mGy estimates in excess of 0.10. Esophageal cancer risk estimates were modified by ethnicity and sex, but not smoking. While the solid cancer rates are attenuated when esophageal cancer is removed (ERR = 0.063 per 100 mGy), a dose-response relationship is present and it remains likely that radiation exposure has increased the risks for most solid cancers in the cohort despite the lack of power to detect statistically significant risks for specific sites.

The acceptability and potential benefits of mindfulness-based interventions in improving psychological well-being for adults with advanced cancer: A systematic review.

PubMed

Zimmermann, Fernanda F; Burrell, Beverley; Jordan, Jennifer

2018-02-01

In spite of supportive care for people affected by cancer being well recognized as a priority for research, there is little solid evidence of the effectiveness of psychological interventions using mindfulness for those with advanced cancer. This systematic review aims to describe, evaluate and synthesize the acceptability and potential benefits of mindfulness-based interventions (MBIs) for the psychological well-being of people with advanced cancers. Eight databases were searched and terms related to advanced stages of cancer and mindfulness were combined systematically to identify relevant published literature. Inclusion criteria were studies with adults only and all types of cancer at stages III and IV. There was considerable variety in the MBI treatment packages including in the extent and centrality of mindfulness in the interventions. Of 312 identified studies, only 8 included MBIs for people with advanced cancer rather than their families or carers. Results from these studies suggests that MBIs are acceptable and beneficial to the advanced cancer population, improving quality of life, use of mindfulness skills, acceptance of their cancer situation and reduction in depression and anxiety. Some adaptations were recommended however regarding delivery, simplified briefer MBIs, abbreviated session time, flexibility concerning locality of treatment and a minimized questionnaire burden for this group. MBI packages reviewed in this study had evidence of acceptability and of effectiveness, indicating potential benefit for this population. Individualized, including home-based interventions may be optimal to allow critically ill patients to participate in treatment. In future, MBIs adapted to the needs of various advanced cancer patients are recommended to address the gap in the field and improve health care. Copyright © 2017 Elsevier Ltd. All rights reserved.

NExT: Advancing Promising Cancer Therapies

Cancer.gov

The NCI Experimental Therapeutics (NExT) program works with researchers and top scientific experts to advance promising or novel cancer therapies from the earliest stages of research to clinical trials. Learn about recent successes from NExT in this Cancer Currents blog post.

Advances in Breast Cancer Therapy

DTIC Science & Technology

2012-09-01

cancer diagnosed by core needle biopsy will be eligible for this study. Additional tumor specimens will be obtained prior to the start of...chemotherapy via core needle biopsies to be used for the ex vivo chemoresponse assay and tumor genomic analysis (gene expression), respectively. All...AD_________________ Award Number: W81XWH-06-2-0021 TITLE: Advances in Breast Cancer Therapy

Technological advances in radiotherapy for cervical cancer.

PubMed

Walsh, Lorraine; Morgia, Marita; Fyles, Anthony; Milosevic, Michael

2011-09-01

To discuss the important technological advances that have taken place in the planning and delivery of both external beam radiotherapy and brachytherapy for patients with locally advanced cervical cancer, and the implications for improved clinical outcomes. Technological advances in external beam radiation treatment and brachytherapy for patients with cervical cancer allow more precise targeting of tumour and relative sparing of surrounding normal organs and tissues. Early evidence is emerging to indicate that these advances will translate into improvements in tumour control and reduced side effects. However, there are patient, tumour and treatment-related factors that can detract from these benefits. Foremost among these is complex, unpredictable and sometimes dramatic internal tumour and normal organ motion during treatment. The focus of current research and clinical development is on tracking internal anatomic change in individual patients and adapting treatment plans as required to assure that optimal tumour coverage and normal tissue sparing is maintained at all times. The success of this approach will depend on clear definitions of target volumes, high resolution daily soft tissue imaging, and new software tools for rapid contouring, treatment planning and quality assurance. Radiation treatment of locally advanced cervical cancer is evolving rapidly, driven by advances in technology, towards more individualized patient care that has the potential to substantially improve clinical outcomes.

Bevacizumab Treatment for Advanced Breast Cancer

PubMed Central

Guarneri, Valentina; Icli, Fikri; Johnston, Stephen; Khayat, David; Loibl, Sibylle; Martin, Miguel; Zielinski, Christoph; Conte, PierFranco; Hortobagyi, Gabriel N.

2011-01-01

Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured. PMID:21976315

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

PubMed

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Insights into next developments in advanced gastric cancer.

PubMed

Obermannová, Radka; Lordick, Florian

2016-07-01

The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.

Advances of Molecular Targeted Therapy in Gastric Cancer.

PubMed

Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

2016-06-01

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

Advances in Molecular Pathology and Treatment of Periampullary Cancers.

PubMed

Chandrasegaram, Manju D; Chen, John W; Price, Timothy J; Zalcberg, John; Sjoquist, Katrin; Merrett, Neil D

2016-01-01

Periampullary cancers (PACs) include the following 4 traditional anatomic subtypes: pancreatic, ampullary, biliary, or duodenal cancers. This review was performed to highlight recent advances in the genomic and molecular understanding of each PAC subtype and the advances in chemotherapeutic and molecular trials in these cancer subtypes. Recent advances have highlighted differences in the genomic and molecular features within each PAC subtype. Ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. K-ras mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42%-52%), biliary (22%-23%), and duodenal cancers (32%-35%), suggesting crucial differences in targetable mutations in these cancer subtypes.Ampullary cancers of intestinal subtype and duodenal cancers seem to share similarities with colorectal cancer, given that they respond to similar chemotherapeutic regimens. This has potential implications for clinical trials and treatment selection, where PACs are often considered together. Future trials should be designed in view of our increased understanding of the different anatomic and histomolecularly profiled subtypes of PAC cancers, which respects their individual molecular characteristics, phenotype, and response to treatment.

Liquid biopsy and its role in an advanced clinical trial for lung cancer.

PubMed

Johann, Donald J; Steliga, Mathew; Shin, Ik J; Yoon, Donghoon; Arnaoutakis, Konstantinos; Hutchins, Laura; Liu, Meeiyueh; Liem, Jason; Walker, Karl; Pereira, Andy; Yang, Mary; Jeffus, Susanne K; Peterson, Erich; Xu, Joshua

2018-02-01

Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the "right" cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary

PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

ClinicalTrials.gov

2018-02-08

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

Responses to advanced cancer: Chinese-Australians.

PubMed

Chui, Ying-Yu; Donoghue, Judith; Chenoweth, Lynn

2005-12-01

This paper describes a study identifying the impact of key aspects of Chinese culture on the responses of mid-aged Chinese-Australians to their advanced cancer in order to make recommendations about their care within the health system. Studies conducted in the 1960s and 1970s focused on understanding people's psychological responses to their experiences of terminal illness, but the issue of culture was not addressed. In recent years, a few studies have been conducted with Chinese-Australians, but were limited to issues related to their information needs and the disclosure of a cancer diagnosis. There is a lack of understanding of the impact of Chinese culture on the experiences of these patients. A grounded theory approach was used to generate a substantive theory to explain how mid-aged Chinese-Australians respond to advancing cancer. Eleven participants were recruited and data were collected from face-to-face interviews, telephone contacts, observation and researcher field notes. Data generation occurred between 1997 and 1999. Four modes of response to advanced cancer were identified: acute crisis, combat, despondency and waiting for death. This paper deals particularly with the combat mode which incorporated five culturally specific strategies used by participants in their struggle against advanced cancer. These were traditional Chinese medicine, traditional Chinese beliefs on the use of food for health maintenance, qi gong (a form of exercise), feng shui (which involves paying attention to spatial organization) and the worship of ancestors and gods. Deeply entrenched within these responses is the influence of Chinese culture, rooted in the beliefs and practices of traditional Chinese medicine and the philosophy of harmony and balance of yin and yang and qi. Health care professionals need to be aware of the cultural practices and beliefs of the different ethnic groups for whom they care, and of the importance of accommodation to and negotiation about these

Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

DTIC Science & Technology

2016-03-01

Award Number: W81XWH-12-1-0323 TITLE: Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach PRINCIPAL...SUBTITLE Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...increasing its sensitivity and specificity through nanotechnology . Hypothesis: Detection of DNA methylation from individuals with cancer can be used to

The basics of CAR T design and challenges in immunotherapy of solid tumors - Ovarian cancer as a model.

PubMed

Xu, Xuequn; Qiu, Jin; Sun, Yi

2017-07-03

Chimeric antigen receptor T cells are T cells genetically engineered with CAR constructs which mainly contain scFV and TCR zeta chain. With promising development in blood cancers, CAR T trials are also applied in solid cancers. However, the treatment effect in solid cancers is lower than expected. This review summarizes difference of CAR T applications in solid and blood cancers. Future challenges of CAR T cell treatment in solid cancer are also discussed using ovarian cancer as an example.

Personal growth during the experience of advanced cancer: a systematic review.

PubMed

Moreno, Patricia I; Stanton, Annette L

2013-01-01

Over the past decade, research has documented the positive consequences individuals attribute to the experience of traumatic, life-threatening events, including enhanced life appreciation, improved social relationships, and a deepened sense of self and meaning. Despite evidence that individuals with cancer frequently perceive growth as a result of their experience, personal growth in the context of advanced cancer has received markedly less attention. In light of the unique challenges accompanying the experience of advanced cancer, the phenomenon of perceiving positive consequences and making meaning of the cancer experience (i.e., personal growth) may be distinct in patients with life-limiting disease as compared with more commonly studied early-stage cancer survivor samples. The purpose of this article was to review studies examining personal growth in adults diagnosed with advanced cancer to encourage medical professionals to consider and respond to their concerns around meaning within palliative care. We conducted a systematic review of the PubMed and PsycINFO electronic databases for studies examining personal growth in patients with advanced cancer published between January 1960 and January 2013. Of the 197 studies reviewed, 12 quantitative studies and 10 qualitative studies met criteria for inclusion. The review revealed that many patients with advanced cancer both cite finding meaning at the end of life as important and perceive positive consequences as a result of their experience. In comparison to early-stage cancer or benign disease, advanced cancer may serve to prompt higher levels of personal growth. However, these findings are mixed and may indicate a complex, nonlinear relationship between cancer prognosis and personal growth. The most promising candidates for promoting personal growth during advanced disease include younger adult age, spirituality, and psychosocial resources (optimism, marriage, and social support from close others and health care

High Temperature Solid Lubricant Materials for Heavy Duty and Advanced Heat Engines

NASA Technical Reports Server (NTRS)

Dellacorte, C.; Wood, J. C.

1994-01-01

Advanced engine designs incorporate higher mechanical and thermal loading to achieve efficiency improvements. This approach often leads to higher operating temperatures of critical sliding elements (e.g. piston ring/cylinder wall contacts and valve guides) which compromise the use of conventional and even advanced synthetic liquid lubricants. For these applications solid lubricants must be considered. Several novel solid lubricant composites and coatings designated PS/PM200 have been employed to dry and marginally oil lubricated contacts in advanced heat engines. These applications include cylinder kits of heavy duty diesels, and high temperature Stirling engines, sidewall seals of rotary engines, and various exhaust valve and exhaust component applications. This paper describes the tribological and thermophysical properties of these tribomaterials and reviews the results of applying them to engine applications. Other potential tribological materials and applications are also discussed with particular emphasis on heavy duty and advanced heat engines.

Advances in Hereditary Colorectal and Pancreatic Cancer

PubMed Central

Underhill, Meghan L.; Germansky, Katharine A.; Yurgelun, Matthew B.

2017-01-01

Purpose Innovations in genetic medicine have lead to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. Methods This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. Findings This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of novel genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. Implications Given the availability of novel diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk for colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention. PMID:27045993

The desire for shared decision making among patients with solid and hematological cancer.

PubMed

Ernst, Jochen; Kuhnt, Susanne; Schwarzer, Andreas; Aldaoud, Ali; Niederwieser, Dietger; Mantovani-Löffler, Luisa; Kuchenbecker, Doris; Schröder, Christina

2011-02-01

The desire for shared decision making arises especially for frequently occurring cases of solid cancer. For hematological cancer conditions, there are no analogous results. This study compares the participation patients' desires concerning medical decisions dealing with their solid and hematological tumors. The 533 inpatients with solid cancer (age<65: 61.0%; female: 39.6 %) and 177 patients with hematological cancer (inpatient: 62.1%, outpatient: 37.9%; age<65: 63.3%; female: 42.4%) were given a questionnaire after admission to a hospital or medical practice. The dependent variable was patient preference for control in decision making for eight different medical areas of decision. Descriptive results showed that patients with solid cancer had a stronger desire to participate in the decisions in six of a total of eight survey fields (p<0.01). When considering medical and socio-demographic control variables, the multivariate regression shows that the differences between the patient groups remain in all areas (p<0.01). Further predictor variables are educational background and age (p<0.05). No influence resulted from the factors of gender, medical or treatment characteristics. The results show differences between patients with hematological cancer and patients with solid tumors, and these differences concern the preference to participate in medical decisions. Hemato-oncological patients desire less active participation and prefer a more dominant role of the physician in the various areas requiring decisions. Physicians should respect this in the course of the treatment. Copyright © 2010 John Wiley & Sons, Ltd.

Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Gralow, Julie; Ozols, Robert F; Bajorin, Dean F; Cheson, Bruce D; Sandler, Howard M; Winer, Eric P; Bonner, James; Demetri, George D; Curran, Walter; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory H; Sawaya, Raymond; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Davidson, Nancy E; Schilsky, Richard L; Lichter, Allen S

2008-01-10

A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the

Trichomonas vaginalis infection and risk of advanced prostate cancer.

PubMed

Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

2016-05-01

The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

PubMed Central

Smith, J. Joshua; Garcia-Aguilar, Julio

2015-01-01

Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

Advancing Public Health in Cancer - Annual Plan

Cancer.gov

Cancer is the leading cause of death from disease among Americans under 85. Learn how NCI advances public health by conducting research to improve the delivery of quality cancer prevention, screening, and treatment to all Americans.

Advanced Breast Cancer as Indicator of Quality Mammography

NASA Astrophysics Data System (ADS)

Gaona, Enrique

2003-09-01

Breast cancer is the most frequently diagnosed cancer and is the second leading cause of cancer death among women in the Mexican Republic. Mammography is the more important screening tool for detecting early breast cancer. Screening mammography involves taking x-rays from two views from each breast, typically from above (cranial-caudal view, CC) and from an oblique or angled view (mediolateral-oblique, MLO). The purpose of this study was to carry out an exploratory survey of the issue of patients with advanced breast cancer who have had a screening mammography. A general result of the survey is that 22.5% of all patients (102) with advanced breast cancer that participated in the study had previous screening mammography. But we should consider that 10% of breast cancers are not detected by mammography. Only 70% of the family doctors prescribed a diagnostic mammography when the first symptoms were diagnosed.

Propellant development for the Advanced Solid Rocket Motor

NASA Technical Reports Server (NTRS)

Landers, L. C.; Stanley, C. B.; Ricks, D. W.

1991-01-01

The properties of a propellant developed for the NASA Advanced Solid Rocket Motor (ASRM) are described in terms of its composition, performance, and compliance to NASA specifications. The class 1.3 HTPB/AP/A1 propellant employs an ester plasticizer and the content of ballistic solids is set at 88 percent. Ammonia evolution is prevented by the utilization of a neutral bonding agent which allows continuous mixing. The propellant also comprises a bimodal AP blend with one ground fraction, ground AP of at least 20 microns, and ferric oxide to control the burning rate. The propellant's characteristics are discussed in terms of tradeoffs in AP particle size and the types of Al powder, bonding agent, and HTPB polymer. The size and shape of the ballistic solids affect the processability, ballistic properties, and structural properties of the propellant. The revised baseline composition is based on maximizing the robustness of in-process viscosity, structural integrity, and burning-rate tailoring range.

Nod for Atezolizumab in Advanced Bladder Cancer.

PubMed

2017-06-01

The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients. ©2017 American Association for Cancer Research.

Prior cancer does not adversely affect survival in locally advanced lung cancer: A national SEER-medicare analysis.

PubMed

Laccetti, Andrew L; Pruitt, Sandi L; Xuan, Lei; Halm, Ethan A; Gerber, David E

2016-08-01

Management of locally advanced non-small cell lung cancer is among the most highly contested areas in thoracic oncology. In this population, a history of prior cancer frequently results in exclusion from clinical trials and may influence therapeutic decisions. We therefore determined prevalence and prognostic impact of prior cancer among these patients. We identified patients>65years of age diagnosed 1992-2009 with locally advanced lung cancer in the Surveillance, Epidemiology, and End Results-Medicare linked dataset. We characterized prior cancer by prevalence, type, stage, and timing. We compared all-cause and lung cancer-specific survival between patients with and without prior cancer using propensity score-adjusted Cox regression. 51,542 locally advanced lung cancer patients were included; 15.8% had a history of prior cancer. Prostate (25%), gastrointestinal (17%), breast (16%), and other genitourinary (15%) were the most common types of prior cancer, and 76% percent of prior cancers were localized or in situ stage. Approximately half (54%) of prior cancers were diagnosed within 5 years of the index lung cancer date. Patients with prior cancer had similar (propensity-score adjusted hazard ratio [HR] 0.96; 95% CI, 0.94-0.99; P=0.005) and improved lung cancer-specific (HR 0.84; 95% CI, 0.81-0.86; P<0.001) survival compared to patients with no prior cancer. For patients with locally advanced lung cancer, prior cancer does not adversely impact clinical outcomes. Patients with locally advanced lung cancer and a history of prior cancer should not be excluded from clinical trials, and should be offered aggressive, potentially curative therapies if otherwise appropriate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advances in Imaging in Prostate and Bladder Cancer.

PubMed

Srivastava, Abhishek; Douglass, Laura M; Chernyak, Victoria; Watts, Kara L

2017-09-01

Recent advancements in urologic imaging techniques aim to improve the initial detection of urologic malignancies and subsequent recurrence and to more accurately stage disease. This allows the urologist to make better informed treatment decisions. In particular, exciting advances in the imaging of prostate cancer and bladder cancer have recently emerged including the use of dynamic, functional imaging with MRI and PET. In this review, we will explore these imaging modalities, in addition to new sonography techniques and CT, and how they hope to improve the diagnosis and management of prostate and bladder cancer.

Advances in radiotherapy for esophageal cancer

PubMed Central

Deng, Wei

2018-01-01

Esophageal cancer is a common type of malignancy worldwide and usually requires multidisciplinary care. Radiotherapy plays an important part in management of the disease. During the past few years, researchers have made much progress about radiotherapy for esophageal cancer, which was revealed in every aspect of clinical practice. Neoadjuvant chemoradiotherapy remains the standard treatment for locally advanced esophageal cancer, whereas neoadjuvant chemotherapy appears to show less toxicities and non-inferior prognosis. What’s more, definitive chemoradiotherapy could be an option for non-surgical candidates and good responders to chemoradiotherapy. Advances in radiation techniques result in higher conformity, homogeneity, more normal tissue sparing and less treatment time. Promising prognoses and less toxicities were also seen in advanced techniques. As radiation dose higher than 50 Gy obtains better local control and survival, simultaneously integrated boost is designed to increase primary tumor dosage and keep prophylactic dose to subclinical areas. Elective nodal irradiation brings about better local control but do not show advantages in survival compared with involved field irradiation (IFI). As a trend, more tolerable chemoradiotherapy regimen would be taken into account in dealing with elderly patients. PMID:29666802

Cancer and Radiation Therapy: Current Advances and Future Directions

PubMed Central

Baskar, Rajamanickam; Lee, Kuo Ann; Yeo, Richard; Yeoh, Kheng-Wei

2012-01-01

In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed. PMID:22408567

Cancer and radiation therapy: current advances and future directions.

PubMed

Baskar, Rajamanickam; Lee, Kuo Ann; Yeo, Richard; Yeoh, Kheng-Wei

2012-01-01

In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.

Home parenteral nutrition for advanced cancer patients: Contributes to survival?

PubMed

Theilla, Miriam; Cohen, Johnathan; Kagan, Ilia; Attal-Singer, Joelle; Lev, Shaul; Singer, Pierre

2017-03-24

Patients with advanced cancer often suffer from severe malnutrition and gastrointestinal obstruction. This population could benefit from home parenteral nutrition (HPN). The aim of this study was to observe the outcome of patients with advanced cancer patients who were eligible for HPN. All patients in the nutrition clinic who received HPN over the past 7 y were included in the present study. We compared patients with advanced cancer with the noncancer population in terms of hospitalization rate and mortality. Of 221 advanced cancer patients, 153 who had no oral/enteral intake and who received HPN survived. Of these, 35% survived for 6 mo, 27% for 1 y, 18.9% survived 2 y, and 3.9% survived for the 7 y of the follow-up. Hospitalization rate was not significantly different from the noncancer population. These results show that HPN is a relevant palliative therapy for patients with advanced cancer patients without oral or enteral feeding access. Copyright © 2017 Elsevier Inc. All rights reserved.

[Prognosis of survival in advanced cancer].

PubMed

de Arriba Méndez, J J

2007-01-01

Accurate prognoses are important in the care of patients with advanced cancer to assist clinicians in their decision making, and to help patients set their goals and priorities. Several studies have demonstrated that doctors are inaccurate and overly optimistic when predicting the survival of patients with advanced and terminal cancer. To improve prognostic accuracy, clinicians can use a number of factors that have proven to be associated with life expectancy: performance status, some signs and symptoms and some laboratory markers. Prognostic scores including most of the factors are also developed. Patients and their families can benefit from realistic prognostic information in a simple and empathetic manner.

Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules

ClinicalTrials.gov

2018-06-22

Advanced Solid Malignancy; Safety and Tolerability; Pharmacokinetics; Pharmacodynamics; Tumour Response; Advanced or Metastatic Breast Cancer; Ovarian Cancer; Cervical Cancer; Endometrial Cancer; PIK3CA; AKT1; PTEN; ER Positive; HER2 Positive

Immunotherapy Combination Approved for Advanced Kidney Cancer

Cancer.gov

FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Surgical resection after TNFerade therapy for locally advanced pancreatic cancer.

PubMed

Chadha, Manpreet K; Litwin, Alan; Levea, Charles; Iyer, Renuka; Yang, Gary; Javle, Milind; Gibbs, John F

2009-09-04

Treatment of pancreatic cancer remains a major oncological challenge and survival is dismal. Most patients, present with advanced disease at diagnosis and are not candidates for curative resection. Preoperative chemoradiation may downstage and improve survival in locally advanced pancreatic cancer. This has prompted investigators to look for novel neoadjuvant therapies. Gene therapy for pancreatic cancer is a novel investigational approach that may have promise. TNFerade is a replication deficient adenovirus vector carrying the human tumor necrosis factor (TNF)-alpha gene regulated under control of a radiation-inducible gene promoter. Transfection of tumor cells with TNFerade maximizes the antitumor effect of TNF-alpha under influence of radiation leading to synergistic effects in preclinical studies. We describe a case of locally advanced unresectable pancreatic cancer treated with a novel multimodal approach utilizing gene therapy with TNFerade and concurrent chemoradiation that was followed by successful surgical resection. Neoadjuvant TNFerade based chemoradiation therapy may be a useful adjunct to treatment of locally advanced pancreatic cancer.

Major clinical research advances in gynecologic cancer in 2015

PubMed Central

2016-01-01

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

Major clinical research advances in gynecologic cancer in 2015.

PubMed

Suh, Dong Hoon; Kim, Miseon; Kim, Hak Jae; Lee, Kyung Hun; Kim, Jae Weon

2016-11-01

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.

Advanced Solid State Lighting for AES Deep Space Hab Project

NASA Technical Reports Server (NTRS)

Holbert, Eirik

2015-01-01

The advanced Solid State Lighting (SSL) assemblies augmented 2nd generation modules under development for the Advanced Exploration Systems Deep Space Habitat in using color therapy to synchronize crew circadian rhythms. Current RGB LED technology does not produce sufficient brightness to adequately address general lighting in addition to color therapy. The intent is to address both through a mix of white and RGB LEDs designing for fully addressable alertness/relaxation levels as well as more dramatic circadian shifts.

Patient perceptions of helpful communication in the context of advanced cancer.

PubMed

Stajduhar, Kelli I; Thorne, Sally E; McGuinness, Liza; Kim-Sing, Charmaine

2010-07-01

Based on a secondary analysis of data from a large qualitative study on cancer care communication, we address the question: what do patients with advanced cancer identify as helpful in their communication encounters with health care providers? Communication is of critical importance to the care of patients with advanced cancer. A better understanding of what such patients identify as helpful in their communication encounters with nurses and other health care providers seems critical to creating evidence-informed recommendations for best practices. Secondary analysis of qualitative interview data. Data from 18 participants interviewed individually and 16 focus group participants, with advanced cancer in the palliative phase of care. Interpretive description methodology informed data collection and analysis. Findings suggest four key elements are critically important to consider in communications with patients in an advanced or palliative phase - respecting the importance of time, demonstrating caring, acknowledging fear and balancing hope and honesty in the provision of information. Communication is an important element in the provision of advanced cancer care. Findings emphasise the complex meanings inherent in cancer care communication and identify central themes that are fundamental to effective cancer care communication. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Herbal medicines for advanced colorectal cancer.

PubMed

Guo, Zhongning; Jia, Xiaoqiang; Liu, Jian Ping; Liao, Juan; Yang, Yufei

2012-05-16

Herbal medicine has been widely used in patients with advanced colorectal cancer in China, but its efficacy has not been confirmed. To evaluate the beneficial effect and safety on Chinese herbal medicine therapy for advanced stage colorectal cancer, and it's influence on the patients' quality of life. The following electronic databases were searched: BIOSIS Previews, Cochrane Controlled Trials Register, Medline EMBASE, Biological Abstracts, until Aug. 2011. Manual searching was performed on 16 types of Chinese journals which started from their respective first publication dates, as well as unpublished conference proceedings. No language restriction was applied. Randomized or quasi-randomised controlled trials on the treatment of advanced stage colorectal cancer by herbal medicines or herbal medicines combined with chemotherapy, regardless of blinding. The data were extracted independently by two reviewers. Methodological quality of the included in trials was assessed according to the following parameters: randomisation, allocation concealment, double blinding, and drop-out rates. A total of 20 randomised controlled trials with 1304 participants were identified. All the 20 trials compared the use of herbal medicines with chemotherapy and chemotherapy alone in the treatment of advanced stage colorectal cancers.Compared with chemotherapy alone, the use of Quxie capsule combined with chemotherapy could decrease mortality rate (RR 0.17, 95% CI 0.03 to 0.97); the use of Jianpi Jiedu formula, Xiaozheng formula and Yiqi Huoxue herbal medicine combined with chemotherapy respectively could improve 1-year survival rate significantly; the use of Xiaozheng Formula in conjunction with chemotherapy could improve 3-year survival rate. There were 10 herbal medicines showing benefit in improving quality of life. Herbal medicines did not show additional benefit in response rate or stability rate. No trials reported serious adverse effect from herbal medicine. Some herbal medicines

Pain experiences of patients with advanced cancer: A qualitative descriptive study.

PubMed

Erol, Ozgul; Unsar, Serap; Yacan, Lale; Pelin, Meryem; Kurt, Seda; Erdogan, Bülent

2018-04-01

Uncontrolled pain, especially in patients with advanced cancer, affects quality of life negatively and causes negative physical and psychological conditions. The aim of this study was to explore the pain experiences of patients with advanced cancer and how they manage with pain, and to present a view of pain management approaches of nurses from the perspectives of the patients. This was a qualitative descriptive study of sixteen hospitalized patients with advanced cancer. Data were collected using semi-structured interviews with patients. Data were analysed by Colaizzi's phenomenological method. This study found that patients with advanced cancer who had pain experienced anxiety, helplessness, hopelessness and many restrictions in daily life as well as inability to manage with pain. Most of the patients with advanced cancer were not satisfied with their nursing care with regard to pain management. The themes that emerged were pain perception and experiences, effects of pain on daily life, pain management and management strategies and the patients' perspectives about nursing approaches to pain. This study demonstrated the difficulties of patients with advanced cancer who experienced pain in their daily lives, yet lack pain management strategies. Furthermore, nurses' caring approaches to patients with advanced cancer who experienced pain was found inadequate. Oncology nurses should provide educational interventions in order to enhance knowledge and skills about pain assessment and non-pharmacologic and pharmacologic strategies used in pain management. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

DTIC Science & Technology

2014-08-01

AD_________________ Award Number: W81XWH-12-1-0323 TITLE: Advanced Lung Cancer Screening: An...Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION...August 2014 2. REPORT TYPE Annual 3. DATES COVERED 1 Aug 2013 – 31 July 2014 4. TITLE AND SUBTITLE Advanced Lung Cancer Screening: An Individualized

Pancreatic cancer: Advances in treatment

PubMed Central

Mohammed, Somala; Van Buren II, George; Fisher, William E

2014-01-01

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing. While patients with pancreatic cancer have traditionally faced a dismal prognosis, over the past several years various advances in diagnosis and treatment have begun to positively impact this disease. Identification of effective combinations of existing chemotherapeutic agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has improved survival for selected patients although concerns regarding their toxicity profiles remain. A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions, such as pancreatic intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic neoplasms. Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management. Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors, and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality. Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes. Lastly, a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents. PMID:25071330

Pancreatic cancer: advances in treatment.

PubMed

Mohammed, Somala; Van Buren, George; Fisher, William E

2014-07-28

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing. While patients with pancreatic cancer have traditionally faced a dismal prognosis, over the past several years various advances in diagnosis and treatment have begun to positively impact this disease. Identification of effective combinations of existing chemotherapeutic agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has improved survival for selected patients although concerns regarding their toxicity profiles remain. A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions, such as pancreatic intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic neoplasms. Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management. Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors, and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality. Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes. Lastly, a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents.

Preoperative therapy in locally advanced esophageal cancer.

PubMed

Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

2016-10-21

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

Evaluating the Needs of Patients Living With Solid Tumor Cancer: A Survey Design.

