Let Life Happen | Breast Cancer, Metastatic Breast Cancer Blog
Hear it all from two-time cancer survivor Barbara Jacoby, whose engaging writing also provides support for victims of domestic violence. Her blog has evolved into a top-notch resource for breast cancer patients, covering such useful topics as what it’s like returning to work after a breast cancer diagnosis, dealing with mammograms, and more.
226 patients with metastatic breast cancer have been enrolled in the AIPAC study
Combination of eftilagimod alpha, an antigen presenting cell (APC) activator, administered in combination with chemotherapy is designed to boost the T-cell immune responses against tumours
Read-out of progression-free survival (PFS) primary endpoint expected to occur in Q1 of calendar year 2020
Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, announces that it has completed patient enrolment of the Phase IIb Active Immunotherapy PAClitaxel (AIPAC) clinical trial in HER2-negative/ Hormone Receptor positive (HR+) metastatic breast cancer (MBC).
The AIPAC study has enrolled 226 patients at more than 30 clinical trial sites across Germany, the UK, France, Hungary, Belgium, Poland and the Netherlands. The trial is evaluating Immutep’s lead product candidate, eftilagimod alpha (efti or IMP321), in combination with paclitaxel, a standard of care chemotherapy, as a chemo-immunotherapy combination in patients with HR+ MBC not eligible for human epidermal receptor 2 (HER2) therapies. This combination is designed to boost the immune response against tumour cells compared to chemotherapy plus placebo. Apoptotic tumour cells induced by chemotherapy release antigenic tumour debris which are then captured by APCs. Boosting the APC network with efti increases cytotoxic T-cell responses which complements the direct cytotoxic effect of the chemotherapy.
The primary endpoint of the AIPAC study is PFS according to RECIST as evaluated by blinded independent central readers. Additional efficacy endpoints include PFS by local read, overall response rate (ORR) and overall survival (OS). The Company expects to report PFS data, together with ORR data, in Q1 of calendar year 2020.
AIPAC is a potentially pivotal clinical trial, meaning it could serve as a basis to pursue appropriate regulatory approval pathways for efti with, for example, the European Medicines Agency (EMA) or the U.S. Food and Drug Agency (FDA), subject to sufficient and clinically meaningful data from the trial and regulatory interactions. Before AIPAC started, the Company received scientific advice from the EMA and is currently exploring ways to bridge its research efforts in HR+ MBC to the United States.
Metastatic breast cancer, also called stage IV breast cancer, is the most advanced stage of breast cancer where it has spread beyond the breast to other organs in the body, most often the bones, lungs, liver or brain. It is estimated that each year there are over 800,000 new cases worldwide of MBC that are HER2 negative and HR positive1. Paclitaxel is a taxane-based standard of care chemotherapy that is widely used for patients in the EU and United States with this cancer.
1 GlobalData PharmaPoint: HER2-Negative/HR+ and Triple Negative Breast Cancer – Global Drug Forecast and Market Analysis to 2025, December 2016
Immutep CEO Marc Voigt commented: “The completion of recruitment for our Phase IIb AIPAC study is an important milestone for Immutep as this is our largest and most advanced clinical trial. As the first PFS data read-out is event-driven, the timeline for reporting remains on track for early in 2020. We sincerely thank our principal investigators, the patients and their families for being part of this study.
“MBC is a serious medical condition where patients have a median life expectancy of approximately two years from the start of first line chemotherapy. This means there is a clear high unmet medical need for new therapies that may deliver improved outcomes compared to current standard of care therapies.”
AIPAC Principal Investigator Dr Hans Wildiers added: “By combining efti with chemotherapy, we hope to boost the body’s immune response against tumour cells and improve treatment outcomes compared to giving chemotherapy alone. Most studies in metastatic breast cancer, including immune therapy, are focusing on blocking the PD-1/PD-L1 checkpoint pathway, but results have been disappointing in this type of hormone sensitive metastatic breast cancer. With efti, we hope to activate the immune system more efficiently in hormone sensitive metastatic breast cancer, the most frequent breast cancer subtype. Through the AIPAC study, we are leading the search for effective immune therapy in this subtype.”
