Author Interviews, Dermatology, Lymphoma / 12.08.2015

[caption id="attachment_16530" align="alignleft" width="150"]Alain H. Rook, M.D. Professor of Dermatology University of Pennsylvania Philadelphia, PA 19104 Dr. Alain H. Rook[/caption] MedicalResearch.com Interview with: Alain H. Rook, M.D. Professor of Dermatology University of Pennsylvania Philadelphia, PA 19104 and [caption id="attachment_16531" align="alignleft" width="150"]Rachael A. Clark, M.D., Ph.D. Department of Dermatology Brigham and Women's Hospital Boston, MA 02115 Dr Rachael Ann Clark[/caption] Rachael A. Clark, M.D., Ph.D. Department of Dermatology Brigham and Women's Hospital Boston, MA 02115   Researchers’ summary: In this paper, Dr. Rachael Clark and I describe a novel topical therapy for mycosis fungoides (MF), which is a skin-limited variant of cutaneous T-cell lymphomas (CTCL), a group of non-Hodgkin's lymphomas which represent cancers derived from skin-homing T cells. Although therapies exist that suppress the inflammatory skin lesions of MF, there are no curative therapies for this otherwise lifelong disease except for stem cell transplantation, which is only carried out in patients with aggressive and progressive disease. This manuscript describes a phase I trial of a novel immunomodulatory compound called resiquimod. This molecule stimulates two key receptors TLR7 and TLR8. Unlike imiquimod, a similar compound that is FDA approved for the treatment of local skin cancers, resiquimod actually stimulates inflammatory cytokine release from the dendritic cells that populate both healthy and inflamed human skin. As a result, this drug can enhance antigen presentation and immune responses. This study demonstrated that topical resiquimod was remarkably effective in that 90% of patients experienced a decrease in the percentage of the malignant T cell clone in skin lesions, and two patients had complete clearance of all disease, including both the treated skin lesions and the untreated lesions. To our knowledge, this is the first demonstration of regression of untreated skin lesions using a topical medication. This suggests that systemic antitumor immunity develops in these patients. Translational studies on the skin before and after treatment showed that the malignant T cell clone declined and inflammatory cytokine production by benign T cells increased after therapy suggesting the medication enhanced antitumor responses. In summary, this manuscript describes a small phase I trial that showed that topical resiquimod is safe, effective therapy for mycosis fungoides and can cause regression of both treated and untreated skin lesions, and may therefore represent a long-term potential cure for this otherwise lifelong disease.
Annals Thoracic Surgery, Author Interviews, Cancer Research, Lung Cancer, Outcomes & Safety / 11.08.2015

MedicalResearch.com Interview with: Raymond Osarogiagbon MD, FACP Thoracic Oncology Research Group Baptist Cancer Center Memphis, Tennessee 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.
Author Interviews, Biomarkers, Breast Cancer / 11.08.2015

Dr Stephen Chan DM, FRCR, FRCP Consultant Oncologist Breast and Gynaecological Cancers Nottingham University Hospitals Trust Honorary Professor at the University of Nottingham Visiting Professor of Cancer Medicine at Nottingham Trent UniversityMedicalResearch.com Interview with: Dr Stephen Chan DM, FRCR, FRCP Consultant Oncologist Breast and Gynaecological Cancers Nottingham University Hospitals Trust Honorary Professor at the University of Nottingham Visiting Professor of Cancer Medicine at Nottingham Trent University MedicalResearch: What is the background for this study? What are the main findings? Dr. Chan: Worldwide each year 1.68 million women are diagnosed with breast cancer and more than half a million die from the disease. Of these new cases around 12% will be classified as triple negative breast cancer (TNBC), meaning that tumour cells from these patients do not show any of the three established clinical markers that can be treated with targeted therapies. These drugs are used in addition to standard chemotherapy to improve the chance of a good treatment response, leading to prolonged disease free survival. Without these additional treatment options triple negative patients are forced to depend entirely on chemotherapy to treat their cancer. Traditionally the sensitivity of a cancer to different types of chemotherapy has been categorised is based on a tumours tissue of origin and stage. There is currently no predictive marker of response that would allow chemotherapy treatment to be tailored to individual patients. With this information a clinician can predict which patients would benefit most from a particular chemotherapy and switch any who would do poorly to an alternative. The result would be a shift to increased treatment efficacy, while avoiding toxicity from ineffective treatment, which would in turn also reduce the cost to the health service. This need is particularly acute in triple negative breast cancer cases where chemotherapy is the cornerstone of treatment. In collaboration with researchers based at Nottingham Trent University our group has been successful in finding new markers, which can predict how a patient will respond to chemotherapy treatment. One of these is HAGE (DDX43), a DEAD box RNA helicase. We have found that high HAGE expression predicts good respond to one of the main first line chemotherapy drugs, called anthracycline (Tarek MA Abdel-Fatah et al, April 2014). Our recent work (Tarek MA Abdel-Fatah, 2015) has shown that the predictive value is strong in triple negative breast cancer cases.
Author Interviews, Genetic Research, Prostate Cancer / 09.08.2015

