11 research outputs found
- My Research Is Their Business, but Iâm Not Their Business- : Patient and Clinician Perspectives on Commercialization of Precision Oncology Data
BackgroundGenetic sequencing and precision oncology have supported clinical breakthroughs but depend upon access to vast arrays of research specimens and data. One way for academic medical centers to fund such infrastructure and research is - commercialization- of access to specimens and data to industry. Here we explore patient and clinician perspectives regarding cancer specimen and data commercialization with the goal of improving such processes in the future.Materials and MethodsThis qualitative analysis was embedded within a prospective precision oncology sequencing study of adults with head and neck cancer. Via semistructured dyadic interviews with patients with cancer and their doctors, we assessed understanding and concerns regarding potential commercialization, opinions regarding investment of profits, and perspectives regarding the return of information directly to participants from industry.ResultsSeveral patient- and clinician- participants did not understand that the consent form already permitted commercialization of patient genetic data and expressed concerns regarding who would profit from the data, how profits would be used, and privacy and access. Patients were generally more comfortable with commercialization than clinicians. Many patients and clinicians were comfortable with investing profits back into research, but clinicians were more interested in investment in head and neck cancer research specifically. Patients generally supported potential return- of- results from a private entity, but their clinicians were more skeptical.ConclusionOur results illustrate the limitations of mandatory disclosures in the informed consent process. The voices of both patients and their doctors are critical to mitigate violations of privacy and a degradation of trust as stakeholders negotiate the terms of academic and commercial engagement.Implications for PracticeFurther education is needed regarding how and why specimens and data in precision oncology research may be commercialized for both patients and providers alike. This process will require increased transparency, comprehension, and engagement of involved stakeholders.To better understand perspectives on cancer specimen and data commercialization, interviews of patients participating in a prospective precision medicine cancer sequencing study were conducted, along with corresponding interviews with the patientsâ referring doctors. This article reports the results and aims to improve the consent process for biospecimen and health data sharing and commercialization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156136/2/onco13272.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156136/1/onco13272_am.pd
Efficacy of axitinib in metastatic head and neck cancer with novel radiographic response criteria
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166220/1/cncr33226_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166220/2/cncr33226.pd
Patient and Provider Perspectives on Enrollment in Precision Oncology Research: Qualitative Ethical Analysis
BackgroundThe genomic frontier continues to revolutionize the practice of oncology. Advances in cancer biology from tumorigenesis to treatment resistance are driven by the molecular underpinnings of malignancy. The framing of precision oncology as both a clinical and research tool is constantly evolving and directly influences conversations between oncologists and their patients. Prior research has shown that patient-participants often have unmet or unrealistic expectations regarding the clinical utility of oncology research and genomic sequencing. This indicates the need for more in-depth investigation of how and why patients choose to participate in such research.
ObjectiveThis study presents a qualitative ethical analysis to better understand patient and provider perspectives on enrollment in precision oncology research.
MethodsPaired semistructured interviews were conducted with patient-participants enrolled in a prospective head and neck precision oncology research platform, along with their oncology providers, at a National Cancer Instituteâdesignated academic cancer center.
ResultsThere were three major themes that emerged from the analysis. (1) There are distinct and unique challenges with informed consent to precision medicine, chiefly involving the ability of both patient-participants and providers to effectively understand the science underlying the research. (2) The unique benefits of precision medicine enrollment are of paramount importance to patients considering enrollment. (3) Patient-participants have little concern for the risks of research enrollment, particularly in the context of a low-burden protocol.
