MedicalResearch.com Interview with:
Angelica Loskog, PhD
Professor of Immunotherapy (adjunct)
Dept of Immunology, Genetics and Pathology
Uppsala University
Uppsala Sweden
Medical Research: What is the background for this study? What are the main findings?
Dr. Loskog: CAR T cells have shown remarkable effect in patients with B cell malignancy in the US using 2nd generation CAR T cells. Acute leukemia (ALL) seems easier to treat than lymphomas and one of the reasons may be difficulties for CAR T cells to penetrate a solid lesion or due to a higher local presence of immunosuppressive cells within a lesion. As one of the first centers outside US we are evaluating 3rd generation CAR T cells in both lymphoma and ALL aiming to compare the responses and investigating biological reasons for the different responses. So far we have treated 11 patients and 6 of them had initial complete responses. Unfortunately, some progressed later.
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MedicalResearch.com Interview with:
Ahmad M. Khalil, PhD
Department of Genetics
School of Medicine
Case Western Reserve University
Cleveland, Ohio 44106-4955
Medical Research: What is the background for this study? What are the main findings?
Dr. Khalil: DNA in human cells is modified chemically by methylation. The process of DNA methylation plays important roles in protecting human DNA and ensures proper gene expression. In cancer cells, the process of DNA methylation becomes deregulated, however, the mechanisms of how this occurs are not known. In our study, we have uncovered a novel mechanism on how colon cancer cells change their DNA methylation, and consequently, become more tumorigenic. We specifically identified a long non-coding RNA that interacts with and regulates the enzyme that modifies DNA with methylation - the enzyme is called DNMT1. This lncRNA become suppressed in colon tumors, which we believe is a key step in loss of DNA methylation in colon cancer cells.
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MedicalResearch.com Interview with:
Prof. Dr. Holger Lode
Clinical Immunology, Pediatrics
University of Greifswald, Greifswald
Medical Research: What is the background for this study?
Response: Neuroblastoma is a cancer in childhood with one of the highest death rates. Standard treatment is already very intensive. It includes chemotherapy, surgery, radiation, high dose chemotherapy followed by autologous stem cell transplantation. However, the progress made in improving survival rates is still poor.
The use of an immune-modulatory treatment with a neuroblastoma specific monoclonal antibody ch14.18 (100 mg/m2 /cycle) in combination with cytokines and 13cis retinoic acid (13 cis RA) has shown benefit for patients with this disease [1]. This antibody targets ganglioside GD2 abundantly expressed on neuroblastoma with limited to no expression on healthy tissue. Low expression of GD2 on pain fibers is associated with an on-target side effect of the treatment, which is the induction of neuropathic pain. Approval of ch14.18 (dinutuximab) for the treatment of children with neuroblastoma has been provided by FDA.
In Europe, ch14.18 was not available for a long time. There were several reasons why the antibody in the US could not be given to children in Europe. Therefore a new development of this side of the Atlantic was initiated following the remanufacturing of the antibody in CHO cells [2] (dinutuximab beta) and was made available within clinical trials of the SIOPEN group. The SIOPEN group is a network of leading European pediatric oncology centers to improve outcome for children with neuroblastoma (http://www.siopen.org), similar to the COG (children`s oncology group in the USA; https://www.childrensoncologygroup.org).
Following the recloning procedure, ch14.18/CHO was first evaluated for safety in a Phase I study [3], which confirmed the tolerability and showed activity at a dosing regimen of 20 mg/m2 given by 8 hour infusions on 5 consecutive days. Dinutuximab beta is further developed by Apeiron Biologics.
The current way to apply 100 mg /m2 / cycle is by 4 short term infusions of 25 mg/m2/day each over 8 hrs on 4 consecutive days. The entire treatment consists of 5 cycles. The drawback is that STI is associated with a high amount of intravenous morphine required to make this treatment tolerable for patients. Also the rate of inflammatory side effects observed is substantial.
Clinical observation indicates that if patients treated by STI suffer from pain despite analgesic treatments, a decrease in speed of antibody infusion improves this on target toxicity. Therefore, we hypothesized that significant prolongation of the time of antibody infusion will improve tolerability of that treatment, but at the same time maintains clinical activity and efficacy in high risk neuroblastoma patients.
