Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predispose women to a higher incidence of egg aneuploidy. However, the exact genetic causes of aneuploid egg production remain unclear, making it difficult to diagnose infertility based on individual genetic variants in mother’s genome. Although, age is a predictive factor for aneuploidy, it is not a highly accurate gauge because aneuploidy rates within individuals of the same age can vary dramatically.
Researchers described a technique combining genomic sequencing with machine-learning methods to predict the possibility a woman will undergo a miscarriage because of egg aneuploidy—a term describing a human egg with an abnormal number of chromosomes. The scientists were able to examine genetic samples of patients using a technique called “whole exome sequencing,” which allowed researchers to home in on the protein coding sections of the vast human genome. Then they created software using machine learning, an aspect of artificial intelligence in which programs can learn and make predictions without following specific instructions. To do so, the researchers developed algorithms and statistical models that analyzed and drew inferences from patterns in the genetic data.
As a result, the scientists were able to create a specific risk score based on a woman’s genome. The scientists also identified three genes—MCM5, FGGY and DDX60L—that when mutated and are highly associated with a risk of producing eggs with aneuploidy. So, the report demonstrated that sequencing data can be mined to predict patients’ aneuploidy risk thus improving clinical diagnosis. The candidate genes and pathways that were identified in the present study are promising targets for future aneuploidy studies. Identifying genetic variations with more predictive power will serve women and their treating clinicians with better information.
Reporter and Curator: Mr. Srinjoy Chakraborty (Junior Research Felllow) and Dr. Sudipta Saha, Ph.D.
Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a serious global health issue with high transmission rates affecting millions of people worldwide. The SARS-CoV-2 is known to damage cells in the respiratory system, thus causing viral pneumonia. The novel SARS-CoV-2 is a close relative to the previously identified severe acute respiratory syndrome-coronavirus (SARS-CoV) and Middle East respiratory syndrome-coronavirus (MERS-CoV) which affected several people in 2002 and 2012, respectively. Ever since the outbreak of covid-19, several reports have poured in about the impact of Covid-19 on pregnancy. A few studies have highlighted the impact of the viral infection in pregnant women and how they are more susceptible to the infection because of the various physiological changes of the cardiopulmonary and immune systems during pregnancy. It is known that SARS-CoV and MERS-CoV diseases have influenced the fatality rate among pregnant women. However, there are limited studies on the impact of the novel corona virus on the course and outcome of pregnancy.
Figure: commonly observed clinical symptoms of COVID-19 in the general population: Fever and cough, along with dyspnoea, diarrhoea, and malaise are the most commonly observed symptoms in pregnant women, which is similar to that observed in the normal population.
The WHO and the Indian Council of Medical Research (ICMR) have proposed detailed guidelines for treating pregnant women; these guidelines must be strictly followed by the pregnant individual and their families. According to the guidelines issued by the ICMR, the risk of pregnant women contracting the virus to that of the general population. However, the immune system and the body’s response to a viral infection is altered during pregnancy. This may result in the manifestation of more severe symptoms. The ICMR guidelines also state that the reported cases of COVID-19 pneumonia in pregnancy are milder and with good recovery. However, by observing the trends of the other coronavirus infection (SARS, MERS), the risks to the mother appear to increase in particular during the last trimester of pregnancy. Cases of preterm birth in women with COVID-19 have been mentioned in a few case report, but it is unclear whether the preterm birth was always iatrogenic, or whether some were spontaneous. Pregnant women with heart disease are at highest risk of acquiring the infection, which is similar to that observed in the normal population. Most importantly, the ICMR guidelines highlights the impact of the coronavirus epidemic on the mental health of pregnant women. It mentions that the since the pandemic has begun, there has been an increase in the risk of perinatal anxiety and depression, as well as domestic violence. It is critically important that support for women and families is strengthened as far as possible; that women are asked about mental health at every contact.
With the available literature available on the impact of SARS and MERS on reproductive outcome, it has been mentioned that SARS infection did increase the risk of miscarriage, preterm birth and, intrauterine foetal growth restriction. However, the same has not been demonstrated in early reports from COVID-19 infection in pregnancy. According to a study that included 8200 participants conducted by the centre for disease control and prevention, pregnant women may be at a higher risk of acquiring severe infection and need for ICU admissions as compared to their non-pregnant counterparts. However, a detailed and thorough study involving a larger proportion of the population is needed today.
The Inequality and Health Disparity seen with the COVID-19 Pandemic Is Similar to Past Pandemics
Curator: Stephen J. Williams, PhD
It has become very evident, at least in during this pandemic within the United States, that African Americans and poorer communities have been disproportionately affected by the SARS-CoV2 outbreak . However, there are many other diseases such as diabetes, heart disease, and cancer in which these specific health disparities are evident as well :
Disease like cancer have been shown to have wide disparities based on socioeconomic status, with higher incidence rates seen in poorer and less educated sub-populations, not just here but underdeveloped countries as well (see Opinion Articles from the Lancet: COVID-19 and Cancer Care in China and Africa) and graphics below)
In an article in Science by Lizzie Wade, these disparities separated on socioeconomic status, have occurred in many other pandemics throughout history, and is not unique to the current COVID19 outbreak. The article, entitled “An Unequal Blow”, reveal how
in past pandemics, people on the margins suffered the most.
