ABSTRACT
Several medicines were approved as first treatments, including Gilead Sciences' Veklury (remdesivir) for patients with COVID-19 who require hospitalization (4);Amivas' artesunate for injection for severe malaria (5);Horizon Therapeutics Ireland DAC's Tepezza (teprotumumab-trbw), an antibody drug conjugate (ADC) for treating thyroid eye disease (6);and Ultragenyx Pharmaceutical's Dojolvi (triheptanoin) and Alnylam Pharmaceuticals' Oxlumo (lumasiran), both first treatments for metabolic disorders-Dojolvi for treating paediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (7) and Oxlumo (lumasiran) for treating the rare genetic disorder, primary hyperoxaluria type 1 (8). Blueprint Medicines Corporation) for treating unresectable or metastatic gastrointestinal stromal tumours harboring a platelet-derived growth factor receptor alpha exon 18 mutation (9);Koselugo (selumetinib, AstraZeneca Pharmaceuticals), for neurofibromatosis type 1 (10);Pemazyre (pemigatinib, Incyte Corporation), for certain types of previously treated, advanced bile duct cancer (cholangiocarcinoma) (11);Tabrecta (capmatinib, Novartis) for non-small cell lung cancer that has spread to other parts of the body and whose tumours have mutations that lead to MET exon 14 skipping (12);and Retevmo (selpercatinib, Loxo Oncology, a subsidiary of Eli Lilly and Company) for treating three types of tumours with alterations of the "rearranged during transfection" gene (13). Gilead, "U.S. FDA Approves Kite's Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma," Press Release, 24 July 2020.
ABSTRACT
Today, cancer patients continue to push for their necessary screenings, advocate for surgeries and, for many of them, independently drive their own care while risking their health in an already overwhelmed medical system. [...]patients have lost their jobs and health insurance, compounding the immense stress and anxiety of everyday life. Simultaneously, COVID has negatively impacted clinical trials, which can be more effective at treating cancer patients with advanced therapies compared to the standard of care. Because the pandemic has exposed, and exacerbated, many long-standing issues that patients have dealt with for years that directly impact biopharma.
ABSTRACT
Background: Anticipating the correlation between SARS-CoV-2 infection and ‘triplenegative breast cancer (TNBC)' remains challenging. It has been reported that people currently diagnosed with cancer have a higher risk of severe complications if they are affected by the viral infection. Cancer treatments, including chemotherapy, targeted therapies, and immunotherapy, may weaken the immune system and possibly cause critical lung damage and breathing problems. Special attention must be paid to the ‘comorbidity condition' while estimating the risk of severe SARSCoV- 2 infection in TNBC patients. Hence the work aims to study the correlation between triplenegative breast cancer (TNBC) and SARS-CoV-2 using biomolecular networking.Methods: The genes associated with SARS CoV-2 have been collected from curated data in Bio- GRID. TNBC-related genes have been collected from expression profiles. Molecular networking has generated a Protein-Protein Interaction (PPI) network and a Protein-Drug Interaction (PDI) network. The network results were further evaluated through molecular docking studies followed by molecular dynamic simulation.Results: The genetic correlation of TNBC and SARS-Cov-2 has been observed from the combined PPI of their proteins. The drugs interacting with the disease's closely associated genes have been identified. The docking and simulation study showed that anti-TNBC and anti-viral drugs interact with these associated targets, suggesting their influence in inhibiting both the disease mutations.Conclusion: The study suggests a slight influence of SARS-CoV-2 viral infection on Triple Negative Breast Cancer. Few anticancer drugs such as Lapatinib, Docetaxel and Paclitaxel are found to inhibit both TNBC and viral mutations. The computational studies suggest these molecules are also useful for TNBC patients to control SARS-CoV-2 infection.