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MedicalResearch.com Interview with:
Kenneth R. Shroyer, MD, PhD
The Marvin Kuschner Professor and Chair
Department of Pathology
Stony Brook Medicine
Stony Brook, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Shroyer: Patients that appear to have the same type of cancer often respond very differently to treatment; while some patients appear to go into long-term regression or are cured, others follow a rapid downhill course and ultimately die of their disease. This suggests that there are fundamental differences between tumors at the biologic level that are not detected by current clinical measures.
In this study, we report the unexpected finding that cancer patients that have high levels of a protein called Keratin 17 (K17) have decreased long-term survival when compared to patients that express little to no K17 in their tumors. In addition, we found that K17 enters the nucleus of tumor cells to mediate the degradation of the master regulator of cell division and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17 increases the resistance of tumor cells to chemotherapy.
These are critical findings because this is the first report that a keratin is an oncoprotein that can enter the nucleus to promote the development of cancer and resistance to chemotherapy.
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MedicalResearch.com Interview with:
Charlotte Lund Rasmussen
Research Unit, Department of Palliative Medicine
Bispebjerg Hospital, Copenhagen, Denmark
Medical Research: What is the background for this study? What are the main findings?
Response: We see that patients with advanced cancer often suffer from fatigue, pain, depression, insomnia and other symptoms, which can have a profound impact on quality of life. Melatonin is a neurohormone and its secretion is closely tied to the circadian rhythm making it a regulator of the sleep-cycle.
Studies have shown that cancer patients have lower levels of melatonin than healthy controls, which may contribute to their fatigue and lowered quality of life. Furthermore, previous studies have found a possible effect of melatonin in cancer therapy, and non-clinical trials have shown melatonin to inhibit cell division in tumors.
To our knowledge, no trials to date have investigated the effects of melatonin on fatigue. Given the role of melatonin in the sleep cycle, the lowered levels of melatonin noted among cancer patients, and results from previous studies, we wanted to investigate melatonin’s effect on fatigue among patients with advanced cancer.
The primary objective of our study was to determine whether oral melatonin administered at night would reduce physical fatigue in patients with advanced cancer who were being treated in a palliative care facility. The effect of melatonin on other cancer-related symptoms including mental fatigue, insomnia, pain, emotional function, loss of appetite, and overall QoL were also investigated.
In this trial we tested a dose of 20 mg of melatonin taken orally at night.
However, melatonin did not improve physical fatigue in patients with advanced cancer. Furthermore, we were unable to identify improvements in any other cancer-related symptoms.
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MedicalResearch.com Interview with:
Sameek Roychowdhury, MD, PhD
Assistant Professor, Internal Medicine, College of Medicine
Assistant Professor, Department of Pharmacology
College of Pharmacy
Department of Internal Medicine
Division of Medical Oncology
Wexner Medical Center
The Ohio State University
Medical Research: What is the background for this study? What are the main findings?
Dr. Roychowdhury: Precision cancer medicine is a new paradigm to match patients to therapies based on the molecular alterations in their cancer. Novel genomic testing of cancer using next generation sequencing can reveal numerous mutations for each patient across many genes and types of cancer, and this requires detailed time-intensive interpretation. Driver mutations can confer a selective growth or survival advantage to cancer cells, while passenger mutations do not.
Cancer Driver Log, or CanDL, is meant to aid interpretation of mutations by providing the latest literature evidence for individual driver mutations, and thereby aiding pathologists, lab directors, and oncologists in interpreting mutations found in their patient’s cancer.
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MedicalResearch.com Interview with:
Dr. Sebastiano Mercadante MD
Director, Anesthesia and Intensive Care Unit and Pain Relief and Palliative Care Unit
La Maddalena Cancer Center, Palermo, Italy
Medical Research: What is the background for this study? What are the main findings?
Dr. Mercadante: Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background (1). Breakthrough cancer pain is a common problem in patients with cancer and is associated with significant morbidity. In a recent report in which a pragmatic definition of breakthrough cancer pain was used (2), the prevalence of BTcP was 75% (3).
