Optimizing molecular testing of lung cancer needle biopsy specimens: potential solutions from an interdisciplinary qualitative study.

BACKGROUND: Molecular testing can detect actionable genomic alterations and tumor cell surface proteins in patients with non-small cell lung cancer (NSCLC). However, utilization remains suboptimal, representing missed treatment opportunities. This study aimed to identify challenges and potential solutions to obtaining percutaneous lung needle biopsy specimens for successful molecular testing in patients with advanced NSCLC. METHODS: This interdisciplinary qualitative study included ten radiologists and four pathologists from academic and community settings across the United States who routinely perform and analyze percutaneous lung needle biopsies. Participants underwent semi-structured one-on-one interviews (Phase 1). Interview questionnaires were constructed based on a literature review of key lines of inquiry and conducted by professional market researchers using the theoretical domains framework. Primary barriers to molecular testing were identified using thematic analysis. Subsequently, multidisciplinary focus groups were convened to identify potential solutions (Phase 2). RESULTS: Four themes emerged as barriers to molecular testing and were matched to the clinical workflow: (1) biopsy request, (2) biopsy procedure, (3) specimen analysis, and (4) communication. The nineteen potential solutions included adding a "checkbox" to indicate molecular testing in the biopsy request, leveraging pre-procedural imaging to guide biopsies, conserving tissue through appropriate allocation strategies and next generation sequencing panels instead of sequential single-gene assays, instituting reflex-molecular testing upon NSCLC diagnosis, tracking and communicating biopsy outcomes at multidisciplinary tumor boards, and improving integration of radiologists and pathologists into oncology care teams. CONCLUSIONS: Potential solutions exist to increase successful molecular testing of lung needle biopsy specimens in patients with advanced NSCLC.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies: Guideline From the College of American Pathologists in Collaboration With the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytopathology, Society of Interventional Radiology, and Society of Thoracic Radiology.

CONTEXT.­: The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. OBJECTIVE.­: To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. METHODS.­: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. RESULTS.­: Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. CONCLUSIONS.­: Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.

A heat-stable microparticle platform for oral micronutrient delivery.

Micronutrient deficiencies affect up to 2 billion people and are the leading cause of cognitive and physical disorders in the developing world. Food fortification is effective in treating micronutrient deficiencies; however, its global implementation has been limited by technical challenges in maintaining micronutrient stability during cooking and storage. We hypothesized that polymer-based encapsulation could address this and facilitate micronutrient absorption. We identified poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate) (1:2:1) (BMC) as a material with proven safety, offering stability in boiling water, rapid dissolution in gastric acid, and the ability to encapsulate distinct micronutrients. We encapsulated 11 micronutrients (iron; iodine; zinc; and vitamins A, B2, niacin, biotin, folic acid, B12, C, and D) and co-encapsulated up to 4 micronutrients. Encapsulation improved micronutrient stability against heat, light, moisture, and oxidation. Rodent studies confirmed rapid micronutrient release in the stomach and intestinal absorption. Bioavailability of iron from microparticles, compared to free iron, was lower in an initial human study. An organotypic human intestinal model revealed that increased iron loading and decreased polymer content would improve absorption. Using process development approaches capable of kilogram-scale synthesis, we increased iron loading more than 30-fold. Scaled batches tested in a follow-up human study exhibited up to 89% relative iron bioavailability compared to free iron. Collectively, these studies describe a broad approach for clinical translation of a heat-stable ingestible micronutrient delivery platform with the potential to improve micronutrient deficiency in the developing world. These approaches could potentially be applied toward clinical translation of other materials, such as natural polymers, for encapsulation and oral delivery of micronutrients.

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

Medical mirroring: granulomatosis with polyangiitis (formerly Wegener's) mimicking immunoglobulin-G4 related disease.

Granulomatosis with polyangiitis (GPA; formerly Wegener's) can present with clinical and histopathological features similar to those of immunoglobulin-G4 related disease (IgG4-RD), a recently described fibro-inflammatory condition. The ability of these two distinct entities to mimic each other closely creates significant pitfalls in diagnosis. We present a unique case in which GPA presented as a peri-aortic fibrotic mass in the retroperitoneum. The patient's other clinical features also overlapped with classic IgG4-RD disease manifestations, but the histopathology in two organs and the serological data confirmed the diagnosis of GPA. Rigorous histopathological review remains the gold standard for the diagnosis of GPA and the distinction of this entity from IgG4-RD and other mimickers.