ABSTRACT
During this process, type II transmembrane serine protease (TMPRSS2) expression seems to be important as a coadjuvant protein to assist SARS-CoV-2 in cell invasion.3,4 Patients who progress to the severe form of the disease have an inflammatory response that leads to a reduction of the expression of cytotoxic CD8+ and CD4+ T lymphocytes. (IFN-.), as well as others, increase.2,4,5 In this context, as with other viral infections, increased expression of regulatory molecules of inflammatory response, like PD-1 and PD-L1, occurs.2, 4-6 COVID19 and Cancer The morbidity and mortality of COVID-19 is higher in elderly and male patients, as well as in those with comorbidities. [...]only observational studies have raised the possibility of the protective effect of IMT, and further data are required to confirm this hypothesis and use it to guide the management of patients with cancer. In the case of SARS-CoV-2 infection in patients receiving IMT, the risk of cytokine release syndrome is high. [...]the second quandary oncologists face is the challenge to correctly diagnosis SARS-CoV-2 infection or IMT-induced pneumonitis.4,6,11 Another important consideration is controlling immune-related AEs in patients who need long-term immunosuppression therapy.
ABSTRACT
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly escalated to a pandemic with significant morbidity and mortality resulting from the associated coronavirus disease 2019 (COVID-19).1 Approximately one-third of patients developing COVID-19 experienced severe complications, including acute respiratory distress syndrome, acute renal failure, acute respiratory injury, septic shock, and severe pneumonia.2 Populations particularly vulnerable to COVID-19 include older adults and immunosuppressed patients. [...]when we looked at some of the early data about which patients are going to have increased mortality from COVID-19, it was those individuals who had cardiovascular disease or diabetes. [...]we have pulled together as an oncology community to determine the safety measures that we can put in place to ensure that someone who may potentially have a cancer diagnosis, or maybe they need a diagnostic image because they felt a lump in their breast or had symptoms related to colorectal cancer, we know cancer doesn't stop because of COVID-19. Regarding chemotherapies and those that reduce the immune system, people will say that any cancer treatment can impact the immune system, and they're right. When it comes to systemic therapies, in addition to those that actually reduce your blood counts and have impact on marrow or impact marrow suppression, there are also data to suggest that immune checkpoint inhibitors like the PD-L1 and the PD-1 Inhibitors may be associated with worse outcomes and may actually be associated with increased morbidity and mortality, although it's fascinating because there was another study seemed to contradict these results.9,10 But all the data that we have suggest that patients getting new checkpoint inhibitors as part of their care may be at increased risk.
ABSTRACT
[...]because of the pandemic, many centers are experiencing staffing shortages in their clinical trial offices, leading to longer times for opening trials and, in some cases, halting new enrollments. Tixagevimab in combination with cilgavimab (Evusheld) is a new SARS-CoV-2 spike protein-directed attachment inhibitor that has gained emergency use authorization for individuals who are moderately to severely immunocompromised because of immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination. Clinical trials of this monoclonal antibody combination showed a reduction in symptomatic SARS-CoV-2 illness as well as severe illness or death in the treatment arm.
ABSTRACT
This work studied the antioxidant and anti-breast cancer properties of hyaluronidase, extracted from a potential marine strain, Staphylococcus aureus (CASMTK1), isolated from Parangipettai coastal waters in southeast coast of India. The Staphylococcal enzyme production was tested under different carbon and nitrogen sources;and recorded the maximum production when the microbial strain was cultured with starch as the carbon source and ammonium sulphate as the inorganic nitrogen source with the enzyme production of 92.5 U/mL and 95.0 U/mL, respectively. The hyaluronidase enzyme production was also tested in different pH and temperature;and recorded the maximum yield of 102.5 U/mL in pH 5 and that of 95.5 U/mL in 45 °C. The partially purified enzyme was subjected to FTIR and FT Raman technique and found the presence of the amide- I and II, Carboxyl, N-H bending, C-H stretching and α-helices and β-sheet proteins between wave number 1500–1700 cm−1. The partially purified enzyme also exhibited strong antioxidant and in-vitro breast cancer properties. The enzyme showed the highest hydroxyl radical scavenging activity of 79% at the 50 µg/mL concentration, and this activity increased in a dose-dependent manner. The enzyme inhibited proliferation of the breast cancer cell line of MCF-7, and it caused 100% cell death at the concentration of 80 µg/mL. The enzyme generated capacity of producing free radicles that damage the cancer cells, and this effect was very nearer to the standard drug, paclitaxel. The enzyme damaged the cancer cells and induced apoptosis in 78% of cancer cells as evident by condensed or fragmented chromatin at 40 µg/mL. Further purification of the enzyme, analysis of its molecular aspects, and elucidation of exact mechanisms of its biological activities will throw new light on the utility of staphylococcal hyaluronidase in anticancer chemotherapy.
