Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA / 24.12.2015
Breast Cancer Patients Report More Treatment Side Effects Than Their Physicians Recognize
MedicalResearch.com Interview with:
Filippo Montemurro, M.D.
Director, Investigative Clinical Oncology (INCO)
Fondazione del Piemonte per l'Oncologia
Candiolo Cancer Institute (IRCCS)
Torino, Italy
Medical Research: What is the background for this study?
Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The "indirectness" of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended.
Based on these premises, we designed a study to pursue two aims;
- the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
- the second was to compare doctors and patients reports of toxicities at corresponding time-points.
Dr. Veenstra[/caption]
MedicalResearch.com Interview with:
Christine Veenstra MD
Clinical Lecturer, Internal Medicine
Medical Oncology
University of Michigan
Ann Arbor, MI 48109-5343
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Veenstra: Patients with cancer face many costs and incur financial burden as they go through diagnosis and treatment. For working patients, cancer diagnosis and treatment may come with the additional burden of time away from work, lost income, and even long-term job loss. Although 40% of US workers do not have access to paid sick leave, we hypothesized that availability of paid sick leave could reduce the need to take unpaid time away from work during cancer treatment and might therefore be associated with job retention and reduced personal financial burden.
In a survey of over 1300 patients with Stage III colorectal cancer, we found that only 55% of those who were employed at the time of their cancer diagnosis retained their jobs. Working patients with paid sick leave were nearly twice as likely to retain their jobs compared with working patients who did not have paid sick leave. This held true even when controlling for income, education and health insurance. Furthermore, working patients without paid sick reported significantly higher personal financial burden than those who had paid sick leave available.
Dr. Najib Rahman[/caption]
MedicalResearch.com Interview with:
Dr Najib Rahman D Phil MSc MRCP
Consultant and Senior Lecturer
Lead for Pleural Diseases
Oxford Centre for Respiratory Medicine
Clinical Director, Oxford Respiratory Trials Unit
Tutor in Clinical Medicine
University College, Oxford
Medical Research: What is the background for this study?
Dr. Rahman : Up to TIME1, the evidence base behind optimal pleurodesis for malignant pleural effusion in terms of tube size and analgesia was poor. Optimal pleurodesis in this context is one which is successful (i.e. the patient needs no further pleural interventions for that malignant effusion), but occurs with the minimum discomfort. This is particularly important as the treatment intent in malignant effusion pleurodesis is palliative.
This is the first adequately powered randomized trial to address two important issues in pleurodesis for malignant pleural effusion - that of whether NSAIDs reduce pleurodesis efficacy, and if smaller chest tubes (12F) are "as good as" larger chest tubes (24F) for pleurodesis success and in terms of pain.
Medical Research: What are the main findings?
Dr. Rahman : The main and somewhat surprising findings are that:
Dr. Tevaarwerk[/caption]
MedicalResearch.com Interview with:
Amye Tevaarwerk, M.D.
Assistant Professor of Medicine
Hematology/Oncology Section
University of Wisconsin School of Medicine and Public Health
Carbone Comprehensive Cancer Center
Wisconsin Institute for Medical Research (WIMR)
Madison, WI
Medical Research: What is the background for this study? What are the main findings?
Dr. Tevaarwerk: These patients were enrolled on a larger clinical trial known as the Symptom Outcomes and Practice Patterns study (SOAPP). SOAPP recruited breast, prostate, colon and lung cancer patients directly during outpatient oncology follow-up visits. All of the patients were recruited between May 2006 and May 2008.
The parent study recruited 3123 patients, of these 680 patients had metastatic disease and 668 had employment data.
Patients were asked if they were working and if there had been a change due to illness. We were able to compare those stably working with those who had changed to "no longer working" and look at factors that associated with this change (age, gender, cancer type, race/ethnicity, time since diagnosis, location of metastatic disease, type of treatment, performance status, number of metastases, symptom burden.)