Dr Helen Ross-Adams Cancer Research UK, LondonMedicalResearch.com Interview with: Dr Helen Ross-Adams Cancer Research UK, London Medical Research: What is the background for this study? What are the main findings? Dr. Ross-Adams: Prostate cancer is the most common non-skin cancer in men in both the UK and US. At the moment, prostate cancer is diagnosed and monitored mainly on the basis of blood tests for prostate specific antigen (PSA), a protein in the blood. MRI scans and examination of biopsy tissue samples under a microscope are also used to decide on the best course of action for each patient. Despite all this, as a community, we still struggle to reliably predict which men with an initial diagnosis of prostate cancer will go on to have a fast-growing, aggressive form of the disease (a ‘tiger’) from men who will have a much slower-growing form of the disease that won’t really cause problems in the man’s lifetime (a ‘pussycat’). This means some men may get treatment they don’t need, while others could benefit from earlier, more intensive treatment. With this in mind, we studied a total of 250 men with prostate cancer and tested their tumour and healthy tissues at the molecular level. The idea was two-fold:
  • Could we identify different sub-types of prostate cancer using this genetic information, and
  • Could we link any of the sub-types we did find with other patient characteristics that clinicians would normally have, like histological staging information or PSA test results?
We looked at their DNA, to see whether any regions were deleted or repeated (copy number alterations), and we also measured the activity levels of thousands of genes in the tumour and healthy prostate tissues (gene expression). Each of these approaches on their own can be used to stratify patients, but we decided to combine this information and hopefully find genes that had a big impact on prostate cancer. Using this approach, we identified five different subtypes of prostate cancer, each with their own ‘molecular profile’:
  • One group had lots of DNA deletions and only low levels of certain genes
  • Another had lots of repeated DNA with high levels of associated genes
  • Two more groups had very ‘quiet’ genomes, with very few changes at the DNA level, and not much disruption at the gene expression level
  • The fifth and final group had an intermediate amount of copy number changes (DNA level), but no major changes at the gene expression level (mRNA level)
When we correlated these different molecular subtypes with the patients’ standard post-surgery follow-up data (the results of 6-monthly PSA tests), we found that these subtypes predicted how well a patient would do after surgery. We ultimately identified 100 key genes (a gene signature) that were most useful in classifying men into one of the 5 cancer subtypes we identified. This was derived from 150 men in Cambridge, UK. To check our findings, we repeated the same work in a group of 100 men from Stockholm, Sweden who had also had prostate surgery, and found that the 100 gene signature worked just as well – it subdivided the men into 5 different groups, each with different rates of relapse. In both cases, men with the most genetic alterations had the greatest chance of relapsing after surgery.  
Author Interviews, Cancer Research, JAMA, Radiation Therapy, University of Michigan / 08.08.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.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.
Author Interviews, Cancer Research, Genetic Research / 02.08.2015