Health Disparities during the Black Death Bubonic Plague Pandemic in the 14th Century (1347-1351)
During the mid 14th century, all of Europe was affected by a plague induced by the bacterium Yersinia pestis, and killed anywhere between 30 – 60% of the European population. According to reports by the time the Black Death had reached London by January 1349 there had already been horrendous reports coming out of Florence Italy where the deadly disease ravished the population there in the summer of 1348 (more than half of the city’s population died). And by mid 1349 the Black Death had killed more than half of Londoners. It appeared that no one was safe from the deadly pandemic, affecting the rich, the poor, the young, the old.
However, after careful and meticulous archaeological and historical analysis in England and other sites, revealed a distinct social and economic inequalities that predominated and most likely guided the pandemics course throughout Europe. According to Dr. Gwen Robbins Schug, a bio-archaeologist at Appalachian State University,
Bio-archaeology and other social sciences have repeatedly demonstrated that these kinds of crises play out along the preexisting fault lines of each society. The people at greatest risk were often those already marginalized- the poor and minorities who faced discrimination in ways that damaged their health or limited their access to medical care even in pandemic times.
At the start of the Black Death, Europe had already gone under a climactic change with erratic weather. As a result, a Great Famine struck Europe between 1315-17. Wages fell and more people fell into poverty while the wealthiest expanded their riches, leading to an increased gap in wealth and social disparity. In fact according to recordkeeping most of Englanders were living below the poverty line.
Author Lizzie Wade also interviewed Dr. Sharon, DeWitte, a biological anthropologist at University of South Carolina, who looks at skeletal remains of Black Death victims to get evidence on their health status, like evidence of malnutrition, osteoporosis, etc. And it appears that most of the victims may have had preexisting health conditions indicative of poorer status. And other evidence show that wealthy landowners had a lower mortality rate than poorer inner city dwellers.
1918 Spanish Flu
Socioeconomic and demographic studies have shown that both Native American Indians and African Americans on the lower end of the socioeconomic status were disproportionately affected by the 1918 Spanish flu pandemic. According to census records, the poorest had a 50% higher mortality rate than wealthy areas in the city of Oslo. In the US, minors and factory workers died at the highest rates. In the US African Americans had already had bouts with preexisting issues like tuberculosis and may have contributed to the higher mortality. In addition Jim Crow laws in the South, responsible for widespread discrimination, also impacted the ability of African Americans to seek proper medical care.
Like other forms of segregation, health-care segregation was originally a function of explicitly racist black codes and Jim Crow laws. Many hospitals, clinics, and doctor’s offices were totally segregated by race, and many more maintained separate wings or staff that could never intermingle under threat of law. The deficit of trained black medical professionals (itself caused by a number of factors including education segregation) meant that no matter where black people received health-care services, they would find their care to be subpar compared to that of whites. While there were some deaths that were directly attributable to being denied emergency service, most of the damage was done in establishing the same cumulative health disparities that plague black people today as a societal fate. The descendants of enslaved people lived much more dangerous and unhealthy lives than white counterparts, on disease-ridden and degraded environments. Within the confines of a segregated health-care system, these factors became poor health outcomes that shaped black America as if they were its genetic material.
R.A.HahnaB.I.TrumanbD.R.Williamsc.Civil rights as determinants of public health and racial and ethnic health equity: Health care, education, employment, and housing in the United States.
Personalized Medicine, Omics, and Health Disparities in Cancer: Can Personalized Medicine Help Reduce the Disparity Problem?
Curator: Stephen J. Williams, PhD
In a Science Perspectives article by Timothy Rebbeck, health disparities, specifically cancer disparities existing in the sub-Saharan African (SSA) nations, highlighting the cancer incidence disparities which exist compared with cancer incidence in high income areas of the world [1]. The sub-Saharan African nations display a much higher incidence of prostate, breast, and cervix cancer and these cancers are predicted to double within the next twenty years, according to IARC[2]. Most importantly,
the histopathologic and demographic features of these tumors differ from those in high-income countries
meaning that the differences seen in incidence may reflect a true health disparity as increases rates in these cancers are not seen in high income countries (HIC).
Most frequent male cancers in SSA include prostate, lung, liver, leukemia, non-Hodgkin’s lymphoma, and Kaposi’s sarcoma (a cancer frequently seen in HIV infected patients [3]). In SSA women, breast and cervical cancer are the most common and these display higher rates than seen in high income countries. In fact, liver cancer is seen in SSA females at twice the rate, and in SSA males almost three times the rate as in high income countries.
Reasons for cancer disparity in SSA
Patients with cancer are often diagnosed at a late stage in SSA countries. This contrasts with patients from high income countries, which have their cancers usually diagnosed at an earlier stage, and with many cancers, like breast[4], ovarian[5, 6], and colon, detecting the tumor in the early stages is critical for a favorable outcome and prognosis[7-10]. In addition, late diagnosis also limits many therapeutic options for the cancer patient and diseases at later stages are much harder to manage, especially with respect to unresponsiveness and/or resistance of many therapies. In addition, treatments have to be performed in low-resource settings in SSA, and availability of clinical lab work and imaging technologies may be limited.