PubMed

Schmidt, April L; Lorenz, Rebecca A; Buchanan, Paula M; McLaughlin, Laura

2018-03-01

To describe the unmet needs of adult patients living with solid tumor cancer. Survey design. Adult patients living with solid tumor cancer from two outpatient clinics were mailed the Sheffield Profile for Assessment and Referral to Care, a holistic screening questionnaire for assessing palliative care needs, and a demographics questionnaire. One hundred fifteen patients returned the instruments, corresponding to a 62% response rate. There were no significant differences by cancer type (breast, non-breast) or gender. However, Caucasians reported significantly more psychological issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14 (12.2%)], respectively, p = .032). Older patients reported more concerns about loss of independence/activity ( p = .012) compared with younger age groups. Patients living with Stage III/IV cancer reported more distressed about independence/activity ( p = .034), family/social issues ( p = .007), and treatment side effects ( p = .027) than patients living with Stage I/II cancer. Patients living with solid tumor cancer have a myriad of unmet needs regardless of age, gender, cancer type, or cancer stage. There appears to be important differences by cancer stage. The Sheffield Profile for Assessment and Referral to Care questionnaire provides a holistic approach for nurses to identify unmet needs and concerns. Future research should explore the preferred methods of receiving support and information.

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

ClinicalTrials.gov

2018-05-15

Advanced Malignant Solid Neoplasm; Recurrent Melanoma; Refractory Malignant Solid Neoplasm; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Major clinical research advances in gynecologic cancer in 2013.

PubMed

Suh, Dong Hoon; Kim, Jae-Weon; Kang, Sokbom; Kim, Hak Jae; Lee, Kyung-Hun

2014-07-01

In 2013, 10 topics were selected for major clinical research advances in gynecologic oncology; these included three topics regarding cervical cancer, three regarding ovarian cancer, two regarding endometrial cancer, and one each regarding breast cancer and radiation oncology. For cervical cancer, bevacizumab was first demonstrated to exhibit outstanding clinical efficacy in a recurrent, metastatic setting. Regarding cervical cancer screening, visual inspections with acetic acid in low-resource settings, p16/Ki-67 double staining, and the follow-up results of four randomized controlled trials of human papillomavirus-based screening methods were reviewed. Laparoscopic para-aortic lymphadenectomy before chemoradiation for locally advanced cervical cancer was the final topic for cervical cancer. Regarding front-line ovarian cancer therapies, dose-dense paclitaxel and carboplatin, intraperitoneal chemotherapy, and other targeted agents administered according to combination or maintenance schedules were discussed. Regarding recurrent ovarian cancer treatment, cediranib, olaparib, and farletuzumab were discussed for platinum-sensitive disease. The final overall survival data associated with a combination of bevacizumab and chemotherapy for platinum-resistant disease were briefly summarized. For endometrial cancer, the potential clinical efficacy of metformin, an antidiabetic drug, in obese patients was followed by integrated genomic analyses from the Cancer Genome Atlas Research Network. For breast cancer, three remarkable advances were reviewed: the long-term effects of continued adjuvant tamoxifen for 10 years, the effects of 2-year versus 1-year adjuvant trastuzumab for human epidermal growth factor receptor 2-positive disease, and the approval of pertuzumab in a neoadjuvant setting with a pathologic complete response as the surrogate endpoint. Finally, the recent large studies of intensity-modulated radiotherapy for gynecologic cancer were briefly summarized.

Case report: Irreversible electroporation for locally advanced pancreatic cancer.

PubMed

Orcutt, Sonia; Kis, Bela; Malafa, Mokenge

2017-01-01

For patients with pancreatic adenocarcinoma who are not candidates for surgical resection, long-term survival is poor, even with currently available systemic and radiation therapy options. However, for those with locally advanced disease who do not have distant metastasis, locoregional control of the tumor has the potential to improve long-term outcomes. A newly developed technology, irreversible electroporation, has advantages over traditional thermal ablation with unresectable cancers in this location. In our case report, we describe the first patient treated with irreversible electroporation at our institution for locally advanced pancreatic cancer. The patient is a 63-year-old man who had a partial response to standard chemotherapy and radiation, but was found on operative assessment to have persistently unresectable disease. He therefore underwent irreversible electroporation to the pancreatic mass. His postoperative course was complicated by delayed gastric emptying and wound infection. Three months after surgery, he had no evidence of distant or recurrent disease. Irreversible electroporation for locally advanced pancreatic cancer is an emerging technique which attempts to improve local control of locally advanced, non-metastatic pancreatic cancer. Early data have demonstrated the potential for improved long-term survival in these patients, although further studies are needed to confirm safety and efficacy of this technique. While there is a positive outlook for the use of irreversible electroporation for locally advanced pancreas cancer, there remain some uncertainties surrounding this therapy, which underscores the importance of future research in this area. Copyright © 2017. Published by Elsevier Ltd.

Biomarkers in Advanced Larynx Cancer

PubMed Central

Bradford, Carol R.; Kumar, Bhavna; Bellile, Emily; Lee, Julia; Taylor, Jeremy; D’Silva, Nisha; Cordell, Kitrina; Kleer, Celina; Kupfer, Robbi; Kumar, Pawan; Urba, Susan; Worden, Francis; Eisbruch, Avraham; Wolf, Gregory T.; Teknos, Theodoros N.; Prince, Mark E.P.; Chepeha, Douglas B.; Hogikyan, Norman D.; Moyer, Jeffrey S.; Carey, Thomas E.

2014-01-01

Objectives/Hypothesis To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. Study Design Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers and correlations with outcome were determined. Methods Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. Results Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (p = 0.0003). Conclusions Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer. PMID:23775802

Visual disturbances in advanced cancer patients: clinical observations.

PubMed

Saita, L; Polastri, D; De Conno, F

1999-03-01

Visual disturbances in advanced cancer patients are very rarely signaled, evaluated, or adequately treated. The main causes of sight disturbances are primary eye tumors, ocular metastases, and some paraneoplastic syndromes. Sight alteration can also be associated with asthenia, fatigue, anemia, and hypovitaminosis. These symptoms can be monocular or binocular, and their gravity and evolution can vary. Based on a survey of 156 patients, we estimate the prevalence of visual disturbances to be 12% in advanced cancer patients.

Periocular Skin Cancer in Solid Organ Transplant Recipients.

PubMed

Perry, Julian D; Polito, Sara C; Chundury, Rao V; Singh, Arun D; Fritz, Michael A; Vidimos, Allison T; Gastman, Brian R; Koyfman, Shlomo A

2016-01-01

To determine the proportion of solid organ transplant recipients developing periocular nonmelanoma skin cancer and to describe the morbidity of these cancers in transplant recipients. Cohort study. Consecutive patients undergoing solid organ transplantation at the Cleveland Clinic between 1990 and 2008. The charts of all patients receiving a solid organ transplant from 1990-2008 evaluated in the dermatology department for a subsequent biopsy-proven head and neck malignancy through April 2015 were reviewed. Patients with a periocular region nonmelanoma skin cancer (NMSC) or a nonperiocular NMSC causing a complication requiring eyelid surgery were included. Charts were reviewed for demographic data; transplant date, type, and source; immunosuppressive agents received at diagnosis; and type of NMSC, number of nonperiocular NMSCs, ophthalmologic findings, and periocular sequelae after the repair. Primary outcome measures included the type, location, final defect size, tumor-node-metastasis classification, presence of perineural invasion, and reconstruction technique(s) used for each periocular NMSC. Secondary outcome measures included the type and treatment of ocular sequelae due to nonperiocular facial NMSC. A total of 3489 patients underwent solid organ transplantation between 1990 and 2008. Of these, 420 patients were evaluated in the dermatology clinic for biopsy-proven NMSC of the head and neck during the study period, and 11 patients (15 malignancies) met inclusion criteria. Nine patients developed 12 periocular malignancies and 3 patients required eyelid surgery for facial malignancies outside the periocular zone. All 11 patients developed a squamous cell carcinoma (14 malignancies), and 1 patient (1 malignancy) also developed a periocular basal cell carcinoma. There was orbital invasion in 4 cases and paranasal and/or cavernous sinus invasion in 3 cases. Two patients underwent exenteration. Seven cases required reconstruction with a free flap or graft

Healthcare professionals' response to cachexia in advanced cancer: a qualitative study.

PubMed

Millar, Claire; Reid, Joanne; Porter, Sam

2013-11-01

To explore healthcare professionals' experience, understanding, and perception of the needs of patients with cachexia in advanced cancer. A qualitative approach based on symbolic interactionism. A regional cancer center in a large teaching hospital in the United Kingdom. 34 healthcare professionals who had experience providing care to patients with cachexia in advanced cancer. Data collection consisted of two phases: focus group and semistructured interviews. Interviews were digitally recorded and transcribed verbatim for analysis. This article reports on findings from the second phase of data collection. Analysis revealed that professional approaches to cachexia were influenced by three overarching and interthinking themes: knowledge, culture, and resources. Healthcare professionals commonly recognized the impact of the syndrome; however, for nonpalliative healthcare professionals, a culture of avoidance and an overreliance on the biomedical model of care had considerable influence on the management of cachexia in patients with advanced cancer. Cachexia management in patients with advanced cancer can be difficult and is directed by a variable combination of the influence of knowledge, culture of the clinical area, and available resources. Distinct differences exist in the management of cachexia among palliative and nonpalliative care professionals. This study presented a multiprofessional perspective on the management of cachexia in patients with advanced cancer and revealed that cachexia is a complex and challenging syndrome that needs to be addressed from a holistic model of care. Cachexia management in patients with advanced cancer is complex and challenging and is directed by a combination of variables. An overreliance on the biomedical model of health and illness occurs in the management of cachexia in patients with advanced cancer. Cachexia needs to be addressed from a holistic model of care to reflect the multidimensional needs of patients and their

Yoga as palliation in women with advanced cancer: a pilot study.

PubMed

Carr, Tracey; Quinlan, Elizabeth; Robertson, Susan; Duggleby, Wendy; Thomas, Roanne; Holtslander, Lorraine

2016-03-01

The purpose of this pilot study was to investigate the palliative potential of home-based yoga sessions provided to women with advanced cancer. Personalised 45-minute yoga sessions were offered to three women with advanced cancer by an experienced yoga teacher. Each woman took part in a one-to-one interview after the completion of the yoga programme and was asked to describe her experiences of the programme's impact. The personalised nature of the yoga sessions resulted in similar positive physical and psychosocial effects comparable to those demonstrated in other studies with cancer patients. Participants described physical, mental, and emotional benefits as well as the alleviation of illness impacts. The enhancement of mind-body and body-spirit connections were also noted. Personalised home-based yoga programmes for people with advanced cancer may produce similar benefits, including palliation, as those institutionally-based programmes for people with non-advanced cancer.

Advances in the treatment of gastric cancer.

PubMed

Ilson, David H

2017-11-01

To review recent studies in esophagogastric cancer. Positive emission tomography (PET) scan in follow-up after curative treatment of esophagogastric cancer did not lead to improved survival. In the preoperative treatment of esophagogastric cancer, the addition of the antivascular endothelial growth factor agent bevacizumab to perioperative chemotherapy with combination epirubicin, cisplatinum, and 5-fluorouracil (5-FU; ECF) failed to improve survival compared with chemotherapy alone. In a head-to-head comparison of preoperative chemotherapy for locally advanced gastric and esophagogastric adenocarcinoma, FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improved overall survival compared with ECF. Assessing response to induction chemotherapy prior to combined preoperative chemoradiotherapy in PET nonresponding patients allowed a change in chemotherapy during subsequent radiotherapy with improved rates of pathologic complete response. In human epidermal growth factor receptor-2-positive advanced esophagogastric adenocarcinoma, second-line treatment with the chemotherapy/trastuzumab drug conjugate emtansine/trastuzumab failed to improve response or overall survival compared with treatment using paclitaxel chemotherapy. The immune checkpoint inhibitor, nivolumab, improved survival in refractory gastric cancer. Recent studies in gastric cancer clarify the optimal preoperative chemotherapy regimen and the use of PET scan as a response measure of preoperative therapy in esophagogastric cancer, and the role of targeted agents and immune checkpoint inhibitors in metastatic disease.

Apatinib for advanced nonsmall-cell lung cancer: A retrospective case series analysis.

PubMed

Yang, Chengxi; Feng, Wen; Wu, Di

2018-01-01

Apatinib, a tyrosine kinase inhibitor which selectively inhibits vascular endothelial growth factor receptor-2, has been shown to be beneficial to patients with a variety of cancers, including advanced nonsmall-cell lung cancer (NSCLC). Thus, this study was aimed to retrospectively assess the efficacy and safety of apatinib in patients with advanced/metastatic NSCLC who failed more than two lines of treatment. Twenty-three NSCLC patients were involved in this study, who received oral apatinib at a daily dose of 250/500/750 mg, with the progression after the failure of second-line therapy. Treatment was continued until disease progression. The tumor assessments were determined according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Safety was evaluated with adverse reactions and toxicities based on the Common Terminology Criteria for Adverse Events (version 4.0). Response and safety for the included patients were evaluated every 8 weeks. In this study, 23 NSCLC patients were followed from January 2015 to December 2016. Available image efficacy was obtained in 22 patients, including 4 identified as partial responses, 17 stable disease, and 1 progressive disease; no complete responses was observed. The objective response rate was 18.2%, and the disease control rate was 95.5%. Median progression free survival and overall survival for apatinib were 203 days (95% CI, 120-269) and 227 days (95% CI, 146-294), respectively. The most frequent treatment-related adverse events were hypertension, gastrointestinal reactions, and hand-foot skin reaction. Apatinib exhibited modest activity and acceptable toxicity for advanced NSCLC after the failure of chemotherapy or other targeted therapy.

Perspectives of newly diagnosed advanced cancer patients receiving dignity therapy during cancer treatment.

PubMed

Dose, Ann Marie; Rhudy, Lori M

2018-01-01

Dignity therapy is a psychosocial intervention that has been used primarily at the end of life to improve quality of life and other patient outcomes, but many individuals are unable to complete it due to health decline and death. The purpose of this study was to identify what individuals with advanced pancreatic or lung cancer with limited life expectancy, undergoing active cancer treatment describe during the dignity therapy intervention as important to them when not immediately facing end of life. Twenty patients undergoing chemotherapy for advanced cancer participated in a dignity therapy intervention study. Initial interviews were analyzed using descriptive content analysis. Family provided the overall context and background for emerging themes of defining events, accomplishments, and God's plan, which led to lessons learned, and resulted in messages of hope. Interviews were often autobiographical in nature and contained much reminiscence, consistent with dignity therapy's intent. Few participants spoke about their cancer diagnoses during the interview. This study adds unique insight into the use of dignity therapy for those still receiving active cancer treatment, different from work by others in which it was offered only at end of life. As part of supportive care, clinicians need to validate the importance of family to those with advanced cancer and to provide opportunities for patients to share what they have learned throughout life and to impart messages of hope to those closest to them.

New advances in targeted gastric cancer treatment.

PubMed

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-08-14

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

New advances in targeted gastric cancer treatment

PubMed Central

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-01-01

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

Solid rocket technology advancements for space tug and IUS applications

NASA Technical Reports Server (NTRS)

Ascher, W.; Bailey, R. L.; Behm, J. W.; Gin, W.

1975-01-01

In order for the shuttle tug or interim upper stage (IUS) to capture all the missions in the current mission model for the tug and the IUS, an auxiliary or kick stage, using a solid propellant rocket motor, is required. Two solid propellant rocket motor technology concepts are described. One concept, called the 'advanced propulsion module' motor, is an 1800-kg, high-mass-fraction motor, which is single-burn and contains Class 2 propellent. The other concept, called the high energy upper stage restartable solid, is a two-burn (stop-restartable on command) motor which at present contains 1400 kg of Class 7 propellant. The details and status of the motor design and component and motor test results to date are presented, along with the schedule for future work.

[Asthenia in advanced cancer and the use of psychostimulants].

PubMed

Portela Tejedor, M A; Sanz Rubiales, A; Martínez, M; Centeno Cortés, C

2011-01-01

Asthenia is the most frequent symptom in patients with advanced cancer and is probably what most affects the quality of life of oncology patients since it interferes in their physical and social activity. Treatment in the majority of cases is symptomatic. There is growing interest in the use of psychostimulants for treating asthenia. Methylphenidate and modafinil are two psychostimulants that have already been tested in controlled studies on asthenia of the patient with advanced cancer; they have proved to be efficient, particularly in patients in very advanced stages who are very tired.

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours.

PubMed

Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

2015-11-17

This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours.

Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study.

PubMed

Harris, Marian H; DuBois, Steven G; Glade Bender, Julia L; Kim, AeRang; Crompton, Brian D; Parker, Erin; Dumont, Ian P; Hong, Andrew L; Guo, Dongjing; Church, Alanna; Stegmaier, Kimberly; Roberts, Charles W M; Shusterman, Suzanne; London, Wendy B; MacConaill, Laura E; Lindeman, Neal I; Diller, Lisa; Rodriguez-Galindo, Carlos; Janeway, Katherine A

2016-01-28

Pediatric cancers represent a unique case with respect to cancer genomics and precision medicine, as the mutation frequency is low, and targeted therapies are less available. Consequently, it is unknown whether clinical sequencing can be of benefit. To assess the feasibility of identifying actionable alterations and making individualized cancer therapy (iCat) recommendations in pediatric patients with extracranial solid tumors. Clinical sequencing study at 4 academic medical centers enrolling patients between September 5, 2012, and November 19, 2013, with 1 year of clinical follow-up. Participants were 30 years or younger with high-risk, recurrent, or refractory extracranial solid tumors. The data analysis was performed October 28, 2014. Tumor profiling performed on archived clinically acquired specimens consisted of mutation detection by a Sequenom assay or targeted next-generation sequencing and copy number assessment by array comparative genomic hybridization. Results were reviewed by a multidisciplinary expert panel, and iCat recommendations were made if an actionable alteration was present, and an appropriate drug was available. Feasibility was assessed using a 2-stage design based on the proportion of patients with recommendations. Of 100 participants (60 male; median [range] age, 13.4 [0.8-29.8] years), profiling was technically successful in 89 (89% [95% CI, 83%-95%]). Median (range) follow-up was 6.8 (2.0-23.6) months. Overall, 31 (31% [95% CI, 23%-41%]) patients received an iCat recommendation and 3 received matched therapy. The most common actionable alterations leading to an iCat recommendation were cancer-associated signaling pathway gene mutations (n = 10) and copy number alterations in MYC/MYCN (n = 6) and cell cycle genes (n = 11). Additional alterations with implications for clinical care but not resulting in iCat recommendations were identified, including mutations indicating the possible presence of a cancer predisposition syndrome

Recent advances and future challenges in cancer immunotherapy.

PubMed

Okuyama, Namiko; Tamada, Koji; Tamura, Hideto

2016-01-01

Remarkable advances have been made in cancer immunotherapy. Recent treatment strategies, especially chimeric antigen receptor-T (CAR-T) cell therapy and immune checkpoint inhibitors, reportedly achieve higher objective responses and better survival rates than previous immunotherapies for patients with treatment-resistant malignancies, creating a paradigm shift in cancer treatment. Several clinical trials of cancer immunotherapy for patients with various malignancies are ongoing. However, those with certain malignancies, such as low-immunogenic cancers, cannot be successfully treated with T-cell immunotherapy, and subsets of immunotherapy-treated patients relapse, meaning that more effective immunotherapeutic strategies are needed for such patients. Furthermore, the safety, convenience, and cost of cancer immunotherapy need to be improved in the near future. Herein, we discuss recent advances and future challenges in cancer immunotherapy, i.e., the identification of neoantigens for the development of individualized immunotherapies, the development of new CAR-T cell therapies, including so-called armored CAR-T cells that can induce greater clinical effects and thereby achieve longer survival, the development of off-the-shelf treatment regimens using non-self cells or cell lines, and effective cancer immunotherapy combinations.

A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.

PubMed

Papadopoulos, Kyriakos P; Burris, Howard A; Gordon, Michael; Lee, Peter; Sausville, Edward A; Rosen, Peter J; Patnaik, Amita; Cutler, Richard E; Wang, Zhengping; Lee, Susan; Jones, Suzanne F; Infante, Jeffery R

2013-10-01

Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.

Nanophotosensitizers toward advanced photodynamic therapy of Cancer.

PubMed

Lim, Chang-Keun; Heo, Jeongyun; Shin, Seunghoon; Jeong, Keunsoo; Seo, Young Hun; Jang, Woo-Dong; Park, Chong Rae; Park, Soo Young; Kim, Sehoon; Kwon, Ick Chan

2013-07-01

Photodynamic therapy (PDT) is a non-invasive treatment modality for selective destruction of cancer and other diseases and involves the colocalization of light, oxygen, and a photosensitizer (PS) to achieve photocytotoxicity. Although this therapeutic method has considerably improved the quality of life and life expectancy of cancer patients, further advances in selectivity and therapeutic efficacy are required to overcome numerous side effects related to classical PDT. The application of nanoscale photosensitizers (NPSs) comprising molecular PSs and nanocarriers with or without other biological/photophysical functions is a promising approach for improving PDT. In this review, we focus on four nanomedical approaches for advanced PDT: (1) nanocarriers for targeted delivery of PS, (2) introduction of active targeting moieties for disease-specific PDT, (3) stimulus-responsive NPSs for selective PDT, and (4) photophysical improvements in NPS for enhanced PDT efficacy. ► Conservation of normal tissues demands non-invasive therapeutic methods. ► PDT is a light-activated, non-invasive modality for selective destruction of cancers.► Success of PDT requires further advances to overcome the limitations of classical PDT. ►Nanophotosensitizers help improve target selectivity and therapeutic efficacy of PDT. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ondansetron in Treating Patients With Advanced Cancer and Chronic Nausea and Vomiting Not Caused by Cancer Treatment

ClinicalTrials.gov

2016-07-01

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Nausea and Vomiting; Precancerous Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Advanced Heart Failure Therapies for Cancer Therapeutics-Related Cardiac Dysfunction.

PubMed

Bianco, Christopher M; Al-Kindi, Sadeer G; Oliveira, Guilherme H

2017-04-01

End-stage heart failure in cancer survivors may result from cardiotoxic chemotherapy and/or chest radiation and require advanced therapies, including left ventricular assist devices (LVADs) and transplantation. Traditionally, such therapies have been underutilized in cancer survivors owing to lack of experience and perceived risk of cancer recurrence. Recent data from large registries, however, have shown excellent outcomes of LVADs and transplantation in cancer survivors, albeit subject to careful selection and special considerations. This article summarizes all aspects of advanced heart failure therapies in patients with cancer therapy-related cardiac dysfunction and underscores the need for careful selection of these candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

Upper gastrointestinal symptoms in patients with advanced cancer: relationship to nutritional and performance status.

PubMed

Bovio, G; Montagna, G; Bariani, C; Baiardi, P

2009-10-01

The goals of the study were to determine the relationship of upper gastrointestinal symptoms with nutritional status and to assess their association with performance status in patients with advanced cancer. We studied 143 patients (50 F, 93 M, mean age 68 +/- 11 years, mean body mass index 22.39 +/- 4.3 kg/m(2)). Assessed symptoms were the following: anorexia, nausea, vomiting, dysphagia for solids, dysphagia for liquids, xerostomia, hypogeusia, dysgeusia, hiccup and chewing disturbances. We determined anthropometric parameters, daily energy intake and serum albumin, prealbumin and transferrin. The most common upper gastrointestinal symptoms were xerostomia (73%), anorexia (49%) and chewing disturbances (40%). Fifty-four percent of patients had weight loss greater than 10%. Seventy-three patients (51%) had daily energy intake lower than their resting energy expenditure. Mean serum prealbumin, albumin and transferrin were below normal range. Mean Eastern Cooperative Oncology Group performance status scale was 3.1 +/- 0.49. Symptoms were often strongly correlated, and usually, patients experienced at least three upper gastrointestinal symptoms at the same time. Anorexia, nausea and vomiting were the symptoms mostly correlated with other symptoms. A correlation was found between vomiting and hiccup. Energy intake (EI) was the nutritional parameter mostly affected by upper gastrointestinal symptoms; moreover, EI is the most predictive factor of upper gastrointestinal symptoms, particularly xerostomia, anorexia and dysphagia for solids. Upper gastrointestinal symptoms are linked to nutritional parameters: In particular, energy intake represents the most predictive variable of symptom occurrence. The performance status is not affected by upper gastrointestinal symptoms. A rigorous nutritional assessment and the managing of upper gastrointestinal symptoms are crucial in patients with advanced cancer.

Observational study of sleep disturbances in advanced cancer.

PubMed

Davies, Andrew Neil; Patel, Shuchita D; Gregory, Amanda; Lee, Bernadette

2017-12-01

To determine the prevalence of nightmares, sleep terrors and vivid dreams in patients with advanced cancer (and the factors associated with them in this group of patients). The study was a multicentre, prospective observational study. Participants were patients with locally advanced/metastatic cancer, who were under the care of a specialist palliative care team. Data were collected on demographics, cancer diagnosis, cancer treatment, current medication, performance status, sleep quality (Pittsburgh Sleep Quality Index), dreams and nightmares, and physical and psychological symptoms (Memorial Symptom Assessment Scale-Short Form). 174 patients completed the study. Sleep quality was poor in 70.5% participants and was worse in younger patients and in inpatients (hospital, hospice). 18% of patients reported nightmares, 8% sleep terrors and 34% vivid dreams. Nightmares were associated with poor sleep quality and greater sleep disturbance; nightmares were also associated with greater physical and psychological burden. Nightmares (and vivid dreams) were not associated with the use of opioid analgesics. Nightmares do not seem to be especially common in patients with advanced cancer, and when they do occur, there is often an association with sleep disturbance, and/or physical and psychological burden. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Concurrent apatinib and local radiation therapy for advanced gastric cancer

PubMed Central

Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

2017-01-01

Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

6. Credit WCT. Photographic copy of photograph, Advanced Solid Rocket ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. Credit WCT. Photographic copy of photograph, Advanced Solid Rocket Motor (ASRM) test in progress at Test Stand 'E.' It was a JPL/Marshall Space Flight Center project. (JPL negative no. 344-4816 19 February 1982) - Jet Propulsion Laboratory Edwards Facility, Test Stand E, Edwards Air Force Base, Boron, Kern County, CA

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors.

PubMed

Bauer, Todd M; Patel, Manish R; Forero-Torres, Andres; George, Thomas J; Assad, Albert; Du, Yining; Hurwitz, Herbert

2018-01-01

Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B). The objective of the dose-finding phase was to identify the maximum tolerated doses (MTDs) of ruxolitinib plus gemcitabine with or without nab-paclitaxel. Among 42 patients enrolled, the median age was 62.5 years, 81.0% had pancreatic cancer, and almost 62% had received prior systemic therapy. Regimen A was tolerated with standard doses of gemcitabine; regimen B was tolerated with reduced doses of gemcitabine/nab-paclitaxel or concomitant granulocyte colony-stimulating factor. The sponsor decided to terminate the study early due to the interim analysis results of the Phase III JANUS 1 study. Discontinuations were mainly due to radiologic or clinical disease progression (81.0% of patients). Median treatment durations were 55.5 days (cohort A0) and 150.5 days (pooled B cohorts). Four patients (pooled B cohorts) had dose-limiting toxicities: grade 3 pneumonia (n=1), grade 4 neutropenia (n=1), and grade 4 thrombocytopenia (n=2). The most common grade 3/4 hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. Serious AEs occurring in ≥2 patients in cohort A0 or pooled B cohorts were abdominal pain, sepsis (cohort A0), dehydration, anemia, and asthenia (pooled B cohorts). Overall response rates (ORRs) were 12.5% in cohort A0 and 38.5% in pooled B cohorts. Among patients with pancreatic cancer, ORR was 23.5% (14.0% cohort A0 30.0% pooled B cohorts). The study was terminated early prior to reaching MTDs per sponsor decision; although ruxolitinib plus gemcitabine with or

Advances of high intensity focused ultrasound (HIFU) for pancreatic cancer.

PubMed

Xiaoping, Li; Leizhen, Zheng

2013-11-01

High intensity focused ultrasound (HIFU) is a novel therapeutic modality. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumours, including pancreatic cancer. Preliminary studies suggest that HIFU may be useful for the palliative therapy of cancer-related pain in patients with unresectable pancreatic cancer. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-05-29

Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

PubMed Central

Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

2015-01-01

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

[Recent advance in chemotherapy for advanced colorectal cancer].

PubMed

Aiba, K

1996-04-01

Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in

Treatment for Chronic Pain in Patients With Advanced Cancer

ClinicalTrials.gov

2016-11-25

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Pain; Precancerous/Nonmalignant Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces.

PubMed

Michaelides, Angelos; Martinez, Todd J; Alavi, Ali; Kresse, Georg; Manby, Frederick R

2015-09-14

This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science.

Physical activity in advanced cancer patients: a systematic review protocol.

PubMed

Lowe, Sonya S; Tan, Maria; Faily, Joan; Watanabe, Sharon M; Courneya, Kerry S

2016-03-11

Progressive, incurable cancer is associated with increased fatigue, increased muscle weakness, and reduced physical functioning, all of which negatively impact quality of life. Physical activity has demonstrated benefits on cancer-related fatigue and physical functioning in early-stage cancer patients; however, its impact on these outcomes in end-stage cancer has not been established. The aim of this systematic review is to determine the potential benefits, harms, and effects of physical activity interventions on quality of life outcomes in advanced cancer patients. A systematic review of peer-reviewed literature on physical activity in advanced cancer patients will be undertaken. Empirical quantitative studies will be considered for inclusion if they present interventional or observational data on physical activity in advanced cancer patients. Searches will be conducted in the following electronic databases: CINAHL; CIRRIE Database of International Rehabilitation Research; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effects (DARE); Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; PEDro: the Physiotherapy Evidence Database; PQDT; PsycInfo; PubMed; REHABDATA; Scopus; SPORTDiscus; and Web of Science, to identify relevant studies of interest. Additional strategies to identify relevant studies will include citation searches and evaluation of reference lists of included articles. Titles, abstracts, and keywords of identified studies from the search strategies will be screened for inclusion criteria. Two independent reviewers will conduct quality appraisal using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies (EPHPP) and the Cochrane risk of bias tool. A descriptive summary of included studies will describe the study designs, participant and activity characteristics, and objective and patient-reported outcomes. This systematic review will summarize the current

Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial.