Christos Nikolaidis Ph.D. Laboratory of Pharmacology Medical School, Democritus University of Thrace Dragana, Alexandroupolis GreeceMedicalResearch.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.
Author Interviews, Cancer Research, End of Life Care, Lancet, Leukemia / 01.08.2015

Prof David C Currow Discipline of Palliative and Supportive Services Flinders University Adelaide, SA, AustraliaMedicalResearch.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.
Author Interviews, Cancer Research, Sexual Health / 30.07.2015

Gwendolyn P. Quinn, Ph.D. Moffitt Cancer Center University of South FloridaMedicalResearch.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. 
Author Interviews, Biomarkers, Breast Cancer / 30.07.2015

Karla M. Gonye, MBA President, sphingotec LLC Cambridge, MassachusettsMedicalResearch.com Interview with: Karla M. Gonye, MBA President, sphingotec LLC Cambridge, Massachusetts MedicalResearch: What is the background for this study? Response:
  • Met- and Leu-Enkephalin: are endogenous pentapeptides of the family of opioid peptides known as opiod-growth factors (OGF)
  • Enkephalins have been widely studied and play a major role in a variety of physiological processes
    • Perception of pain
    • Regulation of stress
    • Regulation of cardiovascular function
    • Regulation of bone formation
    • Regulation of immune responses
  • Alcohol and pain relievers reduce synthesis of Enkephalins
  • Met-Enkephalin (opioid growth factor) inhibits tumor progression and metastasis and enhances natural killer cell activity1,2
  • Mechanisms3-7:
    • Opioids can directly interact with tumor cells to cause a cytotoxic or antiproliferative effect
    • Opioids can modulate host antitumor immune mechanisms
  • Opiods can also induce apoptosis
  • We need enkephalins to help inhibit tumor progression
  • At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that reduced enkephalins in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure enkephalin.
  • This method is published in a separate publication by Ernst et al (2006) in Peptides.
  • To test this hypothesis, Sphingotec measured enkephalin levels in the MDC and MPP study populations to determine if an association could be made between lower enkephalins and risk of breast cancer: We related proenkephalin (P-ENK) in fasting plasma from 1929 healthy women (mean age 58±5.9 years) of the population based Malmö Diet and Cancer Study (MDCS) to incidence of breast cancer (n=123) using multivariate Cox proportional hazards models during 14.8 years of follow-up. For replication, P-ENK was related to risk of breast cancer (n=130) in an older independent sample from the Malmö Preventive Project (MPP) consisting of 1569 women (mean age 70.0±4.4 years), using multivariate logistic regression.
Author Interviews, Biomarkers, Breast Cancer / 29.07.2015

Karla M. Gonye, MBA President, sphingotec LLC Cambridge, MassachusettsMedicalResearch.com Interview with: Karla M. Gonye, MBA President, Sphingotec LLC Cambridge, Massachusetts MedicalResearch: What is the background for this study? Response:
  • In experimental studies, Neurotensin and neurotensin expression was highly associated to breast cancer tissue
    • Dupouy et al (2009) investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal carcinomas (IDCs) and found that NTS is expressed in ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade 3 (p<0.05), larger tumor size (p<0.01), and the number of metastatic lymph nodes (p<0.05).
    • It was concluded from this paper that NTS/NTSR1 is a contributor to breast cancer progression.
    • Souaze et al (2006)also studied IDCs and found 34% of all tumors were positive for neurotensin and 91% positive for the NT1 receptor, suggesting the contribution of neurotensin’s involvement in the signaling cascade within breast cancer progression.  In this study, it was found that disruption of neurotensin receptor signaling by silencing RNA or using a specific NT1 antagonist in nude mice xenografted with an aggressive cell line SR48692, caused the reversion of transforming functions that lead to tumor growth.
    • These findings support the contribution of neurotensin to breast cancer progression.
    • Wu, Z. et al (2013) reviewed the contribution of the neurotensinergic system to cancer progression, as well as the regulation and mechanisms of the system in order to highlight its potential as a therapeutic target, and its prospect for its use as a treatment in certain cancers.
    • This summarizes nicely the oncogenic effects of neurotensin after stimulation signaling proliferation, survival, migration, invasion and neoangeogeneis.
    • Several other papers published demonstrate the effects of neurotensin in cancers including breast cancer.
    • New studies such as Roselli et al (2015) further demonstrate the role of neurotensin in aggressive breast cancer.
    • At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that elevated expression of neurotensin in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure neurotensin.
    • This method is published in Ernst et al (2006) in Peptides.
    • To test the hypothesis, the first clinical study was conducted in a cohort of normal healthy population that was indentified from the Malmo Diet and Cancer study, a prospective epidemiological study of 28,449 men and women. Of this group, a subset of 4632 randomly selected subjects were identified and neurotensin was measured in all subjects. Subjects were adjusted for known breast cancer risk factors such as age, age of menarche, heredity of cancer (all), hormone status, etc. (see Table 3, Melander et al JAMA 2012) so that the factors did not influence outcomes. On a 10-15 follow up period, of these subjects, 123 breast cancer events were found to be associated with higher levels of neurotensin, with the highest quartile associated with the highest levels of neurotensin and the lowest quartile associated with the lowest levels of neurotensin. The association of elevated neurotensin was found to be statistically significant for prediction of breast cancer.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Sexual Health / 29.07.2015