Immutep CSO and CMO, Dr Frederic Triebel said: “APC activators are a new class of drug products that could nicely complement the action of standard of care, either chemotherapy or immune checkpoint inhibitors. Despite recent positive announcements including preliminary anti-CD40 agonist mAb data in a difficult-to-treat “cold tumor” indication such as advanced pancreatic carcinoma, this new class of IO drug products has not yet been validated in a pivotal trial in terms of efficacy. We hope that the results of the AIPAC trial will unequivocally demonstrate the value of APC activators in combined advanced cancer therapies.”
Active Immunotherapy PAClitaxel (AIPAC) is a Phase IIb clinical trial in HER2-negative/ HR positive metastatic breast cancer. Based on Immutep’s LAG-3 technology, the study evaluates the combination of the Company’s lead product candidate, eftilagimod alpha (efti, LAG-3Ig or IMP321), and a taxane-based chemotherapy, called paclitaxel, as an immunotherapy. This combination is aimed at boosting the immune response against tumour cells compared to chemotherapy alone. In AIPAC, 226 hormone receptor positive metastatic breast cancer patients are randomised 1:1 to treatment A (paclitaxel chemotherapy plus placebo) or treatment B (paclitaxel chemotherapy plus eftilagimod alpha) for six months. Thereafter, patients will pass over to the maintenance phase with efti alone.
The primary endpoint of the study is progression-free survival (PFS). The Company expects to report first PFS data in Q1 of calendar year 2020.
For more information regarding the AIPAC trial, visit clinicaltrials.gov (identifier NCT02614833) and https://www.ncbi.nlm.nih.gov/pubmed/30977393).
Immutep is a globally active biotechnology company that is a leader in the development of immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximize value to shareholders. Immutep is listed on the Australian Securities Exchange (IMM), and on the NASDAQ (IMMP) in the United States.
Immutep’s current lead product candidate is eftilagimod alpha (“efti” or “IMP321”), a soluble LAG-3Ig fusion protein based on the LAG-3 immune control mechanism. This mechanism plays a vital role in the regulation of the T cell immune response. Efti is currently in a Phase IIb clinical trial as a chemoimmunotherapy for metastatic breast cancer termed AIPAC; a Phase II clinical trial being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as “MSD” outside the United States and Canada) referred to as TACTI-002 (Two ACTive Immunotherapies) to evaluate a combination of efti with KEYTRUDA® (pembrolizumab) in several different solid tumours (clinicaltrials.gov identifier NCT03625323); a Phase I clinical trial being conducted in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. referred to as INSIGHT-004 to evaluate a combination of efti with avelumab (clinical trials.gov identifier NCT03252938); and a Phase I combination therapy trial in metastatic melanoma termed TACTI-mel (clinicaltrials.gov identifier NCT02676869)
Survivors of childhood brain tumors who received radiotherapy and were very young at the time of diagnosis may experience cognitive and socioeconomic burdens decades after treatment, according to a study published early online in CANCER, a peer-reviewed journal of the American Cancer Society. Interventions such as cognitive therapies and educational and occupational services may be needed to mitigate such long-term effects.
Therapies for children diagnosed with brain tumors have prolonged the lives of many patients, but survivors may experience a variety of effects from their disease and its treatment. To assess such burdens, M. Douglas Ris, PhD, of Baylor College of Medicine and Texas Children’s Hospital, and his colleagues at St. Jude Children’s Research Hospital, compared 181 survivors of pediatric low-grade glioma with 105 siblings of cancer survivors who were participating in the Childhood Cancer Survivor Study. The survivors and siblings all completed a comprehensive battery of standardized cognitive tests and socioeconomic assessments performed at 16 major medical centers in the United States and Canada.
Survivors were a median age of 8 years at the time of diagnosis and they were a median age of 40 years at the time of assessment. Overall, survivors treated with surgery plus radiotherapy at the site of the tumor had lower estimated IQ scores than survivors treated with surgery only, who had lower scores than siblings. Survivors diagnosed at younger ages had low scores on most of the cognitive measures. Survivors—especially those treated with surgery plus radiotherapy—were less educated, earned lower incomes, and had lower prestige occupations than siblings.
“Late effects in adulthood are evident even for children with the least malignant types of brain tumors who were treated with the least toxic therapies available at the time. Also, these neurocognitive and socioeconomic risks are evident many decades after treatment,” said Dr. Ris. “As pediatric brain tumors become more survivable with continued advances in treatments, we need to improve surveillance of these populations so that survivors continue to receive the best interventions during their transition to adulthood and well beyond.”