Molecular differences in SSA versus HIC cancers which may account for disparities
Emerging evidence suggests that there are distinct molecular signatures with SSA tumors with respect to histotype and pathology. For example Dr. Rebbeck mentions that Nigerian breast cancers were defined by increased mutational signatures associated with deficiency of the homologous recombination DNA repair pathway, pervasive mutations in the tumor suppressor gene TP53, mutations in GATA binding protein 3 (GATA3), and greater mutational burden, compared with breast tumors from African Americans or Caucasians[11]. However more research will be required to understand the etiology and causal factors related to this molecular distinction in mutational spectra.
It is believed that there is a higher rate of hereditary cancers in SSA. And many SSA cancers exhibit the more aggressive phenotype than in other parts of the world. For example breast tumors in SSA black cases are twice as likely than SSA Caucasian cases to be of the triple negative phenotype, which is generally more aggressive and tougher to detect and treat, as triple negative cancers are HER2 negative and therefore are not a candidate for Herceptin. Also BRCA1/2 mutations are more frequent in black SSA cases than in Caucasian SSA cases [12, 13].
Initiatives to Combat Health Disparities in SSA
Multiple initiatives are being proposed or in action to bring personalized medicine to the sub-Saharan African nations. These include:
H3Africa empowers African researchers to be competitive in genomic sciences, establishes and nurtures effective collaborations among African researchers on the African continent, and generates unique data that could be used to improve both African and global health.
There is currently a global effort to apply genomic science and associated technologies to further the understanding of health and disease in diverse populations. These efforts work to identify individuals and populations who are at risk for developing specific diseases, and to better understand underlying genetic and environmental contributions to that risk. Given the large amount of genetic diversity on the African continent, there exists an enormous opportunity to utilize such approaches to benefit African populations and to inform global health.
The Human Heredity and Health in Africa (H3Africa) consortium facilitates fundamental research into diseases on the African continent while also developing infrastructure, resources, training, and ethical guidelines to support a sustainable African research enterprise – led by African scientists, for the African people. The initiative consists of 51 African projects that include population-based genomic studies of common, non-communicable disorders such as heart and renal disease, as well as communicable diseases such as tuberculosis. These studies are led by African scientists and use genetic, clinical, and epidemiologic methods to identify hereditary and environmental contributions to health and disease. To establish a foundation for African scientists to continue this essential work into the future work, the consortium also supports many crucial capacity building elements, such as: ethical, legal, and social implications research; training and capacity building for bioinformatics; capacity for biobanking; and coordination and networking.
Advancing precision medicine in a way that is equitable and beneficial to society means ensuring that healthcare systems can adopt the most scientifically and technologically appropriate approaches to a more targeted and personalized way of diagnosing and treating disease. In certain instances, countries or institutions may be able to bypass, or “leapfrog”, legacy systems or approaches that prevail in developed country contexts.
The World Economic Forum’s Leapfrogging with Precision Medicine project will develop a set of tools and case studies demonstrating how a precision medicine approach in countries with greenfield policy spaces can potentially transform their healthcare delivery and outcomes. Policies and governance mechanisms that enable leapfrogging will be iterated and scaled up to other projects.
Successes in personalized genomic research in SSA
As Dr. Rebbeck states:
Because of the underlying genetic and genomic relationships between Africans and members of the African diaspora (primarily in North America and Europe), knowledge gained from research in SSA can be used to address health disparities that are prevalent in members of the African diaspora.
For example members of the West African heritage and genomic ancestry has been reported to confer the highest genomic risk for prostate cancer in any worldwide population [14].
Science 03 Jan 2020:
Vol. 367, Issue 6473, pp. 27-28
DOI: 10.1126/science.aay474
Summary/Abstract
Cancer is an increasing global public health burden. This is especially the case in sub-Saharan Africa (SSA); high rates of cancer—particularly of the prostate, breast, and cervix—characterize cancer in most countries in SSA. The number of these cancers in SSA is predicted to more than double in the next 20 years (1). Both the explanations for these increasing rates and the solutions to address this cancer epidemic require SSA-specific data and approaches. The histopathologic and demographic features of these tumors differ from those in high-income countries (HICs). Basic knowledge of the epidemiology, clinical features, and molecular characteristics of cancers in SSA is needed to build prevention and treatment tools that will address the future cancer burden. The distinct distribution and determinants of cancer in SSA provide an opportunity to generate knowledge about cancer risk factors, genomics, and opportunities for prevention and treatment globally, not only in Africa.
Parkin DM, Ferlay J, Jemal A, Borok M, Manraj S, N’Da G, Ogunbiyi F, Liu B, Bray F: Cancer in Sub-Saharan Africa: International Agency for Research on Cancer; 2018.
Chinula L, Moses A, Gopal S: HIV-associated malignancies in sub-Saharan Africa: progress, challenges, and opportunities. Current opinion in HIV and AIDS 2017, 12(1):89-95.
