Cancer Research Ethics and COVID‐19

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155925/1/onco13303_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155925/2/onco13303.pd

Ethical framework for head and neck cancer care impacted by COVID‐19

The COVID‐19 pandemic has upended head and neck cancer care delivery in ways unforeseen and unprecedented. The impact of these changes parallels other fields in oncology, but is disproportionate due to protective measures and limitations on potentially aerosolizing procedures and related interventions specific to the upper aerodigestive tract. The moral and professional dimensions of providing ethically appropriate and consistent care for our patients in the COVID‐19 crisis are considered herein for head and neck oncology providers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155455/1/hed26193.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155455/2/hed26193_am.pd

Revisiting Expectations in an Era of Precision Oncology

As we enter an era of precision medicine and targeted therapies in the treatment of metastatic cancer, we face new challenges for patients and providers alike as we establish clear guidelines, regulations, and strategies for implementation. At the crux of this challenge is the fact that patients with advanced cancer may have disproportionate expectations of personal benefit when participating in clinical trials designed to generate generalizable knowledge. Patient and physician goals of treatment may not align, and reconciliation of their disparate perceptions must be addressed. However, it is particularly challenging to manage a patient’s expectations when the goal of precision medicineâ personalized responseâ exacerbates our inability to predict outcomes for any individual patient. The precision medicine informed consent process must therefore directly address this issue. We are challenged to honestly, clearly, and compassionately engage a patient population in an informed consent process that is responsive to their vulnerability, as well as everâ evolving indications and evidence. This era requires a continual reassessment of expectations and goals from both sides of the bed.New challenges are faced in this era of precision medicine and targeted therapies. Clear guidelines, regulations, and strategies for implementation are needed. Patients with advanced cancer may have disproportionate expectations of the personal benefit of participating in clinical trials. The informed consent process must address this issue directly and honestly. This era requires a continual reassessment of both patient and physician expectations and goals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142968/1/onco12322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142968/2/onco12322.pd

- My Research Is Their Business, but I’m 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 patients’ 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

Changes in Continental and Sea-salt Atmospheric Loadings in Central Greenland during the Most Recent Deglaciation: Model-based Estimates

By fitting a very simple atmospheric impurity model to high-resolution data on ice accumulation and contaminant f1uxes in the GISP2 ice core, we have estimated changes in the atmospheric concentrations of soluble major ions, insoluble particulates and 10Be during the transition from glacial to Holocene conditions. For many species, changes in concentration in the ice typically overestimate atmospheric changes, and changes in flux to the ice typically underestimate atmospheric changes, because times of increased atmospheric contaminant loading are also times of reduced snowfall. The model interpolates between the flux and concentration records by explicitly allowing [or wet- and dry- deposition processes. Compared to the warm Preboreal that followed, we estimate that the atmosphere over Greenland sampled b y snow accumulated during the Younger Dryas cold event contained on average four-seven times the insoluble particulates and n early seven times the soluble calcium derived from continental sources, and about three times the sea salt but only slightly more cosmogenic 10Be

Individualized outcome prognostication for patients with laryngeal cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142424/1/cncr31087.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142424/2/cncr31087_am.pd

Predictors of poor sleep quality among head and neck cancer patients

Objectives/Hypothesis: The objective of this study was to determine the predictors of sleep quality among head and neck cancer patients 1 year after diagnosis. Study Design: This was a prospective, multisite cohort study of head and neck cancer patients (N = 457). Methods: Patients were surveyed at baseline and 1 year after diagnosis. Chart audits were also conducted. The dependent variable was a self-assessed sleep score 1 year after diagnosis. The independent variables were a 1 year pain score, xerostomia, treatment received (radiation, chemotherapy, and/or surgery), presence of a feeding tube and/or tracheotomy, tumor site and stage, comorbidities, depression, smoking, problem drinking, age, and sex. Results: Both baseline (67.1) and 1-year postdiagnosis (69.3) sleep scores were slightly lower than population means (72). Multivariate analyses showed that pain, xerostomia, depression, presence of a tracheotomy tube, comorbidities, and younger age were statistically significant predictors of poor sleep 1 year after diagnosis of head and neck cancer ( P < .05). Smoking, problem drinking, and female sex were marginally significant ( P < .09). Type of treatment (surgery, radiation and/or chemotherapy), primary tumor site, and cancer stage were not significantly associated with 1-year sleep scores. Conclusions: Many factors adversely affecting sleep in head and neck cancer patients are potentially modifiable and appear to contribute to decreased quality of life. Strategies to reduce pain, xerostomia, depression, smoking, and problem drinking may be warranted, not only for their own inherent value, but also for improvement of sleep and the enhancement of quality of life. Laryngoscope, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75789/1/20924_ftp.pd

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma

BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single‐institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan‐Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive‐year overall survival (OS) was 49%. Five‐year disease‐free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation‐27 [ACE‐27] scale; HR 3.76; 95% confidence interval [CI] 1.56‐9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74‐4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/1/hed24918.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/2/hed24918_am.pd

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma

BackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/1/hed25444.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/2/hed25444_am.pd

Impact of American Joint Committee on Cancer Eighth Edition clinical stage and smoking history on oncologic outcomes in human papillomavirus‐associated oropharyngeal squamous cell carcinoma

BackgroundThe purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification.MethodsKaplan‐Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence‐free survival (LRFS), and distant recurrence‐free survival (DRFS). Concordance statistics (C‐indices) were used to compare discriminating ability.ResultsThe OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C‐indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack‐year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2‐3.1; P < .01) but not LRFS or DRFS.ConclusionThese results support implementation of the AJCC eighth edition for HPV‐associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/1/hed25336_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/2/hed25336.pd