This research was supported by the National Cancer Institute with grants to Baylor College of Medicine and Texas Children’s Hospital (R01CA132899), as well as to the Childhood Cancer Survivor Study at St. Jude Children’s Research Hospital (U24CA55727).
How many times have you found yourself in a position where you were faced with a situation wherein a family member or friend was going through a difficult time after a cancer diagnosis, a treatment protocol, a catastrophic accident or incident or even a death and you were at a loss for words. Despite our best efforts, we just don’t know what to say or do. Such was the situation for Lindsay Donaldson when faced with supporting her mother through her cancer journey. As a result, from her own experience, she discovered a need for a one-way communication to support and inspire her mother that would alleviate the pressure on her mother to feel the need to respond to texts, emails, and other forms of traditional communication. From this need, the CaringBand App was created to send real time, preset messages like “You got this!”, “Thinking about you”, “Praying for you” etc., to that person whenever thoughts of them cross your mind.
No matter what you choose, having the ability to send messages to those who are in need of your support and/or inspiration is so important. Barbara Jacoby
The FREE CaringBand app is now available for download Iphone and Android. Your messages of encouragement can be sent with ease, frequency, and free of pressure for the person receiving the encouragement to respond back to you. And by using any of the sharing features found on the personal profile that you create, you can text, email, or post to social media the person that you wish to encourage. From there, you are also able to share with your family, close friends, coworkers, or on your social media platforms in order to lead others directly to the CaringBand app.
The Caring Band app was created to be used with The CaringBand Light-Up Bracelet if you choose. When you give someone a CaringBand Light-Up Bracelet, they can simply pair the bracelet with their smartphone and turn on notifications for the CaringBand App. Throughout the day, they will be uplifted each time their CaringBand bracelet lights up and/or vibrates when a message is sent through the app and the recipient will know that someone is thinking positive thoughts about them at that particular time.
The bracelet is in the pilot phase of testing right now and will be available for pre-order soon. When you visit the Caring Band website, you can provide your email address to receive updates on the timing of its availability as well as information on ways you can help bring CaringBand to life.
No matter what you choose, having the ability to send messages to those who are in need of your support and/or inspiration is so important. We have all found ourselves in such a position to have the desire to do this but hesitated because we did not want to disturb someone or have the recipient think that they needed to respond. This app allows for us to let someone know in our own time that we are there for them without disturbing them in the middle of a chemotherapy infusion or while they may be sleeping in the middle of the afternoon because they were unable to do so the night before. What a wonderful way to let someone know that they are not alone regardless of where they are or what they are doing without interrupting their schedule – and it is FREE for the simple download of the app or can be enhanced with an interactive bracelet in the near future.
Dune Medical Devices has reached another milestone in their MarginProbe® Post Approval Study (PAS) as Johns Hopkins Hospital and Moffitt Cancer Center complete their patient enrollments for the trial. This PAS, required by the FDA, seeks to substantiate the vast body of data produced since MarginProbe’s original approval, demonstrating its effectiveness at intraoperatively identifying positive margins and subsequent effects on reducing re-excision rates while maintaining cosmetic outcomes after surgery.
Dr. Mehran Habibi, Medical Director of the Johns Hopkins Breast Center, and Dr. Susan Hoover, Surgical Oncologist for Moffitt Cancer Center’s Department of Breast Oncology, are the participating Principal Investigators (PI) for their respective centers in the trial. Johns Hopkins and Moffitt are the number one and number two highest enrolling centers in the study. Dr. Habibi, the Lead PI of the trial, will be working closely with Dr. Hoover to develop a publication cadence for this meaningful and relevant work.
“Johns Hopkins is continuously pursuing the newest technology and advancements in breast cancer diagnosis and treatment,” Dr. Habibi explained. “Participating in this study has allowed us to face the challenge of positive margin rates after lumpectomy head-on.”
Dr. Hoover has also spoken out about Moffitt Cancer Center’s efforts to stay on top of the latest technology for both breast cancer screening and treatment.
“Moffitt is a thought leader in the world of breast disease. We are in constant motion striving to stay ahead of the latest innovations in breast cancer in order to go beyond the current standard of care for our patients,” said Dr. Hoover. “With MarginProbe’s ability to identify positive margins in real-time and potentially lower re-excision rates, participating in this Post-Approval Study put us one step closer to accomplishing this goal.”