Colditz GA: Epidemiology of breast cancer. Findings from the nurses’ health study. Cancer 1993, 71(4 Suppl):1480-1489.
Hamilton TC, Penault-Llorca F, Dauplat J: [Natural history of ovarian adenocarcinomas: from epidemiology to experimentation]. Contracept Fertil Sex 1998, 26(11):800-804.
Garner EI: Advances in the early detection of ovarian carcinoma. J Reprod Med 2005, 50(6):447-453.
Brockbank EC, Harry V, Kolomainen D, Mukhopadhyay D, Sohaib A, Bridges JE, Nobbenhuis MA, Shepherd JH, Ind TE, Barton DP: Laparoscopic staging for apparent early stage ovarian or fallopian tube cancer. First case series from a UK cancer centre and systematic literature review. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2013, 39(8):912-917.
Kolligs FT: Diagnostics and Epidemiology of Colorectal Cancer. Visceral medicine 2016, 32(3):158-164.
Rocken C, Neumann U, Ebert MP: [New approaches to early detection, estimation of prognosis and therapy for malignant tumours of the gastrointestinal tract]. Zeitschrift fur Gastroenterologie 2008, 46(2):216-222.
Srivastava S, Verma M, Henson DE: Biomarkers for early detection of colon cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 2001, 7(5):1118-1126.
Pitt JJ, Riester M, Zheng Y, Yoshimatsu TF, Sanni A, Oluwasola O, Veloso A, Labrot E, Wang S, Odetunde A et al: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. Nature communications 2018, 9(1):4181.
Zheng Y, Walsh T, Gulsuner S, Casadei S, Lee MK, Ogundiran TO, Ademola A, Falusi AG, Adebamowo CA, Oluwasola AO et al: Inherited Breast Cancer in Nigerian Women. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018, 36(28):2820-2825.
Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH et al: Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Human mutation 2018, 39(5):593-620.
Lachance J, Berens AJ, Hansen MEB, Teng AK, Tishkoff SA, Rebbeck TR: Genetic Hitchhiking and Population Bottlenecks Contribute to Prostate Cancer Disparities in Men of African Descent. Cancer research 2018, 78(9):2432-2443.
Other articles on Cancer Health Disparities and Genomics on this Online Open Access Journal Include:
This update is the video from the COVID-19 Series 4.
UPDATED 4/08/2020 see below
The Second in a Series of Virtual Town Halls with Leading Oncologist on Cancer Patient Care during COVID-19 Pandemic: What you need to know
The second virtual Town Hall with Leading International Oncologist, discussing the impact that the worldwide COVID-19 outbreak has on cancer care and patient care issues will be held this Saturday April 4, 2020. This Town Hall Series is led by Dr. Roy Herbst and Dr. Hossain Borghaei who will present a panel of experts to discuss issues pertaining to oncology practice as well as addressing physicians and patients concerns surrounding the risk COVID-19 presents to cancer care. Some speakers on the panel represent oncologist from France and Italy, and will give their views of the situation in these countries.
Speakers include:
Roy S. Herbst, MD, PhD, Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology; Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Associate Cancer Center Director for Translational Research, Yale Cancer Center
Hossain Borghaei, DO, MS , Chief of Thoracic Medical Oncology and Director of Lung Cancer Risk Assessment, Fox Chase Cancer Center
Giuseppe Curigliano, MD, PhD, University of Milan and Head of Phase I Division at IEO, European Institute of Oncology
Paolo Ascierto, MD National Tumor Institute Fondazione G. Pascale, Medical oncologist from National Cancer Institute of Naples, Italy
Dr. Jack West from City of Hope talked about telemedicine: Coordination of the patient experience, which used to be face to face now moved to a telemedicine alternative. For example a patient doing well on personalized therapy, many patients are well suited for a telemedicine experience. A benefit for both patient and physician.
Dr. Rohit Kumar: In small cancer hospitals, can be a bit difficult to determine which patient needs to come in and which do not. For outpatients testing for COVID is becoming very pertinent as these tests need to come back faster than it is currently. For inpatients the issue is personal protection equipment. They are starting to reuse masks after sterilization with dry heat. Best to restructure the system of seeing patients and scheduling procedures.
Dr. Christopher Manley: hypoxia was an issue for COVID19 patients but seeing GI symptoms in 5% of patients. Nebulizers have potential to aerosolize. For patients in surgery prep room surgical masks are fine. Ventilating these patients are a challenge as hypoxia a problem. Myocarditis is a problem in some patients. Diffuse encephalopathy and kidney problems are being seen. So Interleukin 6 (IL6) inhibitors are being used to reduce the cytokine storm presented in patients suffering from COVID19.
Dr. Hope Rugo from UCSF: Breast cancer treatment during this pandemic has been challenging, even though they don’t use too much immuno-suppressive drugs. How we decide on timing of therapy and future visits is crucial. For early stage breast cancer, neoadjuvant therapy is being used to delay surgeries. Endocrine therapy is more often being used. In patients that need chemotherapy, they are using growth factor therapy according to current guidelines. Although that growth factor therapy might antagonize some lung problems, there is less need for multiple visits.
