25 research outputs found
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 patientâs 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
Paired phase II trials evaluating cetuximab and radiotherapy for low risk HPV associated oropharyngeal cancer and locoregionally advanced squamous cell carcinoma of the head and neck in patients not eligible for cisplatin
BackgroundAlternative therapeutic strategies are needed for localized oropharyngeal carcinoma. Cetuximab represents a potential option for those ineligible for cisplatin or, until recently, an agent for deâescalation in low risk HPV+ oropharyngeal carcinoma (OPSCC). Our objective was to define the toxicity and efficacy of cetuximabâradiotherapy.MethodsWe conducted paired phase II trials evaluating cetuximabâradiotherapy in two cohorts (a) low risk HPV+ OPSCC and (b) cisplatin ineligible. The mean followâup was 48âmonths.ResultsFortyâtwo patients were enrolled in cohort A with a 2âyear disease free survival (DFS) of 81%. Twentyâone patients were enrolled in cohort B prior to closure due to adverse outcomes with a 2âyear DFS of 37%. Severe toxicities were seen in 60% of patients, 30% required enteral nutrition.ConclusionAmong cisplatin ineligible patients, cetuximab treatment engendered poor outcomes. Rates of severe toxicities were on par with platinumâbased regimens suggesting that cetuximab is not a benign treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/2/hed26085.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/1/hed26085_am.pd
Impact of American Joint Committee on Cancer Eighth Edition clinical stage and smoking history on oncologic outcomes in human papillomavirusâassociated oropharyngeal squamous cell carcinoma
BackgroundThe purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)âassociated 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)âassociated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification.MethodsKaplanâMeier and Cox regression were used to evaluate overall survival (OS), locoregional recurrenceâfree survival (LRFS), and distant recurrenceâfree survival (DRFS). Concordance statistics (Câindices) 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 Câindices 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, 1â+âpackâyear smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2â3.1; Pâ<â.01) but not LRFS or DRFS.ConclusionThese results support implementation of the AJCC eighth edition for HPVâassociated 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
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Window of opportunity trials in head and neck cancer
Head and neck squamous cell carcinoma (HNSCC) has a large global burden of disease and poor survival outcomes. Recent targeted therapies and immunotherapies have been explored in HNSCC, but there has been limited translation to clinical practice outside of recurrent or metastatic cases. Window of opportunity settings, where novel agents are administered between cancer diagnosis and planned definitive therapy, have begun to be employed in HNSCC. Tumor tissue biopsies are obtained at diagnosis and after the investigation treatment, along with other biospecimens and radiographic exams. Thus, this study design can characterize the safety profiles, pharmacodynamics, and initial tumor responses to novel therapies in a treatment-naĂŻve subject. Early window studies have also identified potential biomarkers to predict sensitivity or resistance to treatments. However, these early investigations have revealed multiple challenges associated with this trial design. In this review, we discuss recent window of opportunity trials in HNSCC and how they inform design considerations for future studies
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
A review of drugs in development for the personalized treatment of head and neck squamous cell carcinoma
IntroductionHead and neck squamous cell carcinoma remains a highly morbid and fatal disease, with poor survival rates among patients with advanced and recurrent disease. Recent advances in next generation sequencing, targeted therapeutics, and precision medicine trials are expanding treatment options for head and neck cancers; thus greater awareness of this rapidly evolving field is important.Areas coveredRecent next-generation sequencing studies in head and neck squamous cell carcinoma, targeted therapy clinical trials involving head and neck squamous cell carcinoma.Expert commentaryThis review discusses the current state of head and neck cancer treatment, and considerations and implications for the incorporation of personalized medicine and targeted therapy for head and neck cancers in a dynamic clinical landscape
Recommended from our members
Window of opportunity trials in head and neck cancer
Head and neck squamous cell carcinoma (HNSCC) has a large global burden of disease and poor survival outcomes. Recent targeted therapies and immunotherapies have been explored in HNSCC, but there has been limited translation to clinical practice outside of recurrent or metastatic cases. Window of opportunity settings, where novel agents are administered between cancer diagnosis and planned definitive therapy, have begun to be employed in HNSCC. Tumor tissue biopsies are obtained at diagnosis and after the investigation treatment, along with other biospecimens and radiographic exams. Thus, this study design can characterize the safety profiles, pharmacodynamics, and initial tumor responses to novel therapies in a treatment-naĂŻve subject. Early window studies have also identified potential biomarkers to predict sensitivity or resistance to treatments. However, these early investigations have revealed multiple challenges associated with this trial design. In this review, we discuss recent window of opportunity trials in HNSCC and how they inform design considerations for future studies
Novel immunotherapeutic approaches in head and neck cancer
Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in immune evasion and may serve as targets for future therapies. Pembrolizumab is now approved as a first line therapy. Despite the promise of currently approved immunotherapies there continues to be low response rates and additional strategies are needed. Here, alterations in the immune microenvironment and current therapeutic strategies are reviewed with a focus on novel immunologic approaches
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