Oral morphine (OM) has been traditionally offered as a breakthrough cancer pain medication in doses of about 1/6 of the daily opioid regimen for years, although this approach has never been supported by any evidence. Different technologies have been developed to provide a rapid onset of effect with potent opioid drugs such as fentanyl (rapid onset opioids, ROOs) delivered by non-invasive routes. Fentanyl products have been shown to be significantly superior to oral opioids, but it has been suggested that the dose of fentanyl should be individually titrated in order to enable effective analgesia to be delivered while minimizing the risk of clinically significant adverse effects. The need of dose titration with rapid onset opioids has never been appropriately assessed and this statement is derived by a series of weaknesses of papers published for regulatory issues. Indeed, the only existing study comparing dose titration and proportional doses, reported that proportional doses of (Fentanyl buccal tablet) FBT are more effective and safe over dose titration method. NICE guidelines did not provide evidence for that, at least at certain time intervals after administration.
To scientifically compare rapid onset opioids and oral morphine, we used a similar approach and made a strict selection of patients, according to a more specific algorithm for a diagnosis o fbreakthrough cancer pain. Thus, patients were randomized to receive in a crossover design Fentanyl buccal tablet and oral morphine, both given in doses proportional to opioid daily doses, for the management of breakthrough cancer pain.
This comparative study has shown that, when giving the drugs for breakthrough cancer pain in doses proportional to the opioid regimen for background pain, Fentanyl was clearly superior for efficacy and rapidity in comparison with oral morphine. The analgesic effect was more intense either at 15 and 30 minutes after study medications were given. A larger number of episodes treated with Fentanyl buccal tablet presented a decrease in pain intensity of ≥33% and ≥50% in comparison with episodes treated with oral morphine, and a relevant difference in SPID30 was reported. Of interest, adverse effects commonly observed in patients receiving opioids were not severe and did not differ between the treatments, suggesting that the use of proportional doses of both drugs are safe, reflecting what is derived by the long-lasting experience with oral morphine.(more…)
MedicalResearch.com Interview with:
Hardeep Singh, MD MPH
Chief, Health Policy, Quality and Informatics Program,
Houston Veterans Affairs Health Services Research Center for Innovations
Michael E. DeBakey Veterans Affairs Medical Center and
Baylor College of Medicine
Houston TX 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Singh: Missed or delayed diagnoses are among the most common patient safety concerns in outpatient settings, and measuring and reducing them is a high priority. Our computerized triggers scanned huge amounts of patient data in the electronic health record and flagged individuals at risk for delays in follow-up of cancer-related abnormal clinical findings. Records of all patients flagged by the computerized trigger algorithm in the intervention group were reviewed to determine the presence of delay and if delay was confirmed, we communicated this information to their clinicians. We found that patients seeing clinicians who were notified of potential delays had more timely diagnostic evaluation for both prostate and colon cancer and more patients in the intervention part of the study had received diagnostic evaluation by the time we completed our final review.
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MedicalResearch.com Interview with:
Dr. Yin Cao MPH, ScD
Postdoctoral Fellow, Department of Nutrition
Harvard T. H. Chan School of Public HealthMedical Research: What is the background for this study? What are the main findings?Dr. Cao: Light-to-moderate drinking, defined as up to 1 drink (roughly corresponds to a 355ml bottle of beer, or a small [118-148 ml] glass of wine or 44ml of liquor) for women and up to 2 drinks for men, is prevalent in many western countries. It is believed that light-to-moderate drinking may be healthy for the heart. However, the influence of light-to-moderate drinking on risk of overall cancer is less clear, although it is well known that heavy alcohol intake increases risk of several cancers, including cancers of colorectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus.
Also because drinkers are more likely to be smokers, and smoking is the major risk factor for all of the alcohol-related cancers (mentioned above) except breast cancer, it is thus difficult to tease out the influence of alcohol on cancer in studies among a mixed population of ever and never smokers. In particular, it is important to know how light and moderate drinking would affect cancer risk particularly among never smokers, who now make up the majority of the population in many western countries.