Johns Hopkins and Moffitt now join Pinnacle Health Cancer Institute, Summit Medical Group, and Northshore University HealthSystem as sites which have completed enrollment in the study. The three sites will follow each patient for six months as required in the next phase of the study. To date, over 300 of the study’s 440 patients have been enrolled. Six additional cancer centers across the country will continue accruing patients until August 2019 when enrollment is anticipated to be complete.
The adoption of MarginProbe by major cancer centers such as Johns Hopkins and Moffitt speaks volumes for the device’s credibility and efficacy, as well as the role it plays in improving the healthcare experience for patients. Nearly 200,000 women receive lumpectomy surgery annually, which precedes a period of uncertainty while awaiting final pathology results. A pathology report indicating a positive margin subjects patients to further surgery and a prolonged treatment timeline. Acceptance of MarginProbe as a Standard of Care will provide significantly more women with the peace of mind that their cancer was fully removed during one procedure, and the ability to complete their treatment plan returning them back to their normal life.
The MarginProbe device utilizes radiofrequency spectroscopy to characterize and differentiate cancerous versus healthy tissue, giving surgeons the ability to identify microscopic residual cancer and DCIS in real-time, removing additional tissue if needed. MarginProbe provides greater confidence for both the surgeon and the patient that all of the cancer is successfully removed in the first surgery and reduces the likelihood of costly, burdensome additional surgeries.
For a list of cancer centers currently enrolling patients in the MarginProbe post-approval trial, please visit www.clinicaltrials.gov and search “MarginProbe”.
About Dune Medical Devices
“Imagine not having to wonder, did we get it all?”
At Dune Medical Devices, we believe in reducing the anxiety that waiting for pathology results places on a patient and their families. Our solutions, which are developed on a first-of-its-kind RF Spectroscopy platform, can differentiate cancerous from healthy tissue based on electromagnetic properties, making it possible for patients and physicians to answer the question, “did we get it all?” For more information, contact firstname.lastname@example.org.
Research spanning 600,000 Danish women, including 58,534 who underwent fertility treatment, found giving birth after assisted reproduction aged 40-plus was linked to a 65 per cent higher chance of a breast cancer diagnosis during the 20 year study.
To produce the eggs for fertilisation women take powerful drugs that stimulate their ovaries.
In turn this increases the levels of oestrogen in the body, a hormone which promotes the growth of breast tissue, and can also drive the growth of cancerous cells.
While the overall rates of cancer were low, across all participants fertility treatment was linked to around two extra cases for every 1,000 women treated.
The University of Copenhagen researchers behind the study said this could be a factor in the findings.
“An increased risk could be due to age-related vulnerability to hormone exposure or to higher doses of hormones during ART [assisted reproductive technology] treatment,” they wrote in a summary of the findings presented at the European Society for Human Reproduction and Embryology (ESHRE) annual meeting in Vienna.
Breast cancer is the most commonly diagnosed form of cancer in the UK and around 55,000 women are diagnosed each year.
The study ran from 1994 to 2015 and matched each woman who had given birth after assisted reproduction with 10 women of a similar background who had given birth naturally.
Cancer rates during the study were low overall. There were 3,894 cases in total, and around 0.6 per of the women were diagnosed with breast cancer – this rose to 0.8 per cent in the women who had IVF.
“This is a wake-up call about the use of high dose stimulation in IVF, especially in women over the age of 40,” said Professor Geeta Nargund, of London’s St George’s Hospital and Create Fertility.
She said doctors should start counselling older patients about these increased risks and should look to minimise the dosages they are administering.
However, the latest findings have yet to be peer reviewed and they also can’t rule out that other factors, which might impact on fertility and cancer risk, could be behind the rise.
Having children later is known to increase risk, while breastfeeding can help reduce it, but obesity, diet and smoking all play a role.
“This is an interesting preliminary finding but shouldn’t alarm people,” said Roy Farquharson, president of the ESHRE.
He said that 40 years of research into the effects of the drugs used in IVF and other forms of assisted reproduction had concluded that the long-term cancer risks are low.
“For years we have been trying to find out whether it’s infertility or IVF and we have not been able to do that successfully. If there is an effect [from IVF treatment] it’s marginal.”
