Therapeutic products are now being developed that target particular molecular lesions found in various types of cancers. The ability to correctly identify patients whose cancers have targetable ...lesions generally depends on a well-validated diagnostic test. Development and use of diagnostic tests together with therapies in clinical trials yields the information necessary to make a regulatory determination that both products are safe and effective, likely have clinical utility when used together, and reach the market for patient benefit. This model, called co-development, has been developed relatively recently, and is being put to use in numerous cancer therapeutic development programs. The U.S. Food and Drug Administration (FDA) has articulated a policy that requires the coapproval of a diagnostic with a therapeutic product when the diagnostic is essential to the safe and effective use of the therapeutic product. At the same time, FDA has implemented a number of processes to manage the model without slowing the approval of the co-developed products. New diagnostic technologies, together with a rapid uptick in interest in targeted drugs, will challenge the still-evolving regulatory paradigm, but will likely result in some simplified approaches presenting new challenges in determining safety and effectiveness, but all with the promise of greater benefit to patients with cancer. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development."
Background
Image‐guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern ...biologic characterization of neuroblastoma.
Procedure
A multi‐institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3‐year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children's Oncology Group for risk stratification.
Results
A total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy.
Conclusions
PCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real‐time pathology assessment of specimen quality.
eHealth literacy in older adults with cancer Hoogland, Aasha I.; Mansfield, Jori; Lafranchise, Elizabeth A. ...
Journal of geriatric oncology,
07/2020, Volume:
11, Issue:
6
Journal Article
Peer reviewed
Open access
Recent advances in health monitoring technology have coincided with increases in the number of older adults with cancer, many of whom report difficulty using health information technology (HIT). ...Previous studies have identified lower electronic health (eHealth) literacy among older adults (≥65 years) compared to younger adults (<65), but studies in older adults with cancer are limited. The goal of this study was to examine age differences in eHealth literacy and use of technology devices/HIT in patients with cancer, and characterize receptivity towards using home-based HIT to communicate with the oncology care team.
Patients (n = 198) in a Radiation Oncology clinic were offered an anonymous written questionnaire assessing demographics, eHealth literacy (eHealth Literacy Scale), current use of HIT, and interest in using home-based HIT.
Compared to younger patients, older patients had significantly lower eHealth literacy (p < .01), and were less likely to feel confident evaluating health resources on the Internet (p < .01) or knowing how to use the health information found on the Internet to help them (p < .01) or answer health questions (p = .01). Older patients were also less likely than younger patients to have an email address (p = .04), own a smartphone (p < .01), or use the online patient portal (p = .03). Regardless of age, most patients were not opposed to using home-based HIT to communicate with their oncology care team. Future studies on HIT use in older adults with cancer should further evaluate barriers to using HIT and ways to maximize implementation and accessibility.
Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, ...influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen‐related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected. Cancer (Cancer Cytopathol) 2011. Published 2011 by the American Cancer Society.
Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. The BRISQ guidelines are proposed as an important and timely tool to strengthen communication and publications on biospecimen‐related research.
To determine the impact of tumor characteristics and treatment approach on (1) local recurrence, (2) scoliosis development, and (3) patient-reported quality of life in children with sarcoma of the ...chest wall.
Children with chest wall sarcoma require multimodal therapy including chemotherapy, surgery, and/or radiation. Despite aggressive therapy which places them at risk for functional impairment and scoliosis, these patients are also at significant risk for local recurrence.
A multi-institutional review of 175 children (median age 13 years) with chest wall sarcoma treated at seventeen Pediatric Surgical Oncology Research Collaborative institutions between 2008 and 2017 was performed. Patient-reported quality of life was assessed prospectively using PROMIS surveys.
The most common diagnoses were Ewing sarcoma (67%) and osteosarcoma (9%). Surgical resection was performed in 85% and radiation in 55%. A median of 2 ribs were resected (interquartile range = 1-3), and number of ribs resected did not correlate with margin status ( P = 0.36). Local recurrence occurred in 23% and margin status was the only predictive factor(HR 2.24, P = 0.039). With a median follow-up of 5 years, 13% developed scoliosis (median Cobb angle 26) and 5% required corrective spine surgery. Scoliosis was associated with posteriorrib resection (HR 8.43; P= 0.003) and increased number of ribs resected (HR 1.78; P = 0.02). Overall, patient-reported quality of life is not impaired after chest wall tumor resection.