Our main findings are that, light-to-moderate drinking minimally increases risk of overall cancer. For men, the association with alcohol related cancers was primarily observed among smokers, and light to moderate drinking did not appreciably increase risk in never smokers. Among women, even consumption of up to one drink per day was associated with increased risk of alcohol-related cancers (mainly breast cancer) for both never and ever smokers.
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MedicalResearch.com Interview with:Thomas F. Imperiale, MD
Indiana University Medical Center
Regenstrief Institute
Indianapolis, IN 46202
Medical Research: What is the background for this study?
Dr. Imperiale: The background is that colorectal cancer (CRC) screening is effective and cost-effective, but it is underutilized (35% of eligible persons in the U.S. are not current with screening; 28% have never been screened) and inefficient (persons at low risk have colonoscopy; persons at high risk have stool blood testing or nothing). We know about several risk factors for colorectal cancer and advanced, precancerous polyps. We wanted to see how those factors perform together in stratifying (or separating) risk among the 85% of the U.S. population that is considered to be “average-risk”.
Medical Research: What are the main findings?
Dr. Imperiale: We found that age, sex, whether a first-degree relative has or had colorectal cancer, cigarette smoking, and waist circumference do a good job in separating risk into the 4 categories described in the paper. When tested in the validation subgroup, the risk estimates reproduced themselves fairly well.(more…)
MedicalResearch.com Interview with: Raymond Osarogiagbon MD, FACP
Thoracic Oncology Research Group
Baptist Cancer Center
Memphis, Tennessee
Medical Research: What is the background for this study? What are the main findings?Dr. Osarogiagbon: Lung cancer care is complicated, but can be broken down into 5 steps: x-ray detection, biopsy, x-ray tests of cancer spread (the ‘stage’), biopsy of suspicious areas where cancer may have spread, and treatment.
Looking only at patients who had surgery for a suspected lung cancer, we worked backwards to see how their care went through the key steps and how long it took.
We found that patients often skip some of the crucial steps. For example, 22% did not have a staging PET/CT scan, 88% did not have an invasive staging test. Only 10% had the recommended combination of 3 staging tests leading up to surgery: a CT scan, PET/CT scan, and invasive staging test.
It took a month and a half to more than 6 months for the middle half of patients to go from first abnormal x-ray sign of possible lung cancer to surgery.
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MedicalResearch.com Interview with:
Reshma Jagsi, MD, DPhil
Associate Professor and Deputy Chair
Department of Radiation Oncology
University of Michigan
Medical Research: What is the background for this study? What are the main findings?
Response: In recent years, there has been accumulating evidence from clinical trials that have supported the long-term safety and effectiveness of shorter courses of radiation therapy—“hypofractionated radiation therapy”—for patients with breast cancer. However, little has been known about the experiences of patients during treatment, especially when this new approach is administered outside the setting of closely controlled clinical trials. Our study examined the side effects and patient-reported experiences during radiation treatment of over 2000 breast cancer patients in the state of Michigan. It found that women who received hypofractionated treatment were less likely to report side effects (including skin reaction and fatigue) than patients treated with more traditional courses of radiation treatment, delivered daily over 5-6 weeks or longer.
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MedicalResearch.com Interview with: Christos Nikolaidis Ph.D.
Laboratory of Pharmacology
Medical School, Democritus University of Thrace
Dragana, Alexandroupolis Greece
Medical Research: What is the background for this study?
Response: Epigenetic changes are part of the natural history of cervical neoplasia. Tracking these changes at the molecular level is necessary for understanding disease progression, response to treatment and prognosis. Epigenetic biomarkers can potentially assess the stage of cervical intraepithelial neoplasia (CIN). This information can be used for screening purposes, to improve the overall quality of cervical cancer diagnostics.
Medical Research: What are the main findings?
Response: Paired boxed 1 (PAX1) gene methylation status has been widely used as a biomarker for cervical cancer screening. We have conducted a meta-analysis of the diagnostic test accuracy of PAX1 methylation, on moderate cervical dysplasia or worse (CIN2+) versus normal epithelium, and severe cervical dysplasia or worse (CIN3+) versus normal epithelium, for a total population of 1385 women. The results of this assay were generally satisfactory for CIN2+ vs normal, and extremely satisfactory for CIN3+ vs normal (Sensitivity=0.77, Specificity=0.92, AUC=0.931). This raises the possibility of utilizing this biomarker to improve current diagnostic protocols.