ABSTRACT
Researchers compared organ preservation rates - defined as alive, total mesorectal excision-free and having no evidence of disease in the pelvis - among 332 patients with rectal cancer (median age, 57 years;62.1% men) who underwent short-course (n = 76) vs. long-course (n = 256) chemoradiation total neoadjuvant therapy. Patient and tumor characteristics appeared similar between the groups, with no significant differences in high-risk features, and most patients (81.6%) had clinical stage III disease. Results showed 2-year OS rates of 95% with long-course vs. 92% with short-course chemoradiation, DFS rates of 78% vs. 70%, and distant recurrence rates of 20% vs. 21%. [...]researchers observed a 2-year organ preservation rate of 40% (95% CI, 35-47) with long-course vs. 29% (95% CI, 20-42) with short-course chemoradiation and, among those managed with a watch-and-wait approach, 88% (95% CI, 81-94) with long-course and 67% (95% CI, 51-87) with short-course chemoradiation.
ABSTRACT
Methods Patient Cohort Under a protocol approved by the University Hospitals Seidman Cancer Center Institutional Review Board, a search of all appointment data from patients with cancer in the in the Seidman Cancer Center was performed. For each of the 4 groups of appointment types, rates of cancellation (cancellation count divided by appointment count) were stratified by age group (0-39 years, 40-64 years, 65 years or older),10 sex (male or female), and race (White, Black, or other) on a monthly basis. Descriptive statistics were used to assess any association of cancellation rate between 2019 and 2020 for both overall data, and stratified by age group, sex, and race for each appointment type respectively, where the ÷2 test of independence was used for comparison. The trend comparison of appointment rates was also examined by trend plot both for overall data and stratified by age group, sex, and race for each appointment type respectively.
ABSTRACT
Patients with cancer who contracted COVID-19 had high risk for inpatient hospital admission and death, according to study results. "COVID-19 in patients with solid tumors and hematologic malignancies undergoing active therapy is associated with poor outcomes, including a high risk [for] inpatient mortality," Alok A. Khorana, MD, professor of medicine at Cleveland Clinic Lerner College of Medicine, told HemOnc Today. The Leukemia b Lymphoma Society encourages all patients with blood cancer to get vaccinated because the side-effect profile of vaccination is no different for them than the general population.