Martha F. Goetsch, MD, MPH Oregon Health & Science University Portland, OR 97239MedicalResearch.com Interview with: Martha F. Goetsch, MD, MPH Oregon Health & Science University Portland, OR 97239 MedicalResearch: What is the background for this study? Dr. Goetsch: Women who are survivors of breast cancer now number about 3 million in the US.  Therapy for breast cancer is anchored in creating a state of postmenopause in which estrogen is eliminated from the system. One of the most difficult symptoms of lack of estrogen is dyspareunia, the term for pain with intercourse. The old term “vulvovaginal atrophy” has been changed to “genitourinary syndrome of menopause” by agreement of two specialty societies. Because of my focus in the gynecologic specialty of vulvar pain, I have felt that this menopausal symptom is more than a condition of atrophy.  Additionally, my clinical experience has led me to believe that the exquisite tenderness is located in the vulvar vestibule rather than in the vagina. The vestibule is the inner vulva or entryway before the vagina. This study was devised to answer these hypotheses. I predicted that the population most likely to represent the worst examples of postmenopausal dyspareunia was the population of women who cannot use estrogen due to being survivors of breast cancer. I treated the problem as a pain problem rather than solely a problem of dryness.
Author Interviews, Dermatology, Melanoma / 28.07.2015

MedicalResearch.com Interview with: Christina Y. Lee BA Department of Dermatology Pedram Gerami, MD Robert H. Lurie Cancer Center Feinberg School of Medicine Northwestern University Chicago, Illinois Medical Research: What is the background for this study? What are the main findings? Response: Melanoma is responsible for the majority of skin cancer-related mortality. While AJCC staging of melanoma provides highly valuable information that helps predict the behavior of cutaneous melanoma, there are likely a number of other variables not included that may help predict which melanomas may result in metastasis. Some of these data points are not be easily assessed or available in large databases. In this study, we sought to assess a broad range of specific clinical factors directly obtained from clinic notes that may help predict melanoma behavior. The study consisted of a large cohort of patients with clinical follow up from our melanoma center at Northwestern University. Some examples of evaluated characteristics include a documented history of tanning bed use, blistering sunburns, or outdoor activity. In our study, patients who were older or immunosuppressed at the time of diagnosis were associated with aggressive tumor behavior in multivariate statistical analysis, when controlled for traditional AJCC factors such as  tumor depth, ulceration, and mitotic figures.
Author Interviews, Lymphoma, Nutrition / 27.07.2015