PubMed

Frenel, Jean-Sebastien; Le Tourneau, Christophe; O'Neil, Bert; Ott, Patrick A; Piha-Paul, Sarina A; Gomez-Roca, Carlos; van Brummelen, Emilie M J; Rugo, Hope S; Thomas, Shari; Saraf, Sanatan; Rangwala, Reshma; Varga, Andrea

2017-12-20

Purpose The KEYNOTE-028 trial ( ClinicalTrials.gov identifier: NCT02054806) was designed to assess the safety and efficacy of pembrolizumab in 20 programmed death ligand 1-positive, advanced solid tumor cohorts. Here, we present the results from the cohort of patients with advanced cervical cancer. Methods Patients were treated with pembrolizumab 10 mg/kg every 2 weeks for up to 24 months. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary end point was overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, by investigator review. Safety was a secondary end point. Results Twenty-four patients were enrolled in the cervical cancer cohort. The median age was 42 years (range, 26 to 62 years), 22 patients (92%) had received prior radiation therapy, and 15 patients (63%) had received two or more lines of therapy, including bevacizumab (10 of 24 patients), for advanced disease. At the data cutoff, median follow-up duration was 11.0 months (range, 1.3 to 32.2 months). Overall response rate was 17% (95% CI, 5% to 37%); four patients (17%) achieved a confirmed partial response, and three patients (13%) had stable disease. Median duration of response for the four patients who achieved a partial response was 5.4 months (4.1 to 7.5 months). Treatment related adverse events (AEs) were experienced by 18 patients (75%); only rash (n = 5; 21%) and pyrexia (n = 4; 17%) and occurred in ≥ 10% of patients. Five patients experienced grade 3 treatment-related AEs. No grade 4 treatment-related AEs or deaths were observed. Conclusion In patients with programmed death ligand 1-positive advanced cervical cancer, pembrolizumab demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other tumor types.

Advances in Systemic Therapy for Metastatic or Advanced Gastric Cancer.

PubMed

Shitara, Kohei; Ohtsu, Atsushi

2016-10-01

In recent years, various new agents have been investigated for the treatment of advanced gastric cancer (AGC). The anti-HER2 antibody trastuzumab has been shown to prolong the overall survival of patients with HER2-positive AGC and has become a standard treatment. However, lapatinib, or ado-trastuzumab emtansine (T-DM1), did not show survival benefit in AGC, although it has shown remarkable efficacy for HER2-positive breast cancer. The efficacy of the anti-vascular endothelial growth factor receptor monoclonal antibody ramucirumab for pretreated gastric cancer is a milestone for antiangiogenic therapy for AGC. Early clinical trials of TAS-118, TAS-102, and STAT3 inhibitors; IMAB362 (anti-Claudin 18.2); and immune checkpoint inhibitors are all encouraging. These findings warrant further evaluation in larger clinical trials. Copyright © 2016 by the National Comprehensive Cancer Network.

Targeted genetic and viral therapy for advanced head and neck cancers.

PubMed

Huang, Pin-I; Chang, Ju-Fang; Kirn, David H; Liu, Ta-Chiang

2009-06-01

Head and neck cancers usually present with advanced disease and novel therapies are urgently needed. Genetic therapy aims at restoring malfunctioned tumor suppressor gene(s) or introducing proapoptotic genes. Oncolytic virotherapeutics induce multiple cycles of cancer-specific virus replication, followed by oncolysis, virus spreading and infection of adjacent cancer cells. Oncolytic viruses can also be armed to express therapeutic transgene(s). Recent advances in preclinical and clinical studies are revealing the potential of both therapeutic classes for advanced head and neck cancers, including the approval of two products (Gendicine and H101) by a governmental agency. This review summarizes the available clinical data to date and discusses the challenges and future directions.

Advances in pancreatic cancer research: moving towards early detection.

PubMed

He, Xiang-Yi; Yuan, Yao-Zong

2014-08-28

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

Effects of rehabilitation among patients with advances cancer: a systematic review.

PubMed

Salakari, Minna R J; Surakka, Tiina; Nurminen, Raija; Pylkkänen, Liisa

2015-05-01

In parallel with the rising incidence of cancer and improved treatment, there is a continuous increase in the number of patients living with cancer as a chronic condition. Many cancer patients experience long-term disability and require continuous oncological treatment, care and support. The aim of this review is to evaluate the most recent data on the effects of rehabilitation among patients with advanced cancer. A systematic review was conducted according to Fink's model. Only randomized controlled trials (RCTs) published in 2009-2014 were included. Medline/PubMed and Cochrane databases were searched; five groups of keywords were used. The articles were evaluated for outcome and methodological quality. Thirteen RCTs (1169 participants) were evaluated. Most studies were on the effects of physical exercise in patients with advanced cancer (N = 7). Physical exercise was associated with a significant improvement in general wellbeing and quality of life. Rehabilitation had positive effects on fatigue, general condition, mood, and coping with cancer. Rehabilitation is needed also among patients with advanced disease and in palliative care. Exercise improves physical performance and has positive effects on several other quality of life domains. More data and RCTs are needed, but current evidence gives an indication that rehabilitation is suitable and can be recommended for patients living with advanced cancer.

Functional rehabilitation in advanced intraoral cancer.

PubMed

Barret, Juan P; Roodenburg, Jan L

2017-02-01

Modern treatment of advanced intraoral cancer involves multidisciplinary teams with use of complicated reconstructive techniques to provide improved survival with optimal rehabilitation. Mastication is an important part of this process, and it can be severely impaired by tumor ablation. Whether flap reconstruction is a determinant factor in dental rehabilitation is still in debate. Thirty-five patients with advanced intraoral cancer were reviewed to determine dental rehabilitation of different reconstructive techniques. The patients were treated with a multidisciplinary team approach. The patients' demographics, primary treatment, reconstructive surgery, dental rehabilitation, and functional outcome were recorded and analyzed. Nine patients had Stadium III disease, and 26 patients had stadium IV. Thirty-two patients (91.42%) received postoperative radiotherapy. Masticatory and dental functional rehabilitation of patients was very poor. Only 15 patients (42.86%) could eat a normal diet, whereas 18 patients (51.42%) could manage only soft diets, and 2 patients (5.72%) could only be fed with a liquid diet. Denture rehabilitation was even more frustrating and had a direct impact on masticatory rehabilitation. Only 10 patients (28.57%) could use dentures postoperatively and 40% of patients (14 patients) could not use any denture at all. Above all reconstructive techniques, the free radial forearm flap provides the best functional outcome. Reconstruction of advanced intraoral cancer results in poor denture rehabilitation, especially when bulky flaps are used. If massive resections are necessary, the free radial forearm flap reconstruction provides the best functional outcome.

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

PubMed

Srdic, Drazena; Plestina, Sanja; Sverko-Peternac, Ana; Nikolac, Nora; Simundic, Ana-Maria; Samarzija, Miroslav

2016-11-01

Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients

Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors

ClinicalTrials.gov

2015-05-22

Adult Solid Neoplasm; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Spectrum of Cancer Risk among U.S. Solid Organ Transplant Recipients: The Transplant Cancer Match Study

PubMed Central

Engels, Eric A.; Pfeiffer, Ruth M.; Fraumeni, Joseph F.; Kasiske, Bertram L.; Israni, Ajay K.; Snyder, Jon J.; Wolfe, Robert A.; Goodrich, Nathan P.; Bayakly, A. Rana; Clarke, Christina A.; Copeland, Glenn; Finch, Jack L.; Fleissner, Mary Lou; Goodman, Marc T.; Kahn, Amy; Koch, Lori; Lynch, Charles F.; Madeleine, Margaret M.; Pawlish, Karen; Rao, Chandrika; Williams, Melanie A.; Castenson, David; Curry, Michael; Parsons, Ruth; Fant, Gregory; Lin, Monica

2012-01-01

Context Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Since most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. Objective Describe the overall pattern of cancer among solid organ transplant recipients. Design Cohort study using linked data from the U.S. Scientific Registry of Transplant Recipients (1987–2008) and 13 state/regional cancer registries. Participants and Setting Solid organ transplant recipients in the U.S. Main Outcome Measure Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared to the general population. Results Registry linkages yielded data on 175,732 solid organ transplants (58.4% kidney, 21.6% liver, 10.0% heart, 4.0% lung). Overall cancer risk was elevated (N=10,656 cases, incidence 1374.7 per 100,000 person-years; SIR 2.10, 95%CI 2.06–2.14; EAR 719.3, 95%CI 693.3–745.6, per 100,000 person-years). Risk was increased (p<0.001) for 32 different malignancies, some related to known infections (e.g., anal cancer, Kaposi sarcoma) and others unrelated (e.g., melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (N=1504, incidence 194.0; SIR 7.54, 95%CI 7.17–7.93; EAR 168.3, 95%CI 158.6–178.4) and cancers of the lung (N=1344, incidence 173.4; SIR 1.97, 95%CI 1.86–2.08; EAR 85.3, 95%CI 76.2–94.8), liver (N=930, incidence 120.0; SIR 11.56, 95%CI 10.83–12.33; EAR 109.6, 95%CI 102.0–117.6), and kidney (N=752, incidence 97.0; SIR 4.65, 95%CI 4.32–4.99; EAR 76.1, 95%CI 69.3–83.3). Lung cancer risk was most elevated in lung recipients (SIR 6.13, 95%CI 5.18–7.21) but also increased among other recipients (SIR 1.46, 95%CI 1.34–1.59 for kidney; 1.95, 1.74–2.19 for liver; 2.67, 2.40–2.95 for heart). Liver cancer was elevated only

Management of Locally Advanced Cancer Cervix an Indian Perspective.

PubMed

Singh, J K; Chauhan, Richa

2015-01-01

Cervical cancer has a major impact on the lives of Indian women with an estimated 122, 844 new cases of cervical cancer in the year 2012. About 80% of these cases present in a locally advanced stage leading to high morbidity and mortality. Because of lack of public awareness and infrastructure for screening and early detection in developing countries, this late presentation is likely to continue in the coming years. Radiation therapy has been the treatment of choice for patients with locally advanced cancer cervix. Many clinical trials and meta-analyses have shown a significant improvement in overall and progression-free survival with decreased local and distant recurrences with the use of concurrent chemotherapy with radiation. Most of these trials have been done in women from developed countries where the patient and disease profile are entirely different from ours. Recently, few trials from India have also shown promising results in locally advanced cancer cervix with concurrent chemoradiotherapy but toxicities remain a major concern. Further exploration is required for the use of concurrent chemo radiation prior to incorporating it into routine clinical practice.

[Prognostic factors of advanced stage non-small-cell lung cancer].

PubMed

Kwas, H; Guermazi, E; Khattab, A; Hrizi, C; Zendah, I; Ghédira, H

2017-09-01

Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years. To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages. A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013. The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment. The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Interaction patterns between parents with advanced cancer and their adolescent children.

PubMed

Sheehan, Denice Kopchak; Draucker, Claire Burke

2011-10-01

Advanced cancer profoundly affects those with the illness and their families. The interaction patterns between parents with advanced cancer and their adolescent children are likely to influence how a family experiences a parent's dying process. There is little information on such interactions. This study aimed to develop an explanatory model that explains interaction patterns between parents with advanced cancer and their adolescent children and to identify strategies to prepare children for their lives after a parent dies. Semi-structured interviews were conducted with 9 parents with advanced cancer, 7 of their spouses/partners, and 10 of their adolescent children. The interviews were recorded, transcribed verbatim, and analyzed using a constructionist grounded theory approach. Twenty-six family participants were interviewed. Their main concern was not having enough time together. In response, they described a four-stage process for optimizing the time they had left together: coming to know our time together is limited, spending more time together, extending our time together, and giving up our time together to end the suffering. The adolescents and their ill parents did not change their interaction patterns until they realized their time together was limited by the advanced cancer. Then they spent more time together to make things easier for each other. Time was of great importance to the parents and adolescents; all the participants structured their stories in relation to the concept of time. The model reflects the dynamic process by which families continuously adapt their relationships in the face of advanced cancer. 2010 John Wiley & Sons, Ltd.

Surgery for advanced epithelial ovarian cancer.

PubMed

Hacker, Neville F; Rao, Archana

2017-05-01

Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively. Copyright © 2016. Published by Elsevier Ltd.

Management of cancer-associated thrombosis in people with advanced disease.

PubMed

Noble, Simon; Johnson, Miriam J

2012-06-01

The management of venous thromboembolism in the cancer population is clearly established. Low molecular weight heparin has a greater efficacy than warfarin in the treatment of cancer-associated thrombosis and is recommended as the preferred therapy. However, the evidence informing these recommendations excluded patients with poor prognosis or performance status, thrombocytopenia, bleeding or brain metastases. Furthermore, there is limited data on the management of venous thromboembolism resistant to anticoagulation, a phenomenon frequently encountered in the advanced cancer population. This paper will review the management of cancer-associated thrombosis with a particular focus on challenging clinical situations faced by palliative care teams looking after patients with advanced disease.

Advances for Studying Clonal Evolution in Cancer

PubMed Central

Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

2013-01-01

The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

Advances for studying clonal evolution in cancer.

PubMed

Ding, Li; Raphael, Benjamin J; Chen, Feng; Wendl, Michael C

2013-11-01

The "clonal evolution" model of cancer emerged and "evolved" amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other's survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Advances in immunotherapy for non-small cell lung cancer.

PubMed

Reckamp, Karen L

2015-12-01

In most patients, lung cancer presents as advanced disease with metastases to lymph nodes and/or distant organs, and survival is poor. Lung cancer is also a highly immune-suppressing malignancy with numerous methods to evade antitumor immune responses, including deficiencies in antigen processing and presentation, release of immunomodulatory cytokines, and inhibition of T-cell activation. Advances in understanding the complex interactions of the immune system and cancer have led to novel therapies that promote T-cell activation at the tumor site, resulting in prolonged clinical benefit. Immune checkpoint inhibitors, specifically programmed death receptor 1 pathway antibodies, have demonstrated impressively durable responses and improved survival in patients with non-small cell lung cancer. This article will review the recent progress made in immunotherapy for lung cancer with data from trials evaluating programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 monoclonal antibodies in addition to cancer vaccines. The review will focus on studies that have been published and the latest randomized trials exploring immune therapy in lung cancer. These results form the framework for a new direction in the treatment of lung cancer toward immunotherapy.

Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature.

PubMed

Srivatsa, N; Nagaraja, H; Shweta, S; Raghunath, S K

2017-06-01

Twenty-five to thirty percent of patients with prostate cancer present with locally advanced disease. While risk stratification remains the same with high incidence of upstaging of disease on imaging and histopathological evaluation; there have been progressive refinements in surgical therapy. With availability of reasonably robust data, radical prostatectomy in men with locally advanced prostate cancers seems to effect improvement in both cancer specific and overall survival rates in comparison to the current standard of care of radiation with androgen deprivation therapy. Studies using radical prostatectomy as a part of multimodality approach have also shown promising results. There is an imminent need for well-designed prospective studies of benefits of radical prostatectomy over radiation and androgen deprivation as well as benefits of multimodality therapy over monotherapy. Surgery for patients with locally advanced prostate cancer is technically challenging. Surgical outcomes are comparable to those of organ-confined disease when performed in high-volume centers. Neoadjuvant therapies prior to radical prostatectomy might improve surgical outcomes, but whether they will translate into a better cancer specific and overall survival are yet to be ascertained.

Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

PubMed

Lee, G L; Pang, G S Y; Akhileswaran, R; Ow, M Y L; Fan, G K T; Wong, C C F; Wee, H L; Cheung, Y B

2016-03-01

Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

Cancer.gov

Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

PubMed

Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

2012-10-01

This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

Analysis of advanced solid rocket motor ignition phenomena

NASA Technical Reports Server (NTRS)

Foster, Winfred A., Jr.; Jenkins, Rhonald M.

1995-01-01

This report presents the results obtained from an experimental analysis of the flow field in the slots of the star grain section in the head-end of the advanced solid rocket motor during the ignition transient. This work represents an extension of the previous tests and analysis to include the effects of using a center port in conjunction with multiple canted igniter ports. The flow field measurements include oil smear data on the star slot walls, pressure and heat transfer coefficient measurements on the star slot walls and velocity measurements in the star slot.

Cancer nanoimmunotherapy using advanced pharmaceutical nanotechnology.

PubMed

Li, Wei; Wei, Huafeng; Li, Huafei; Gao, Jie; Feng, Si-Shen; Guo, Yajun

2014-11-01

Immunotherapy is a promising option for cancer treatment that might cure cancer with fewer side effects by primarily activating the host's immune system. However, the effect of traditional immunotherapy is modest, frequently due to tumor escape and resistance of multiple mechanisms. Pharmaceutical nanotechnology, which is also called cancer nanotechnology or nanomedicine, has provided a practical solution to solve the limitations of traditional immunotherapy. This article reviews the latest developments in immunotherapy and nanomedicine, and illustrates how nanocarriers (including micelles, liposomes, polymer-drug conjugates, solid lipid nanoparticles and biodegradable nanoparticles) could be used for the cellular transfer of immune effectors for active and passive nanoimmunotherapy. The fine engineering of nanocarriers based on the unique features of the tumor microenvironment and extra-/intra-cellular conditions of tumor cells can greatly tip the triangle immunobalance among host, tumor and nanoparticulates in favor of antitumor responses, which shows a promising prospect for nanoimmunotherapy.

Solid cancer, antiphospholipid antibodies, and venous thromboembolism.

PubMed

Font, Carme; Vidal, Laura; Espinosa, Gerard; Tàssies, Dolors; Monteagudo, Joan; Farrús, Blanca; Visa, Laura; Cervera, Ricard; Gascon, Pere; Reverter, Joan C

2011-02-01

The pathogenic role of antiphospholipid antibodies (aPL) in the development of venous thromboembolism (VTE) in patients with malignancies has not been established. From May 2006 to April 2008, 258 consecutive patients with solid-organ malignancies who developed VTE (VTE+) were recruited. A group of 142 patients matched for age, sex and tumor type cancer patients without VTE (VTE-) and an age-and-sex matched group of 258 healthy subjects were also included. A second blood sample was taken in positive aPL patients at least 12 weeks later. Twenty-one (8.1%) VTE+ patients, 2 (1.4%) VTE- patients (p=0.006) and 2 (0.8%) healthy subjects (p<0.001) were positive for aPL. Persistent aPL positivity was observed in only 4 out of 15 available VTE+ patients. No differences in demographic characteristics, clinical pattern and outcome were observed in VTE+ patients according to aPL status. The low prevalence and transience of aPL positivity in patients with solid-organ malignancies with VTE argues against a pathogenic role in the development of thrombosis in this setting. The published evidence of the relationship between cancer, aPL, and thrombosis is reviewed. Copyright © 2010 Elsevier B.V. All rights reserved.

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

PubMed

Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p  = .006) and hospitalization (50% vs. 15%, p  = .03) than those with CTRS <10. Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

PubMed Central

Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

2015-01-01

Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). Results: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. Conclusions: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. PMID:26512876

Phase II study of erlotinib in patients with advanced biliary cancer.

PubMed

Philip, Philip A; Mahoney, Michelle R; Allmer, Cristine; Thomas, James; Pitot, Henry C; Kim, George; Donehower, Ross C; Fitch, Tom; Picus, Joel; Erlichman, Charles

2006-07-01

Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months. Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally. Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash. Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

Major clinical research advances in gynecologic cancer in 2017.

PubMed

Suh, Dong Hoon; Kim, Miseon; Lee, Kyung Hun; Eom, Keun Yong; Kjeldsen, Maj Kamille; Mirza, Mansoor Raza; Kim, Jae Weon

2018-03-01

In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer. For ovarian cancer, 5 topics were selected including poly(ADP-ribose) polymerases inhibitors and immunotherapy. The other potential practice changers covered in this review were lymphadenectomy in advanced disease, secondary cytoreductive surgery in recurrent disease, weekly dose-dense regimen for first-line chemotherapy, incorporation of bevacizumab maintenance in platinum-sensitive recurrent disease, and effect of platinum-free interval prolongation. Conflicting opinions of academic societies on periodic pelvic examination were introduced in conjunction with relevant literature review. For the field of radiation oncology, results of 2 big trials, The Postoperative Radiation Therapy in Endometrial Carcinoma-3 and Gynecologic Oncology Group-258, for endometrial cancer and recent advance in high-dose-rate brachytherapy for cervical cancer were reported. Topics for breast cancer covered adjuvant capecitabine after preoperative chemotherapy, adjuvant pertuzumab and trastuzumab in early human epidermal growth factor receptor 2-positive disease, olaparib for metastatic cancer in patients with a germline BRCA mutation, 20-year risks of recurrence after stopping endocrine therapy at 5 years, and contemporary hormonal contraception and the risk of breast cancer. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Functional rehabilitation in advanced intraoral cancer

PubMed Central

Roodenburg, Jan L.

2017-01-01

Introduction: Modern treatment of advanced intraoral cancer involves multidisciplinary teams with use of complicated reconstructive techniques to provide improved survival with optimal rehabilitation. Mastication is an important part of this process, and it can be severely impaired by tumor ablation. Whether flap reconstruction is a determinant factor in dental rehabilitation is still in debate. Patients and methods: Thirty-five patients with advanced intraoral cancer were reviewed to determine dental rehabilitation of different reconstructive techniques. The patients were treated with a multidisciplinary team approach. The patients’ demographics, primary treatment, reconstructive surgery, dental rehabilitation, and functional outcome were recorded and analyzed. Results: Nine patients had Stadium III disease, and 26 patients had stadium IV. Thirty-two patients (91.42%) received postoperative radiotherapy. Masticatory and dental functional rehabilitation of patients was very poor. Only 15 patients (42.86%) could eat a normal diet, whereas 18 patients (51.42%) could manage only soft diets, and 2 patients (5.72%) could only be fed with a liquid diet. Denture rehabilitation was even more frustrating and had a direct impact on masticatory rehabilitation. Only 10 patients (28.57%) could use dentures postoperatively and 40% of patients (14 patients) could not use any denture at all. Above all reconstructive techniques, the free radial forearm flap provides the best functional outcome. Conclusions: Reconstruction of advanced intraoral cancer results in poor denture rehabilitation, especially when bulky flaps are used. If massive resections are necessary, the free radial forearm flap reconstruction provides the best functional outcome. PMID:29177211

The space shuttle advanced solid rocket motor: Quality control and testing

NASA Technical Reports Server (NTRS)

1991-01-01

The Congressional committees that authorize the activities of NASA requested that the National Research Council (NRC) review the testing and quality assurance programs for the Advanced Solid Rocket Motor (ASRM) program. The proposed ASRM design incorporates numerous features that are significant departures from the Redesigned Solid Rocket Motor (RSRM). The NRC review concentrated mainly on these features. Primary among these are the steel case material, welding rather than pinning of case factory joints, a bolted field joint designed to close upon firing the rocket, continuous mixing and casting of the solid propellant in place of the current batch processes, use of asbestos-free insulation, and a lightweight nozzle. The committee's assessment of these and other features of the ASRM are presented in terms of their potential impact on flight safety.

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study

PubMed Central

Kulich, M.; Řeřicha, V.; Řeřicha, R.; Shore, D.L.; Sandler, D.P.

2011-01-01

Objectives Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. Methods A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n = 1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Results Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73 – 1.04, n = 1020), 0.87 for all digestive cancers (95% CI 0.69 – 1.09, n = 561), 2.39 for gallbladder cancer (95% CI 0.52 – 10.98, n = 13), 0.79 for larynx cancer (95% CI 0.38 – 1.64, n = 62), 2.92 for malignant melanoma (95% CI 0.91 – 9.42, n = 23), 0.84 for bladder cancer (95% CI 0.43 – 1.65, n = 73), and 1.13 for kidney cancer (95% CI 0.62 – 2.04, n = 66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Conclusions Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. PMID:21256480

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

PubMed

Kulich, M; Reřicha, V; Reřicha, R; Shore, D L; Sandler, D P

2011-04-01

Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. Copyright © 2011 Elsevier Inc. All rights reserved.

A pilot study on understanding the journey of advanced prostate cancer patients.

PubMed

Wagholikar, Amol; Fung, Maggie; Nelson, Colleen

2011-01-01

To understand the journey of advanced prostate cancer patients for supporting development of an innovative patient journey browser. Prostate cancer is one of the common cancers in Australia. Due to the chronic nature of the disease, it is important to have effective disease management strategy and care model. Multi-disciplinary care is a well-proven approach for chronic disease management. The Multi-disciplinary team (MDT) can function more effectively if all the required information is available for the clinical decision support. The development of innovative technology relies on an accurate understanding of the advanced prostate cancer patient's journey over a prolonged period. This need arises from the fact that advanced prostate cancer patients may follow various treatment paths and change their care providers. As a result of this, it is difficult to understand the actual sources of patient's clinical records and their treatment patterns. The aim of the research is to understand variable sources of clinical records, treatment patterns, alternative therapies, over the counter (OTC) medications of advanced prostate cancer patients. This study provides better and holistic understanding of advanced prostate cancer journey. The study was conducted through an on-line survey developed to seek and analyse the responses from the participants. The on-line questionnaire was carefully developed through consultations with the clinical researchers at the Australian Prostate Cancer Research Centre-Queensland, prostate cancer support group representatives and health informaticians at the Australian E-Health Research Centre. The non-identifying questionnaire was distributed to the patients through prostate cancer support groups in Queensland, Australia. The pilot study was carried out between August 2010 and December 2010. The research made important observations about the advanced prostate cancer journey. It showed that General Practitioner (GP) was the common source of

Perception of Curability Among Advanced Cancer Patients: An International Collaborative Study.

PubMed

Yennurajalingam, Sriram; Rodrigues, Luis Fernando; Shamieh, Omar; Tricou, Colombe; Filbet, Marilène; Naing, Kyaw; Ramaswamy, Akhileshwaran; Perez-Cruz, Pedro Emilio; Bautista, Mary Jocelyn S; Bunge, Sofia; Muckaden, Mary Ann; Sewram, Vikash; Fakrooden, Sarah; Noguera-Tejedor, Antonio; Rao, Shobha S; Liu, Diane; Park, Minjeong; Williams, Janet L; Lu, Zhanni; Cantu, Hilda; Hui, David; Reddy, Suresh K; Bruera, Eduardo

2018-04-01

There are limited data on illness understanding and perception of cure among advanced cancer patients around the world. The aim of the study was to determine the frequency and factors associated with inaccurate perception of curability among advanced cancer patients receiving palliative care across the globe. Secondary analysis of a study to understand the core concepts in end-of-life care among advanced cancer patients receiving palliative care from 11 countries across the world. Advanced cancer patients were surveyed using a Patient Illness Understanding survey and Control Preference Scale. Descriptive statistics and multicovariate logistic regression analysis were performed. Fifty-five percent (763/1,390) of patients receiving palliative care inaccurately reported that their cancer is curable. The median age was 58, 55% were female, 59% were married or had a partner, 48% were Catholic, and 35% were college educated. Sixty-eight percent perceived that the goal of therapy was "to get rid of their cancer," and 47% perceived themselves as "seriously ill." Multicovariate logistic regression analysis shows that accurate perception of curability was associated with female gender (odds ratio [OR] 0.73, p  = .027), higher education (OR 0.37, p  < .0001), unemployment status (OR 0.69, p  = .02), and being from France (OR 0.26, p  < .0001) and South Africa (OR 0.52, p  = .034); inaccurate perception of curability was associated with better Karnofsky performance status (OR 1.02 per point, p  = .0005), and being from Philippines (OR 15.49, p  < .0001), Jordan (OR 8.43, p  < .0001), Brazil (OR 2.17, p  = .0037), and India (OR 2.47, p  = .039). Inaccurate perception of curability in advanced cancer patients is 55% and significantly differs by gender, education, performance status, employment status, and country of origin. Further studies are needed to develop strategies to reduce this misperception of curability in advanced cancer

Mathematical modeling of solid cancer growth with angiogenesis

PubMed Central

2012-01-01

Background Cancer arises when within a single cell multiple malfunctions of control systems occur, which are, broadly, the system that promote cell growth and the system that protect against erratic growth. Additional systems within the cell must be corrupted so that a cancer cell, to form a mass of any real size, produces substances that promote the growth of new blood vessels. Multiple mutations are required before a normal cell can become a cancer cell by corruption of multiple growth-promoting systems. Methods We develop a simple mathematical model to describe the solid cancer growth dynamics inducing angiogenesis in the absence of cancer controlling mechanisms. Results The initial conditions supplied to the dynamical system consist of a perturbation in form of pulse: The origin of cancer cells from normal cells of an organ of human body. Thresholds of interacting parameters were obtained from the steady states analysis. The existence of two equilibrium points determine the strong dependency of dynamical trajectories on the initial conditions. The thresholds can be used to control cancer. Conclusions Cancer can be settled in an organ if the following combination matches: better fitness of cancer cells, decrease in the efficiency of the repairing systems, increase in the capacity of sprouting from existing vascularization, and higher capacity of mounting up new vascularization. However, we show that cancer is rarely induced in organs (or tissues) displaying an efficient (numerically and functionally) reparative or regenerative mechanism. PMID:22300422

Impact of reconstructive microsurgery in patients with advanced oral cavity cancers.

PubMed

Hanasono, Matthew M; Friel, Michael T; Klem, Christopher; Hsu, Patrick W; Robb, Geoffrey L; Weber, Randal S; Roberts, Dianna B; Chang, David W

2009-10-01

Our goal was to determine the impact of reconstructive microsurgery on the treatment of advanced oral cavity cancers. We reviewed 484 patients undergoing resection of T3-4 oral cavity squamous cell cancers from 1980 to 2004. To examine how reconstructive microsurgery affects outcomes, we compared 135 patients treated prior to the introduction of free tissue transfer and 349 patients treated after the introduction of free tissue transfer. Cancers treated after the introduction of free flaps included a significantly higher proportion of T4 compared to T3 lesions and significantly more advanced N classification lesions. Although cancers were more advanced, survival and recurrence rates were maintained and the rate of positive pathologic margins decreased significantly. In addition, fistula and tracheostomy dependence rates decreased and rates of intelligible speech increased. Reconstructive microsurgery contributes to improved oncologic outcomes in addition to better function and lower morbidity in oral cavity cancer treatment. (c) 2009 Wiley Periodicals, Inc.