ABSTRACT
[...]we highlight ongoing investigational treatment approaches that are so relevant to the care of oncology patients during this extraordinary pandemic. While many therapeutic strategies are currently being evaluated as possible COVID-19 treatments, there are currently no highly effective antiviral therapies or vaccines available to combat this virus, and mortality in severe disease remains high.6 Risk factors for severe illness resulting from COVID-19 are age greater than 65 years, diabetes, chronic lung disease, and obesity,7 and cancer patients who contract COVID-19, in particular, have been shown to have worse outcomes.8 In the initial experience reported from Wuhan, China, 1% of cancer patients were noted to contract COVID-19, compared with just 0.29% incidence in the general population.8 This may be attributed to greater detection rates in more closely surveilled cancer patients, but it could also be associated with nosocomial exposures and diminished im mune defenses.8 Cancer patients were also observed to be at higher risk for the development of severe COVID-19, which may be due to generally advanced age, increased prevalence of tobacco use, and higher incidence of comorbid pulmonary disease.9 Liang et al also demonstrated that cancer patients were more likely to require intensive care or experience mortality as compared with other COVID-19 patients (39% vs 8%).9 Cancer treatment may also increase COVID-19 susceptibility. Lin et al recommend LMWH at 100 U/kg every 12 hours for at least 3 to 5 days.8 In addition, a study performed in Tongji Hospital in Wuhan reviewed 449 patients with severe COVID-19, with 94 patients receiving LMWH (40-60 mg/day) and 5 receiving unfractionated heparin (1000-15,000 U/day) for 7 days or longer;the results showed that the 28-day mortality for LMWH or unfractionated heparin users with a sepsis-induced coagulopathy score of ≥4 and D-dimers >6 times the upper limit of normal was lower than that of non-LMWH or unfractionated heparin users.14 This has led several institutions, including our own, to institute anticoagulation protocols based on various parameters such as D-dimer levels.17 Pathophysiology of COVID-19 Coronaviruses are large, single-stranded, positive-sense RNA strand that encapsulate within a membrane envelope surrounded by glycoprotein spikes, forming a crown-like appearance.18 Less-pathogenic endemic human coronaviruses such as OC43, HKU1, NL63, and 229E exist, causing seasonally, self-limited upper respiratory symptoms.19 In contrast, more severe respiratory symptoms are caused by zoonotic human coronaviruses, including severe acute respiratory distress syndrome coronavirus (SARSCoV) discovered in November 2002 in Guangdong, China;Middle Eastern respiratory syndrome-related coronavirus (MERS-CoV) identified in 2012 in Saudi Arabia;and COVID-19.18 The subfamily, Coronavirinae, is divided into 4 classes of coronaviruses: α, β, δ, and γ. ACE2 has been shown to promote anti-inflammatory and antifibrotic effects, and it protects these cells from ARDS.19 In SARS-CoV-2, ACE2 ectodomain can shed as a result of spikes from the viral glycoprotein, reducing the catalytic function of ACE2 and promoting ARDS.19 In addition, SARS-CoV-2 has been shown to reduce synthesis of interferon-α and interferon-β and to increase inflammatory cytokines and chemokines.20 In lung adenocarcinomas, ACE2 gene expression
ABSTRACT
Objective: To determine the frequency of hand-foot syndrome and associated factors among patients receiving Capecitabine for the management of cancer in a tertiary care setting. Study Design: Cross-sectional study. Place and Duration of Study: Oncology Department Combined Military Hospital, Rawalpindi Pakistan from Dec 2020 to May 2021. Methodology: One hundred patients with malignant conditions taking Capecitabine for more than two weeks were included in the study. A detailed relevant dermatological examination was carried out on all the patients to diagno se hand-foot syndrome based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Grading of Hand-Foot Syndrome. Results: Out of 100 cancer patients using Capecitabine for more than two weeks included in the study. Sixty-eight showed the presence of hand-foot syndrome, while 32 did not show any features of hand-foot syndrome. Combination treatment was statistically significantly associated with hand-foot syndrome among the patients included in our study (p-value<0.001). Conclusion: Hand-foot syndrome was a common side effect seen in patients managed with Capecitabine for their cancerous condition. Patients using other chemotherapeutic agents along with Capecitabine were more at risk of having hand-foot syndrome than those taking Capecitabine alone.
ABSTRACT
Distinguished Professor of Medicine, Rutgers Robert Wood Johnson Medical School Associate Director for Clinical Research, Rutgers Cancer Institute of New Jersey Director of Oncology Research, RWJBarnabas Health In this issue of ONCOLOGYR, investigators who were led by John Nakayama, MD, from the Seidman Cancer Center at Case Western Reserve University in Cleveland, have provided a very large sample of patients with cancer and compared cancellation rates of oncology appointments in 2020 and 2019. The authors report on the clinical, lab, radiation, and surgery appointments for these time periods and compare the cancellation rates in the control year versus the experience year presumably by reviewing all their electronic medical record data. [...]some patients may have switched to more local practices.