Mara Meyer Epstein, ScD Assistant Professor Meyers Primary Care Institute University of Massachusetts Medical SchoolMedicalResearch.com Interview with: Mara Meyer Epstein, ScD Assistant Professor Meyers Primary Care Institute University of Massachusetts Medical School MedicalResearch: What is the background for this study? What are the main findings? Dr. Epstein: Hodgkin lymphoma is a relatively rare cancer, with about 9,000 new cases diagnosed in the US each year. Hodgkin lymphoma is most commonly diagnosed in earlier (aged 15-34 years) or later adulthood (aged ≥50 years). The causes of the disease are not well understood, and most identified risk factors are not modifiable (for example, age, sex, family history, and infection with Epstein-Barr virus [EBV]). Previous studies have suggested that chronic inflammation may play a role in the development of Hodgkin lymphoma. Therefore, it is possible that a factor that can influence inflammation, such as diet, may be associated with risk of Hodgkin lymphoma. Discovering modifiable risk factors for Hodgkin lymphoma could offer a means for preventing this disease. The few existing studies of diet and Hodgkin lymphoma risk have focused on individual nutrients or foods; this is the first study to examine dietary pattern and risk of Hodgkin lymphoma. By examining dietary patterns instead of individual foods, we sought to assess Hodgkin lymphoma risk from the food combinations that may more closely reflect typical dietary habits. The current study includes 435 cases of Hodgkin lymphoma and 563 controls with no history of cancer from Massachusetts and Connecticut who were enrolled in the study between 1997 and 2000. Cases and controls provided information about their average intake of 61 food and beverage items over the year prior to the study. By evaluating foods commonly consumed by the study participants, we identified four major dietary patterns; high vegetable intake, high meat intake, high intake of fruit and low-fat dairy, and high intake of desserts and sweets. We looked for associations between each dietary pattern and risk of Hodgkin lymphoma overall, and also separately by age group (<50 years or ≥50 years old), tumor EBV status (positive or negative), and by tumor cell pattern (nodular sclerosis or mixed cellularity). The dietary pattern characterized by high intake of desserts and sweets was associated with a statistically significant increased risk of Hodgkin lymphoma among younger adults, and in particular, a 2-fold increased risk among younger adults with EBV-negative tumors. The dietary pattern featuring high meat intake was associated with a 3-fold increased risk of Hodgkin lymphoma among older adults, and again, we saw a stronger association among older adults with EBV-negative tumors, although the number of such cases in this group was small. We did not observe a clear association between the high vegetable dietary pattern, or the dietary pattern high in fruit and low-fat dairy intake, with Hodgkin lymphoma risk, and we also did not find any clear associations with EBV-positive tumors, which were relatively infrequent in the study population. The findings described above were obtained from statistical calculations that also took into account known Hodgkin lymphoma risk factors, other lifestyle factors, total caloric intake, and body mass index.
Author Interviews, Cancer Research, Genetic Research, MD Anderson / 24.07.2015

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 77030MedicalResearch.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.
Author Interviews, Chemotherapy / 24.07.2015

Adam G Alani, PhD Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy Oregon State University-Oregon Health & Science University Affiliate Assistant Professor Department of Biomedical Engineering School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon 97201-5042 MedicalResearch.com Interview with: Adam G Alani, PhD Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy University Affiliate Assistant Professor Department of Biomedical Engineering School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon Medical Research: What is the background for this study? What are the main findings? Dr. Alani: Doxorubicin, a potent anticancer agent is being under-utilized in the clinic due to its life threatening cardiotoxicity.  This cardiotoxicity has imposed a life dose limit of 450 -550 mg/m2 which restricts clinicians use of this drug for subsequent relapses when a patient has responded to the drug favorably in the past.  In our lab, we are looking to pair this drug with natural products that have shown both cardioprotective effects and while enhancing the potency of common chemotherapeutics like doxorubicin.  Using this complementary approach with a high dose of doxorubicin known to cause cardiotoxicity, we have fully/ partially mitigated this cardiotoxicity in healthy mice. The goal is not to change the dosing regimen for doxorubicin, but to pair it with our nanoscale drug delivery systems containing these natural products as complementary therapy.
Author Interviews, Cancer Research, NIH / 24.07.2015