By: A.K. Gupta, Senior VP and Chief Information Officer, UBC
The biopharma industry faces myriad challenges in the pursuit of its mission to bring new treatments to patients in need of cures, chief among them the “Iron Triangle” of time, cost, and quality with respect to clinical research. The cost of conducting clinical trials is escalating, quality remains paramount and the importance of accelerating insights into the safety and effectiveness of medicines has never been greater. Confronting these challenges is the industry-defining objective for drug developers in the decade to come. The importance of this undertaking cannot be overstated when we consider the afflicted patient populations that are waiting on us to deliver efficacious and safe treatments.
Technology Breakthroughs Key to Transforming Clinical Research
The obstacles have been unyielding and the solutions have been slow to gain traction, however, now more than ever, breakthroughs in technology hold the promise of transforming clinical research. Technological advancements in data interoperability are rapidly making an impact today, fueled by the network effect of data and partnerships. Advancements in virtualized research are being driven by a focus on patient-centricity, “natural” smart interfaces, and an ever-expanding list of devices that are always present, always connected, continually getting smarter, and have access to next generation networks with an unimaginable amount of information and technology services. Intelligent architectures and real-world data infrastructures are allowing for the creation of core technology platforms that bring together a diverse, complex, and disruptive set of technology capabilities. Real-world data infrastructures are purpose-built with the sole focus of disrupting and modernizing critical domains of research and drug development. Designed upon a foundation of cognitive computing, artificial intelligence thru machine learning and augmented intelligence is empowering clinical experts through automation, data-driven decision making, and various stages of intelligence — assisted, augmented, and autonomous. Innovative solutions in the areas of study design, patient identification, data collection, and evidence generation will significantly impact drug development and enable realization of the vision set forth in the 21st Century Cures Act and subsequent FDA Framework for Real World Evidence.
Data Interoperability & Network Effect
In a recent speech, the new acting FDA Commissioner Dr. Ned Sharpless issued a challenge to industry: “If we want to harness the full potential of therapies to transform care, we need to become more efficient, more collaborative, and more data driven so that we can learn from every patient’s journey1.” In the years ahead, healthcare data interoperability will play a lead role in meeting the commissioner’s and the larger market’s challenge. New technologies and solutions in this arena allow us to profoundly enrich what we know about a patient profile, their clinical encounters and the outcomes in ways that were not possible to address, or, were cost-prohibitive in the past.
Combining and enriching traditional randomized controlled clinical trial data with real-world data sources (EHR, health information exchanges, integrated delivery networks, claims, labs, genomics, data markets, sensors, devices, wearable, etc.) enable insights that are not feasible using traditional data collection methods. This in turn increases the reliability and value of the study data and meaningful inferences, leading to a better understanding of real-world patient outcomes. Real-world data exists in many forms and is available from many sources (e.g. integrations, partnerships, commercial availability); however, finding and acquiring this data is only the beginning. Maximum value is achieved by linking data from these disparate data sources at the patient level to form a single comprehensive dataset. Advanced analytics, simulations, and statistically driven data visualization — powered by unsupervised learning techniques can then mine for relationships and insights that would never appear were the datasets analyzed independently.
The ubiquitous digitization of the healthcare data landscape presents untapped opportunities to reduce the cost of research while simultaneously improving quality and reliability via a wide range of use cases — from centralized identification and recruitment of both sites and subjects to automated population of CRF forms. Interoperability with the systems HCPs use every day (e.g. pushing study-related reminders or flagging patients as potential subjects) can streamline site engagement. Efficiencies like these not only reduce the cost of clinical research: they reduce the burden on sites, thereby increasing their willingness to participate.
These solutions introduce transformative improvement to the availability, breadth, depth, accuracy, and velocity of data collection. Clinical trials and non-interventional research approaches are enriched through the efficient acquisition and intelligent processing of RWD from medical/pharmacy claims, lab data, wearables, biomarkers, and other sources.
Healthcare data digitization sets the stage for patients to have greater access to and ownership of their healthcare records than ever before. The network effect of these partnerships and data interoperability standards will catalyze the movement toward virtualized trial designs; fueled through modernized approaches to rapid feasibility, appropriate patient identification and segmentation for protocol specific goals, enrollment, engagement, and multi-modal collection of patient-generated data throughout the clinical trial lifecycle. The traditional approach of “bringing the patient to the study” at brick-and-mortar facilities will be augmented and replaced by tactics that “bring the study to the patient.”