ABSTRACT
[...]linking government reimbursement rates to private-sector prices causes firms to raise prices for nongovernment payers in order to extract larger sums from Medicare and Medicaid. The first is market exclusivity: the combination of patent rights and other statutory mechanisms that allow firms to block competitors for a fixed period.10 The second-largely overlooked by legal scholarship until recently11-is federally subsidized health insurance: principally Medicare, Medicaid, Veterans Health Administration coverage, and subsidized health insurance plans provided through Affordable Care Act (ACA) marketplaces. Vaccines generate large positive externalities by providing herd immunity, but in a market-based system, vaccine manufacturers can typically charge only the patients who receive their vaccines, not the other members of the population who benefit from herd immunity.18 Moreover, the benefits of risk-reducing products such as vaccines often vary from person to person, but vaccine manufacturers generally can't tailor their prices to individual risk.19 So although vaccines are hugely valuable to society, our market-exclusivity-based reward structure allows vaccine makers to capture only a tiny sliver of their products' social value-with the consequence that firms invest less in vaccines than in other drugs that yield larger profits but smaller social benefits. Cancer prevention provides another vivid illustration of the failures of the U.S. drug pricing system. Since the 1970s, drugs designed to prevent cancer have accounted for only around 196 of all cancer-drug clinical trials, and drugs designed to treat cancer before it spreads to surrounding tissues have accounted for an even smaller share.20 One likely source of this skew is the shorter period of effective market exclusivity for preventives and early-stage treatments.
ABSTRACT
Important to the success of this model would likely be the degree of clinician experience (ie, how comprehensive their genetic counseling training has been), the clinician's comfort level, and the supporting staff or resources available to the clinician to operate a provider-led germline testing model.4 Members of a consensus panel discussing germline testing have pointed out that clinicians who lack genetics training may experience numerous obstacles when counseling patients, in particular obstacles related to limited knowledge of the downstream impact of genetic testing, such as health insurance coverage, implications for life insurance, and protections afforded by the Genetic Information Nondiscrimination Act.5 Discussions about the importance and management of variants of unknown significance could be confusing for the patient even in the posttesting stage without appropriate knowledge and training on the clinician's part. Mauer et al have described the value of virtual counseling and technological adaptations, including billing practices and coordination of education and outreach opportunities, that have been made during the pandemic and have helped genetic counselors.6 Such adaptations represent only a few of the evolving strategies that we as medical oncologists, in conjunction with our health care team, must seek out and implement to help our genetic counseling colleagues reach an expanding population of prostate cancer patients in need of evidence-based germline testing. Inherited DNA-repair gene mutations in men with metastatic prostate cancer.
ABSTRACT
Efficacy and safety of ginger on the side effects of chemotherapy in breast cancer patients: systematic review and meta-analysis. Based on these studies, the authors undertook a systemic review and meta-analysis to assess the efficacy and safety of using ginger in the symptomatic management of chemotherapy side effects in breast cancer patients. [...]more large, highquality RCTs using uniform methodology are required to evaluate ginger's safety and efficacy in this population. [...]the current study assessed the potential of E. purpurea in preventing and treating respiratory tract infections (RTIs) in people with respiratory viral infections, including SARS-CoV-2.
ABSTRACT
Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.