Local recurrence occurs in one-quarter of children with chest wall sarcoma and is independent of tumor type. Scoliosis occurs in 13% of patients, but patient-reported quality of life is excellent.
Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long‐term survival. Open thoracotomy allows palpation of nodules not identified on imaging but ...the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease‐free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi‐institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan‐Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow‐up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan‐Meier analysis showed no significant difference in 5‐year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09‐4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52‐1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64‐2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.
What's new?
In patients with osteosarcoma that has metastasized to the lungs, complete surgical resection is crucial for long‐term survival. But is full thoracotomy necessary? In this study, the authors found that, in patients with limited metastases, both mortality and risk of pulmonary recurrence were similar for patients who had thoracoscopic surgery vs. those who underwent thoracotomy. Thoracotomy did improve survival for patients with more extensive disease, however. These results indicate that the less invasive, lower‐risk thoracoscopic approach may be preferable for a subset of patients.
This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and ...clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussion is complementary to theoretical frameworks described in previously published guidance and literature reports by the U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development."
This quality improvement initiative aimed to minimize opioid prescribing after oncologic pediatric surgery.
Retrospective surgical data collected at a pediatric cancer hospital from July 2016 to June ...2018 included hospitalization details, oral morphine equivalents prescribed, unplanned visits/calls because of pain, and parental/patient satisfaction with pain control. The quality improvement initiative promoted opioid prescription at discharge on the basis of prior inpatient requirements and education regarding nonopioid analgesia. Upon commencing this project in July 2018, we collected data prospectively.
The retrospective and the prospective cohorts included 271 and 99 patients, respectively. Mean (SD) oral morphine equivalents (mg/kg) prescribed upon discharge was significantly reduced in the prospective (0.75±1.34) versus retrospective cohorts (5.48±6.94, P<0.001). The unplanned visits/calls regarding pain were 23 (retrospective, 8.5%) and 2 (prospective, 2.0%). In total, 44 patients (44.4%) received an opioid prescription at discharge in the prospective cohort, significantly fewer than retrospective cohort (251, 92.6%, P<0.001), and used a mean of 34.3 of 159.8 (21.5%) doses dispensed. Length of stay was comparable (P=0.88) between cohorts. Prospective satisfaction rate was 96.2%, leaving 3 patients (3.8%) not satisfied with their pain control regimen.
Dramatic reduction of opioid prescriptions after oncologic surgery can be achieved without detriment to patient satisfaction or readmissions.
Level V.
Only two industrialized countries, the United States and New Zealand, allow direct-to-consumer advertising (DTCA) of prescription medicines, although New Zealand is planning a ban. The challenge for ...these governments is ensuring that DTCA is more beneficial than harmful. Proponents of DTCA argue that it helps to inform the public about available treatments and stimulates appropriate use of drugs for high-priority illnesses (such as statin use in people with ischemic heart disease). Critics argue that the information in the adverts is often biased and misleading, and that DTCA raises prescribing costs without net evidence of health benefits.
This report describes the volatile organic compounds (VOCs) associated with human cerumen (earwax) and the effects of ethnicity/race and variation on the ATP-binding cassette, sub-family C, member 11 ...gene (ABCC11). A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent. Employing gas chromatography/mass spectrometry (GC/MS) we have identified the nature and relative abundance of cerumen VOCs from 32 male donors. Our results show that cerumen contains a complex mixture of VOCs and that the amounts of these compounds vary across individuals as well as across ethnic/racial groups. In six of the seven compounds whose detected concentrations were found to be statistically different across groups, individuals of African descent (AfD) > Caucasian descent (CaD) > Asians descent (AsD). Our findings also reveal that ABCC11 genotype alone does not predict the type and relative levels of volatiles found in human cerumen, and suggest that other biochemical pathways must be involved. Examination of the composition and diversity of external auditory canal microbiota in a small subset of our subject population revealed that the ear microbiota may not be directly correlated with either ethnic group membership or ABCC11 genotype.
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