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MedicalResearch.com Interview with:
Prof David C Currow
Discipline of Palliative and Supportive Services
Flinders University
Adelaide, SA, Australia
Medical Research: What is the background for this study? Prof. Currow: This study grew out of a desire to better understand the symptom burden experienced by people with hematological malignancies at the end of life. This has been very poorly documented and although there are lots of strong opinions, there are very few data at a population level.
Medical Research: What are the main findings?Prof. Currow: The main finding is that community-dwelling people with hematological malignancies at the end of life have a burden of symptoms that looked almost identical to people with solid tumours. Given much lower rates of access to the hospice and palliative care, this suggests that these people and their family caregivers are missing out on opportunities for better symptom control and better support. (more…)
MedicalResearch.com Interview with:
Gwendolyn P. Quinn, Ph.D.
Moffitt Cancer Center
University of South Florida
MedicalResearch: What is the background for this study? What are the main findings?Dr. Quinn: Our research group has been conducting studies of the LGBTQ community and their healthcare experiences combined with providers knowledge and attitudes about LGBTQ and cancer care. This led us to examine the literature on cancer and LGBTQ. The main findings point to the lack of rigorous data about cancer in the LGBTQ community. Our review revealed that 7 cancers (anal, breast, cervical, colorectal, colon and rectal, endometrial, lung and prostate cancers) may occur more frequently in the community due to elevated prevalence of risk factors and behaviors such as obesity and substance use; however, there are limited data on outcomes, morbidity and mortality. The lack of data makes it difficult for providers to fully inform patients about early detection, prevention, and treatment options and outcomes. Further, the lack of psychosocial data makes it difficult to provide supportive care recommendations and other forms of support. (more…)
MedicalResearch.com Interview with:
Eduardo Vilar-Sanchez, MD, PhD
Assistant Professor, Department of Clinical Cancer Prevention
Division of OVP, Cancer Prevention and Population Science
The University of Texas MD Anderson Cancer Center
Houston, TX 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Vilar-Sanchez: I am a physician scientist at The University of Texas MD Anderson Cancer Center (MDA), a medical oncologist specializing in cancer genetics, especially colorectal cancer (CRC) syndromes. At MD Anderson, I have medical practice consisting primarily of colorectal cancer, as part of the clinical cancer arm of MD Anderson.
I became interested in this topic because it is now well recognized that colorectal cancer is increasing in prevalence in young individuals. CRC is the third most common cancer in the US with 90% diagnosed in patients older than 50. While most CRC patients develop cancer in their 60s or 70s, the incidence is now rising in individuals younger than 50. Over the next two decades, it is projected that the incidence of CRC in young adults under 35 will double.
Only 5% of all CRC patients have a known hereditary predisposition cancer syndrome. Patients diagnosed at or under age 35 represent an extreme phenotypic presentation, constituting only 1.5% of all CRC cases.
We retrospectively reviewed all patients with CRC patients age 35 or under, who were evaluated by the Genetic Services group at MD Anderson. In this group, a surprising 30% had a recognized hereditary cancer syndrome, a marked increase compared to the general CRC population.
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MedicalResearch.com Interview with:
Dr. Pam Marcus PhD
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
National Institutes of Health
Bethesda, MD 20892
MedicalResearch: Why do we need to consider targeted cancer screening?Dr. Marcus: Cancer screening, the routine testing of asymptomatic individuals without a history of the disease of interest, is an important approach to cancer prevention and control. There is compelling evidence that screening for at least four cancers reduces disease-specific mortality, but population-based cancer screening also leads to unfavorable events. Only a minority of those screened will benefit, and many will have false-positive exams. Some screenees will experience undesirable sequelae, ranging from minor inconveniences to serious adverse events due to the exam itself or diagnostic evaluation.
MedicalResearch: What is the goal of targeted cancer screening in average-risk individuals?Dr. Marcus: Targeted cancer screening attempts to segregate those who will benefit from screening from those who will not through use of information on disease risk. Average risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without co-morbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. The goal of targeted cancer screening in average risk individuals is to reduce the number of individuals who need to be screened while preserving the overarching benefit of reduced cancer-specific mortality in the general population. Targeted cancer screening is an example of precision medicine; visit http://www.nih.gov/precisionmedicine/goals.htm to learn more about the National Institute of Health’s Precision Initiative.