ABSTRACT
Coordination of Care Since the COVID-19 pandemic unfolded, strains on the healthcare system have been widespread and pervasive (Kumar & Dey, 2020). At times, this crisis has put the oncology patient in a particularly unique position. As oncology care is a time-sensitive endeavor, treatment delays are critical to mitigate against and understand (Du et al., 2022). Delays or interruptions in cancer treatment can lead to progressive symptoms and worsened survival (Kumar & Dey, 2020). In addition, psychological implications for cancer patients are prominent (Dermody & Shuman, 2022). In the beginning of the pandemic, oncology patients who tested positive for COVID-19 were admitted to a respiratory isolation area in the hospital system not specialized in oncology, to provide physical separation from other vulnerable oncology patients in the cancer hospital. As a result, specialized oncologic treatments were not always available, which caused potential delays in necessary interventions. The aim of this project was to create a safe space for oncology patients, with an active COVID-19 infection, who additionally required timely oncologic treatments requiring an inpatient admission (acute leukemia, CAR T-cell administration, stem cell transplant, surgical intervention). The cancer hospital designed a 9-bed HEPA-filtrated area, with five rooms capable of being converted into ICU rooms for critically-ill patients. This area was termed the "Respiratory Isolation Flex Unit (RIFU)." Nursing leadership developed guidelines and policies around its appropriate use to ensure patient safety. Not only was a physical space required to allow for these types of admissions, but appropriate nursing specialty was vital as well. Institutional processes were developed to allow for nursing staff who were specialty trained in chemotherapy, critical care, stem cell transplant, etc. to be available for these patients. Cancer patients with a positive COVID-19 test upon admission were appropriately assigned to the RIFU and able to receive timely treatment, education, and monitoring with specialty trained nursing staff. Nursing staff had positive experiences caring for this unique patient population and collaborated to ensure a consistent "patient first" mentality. These innovative solutions allowed the cancer hospital to rise to the occasion and provide essential oncology treatments during these unprecedented times to patients with active COVID-19 infections. By preventing delays in important treatments and allowing for continued specialized care, we strived to positively impact outcomes and patient experiences.
ABSTRACT
Patients with head and neck cancer (HNC) experience severe symptoms and associated functional limitations during the cancer treatment. The NYU Electronic Patient Visit Assessment (ePVA) was developed for early detection and interventions for uncontrolled symptoms in HNC. This randomized, non-blinded, phase 0/I study assessed the feasibility of conducting a large randomized clinical trial to evaluate the efficacy of the ePVA to improve pain management and Health-Related Quality of Life in patients with HNC. Methods: The study was conducted at an NCI -Designated Comprehensive Cancer Center in the Northeastern United States. 32 Participants were randomized to: 1) ePVA intervention or 2) usual care. The intervention consisted of participants completing the ePVA every other week during radiation therapy (RT), then weeks 4, 12, and 24 after end of RT. Automated reports of ePVA data, including pain reports and patient-reports of pain medications, were sent to providers to inform their clinical decisions. Because of COVID-19, the study team converted all study procedures to remote telehealth. Potential participants were contacted 5 to 7 days before starting radiation therapy, and informed consent was obtained using REDCap e-consent. The study team met accrual goals by enrolling 32 participants, with a recruitment rate of 68%. The primary reason that potential participants did not enroll in the study was their feeling overwhelmed with the diagnosis and start of treatment. Participants' mean age was 60, and the study population was primarily male (69%), white (81%), and non-Hispanic (81%). The two study groups' gender, race, cancer stage, and treatment were balanced across study arms. 88% (28 of 32) of participants completed 6 of 7 planned data time points, meeting feasibility criteria for a large multi-site randomized clinical trial. On average, the ePVA arm had non-significant trends toward less pain and mildly better HRQoL than patients with usual care. These findings indicate the feasibility of conducting a large randomized clinical trial of a digital remote monitoring system. Other findings include encouraging but non-significant trends toward better pain control and HRQoL in this small sample size, but generalizations of this study data are limited because of the small sample size.
ABSTRACT
The combined effects of longer life, noncommunicable diseases, and injuries increase the need for rehabilitation services. Although physical therapists' unique skill set on movement-related dysfunction allows for broad contributions to health care, physical therapy (PT) remains underutilized. This article situates the problem within the broader primary care context, focusing on PT's ability to mitigate disability and dysfunction in complex syndromes including pelvic floor incontinence, vertigo, cancer, chronic neuromusculoskeletal pain, and long coronavirus disease (ie, lingering effects after acute coronavirus disease infection passes). The path from PT research to clinical implementation remains dependent on factors beyond research evidence. This overview underscores the need to address this evidence to practice gap.