For metastatic breast cancer, high risk ER positive are receiving endocrine therapy and using telemedicine for followups. For chemotherapy they are trying to reduce the schedules or frequency it is given. Clinical trials have been put on hold, mostly pharmokinetic studies are hard to carry out unless patients can come in, so as they are limiting patient visits they are putting these type of clinical studies on hold.
Dr. Harriet Kluger: Melanoma community of oncologists gathered together two weeks ago to discuss guidelines and best practices during this pandemic. The discussed that there is a lack of data on immunotherapy long term benefit and don’t know the effectiveness of neoadjuvant therapy. She noted that many patients on BRAF inhibitors like Taflinar (dabrafenib) or Zelboraf (vemurafenib) might get fevers as a side effect from these inhibitors and telling them to just monitor themselves and get tested if they want. Yale has also instituted a practice that, if a patient tests positive for COVID19, Yale wants 24 hours between the next patient visit to limit spread and decontaminate.
Marianne Davies: Blood work is now being done at satellite sites to limit number of in person visits to Yale. Usually they did biopsies to determine resistance to therapy but now relying on liquid biopsies (if insurance isn’t covering it they are working with patient to assist). For mesothelioma they are dropping chemotherapy that is very immunosuppressive and going with maintenance pembrolizumab (Keytruda). It is challenging in that COPD mimics the symptoms of COVID and patients are finding it difficult to get nebulizers at the pharmacy because of shortages; these patients that develop COPD are also worried they will not get the respirators they need because of rationing.
Dr. Barbara Burtness: Head and neck cancer. Dr. Burtness stresses to patients that the survival rate now for HPV positive head and neck is much better and leaves patients with extra information on their individual cancers. She also noted a registry or database that is being formed to track data on COVID in patients undergoing surgery and can be found here at https://globalsurg.org/covidsurg/
About CovidSurg
There is an urgent need to understand the outcomes of COVID-19 infected patients who undergo surgery.
Capturing real-world data and sharing international experience will inform the management of this complex group of patients who undergo surgery throughout the COVID-19 pandemic, improving their clinical care.
CovidSurg has been designed by an international collaborating group of surgeons and anesthetists, with representation from Canada, China, Germany, Hong Kong, Italy, Korea, Singapore, Spain, United Kingdom, and the United States.
Dr. Burtness had noted that healthcare care workers are at high risk of COVID exposure during ear nose and throat (ENT) procedures as the coronavirus resides in the upper respiratory tract. As for therapy for head and neck cancers, they are staying away from high dose cisplatin because of the nephrotoxicity seen with high dose cisplatin. An alternative is carboplatin which generally you do not see nephrotoxicity as an adverse event (a weekly carboplatin). Changing or increasing dose schedule (like 6 weeks Keytruda) helps reduce immunologic problems related to immunosupression and patients do not have to come in as often.
Italy and France
Dr. Paolo Ascierto: with braf inhibitors, using in tablet form so patients can take from home. Also they are moving chemo schedules for inpatients so longer dosing schedules. Fever still a side effect from braf inhibitors and they require a swab to be performed to ascertain patient is COVID19 negative. Also seeing pneumonitis as this is an adverse event from checkpoint inhibitors so looking at CT scans and nasal swab to determine if just side effect of I/O drugs or a COVID19 case. He mentioned that their area is now doing okay with resources.
Dr. Guiseppe Curigliano mentioned about the redesign of the Italian health system with spokes and hubs of health care. Spokes are generalized medicine while the hubs represent more specialized centers like CV hubs or cancer hubs. So for instance, if a melanoma patient in a spoke area with COVID cases they will be referred to a hub. He says they are doing better in his area
In the question and answer period, Dr. West mentioned that they are relaxing many HIPAA regulations concerning telemedicine. There is a website on the Centers for Connective Health Policy that shows state by state policy on conducting telemedicine. On immuno oncology therapy, many in the panel had many questions concerning the long term risk to COVID associated with this type of therapy. Fabrice mentioned they try to postpone use of I/O and although Dr. Kluger said there was an idea floating around that PD1/PDL1 inhibitors could be used as a prophylactic agent more data was needed.
Please revisit this page as the recording of this Town Hall will be made available next week.