Spontaneous Spreading of a Droplet: The Role of Solid Continuity and Advancing Contact Angle.

PubMed

Jiang, Youhua; Sun, Yujin; Drelich, Jaroslaw W; Choi, Chang-Hwan

2018-05-01

Spontaneous spreading of a droplet on a solid surface is poorly understood from a macroscopic level down to a molecular level. Here, we investigate the effect of surface topography and wettability on spontaneous spreading of a water droplet. Spreading force is measured for a suspended droplet that minimizes interference of kinetic energy in the spontaneous spreading during its contact with solid surfaces of discontinuous (pillar) and continuous (pore) patterns with various shapes and dimensions. Results show that a droplet cannot spread spontaneously on pillared surfaces regardless of their shapes or dimensions because of the solid discontinuity. On the contrary, a droplet on pored surfaces can undergo spontaneous spreading whose force increases with a decrease in the advancing contact angle. Theoretical models based on both the system free energy and capillary force along the contact line validate the direct and universal dependency of the spontaneous spreading force on the advancing contact angle.

Current advances in T-cell-based cancer immunotherapy

PubMed Central

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

Current advances in T-cell-based cancer immunotherapy.

PubMed

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

PubMed

Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

2018-05-01

To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption

Experimental Therapy of Advanced Breast Cancer: Targeting NFAT1-MDM2-p53 Pathway.

PubMed

Qin, Jiang-Jiang; Wang, Wei; Zhang, Ruiwen

2017-01-01

Advanced breast cancer, especially advanced triple-negative breast cancer, is typically more aggressive and more difficult to treat than other breast cancer phenotypes. There is currently no curable option for breast cancer patients with advanced diseases, highlighting the urgent need for novel treatment strategies. We have recently discovered that the nuclear factor of activated T cells 1 (NFAT1) activates the murine double minute 2 (MDM2) oncogene. Both MDM2 and NFAT1 are overexpressed and constitutively activated in breast cancer, particularly in advanced breast cancer, and contribute to its initiation, progression, and metastasis. MDM2 regulates cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion through both p53-dependent and -independent mechanisms. We have proposed to target the NFAT1-MDM2-p53 pathway for the treatment of human cancers, especially breast cancer. We have recently identified NFAT1 and MDM2 dual inhibitors that have shown excellent in vitro and in vivo activities against breast cancer, including triple-negative breast cancer. Herein, we summarize recent advances made in the understanding of the oncogenic functions of MDM2 and NFAT1 in breast cancer, as well as current targeting strategies and representative inhibitors. We also propose several strategies for inhibiting the NFAT1-MDM2-p53 pathway, which could be useful for developing more specific and effective inhibitors for breast cancer therapy. Copyright © 2017. Published by Elsevier Inc.

Development of improved ablative materials for ASRM. [Advanced Solid Rocket Motor

NASA Technical Reports Server (NTRS)

Canfield, A.; Armour, W.; Clinton, R.

1991-01-01

A program to improve ablative materials for the Advanced Solid Rocket Motor (ASRM) is briefly discussed. The main concerns with the baseline material are summarized along with the measures being undertaken to obtain improvements. The materials involved in the program, all of which have been manufactured and are now being evaluated, are mentioned.

Low-dose ionizing radiation increases the mortality risk of solid cancers in nuclear industry workers: A meta-analysis

PubMed Central

Qu, Shu-Gen; Gao, Jin; Tang, Bo; Yu, Bo; Shen, Yue-Ping; Tu, Yu

2018-01-01

Low-dose ionizing radiation (LDIR) may increase the mortality of solid cancers in nuclear industry workers, but only few individual cohort studies exist, and the available reports have low statistical power. The aim of the present study was to focus on solid cancer mortality risk from LDIR in the nuclear industry using standard mortality ratios (SMRs) and 95% confidence intervals. A systematic literature search through the PubMed and Embase databases identified 27 studies relevant to this meta-analysis. There was statistical significance for total, solid and lung cancers, with meta-SMR values of 0.88, 0.80, and 0.89, respectively. There was evidence of stochastic effects by IR, but more definitive conclusions require additional analyses using standardized protocols to determine whether LDIR increases the risk of solid cancer-related mortality. PMID:29725540

Low-dose ionizing radiation increases the mortality risk of solid cancers in nuclear industry workers: A meta-analysis.

PubMed

Qu, Shu-Gen; Gao, Jin; Tang, Bo; Yu, Bo; Shen, Yue-Ping; Tu, Yu

2018-05-01

Low-dose ionizing radiation (LDIR) may increase the mortality of solid cancers in nuclear industry workers, but only few individual cohort studies exist, and the available reports have low statistical power. The aim of the present study was to focus on solid cancer mortality risk from LDIR in the nuclear industry using standard mortality ratios (SMRs) and 95% confidence intervals. A systematic literature search through the PubMed and Embase databases identified 27 studies relevant to this meta-analysis. There was statistical significance for total, solid and lung cancers, with meta-SMR values of 0.88, 0.80, and 0.89, respectively. There was evidence of stochastic effects by IR, but more definitive conclusions require additional analyses using standardized protocols to determine whether LDIR increases the risk of solid cancer-related mortality.

Racial/Ethnic, socioeconomic, and geographic disparities of cervical cancer advanced-stage diagnosis in Texas.

PubMed

Zhan, F Benjamin; Lin, Yan

2014-01-01

Advanced-stage diagnosis is among the primary causes of mortality among cervical cancer patients. With the wide use of Pap smear screening, cervical cancer advanced-stage diagnosis rates have decreased. However, disparities of advanced-stage diagnosis persist among different population groups. A challenging task in cervical cancer disparity reduction is to identify where underserved population groups are. Based on cervical cancer incidence data between 1995 and 2008, this study investigated advanced-stage cervical cancer disparities in Texas from three social domains: Race/ethnicity, socioeconomic status (SES), and geographic location. Effects of individual and contextual factors, including age, tumor grade, race/ethnicity, as well as contextual SES, spatial access to health care, sociocultural factors, percentage of African Americans, and insurance expenditures, on these disparities were examined using multilevel logistic regressions. Significant variations by race/ethnicity and SES were found in cervical cancer advanced-stage diagnosis. We also found a decline in racial/ethnic disparities of advanced cervical cancer diagnosis rate from 1995 to 2008. However, the progress was slower among African Americans than Hispanics. Geographic disparities could be explained by age, race/ethnicity, SES, and the percentage of African Americans in a census tract. Our findings have important implications for developing effective cervical cancer screening and control programs. We identified the location of underserved populations who need the most assistance with cervical cancer screening. Cervical cancer intervention programs should target Hispanics and African Americans, as well as individuals from communities with lower SES in geographic areas where higher advanced-stage diagnosis rates were identified in this study. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Mental health, treatment preferences, advance care planning, location, and quality of death in advanced cancer patients with dependent children.

PubMed

Nilsson, Matthew E; Maciejewski, Paul K; Zhang, Baohui; Wright, Alexi A; Trice, Elizabeth D; Muriel, Anna C; Friedlander, Robert J; Fasciano, Karen M; Block, Susan D; Prigerson, Holly G

2009-01-15

Clinicians observe that advanced cancer patients with dependent children agonize over the impact their death will have on their children. The objective of this study was to determine empirically whether advanced cancer patients with and without dependent children differ in treatment preferences, mental health, and end-of-life (EOL) outcomes. Coping with Cancer is a National Cancer Institute/National Institute of Mental Health-funded, multi-institutional, prospective cohort study of 668 patients with advanced cancer. Patients with and without dependent children were compared on rates of psychiatric disorders, advance care planning (ACP), EOL care, quality of their last week of life, and location of death. In adjusted analyses, patients with advanced cancer who had dependent children were more likely to meet panic disorder criteria (adjusted odds ratio [AOR], 5.41; 95% confidence interval [95% CI], 2.13-13.69), more likely to be worried (mean difference in standard deviations [delta], 0.09; P=.006), and more likely to prefer aggressive treatment over palliative care (AOR, 1.77; 95% CI, 1.07-2.93). Patients with dependent children were less likely to engage in ACP (eg, do not resuscitate orders: AOR, 0.44; 95% CI, 0.26-0.75) and had a worse quality of life in the last week of life (delta, 0.15; P=.007). Among spousal caregivers, those with dependent children were more likely to meet criteria for major depressive disorder (AOR, 4.53; 95% CI, 1.47-14) and generalized anxiety disorder (AOR, 3.95; 95% CI, 1.29-12.16). Patients with dependent children were more anxious, were less likely to engage in ACP, and were more likely to have a worse quality of life in their last week of life. Advanced cancer patients and spousal caregivers with dependent children represent a particularly distressed group that warrants further clinical attention, research, and support. Copyright (c) 2009 American Cancer Society.

Recent Progress in Pancreatic Cancer

PubMed Central

Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

2013-01-01

Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

Recent advances in mass spectrometry-based proteomics of gastric cancer.

PubMed

Kang, Changwon; Lee, Yejin; Lee, J Eugene

2016-10-07

The last decade has witnessed remarkable technological advances in mass spectrometry-based proteomics. The development of proteomics techniques has enabled the reliable analysis of complex proteomes, leading to the identification and quantification of thousands of proteins in gastric cancer cells, tissues, and sera. This quantitative information has been used to profile the anomalies in gastric cancer and provide insights into the pathogenic mechanism of the disease. In this review, we mainly focus on the advances in mass spectrometry and quantitative proteomics that were achieved in the last five years and how these up-and-coming technologies are employed to track biochemical changes in gastric cancer cells. We conclude by presenting a perspective on quantitative proteomics and its future applications in the clinic and translational gastric cancer research.

Prognostic significance of obstructive uropathy in advanced prostate cancer.

PubMed

Oefelein, Michael G

2004-06-01

To report the incidence and prognostic implications of obstructive uropathy (OU) in patients with advanced prostate cancer receiving androgen deprivation therapy and to define the impact initial local therapy has on the development of OU in patients with prostate cancer who develop recurrence and begin androgen deprivation therapy. From a population of 260 patients with advanced prostate cancer diagnosed between 1986 and 2003, OU was identified in 51 patients. The OU treatment options included ureteral stent, percutaneous nephrostomy, transurethral resection of the prostate, Foley catheter placement, and urinary diversion. Overall survival and the factors that influenced survival were calculated using standard statistical methods. OU was diagnosed in 15 (16%) of 80 patients who received local therapy with curative intent and in whom local therapy subsequently failed and in 36 (19%) of 180 patients who had never received local therapy (P = 0.7, chi-square test). Of these 51 patients, 39 had bladder neck obstruction and 16 had ureteral obstruction. Overall survival was significantly worse for the men with OU compared with those without OU (41 versus 54 months). OU was associated with tumor stage and androgen-insensitive prostate cancer. OU results in significantly reduced survival in men with prostate cancer. In a select group of patients with prostate cancer with progression after local therapy (primarily radiotherapy), no statistically significant reduction in the development of OU was observed relative to patients matched for stage, grade, and pretreatment prostate-specific antigen level treated with androgen deprivation therapy alone. Aggressive advanced stage and hormone-insensitive disease are variables associated with OU.

Cancer Risk After Pediatric Solid Organ Transplantation.

PubMed

Yanik, Elizabeth L; Smith, Jodi M; Shiels, Meredith S; Clarke, Christina A; Lynch, Charles F; Kahn, Amy R; Koch, Lori; Pawlish, Karen S; Engels, Eric A

2017-05-01

The effects of pediatric solid organ transplantation on cancer risk may differ from those observed in adult recipients. We described cancers in pediatric recipients and compared incidence to the general population. The US transplant registry was linked to 16 cancer registries to identify cancer diagnoses among recipients <18 years old at transplant. Standardized incidence ratios (SIRs) were estimated by dividing observed cancer counts among recipients by expected counts based on the general population rates. Cox regression was used to estimate the associations between recipient characteristics and non-Hodgkin's lymphoma (NHL) risk. Among 17 958 pediatric recipients, 392 cancers were diagnosed, of which 279 (71%) were NHL. Compared with the general population, incidence was significantly increased for NHL (SIR = 212, 95% confidence interval [CI] = 188-238), Hodgkin's lymphoma (SIR = 19, 95% CI = 13-26), leukemia (SIR = 4, 95% CI = 2-7), myeloma (SIR = 229, 95% CI = 47-671), and cancers of the liver, soft tissue, ovary, vulva, testis, bladder, kidney, and thyroid. NHL risk was highest during the first year after transplantation among recipients <5 years old at transplant (SIR = 313), among recipients seronegative for Epstein-Barr virus (EBV) at transplant (SIR = 446), and among intestine transplant recipients (SIR = 1280). In multivariable analyses, seronegative EBV status, the first year after transplantation, intestine transplantation, and induction immunosuppression were independently associated with higher NHL incidence. Pediatric recipients have a markedly increased risk for many cancers. NHL constitutes the majority of diagnosed cancers, with the highest risk occurring in the first year after transplantation. NHL risk was high in recipients susceptible to primary EBV infection after transplant and in intestine transplant recipients, perhaps due to EBV transmission in the donor organ. Copyright © 2017 by the American Academy of Pediatrics.

Major clinical research advances in gynecologic cancer in 2014.

PubMed

Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

2015-04-01

In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

Managing occupations in everyday life for people with advanced cancer living at home.

PubMed

Peoples, Hanne; Brandt, Åse; Wæhrens, Eva E; la Cour, Karen

2017-01-01

People with advanced cancer are able to live for extended periods of time. Advanced cancer can cause functional limitations influencing the ability to manage occupations. Although studies have shown that people with advanced cancer experience occupational difficulties, there is only limited research that specifically explores how these occupational difficulties are managed. To describe and explore how people with advanced cancer manage occupations when living at home. A sub-sample of 73 participants from a larger occupational therapy project took part in the study. The participants were consecutively recruited from a Danish university hospital. Qualitative interviews were performed at the homes of the participants. Content analysis was applied to the data. Managing occupations were manifested in two main categories; (1) Conditions influencing occupations in everyday life and (2) Self-developed strategies to manage occupations. The findings suggest that people with advanced cancer should be supported to a greater extent in finding ways to manage familiar as well as new and more personally meaningful occupations to enhance quality of life.

First Brazilian Consensus of Advanced Prostate Cancer: Recommendations for Clinical Practice.

PubMed

Sasse, Andre Deeke; Wiermann, Evanius Garcia; Herchenhorn, Daniel; Bastos, Diogo Assed; Schutz, Fabio A; Maluf, Fernando Cotait; Coura, George; Morbeck, Igor Alexandre Protzner; Cerci, Juliano J; Smaletz, Oren; Lima, Volney Soares; Adamy, Ari; Campos, Franz Santos de; Carvalhal, Gustavo Franco; Cezar, Leandro Casemiro; Dall'Oglio, Marcos Francisco; Sadi, Marcus Vinicius; Reis, Rodolfo Borges Dos; Nogueira, Lucas

2017-01-01

Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions. Copyright® by the International Brazilian Journal of Urology.

Analysis of quasi-hybrid solid rocket booster concepts for advanced earth-to-orbit vehicles

NASA Technical Reports Server (NTRS)

Zurawski, Robert L.; Rapp, Douglas C.

1987-01-01

A study was conducted to assess the feasibility of quasi-hybrid solid rocket boosters for advanced Earth-to-orbit vehicles. Thermochemical calculations were conducted to determine the effect of liquid hydrogen addition, solids composition change plus liquid hydrogen addition, and the addition of an aluminum/liquid hydrogen slurry on the theoretical performance of a PBAN solid propellant rocket. The space shuttle solid rocket booster was used as a reference point. All three quasi-hybrid systems theoretically offer higher specific impulse when compared with the space shuttle solid rocket boosters. However, based on operational and safety considerations, the quasi-hybrid rocket is not a practical choice for near-term Earth-to-orbit booster applications. Safety and technology issues pertinent to quasi-hybrid rocket systems are discussed.

New Players for Advanced Prostate Cancer and the Rationalisation of Insulin-Sensitising Medication

PubMed Central

Gunter, Jennifer H.; Sarkar, Phoebe L.; Lubik, Amy A.; Nelson, Colleen C.

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer. PMID:23573093

New players for advanced prostate cancer and the rationalisation of insulin-sensitising medication.

PubMed

Gunter, Jennifer H; Sarkar, Phoebe L; Lubik, Amy A; Nelson, Colleen C

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of "old players" for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.

Parent-Child Communication and Adjustment Among Children With Advanced and Non-Advanced Cancer in the First Year Following Diagnosis or Relapse.

PubMed

Keim, Madelaine C; Lehmann, Vicky; Shultz, Emily L; Winning, Adrien M; Rausch, Joseph R; Barrera, Maru; Gilmer, Mary Jo; Murphy, Lexa K; Vannatta, Kathryn A; Compas, Bruce E; Gerhardt, Cynthia A

2017-09-01

To examine parent-child communication (i.e., openness, problems) and child adjustment among youth with advanced or non-advanced cancer and comparison children. Families (n = 125) were recruited after a child's diagnosis/relapse and stratified by advanced (n = 55) or non-advanced (n = 70) disease. Comparison children (n = 60) were recruited from local schools. Children (ages 10-17) reported on communication (Parent-Adolescent Communication Scale) with both parents, while mothers reported on child adjustment (Child Behavior Checklist) at enrollment (T1) and one year (T2). Openness/problems in communication did not differ across groups at T1, but problems with fathers were higher among children with non-advanced cancer versus comparisons at T2. Openness declined for all fathers, while changes in problems varied by group for both parents. T1 communication predicted later adjustment only for children with advanced cancer. Communication plays an important role, particularly for children with advanced cancer. Additional research with families affected by life-limiting conditions is needed. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

ClinicalTrials.gov

2017-02-10

Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Prognosis in advanced lung cancer--A prospective study examining key clinicopathological factors.

PubMed

Simmons, Claribel P; Koinis, Filippos; Fallon, Marie T; Fearon, Kenneth C; Bowden, Jo; Solheim, Tora S; Gronberg, Bjorn Henning; McMillan, Donald C; Gioulbasanis, Ioannis; Laird, Barry J

2015-06-01

In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0-1) to 33% (mGPS2, ECOG 3). Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Conducting Biobehavioral Research in Patients With Advanced Cancer: Recruitment Challenges and Solutions.

PubMed

Gilbertson-White, Stephanie; Bohr, Nicole; Wickersham, Karen E

2017-10-01

Despite significant advances in cancer treatment and symptom management interventions over the last decade, patients continue to struggle with cancer-related symptoms. Adequate baseline and longitudinal data are crucial for designing interventions to improve patient quality of life and reduce symptom burden; however, recruitment of patients with advanced cancer in longitudinal research is difficult. Our purpose is to describe challenges and solutions to recruitment of patients with advanced cancer in two biobehavioral research studies examining cancer-related symptoms. Study 1: Symptom data and peripheral blood for markers of inflammation were collected from newly diagnosed patients receiving chemotherapy on the first day of therapy and every 3-4 weeks for up to 6 months. Study 2: Symptom data, blood, and skin biopsies were collected from cancer patients taking epidermal growth factor receptor inhibitors at specific time points over 4 months. Screening and recruitment results for both studies are summarized. Timing informed consent with baseline data collection prior to treatment initiation was a significant recruitment challenge for both the studies. Possible solutions include tailoring recruitment to fit clinic needs, increasing research staff availability during clinic hours, and adding recruitment sites. Identifying solutions to these challenges will permit the conduct of studies that may lead to identification of factors contributing to variability in symptoms and development of tailored patient interventions for patients with advanced cancer.

Total colonoscopy detects early colorectal cancer more frequently than advanced colorectal cancer in patients with fecal occult blood.

PubMed

Ozaki, Takuji; Tokunaga, Akira; Chihara, Naoto; Yoshino, Masanori; Bou, Hideki; Ogata, Masao; Watanabe, Masanori; Suzuki, Hideyuki; Uchida, Eiji

2010-08-01

The efficacy of total colonoscopy following a positive result of the fecal occult blood test (FOBT) for the early detection of colorectal cancer and polyps was evaluated. A total of 1,491 patients with positive FOBT results underwent total colonoscopy at the Institute of Gastroenterology, Nippon Medical School, Musashi Kosugi Hospital, from April 2002 through July 2009. Abnormalities were found in 1,312 of the 1,491 patients (88.0%). Ninety-six of the 1,491 patients (6.4%) were found to have early cancer, but 59 patients (4.0%) were found to have advanced cancer. The early cancers were treated with endoscopic mucosal resection or endoscopic submucosal dissection in 81 patients, with laparoscopy-assisted colectomy in 10 patients, and with open surgery in 5 patients. Fifty-one of the 59 patients with advanced colorectal cancer underwent conventional open surgery, and 8 patients underwent laparoscopic surgery. The cancers detected were more likely to be early cancers than advanced cancers. In addition to malignancies, other abnormalities found included inner or external hemorrhoids, diverticula of the colon, ulcerative colitis, ischemic colitis, infectious colitis, and colorectal polyps. Our results show that a high percentage of lesions detected with total colonoscopy following a positive FOBT result are early colorectal cancers and polyps.

New clinical trial explores precision treatment for advanced pancreatic cancer | Center for Cancer Research

Cancer.gov

A new phase II clinical trial to assess the safety and efficacy of a drug called selumetinib for treating patients with advanced pancreatic cancer whose tumors harbor a specific genetic marker has opened at the Center for Cancer Research and is currently recruiting participants. Read more...

New advances in focal therapy for early stage prostate cancer.

PubMed

Tay, Kae Jack; Schulman, Ariel A; Sze, Christina; Tsivian, Efrat; Polascik, Thomas J

2017-08-01

Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

Effect of hydronephrosis on survival in advanced stage cervical cancer.

PubMed

Goklu, Mehmet Rıfat; Seckin, Kerem Doga; Togrul, Cihan; Goklu, Yasemin; Tahaoglu, Ali Emre; Oz, Murat; Ertas, Ibrahim Egemen

2015-01-01

Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (p<0.05). There was no significant survival difference between patients with unilateral and bilateral hydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (p<0.05). Hydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be

Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

PubMed

Soekmadji, Carolina; Corcoran, Niall M; Oleinikova, Irina; Jovanovic, Lidija; Ramm, Grant A; Nelson, Colleen C; Jenster, Guido; Russell, Pamela J

2017-10-01

The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation. © 2017 Wiley Periodicals, Inc.

Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; Glioblastoma; IDH1 Gene Mutation; IDH2 Gene Mutation; Recurrent Cholangiocarcinoma; Recurrent Glioma; Recurrent Malignant Solid Neoplasm; WHO Grade II Glioma; WHO Grade III Glioma

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

Factors influencing the quality of life of patients with advanced cancer.

PubMed

Park, Sun-A; Chung, Seung Hyun; Lee, Youngjin

2017-02-01

The present study aimed to determine the predictors of quality of life (QOL) of patients with advanced cancer. A cross-sectional study involving 494 patients with advanced cancer was conducted using the Memorial Symptom Assessment Scale-Short Form, the Karnofsky Performance Status Scale, the World Health Organization Disability Assessment Schedule (Korean version), and the European Organization for Research and Treatment of Cancer Quality of Life Core 30. Regression analyses showed that physical and psychological symptoms significantly predicted the patients' QOL and explained 28.8% of the variance in QOL. Moreover, lack of energy was the patients' most prevalent symptom. The results of the present study will serve as fundamental data upon which the development of an intervention will be based so as to enhance the patients' QOL. Accordingly, an effective management of symptoms and performance maintenance should be considered in the future as key factors in providing support and establishing palliative care systems for patients with advanced cancer. Copyright © 2016. Published by Elsevier Inc.

How women with advanced cancer pray: a report from two focus groups.

PubMed

Smith, Amy Rex; DeSanto-Madeya, Susan; Pérez, John E; Tracey, Elizabeth F; DeCristofaro, Susan; Norris, Rebecca L; Mukkamala, Shruti L

2012-05-01

To explore the meaning, function, and focus of prayer for patients with advanced cancer, and to identify the effects of prayer on their coping. Qualitative, descriptive design using focus groups. Three cancer centers that are part of a university-affiliated comprehensive cancer network in the northeastern United States. 13 adult, female outpatients receiving active treatment for ovarian or lung cancer. Two semistructured, focus group interviews were conducted. Audiotapes were transcribed verbatim. Data were coded and analyzed using standard content analysis procedures. Prayer and coping. Four themes emerged: finding one's own way, renewed appreciation for life, provision of strength and courage, and gaining a stronger spiritual connection. In addition, praying for others, conversational prayer, petitionary prayer, ritual prayer, and thanksgiving prayer were used most often by participants to cope. The findings support prayer as a positive coping mechanism for women with advanced ovarian or lung cancer. The study provides knowledge about prayer as a source of spiritual and psychological support. Oncology nurses should consider the use of prayer for patients coping with advanced cancer.

The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients.

PubMed

Zill, Oliver A; Banks, Kimberly C; Fairclough, Stephen R; Mortimer, Stefanie; Vowles, James V; Mokhtari, Reza; Gandara, David R; Mack, Philip C; Odegaard, Justin I; Nagy, Rebecca J; Baca, Arthur M; Eltoukhy, Helmy; Chudova, Darya I; Lanman, Richard B; Talasaz, AmirAli

2018-05-18

Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality. Patterns and prevalence of cfDNA alterations in major driver genes for non-small cell lung, breast, and colorectal cancer largely recapitulated those from tumor tissue sequencing compendia (TCGA and COSMIC; r=0.90-0.99), with the principle differences in alteration prevalence being due to patient treatment. This highly sensitive cfDNA sequencing assay revealed numerous subclonal tumor-derived alterations, expected as a result of clonal evolution, but leading to an apparent departure from mutual exclusivity in treatment-naïve tumors. Upon applying novel cfDNA clonality and copy-number driver identification methods, robust mutual exclusivity was observed among predicted truncal driver cfDNA alterations (FDR=5x10 -7 for EGFR and ERBB2 ), in effect distinguishing tumor-initiating alterations from secondary alterations. Treatment-associated resistance, including both novel alterations and parallel evolution, was common in the cfDNA cohort and was enriched in patients with targetable driver alterations (>18.6% patients). Together these retrospective analyses of a large cfDNA sequencing data set reveal subclonal structures and emerging resistance in advanced solid tumors. Copyright ©2018, American Association for Cancer Research.

Recent advances in carbon based nanosystems for cancer theranostics.

PubMed

Augustine, Shine; Singh, Jay; Srivastava, Manish; Sharma, Monica; Das, Asmita; Malhotra, Bansi D

2017-05-02

One of the major challenges in our contemporary society is to facilitate healthy life for all human beings. In this context, cancer has become one of the most deadly diseases around the world, and despite many advances in theranostics techniques the treatment of cancer still remains an important problem. With recent advances made in the field of nano-biotechnology, carbon-based nanostructured materials have drawn special attention because of their unique physicochemical properties, giving rise to great potential for the diagnosis and therapy of cancer. This review deals with four different types of carbon allotrope including carbon nanotubes, graphene, fullerenes and nanodiamonds and summarizes the results of recent studies that are likely to have implications in cancer theranostics. We discuss the applications of these carbon allotropes for cancer imaging and drug delivery, hyperthermia, photodynamic therapy and acoustic wave assisted theranostics. We focus on the results of different studies conducted on functionalized/conjugated carbon nanotubes, graphene, fullerenes and nanodiamond based nanostructured materials reported in the literature in the current decade. The emphasis has been placed on the synthesis strategies, structural design, properties and possible mechanisms that are perhaps responsible for their improved theranostic characteristics. Finally, we discuss the critical issues that may accelerate the development of carbon-based nanostructured materials for application in cancer theranostics.

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

Lapatinib for treatment of advanced or metastasized breast cancer: systematic review.

PubMed

Riera, Rachel; Soárez, Patrícia Coelho de; Puga, Maria Eduarda Dos Santos; Ferraz, Marcos Bosi

2009-09-01

Around 16% to 20% of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) and manual search. Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51% (95% confidence interval, CI: 0.34-0.71; P < 0.001), compared with capecitabine alone, without any increase in severe adverse effects. The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

Advances in molecular imaging for breast cancer detection and characterization

PubMed Central

2012-01-01

Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

Cancer of the head and neck region in solid organ transplant recipients.

PubMed

Rabinovics, Naomi; Mizrachi, Aviram; Hadar, Tuvia; Ad-El, Dean; Feinmesser, Raphael; Guttman, Dan; Shpitzer, Thomas; Bachar, Gideon

2014-02-01

Solid organ recipients are at an increased risk of developing various malignancies. We investigated the incidence, clinical features, and outcome of patients diagnosed with head and neck cancer after organ transplantation. A retrospective analysis was undertaken of patients who underwent solid organ transplantation (kidney, liver, lung, heart) treated at our institution from 1992 to 2010. Of 2817 organ recipients, 175 patients (6.1%) developed 391 head and neck malignancies. Cutaneous malignancies were the most common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC; 42%). The average interval from transplantation to diagnosis of head and neck malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen percent of patients presented with an aggressive pattern of head and neck cancer, including 24% of patients with cutaneous SCC. Organ transplantation recipients are at a higher risk to develop head and neck cancer with an aggressive behavior characterized by multiple recurrences and decreased survival. Copyright © 2013 Wiley Periodicals, Inc.

Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

PubMed

Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S; Dreicer, Robert; Epstein, Andrew S; Gillison, Maura L; Graham, David L; Jones, Joshua; Ko, Andrew H; Lopez, Ana Maria; Maki, Robert G; Rodriguez-Galindo, Carlos; Schilsky, Richard L; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold

2018-04-01

A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal

EMD 121974 in Treating Patients With Locally Advanced or Metastatic Cancer

ClinicalTrials.gov

2014-09-16

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Post-Discharge Survival Outcomes of Patients with Advanced Cancer from the University of Texas MD Anderson Cancer Center Investigational Cancer Therapeutics (Phase I Trials) Inpatient Unit.