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 20892MedicalResearch.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.
Author Interviews, Breast Cancer, Journal Clinical Oncology, NIH / 24.07.2015

Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780MedicalResearch.com Interview with: Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780 Medical Research: What is the background for this study? Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the  trends in age- and stage-specific breast cancer death rates after diagnosis. We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ.  We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant). Medical Research: What are the main findings? Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter.  For women under age 70, rates also fell for women with distant disease. Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis.
Author Interviews, Lancet, Melanoma, Radiation Therapy / 23.07.2015

MedicalResearch.com Interview with: Michael A Henderson MBBS BMedSc MD FRACS Professor of Surgery, University of Melbourne Deputy Director Division of Cancer Surgery Head Skin and Melanoma Service Division of Cancer Surgery Peter MacCallum Cancer Centre East Melbourne Victoria  Australia Medical Research: What is the background for this study? What are the main findings? Dr. Henderson:  A number of retrospective reviews of adjuvant radiotherapy after lymphadenectomy for patients at high risk of further lymph node field relapse had all suggested that the risk of lymph node field relapse was reduced but there was controversy about whether there was any impact on survival. In addition many clinicians were concerned about the side effects of radiotherapy and in the absence of a proven survival benefit were reluctant to recommend it. Previously a phase 2 trial of adjuvant radiotherapy conducted by one of our co-authors Prof Bryan Burmiester confirmed that the morbidity of lymph node field radiotherapy was limited and the risks of recurrence was reduced. On that basis the current ANZMTG TROG randomised multicentre trial was initiated. In summary this final report updates information on overall survival, lymph node field relapse etc and provides information for the first time on long term toxicity of treatment, quality of life and lymphedema. Adjuvant lymph node field radiotherapy for patients at high risk of further lymph node field relapse reduces the risk of further lymph node field relapse by 50% but it has no effect on survival. Although radiotherapy toxicity was common (3 in 4 patients), mostly involving skin and subcutaneous tissue it was mild-to-moderate in severity and had little impact upon the patient's quality of life as measured by the FACT-G quality of life tool. Specific regional symptoms were more common in the radiated group. Limb volume measurements confirmed a significant but modest increase for patients receiving inguinal radiation (15%) but not for axillary radiation. In the design of this trial, a decision was made to allow patients in the observation arm who developed an isolated lymph node field relapse to be salvaged by surgery and or radiotherapy. There were only two patients in the radiotherapy arm who developed an isolated lymph node field relapse and both died of metastatic disease. In the observation arm 26 patients developed an isolated lymph node field relapse and the majority (23) achieved lymph node field control with a combination of surgery and or radiotherapy. The five-year survival FROM development of a lymph node field relapse in this group was 34% which is comparable to the overall survival of the entire cohort (42% five-year overall survival). This information whilst a subset analysis suggests that if it would be reasonable in some patients to consider a policy of observation only, reserving further surgery and or radiotherapy for a second relapse.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Race/Ethnic Diversity / 21.07.2015

Helmneh Sineshaw, MD, MPH Senior Epidemiologist, Health Services Researcher American Cancer Society, Inc Atlanta, GA 30303MedicalResearch.com Interview with: Helmneh Sineshaw, MD, MPH Senior Epidemiologist, Health Services Researcher American Cancer Society, Inc Atlanta, GA 30303 MedicalResearch: What is the background for this study? Dr. Sineshaw: Male breast cancer is a rare disease, and its incidence rate is increasing. Younger black men have a higher breast cancer incidence than their white counterparts. Although black/white disparities in treatment receipt and survival among women with breast cancer have been widely documented in the literature, there have been few similar studies in men with breast cancer. Previous studies were based on smaller sample size, older databases, or using data from elderly patients.
Author Interviews, Breast Cancer, Radiology / 21.07.2015