Virtualized clinical trials, registries, and other observational initiatives represent another critical and relatively inexpensive source of research data, which is collected directly from patients. The explosion of IoT, mobile devices, and wearables mean that the average human in the developed world walks around with both an ever-increasing array of physical-world sensors and an engagement platform that is nearly impossible to ignore.
Chatbots powered by cutting-edge AI engage patients in conversation over channels with which the patient is already comfortable (e.g. SMS, social media chat) in order both to collect data and to guide the patient through the protocol.
These intelligent interfaces and other IoT enabled home medical devices (e.g. EKG sensors) are also becoming more common as telemedicine gains traction. Inclusion of these devices will form an increasingly critical part of protocol design, especially as pending and ongoing legislation facilitates and allows for this information to serve as part of the body of the submission for regulatory approval and managed market access consideration related to value of the product versus the cost of care.
Real-World Data Infrastructure Powered by AI
The automated transformation of disparate and unstructured real-world data into high-quality research-grade datasets holds great promise when it comes to delivering life-changing cures faster and cheaper, albeit with significant obstacles. Integrating with different systems at each site has historically been cost prohibitive due to disparate and competing data standards. Forces within healthcare are beginning to pull individual EHR implementations out of their silos and into interconnected networks, which act as both an exchange for health data as well as a single point of integration. Patient data privacy concerns can derail attempts to link datasets, however, de-identification solutions utilizing identity hashing algorithms enable linking patient data with a high degree of confidence without ever needing to expose personally identifiable information. Data ownership will continue to be an important piece of the puzzle, as, PHI and other privacy concerns related to data access, and, the “empowered patient” start to influence study participation and data liquidity.
Whereas healthcare data is mostly digitized, the data is often only partially structured. However, as cloud technologies democratize machine learning, natural language understanding (NLU) promises to free data points locked in narrative text, voice and other unstructured formats. Armed with semantic understanding and deep and expressive ontologies, these algorithms will be able to create research grade datasets through cognitive AI processing. Augmented intelligence powered by machine learning capabilities and big data will empower clinical experts to make faster and better decisions.
As solutions emerge, it will be critical that biopharma companies select partners that are invested in the clinical expertise, the technologies and the relationships across the healthcare delivery system needed to navigate this dynamic and complex landscape. The data network effect along with the partnership network effect will make it more critical than ever to select core partners that are strategic inflection points. Expertise and core competencies across a wide range of technical domains are essential attributes to target as drug developers form these mission critical collaborations. Competitive advantages will accrue to industry participants that capitalize on these emerging technologies that will transform drug development, accelerate answers to researcher’s questions, and deliver safe and effective medicines to patients in need of treatment.(PV)
The guidelines for screening women for breast cancer are a bit confusing. The American Cancer Society recommends annual mammograms for women older than 45 years with average risk, but other groups like the U.S. Preventative Services Task Force (USPSTF) recommend less aggressive breast screening.
This controversy centers on mammography’s frequent false-positive detections — or false alarms — which lead to unnecessary stress, additional imaging exams and biopsies. USPSTF argues that the harms of early and frequent mammography outweigh the benefits.
However, a recent Stanford study suggests a better way to reduce these false alarms without increasing the number of missed cancers. Using over 112,000 mammography cases collected from 13 radiologists across two teaching hospitals, the researchers developed and tested a machine-learning model that could help radiologists improve their mammography interpretation.
Each mammography case included the radiologist’s observations and diagnostic classification from the mammogram, the patient’s risk factors and the “ground-truth” of whether or not the patient had breast cancer based on follow-up procedures. The researchers used the data to train and evaluate their computer model.
They compared the radiologists’ performance against their machine-learning model, doing a separate analysis for each of the 13 radiologists. They found significant variability among radiologists.
Based on accepted clinical guidelines, radiologists should recommend follow-up imaging or a biopsy when a mammographic finding has a 2% probability of being malignant. However, the Stanford study found participating radiologists used a threshold that varied from 0.6 to 3%. In the future, similar quantitative observations could be used to identify sources of variability and to improve radiologist training, the paper said.