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MedicalResearch.com Interview with:
Dr. Vincent L. Cryns MD
Chief of the Division of Endocrinology, Diabetes and Metabolism
Department of Medicine
University of Wisconsin Carbone Cancer Center
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin
Medical Research: What is the background for this study? What are the main findings?Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or die. What’s been missing is a molecular explanation for these effects that would allow us incorporate this approach into a rationally designed clinical trial. In our work, we have demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a “fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a targeted cancer therapy. (more…)
MedicalResearch.com Interview with:
Haining Yang MD Ph.DAssociate ProfessorThoracic Oncology Program
University of Hawaii Cancer Center
University of Hawaii, Honolulu, HI
Medical Research: What is the background for this study?
Dr. Yang: Mesothelioma is often caused by asbestos and other carcinogenic mineral fibers. When these fibers lodge in the pleura, mesothelial cells and macrophages try to phagocytize and eliminate them. However, asbestos is very bio-persistent and cannot be eliminated, which caused cells undergoing programmed necrosis that leads to the release of HMGB1 into the extracellular space. HMGB1 is a damage-associated molecular pattern molecule (DAMP) that causes inflammation. Asbestos exposure induces HMGB1 release and chronic inflammatory process that overtime may lead to malignancy. Mesothelioma cells develop out of an environment that is rich in HMGB1 and are often dependent on HMGB1 for their own growth. In fact, most mesothelioma cells actively secrete HMGB1 extra-cellularly to promote their own tumor growth. Accordingly HMGB1 levels are high in the serum of mesothelioma patients (reviewed in Yang and Carbone, Clinical Cancer Res 2013). We tested several anti-inflammatory agents to see if we were able to reduce HMGB1-induced mesothelioma cell growth, and none of them worked except for aspirin, that led us to conduct a series of experiments in vitro and in vivo to test the hypothesis that aspirin inhibits HMGB1 activities, and that by doing so, inhibits mesothelioma growth.Medical Research: What are the main findings?
Dr. Yang: We found that aspirin inhibits the growth of human mesothelioma cells in a xenograft model, moreover in vitro experiments demonstrated that this effects was specifically mediated via inhibition of HMGB1 and not via COX2 inhibition. We propose that the so far enigmatic anticancer activity of aspirin is mediated, at least partially, via inhibition of HMGB1, and that aspirin may help delay the onset of mesothelioma and may help inhibit the growth of mesothelioma.(more…)
MedicalResearch.com Interview with:
MB. Pinkham, Clinical Oncology
Christie NHS Foundation Trust
Manchester UK
Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months.
The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions.
Medical Research: What are the main findings?
Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors.
For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response.
For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking.
Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted.
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MedicalResearch.com Interview with: Junichi Nishimura MD, PhD
Assistant professor
Osaka University in Japan
Medical Research: What is the background for this study? What are the main findings?
Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse events which decrease the patient’s QOL. However, there was no study investigating whether 3-drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant) reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre, randomized phase III study to evaluate the usefulness of the combined use of aprepitant in colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-drug combination therapy significantly increased the inhibition rate of vomiting which was the primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no vomiting and no rescue medication use), and complete protection (no vomiting , no rescue medication use and no moderate or worsened nausea) was significantly higher in aprepitant group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea between males and females in delayed phase. When patients were grouped by sex regardless of the assigned treatment group, females were more affected by nausea and vomiting than males. Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased chance of complete protection.
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MedicalResearch.com Interview with:
Howard S. Hochster, MD
Associate Director, Yale Cancer Center
Professor of Medicine, Yale School of Medicine
New Haven, CT 06520
Medical Research: What is the background for this study? What are the main findings?
Dr. Hochster: TAS-102 is a novel anti-metabolite, recently combined with a metabolic inhibitor to make it orally bioavailable and active in the treatment of cancer. In pre-clinical studies, it is non-cross reactive with 5FU. What this means practically is that we have another chemotherapy agent that can be used for patients with colon cancer. This drug will be an addition to the approved chemotherapy agents 5FU, oxaliplatin and irinotecan. It may be combinable with these and with targeted agents to provide new active regimens.