Alison L. Chetlen, D.O. Associate Professor, Department of Radiology Penn State Milton S. Hershey Medical Center Hershey, PA 17033MedicalResearch.com Interview with: Alison L. Chetlen, D.O. Associate Professor, Department of Radiology Penn State Milton S. Hershey Medical Center Hershey, PA 17033 Medical Research: What is the background for this study? Dr. Chetlen:  Breast cancer risk assessment provides a means of identifying women who are at risk for development of this disease.   Identifying individuals at high risk for breast cancer allows for genetic testing, supplemental breast cancer screening, possibly prophylactic surgery or chemoprevention in hopes of decreasing mortality from breast cancer.  Despite the advantages of cancer genetic risk assessment and testing, most individuals in the general population who would benefit from such services currently do not receive them.  Medical Research: What are the main findings? Dr. Chetlen:  After implementation of a specific high-risk recommendation within our standardized mammography report along with a letter written in “lay” language informing patients of their high-risk status, the number of referrals to our high-risk clinic increased only modestly.   Despite these specific recommendations to both physicians and patients, over 85% of high risk patients did not consult a high-risk provider regarding their elevated lifetime risk of breast cancer.
Author Interviews, Breast Cancer / 20.07.2015

Niels de Jonge, Ph.D Head of the Innovative Electron Microscopy group German Cancer Research Center (DKFZ) in Heidelberg University of FreiburgMedicalResearch.com Interview with: Niels de Jonge, Ph.D Head of the Innovative Electron Microscopy group German Cancer Research Center (DKFZ) in Heidelberg University of Freiburg Medical Research: What is the background for this study? What are the main findings? Response: HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood. We now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth.
Author Interviews, Lancet, Lymphoma / 17.07.2015

MedicalRDr Yeow Tee Goh Department of Haematology Singapore General Hospital Republic of Singaporeesearch.com Interview with: Dr Yeow Tee Goh MBBS Department of Haematology Singapore General Hospital Republic of Singapore Medical Research: What is the background for this study? What are the main findings? Dr. Goh: Relapsed or refractory peripheral T-cell lymphoma after conventional chemotherapy is associated with a very poor prognosis and there is currently no recommendation on the standard approach to helping these patients. Novel targeted treatments for relapsed or refractory peripheral T-cell lymphoma such as romidepsin, pralatrexate, belinostat, and brentuximab vedotin has been approved by the US Food and Drug Administration (FDA) based on the results of their Phase II studies. With the exception of the remarkable efficacy of brentuximab vedotin in systemic anaplastic large cell lymphoma (86% of patients responding to treatment), the efficacy of romidepsin, pralatrexate, and belinostat in relapsed or refractory peripheral T-cell lymphoma is only modest with objective response rates between 25% and 29%. To our knowledge, no other clinical study has reported on the use of novel combination of targeted agents in in relapsed or refractory peripheral T-cell lymphoma. In our study, Of 23 patients assessable for responses, 10 (43%, 95% CI 23–63) patients had an objective response, of which 5 were complete responses. The combined proteasome and histone deacetylase inhibitor treatment shows promising activity for patients with peripheral T-cell lymphoma.
Author Interviews, Breast Cancer, Cancer Research, Nutrition / 16.07.2015

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, WisconsinMedicalResearch.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.
Author Interviews, Cancer Research / 16.07.2015

Dr-Haining-Yang MedicalResearch.com Interview with: Haining Yang MD Ph.D Associate Professor Thoracic 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.
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.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.
Author Interviews, Colon Cancer, Duke, Weight Research / 10.07.2015

S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research InstituteMedicalResearch.com Interview with: S. Yousuf Zafar, MD, MHS Associate Professor of Medicine Duke Cancer Institute Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Zafar: Multiple studies have suggested that obesity and colorectal cancer are related. For instance, obesity has been linked with an increased incidence of colon cancer. Obesity has also been associated with a greater risk of colon cancer recurrence. To date, no study has looked at the role of obesity in outcomes for patients with metastatic colorectal cancer. In our study of over 6000 patients receiving treatment for metastatic olcolorectal cancer, we found that patients with the lowest body mass index (BMI) were at greatest risk for worse survival. This does not mean that obesity is good. More likely, it means that those who are very underweight are least able to tolerate the best treatment, or being very underweight is a biologic marker of poor prognosis.
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