UPDATED 4/08/2020
Below find theLIVE RECORDING and TAKEAWAYSby the speakers
Town Hall Takeaways
Utilize Telehealth to Its Fullest Benefit
· Patients doing well on targeted therapy or routine surveillance are well suited to telemedicine
· Most patients are amenable to this, as it is more convenient for them and minimizes their exposure
· A patient can speak to multiple specialists with an ease that was not previously possible
· CMS has relaxed some rules to accommodate telehealth, though private insurers have not moved as quickly, and the Center for Connected Health Policy maintains a repository of current state-by-state regulations: https://www.cchpca.org/
Practice Management Strategies
· In the face of PPE shortages, N95 masks can be decontaminated using UV light, hydrogen peroxide, or autoclaving with dry heat; the masks can be returned to the original user until the masks are no longer suitable for use
· For blood work or scans, the use of external satellite facilities should be explored
· Keep pumps outside of the room so nurses can attend to them quickly
· Limit the use of nebulizers, CPAPs, and BiPAPs due to risk of aerosolization
· Caution is urged in the presence of cardiac complications, as ventilated patients may appear to improve, only to suffer severe myocarditis and cardiac arrest following extubation
· When the decision is made to intubate, intubate quickly, as less invasive methods result in aerosolization and increased risks to staff
Study the Lessons of Europe
· The health care system in Italy has been reorganized into “spokes” and “hubs,” with a number of cancer hubs; if there is a cancer patient in a spoke hospital with many COVID patients, this patient may be referred to a hub hospital
· Postpone adjuvant treatments whenever possible
· Oral therapies, which can be managed at home, are preferred over therapies that must be administered in a healthcare setting
· Pneumonitis patients without fevers may be treated with steroids, but nasal swab testing is needed in the presence of concomitant fever
· Any staff who are not needed on site should be working from home, and rotating schedules can be used to keep people healthy
· Devise an annual epidemic control plan now that we have new lessons from COVID
We Must Be Advocates for Our Cancer Patients
· Be proactive with other healthcare providers on behalf of patients with a good prognosis
· Consider writing letters for cancer patients for inclusion into their chart, or addendums on notes, then encourage patients to print these out, or give it to them during their visit
· The potential exists for a patient to be physiologically stable on a ventilator, but intolerant of decannulation; early discussions are necessary to determine reasonable expectations of care
· Be sure to anticipate a second wave of patients, comprised of cancer patients for whom treatments and surgery have been delayed!
Tumor-Specific Learnings
Ø Strategies in Breast Cancer:
· In patients with early-stage disease, promote the use of neoadjuvant therapy where possible to delay the need for surgery
· For patients with metastatic disease in the palliative setting, transition to less frequent chemotherapy dosing if possible
· While growth factors may pose a risk in interstitial lung disease, new guidelines are emerging
· The use of BRAF/MEK inhibitors can cause fevers that are drug-related, and access to an alternate clinic where patients can be assessed is a useful resource
Ø Strategies in Lung Cancer:
· For patients who are stable on an oral, targeted therapy, telehealth check-in is a good option
· For patients who progress on targeted therapies, increased use of liquid biopsies when appropriate can minimize use of bronchoscopy suites and other resources
· For patients on pembrolizumab monotherapy, consider switching to a six-week dosing of 400 mg
· Many lung cancer patients worry about “discrimination” should they develop a COVID infection; it is important to support patients and help manage expectations and concerns
UPDATED 5/11/2020
Townhall on COVID-19 and Cancer Care with Leading Oncologists Series 4
Addressing the Challenges of Cancer Care in the Community
The second virtual Town Hall with Leading International Oncologist, discussing the impact that the worldwide COVID-19 outbreak has on cancer care and patient care issues will be held this Saturday April 4, 2020. This Town Hall Series is led by Dr. Roy Herbst and Dr. Hossein Borghaei who will present a panel of experts to discuss issues pertaining to oncology practice as well as addressing physicians and patients concerns surrounding the risk COVID-19 presents to cancer care. Some speakers on the panel represent oncologist from France and Italy, and will give their views of the situation in these countries.
This series is being hosted in partnership with Axiom Healthcare Strategies, Inc..
The Town Hall proceedings and live notes will be made available on this site and Live Notes will be Tweeted in Real Time using the #CancerCareandCOVID19 and @pharma_BI
The goal of these town halls is to improve outcomes of cancer patients across the globe, by sharing insights and lessons learned from oncologists fighting COVID-19. Dr. Roy Herbst and Dr. Hossein Borghaei will be joined by a panel of thought leaders with expertise in a variety of solid tumors to discuss how COVID-19 has impacted patient care in oncology.
Following the session, a video, transcript, and key takeaways will be released on Monday 4/6.
Time
For Live Notes From the Last Town Hall Meeting Specifically on Lung Cancer and COVID19 please go to
Responses to the #COVID-19 outbreak from Oncologists, Cancer Societies and the NCI: Important information for cancer patients
Curator: Stephen J. Williams, Ph.D.
UPDATED 3/20/2020
Among the people who are identified at risk of coronovirus 2019 infection and complications of the virus include cancer patients undergoing chemotherapy, who in general, can be immunosuppressed, especially while patients are undergoing their treatment. This has created anxiety among many cancer patients as well as their care givers and prompted many oncologist professional groups, cancer societies, and cancer centers to formulate some sort of guidelines for both the cancer patients and the oncology professional with respect to limiting the risk of infection to coronavirus (COVID19).
This information will be periodically updated and we are working to get a Live Twitter Feed to bring oncologist and cancer patient advocacy groups together so up to date information can be communicated rapidly. Please see this page regularly for updates as new information is curated.
IN ADDITION, I will curate a listing of drugs with adverse events of immunosuppression for people who might wonder if the medications they are taking are raising their risk of infections.