PubMed

Kinahan, Holly; Maiti, Abhishek; Hess, Kenneth; Dempsey, Jennifer; Beatty, Laura; Baldwin, Sarah; Hong, David S; Naing, Aung; Fu, Siqing; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Janku, Filip; Karp, Daniel; Reddy, Suresh; Yennu, Sriram; Epner, Daniel; Bruera, Eduardo; Meric-Bernstam, Funda; Falchook, Gerald; Subbiah, Vivek

2017-01-01

Patients with advanced cancer who progress on standard therapy are potential candidates for phase I clinical trials. Due to their aggressive disease and complex comorbid conditions, these patients often need inpatient admission. This study assessed the outcomes of such patients after they were discharged to hospice care. We performed a retrospective analysis of patients with solid tumor malignancies who were discharged to hospice care from the inpatient service. One hundred thirty-three patients were included in the study cohort. All patients had metastatic disease and an Eastern Cooperative Oncology Group performance status ≥3. The median survival after discharge to hospice from an inpatient setting was 16 days, with a survival rate of 5% at 3 months after discharge. The median survival after the last cancer treatment was 46 days, with survival of 17% at 3 months, and 5% at 6 months. Patients with lactate dehydrogenase (LDH) >618 IU/L had a median post-discharge survival of 11 days versus 20 days for patients with LDH ≤618 IU/L. Patients with metastatic cancer participating in phase I trials who have poor performance status and require inpatient admission have a very short survival after discharge to hospice. A high LDH level predicts an even shorter survival. © 2016 S. Karger AG, Basel.

Clinical cancer advances 2008: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Winer, Eric; Gralow, Julie; Diller, Lisa; Karlan, Beth; Loehrer, Patrick; Pierce, Lori; Demetri, George; Ganz, Patricia; Kramer, Barnett; Kris, Mark; Markman, Maurie; Mayer, Robert; Pfister, David; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory; Sandler, Howard; Sawaya, Raymond; Schuchter, Lynn; Sweetenham, John; Vahdat, Linda; Schilsky, Richard L

2009-02-10

A message from ASCO'S president: Nearly 40 years ago, President Richard Nixon signed the National Cancer Act, mobilizing the country's resources to make the "conquest of cancer a national crusade." That declaration led to a major investment in cancer research that has significantly improved cancer prevention, treatment, and survival. As a result, two thirds of people diagnosed with cancer today will live at least 5 years after diagnosis, compared with just half in the 1970s. In addition, there are now more than 12 million cancer survivors in the United States--up from 3 million in 1971. Scientifically, we have never been in a better position to advance cancer treatment. Basic scientific research, fueled in recent years by the tools of molecular biology, has generated unprecedented knowledge of cancer development. We now understand many of the cellular pathways that can lead to cancer. We have learned how to develop drugs that block those pathways; increasingly, we know how to personalize therapy to the unique genetics of the tumor and the patient. Yet in 2008, 1.4 million people in the United States will still be diagnosed with cancer, and more than half a million will die as a result of the disease. Some cancers remain stubbornly resistant to treatment, whereas others cannot be detected until they are in their advanced, less curable stages. Biologically, the cancer cell is notoriously wily; each time we throw an obstacle in its path, it finds an alternate route that must then be blocked. To translate our growing basic science knowledge into better treatments for patients, a new national commitment to cancer research is urgently needed. However, funding for cancer research has stagnated. The budgets of the National Institutes of Health and the National Cancer Institute have failed to keep pace with inflation, declining up to 13% in real terms since 2004. Tighter budgets reduce incentives to support high-risk research that could have the largest payoffs. The most

De novo head and neck cancer arising in solid organ transplantation recipients: The Asan Medical Center experience.

PubMed

Park, Marn Joon; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Lee, Yoon Se

2018-08-01

De novo cancers of head and neck area in solid organ transplantation recipients show standardized incidence ratio (SIR) of 3.8. Immunosuppression following transplantation is suggested to play as a crucial factor in pathogenesis of secondary malignancy. Prognosis of head and neck cancer arising in solid organ transplantation recipients is proven to have poor prognosis. The incidence, risk, prognosis, and survival of de novo malignancy of head and neck area in solid organ transplantation recipients in single-tertiary medical center followed up for 20 years. A retrospective medical record review of the patients who received solid organ transplantation in Asan Medical Center from 1997 to 2016 was conducted. Patients confirmed as de novo malignancy in the head and neck area after organ transplantation were included, and presented as in the case-series format. Patients with previous history of head and neck malignancy, irradiation history of head and neck area, cutaneous malignant lesion, hematopoietic malignant lesion, malignancy of thyroid and parathyroid gland and metastatic lesions newly developed in head and neck area were excluded. The incidence of head and neck malignancy in South Korea were reviewed from the National Cancer Information Center of South Korea. For the statistical analysis, standardized incidence ratio (SIR) was obtained with 95% confidence interval. Solid organ transplantation recipients show 20 times higher incidence of de novo cancer of head and neck area compared to general population. Of 13 de novo head and neck malignancy arising after solid organ transplantation, 2 (15.4%) patients were unable to withstand definitive management due to poor general condition. 2 (15.4%) patients had loco-regional recurrence, 1 (7.7%) patient with distant metastasis, and 3 (23.1%) patients died of cancer progression. Immunosuppression following solid organ transplantation gives a twenty-fold increased risk for the development of de novo head and neck cancer. A

Refining Preoperative Therapy for Locally Advanced Rectal Cancer

Cancer.gov

In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center.

PubMed

Marín, Mar; Gudiol, Carlota; Garcia-Vidal, Carol; Ardanuy, Carmen; Carratalà, Jordi

2014-05-01

endogenous source of BSI (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.06-12.02), shock at presentation (OR, 3.63; 95% CI, 1.63-8.09), and corticosteroid therapy (OR, 3.245; 95% CI, 1.43-7.32). The independent risk factors for overall case-fatality rate were the presence of a chronic advanced cancer (OR, 35.39; 95% CI, 2.48-504.91), shock at presentation (OR, 25.84; 95% CI, 3.73-179.0), and corticosteroid therapy (OR, 6.98; 95% CI, 1.61-30.21).BSI in patients with solid tumors occurred mainly among those with hepatobiliary cancer, and cholangitis was the most frequent source; gram-negative bacilli were the most frequent causative agents. MDR organisms were relatively common, particularly in patients who had previously received antibiotics and had been hospitalized; these patients were frequently treated with inadequate empirical antibiotic therapy and had a poorer outcome. The case-fatality rate of patients with solid tumors and BSI was high and was associated with chronic advanced cancer, corticosteroid therapy, and shock at presentation.

Recent technological advances in using mouse models to study ovarian cancer.

PubMed

House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

2014-01-01

Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC.

Recent Technological Advances in Using Mouse Models to Study Ovarian Cancer

PubMed Central

House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

2014-01-01

Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC. PMID:24592355

Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics.

PubMed

Akhter, Md Habban; Rizwanullah, Md; Ahmad, Javed; Ahsan, Mohamed Jawed; Mujtaba, Md Ali; Amin, Saima

2018-08-01

Cancer has been growing nowadays consequently high number of death ascertained worldwide. The medical intervention involves chemotherapy, radiation therapy and surgical removal. This conventional technique lacking targeting potential and harm the normal cells. In drug treatment regimen, the combination therapy is preferred than single drug treatment module due to higher internalization of chemotherapeutics in the cancer cells both by enhance permeation retention effect and by direct cell apoptosis. The cancer therapeutics involves different methodologies of delivering active moiety to the target site. The active and passive transport mode of chemotherapeutic targeting utilizes advance nanocarriers. The nanotechnological strategic treatment applying advance nanocarrier greatly helps in mitigating the cancer prevalence. The nanocarrier-incorporating nanodrug directed for specific area appealed scientist across the globe and issues to be addressed in this regard. Therefore, various techniques and approaches invented to meet the objectives. With the advances in nanomedicine and drug delivery, this review briefly focused on various modes of nanodrug delivery including nanoparticles, liposomes, dendrimer, quantum dots, carbon nanotubes, metallic nanoparticles, nanolipid carrier (NLC), gold nanoshell, nanosize cantilevers and nanowire that looks promising and generates a novel horizon in cancer therapeutics.

Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

ClinicalTrials.gov

2012-12-13

Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

NASA's Advanced solid rocket motor

NASA Technical Reports Server (NTRS)

Mitchell, Royce E.

1993-01-01

The Advanced Solid Rocket Motor (ASRM) will not only bring increased safety, reliability and performance for the Space Shuttle Booster, it will enhance overall Shuttle safety by effectively eliminating 174 failure points in the Space Shuttle Main Engine throttling system and by reducing the exposure time to aborts due to main engine loss or shutdown. In some missions, the vulnerability time to Return-to-Launch Site aborts is halved. The ASRM uses case joints which will close or remain static under the effects of motor ignition and pressurization. The case itself is constructed of the weldable steel alloy HP 9-4-0.30, having very high strength and with superior fracture toughness and stress corrosion resistance. The internal insulation is strip-wound and is free of asbestos. The nozzle employs light weight ablative parts and is some 5,000 pounds lighter than the Shuttle motor used to date. The payload performance of the ASRM-powered Shuttle is 12,000 pounds higher than that provided by the present motor. This is of particular benefit for payloads delivered to higher inclinations and/or altitudes. The ASRM facility uses state-of-the-art manufacturing techniques, including continuous propellant mixing and direct casting.

Recent advances in vacuum sciences and applications

NASA Astrophysics Data System (ADS)

Mozetič, M.; Ostrikov, K.; Ruzic, D. N.; Curreli, D.; Cvelbar, U.; Vesel, A.; Primc, G.; Leisch, M.; Jousten, K.; Malyshev, O. B.; Hendricks, J. H.; Kövér, L.; Tagliaferro, A.; Conde, O.; Silvestre, A. J.; Giapintzakis, J.; Buljan, M.; Radić, N.; Dražić, G.; Bernstorff, S.; Biederman, H.; Kylián, O.; Hanuš, J.; Miloševič, S.; Galtayries, A.; Dietrich, P.; Unger, W.; Lehocky, M.; Sedlarik, V.; Stana-Kleinschek, K.; Drmota-Petrič, A.; Pireaux, J. J.; Rogers, J. W.; Anderle, M.

2014-04-01

Recent advances in vacuum sciences and applications are reviewed. Novel optical interferometer cavity devices enable pressure measurements with ppm accuracy. The innovative dynamic vacuum standard allows for pressure measurements with temporal resolution of 2 ms. Vacuum issues in the construction of huge ultra-high vacuum devices worldwide are reviewed. Recent advances in surface science and thin films include new phenomena observed in electron transport near solid surfaces as well as novel results on the properties of carbon nanomaterials. Precise techniques for surface and thin-film characterization have been applied in the conservation technology of cultural heritage objects and recent advances in the characterization of biointerfaces are presented. The combination of various vacuum and atmospheric-pressure techniques enables an insight into the complex phenomena of protein and other biomolecule conformations on solid surfaces. Studying these phenomena at solid-liquid interfaces is regarded as the main issue in the development of alternative techniques for drug delivery, tissue engineering and thus the development of innovative techniques for curing cancer and cardiovascular diseases. A review on recent advances in plasma medicine is presented as well as novel hypotheses on cell apoptosis upon treatment with gaseous plasma. Finally, recent advances in plasma nanoscience are illustrated with several examples and a roadmap for future activities is presented.

Advances toward LSD1 inhibitors for cancer therapy.

PubMed

Fu, Xiaoli; Zhang, Peng; Yu, Bin

2017-07-01

LSD1 has become an important biologically validated epigenetic target for cancer therapy since its identification in 2004. LSD1 mediates many cellular signaling pathways and is involved in the initiation and development of cancers. Aberrant overexpression of LSD1 has been observed in different types of cancers, and inactivation by small molecules suppresses cancer cell differentiation, proliferation, invasion and migration. To date, a large number of LSD1 inhibitors have been reported, RG6016, GSK-2879552, INCB059872, IMG-7289 and CC-90011 are currently undergoing clinical assessment for the treatment of acute myeloid leukemia, small-cell lung cancer, etc. In this review, we briefly highlight recent advances of LSD1 inhibitors mainly covering the literatures from 2015 to 2017 and tentatively propose our perspectives on the design of new LSD1 inhibitors for cancer therapy.

Recent advances in cancer metabolism: a technological perspective.

PubMed

Kang, Yun Pyo; Ward, Nathan P; DeNicola, Gina M

2018-04-16

Cancer cells are highly dependent on metabolic pathways to sustain both their proliferation and adaption to harsh microenvironments. Thus, understanding the metabolic reprogramming that occurs in tumors can provide critical insights for the development of therapies targeting metabolism. In this review, we will discuss recent advancements in metabolomics and other multidisciplinary techniques that have led to the discovery of novel metabolic pathways and mechanisms in diverse cancer types.

[Neoadjuvant chemotherapy for advanced gastric cancer using FLEP therapy].

PubMed

Mochizuki, F; Fujii, M; Kasakura, Y; Kochi, M; Imai, S; Eguchi, T; Tsuneda, Y; Kanamori, N; Kaiga, T; Kobayashi, M

2000-10-01

Combination chemotherapy with 5-FU, LV, ETP and CDDP (FLEP) for advanced gastric cancer uses a combination of regional and systemic delivery for the control of both local and disseminated disease in the intra- and extra-abdominal regions. We performed this regimen as neoadjuvant chemotherapy (NAC). Fifteen patients with unresectable primary advanced gastric cancer underwent FLEP. The treatment regimen was 5-FU at 370 mg/m2, LV at 30 mg/body (days 1 to 5, i.v. 24 h) and ETP and CDDP each at 70 mg/m2 (days 7 and 21, ia 2 h). This regimen was repeated every four weeks. The overall response rate was 46.7% (7/15), and the 50% and median survival times were 11.43 and 12.35 months, respectively. The adverse events were Grade 3 leukocytopenia, Grade 3 thrombocytopenia, and Grade 3 stomatitis in 20.0%, 13.3%, and 6.7% of the patients, respectively. The 50% and median survival time overall were 11.43 and 12.35 months, respectively. Of the 15 NAC patients, curability B patients showed a statistically higher survival rate than curability C and unresected patients. In conclusion, FLEP was effective for unresectable advanced gastric cancer.

Patterns of Resuscitation Care and Survival After In-Hospital Cardiac Arrest in Patients With Advanced Cancer.

PubMed

Bruckel, Jeffrey T; Wong, Sandra L; Chan, Paul S; Bradley, Steven M; Nallamothu, Brahmajee K

2017-10-01

Little is known regarding patterns of resuscitation care in patients with advanced cancer who suffer in-hospital cardiac arrest (IHCA). In the Get With The Guidelines - Resuscitation registry, 47,157 adults with IHCA with and without advanced cancer (defined as the presence of metastatic or hematologic malignancy) were identified at 369 hospitals from April 2006 through June 2010. We compared rates of return of spontaneous circulation (ROSC) and survival to discharge between groups using multivariable models. We also compared duration of resuscitation effort and resuscitation quality measures. Overall, 6,585 patients with IHCA (14.0%) had advanced cancer. Patients with advanced cancer had lower multivariable-adjusted rates of ROSC (52.3% [95% CI, 49.5% to 55.3%] v 56.6% [95% CI, 53.8% to 59.5%]; P < .001) and survival to discharge (7.4% [95% CI, 6.6% to 8.4%] v 13.4% [95% CI, 12.1% to 14.8%]; P < .001). Among nonsurvivors who died during resuscitation, patients with advanced cancer had better performance on most resuscitation quality measures. Among patients with ROSC, patients with advanced cancer were made Do Not Attempt Resuscitation (DNAR) more frequently within 48 hours (adjusted relative risk, 1.30 [95% CI, 1.24 to 1.37]; P < .001). Adjustment for DNAR status explained some of the immediate effect of advanced cancer on survival; however, survival remained significantly lower in patients with cancer. Patients with advanced cancer can expect lower survival rates after IHCA compared with those without advanced cancer, and they are more frequently made DNAR within 48 hours of ROSC. These findings have important implications for discussions of resuscitation care wishes with patients and can better inform end-of-life discussions.

Advances in Theory of Solid-State Nuclear Magnetic Resonance.

PubMed

Mananga, Eugene S; Moghaddasi, Jalil; Sana, Ajaz; Akinmoladun, Andrew; Sadoqi, Mostafa

Recent advances in theory of solid state nuclear magnetic resonance (NMR) such as Floquet-Magnus expansion and Fer expansion, address alternative methods for solving a time-dependent linear differential equation which is a central problem in quantum physics in general and solid-state NMR in particular. The power and the salient features of these theoretical approaches that are helpful to describe the time evolution of the spin system at all times are presented. This review article presents a broad view of manipulations of spin systems in solid-state NMR, based on milestones theories including the average Hamiltonian theory and the Floquet theory, and the approaches currently developing such as the Floquet-Magnus expansion and the Fer expansion. All these approaches provide procedures to control and describe the spin dynamics in solid-state NMR. Applications of these theoretical methods to stroboscopic and synchronized manipulations, non-synchronized experiments, multiple incommensurated frequencies, magic-angle spinning samples, are illustrated. We also reviewed the propagators of these theories and discussed their convergences. Note that the FME is an extension of the popular Magnus Expansion and Average Hamiltonian Theory. It aims is to bridge the AHT to the Floquet Theorem but in a more concise and efficient formalism. Calculations can then be performed in a finite-dimensional Hilbert space instead of an infinite dimensional space within the so-called Floquet theory. We expected that the FME will provide means for more accurate and efficient spin dynamics simulation and for devising new RF pulse sequence.

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials.

PubMed

Bonnetain, F; Borg, C; Adams, R R; Ajani, J A; Benson, A; Bleiberg, H; Chibaudel, B; Diaz-Rubio, E; Douillard, J Y; Fuchs, C S; Giantonio, B J; Goldberg, R; Heinemann, V; Koopman, M; Labianca, R; Larsen, A K; Maughan, T; Mitchell, E; Peeters, M; Punt, C J A; Schmoll, H J; Tournigand, C; de Gramont, A

2017-09-01

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All

Managing toxicities and optimal dosing of targeted drugs in advanced kidney cancer

PubMed Central

Seruga, B.; Gan, H.K.; Knox, J.J.

2009-01-01

The toxicities of new, targeted drugs may diminish their effectiveness in advanced kidney cancer if those toxicities are not recognized and properly addressed early in patient treatment. Most of the drug-related toxicities in advanced kidney cancer are manageable with supportive care, obviating a need for long interruptions, dose reductions, or permanent discontinuation of the treatment. PMID:19478903

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

PubMed

Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

2018-02-01

Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

Leveraging the immune system to treat advanced thyroid cancers.

PubMed

French, Jena D; Bible, Keith; Spitzweg, Christine; Haugen, Bryan R; Ryder, Mabel

2017-06-01

Inflammation has long been associated with the thyroid and with thyroid cancers, raising seminal questions about the role of the immune system in the pathogenesis of advanced thyroid cancers. With a growing understanding of dynamic tumour-immune cell interactions and the mechanisms by which tumour cells evade antitumour immunity, the field of cancer immunotherapy has been revolutionised. In this Review, we provide evidence to support the presence of an antitumour immune response in advanced thyroid cancers linked to cytotoxic T cells and NK cells. This antitumour response, however, is likely blunted by the presence of immunosuppressive pathways within the microenvironment, facilitated by tumour-associated macrophages or increased expression of negative regulators of cytotoxic T-cell function. Current and future efforts to incorporate immune-based therapies into existing tumour cell or endothelial-derived therapies-eg, with kinase inhibitors targeting tumour-associated macrophages or antibodies blocking negative regulators on T cells-could provide improved and durable responses for patients with disease that is otherwise refractory to treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crizotinib for Advanced Non-Small Cell Lung Cancer

Cancer.gov

A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

Recent non-interventional advances in cancer pain among Singapore patients.

PubMed

Saw, Constance L L; Chew, Lita; Goh, Cynthia

2012-09-01

Pain is a common symptom in cancer patients, but very little information about the prevalence, severity, and treatment of pain in cancer patients in Singapore is available. Therefore, our prospective survey in the National Cancer Centre (NCC) outpatients is incorporated in this report. In addition, a review concerning the recent advances on non-interventional pain management in cancer treatment, which is relevant in the context, is discussed. For the prospective survey, a questionnaire was distributed for self-administration by patients while waiting for consultation at the NCC outpatient departments. Literature searches on advances in pain management were conducted, reviewed and discussed. In the last decade, there have been advances in pain pharmacology ranging from wider therapeutic options and management approaches to novel delivery techniques. Acupuncture and massage therapy became increasingly popular among cancer patients. Some clinical trials of acupuncture show benefits in palliation of cancer pain. From the prospective survey, 41.2% of the responders reported pain in the past week, and only 70.8% talked to their doctors about their pain. One third of the patients received analgesics. Of these, 86.5% said that they were taking the prescribed medications, however, 37.4% admitted to having difficulties taking them. Non-drug methods were used by 25.4% of the patients. Medicated oil, cream or gel was used by 49.3%; only 2.6% reported use of Chinese herbs. Pain is a significant symptom in outpatients attending a cancer centre, affecting 41.2% of the patients. Although majority of patients who suffered from pain reported this to doctors, much more medical effort is needed to help patients to relieve their pain and proper complementary therapy could be considered.

Practical management of everolimus-related toxicities in patients with advanced solid tumors.

PubMed

Grünwald, Viktor; Weikert, Steffen; Pavel, Marianne E; Hörsch, Dieter; Lüftner, Diana; Janni, Wolfgang; Geberth, Matthias; Weber, Matthias M

2013-01-01

Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular protein kinase downstream of the phosphatidylinositol 3-kinase/AKT pathway involved in key components of tumorigenesis, including cell growth, proliferation, and angiogenesis. In the advanced cancer setting, based on favorable results from phase III trials, everolimus is indicated for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, and advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma. Although it is generally well tolerated, with most adverse events of mild to moderate severity and manageable, everolimus exhibits a distinct adverse event profile that warrants guidance for proper diagnostic and medical management. This guidance is particularly important given the potential for widespread long-term use of everolimus. This review will focus on the most relevant toxicities associated with mTOR inhibitors and on their management. Practical treatment recommendations are presented for stomatitis, noninfectious pneumonitis, rash, selected metabolic abnormalities, and infections. Provided these events are rapidly identified and treated, the vast majority should resolve with minimal effect on treatment outcomes and patients' quality of life. Copyright © 2013 S. Karger AG, Basel.

Correlation between the international consensus definition of the Cancer Anorexia-Cachexia Syndrome (CACS) and patient-centered outcomes in advanced non-small cell lung cancer.

PubMed

LeBlanc, Thomas W; Nipp, Ryan D; Rushing, Christel N; Samsa, Greg P; Locke, Susan C; Kamal, Arif H; Cella, David F; Abernethy, Amy P

2015-04-01

The cancer anorexia-cachexia syndrome (CACS) is common in patients with advanced solid tumors and is associated with adverse outcomes including poor quality of life (QOL), impaired functioning, and shortened survival. To apply the recently posed weight-based international consensus CACS definition to a population of patients with advanced non-small cell lung cancer (NSCLC) and explore its impact on patient-reported outcomes. Ninety-nine patients participated in up to four study visits over a six-month period. Longitudinal assessments included measures of physical function, QOL, and other clinical variables such as weight and survival. Patients meeting the consensus CACS criteria at Visit 1 had a significantly shorter median survival (239.5 vs. 446 days; hazard ratio, 2.06, P < 0.05). Physical function was worse in the CACS group (mean Karnofsky Performance Status score 68 vs. 77, Eastern Cooperative Oncology Group Performance Status score 1.8 vs. 1.3, P < 0.05 for both), as was QOL (Functional Assessment of Cancer Therapy-General [FACT-G] Lung Cancer subscale of 17.2 vs. 19.9, Anorexia/Cachexia subscale of 31.4 vs. 37.9, P < 0.05 for both). Differences in the FACT-G and the Functional Assessment of Chronic Illness Therapy-Fatigue subscale approached but did not reach statistical significance. Longitudinally, all measures of physical function and QOL worsened regardless of CACS status, but the rate of decline was more rapid in the CACS group. The weight-based component of the recently proposed international consensus CACS definition is useful in identifying patients with advanced NSCLC who are likely to have significantly inferior survival and who will develop more precipitous declines in physical function and QOL. This definition may be useful for clinical screening purposes and identify patients with high palliative care needs. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Financial distress in patients with advanced cancer

PubMed Central

Brosse, Christelle; Rhondali, Wadih; Ruer, Murielle; Monsarrat, Léa; Michaud, Patrick; Schott, Anne Marie; Delgado-Guay, Marvin; Bruera, Eduardo; Sanchez, Stéphane; Filbet, Marilène

2017-01-01

Purpose We examined the frequency and severity of financial distress (FD) and its association with quality of life (QOL) and symptoms among patients with advanced cancer in France. Design In this cross-sectional study, 143 patients with advanced cancer were enrolled. QOL was assessed using the Functional Assessment of Cancer General (FACT-G) and symptoms assessed using Edmonton Assessment System (ESAS) and Hospital Anxiety and Depression Scale (HADS). FD was assessed using a self-rated numeric scale from 0 to 10. Results Seventy-three (51%) patients reported having FD. Patients reported having FD were most likely to be younger (53.8 (16,7SD) versus 62 (10.5SD), p<0.001), single (33 (62%) versus 40(44%), p = 0.03) and had a breast cancer (26 (36%), p = 0.024). Patients with FD had a lower FACT-G score (59 versus 70, p = 0.005). FD decreased physical (14 versus 18, p = 0.008), emotional (14 versus 16, p = 0.008), social wellbeing (17 versus 19, p = 0.04). Patients with FD had higher HADS-D (8 versus 6 p = 0.007) and HADS-A (9 versus 7, p = 0.009) scores. FD was linked to increased ESAS score (59 (18SD) versus 67 (18SD), p = 0.005) and spiritual suffering (22(29SD) versus 13(23SD), p = 0.045). Conclusion The high rate of patient-reported FD was unexpected in our studied population, as the French National Health Insurance covers specific cancer treatments. The FD was associated with a poorer quality of life. Having a systematic assessment, with a simple tool, should lead to future research on interventions that will increase patients’ QOL. PMID:28545063

Financial distress in patients with advanced cancer.

PubMed

Barbaret, Cécile; Brosse, Christelle; Rhondali, Wadih; Ruer, Murielle; Monsarrat, Léa; Michaud, Patrick; Schott, Anne Marie; Delgado-Guay, Marvin; Bruera, Eduardo; Sanchez, Stéphane; Filbet, Marilène

2017-01-01

We examined the frequency and severity of financial distress (FD) and its association with quality of life (QOL) and symptoms among patients with advanced cancer in France. In this cross-sectional study, 143 patients with advanced cancer were enrolled. QOL was assessed using the Functional Assessment of Cancer General (FACT-G) and symptoms assessed using Edmonton Assessment System (ESAS) and Hospital Anxiety and Depression Scale (HADS). FD was assessed using a self-rated numeric scale from 0 to 10. Seventy-three (51%) patients reported having FD. Patients reported having FD were most likely to be younger (53.8 (16,7SD) versus 62 (10.5SD), p<0.001), single (33 (62%) versus 40(44%), p = 0.03) and had a breast cancer (26 (36%), p = 0.024). Patients with FD had a lower FACT-G score (59 versus 70, p = 0.005). FD decreased physical (14 versus 18, p = 0.008), emotional (14 versus 16, p = 0.008), social wellbeing (17 versus 19, p = 0.04). Patients with FD had higher HADS-D (8 versus 6 p = 0.007) and HADS-A (9 versus 7, p = 0.009) scores. FD was linked to increased ESAS score (59 (18SD) versus 67 (18SD), p = 0.005) and spiritual suffering (22(29SD) versus 13(23SD), p = 0.045). The high rate of patient-reported FD was unexpected in our studied population, as the French National Health Insurance covers specific cancer treatments. The FD was associated with a poorer quality of life. Having a systematic assessment, with a simple tool, should lead to future research on interventions that will increase patients' QOL.

Inflammation and cancer: advances and new agents.

PubMed

Crusz, Shanthini M; Balkwill, Frances R

2015-10-01

Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response.

Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer.

PubMed

Yasuda, Hiroyasu

2008-09-01

Hypoxia exists in solid tumor tissues due to abnormal vasculature, vascular insufficiency, treatment or malignancy related anemia, and low intratumor blood flow. Hypoxic status in solid tumor promotes accumulation of hypoxia-inducible factor-1 alpha which is promptly degraded by proteasomal ubiquitination under normoxic conditions. However, under hypoxic conditions, the ubiquitination system for HIF-1 alpha is inhibited by inactivation of prolyl hydroxylase which is responsible for hydroxylation of proline in the oxygen-dependent degradation domain of HIF-1 alpha. HIF-1 alpha is an important transcriptional factor that codes for hundreds of genes involved in erythropoiesis, angiogenesis, induction of glycolytic enzymes in tumor tissues, modulation of cancer cell cycle, cancer proliferation, and cancer metastasis. Hypoxia and accumulation of HIF-1 alpha in solid tumor tissues have been reported to associate with resistance to chemotherapy, radiotherapy, and immunotherapy and poor prognosis. Production of vascular endothelial growth factor (VEGF) in cancer cells is regulated by the activated HIF-1 mediated system. An increase in VEGF levels subsequently induces HIF-1 alpha accumulation and promotes tumor metastasis by angiogenesis. Recently, angiogenesis targeting therapy using humanized VEGF antibody and VEGF receptor tyrosine kinase inhibitors have been used in solid cancer therapy. Nitric oxide (NO) is a unique chemical gaseous molecule that plays a role as a chemical messenger involved in vasodilator, neurotransmitter, and anti-platelet aggregation. In vivo, NO is produced and released from three different isoforms of NO synthase (NOS) and from exogenously administered NO donors. In cancer science, NO has been mainly discussed as an oncogenic molecule over the past decades. However, NO has recently been noted in cancer biology associated with cancer cell apoptosis, cancer cell cycle, cancer progression and metastasis, cancer angiogenesis, cancer chemoprevention

Recent Advances and Perspectives in Cancer Drug Design.