Dr. Li Ding[/caption]
MedicalResearch.com Interview with:
Dr. Li Ding PhD
Director, Medical Genomics group
McDonnell Genome Institute
Department of Medicine
Washington University in St. Louis
St. Louis, Missouri
Medical Research: What is the background for this study? What are the main findings?
Dr. Li Ding: Next-generation sequencing technologies have provided unprecedented opportunities for building a comprehensive catalog of point mutations, simple insertion and deletion mutations (indels) and structural variants in human cancers. Although significant progress has been made for documenting these common events through studies from individual research labs and large consortiums, there has been little progress in the discovery of complex indels after the transition from Sanger sequencing to NGS technologies. It is well known in the scientific community that indel detection using short next generation sequencing reads is a challenging problem. Our study, for the first time, directly addresses complex indel detection that has been barely touched in the cancer field. More importantly, our analysis discovered 285 complex indels in cancer genes such as PIK3R1, GATA3, and TP53, revealing an unexpected high prevalence of these events in human cancers.
Lindsey Torre[/caption]
MedicalResearch.com Interview with:
Lindsey Torre, MSPH
Epidemiologist, Surveillance Research
Surveillance Research group at the American Cancer Society
Medical Research: What is the background for this study? What are the main findings?
Response: This study updates a previous study published in 2010 using the latest available data on cancer incidence and mortality from cancer and vital registration around the world. We found that while high-income countries still have the highest cancer rates in the world, some low- and middle-income countries now also have elevated cancer rates. Also, mortality rates for common cancers such as lung, breast, and colorectum are declining in high-income countries, while they are increasing in low-income countries. At the same time, low-income countries still have a disproportionate burden of infection-related cancers, such as stomach, liver, and cervix.
Dr. Eileen Shinn[/caption]
MedicalResearch.com Interview with:
Dr. Eileen H. Shinn PhD
Assistant Professor, Department of Behavioral Science
Cancer Prevention and Population Sciences
MD Anderson Cancer Center
The University of Texas
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Shinn: Recent studies with leukemia, breast, lung, renal and liver cancer patients have shown that patients with depression have worsened survival. These effect sizes are small, but independent of any of the traditional factors that are known to impact survival, such as extent of cancer, types of treatment administered and baseline health and age of the patient. The current thinking is that cancer patients who are depressed have chronically heightened responses to stress; the constant release of stress hormones trigger changes in the tumor itself (such as noradrenergically-driven tumor angiogenesis) or may weakens the body’s immune function and ability to resist tumor growth.
When we measured depression in newly diagnosed patients with oropharyngeal cancer (cancer of the base of tongue and tonsil), we found that those patients who scored as depressed were 3.5 times more likely to have died within the five year period after their diagnosis, compared to nondepressed patients. We also found that patients who were depressed were also 3.8 times more likely to have their cancer recur within the first five years after diagnosis. We also found that patients who continued to smoke after diagnosis were more likely to recur within the first five years. These effect sizes were larger than those typically found in recent studies. We believe that the larger effect size may be due to the tight eligibility criteria ( e.g., we did not include patients who already had recurrent disease, we only included patients with one specific type of head and neck cancer, oropharyngeal) and also due to controlling other known factors (all patients completed individualized treatment regimens of radiation/ chemoradiation at a comprehensive cancer center and patients with more advanced disease stage were more likely to have received treatment intensification compared to patients with early stage disease). In all, we had 130 patients, one of the largest prospective studies with oropharyngeal cancer to examine the effect of depression on cancer outcome.
Dr. Chia-Yu Chu[/caption]
MedicalResearch.com Interview with:
Chia-Yu Chu, MD, PhD
Associate Professor, Department of Dermatology
National Taiwan University Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Chia-Yu Chu: It has been well known that EGFR TKIs could cause skin toxicities (acneiform eruptions, pruritus, xerosis and paronychia). However, incidences of these skin toxicities have varied according to the different clinical trials, some of which even simply use “skin rash” instead of specific cutaneous findings in the reports.