From the Cancer Letter:The following is a guest editorial by American Society of Clinical Oncology (ASCO) Executive Vice President and Chief Medical Officer Richard L. Schilsky MD, FACP, FSCT, FASCO. This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.
The worldwide spread of the coronavirus (COVID-19) presents unprecedented challenges to the cancer care delivery system.
Our patients are already dealing with a life-threatening illness and are particularly vulnerable to this viral infection, which can be even more deadly for them.Further, as restrictions in daily movement and social distancing take hold, vulnerable patients may be disconnected from friends, family or other support they need as they manage their cancer.
As providers, we rely on evidence and experience when treating patients but now we face uncertainty. There are limited data to guide us in the specific management of cancer patients confronting COVID-19 and, at present, we have no population-level guidance regarding acceptable or appropriate adjustments of treatment and practice operations that both ensure the best outcome for our patients and protect the safety of our colleagues and staff.
As normal life is dramatically changed, we are all feeling anxious about the extreme economic challenges we face, but these issues are perhaps even more difficult for our patients, many of whom are now facing interruption
As we confront this extraordinary situation, the health and safety of members, staff, and individuals with cancer—in fact, the entire cancer community—is ASCO’s highest priority.
ASCO has been actively monitoring and responding to the pandemic to ensure that accurate information is readily available to clinicians and their patients. Recognizing that this is a rapidly evolving situation and that limited oncology-specific, evidence-based information is available, we are committed to sharing what is known and acknowledging what is unknown so that the most informed decisions can be made.
To help guide oncology professionals as they deal with the impact of coronavirus on both their patients and staff, ASCO has collated questions from its members, postedresponses at asco.organd assembled a compendium of additional resources we hope will be helpful as the virus spreads and the disease unfolds. We continue to receive additional questions regarding clinical care and we are updating our FAQs on a regular basis.
We hope this information is helpful even when it merely confirms that there are no certain answers to many questions. Our answers are based on the best available information we identify in the literature, guidance from public health authorities, and input received from oncology and infectious disease experts.
For patients, we have posted a blog byDr. Merry Jennifer Markham, chair of ASCO’s Cancer Communications Committee. This can be found onCancer.Net, ASCO’s patient information website, and it provides practical guidance to help patients reduce their risk of exposure, better understand COVID-19 symptoms, and locate additional information.
This blog is available both in English and Spanish. Additional blog posts addressing patient questions will be posted as new questions are received and new information becomes available.
Find below a Tweet from Dr.Markham which includes links to her article on COVID-19 for cancer patients
JNCCN: How to Manage Cancer Care during COVID-19 Pandemic
Experts from the Seattle Cancer Care Alliance (SCCA)—a Member Institution of the National Comprehensive Cancer Network® (NCCN®)—are sharing insights and advice on how to continue providing optimal cancer care during the novel coronavirus (COVID-19) pandemic. SCCA includes the Fred Hutchinson Cancer Research Center and the University of Washington, which are located in the epicenter of the COVID-19 outbreak in the United States. The peer-reviewed article sharing best practices is available for free online-ahead-of-print via open access at JNCCN.org.
Coronavirus disease 2019 (COVID-19) Resources for the Cancer Care Community
NCCN recognizes the rapidly changing medical information relating to COVID-19 in the oncology ecosystem, but understands that a forum for sharing best practices and specific institutional responses may be helpful to others. Therefore, we are expeditiously providing documents and recommendations developed by NCCN Member Institutions or Guideline Panels as resources for oncology care providers. These resources have not been developed or reviewed by the standard NCCN processes, and are provided for information purposes only. We will post more resources as they become available so check back for additional updates.
Both the resources at cancer.gov (NCI) as well as the resources from ASCO are updated as new information is evaluated and more guidelines are formulated by members of the oncologist and cancer care community and are excellent resources for those living with cancer, and also those who either care for cancer patients or their family and relatives.
Related Resources for Patients (please click on links)
@DrMarkham Dr. Markham is Chief of Heme-Onc & gyn med onc@UF | AD Med Affairs@UFHealthCancerand has collected very good information for patients concerning #Covid19
Cancer patients on chemotherapy concerned about traveling for treatment during the #COVID19 crisis may have another option. Find out about the pros and cons of taking an oral medication. https://t.co/4djwfji5WR#CTCABlog
— Cancer Treatment Centers of America (CTCA) (@CancerCenter) March 19, 2020
UPDATED 3/20/2020 INFORMATION FROM NCI DESIGNATED CANCER CENTERS FOR PATIENTS/PROVIDERS
The following is a listing with links of NCI Designated Comprehensive Cancer Centers and some select designated Cancer Centers* which have information on infectious risk guidance for cancer patients as well as their physicians and caregivers. There are 51 NCI Comprehensive Cancer Centers and as more cancer centers formulate guidance this list will be updated.
The webinar started with a brief introduction of attendees , most who are breast cancer survivors. Survivingbreastcancer.org is an organization committed to supplying women affected with breast cancer up to date information, including podcasts, webinars, and information for treatment, care, and finding support and support groups.