ConclusionsPatient-participants and their providers offer complementary and nuanced perspectives on their motivation to engage in precision oncology research. This reflects both the inherent promise and enthusiasm within the field, as well as the limitations and challenges of ensuring that both patient-participants and clinicians understand the complexities of the science involved
SearcHPV: A novel approach to identify and assemble human papillomavirusâhost genomic integration events in cancer
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170218/1/cncr33691-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170218/2/cncr33691.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170218/3/cncr33691_am.pd
Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma
Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI, OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers
Association of human papillomavirus integration with better patient outcomes in oropharyngeal squamous cell carcinoma
BackgroundThe molecular drivers of human papillomavirusârelated head and neck squamous cell carcinoma (HPVâ+âHNSCC) are not entirely understood. This study evaluated the relationship between HPV integration, expression of E6/E7, and patient outcomes in p16+ HNSCCs.MethodsHPV type was determined by HPV PCRâMassArray, and integration was called using detection of integrated papillomavirus sequences polymerase chain reaction (PCR). We investigated whether fusion transcripts were produced by reverse transcriptase polymerase chain reaction (RTâPCR). E6/E7 expression was assessed by quantitative RTâPCR. We assessed if there was a relationship between integration and E6/E7 expression, clinical variables, or patient outcomes.ResultsMost samples demonstrated HPV integration, which sometimes resulted in a fusion transcript. HPV integration was positively correlated with age at diagnosis and E6/E7 expression. There was a significant difference in survival between patients with vs without integration.ConclusionsContrary to previous reports, HPV integration was associated with improved patient survival. Therefore, HPV integration may act as a molecular marker of good prognosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166276/1/hed26501_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166276/2/hed26501.pd
Recommended from our members
154 Marrow-infiltrating lymphocytes (MILs): A novel adoptive immunotherapy for hematological and solid tumors
Recommended from our members
154â Marrow-infiltrating lymphocytes (MILs): A novel adoptive immunotherapy for hematological and solid tumors
Background Marrow infiltrating lymphocytes (MILsTM) are the product of activating and expanding bone marrow T cells.1 The bone marrow is a specialized niche in the immune system enriched for antigen-experienced, memory T cells. In patients with multiple myeloma and other hematological malignancies that relapse post-transplant, MILs have been shown to contain tumor antigen-specific T cells and adoptive cell therapy (ACT) using MILs has demonstrated antitumor activity.2 3 The bone marrow has been shown to harbor tumor-antigen specific T cells in patients with melanoma,4 5 glioblastoma,6 breast,7 non-small-cell lung8 and pancreatic cancers.9 Here, we sought to determine if tumor-specific MILs could be expanded from the bone marrow of patients with a range of different solid tumors. Methods Bone marrow and blood samples were collected from patients with advanced and metastatic cancers. To date, samples have been collected from a minimum of four patients with non-small cell lung cancer (NSCLC), prostate cancer, head and neck cancer, glioblastoma, and breast cancer. Samples from patients with multiple myeloma were used as a reference control. Utilizing a 10-day proprietary process, MILs and peripheral blood lymphocytes (PBLs) were activated and expanded from patient bone marrow and blood samples, respectively. T cell lineage-specific markers (CD3, CD4 and CD8) were characterized by flow cytometry pre- and post-expansion.Tumor-specific T cells were quantitated in expanded MILs and PBLs using a previously described cytokine-secretion assay [2]. Briefly, autologous antigen-presenting cells (APCs) were pulsed with lysates from allogeneic cancer cell lines and co-cultured with activated MILs or PBLs. APCs pulsed with irrelevant mis-matched cancer cell line lysates or media alone were used as negative controls. Tumor-specific T cells were defined as the IFNgamma-producing population by flow cytometry. Results MILs were successfully expanded from all patient bone marrow samples tested, regardless of tumor type. Cytokine-producing tumor-specific CD4+ and CD8+ T cells were detected in each of the expanded MILs. In contrast, tumor-specific T cells were not detected in any of the matched activated and expanded PBLs. Conclusions MILs have been successfully grown for all solid tumor types evaluated, including NSCLC, prostate, head and neck, glioblastoma and breast cancer. Clinical studies have been completed in patients with multiple myeloma and other hematological cancers. 2 3 A phase IIa trial to evaluate MILs in combination with a checkpoint inhibitor is underway in patients with anti-PD1/PDL1-refractory NSCLC (ClinicalTrials.gov Identifier: NCT04069936). The preclinical data presented herein demonstrate that expanding MILs is feasible. MILs-based therapies hold therapeutic promise across a wide range of tumor indications. Ethics Approval This study was approved by each participating instituionâs IRB.
References Borrello I and Noonan KA. Marrow-Infiltrating Lymphocytes - Role in Biology and Cancer Therapy. Front Immunol 2016 March 30; 7(112) Noonan KA, Huff CA, Davis J, et al. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci. Transl. Med 2015;7:288ra78. Biavati L, Noonan K, Luznik L, Borrello I. Activated allogeneic donor-derived marrow-infiltrating lymphocytes display measurable in vitro antitumor activity. J Immunother 2019 Apr;42(3):73â80. MĂŒller-Berghaus J, Ehlert K, Ugurel S, et al. Melanoma-reactive T cells in the bone marrow of melanoma patients: association with disease stage and disease duration. Cancer Res 2006;66(12):5997â6001. Letsch A, Keilholz U, Assfalg G, et al., Bone marrow contains melanoma-reactive CD8+ effector T Cells and, compared with peripheral blood, enriched numbers of melanoma-reactive CD8+ memory T cells. Cancer Res 2003 Sep 1;63(17):5582â5586. Chongsathidkiet P, Jackson C, Koyama S, et al., Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nature Medicine 2018 Aug 13; 24:1459â1468. Feuerer M, Rocha M, Bai L, et al. Enrichment of memory T cells and other profound immunological changes in the bone marrow from untreated breast cancer patients. Int J Cancer 2001; 92(1):96â105. Safi S, Yamauchi Y, Stamova S, et al. Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer. Oncoimmunology 2019;8(12):e1671762. Schmitz-Winnenthal FH, Volk C, ZâGraggen K, et al. High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients. Cancer Res 2005;65(21):10079â87.
http://dx.doi.org/10.1136/jitc-2020-SITC2020.015