Afatinib, in contrast to first generation EGFR TKIs like gefitinib and erlotinib, is a second generation EGFR TKI with irreversible inhibition to not only EGFR, but also HER2 and ErbB4. Whether afatinib cause more skin toxicities remained unknown.
Many of our patients received 2 or even 3 different EGFR TKIs with adequate drug exposure and washout period. Therefore, we had an opportunity to compare skin toxicities in “same patients” receiving different EGFR TKIs, and we found that around 30% of patients receiving afatinib developed paronychia whereas only 10% in gefetinib or erlotinib. This was the only significant difference between the 3 drugs. We also found afatinib treated patients needed significantly more dermatologic visits within 180 days of treatments and the reason was due to higher incidence of afatinib-related paronychia. Interestingly, regardless of causative agents, once skin toxicities developed they could be managed effectively in the same manners.
Dr. Al-Kindi[/caption]
MedicalResearch.com Interview with:
Sadeer G Al-Kindi, MD
Fellow, Harrington Heart and Vascular Institute
Onco-Cardiology Program, Advanced Heart Failure and Transplant Center, Harrington Heart and Vascular Institute,
University Hospitals Case Medical Center
Cleveland, OH
Medical Research: What is the background for this study?
Dr. Al-Kindi: Cardiovascular disease and cancer are the most common causes of death in the United States. They often have the same risk factors (for example, smoking, advancing age, obesity). Many cancers are treated with drugs that can have detrimental effect on the heart thus limiting their use. Some studies have suggested that cardiovascular diseases can worsen outcomes in patients with cancer. The emergence of onco-cardiology programs led to multidisciplinary care of patients with cancer and heart disease. Given this tight relationship between cancers and cardiovascular disease, we hypothesized that heart disease and its risk factors are very common in patients diagnosed with cancer.
Medical Research: What are the main findings?
Dr. Al-Kindi: Using a very large clinical database of 1/8th of the US population, we identified patients with most common cancers that are treated with cardiotoxic medications and identified the prevalence of cardiovascular diseases. Overall, prevalence was 33% for hematologic malignancies (leukemia and lymphoma), 43% for lung cancers, 17% for breast cancers, 26% for colon cancers, 35% for renal cancers, and 26% for head and neck cancers. Peripheral artery disease, coronary artery disease and cerebrovascular diseases were the most common, followed by heart failure, and carotid artery disease. Despite the high prevalence, only about a half of these patients were on the cardiovascular medicines and half were referred to cardiologists.
Dr. Oktay[/caption]
MedicalResearch.com Interview with:
Kutluk Oktay, MD, PhD.
Professor of Obstetrics & Gynecology, Medicine, and Cell Biology & Anatomy
Director, Division of Reproductive Medicine & Institute for Fertility Preservation
Innovation Institute for Fertility and In Vitro Fertilization
New York Medical College, Valhalla, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Oktay: Cancer treatments cause infertility and early menopause in a growing number of young women around the world and US. One of the strategies to preserve fertility, which was developed by our team, is to cryopreserve ovarian tissue before chemotherapy and later transplant it back to the patient when they are cured of the cancer and ready to have children. However, success of ovarian transplantation has been limited due to limitation in blood flow to grafts. In this study we described a new approach which seems to improve graft function. The utility of an extracellular tissue matrix and robotic surgery seems to enhance graft function. With this approach both patients conceived with frozen embryos to spare and one has already delivered.
Dr. Klempner[/caption]
MedicalResearch.com Interview with:
Samuel Klempner, M.D. Assistant Professor
Division of Hematology/Oncology
UC Irvine Health
Orange, CA 92868
Medical Research: What is the background for this study? What are the main findings?
Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options. This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types. Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an 
Dr. Shah[/caption]
MedicalResearch.com Interview with:
Dr. Jatin J. Shah, MD
Associate Professor, Department of Lymphoma/Myeloma
Assistant Professor, Lymphoma/Myeloma
Division of Cancer Medicine
The University of Texas, MD Anderson Cancer Center
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells.
The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma.