PubMed

Magalhaes, Luma G; Ferreira, Leonardo L G; Andricopulo, Adriano D

2018-01-01

Cancer is one of the leading causes of death worldwide. With the increase in life expectancy, the number of cancer cases has reached unprecedented levels. In this scenario, the pharmaceutical industry has made significant investments in this therapeutic area. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments. Several noteworthy advances have been made, among which the development of targeted therapies is the most significant. Monoclonal antibodies and antibody-small molecule conjugates have emerged as a worthwhile approach to improve drug selectivity and reduce adverse effects, which are the main challenges in cancer drug discovery. This review will examine the current panorama of drug research and development (R&D) with emphasis on some of the major advances brought to clinical trials and to the market in the past five years. Breakthrough discoveries will be highlighted along with the medicinal chemistry strategies used throughout the discovery process. In addition, this review will provide perspectives and updates on the discovery of novel molecular targets as well as drugs with innovative mechanisms of action.

CAREGIVERS’ DIFFERING NEEDS ACROSS KEY EXPERIENCES OF THE ADVANCED CANCER DISEASE TRAJECTORY

PubMed Central

Bernard-DuBenske, Lori L.; Wen, Kuang-Yi; Gustafson, David H.; Guarnaccia, Charles A.; Cleary, James F.; Dinauer, Susan K.; McTavish, Fiona M.

2013-01-01

Familial caregivers are providing increasing amounts of care to advanced cancer patients. Increased understanding of caregivers’ needs is vital in providing necessary support to lessen caregiver burden and morbidity. Current literature has identified caregiver and patient needs at broad stages of the cancer trajectory; however, such broad stages may be too general to inform a practice of targeting specific interventions when they have the greatest utility. This study examines a variety of particular needs across a number of more discrete illness-related transition experiences specifically in the advanced cancer disease trajectory. One hundred fifty-nine female informal caregivers of people with advanced cancer completed a needs assessment survey. Analyses of these cross-sectional retrospective-report data reveal that cancer caregiver needs vary across specific key experiences occurring within the broader stages of illness identified by current literature. Furthermore, caregivers have unique needs during bereavement. While the sample characteristics are demographically limited, this study provides preliminary evidence that the broad stages are not specific enough increments for effectively examining caregiver needs, and supports the need for more precise distribution of cancer-related information at more discrete times in the illness course. PMID:18662420

Nursing care dependence in the experiences of advanced cancer inpatients.

PubMed

Piredda, Michela; Bartiromo, Chiara; Capuzzo, Maria Teresa; Matarese, Maria; De Marinis, Maria Grazia

2016-02-01

Increasing burden of cancer in Europe and socio-demographic trends imply that more cancer patients will face high levels of dependency. Care dependency is often perceived as a distressing experience by cancer patients who are concerned about becoming a burden to others. The experience of care dependence has been scarcely investigated in advanced cancer patients, especially in the hospital setting. This study aimed at describing advanced cancer patients' experiences of care dependence in hospital and of the factors perceived by them as contributing to decrease or increase this dependence. The study used a descriptive phenomenological approach based on Husserl's (1913) life world perspective. Data collection and analysis followed Giorgi's (1997) five basic methodological steps. Data were gathered by semi-structured interviews with thirteen advanced cancer adult inpatients of a teaching hospital. The interviews were audio-recorded and the recordings transcribed word for word. Three themes emerged: 'dependency discovers new meanings of life', 'active coping with dependency' and 'the care cures the dependent person'. The essential meaning of care dependency was the possibility to become aware of being a person as both an object and subject of care. Dependence appears as an experience with strong relational connotations, which enable patients to see differently their life, themselves, the world and others. Dependency is revealed as a natural experience, only partly in accordance with previous studies. Deeper insight into the meaning patients attach to care dependency can enable nurses to better meet the patient's needs, e.g. by improving caring relationships with patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Subgroup effects of occupational therapy-based intervention for people with advanced cancer.

PubMed

Sampedro Pilegaard, Marc; Oestergaard, Lisa Gregersen; la Cour, Karen; Thit Johnsen, Anna; Brandt, Åse

2018-03-23

Many people with advanced cancer have decreased ability to perform activities of daily living (ADL). We recently performed a randomized, controlled trial (RCT) assessing the efficacy of an occupational therapy-based program, the 'Cancer Home-Life Intervention' in people with advanced cancer (N = 242) and found no overall effects on ADL ability. However, heterogeneity of treatment effect may disguise subgroup differences. To investigate whether subgroups of people with advanced cancer gain positive effects from the 'Cancer Home-Life Intervention' on ADL ability. An exploratory subgroup analysis including 191 participants from a RCT. The outcome was ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Subgroups were defined by age, gender, years of education, type of primary tumor, functional level, and activity problems. The 'Cancer Home-Life Intervention' had no statistically significant effect in the six subgroups. Modifying effects of age (0.30 [95% CI: -0.05 to 0.64]) and gender (0.23 [95% CI: -0.11 to 0.57]) were not found. There were no subgroup effects of the 'Cancer Home-Life Intervention'on ADL motor ability. Some indications suggest greater effects for those aged below 69 years; however, this result should be interpreted with caution.

Advances in Decoding Breast Cancer Brain Metastasis

PubMed Central

Zhang, Chenyu; Yu, Dihua

2016-01-01

The past decade has witnessed impressive advances in cancer treatment ushered in by targeted and immunotherapies. However, with significantly prolonged survival, upon recurrence, more patients become inflicted by brain metastasis, which is mostly refractory to all currently available therapeutic regimens. Historically, brain metastasis is an understudied area in cancer research, partly due to the dearth of appropriate experimental models that closely simulate the special biological features of metastasis in the unique brain environment; and to the sophistication of techniques required to perform in-depth studies of the extremely complex and challenging brain metastasis. Yet, with increasing clinical demand for more effective treatment options, brain metastasis research has rapidly advanced in recent years. The present review spotlights the recent major progresses in basic and translational studies of brain metastasis with focuses on new animal models, novel imaging technologies, omics “big data” resources, and some new and exciting biological insights on brain metastasis. PMID:27873078

PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

ClinicalTrials.gov

2018-06-24

Small Cell Lung Cancer; Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Castration Resistant Prostate Adenocarcinoma; Soft Tissue Sarcoma; Ovarian Adenocarcinoma; Advanced Well-differentiated Neuroendocrine Tumors; Diffuse Large B Cell Lymphoma

Fatigue in Patients With Advanced Terminal Cancer Correlates With Inflammation, Poor Quality of Life and Sleep, and Anxiety/Depression.

PubMed

Rodrigues, Alex Rua; Trufelli, Damila Cristina; Fonseca, Fernando; de Paula, Larissa Carvalho; Giglio, Auro Del

2016-12-01

To assess which laboratory and clinical factors are associated with fatigue in patients with terminal cancer. We evaluated 51 patients with advanced incurable solid tumors using the Chalder Fatigue Questionnaire (CFQ) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale for fatigue; the Pittsburgh Sleep Quality Index (PSQI-BR) for sleep quality; the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression; the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire, Version 3.0 (QLQ C-30); and Functional Assessment of Cancer Therapy (FACT) for quality of life. We also analyzed several inflammatory markers and the modified Glasgow prognostic score (mGPS). We observed severe fatigue in 19 (38%) patients (FACIT-F score >36). There was a significant correlation between fatigue as evaluated by the CFQ and quality of sleep and between the CFQ mental fatigue subscale scores and TNF-α level. When fatigue was evaluated using the FACIT-F scale, we observed a significant association between fatigue and anxiety/depression, quality of sleep, mGPS, and hemoglobin levels. Fatigue measured both with the CFQ and FACIT-F scale correlated with poor quality of life according to the EORTC QLQ C-30. In patients with advanced cancer, fatigue is a common symptom associated with the presence of inflammation, poor quality of sleep, depression/anxiety, and poor quality of life. © The Author(s) 2015.

Advancements in Binder Systems for Solid Freeform Fabrication

NASA Technical Reports Server (NTRS)

Cooper, Ken; Munafo, Paul (Technical Monitor)

2002-01-01

Paper will present recent developments in advanced material binder systems for solid freeform fabrication (SFF) technologies. The advantage of SFF is the capability to custom fabricate complex geometries directly from computer aided design data in layer- by-layer fashion, eliminated the need for traditional fixturing and tooling. Binders allow for the low temperature processing of 'green' structural materials, either metal, ceramic or composite, in traditional rapid prototyping machines. The greatest obstacle comes when green parts must then go through a sintering or burnout process to remove the binders and fully densify the parent material, without damaging or distorting the original part geometry. Critical issues and up-to-date assessments will be delivered on various material systems.

How children cope when a parent has advanced cancer.

PubMed

Kennedy, Vida L; Lloyd-Williams, Mari

2009-08-01

When parents are diagnosed with cancer, children experience significant distress. There is little information regarding the nature of this distress and how children cope, particularly when a parent is diagnosed with advanced cancer. This study aimed to explore how children cope, and to identify areas where there may be barriers to children accessing support to enable them to cope. Semi-structured interviews were conducted with ill parents with advanced cancer and well parents and/or any children above the age of 7. Interviews were recorded and transcribed fully, and analysed using a constructionist grounded theory approach. Twenty-eight family participants were interviewed. Four major themes emerged from the data including response to diagnosis, mechanisms of coping, life changes, and positive aspects. Children described being distressed by their parents diagnosis and having concerns related to their parents and their own health. Distraction and maintaining normality were described as the dominant strategies of coping for children, and increased responsibilities and decreased social activity were considered to be the most noticeable of life changes. Parents did not recognise the impact on children to the same degree as described by children and focused on limiting the impact by maintaining normality. Positive aspects described by children and parents included strengthening of relationships and learning to value family members and the important things in life. Open communication within the family may lead to more effective coping and a positive experience for children whose parents have been diagnosed with advanced cancer.

Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer.

PubMed

Pritchard, Colin C; Morrissey, Colm; Kumar, Akash; Zhang, Xiaotun; Smith, Christina; Coleman, Ilsa; Salipante, Stephen J; Milbank, Jennifer; Yu, Ming; Grady, William M; Tait, Jonathan F; Corey, Eva; Vessella, Robert L; Walsh, Tom; Shendure, Jay; Nelson, Peter S

2014-09-25

A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers.

Cumulative incidence of cancer after solid organ transplantation.

PubMed

Hall, Erin C; Pfeiffer, Ruth M; Segev, Dorry L; Engels, Eric A

2013-06-15

Solid organ transplantation recipients have elevated cancer incidence. Estimates of absolute cancer risk after transplantation can inform prevention and screening. The Transplant Cancer Match Study links the US transplantation registry with 14 state/regional cancer registries. The authors used nonparametric competing risk methods to estimate the cumulative incidence of cancer after transplantation for 2 periods (1987-1999 and 2000-2008). For recipients from 2000 to 2008, the 5-year cumulative incidence, stratified by organ, sex, and age at transplantation, was estimated for 6 preventable or screen-detectable cancers. For comparison, the 5-year cumulative incidence was calculated for the same cancers in the general population at representative ages using Surveillance, Epidemiology, and End Results data. Among 164,156 recipients, 8520 incident cancers were identified. The absolute cancer risk was slightly higher for recipients during the period from 2000 to 2008 than during the period from 1987 to 1999 (5-year cumulative incidence: 4.4% vs. 4.2%; P = .006); this difference arose from the decreasing risk of competing events (5-year cumulative incidence of death, graft failure, or retransplantation: 26.6% vs. 31.9%; P < .001). From 2000 to 2008, the 5-year cumulative incidence of non-Hodgkin lymphoma was highest at extremes of age, especially in thoracic organ recipients (ages 0-34 years: range, 1.74%-3.28%; aged >50 years; range, 0.36%-2.22%). For recipients aged >50 years, the 5-year cumulative incidence was higher for colorectal cancer (range, 0.33%-1.94%) than for the general population at the recommended screening age (aged 50 years: range, 0.25%-0.33%). For recipients aged >50 years, the 5-year cumulative incidence was high for lung cancer among thoracic organ recipients (range, 1.16%-3.87%) and for kidney cancer among kidney recipients (range, 0.53%-0.84%). The 5-year cumulative incidence for prostate cancer and breast cancer was similar or lower in

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells

PubMed Central

Wu, Ching-Yuan; Cherng, Jong-Yuh; Yang, Yao-Hsu; Lin, Chun-Liang; Kuan, Feng-Che; Lin, Yin-Yin; Lin, Yu-Shih; Shu, Li-Hsin; Cheng, Yu-Ching; Liu, Hung Te; Lu, Ming-Chu; Lung, Jthau; Chen, Pau-Chung; Lin, Hui Kuan; Lee, Kuan-Der; Tsai, Ying-Huang

2017-01-01

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C–C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation. PMID:29207614

Recent advances in solid polymer electrolyte fuel cell technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ticianelli, E.A.; Srinivasan, S.; Gonzalez, E.R.

1988-01-01

With methods used to advance solid polymer electrolyte fuel cell technology, we are close to obtaining the goal of 1 A/cm/sup 2/ at 0.7. Higher power densities have been reported (2 A/cm/sup 2/ at 0.5 V) but only with high catalyst loading electrodes (2 mg/cm/sup 2/ and 4 mg/cm/sup 2/ at anode and cathode, respectively) and using a Dow membrane with a better conductivity and water retention characteristics. Work is in progress to ascertain performances of cells with Dow membrane impregnated electrodes and Dow membrane electrolytes. 5 refs., 6 figs.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

PubMed

Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Davis, Mellar P; Rivera, Nilo; Khoshknabi, Dilara Seyidova

2010-02-01

Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. To evaluate MP-associated symptoms or side effects (S/E). Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

PubMed

Enderling, Heiko; Hahnfeldt, Philip

2011-08-01

Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Eight Cases of Esophagus and Tracheobronchial Stenting for Advanced Esophageal Cancer].

PubMed

Nakahara, Yujiro; Takachi, Ko; Tsujimura, Naoto; Wakasugi, Masaki; Hirota, Masaki; Matsumoto, Takashi; Takemoto, Hiroyoshi; Nishioka, Kiyonori; Oshima, Satoshi

2017-11-01

Malignant stricture and fistula of the esophagus and tracheobronchus adversely affect the quality of life(QOL)in patients with advanced esophageal cancer. Stenting is one ofthe therapies available for these patients. We investigated the outcomes ofesophagus and tracheobronchial stenting in our institution. Eight patients with advanced esophageal cancer underwent double stenting from 2010 to 2016. Among them, 4 patients underwent double stenting as planned. One patient underwent an emergency tracheal stenting because ofstenosis ofthe trachea caused by esophageal stenting. Three patients underwent tracheobronchial stenting later on because ofan increase in the tumor size after esophageal stenting. Dysphagia score was improved in 5(67.5%)out ofthe 8 patients. Respiratory symptoms were improved in all patients, and 4 patients(50.0%) were discharged. The median survival time after esophageal stenting was 70.5 days. Esophagus and tracheobronchial stenting for advanced esophageal cancer was useful for the improvement of the QOL.

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

PubMed

Rugo, Hope S; Delord, Jean-Pierre; Im, Seock-Ah; Ott, Patrick A; Piha-Paul, Sarina A; Bedard, Philippe L; Sachdev, Jasgit; Tourneau, Christophe Le; van Brummelen, Emilie M J; Varga, Andrea; Salgado, Roberto; Loi, Sherene; Saraf, Sanatan; Pietrangelo, Dina; Karantza, Vassiliki; Tan, Antoinette R

2018-03-20

Purpose: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor-positive (ER + )/human epidermal growth factor receptor 2-negative (HER2 - ) advanced breast cancer with programmed death ligand 1-positive (PD-L1-positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. Experimental Design: Patients with ER + /HER2 - advanced breast cancer with PD-L1-positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review. Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3-15). Median follow-up was 9.7 months (range, 0.7-31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%-31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for ≥24 weeks]) was 20% (95% CI, 7-41). Median duration of response was 12.0 months (range, 7.4-15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred. Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1-positive, ER + /HER2 - breast cancer. Clin Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

Evaluation of Instrumental Activities of Daily Living in Greek Patients with Advanced Cancer

ERIC Educational Resources Information Center

Mystakidou, Kyriaki; Parpa, Efi; Tsilika, Eleni; Panagiotoua, Irene; Roumeliotou, Anna; Symeonidi, Matina; Galanos, Antonis; Kouvaris, Ioannis

2013-01-01

Translation of the instrumental activities of daily living (IADL) was carried out and its psychometric properties were assessed in a Greek sample of patients with advanced cancer. The scale was translated with the forward-backward procedure into the Greek language. It was initially administered to 136 advanced cancer patients. To assess…

[The necessary perseverance of surgery for the treatment of locally advanced colorectal cancer].

PubMed

Gu, Jin

2018-03-25

Colorectal cancer, a malignant tumor arising from the colon or rectum, is a common cancer in China, with most patients diagnosed at the advanced stage or locally advanced stage. Large tumor size results in the invasion of adjacent organs and the multiple organ involvement, which poses certain challenges for clinical treatment. When facing advanced stage colorectal cancer, some surgeons do not consider surgery, a reasonable option. However, in fact, multi-disciplinary treatment can achieve relatively good treatment outcomes in patients with advanced stage or locally advanced stage colorectal cancer. Therefore, reasonable surgery should not be hastily abandoned. For patients with large tumors without distant metastases but with multiple organ involvement, directly surgical resection is difficult, therefore, preoperative adjuvant therapy can be considered. The basic principle of surgical treatment is to accomplish maximum protection of organ functions and to perform reasonable regional lymph node dissection on the basis of achieving R0 resection. Common surgical procedures for locally advanced colorectal cancer are as follows: (1)Right-sided colon cancer with duodenal invasion: first, the colon must be freed from three directions, namely the right posterior surface of the colon, the left side of the tumor, and the upper side of the tumor inferior to the pylorus, so as to expose and assess the spatial relationship between the tumor and the duodenum; the actual tumor invasion depth in the duodenum may be shallow. (2) Splenic flexure colon cancer with invasion of the cauda pancreatis and hilum lienis: multivisceral resection must be performed without separating the attachment between the tumor and spleen. The tumor border can be found more easily through manipulations starting from the descending colon. (3) Giant sigmoid colorectal cancer with bladder invasion: invasion usually occurs at the bladder fundus. Therefore, during surgery, the attachment between the rectum and

Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-12-22

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Solid Neoplasm; Male Breast Carcinoma; Recurrent Adult Brain Neoplasm; Recurrent Breast Carcinoma; Recurrent Colon Carcinoma; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Carcinoma; Recurrent Rectal Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Breast Cancer; Stage IIIC Colon Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Health disparities and impact on outcomes in children with primary central nervous system solid tumors.

PubMed

Austin, Mary T; Hamilton, Emma; Zebda, Denna; Nguyen, Hoang; Eberth, Jan M; Chang, Yuchia; Elting, Linda S; Sandberg, David I

2016-11-01

OBJECTIVE Health disparities in access to care, early detection, and survival exist among adult patients with cancer. However, there have been few reports assessing how health disparities impact pediatric patients with malignancies. The objective in this study was to examine the impact of racial/ethnic and social factors on disease presentation and outcome for children with primary CNS solid tumors. METHODS The authors examined all children (age ≤ 18 years) in whom CNS solid tumors were diagnosed and who were enrolled in the Texas Cancer Registry between 1995 and 2009 (n = 2421). Geocoded information was used to calculate the driving distance between a patient's home and the nearest pediatric cancer treatment center. Socioeconomic status (SES) was determined using the Agency for Healthcare Research and Quality formula and 2007-2011 US Census block group data. Logistic regression was used to determine factors associated with advanced-stage disease. Survival probability and hazard ratios were calculated using life table methods and Cox regression. RESULTS Children with advanced-stage CNS solid tumors were more likely to be < 1 year old, Hispanic, and in the lowest SES quartile (all p < 0.05). The adjusted odds ratios of presenting with advanced-stage disease were higher in children < 1 year old compared with children > 10 years old (OR 1.71, 95% CI 1.06-2.75), and in Hispanic patients compared with non-Hispanic white patients (OR 1.56, 95% CI 1.19-2.04). Distance to treatment and SES did not impact disease stage at presentation in the adjusted analysis. Furthermore, 1- and 5-year survival probability were worst in children 1-10 years old, Hispanic patients, non-Hispanic black patients, and those in the lowest SES quartile (p < 0.05). In the adjusted survival model, only advanced disease and malignant behavior were predictive of mortality. CONCLUSIONS Racial/ethnic disparities are associated with advanced-stage disease presentation for children with CNS solid tumors

Blocking DNA Repair in Advanced BRCA-Mutated Cancer

Cancer.gov

In this trial, patients with relapsed or refractory advanced cancer and confirmed BRCA mutations who have not previously been treated with a PARP inhibitor will be given BMN 673 by mouth once a day in 28-day cycles.

Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer.

PubMed

Miura, Tomofumi; Mitsunaga, Shuichi; Ikeda, Masafumi; Ohno, Izumi; Takahashi, Hideaki; Suzuki, Hidetaka; Irisawa, Ai; Kuwata, Takeshi; Ochiai, Atsushi

2018-05-18

Acyl ghrelin is an orexigenic peptide. Active ghrelin ratio, the ratio of acyl ghrelin to total ghrelin, has an important role in physiological functions and gastrointestinal symptoms. However, low active ghrelin ratio-related characteristics, gastrointestinal symptoms, and chemotherapy-induced gastrointestinal toxicity in patients with advanced pancreatic cancer have not been previously evaluated. The goal of this study was to identify low active ghrelin ratio-related factors in treatment-naïve advanced pancreatic cancer patients. Patients with treatment-naïve advanced pancreatic cancer were eligible for inclusion in this study. Active ghrelin ratio and clinical parameters of patients were prospectively recorded. Factors correlated with low active ghrelin ratio and survival were analyzed. In total, 92 patients were analyzed. Low active ghrelin ratio-related factors were advanced age (P < 0.01), severe appetite loss (P < 0.01), and decreased cholinesterase (P < 0.01). The adverse events of grade 2 or higher anorexia tended to increase in patients with low active ghrelin ratio. However, no differences were found in survival and body composition between low and high active ghrelin ratio groups. Low active ghrelin ratio was related to lack of appetite and low cholinesterase and tended to be related to anorexia grade 2 or higher in patients with treatment-naïve advanced pancreatic cancer.

High rates of advanced gastric cancer in community of Flushing, New York.

PubMed

Dinani, Amreen; Desai, Amit; Kohn, Nina; Gutkin, Ellen; Nussbaum, Michel; Somnay, Kaumudi

2012-03-01

Gastric cancer remains a major public health issue and is a leading cause of death worldwide, accounting for 600,000 deaths annually. Over the last decades, there has been a steady decline in the incidence rates of gastric cancer. Furthermore, the incidence rates of gastric cancer in different parts of the country vary due to epidemiological and migration trends. Despite these trends, several studies that have continued to observe high rates of gastric cancer in populations that come from high-risk regions. The aim of the study was to describe the gastric cancer patients presenting NYHQ with an emphasis on those presenting at a young age and advanced disease. A subanalysis of the Asian population was also done, which is considered a high-risk group. Consecutive chart review of patients admitted with gastric cancer from January 2000 to August 2008 was extracted from the Oncology registry at NYHQ. Parameters that were evaluated were age, sex, race, type of gastric cancer, and stage of gastric cancer at initial presentation. The SAS/PC software package (SAS Institute Inc., Cary, NC) was employed for statistical analyses. Four hundred fifty-seven patients were diagnosed with gastric cancer. Approximately one third of the total patients were younger than 60 years of age. Of the Asian patients, almost half the patients (48.8%) had advanced disease of which two thirds were under the age of 60 years. The rates of advanced gastric cancer observed at NYHQ are significant and comparable to recent epidemiology literature on rates in Asian populations in Asia. Communities, like Flushing, NY, may benefit from early detection of gastric cancers, similar to those instituted in Japan and Taiwan.

Laparoscopic splenic hilar lymphadenectomy for advanced gastric cancer.

PubMed

Hosogi, Hisahiro; Okabe, Hiroshi; Shinohara, Hisashi; Tsunoda, Shigeru; Hisamori, Shigeo; Sakai, Yoshiharu

2016-01-01

Laparoscopic distal gastrectomy has recently become accepted as a surgical option for early gastric cancer in the distal stomach, but laparoscopic total gastrectomy (LTG) has not become widespread because of technical difficulties of esophagojejunal anastomosis and splenic hilar lymphadenectomy. Splenic hilar lymphadenectomy should be employed in the treatment of advanced proximal gastric cancer to complete D2 dissection, but laparoscopically it is technically difficult even for skilled surgeons. Based on the evidence that prophylactic combined resection of spleen in total gastrectomy increased the risk of postoperative morbidity with no survival impact, surgeons have preferred laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPL) for advanced tumors without metastasis to splenic hilar nodes or invasion to the greater curvature of the stomach, and reports with LSPL have been increasing rather than LTG with splenectomy. In this paper, recent reports with laparoscopic splenic hilar lymphadenectomy were reviewed.

Factors influencing diagnosis delay of advanced breast cancer in Moroccan women.

PubMed

Maghous, A; Rais, F; Ahid, S; Benhmidou, N; Bellahamou, K; Loughlimi, H; Marnouche, E; Elmajjaoui, S; Elkacemi, H; Kebdani, T; Benjaafar, N

2016-06-07

Delay in the diagnosis of breast cancer in symptomatic women of 3 months or more is associated with advanced stage and low survival. We conducted this study to learn more about the extent and reasons behind diagnosis delay of advanced breast cancer in Moroccan women. A group of patients with advanced breast cancer were interviewed at the National Institute of Oncology in Rabat during the period from February to December 2014. Diagnosis delay was devised into patient delay and system delay. Patient delay was defined as time from first symptoms until first medical consultation. System delay was defined as time from first presentation to a health care provider until definite diagnosis or treatment. Prospective information and clinical data were collected on a form during an interview with each patient and from medical records. In all, 137 patients were interviewed. The mean age of women was 48.3 ± 10.4 years. The median of consultation time was 6[4,12] months and the median of diagnosis time was 1[1,3] months. Diagnosis delay was associated to a personal reason in 96 (70.1 %) patients and to a medical reason in 19 (13.9 %) patients. A number of factors predicted diagnosis delay: symptoms were not considered serious in 66 (55.9 %) patients; traditional therapy was applied in 15 (12.7 %) patients and fear of cancer diagnosis and/or treatment in 14 (11.9 %) patients. A use of traditional methods was significantly associated with rural residence and far away from basic health center (p = 0.000). Paradoxically, a family history of breast cancer was significantly higher in who report a fear of cancer diagnosis and/or treatment to diagnosis delay (p < 0.001). Also, a significantly higher risk of more than 6 months delay was found among rural women (P = 0.035) and women who live far away from specialized care center (P = 0.001). Diagnosis delay is very serious problem in Morocco. Diagnosis delay was associated with complex interactions between

Comprehensive Approaches to Managing Delirium in Patients with Advanced Cancer

PubMed Central

Kang, Jung Hun; Shin, Seong Hoon; Bruera, Eduardo

2013-01-01

Delirium is a frequently under-recognized complication in patients with advanced cancer. Uncontrolled delirium eventually leads to significant distress to patients and their families. However, delirium episodes can be reversed in half of these patients by eliminating precipitating factors and using appropriate interventions. The purpose of this narrative review is to discuss the most recent updates in the literature on the management of delirium in patients with advanced cancer. This article addresses the epidemiology, cause, pathophysiology, clinical characteristics, and assessment of delirium as well as various treatment options, including nonpharmacologic intervention and palliative sedation. PMID:22959227

Estimating prevalence of functional iron deficiency anaemia in advanced cancer.

PubMed

Neoh, Karen; Stanworth, Simon; Pasricha, Sant-Rayn; Bennett, Michael I

2017-04-01

Anaemia is a common complication of cancer causing symptoms including fatigue. It is also associated with shorter survival. Cancer causes systemic inflammation which interrupts iron metabolism leading to a functional iron deficiency (FID). There are few data on prevalence or aetiology of anaemia in those with advanced cancer. We aimed to establish the prevalence of anaemia and estimate extent of FID anaemia in patients with advanced cancer. All patients with advanced cancer referred to two UK specialist palliative care services over 1 year were identified. Demographic and clinical data were linked with routinely collected haematological and biochemical profiles. We assessed the numbers of patients with abnormal values for haemoglobin, % hypochromic red cells (>5% indicates iron-restricted erythropoiesis) and CRP (>10 indicates systemic inflammation). We judged that FID anaemia was likely when patients had all three abnormalities and ferritin 30-800 ng/ml. Out of 2416 patients, 1797 had a cancer diagnosis and laboratory data available. Mean haemoglobin was 116 g/l. Sixty-three percent of patients were anaemic, mild 25%, moderate 35% and severe 3%. Women had significantly higher mean haemoglobin than men, and there was wide variation in anaemia prevalence across tumour sites. Thirty-nine percent of patients who had all four parameters checked met our criteria for FID anaemia. There were significant relationships between haemoglobin, % hypochromic red cells and CRP (p = 0.0001). Anaemia was common in this population, and we estimate this was caused by FID in 66% of anaemic patients. Further research is needed to validate our diagnostic criteria before this approach can be used in clinical practice.

Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

PubMed

Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

2014-11-21

In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

Advance Care Planning Does Not Adversely Affect Hope or Anxiety Among Patients With Advanced Cancer.

PubMed

Green, Michael J; Schubart, Jane R; Whitehead, Megan M; Farace, Elana; Lehman, Erik; Levi, Benjamin H

2015-06-01

Many physicians avoid advance care planning (ACP) discussions because they worry such conversations will lead to psychological distress. To investigate whether engaging in ACP using online planning tools adversely affects hope, hopelessness, or anxiety among patients with advanced cancer. Patients with advanced cancer and an estimated survival of two years or less (Intervention group) and a Control group were recruited at a tertiary care academic medical center (2007-2012) to engage in ACP using an online decision aid ("Making Your Wishes Known"). Pre/post and between-group comparisons were made, including hope (Herth Hope Index), hopelessness (Beck Hopelessness Scale), and anxiety (State Trait Anxiety Inventory). Secondary outcomes included ACP knowledge, self-determination, and satisfaction. A total of 200 individuals completed the study. After engaging in ACP, there was no decline in hope or increase in hopelessness in either the Control or Intervention group. Anxiety was likewise unchanged in the Control group but decreased slightly in the Intervention group. Knowledge of ACP (% correct answers) increased in both the groups, but more so in the Intervention group (13% increase vs. 4%; P<0.01). Self-determination increased slightly in both groups, and satisfaction with the ACP process was greater (P<0.01) in the Intervention than Control group. Engaging in ACP with online planning tools increases knowledge without diminishing hope, increasing hopelessness, or inducing anxiety in patients with advanced cancer. Physicians need not avoid ACP out of concern for adversely affecting patients' psychological well-being. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Environmental performance evaluation of an advanced-design solid-state television camera

NASA Technical Reports Server (NTRS)

1979-01-01

The development of an advanced-design black-and-white solid-state television camera which can survive exposure to space environmental conditions was undertaken. A 380 x 488 element buried-channel CCD is utilized as the image sensor to ensure compatibility with 525-line transmission and display equipment. Specific camera design approaches selected for study and analysis included: (1) component and circuit sensitivity to temperature; (2) circuit board thermal and mechanical design; and (3) CCD temperature control. Preferred approaches were determined and integrated into the final design for two deliverable solid-state TV cameras. One of these cameras was subjected to environmental tests to determine stress limits for exposure to vibration, shock, acceleration, and temperature-vacuum conditions. These tests indicate performance at the design goal limits can be achieved for most of the specified conditions.

Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

PubMed

Jacobs, Bruce L; Zhang, Yun; Schroeck, Florian R; Skolarus, Ted A; Wei, John T; Montie, James E; Gilbert, Scott M; Strope, Seth A; Dunn, Rodney L; Miller, David C; Hollenbeck, Brent K

2013-06-26

The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P < .001) and from 36% (95% CI, 35%-38%) to 57% (95% CI, 55%-59%) among men with high risk of noncancer mortality (P < .001). The use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P < .001). Among all patients diagnosed in SEER, the use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95

The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer.

PubMed

Soekmadji, Carolina; Nelson, Colleen C

2015-01-01

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Management of locally advanced and metastatic colon cancer in elderly patients.

PubMed

Kurniali, Peter C; Hrinczenko, Borys; Al-Janadi, Anas

2014-02-28

Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient's functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.

Identity and home: Understanding the experience of people with advanced cancer.

PubMed

Maersk, Jesper Larsen; Cutchin, Malcolm P; la Cour, Karen

2018-05-01

The purpose of this study was to explore how the identity of people with advanced cancer is influenced by their experiences of living at home. A total of 28 in-depth interviews were conducted with 22 people with advanced cancer and four spouses. Grounded theory guided the collection and analysis of data. Home tours and associated field notes augmented the interview data. The analysis revealed that support of participants' identity was reflected in their abilities to live and occupy the home during daily activities, and in the ways the home and objects functioned as referents to themselves and their past. Threats to their identity ensued as the home environment became unmanageable during daily activities and as homecare professionals and assistive devices entered the home. By supporting people with advanced cancer in maintaining daily activities in the home and reducing changes in the home caused by homecare it is possible to reduce loss of identity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recent Advances in Prostate Cancer Treatment and Drug Discovery.

PubMed

Nevedomskaya, Ekaterina; Baumgart, Simon J; Haendler, Bernard

2018-05-04

Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

Supporting women with advanced breast cancer: the impact of altered functional status on their social roles.

PubMed

Chen, Bai Qi Peggy; Parmar, Monica P; Gartshore, Kimberley

2014-01-01

Despite early detection of breast cancer and the progress of treatment modalities, metastasis-specific symptoms continue to impact women's functional status and daily living. The aim of this study was to explore the experience of altered functional status and social roles of women with advanced breast cancer. Using qualitative descriptive methodology, semi-structured interviews were conducted with 10 women diagnosed with advanced breast cancer and altered functional status attending a tertiary care cancer centre. Results illustrated the adaptive experience of women living with their illness as they reshaped their social roles to fit with their altered functional status and advanced disease. These findings highlight the opportunity for supportive care nursing interventions to facilitate the behavioural and cognitive transitions that are experienced by women with advanced breast cancer and altered functional status. These results may have implications for women with other advanced chronic diseases, though more research is required.

Conceptualizing prognostic awareness in advanced cancer: a systematic review.

PubMed

Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

2014-09-01

This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. © The Author(s) 2013.

Conceptualizing prognostic awareness in advanced cancer: A systematic review

PubMed Central

Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

2015-01-01

This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Cardiovascular Toxicity of Multi-Tyrosine Kinase Inhibitors in Advanced Solid Tumors: A Population-Based Observational Study

PubMed Central

Srikanthan, Amirrtha; Ethier, Josee-Lyne; Ocana, Alberto; Seruga, Bostjan; Krzyzanowska, Monika K.; Amir, Eitan

2015-01-01

Background Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors. Methods A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death. Results 1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents. Conclusions TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer. PMID:25815472

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

PubMed

Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

2017-10-01

The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Aesthetic engagements: "being" in everyday life with advanced cancer.

PubMed

la Cour, Karen; Hansen, Helle Ploug

2012-03-01

Living with advanced cancer can present an overwhelming challenge. It may impact the everyday life of the individual with respect to an array of psychological, physical, social, and existential issues. We focus on ways in which people with advanced cancer experience and use their engagement in daily activities when confronting nearing death. Through a phenomenological analysis based on Heidegger's thinking, we illuminate the complexities of "being toward death" and the human striving for authentic being through engagement in daily living. The main findings demonstrate how sensory experiences support being through an appreciation of everyday aesthetics. Furthermore, the making of material things was identified as a means to express the value of self and others in relation to the involved individual's past, present, and future.

Advances in single-cell RNA sequencing and its applications in cancer research.

PubMed

Zhu, Sibo; Qing, Tao; Zheng, Yuanting; Jin, Li; Shi, Leming

2017-08-08

Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years' development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection. One appealing area of single-cell RNA-seq is cancer research, and it is regarded as a promising way to enhance prognosis and provide more precise target therapy by identifying druggable subclones. Indeed, progresses have been made regarding solid tumor analysis to reveal intratumoral heterogeneity, correlations between signaling pathways, stemness, drug resistance, and tumor architecture shaping the microenvironment. Furthermore, through investigation into circulating tumor cells, many genes have been shown to promote a propensity toward stemness and the epithelial-mesenchymal transition, to enhance anchoring and adhesion, and to be involved in mechanisms of anoikis resistance and drug resistance. This review focuses on advances and progresses of single-cell RNA-seq with regard to the following aspects: 1. Methodologies of single-cell RNA-seq 2. Single-cell isolation techniques 3. Single-cell RNA-seq in solid tumor research 4. Single-cell RNA-seq in circulating tumor cell research 5.

Advances in single-cell RNA sequencing and its applications in cancer research

PubMed Central

Zhu, Sibo; Qing, Tao; Zheng, Yuanting; Jin, Li; Shi, Leming

2017-01-01

Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years’ development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection. One appealing area of single-cell RNA-seq is cancer research, and it is regarded as a promising way to enhance prognosis and provide more precise target therapy by identifying druggable subclones. Indeed, progresses have been made regarding solid tumor analysis to reveal intratumoral heterogeneity, correlations between signaling pathways, stemness, drug resistance, and tumor architecture shaping the microenvironment. Furthermore, through investigation into circulating tumor cells, many genes have been shown to promote a propensity toward stemness and the epithelial-mesenchymal transition, to enhance anchoring and adhesion, and to be involved in mechanisms of anoikis resistance and drug resistance. This review focuses on advances and progresses of single-cell RNA-seq with regard to the following aspects: 1. Methodologies of single-cell RNA-seq 2. Single-cell isolation techniques 3. Single-cell RNA-seq in solid tumor research 4. Single-cell RNA-seq in circulating tumor cell research 5. Perspectives PMID:28881849

Hydration in advanced cancer: can bioelectrical impedance analysis improve the evidence base? A systematic review of the literature.

PubMed

Nwosu, Amara Callistus; Mayland, Catriona R; Mason, Stephen R; Khodabukus, Andrew F; Varro, Andrea; Ellershaw, John E

2013-09-01

Decisions surrounding the administration of clinically assisted hydration to patients dying of cancer can be challenging because of the limited understanding of hydration in advanced cancer and a lack of evidence to guide health care professionals. Bioelectrical impedance analysis (BIA) has been used to assess hydration in various patient groupings, but evidence for its use in advanced cancer is limited. To critically appraise existing methods of hydration status assessment in advanced cancer and review the potential for BIA to assess hydration in advanced cancer. Searches were carried out in four electronic databases. A hand search of selected peer-reviewed journals and conference abstracts also was conducted. Studies reporting (de)hydration assessment (physical examination, biochemical measures, symptom assessment, and BIA) in patients with advanced cancer were included. The results highlight how clinical examination and biochemical tests are standard methods of assessing hydration, but limitations exist with these methods in advanced cancer. Furthermore, there is disagreement over the evidence for some commonly associated symptoms with dehydration in cancer. Although there are limitations with using BIA alone to assess hydration in advanced cancer, analysis of BIA raw measurements through the method of bioelectrical impedance vector analysis may have a role in this population. The benefits and burdens of providing clinically assisted hydration to patients dying of cancer are unclear. Bioelectrical impedance vector analysis shows promise as a hydration assessment tool but requires further study in advanced cancer. Innovative methodologies for research are required to add to the evidence base and ultimately improve the care for the dying. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

A Blueprint to Advance Colorectal Cancer Immunotherapies.

PubMed

Le, Dung T; Hubbard-Lucey, Vanessa M; Morse, Michael A; Heery, Christopher R; Dwyer, Andrea; Marsilje, Thomas H; Brodsky, Arthur N; Chan, Emily; Deming, Dustin A; Diaz, Luis A; Fridman, Wolf H; Goldberg, Richard M; Hamilton, Stanley R; Housseau, Franck; Jaffee, Elizabeth M; Kang, S Peter; Krishnamurthi, Smitha S; Lieu, Christopher H; Messersmith, Wells; Sears, Cynthia L; Segal, Neil H; Yang, Arvin; Moss, Rebecca A; Cha, Edward; O'Donnell-Tormey, Jill; Roach, Nancy; Davis, Anjelica Q; McAbee, Keavy; Worrall, Sharyn; Benson, Al B

2017-11-01

Immunotherapy is rapidly becoming a standard of care for many cancers. However, colorectal cancer had been generally resistant to immunotherapy, despite features in common with sensitive tumors. Observations of substantial clinical activity for checkpoint blockade in colorectal cancers with defective mismatch repair (microsatellite instability-high tumors) have reignited interest in the search for immunotherapies that could be extended to the larger microsatellite stable (MSS) population. The Cancer Research Institute and Fight Colorectal Cancer convened a group of scientists, clinicians, advocates, and industry experts in colorectal cancer and immunotherapy to compile ongoing research efforts, identify gaps in translational and clinical research, and provide a blueprint to advance immunotherapy. We identified lack of a T-cell inflamed phenotype (due to inadequate T-cell infiltration, inadequate T-cell activation, or T-cell suppression) as a broad potential explanation for failure of checkpoint blockade in MSS. The specific cellular and molecular underpinnings for these various mechanisms are unclear. Whether biomarkers with prognostic value, such as the immunoscores and IFN signatures, would also predict benefit for immunotherapies in MSS colon cancer is unknown, but if so, these and other biomarkers for measuring the potential for an immune response in patients with colorectal cancer will need to be incorporated into clinical guidelines. We have proposed a framework for research to identify immunologic factors that may be modulated to improve immunotherapy for colorectal cancer patients, with the goal that the biomarkers and treatment strategies identified will become part of the routine management of colorectal cancer. Cancer Immunol Res; 5(11); 942-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

PubMed

Albrecht, Tara A; Taylor, Ann Gill

2012-06-01

The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives.

Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

PubMed

Patel, Jyoti D; Krilov, Lada; Adams, Sylvia; Aghajanian, Carol; Basch, Ethan; Brose, Marcia S; Carroll, William L; de Lima, Marcos; Gilbert, Mark R; Kris, Mark G; Marshall, John L; Masters, Gregory A; O'Day, Steven J; Polite, Blasé; Schwartz, Gary K; Sharma, Sunil; Thompson, Ian; Vogelzang, Nicholas J; Roth, Bruce J

2014-01-10

Since its founding in 1964, the American Society of Clinical Oncology (ASCO) has been committed to improving cancer outcomes through research and the delivery of quality care. Research is the bedrock of discovering better treatments--providing hope to the millions of individuals who face a cancer diagnosis each year. The studies featured in "Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" represent the invaluable contributions of thousands of patients who participate in clinical trials and the scientists who conduct basic and clinical research. The insights described in this report, such as how cancers hide from the immune system and why cancers may become resistant to targeted drugs, enable us to envision a future in which cancer will be even more controllable and preventable. The scientific process is thoughtful, deliberate, and sometimes slow, but each advance, while helping patients, now also points toward new research questions and unexplored opportunities. Both dramatic and subtle breakthroughs occur so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training. Our nation's longstanding investment in federally funded cancer research has contributed significantly to a growing array of effective new treatments and a much deeper understanding of the drivers of cancer. But despite this progress, our position as a world leader in advancing medical knowledge and our ability to attract the most promising and talented investigators are now threatened by an acute problem: Federal funding for cancer research has steadily eroded over the past decade, and only 15% of the ever-shrinking budget is actually spent on clinical trials. This dismal reality threatens the pace of progress against cancer and undermines our ability to address the continuing needs of our patients. Despite this

New clinical advances in immunotherapy for the treatment of solid tumours

PubMed Central

Zavala, Valentina A; Kalergis, Alexis M

2015-01-01

Advances in understanding the mechanisms of cancer cells for evading the immune system surveillance, including how the immune system modulates the phenotype of tumours, have allowed the development of new therapies that benefit from this complex cellular network to specifically target and destroy cancer cells. Immunotherapy researchers have mainly focused on the discovery of tumour antigens that could confer specificity to immune cells to detect and destroy cancer cells, as well as on the mechanisms leading to an improved activation of effector immune cells. The Food and Drug Administration approval in 2010 of ipilumumab for melanoma treatment and of pembrolizumab in 2014, monoclonal antibodies against T-lymphocyte-associated antigen 4 and programmed cell death 1, respectively, are encouraging examples of how research in this area can successfully translate into clinical use with promising results. Currently, several ongoing clinical trials are in progress testing new anti-cancer therapies based on the enhancement of immune cell activity against tumour antigens. Here we discuss the general concepts related to immunotherapy and the recent application to the treatment of cancer with positive results that support their consideration of clinical application to patients. PMID:25826229

Systemic Inflammation-Based Biomarkers and Survival in HIV-Positive Subject With Solid Cancer in an Italian Multicenter Study.

PubMed

Raffetti, Elena; Donato, Francesco; Pezzoli, Chiara; Digiambenedetto, Simona; Bandera, Alessandra; Di Pietro, Massimo; Di Filippo, Elisa; Maggiolo, Franco; Sighinolfi, Laura; Fornabaio, Chiara; Castelnuovo, Filippo; Ladisa, Nicoletta; Castelli, Francesco; Quiros Roldan, Eugenia

2015-08-15

Recently, some systemic inflammation-based biomarkers have been demonstrated useful for predicting risk of death in patients with solid cancer independently of tumor characteristics. This study aimed to investigate the prognostic role of systemic inflammation-based biomarkers in HIV-infected patients with solid tumors and to propose a risk score for mortality in these subjects. Clinical and pathological data on solid AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC), diagnosed between 1998 and 2012 in an Italian cohort, were analyzed. To evaluate the prognostic role of systemic inflammation- and nutrition-based markers, univariate and multivariable Cox regression models were applied. To compute the risk score equation, the patients were randomly assigned to a derivation and a validation sample. A total of 573 patients (76.3% males) with a mean age of 46.2 years (SD = 10.3) were enrolled. 178 patients died during a median of 3.2 years of follow-up. For solid NADCs, elevated Glasgow Prognostic Score, modified Glasgow Prognostic Score, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and Prognostic Nutritional Index were independently associated with risk of death; for solid ADCs, none of these markers was associated with risk of death. For solid NADCs, we computed a mortality risk score on the basis of age at cancer diagnosis, intravenous drug use, and Prognostic Nutritional Index. The areas under the receiver operating characteristic curve were 0.67 (95% confidence interval: 0.58 to 0.75) in the derivation sample and 0.66 (95% confidence interval: 0.54 to 0.79) in the validation sample. Inflammatory biomarkers were associated with risk of death in HIV-infected patients with solid NADCs but not with ADCs.

Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

NASA Astrophysics Data System (ADS)

Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

2017-09-01

The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

New Advances and Challenges of Targeting Cancer Stem Cells.

PubMed

Dashzeveg, Nurmaa K; Taftaf, Rokana; Ramos, Erika K; Torre-Healy, Luke; Chumakova, Anastasia; Silver, Daniel J; Alban, Tyler J; Sinyuk, Maksim; Thiagarajan, Praveena S; Jarrar, Awad M; Turaga, Soumya M; Saygin, Caner; Mulkearns-Hubert, Erin; Hitomi, Masahiro; Rich, Jeremy N; Gerson, Stanton L; Lathia, Justin D; Liu, Huiping

2017-10-01

The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20-23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop. The reported advances of CSC research and therapies fostered new collaborations across national and international borders, and inspired the next generation's young scientists. Cancer Res; 77(19); 5222-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Advancing breast cancer survivorship among African-American women.

PubMed

Coughlin, Steven S; Yoo, Wonsuk; Whitehead, Mary S; Smith, Selina A

2015-09-01

Advances have occurred in breast cancer survivorship but, for many African-American women, challenges and gaps in relevant information remain. This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African-American women. For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African-American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African-American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. There is a need for a better understanding of breast cancer survivorship among African-American women. Additional evaluations of interventions for improving the quality of life and survival of African-American breast cancer survivors are desirable.

Factors associated with attrition from a randomized controlled trial of meaning-centered group psychotherapy for patients with advanced cancer

PubMed Central

Applebaum, Allison J.; Lichtenthal, Wendy G.; Pessin, Hayley A.; Radomski, Julia N.; Gökbayrak, N. Simay; Katz, Aviva M.; Rosenfeld, Barry; Breitbart, William

2013-01-01

Objective The generalizability of palliative care intervention research is often limited by high rates of study attrition. This study examined factors associated with attrition from a randomized controlled trial comparing meaning-centered group psychotherapy (MCGP), an intervention designed to help advanced cancer patients sustain or enhance their sense of meaning to the supportive group psychotherapy (SGP), a standardized support group. Methods Patients with advanced solid tumor cancers (n = 153) were randomized to eight sessions of either the MCGP or SGP. They completed assessments of psychosocial, spiritual, and physical well-being pretreatment, midtreatment, and 2 months post-treatment. Attrition was assessed in terms of the percent of participants who failed to complete these assessments, and demographic, psychiatric, medical, and study-related correlates of attrition were examined for the participants in each of these categories. Results The rates of attrition at these time points were 28.1%, 17.7%, and 11.1%, respectively; 43.1% of the participants (66 of 153) completed the entire study. The most common reason for dropout was patients feeling too ill. Attrition rates did not vary significantly between study arms. The participants who dropped out pretreatment reported less financial concerns than post-treatment dropouts, and the participants who dropped out of the study midtreatment had poorer physical health than treatment completers. There were no other significant associations between attrition and any demographic, medical, psychiatric, or study-related variables. Conclusions These findings highlight the challenge of maintaining advanced cancer patients in longitudinal research and suggest the need to consider alternative approaches (e.g., telemedicine) for patients who might benefit from group interventions but are too ill to travel. PMID:21751295

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

PubMed

Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Thyroid Hormone in the Clinic and Breast Cancer.

PubMed

Hercbergs, Aleck; Mousa, Shaker A; Leinung, Matthew; Lin, Hung-Yun; Davis, Paul J

2018-06-01

There is preclinical and recent epidemiological evidence that thyroid hormone supports breast cancer. These observations raise the issue of whether management of breast cancer in certain settings should include consideration of reducing the possible contribution of thyroid hormone to the advancement of the disease. In a preliminary experience, elimination of the clinical action of endogenous L-thyroxine (T 4 ) in patients with advanced solid tumors, including breast cancer, has favorably affected the course of the cancer, particularly when coupled with administration of exogenous 3,5,3'-triiodo-L-thyronine (T 3 ) (euthyroid hypothyroxinemia). We discuss in the current brief review the possible clinical settings in which to consider whether endogenous thyroid hormone-or exogenous thyroid hormone in the patient with hypothyroidism and coincident breast cancer-is significantly contributing to breast cancer outcome.

Safety and pharmacokinetics of veliparib extended-release in patients with advanced solid tumors: a phase I study.

PubMed

Werner, Theresa L; Sachdev, Jasgit; Swisher, Elizabeth M; Gutierrez, Martin; Kittaneh, Muaiad; Stein, Mark N; Xiong, Hao; Dunbar, Martin; Sullivan, Danielle; Komarnitsky, Philip; McKee, Mark; Tan, Antoinette R

2018-05-07

The poly(ADP-ribose) polymerase-1/2 inhibitor veliparib is active against tumors deficient in homologous DNA damage repair. The pharmacokinetics and safety of veliparib extended-release (ER) were evaluated in patients with advanced solid tumors. This phase I study assessed veliparib-ER up to 800 mg once daily or 600 mg twice daily. Dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), and maximum tolerated dose (MTD) were assessed in cycle 1 and safety/tolerability during continuous administration (28-day cycles). Seventy-one patients (n = 53 ovarian, n = 17 breast, n = 1 prostate carcinoma) received veliparib; 50 had deleterious breast cancer susceptibility (BRCA) gene mutations. Single-dose veliparib-ER 200 mg (fasting) led to 58% lower peak concentration and similar area under the concentration-time curve compared with veliparib immediate-release (IR). Three patients experienced DLTs (grade 2: asthenia; grade 3: nausea/vomiting, seizure). RP2D and MTD for veliparib-ER were 400 mg BID. The most frequent adverse events (AEs) were nausea (78.9%) and vomiting (50.7%). The most common grade 3/4 treatment-related AEs were as follows: thrombocytopenia (7.0%), nausea, and anemia (4.2% each). Overall, 12 (27.3%) patients with ovarian and 10 (62.5%) patients with breast carcinoma had a partial response. Veliparib-ER, versus veliparib-IR, exhibited an improved pharmacokinetic profile and was well tolerated in patients with ovarian and BRCA-mutated breast cancers. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Advanced Cancer Patients' Perceptions of Dignity: The Impact of Psychologically Distressing Symptoms and Preparatory Grief.

PubMed

Kostopoulou, Sotiria; Parpa, Efi; Tsilika, Eleni; Katsaragakis, Stylianos; Papazoglou, Irene; Zygogianni, Anna; Galanos, Antonis; Mystakidou, Kyriaki

2018-04-01

The present study assesses the relationship between patient dignity in advanced cancer and the following variables: psychological distress, preparatory grief, and sociodemographic and clinical characteristics. The sample consisted of 120 patients with advanced cancer. The self-administered questionnaires were as follows: the Preparatory Grief in Advanced Cancer Patients (PGAC), the Patient Dignity Inventory-Greek (PDI-Gr), the Greek Schedule for Attitudes toward Hastened Death (G-SAHD), and the Greek version of the Hospital Anxiety and Depression Scale (G-HADS). Moderate to strong statistically significant correlations were found between the 4 subscales of PDI-Gr (psychological distress, body image and role identity, self-esteem, and social support) with G-HADS, G-SAHD, and PGAC ( P < .005), while physical distress and dependency was moderately correlated with depression. Multifactorial analyses showed that preparatory grief, depression, and age influenced psychological distress, while preparatory grief, depression, and performance status influenced body image and role identity. Preparatory grief, psychological distress, and physical symptoms had significant associations with perceptions of dignity among patients with advanced cancer. Clinicians should assess and attend to dignity-distressing factors in the care of patients with advanced cancer.

Awareness of incurable cancer status and health-related quality of life among advanced cancer patients: a prospective cohort study.

PubMed

Lee, Myung Kyung; Baek, Sun Kyung; Kim, Si-Young; Heo, Dae Seog; Yun, Young Ho; Park, Sook Ryun; Kim, Jun Suk

2013-02-01

Many patients near death report an interest in knowing their prognoses. Patients' awareness of disease status may lead to more appropriate care and maintained or improved quality of life. However, it is not known whether advanced cancer patients' awareness of disease status is associated with patients' quality of life. We aimed to examine the effect of patients' awareness of disease status on the health-related quality of life (HRQOL) among advanced cancer patients undergoing palliative chemotherapy. In this prospective cohort study, patients were followed-up at 4-6 weeks and 2-3 months after the initial palliative chemotherapy. Patients' awareness of disease status, and demographic and clinical characteristics were assessed at baseline, and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) and HRQOL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were assessed three times. In total, 100 patients with advanced cancer starting palliative chemotherapy were recruited from two tertiary university hospitals and from the Korea National Cancer Center. Patients with advanced cancer undergoing palliative chemotherapy experienced deteriorated HRQOL. Of these, the patients who were aware of their disease status as incurable had significantly higher role (p=0.002), emotional (p=0.025), and social functioning (p=0.002), and lower fatigue (p=0.008), appetite loss (p=0.039), constipation (p=0.032), financial difficulties (p=0.019), and anxiety (p=0.041) compared with patients unaware of disease status. Our findings demonstrate the importance of patients' awareness of disease status to HRQOL.

Physician allocation of Medicare resources for patients with advanced cancer.

PubMed

Rocke, Daniel J; Lee, Walter T; Beumer, Halton W; Taylor, Donald H; Schulz, Kristine; Thomas, Steven; Puscas, Liana

2013-08-01

Little is known about what patients and physicians value in end-of-life care, or how these groups would craft a health plan for those with advanced cancer. The study objective was to assess how otolaryngology, head and neck surgery (OHNS) physicians would structure a Medicare benefit plan for patients with advanced cancer, and to compare this with cancer patient and cancer patient caregiver preferences. OHNS physicians used an online version of a validated tool for assessing preferences for health plans in the setting of limited resources. These data were compared to cancer patient and caregiver preferences. OHNS physicians nationwide were assessed with comparison to similar data obtained in a separate study of cancer patients and their caregivers treated at Duke University Medical Center. Otolaryngology physicians (n=767) completed the online assessment and this was compared with data from 146 patients and 114 caregivers. OHNS physician allocations differed significantly in 14 of the 15 benefit categories when compared with patients and caregivers. Physicians elected more coverage in the Advice, Emotional Care, Palliative Care, and Treatment for Cancer benefit categories. Patients and their caregivers elected more coverage in the Cash, Complementary Care, Cosmetic Care, Dental and Vision, Drug Coverage, Home Improvement, House Calls, Nursing Facility, Other Medical Care, and Primary Care benefit categories. Otolaryngology physicians have significantly different values in end-of-life care than cancer patients and their caregivers. This information is important for efficient allocation of scarce Medicare resources and for effective end-of-life discussions, both of which are key for developing appropriate health policy.

Liquid biopsy in liver cancer.

PubMed

Labgaa, Ismail; Villanueva, Augusto

2015-04-01

Liver cancer has become the second cause of cancer-related death worldwide. Most patients are still diagnosed at intermediate or advanced stage, where potentially curative treatment options are not recommended. Unlike other solid tumors, there are no validated oncogenic addiction loops and the only systemic agent to improve survival in advanced disease is sorafenib. All phase 3 clinical trials testing molecular therapies after sorafenib have been negative, none of which selected patients based on predictive biomarkers of response. Theoretically, analysis of circulating cancer byproducts (e.g., circulating tumor cells, cell-free nucleic acids), namely "liquid biopsy," could provide easy access to molecular tumor information, improve patients' stratification and allow to assess tumor dynamics over time. Recent technical developments and preliminary data from other malignancies indicate that liquid biopsy might have a role in the future management of cancer patients.

Immunotherapy in urothelial cancer, part 1: T-cell checkpoint inhibition in advanced or metastatic disease.

PubMed

Yu, Steven S; Dorff, Tanya B; Ballas, Leslie K; Sadeghi, Sarmad; Skinner, Eila C; Quinn, David I

2017-06-01

Cancer of the urothelium is the sixth most common cancer in the United States and is seen predominantly in men. Most cases of this disease present as non-muscle-invasive bladder cancer (NMIBC), with cancer recurrence or progression to muscle-invasive cancer in more than 50% of patients after initial therapy. NMIBC is an immune-responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. More recently, immunotherapy has seen much progress in a variety of cancers, including advanced and metastatic bladder cancer, in which historical 5-year survival rates are approximately 15%. The advent of T-cell checkpoint inhibitors, especially those directed at programmed death 1 (PD-1) and its ligand (PD-L1), has had a significant effect on the therapy of advanced urothelial cancer. This had led to accelerated approval by the US Food and Drug Administration for atezolizumab and nivolumab in advanced urothelial cancer previously treated with platinum-based chemotherapy. In addition, level 1 evidence supports the use of pembrolizumab over single-agent tubulin-directed chemotherapy in the same setting. Several other treatments with immune-mediating mechanisms of action are in development and hold great promise, including monoclonal antibodies directed at other checkpoint molecules, oncolytic virus therapy, adoptive T-cell therapy, combination immunotherapy, and antibody-drug conjugates. This review focuses on the recent development of T-cell checkpoint inhibitors in advanced and metastatic urothelial cancer and addresses their potential use in combination. It also discusses a spectrum of novel immunotherapies with potential use in urothelial cancer.

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

Multivisceral resection for advanced rectal cancer: outcomes and experience at a single institution.