The main findings of the study were published in NEJM, May 15, 2015. The study enrolled 800 patients randomized (2:1 ratio) to drug vs placebo. Patients with advanced colon cancer who had been treated with all the previously approved drugs were eligible. The drug was active in reducing time to tumor growth (Progression Free Survival) by 50% and improved overall survival for treated patients by about 25%.
The data I presented at ESMO included a further analysis on specific genomic subsets of patients within the 800 patient study. All patients were tested locally for RAS mutations and about 50% had such mutations (as expected). There was no differences in benefit or toxicity for those with RAS wild-type tumors or RAS mutated tumors. We also looked at those with BRAF mutations, but only 15% of patients were tested and this mutation occurs in about 8% of colon cancer, so we had very few patients with BRAF mutation. Given this limitation, it appeared that this did not make a difference for benefit or toxicity either.
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MedicalResearch.com Interview with:
Jennifer Mack, MD, MPH
Pediatric oncologist
Dana-Farber/Boston Children’s Cancer and Blood Disorders CenterMedical Research: What is the background for this study? What are the main findings?
Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%).
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MedicalResearch.com Interview with:
Amol Narang MD
Radiation Oncology Resident
Johns Hopkins Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Narang: The care provided to cancer patients at end-of-life can be intense, including frequent ER visit, hospitalizations, and ICU stays in the last month of life, administration of chemotherapy in last two weeks of life, and late referrals to hospice. Providing high-intensity treatments at end-of-life has been associated with reduced patient quality-of-life and increased caregiver bereavement. Advance care planning represents an opportunity for patients to indicate their preferences for end-of-life care to try to ensure that the care that they receive at end-of-life is consistent with their values, and has been endorsed by oncologic professional societies, such as ASCO and the NCCN. As such, we wanted to assess if oncologists’ long-standing recognition of the merits of advance care planning has translated into increased participation in advance care planning by cancer patients, and to determine which forms of advance care planning are associated with intensity of care given at end-of-life.
From 2000-12, we found that the only type of advance care planning that increased was the assignment of a power of attorney (52% in 2000 to 74% in 2012). However, having a power of attorney was not associated with receiving less aggressive end-of-life care. On the other hand, having a living wills and engaging in a discussion with a provider or loved one about preferences for end-of-life care were both associated with reduced treatment intensity. However, the frequency with which cancer patients created a living or discussed their preferences for end-of-life care did not increase over the study period; importantly, 40% of patients dying of cancer never communicated their preferences for care at end-of-life with anyone.
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MedicalResearch.com Interview with:
Aung Ko Win, MBBS MPH PhD
Research Fellow
NHMRC Early Career Clinical Research Fellow
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health
The University of Melbourne VIC 3010
Australia
Medical Research: What is the background for this study?
Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome.
A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome. (more…)
MedicalResearch.com Interview with:
Aung Ko Win, MBBS MPH PhD
Research Fellow
NHMRC Early Career Clinical Research Fellow
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health
The University of Melbourne VIC 3010
Australia
Medical Research: What is the background for this study? What are the main findings?
Response: About 2-5% of uterine cancer are associated with an underlying genetic condition mainly Lynch syndrome. Lynch syndrome is caused by a mutation in one of the mismatch repair genes. At least 1 in 1000 people in the population have a mutation that causes Lynch syndrome and these people have a very high risk of cancers mainly bowel and uterine cancers. One in three women with a mutation in one of the mismatch repair genes are likely to develop a uterine cancer in their lifetime. The only way to reduce the risk of uterine cancer for these women is to remove the uterus. There is no current recommendation for screening method to detect uterine cancer early. Almost nothing is known about if and how lifestyle factors and hormonal factors can modify their risk of uterine cancer.
By studying 1128 women with a mutation that causes Lynch syndrome who were recruited from Australia, New Zealand, Canada and the USA, we found that later age at first menstrual cycle, having one or more live births, and using hormonal contraceptive use for one year or longer were associated with a lower risk of uterine cancer.