The study included 1,214 malignant cases, which represents 1.1 percent of the total number. Overall, the radiologists reported 176 false negatives indicating cancers missed at the time of the mammograms. They also reported 12,476 false positives or false alarms. In comparison, the machine-learning model missed one additional cancer but it decreased the number of false alarms by 3,612 cases relative to the radiologists’ assessment.
The study concluded: “Our results show that we can significantly reduce screening mammography false positives with a minimal increase in false negatives.”
However, their computer model was developed using data from 1999 to 2010, the era of analog film mammography. In future work, the researchers plan to update the computer algorithm to use the newer descriptors and classifications for digital mammography and three-dimensional breast tomosynthesis.
Ross Shachter, PhD, a Stanford associate professor of management science and engineering and lead author on the paper, summarized in a recent Stanford Engineering news release, “Our approach demonstrates the potential to help all radiologists, even experts, perform better.”
Phase I clinical trials are the foundation for how we develop new cancer drugs. Typically, they involve only several dozen patients and study a new medicine’s effect on a variety of cancer types.
David S. Hong, M.D., sat down with us to explain more about Phase I clinical trials and answer some of patients’ most frequently asked questions.
What is a Phase I clinical trial?
Phase I clinical trials are the first time human beings are being treated with an experimental drug. It starts with researchers figuring out a pathway to kill cancer. A drug company then develops a medication that mimics that process. The primary purpose of a Phase I is to figure out how much of the drug we can safely give patients and see a benefit.
But that’s not the only purpose. Phase I trials also help us figure out which cancers benefit from these drugs.
Who should consider participating in a Phase I clinical trial?
Phase I clinical trials aren’t for everyone. Most patients who choose Phase I clinical trials are running out of options. Typically, they have metastatic disease, haven’t had success with standard chemotherapy, have mild or no symptoms and don’t want to go to hospice. They’re willing to see if they can help others, and possibly themselves, by participating in a Phase I clinical trial.
What questions do you hear most from patients considering Phase I clinical trials?
“Is there a placebo?” Unlike Phase III clinical trials, there’s usually not a placebo in a Phase I trial. Everyone gets the drug, just at different dose levels.
There are also a lot of questions about schedules. Phase I clinical trials are very intensive and require multiple visits from the patient. Since it’s the first time this drug has been used in human beings, we’re very vigilant.
We also get a lot of questions about side effects. Typical side effects include nausea, vomiting and diarrhea. But side effects are different for each patient in each trial. We try to give patients an overview of the most common side effects, those that are most concerning and then all possible side effects. Most side effects are reversible and treatable. We either stop the drug or we give another medication to address the side effects.
How long will a patient be enrolled in a Phase I clinical trial?
Patients can usually stay on a Phase I clinical trial as long as they benefit. A traditional Phase I clinical trial lasts about two years (from the time we start enrolling to the time that we actually close out a study).
What happens if a patient’s condition doesn’t improve?
If a patient’s clinical condition declines, it may just be because of side effects and we can address those issues. Or, it’s because the tumors are growing. We re-image patients on a regular basis, and we do measurements on the patient following a preset criteria. Depending on the drug and the set criteria, we’ll take the patient off the study if a tumor grows a certain percentage. What happens next depends on how the patient is doing overall. Many patients go on to another Phase I study or back to their medical oncologist because he or she has one more therapy to try. Or, if they are out of options, they may decide to go to hospice.
What are some of the most promising Phase I clinical trials we have at MD Anderson right now?
There’s lots of exciting research happening. In a Phase I trial of the drug LOXO-101, we’ve seen tumors shrink in patients with cancers that are linked to the gene fusion of NTRK. We’ve also seen promising results in a Phase I trial of a combination of inhibitor drugs that target a cancer cell’s signaling. Lastly, we have many immunotherapy Phase I clinical trials, but one that’s exciting is the upcoming MAGE-A10 study on the use of engineered cells of the immune system (called CAR-T cell and T-cell receptor therapies).
What advice do you have for caregivers of patients enrolling in Phase I trials?
My number one piece of advice is don’t push your loved one to do a Phase I. It’s not always the best choice for the patient.
Two, be prepared to support this patient timewise. It’s an intensive and time-consuming process.
Three, ask questions. You need to be informed.
Anything else you want patients to know about Phase I clinical trials?