PubMed

Crawshaw, Benjamin P; Augestad, Knut M; Keller, Deborah S; Nobel, Tamar; Swendseid, Brian; Champagne, Bradley J; Stein, Sharon L; Delaney, Conor P; Reynolds, Harry L

2015-03-01

Multivisceral resection is often required in the treatment of locally advanced rectal cancers. Such resections are relatively rare and oncologic outcomes, especially when sphincter preservation is performed, are not fully demonstrated. A retrospective review was conducted of patients who underwent multivisceral resection for locally advanced rectal cancer with and without sphincter preservation. Sixty-one patients underwent multivisceral resection for rectal cancer from 2005 to 2013 with a median follow-up of 27.8 months. Five-year overall and disease-free survival were 49.2% and 45.3%, respectively. Thirty-four patients (55.7%) had sphincter-sparing operations with primary coloanal anastomosis and temporary stoma. There was no significant difference in overall or disease-free survival, or recurrence with sphincter preservation compared with those with permanent stoma. Multivisceral resection for locally advanced rectal cancer has acceptable oncologic and clinical outcomes. Sphincter preservation and subsequent reestablishment of gastrointestinal continuity does not impact oncologic outcomes and should be considered in many patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Coping Well with Advanced Cancer: A Serial Qualitative Interview Study with Patients and Family Carers

PubMed Central

Roberts, Diane; Appleton, Lynda; Calman, Lynn; Large, Paul; Lloyd-Williams, Mari; Grande, Gunn

2017-01-01

Objectives To understand successful strategies used by people to cope well when living with advanced cancer; to explore how professionals can support effective coping strategies; to understand how to support development of effective coping strategies for patients and family carers. Design Qualitative serial (4–12 week intervals) interview study with people with advanced cancer and their informal carers followed by focus groups. The iterative design had a novel focus on positive coping strategies. Interview analysis focused on patients and carers as individuals and pairs, exploring multiple dimensions of their coping experiences. Focus group analysis explored strategies for intervention development. Participants 26 people with advanced (stage 3–4) breast, prostate, lung or colorectal cancer, or in receipt of palliative care, and 24 paired nominated informal/family carers. Setting Participants recruited through outpatient clinics at two tertiary cancer centres in Merseyside and Manchester, UK, between June 2012 and July 2013. Results 45 patient and 41 carer interviews were conducted plus 4 focus groups (16 participants). People with advanced cancer and their informal/family carers develop coping strategies which enable effective management of psychological wellbeing. People draw from pre-diagnosis coping strategies, but these develop through responding to the experience of living with advanced cancer. Strategies include being realistic, indulgence, support, and learning from others, which enabled participants to regain a sense of wellbeing after emotional challenge. Learning from peers emerged as particularly important in promoting psychological wellbeing through the development of effective ‘everyday’, non-clinical coping strategies. Conclusions Our findings challenge current models of providing psychological support for those with advanced cancer which focus on professional intervention. It is important to recognise, enable and support peoples’ own

Developing a common framework for integrated solid waste management advances in Managua, Nicaragua.

PubMed

Olley, Jane E; IJgosse, Jeroen; Rudin, Victoria; Alabaster, Graham

2014-09-01

This article describes the municipal solid waste management system in Managua, Nicaragua. It updates an initial profile developed by the authors for the 2010 UN-HABITAT publication Solid Waste Management in the World's Cities and applies the methodology developed in that publication. In recent years, the municipality of Managua has been the beneficiary of a range of international cooperation projects aimed at improving municipal solid waste management in the city. The article describes how these technical assistance and infrastructure investments have changed the municipal solid waste management panorama in the city and analyses the sustainability of these changes. The article concludes that by working closely with the municipal government, the UN-HABITAT project Strengthening Capacities for Solid Waste Management in Managua was able to unite these separate efforts and situate them within a strategic framework to guide the evolution of the municipal solid waste management system in the forthcoming years. The creation of this multi-stakeholder platform allowed for the implementation of joint activities and ensured coherence in the products generated by the different projects. This approach could be replicated in other cities and in other sectors with similar effect. Developing a long term vision was essential for the advancement of municipal solid waste management in the city. Nevertheless, plan implementation may still be undermined by the pressures of the short term municipal administrative government, which emphasize operational over strategic investment. © The Author(s) 2014.

Draft environmental impact statement: Space Shuttle Advanced Solid Rocket Motor Program

NASA Technical Reports Server (NTRS)

1988-01-01

The proposed action is design, development, testing, and evaluation of Advanced Solid Rocket Motors (ASRM) to replace the motors currently used to launch the Space Shuttle. The proposed action includes design, construction, and operation of new government-owned, contractor-operated facilities for manufacturing and testing the ASRM's. The proposed action also includes transport of propellant-filled rocket motor segments from the manufacturing facility to the testing and launch sites and the return of used and/or refurbished segments to the manufacturing site.

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

PubMed Central

Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

2017-01-01

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors. PMID:28052652

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review.

PubMed

Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

2017-10-01

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

Processes of code status transitions in hospitalized patients with advanced cancer.

PubMed

El-Jawahri, Areej; Lau-Min, Kelsey; Nipp, Ryan D; Greer, Joseph A; Traeger, Lara N; Moran, Samantha M; D'Arpino, Sara M; Hochberg, Ephraim P; Jackson, Vicki A; Cashavelly, Barbara J; Martinson, Holly S; Ryan, David P; Temel, Jennifer S

2017-12-15

Although hospitalized patients with advanced cancer have a low chance of surviving cardiopulmonary resuscitation (CPR), the processes by which they change their code status from full code to do not resuscitate (DNR) are unknown. We conducted a mixed-methods study on a prospective cohort of hospitalized patients with advanced cancer. Two physicians used a consensus-driven medical record review to characterize processes that led to code status order transitions from full code to DNR. In total, 1047 hospitalizations were reviewed among 728 patients. Admitting clinicians did not address code status in 53% of hospitalizations, resulting in code status orders of "presumed full." In total, 275 patients (26.3%) transitioned from full code to DNR, and 48.7% (134 of 275 patients) of those had an order of "presumed full" at admission; however, upon further clarification, the patients expressed that they had wished to be DNR before the hospitalization. We identified 3 additional processes leading to order transition from full code to DNR acute clinical deterioration (15.3%), discontinuation of cancer-directed therapy (17.1%), and education about the potential harms/futility of CPR (15.3%). Compared with discontinuing therapy and education, transitions because of acute clinical deterioration were associated with less patient involvement (P = .002), a shorter time to death (P < .001), and a greater likelihood of inpatient death (P = .005). One-half of code status order changes among hospitalized patients with advanced cancer were because of full code orders in patients who had a preference for DNR before hospitalization. Transitions due of acute clinical deterioration were associated with less patient engagement and a higher likelihood of inpatient death. Cancer 2017;123:4895-902. © 2017 American Cancer Society. © 2017 American Cancer Society.

Emergency department-initiated palliative care for advanced cancer patients: protocol for a pilot randomized controlled trial.

PubMed

Kandarian, Brandon; Morrison, R Sean; Richardson, Lynne D; Ortiz, Joanna; Grudzen, Corita R

2014-06-25

For patients with advanced cancer, visits to the emergency department (ED) are common. Such patients present to the ED with a specific profile of palliative care needs, including burdensome symptoms such as pain, dyspnea, or vomiting that cannot be controlled in other settings and a lack of well-defined goals of care. The goals of this study are: i) to test the feasibility of recruiting, enrolling, and randomizing patients with serious illness in the ED; and ii) to evaluate the impact of ED-initiated palliative care on health care utilization, quality of life, and survival. This is a protocol for a single center parallel, two-arm randomized controlled trial in ED patients with metastatic solid tumors comparing ED-initiated palliative care referral to a control group receiving usual care. We plan to enroll 125 to 150 ED-advanced cancer patients at Mount Sinai Hospital in New York, USA, who meet the following criteria: i) pass a brief cognitive screen; ii) speak fluent English or Spanish; and iii) have never been seen by palliative care. We will use balanced block randomization in groups of 50 to assign patients to the intervention or control group after completion of a baseline questionnaire. All research staff performing assessment or analysis will be blinded to patient assignment. We will measure the impact of the palliative care intervention on the following outcomes: i) timing and rate of palliative care consultation; ii) quality of life and depression at 12 weeks, measured using the FACT-G and PHQ-9; iii) health care utilization; and iv) length of survival. The primary analysis will be based on intention-to-treat. This pilot randomized controlled trial will test the feasibility of recruiting, enrolling, and randomizing patients with advanced cancer in the ED, and provide a preliminary estimate of the impact of palliative care referral on health care utilization, quality of life, and survival. Clinical Trials.gov identifier: NCT01358110 (Entered 5/19/2011).

Bloodstream infections in patients with solid tumors

PubMed Central

Gudiol, Carlota; Aguado, José María; Carratalà, Jordi

2016-01-01

ABSTRACT Little information is currently available regarding bloodstream infection (BSI) in patients with solid tumors who, for a variety of reasons, are particularly predisposed to develop this condition. In this review we focus on the incidence, epidemiology, clinical features, etiology, antimicrobial resistance, and outcomes of BSI of adult cancer patients with solid tumors. Most episodes of BSI occur in non-neutropenic patients, in whom the site of primary or metastatic tumor often serves as the portal of entry. The urinary tract and the abdomen are the most frequent sources of infection, and cholangitis is the most common recurrent source of BSI. Gram-negative bacilli are becoming the leading cause of BSI in patients with solid tumors, and the rate of multidrug resistance is increasingly being recognized. The case-fatality rate in patients with solid tumors and BSI is high, especially among those with comorbidities, advanced neoplasms, corticosteroid therapy, and shock at presentation. PMID:26787095

Combination Therapy Shows Promise for Treating Advanced Breast Cancer

Cancer.gov

Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

PubMed Central

Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

2015-01-01

Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

Communication with children about a parent's advanced cancer and measures of parental anxiety and depression: a cross-sectional mixed-methods study.

PubMed

Hailey, Claire E; Yopp, Justin M; Deal, Allison M; Mayer, Deborah K; Hanson, Laura C; Grunfeld, Gili; Rosenstein, Donald L; Park, Eliza M

2018-01-01

Parents with advanced cancer are faced with difficult decision-making about communication about their illness with their children. The objectives of this study were to describe how parents communicated with their children about advanced cancer and to explore associations between communication and parental depression and anxiety. This was a cross-sectional, mixed-methods study of 42 patients with stage IV solid tumor malignancies who had at least one child less than 18 years of age. Participants completed a semi-structured interview and the Hospital Anxiety and Depression Scale (HADS). We used multiple linear regression to evaluate the association between extent of communication and HADS Anxiety and Depression scores. Interview data were analyzed using standard qualitative content and thematic techniques and triangulated with survey data. Higher HADS Anxiety scores, but not HADS Depression scores, were cross-sectionally associated with greater extent of parental communication (p = 0.003), even when controlling for performance status and children's ages. In qualitative analyses, parents who acknowledged the terminal nature of their illness or experienced higher symptom burden were more likely to report that they also communicated more extensively with children. A third of parents (n = 14, 33%) described difficulty with illness-related communication with their children. In this pilot study, parents with advanced cancer who reported more illness-related communication with their children also reported more symptoms of general anxiety. Future interventions should address psychological distress relevant to parenting and further assess how parental communication may be linked to parental mood symptoms.

Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

PubMed

Rosa, Marilin

2015-04-01

Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

Optimizing secondary prevention of cervical cancer: Recent advances and future challenges.

PubMed

Ogilvie, Gina; Nakisige, Carolyn; Huh, Warner K; Mehrotra, Ravi; Franco, Eduardo L; Jeronimo, Jose

2017-07-01

Although human papillomavirus (HPV) vaccines offer enormous promise for the ultimate control and possible elimination of cervical cancer, barriers to uptake and coverage of the vaccine both in high- and low/middle-income settings mean that advances in secondary prevention continue to be essential to prevent unnecessary deaths and suffering from cervical cancer for decades to come. While cytology (the Pap smear) has reduced cervical cancer incidence and prevalence in jurisdictions where it has been systematically implemented in population-based programs-mainly in high-income settings-limitations inherent to this method, and to program delivery, leave many women still vulnerable to cervical cancer. Recent evidence has confirmed that screening based on HPV testing prevents more invasive cervical cancer and precancerous lesions, and offers innovative options such as self-collection of specimens to improve screening uptake broadly. In this paper, we review key advances, future opportunities, and ongoing challenges for secondary prevention of cervical cancer using HPV-based testing. © 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

Advancing Breast Cancer Survivorship among African American Women

PubMed Central

Coughlin, Steven S.; Yoo, Wonsuk; Whitehead, Mary S.; Smith, Selina A.

2015-01-01

Purpose Advances have occurred in breast cancer survivorship but, for many African American women, challenges and gaps in relevant information remain. Methods This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African American women. Results For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. Conclusions There is a need for a better understanding of breast cancer survivorship among African American women. Additional evaluations of interventions for improving the quality of life and survival of African American breast cancer survivors are desirable. PMID:26303657

Respiratory Symptoms, Sleep, and Quality of Life in Patients With Advanced Lung Cancer.

PubMed

Lou, Vivian W Q; Chen, Elaine J; Jian, Hong; Zhou, Zhen; Zhu, Jingfen; Li, Guohong; He, Yaping

2017-02-01

Maintenance of quality of life and symptom management are important in lung cancer therapy. To the author's knowledge, the interplay of respiratory symptoms and sleep disturbance in affecting quality of life in advanced lung cancer remains unexamined. The study was designed to examine the relationships among respiratory symptoms, sleep disturbance, and quality of life in patients with advanced lung cancer. A total of 128 patients with advanced lung cancer (from chest oncology inpatient-units in Shanghai, China) participated in the study. They completed two questionnaires: the Functional Assessment of Cancer Therapy-Lung and the Pittsburgh Sleep Quality Index. Symptomatic breathing difficulty, coughing, shortness of breath, and tightness in the chest were reported in 78.1%, 70.3%, 60.9%, and 60.2% of the patients, respectively. Sleep disturbance affected 62.5% of the patients. The patients with severe respiratory symptoms were more likely to be poor sleepers and to have a lower quality of life. After the covariates were controlled for, regression analysis showed that respiratory symptoms and sleep disturbance were significant indicators of quality of life. In addition, some of the effect of the respiratory symptoms on quality of life was mediated by sleep disturbance. Respiratory symptoms and sleep disturbance were common in the advanced lung cancer patients and had a negative impact on their quality of life; sleep disturbance may mediate the relationship between respiratory symptoms and quality of life. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Quo vadis radiotherapy? Technological advances and the rising problems in cancer management.

PubMed

Allen, Barry J; Bezak, Eva; Marcu, Loredana G

2013-01-01

Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.

Contemporary management of voice and swallowing disorders in patients with advanced lung cancer.

PubMed

Brady, Grainne C; Carding, Paul N; Bhosle, Jaishree; Roe, Justin W G

2015-06-01

Advanced lung cancer can cause changes to swallowing and communication function. Direct tumour invasion, dyspnoea and deconditioning can all impact on swallowing function and communication. Cancer treatment, if administered, may cause or compound symptoms. In this study, the nature of swallowing and communication difficulties in patients with advanced lung cancer will be discussed, and management options including medical management, speech and language therapy (SLT) intervention, and surgical interventions will be considered. Advanced lung cancer can result in voice and swallowing difficulties, which can increase symptom burden and significantly impact on quality of life (QOL). There is a growing evidence base to support the use of injection laryngoplasty under local anaesthetic to offer immediate improvement in voice, swallowing and overall QOL. There is limited literature on the nature and extent of voice and swallowing impairment in patients with lung cancer. Well designed studies with robust and sensitive multidimensional dysphagia and dysphonia assessments are required. Outcome studies examining interventions with clearly defined treatment goals are required. These studies should include both functional and patient-reported outcome measures to develop the evidence base and to ensure that interventions are both timely and appropriate.

"EXHALE": exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients.

PubMed

Quist, Morten; Langer, Seppo W; Rørth, Mikael; Christensen, Karl Bang; Adamsen, Lis

2013-10-14

Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb-IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO₂peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. http://ClinicalTrials.gov, NCT01881906.

Clinical evaluation of radiotherapy for advanced esophageal cancer after metallic stent placement

PubMed Central

Yu, You-Tao; Yang, Guang; Liu, Yan; Shen, Bao-Zhong

2004-01-01

AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer after expandable metallic stent placement. METHODS: Ten cases of advanced esophageal cancer were evaluated, 7 having complete obstruction and 3 with digestive-respiratory fistula. Ten nitinol stents were placed at the site of stenosis. Patients were treated with a total dose of 1200 cGy divided into 3 fractions of 400 cGy 4-7 d after stents placement. RESULTS: All the 10 stents were placed successfully at one time. After radiotherapy for advanced esophageal cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean survival of 17 mo. No re-stenosis occurred among all the 10 cases. CONCLUSION: Stent placement combined with radiotherapy for esophageal cancer is helpful to prolong patients’ survival and reduce occurrence of re-stenosis. PMID:15237455

Interval debulking surgery in advanced epithelial ovarian cancer.

PubMed

Pecorelli, Sergio; Odicino, Franco; Favalli, Giuseppe

2002-08-01

Cytoreductive surgery and chemotherapy are the mainstay for the treatment of advanced epithelial ovarian cancer. In order to minimize the tumour burden before chemotherapy, cytoreductive surgery is usually performed first. The importance of the amount of residual disease as the main prognostic factor for patients suffering from advanced disease has been almost universally accepted even in the absence of prospective randomized trials addressing the benefit of cytoreductive surgery. In the last decade, the value of debulking surgery after induction chemotherapy - interval debulking surgery, IDS - has been widely debated, especially after the completion of a prospective randomized study from the EORTC addressing the introduction of a surgical procedure with debulking intent preceded and followed by cytoreductive chemotherapy. The rationale of such a strategy in the context of the primary treatment of advanced ovarian cancer lies in a higher cytoreductibility to the 'optimal' status forwarded, and possibly facilitated, by chemotherapy. The results demonstrated a prolongation of both progression-free survival and median survival in favour of patients randomized to IDS (5 and 6 months, respectively). Multivariate analysis revealed IDS to be an independent prognostic factor which reduced the risk of death by 33% at 3 years and by 48% in subsequent re-evaluation after more than 6 years of observation. Despite the above, results have been questioned by many, leading the GOG to perform a similar study which has been concluded very recently. Nevertheless, the main concern regarding the application of IDS in all instances relates to the morbidity of two major surgical procedures integrated within a short period during which cytotoxic chemotherapy is also administered. Neoadjuvant chemotherapy has been recently proposed to avoid a non-useful surgical procedure in patients considered 'optimally unresectable' after diagnosis of advanced ovarian cancer. Whether or not this newer

Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

PubMed

Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

2016-11-01

The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Advance care planning within survivorship care plans for older cancer survivors: A systematic review.

PubMed

O'Caoimh, Rónán; Cornally, Nicola; O'Sullivan, Ronan; Hally, Ruth; Weathers, Elizabeth; Lavan, Amanda H; Kearns, Tara; Coffey, Alice; McGlade, Ciara; Molloy, D William

2017-11-01

Advances in the medical treatment of cancer have increased the number of survivors, particularly among older adults, who now represent the majority of these. Survivorship care plans (SCPs) are documents that cancer patients receive summarising their care, usually at the end of treatment but preferably from initial diagnosis. These may increase patient satisfaction and represent an opportunity to initiate preventative strategies and address future care needs. Advance care planning (ACP), incorporating advance healthcare decision-making, including formal written directives, increases satisfaction and end-of-life care. This paper systematically reviews evaluations of ACP within SCPs among older (≥65 years) cancer survivors. No studies meeting the inclusion criteria were identified by search strategies conducted in PubMed/MEDLINE and the Cochrane databases. One paper examined cancer survivors' mainly positive views of ACP. Another discussed the use of a SCP supported by a 'distress inventory' that included an advance care directive (living will) as an issue, though no formal evaluation was reported. Although ACP is important for older adults, no study was found that evaluated its role within survivorship care planning. Despite the risk of recurrence and the potential for morbidity and mortality, especially among older cancer survivors, ACP is not yet a feature of SCPs. Copyright © 2017 Elsevier B.V. All rights reserved.

A Phase I Study of Sunitinib plus Bevacizumab in Advanced Solid Tumors

PubMed Central

Rini, Brian I.; Garcia, Jorge A.; Cooney, Matthew M.; Elson, Paul; Tyler, Allison; Beatty, Kristi; Bokar, Joseph; Mekhail, Tarek; Bukowski, R.M.; Budd, G. Thomas; Triozzi, Pierre; Borden, Ernest; Ivy, Percy; Chen, Helen X.; Dolwati, Afshin; Dreicer, Robert

2009-01-01

Purpose Bevacizumab is an antibody against vascular endothelial growth factor (VEGF); sunitinib is an inhibitor of VEGF and related receptors. The safety and maximum tolerated dose (MTD) of sunitinib plus bevacizumab was assessed in this phase I trial. Experimental Design Patients with advanced solid tumors were treated on a 3+3 trial design. Patients received sunitinib daily (starting dose level 25 mg) for 4 weeks on followed by 2 weeks off and bevacizumab (starting dose level 5 mg/kg) on days 1, 15 and 29 of a 42-day cycle. Dose-limiting toxicities (DLTs) during the first 6-week cycle were used to determine the MTD. Results Thirty-eight patients were enrolled. Pts received a median of 3 cycles of treatment (range, 1–17+). There was one DLT (grade 4 hypertension) at 37.5 mg sunitinib and 5 mg/kg bevacizumab. Grade 3 or greater toxicity was observed in 87% of patients including hypertension (47%), fatigue (24%), thrombocytopenia (18%), proteinuria (13%), and hand-foot syndrome (13%). Dose modifications and delays were common at higher dose levels. No clinical or laboratory evidence of microangiopathic hemolytic anemia was observed. Seven patients had a confirmed RECIST-defined PR (18%; 95% confidence interval: 8–34%). Nineteen of the 32 patients with a post-baseline scan (59%) had at least some reduction in overall tumor burden (median 32%, range 3–73%). Conclusions The combination of sunitinib and bevacizumab in patients with advanced solid tumors is feasible, albeit with toxicity at higher dose levels and requiring dose modification with continued therapy. Anti-tumor activity was observed across multiple solid tumors. PMID:19773375

Conducting Reflective, Hands-On Research with Advanced Characterization Instruments: A High-Level Undergraduate Practical Exploring Solid-State Polymorphism

ERIC Educational Resources Information Center

Coles, S. J.; Mapp, L. K.

2016-01-01

An undergraduate practical exercise has been designed to provide hands-on, instrument-based experience of advanced characterization techniques. A research experience approach is taken, centered around the concept of solid-state polymorphism, which requires a detailed knowledge of molecular and crystal structure to be gained by advanced analytical…

Cytogenomics of Feline Cancers: Advances and Opportunities.

PubMed

Thomas, Rachael

2015-08-31

Relative to the dog, integration of the cat into the "One Health" concept has been more restricted, particularly in the field of molecular oncology. Beyond the continual need to enhance the sophistication of feline healthcare per se , the unique spectrum of naturally-occurring cancers in the cat offers tremendous opportunities for comparative and translational advances that may have mutual benefit for human and veterinary medicine. The study of feline cancers additionally may generate new insight into underexplored aspects of tumor biology that are less accessible in other species, such as the relationship between chronic inflammation and neoplasia, and the role of viruses in malignant transformation. Several factors that have hindered molecular studies of feline cancers have now been surmounted, with the most fundamental step forward coming from the development of a high-quality reference genome sequence assembly for the cat. This article reviews landmark studies that have led to our current appreciation of feline genome architecture, and outlines techniques used in cancer cytogenomics, from conventional karyotyping analysis through to the development of genomic microarrays and beyond. A summary of progress in the identification and characterization of chromosomal aberrations in feline cancers is provided using examples from studies of injection-site sarcomas, lymphomas and mammary tumors.

Recent Advances in Microwave Imaging for Breast Cancer Detection

PubMed Central

Kwon, Sollip

2016-01-01

Breast cancer is a disease that occurs most often in female cancer patients. Early detection can significantly reduce the mortality rate. Microwave breast imaging, which is noninvasive and harmless to human, offers a promising alternative method to mammography. This paper presents a review of recent advances in microwave imaging for breast cancer detection. We conclude by introducing new research on a microwave imaging system with time-domain measurement that achieves short measurement time and low system cost. In the time-domain measurement system, scan time would take less than 1 sec, and it does not require very expensive equipment such as VNA. PMID:28096808

Fusion genes in solid tumors: an emerging target for cancer diagnosis and treatment.

PubMed

Parker, Brittany C; Zhang, Wei

2013-11-01

Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

Bevacizumab improves survival for patients with advanced cervical cancer

Cancer.gov

Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

[Twenty-Five Cases of Locally Advanced Rectal Cancer That Underwent Laparoscopic Surgery after Preoperative Chemotherapy].

PubMed

Okuda, Hiroshi; Nakahara, Masahiro; Yano, Takuya; Bekki, Tomoaki; Takechi, Hitomi; Yoshikawa, Toru; Mochizuki, Tetsuya; Abe, Tomoyuki; Fujikuni, Nobuaki; Sasada, Tatsunari; Yamaki, Minoru; Amano, Hironobu; Noriyuki, Toshio

2017-11-01

Several recent reports have described the administration of preoperative chemotherapy for locally advanced rectal cancer. In our hospital, preoperative chemotherapy based on oxaliplatin was administered for locally advanced rectal cancer with a tumor diameter of 5 cm or more and half semicircularity or more, and curative resection with laparoscopic surgery was performed after tumor shrinkage. We have experienced 25 cases that underwent preoperative chemotherapy for local advanced rectal cancer in our hospital from May 2012 to April 2016. No tumor increased in size during preoperative chemotherapy and there were no cases where R0 resection was impossible. In addition, no distant metastasis during chemotherapy was observed. Postoperative complications were observed in 3 cases(12%), and anastomotic leakage was observed in 1 case (4%), but conservative treatment was possible. Multidisciplinary treatment of preoperative chemotherapy and surgery should be considered as a therapeutic strategy for locally advanced rectal cancer, mainly in medical institutions without radiation treatment facilities.

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials.

PubMed

Kelly, Karen; Infante, Jeffrey R; Taylor, Matthew H; Patel, Manish R; Wong, Deborah J; Iannotti, Nicholas; Mehnert, Janice M; Loos, Anja H; Koch, Helga; Speit, Isabell; Gulley, James L

2018-05-01

Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti-PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment-related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune-related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion-related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms. Of the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%). Avelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010-7. © 2018 The Authors

Advances in Radiotherapy Management of Esophageal Cancer.

PubMed

Verma, Vivek; Moreno, Amy C; Lin, Steven H

2016-10-21

Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC.

Advances in Radiotherapy Management of Esophageal Cancer

PubMed Central

Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

2016-01-01

Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer.

PubMed

Choi, S; Ryu, E

2018-01-01

People with advanced lung cancer experience later symptoms after treatment that is related to poorer psychosocial and quality of life (QOL) outcomes. The purpose of this study was to identify the effect of symptom clusters and depression on the QOL of patients with advanced lung cancer. A sample of 178 patients with advanced lung cancer at the National Cancer Center in Korea completed a demographic questionnaire, the M.D. Anderson Symptom Inventory-Lung Cancer, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy-General scale. The most frequently experienced symptom was fatigue, anguish was the most severe symptom-associated distress, and 28.9% of participants were clinically depressed. Factor analysis was used to identify symptom clusters based on the severity of patients' symptom experiences. Three symptom clusters were identified: treatment-associated, lung cancer and psychological symptom clusters. The regression model found a significant negative impact on QOL for depression and lung cancer symptom cluster. Age as the control variable was found to be significant impact on QOL. Therefore, psychological screening and appropriate intervention is an essential part of advanced cancer care. Both pharmacological and non-pharmacological approaches for alleviating depression may help to improve the QOL of lung cancer patients. © 2016 John Wiley & Sons Ltd.

Fatal hemoptysis in patients with advanced esophageal cancer treated with apatinib

PubMed Central

Wang, Wei; Zhang, Lin; Xie, Yan; Zhen, Tianchang; Su, Gongzhang; Zang, Qi

2018-01-01

Targeted therapy is commonly used for treating advanced malignant tumors. Compared with cytotoxic drugs, targeted drugs have the characteristics of good curative results, less adverse effects, and convenient oral administration. Hence, they are especially suitable for patients with cancer who are not able to tolerate chemotherapy. Anti-angiogenic therapy can achieve the objective by inhibiting the formation of new blood vessels in tumors. Apatinib is a novel tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2. It has been proven to be effective and safe in treating patients with gastric carcinoma and gastroesophageal junction carcinoma. So far, no reports are available on the treatment of esophageal cancer with apatinib. Two patients with advanced esophageal cancer were treated with oral apatinib because of their poor physical condition. After treatment, the dyspnea symptoms disappeared and quality of life significantly improved. Chest computed tomography showed massive necrosis of tumor tissues in each patient. The tumors significantly reduced and a cavity was formed locally in each patient. However, both patients died of massive hemoptysis, probably due to the rupture of the bronchial artery eroded by tumors. The results indicated that apatinib was effective in treating some patients with advanced esophageal cancer, and adverse effects were controllable. However, doctors should choose appropriate candidates according to apatinib’s indications. In addition, the use of apatinib should be carefully controlled for patients with esophageal cancer, especially in those with large vessels and trachea or bronchus eroded by tumor, so as to avoid or reduce the occurrence of fatal hemorrhage. PMID:29765235

Fatal hemoptysis in patients with advanced esophageal cancer treated with apatinib.

PubMed

Wang, Wei; Zhang, Lin; Xie, Yan; Zhen, Tianchang; Su, Gongzhang; Zang, Qi

2018-01-01

Targeted therapy is commonly used for treating advanced malignant tumors. Compared with cytotoxic drugs, targeted drugs have the characteristics of good curative results, less adverse effects, and convenient oral administration. Hence, they are especially suitable for patients with cancer who are not able to tolerate chemotherapy. Anti-angiogenic therapy can achieve the objective by inhibiting the formation of new blood vessels in tumors. Apatinib is a novel tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor-2. It has been proven to be effective and safe in treating patients with gastric carcinoma and gastroesophageal junction carcinoma. So far, no reports are available on the treatment of esophageal cancer with apatinib. Two patients with advanced esophageal cancer were treated with oral apatinib because of their poor physical condition. After treatment, the dyspnea symptoms disappeared and quality of life significantly improved. Chest computed tomography showed massive necrosis of tumor tissues in each patient. The tumors significantly reduced and a cavity was formed locally in each patient. However, both patients died of massive hemoptysis, probably due to the rupture of the bronchial artery eroded by tumors. The results indicated that apatinib was effective in treating some patients with advanced esophageal cancer, and adverse effects were controllable. However, doctors should choose appropriate candidates according to apatinib's indications. In addition, the use of apatinib should be carefully controlled for patients with esophageal cancer, especially in those with large vessels and trachea or bronchus eroded by tumor, so as to avoid or reduce the occurrence of fatal hemorrhage.