Some of the comments of survivors:
being strong
making sure to not feel overwhelmed on initial diagnosis
get good information
sometimes patients have to know to ask for genetic testing as physicians may not offer it
Laura Carfang discussed her study results presented at a bioethics conference in Clearwater, FL on issues driving breast cancer patient’s as well as at-risk women’s decision making process for genetic testing. The study was a phenomenological study in order to determine, through personal lived experiences, what are pivotal choices to make genetic testing decisions in order to improve clinical practice.
The research involved in depth interviews with 6 breast cancer patients (all women) who had undergone breast cancer genetic testing.
Main themes coming from the interviews
information informing decisions before diagnosis: they did not have an in depth knowledge of cancer or genetics or their inherent risk before the diagnosis.
these are my genes and I should own it: another common theme among women who were just diagnosed and contemplating whether or not to have genetic testing
information contributing to decision making after diagnosis: women wanted the option, and they wanted to know if they carry certain genetic mutations and how it would guide their own personal decision to choose the therapy they are most comfortable with and gives them the best chance to treat their cancer (the decision and choice is very personal)
communicating to family members and children was difficult for the individual affected; women found that there were so many ramifications about talking with family members (how do I tell children, do family members really empathize with what I am going through). Once women were tested they felt a great strain because they now were more concerned with who in their family (daughters) were at risk versus when they first get the diagnosis the bigger concern was obtaining information.
Decision making to undergo genetic testing not always linear but a nonlinear process where women went from wanting to get tested for the information to not wanting to get tested for reasons surrounding negative concerns surrounding knowing results (discrimination based on results, fear of telling family members)
Complex decision making involves a shift or alteration in emotion
The Mayo Clinic has come out with full support of genetic testing and offer to any patient.
Additional resources discussed was a book by Leslie Ferris Yerger “Probably Benign” which discusses misdiagnoses especially when a test comes back as “probably benign” and how she found it was not.
There is a good reference to read on The Hallmarks of Cancer published first in 2000 and then updated with 2 new hallmarks in 2011 (namely the ability of cancer cells to reprogram their metabolism and 2. the ability of cancer cells to evade the immune system)
Please also go to other articles on this site which are relevant to this lecture. You can use the search box in the upper right hand corner of the Home Page or these are few links you might find interesting
Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Considerable differences exist in the prevalence and manifestation of atherosclerotic cardiovascular disease (CVD) and heart failure (HF) between men and women. Premenopausal women have a lower risk of CVD and HF compared with men; however, this risk increases after menopause. Sex hormones, particularly androgens, are associated with CVD risk factors and events and have been postulated to mediate the observed sex differences in CVD.
B-type natriuretic peptides (BNPs) are secreted from cardiomyocytes in response to myocardial wall stress. BNP plays an important role in cardiovascular remodelling and volume homeostasis. It exerts numerous cardioprotective effects by promoting vasodilation, natriuresis, and ventricular relaxation and by antagonizing fibrosis and the effects of the renin-angiotensin-aldosterone system. Although the physiological role of BNP is cardioprotective, pathologically elevated N-terminal pro–BNP (NT-proBNP) levels are used clinically to indicate left ventricular hypertrophy, dysfunction, and myocardial ischemia. Higher NT-proBNP levels among individuals free of clinical CVD are associated with an increased risk of incident CVD, HF, and cardiovascular mortality.
BNP and NT-proBNP levels are higher in women than men in the general population. Several studies have proposed the use of sex- and age-specific reference ranges for BNP and NT-proBNP levels, in which reference limits are higher for women and older individuals. The etiology behind this sex difference has not been fully elucidated, but prior studies have demonstrated an association between sex hormones and NT-proBNP levels. Recent studies measuring endogenous sex hormones have suggested that androgens may play a larger role in BNP regulation by inhibiting its production.
Data were collected from a large, multiethnic community-based cohort of individuals free of CVD and HF at baseline to analyze both the cross-sectional and longitudinal associations between sex hormones [total testosterone (T), bioavailable T, freeT, dehydroepiandrosterone (DHEA), SHBG, and estradiol] and NT-proBNP, separately for women and men. It was found that a more androgenic pattern of sex hormones was independently associated with lower NT-proBNP levels in cross-sectional analyses in men and postmenopausal women.
This association may help explain sex differences in the distribution of NT-proBNP and may contribute to the NP deficiency in men relative to women. In longitudinal analyses, a more androgenic pattern of sex hormones was associated with a greater increase in NT-proBNP levels in both sexes, with a more robust association among women. This relationship may reflect a mechanism for the increased risk of CVD and HF seen in women after menopause.
Additional research is needed to further explore whether longitudinal changes in NT-proBNP levels seen in our study are correlated with longitudinal changes in sex hormones. The impact of menopause on changes in NT-proBNP levels over time should also be explored. Furthermore, future studies should aim to determine whether sex hormones directly play a role in biological pathways of BNP synthesis and clearance in a causal fashion. Lastly, the dual role of NTproBNP as both
a cardioprotective hormone and
a biomarker of CVD and HF, as well as
the role of sex hormones in delineating these processes,
should be further explored. This would provide a step toward improved clinical CVD risk stratification and prognostication based on
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