What we’re seeing in the Phase I environment is a lot of hope. Within the past decade, there’s been an explosion of new drugs. There are over a thousand new cancer drugs in the pipeline. We’re seeing a lot more activity than before; drugs that are actually working in lots of different tumors types than before. We’re also getting much more sophisticated in how we identify patients. I’m an optimist, and I wouldn’t be in this field if I wasn’t.
Millions of people around the world suffer from cancer-related fatigue
Untire, the first mobile app to address Cancer-Related Fatigue (CRF), is now available for free. Fatigue is the most common side effect of cancer and its treatment. Almost 40% of all cancer patients and survivors suffer from severe and prolonged fatigue. Untire’s easy-to-use self-management program provides support to the millions of cancer patients and survivors suffering worldwide.
CRF is characterized by feelings of exhaustion and weakness. The lack of energy often impacts daily living, reduces quality of life with debilitating social and economic consequences.
Untire offers a comprehensive program based on proven methods with education on topics such as anxiety and sleep disorders along with stress-reduction activities and physical exercises. This digital medicine was developed by Dr. Bram Kuiper, a clinical psychologist in oncology for over thirty years.
Untire is available for free in the App Store and Google Play in 25 EU Countries, United States, Canada, United Kingdom, Australia, New Zealand and South Africa. It is designed to help all cancer patients and survivors regardless of age, cancer stage or cancer type. For more information visit www.untire.me
In the United States alone, this impacts over eight million people and tens of millions worldwide. Although fatigue is the most common side effect of cancer, it lacks awareness amongst patients and providers. Doctors, nurses and other care providers often do not have an answer to the problem.
“We are proud that we can provide this new resource, which is so important for cancer patients and healthcare providers,” says Dr. Kuiper. “There is now great interest, among patients, patient advocacy groups, hospitals, oncologists and nurses to use the app in blended care; the combination of regular medical treatments and online support.”
Tired of Cancer has commissioned a Randomized-Control-Trial study with the University of Groningen (Netherlands) that includes more than a thousand users of the Untire app, in six countries. “The first results, as we see them, from weekly measurements in the app, are more than encouraging,” says Dr. Kuiper. ” Final results will be available in 2019, but we are already convinced that the Untire app can make a huge contribution to solving the major problem of fatigue that so many people face with cancer.”
About Tired of Cancer:
In 2013, Dr. Bram Kuiper and co-founder Door Vonk, MA sought out a solution that would help millions of cancer and former cancer patients worldwide in their fight against fatigue. Since 2017, they have devoted themselves entirely to the development of Untire. Tired of Cancer’s mission is to help as many cancer patients and survivors as possible all over the world to regain energy and improve quality of life. As a social enterprise, Tired of Cancer is committed to investing future revenues into further development of Untire as well as research and development for new cancer fatigue solutions. It is part of the Horizon 2020 program of the European Research and Innovation program. For more information, visit www.tiredofcancerapp.com or www.untire.me
As part of our mission to eliminate cancer, MD Anderson researchers conduct hundreds of clinical trials to test new treatments for both common and rare cancers. Look through our database to find studies for which you may be eligible.
What are clinical trials?
Clinical trials are research studies in which patients may volunteer to take part. MD Anderson uses clinical trials to find better ways to prevent, diagnose and treat cancer. Doctors use treatment trials to learn more about how to fight cancer. This guide is for patients who may join a treatment trial.
Clinical trials are part of a long, careful process, which may take many years. First, doctors study a new treatment in the lab. Then they often study the treatment in animals. If a new treatment shows promise, doctors then test the treatment in people. Doctors do this in three to four steps, or phases. Your doctor may offer you a clinical trial as a treatment option.
How am I protected?
MD Anderson’s most important job is to protect patients. First, MD Anderson protects patients in clinical trials by following well-planned protocols.
Explains the treatment plan
Lists the medical tests patients will receive
Gives the number of how many patients will take part in the clinical trial
Lists eligibility criteria, which are guidelines to decide who may join the clinical trial
Explains safety information
Second, MD Anderson protects patients by using a careful informed consent process.
Third, our Institutional Review Boards (IRBs) protect patients by reviewing protocols and monitoring trials. The IRBs are committees of doctors, nurses, chaplains, social workers, lawyers and patients. They make sure that trials follow federal laws and that patients are protected.
The U.S. Food and Drug Administration (FDA) audits the IRBs’ files. Also, FDA officials may visit MD Anderson at any time and review anything they choose related to clinical trials.