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MedicalResearch.com Interview with:
Wen-Qing Li Ph.D
Department of Dermatology Warren Alpert Medical School
Department of Epidemiology, School of Public Health,
Brown University, Providence, RI
Medical Research: What is the background for this study?
Response: Rosacea is a chronic inflammatory cutaneous disorder and may be an end-organ response in a systemic disorder. We systemically examined the association between personal history of rosacea and risk of cancer based on 75088 whites in the Nurses’ Health Study II, during a follow-up of 20 years.
Medical Research: What are the main findings?
Response: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and Basal Cell Cancer. Analyses did not find significant associations for other individual cancer types. (more…)
MedicalResearch.com Interview with:
Chao Cheng, Ph.D.
Assistant Professor
Department of Genetics
Institute for Quantitative Biomedical Sciences
Geisel School of Medicine at Dartmouth
Hanover NH, 03755
Medical Research: What is the background for this study?
Dr. Cheng: Bladder cancer is a common tumor type, with non-muscle-invasive bladder cancer (NMIBC) representing the majority of cases. Bacillus Calmette-Guerin (BCG) treatment is an effective immunotherapy that is commonly used to treat cancers of this subtype. However, this treatment fails to suppress tumor recurrence in up to 40% of patients. For this reason, biomarkers that predict the recurrence/progression of bladder cancer and patient response to BCG therapy are needed to tailor treatment strategies to individual patients.
Medical Research: What are the main findings?
Dr. Cheng: We had previously developed an E2F4 signature that consisted of the E2F4 transcription factor and its target genes identified by ChIP-seq and ChIP-chip experiments. Here, we found that the E2F4 signature is predictive of the progression of both non-muscle-invasive and muscle-invasive bladder cancer. Furthermore, this signature is also predictive of patient responsiveness to intravesical BCG immunotherapy. Our results suggest that patients with positive E2F4 scores (indicating high E2F4 activity) benefit significantly from BCG therapy, while the progression of patients with negative E2F4 scores (indicating low E2F4 activity) does not show significant difference from untreated patients.
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MedicalResearch.com Interview with:
Ashley S. Felix, PhD
Bethesda, MD
MedicalResearch: What is the background for this study? What are the main findings?Dr. Felix: Endometrial cancer prognosis is strongly affected by disease stage, or the extent of spread from the primary site. Endometrial cancers can spread via the lymph nodes, blood vessels, through the uterine wall, or through the fallopian tube into the peritoneal cavity. The last of these mechanisms is poorly understood, but appears to be a more common mode of spread for aggressive histologic subtypes of endometrial cancer. We hypothesized that women who previously underwent tubal ligation (TL) and later developed endometrial cancer would have lower stage disease, possibly by blocking passage of tumor cells along the fallopian tubes. Further, we hypothesized that TL would be associated with better prognosis, due to its relationship with lower stage.
We found that women in our study who previously had tubal ligation were more likely to have lower stage endometrial cancer compared with women who did not report a previous tubal ligation. Specifically, tubal ligation was inversely associated with stage III and stage IV cancer across all subtypes of the disease, including aggressive histologic subtypes. Further, in statistical models of tubal ligation, tumor stage, and mortality, we observed no independent association with improved survival, suggesting that tubal ligation impacts mortality mainly through its effects on stage.
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MedicalResearch.com Interview with:
Angelica Loskog, PhD
Professor of Immunotherapy (adjunct)
Dept of Immunology, Genetics and Pathology
Uppsala University
Uppsala Sweden
Medical Research: What is the background for this study? What are the main findings?
Dr. Loskog: CAR T cells have shown remarkable effect in patients with B cell malignancy in the US using 2nd generation CAR T cells. Acute leukemia (ALL) seems easier to treat than lymphomas and one of the reasons may be difficulties for CAR T cells to penetrate a solid lesion or due to a higher local presence of immunosuppressive cells within a lesion. As one of the first centers outside US we are evaluating 3rd generation CAR T cells in both lymphoma and ALL aiming to compare the responses and investigating biological reasons for the different responses. So far we have treated 11 patients and 6 of them had initial complete responses. Unfortunately, some progressed later.
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