Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
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 ...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.展开更多
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 tran...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-na?ve 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.展开更多
The incidence of human papillomavirus(HPV)-related oropharyngeal squamous cell carcinoma(OPSCC)will continue to rise in the United States over the next several decades.Thus,efforts to reduce treatment intensity,mitiga...The incidence of human papillomavirus(HPV)-related oropharyngeal squamous cell carcinoma(OPSCC)will continue to rise in the United States over the next several decades.Thus,efforts to reduce treatment intensity,mitigate long-term physical and psychological sequelae of treatment,and simplify surveillance regimens for patients with HPV-related OPSCC are critical.Liquid biomarkers,namely plasma circulating tumor HPV DNA(ctDNA),have shown considerable promise for improvements in these domains by guiding personalized and adaptive treatment de-escalation paradigms and predicting disease recurrence in the survivorship period.Preliminary reports suggest an even broader impact of plasma HPV ctDNA assays for HPV-related OPSCC surveillance beyond the mere detection of cancer recurrence and metastasis.For instance,such assays may reduce the need for costly imaging studies,alleviate the financial toxicities of survivorship care,and improve care access and patient satisfaction.Currently,veterans and underserved populations are disproportionately affected by the financial burden of cancer surveillance and survivorship care.These disparities negatively impact oncologic outcomes,healthcare access,and utilization,specifically among veterans with HPV-related OPSCC.As such,we posit that HPV ctDNA monitoring may be of unique benefit and impact in the surveillance period for these patients specifically.Herein,we provide a narrative review of the current literature supporting the formal clinical evaluation of HPV ctDNA monitoring in veterans with HPV-related OPSCC.展开更多
Aim:To describe a novel technique for the reconstruction of geometrically complex defects of the midface using an osteotomized folded scapular tip-free flap.Methods:Five patients underwent maxillectomy with defects di...Aim:To describe a novel technique for the reconstruction of geometrically complex defects of the midface using an osteotomized folded scapular tip-free flap.Methods:Five patients underwent maxillectomy with defects disrupting two or more of the following facial axes:orbital,nasofacial,and palatal axes.Patients underwent primary reconstruction using an angular artery-based scapular tip-free flap with an osteotomy to fold the flap.Harvest techniques,including placement of osteotomies,folding and plating,surgical esthetic,and functional outcomes,are presented.Results:Osteotomies placed in the scapular tip-free flap allowed folding of the osseous flap and improved restoration of all three facial axes with a single flap.In one patient,the tip of the scapula was used to reconstruct the nasofacial axis,while the body and lateral border were used to reconstruct the palate.In four patients,the tip of the scapula was used to reconstruct the orbital axis,while the body and lateral border were used to reconstruct the nasofacial axis.Patients had successful oronasal separation,healed wounds withstanding adjuvant therapy,satisfactory orbital positioning and facial projection,preserved masticatory surfaces and opportunity for dental implants.Conclusion:The midface is geometrically complex and is one of the most challenging head and neck sites to reconstruct.Ablative defects in this area can disrupt facial axes resulting in poor esthetic and functional outcomes.This study demonstrates the reconstructive advantages of a novel osteotomized folded scapular tip-free flap.展开更多
Free tissue transfer has become the gold standard for reconstruction within the head and neck.However,there are still many instances where pedicled locoregional flaps are the optimal reconstructive option.When myofasc...Free tissue transfer has become the gold standard for reconstruction within the head and neck.However,there are still many instances where pedicled locoregional flaps are the optimal reconstructive option.When myofascial tissue is needed,several options have been described throughout the literature.Various trapezius flaps have been used,although these have variable vascular anatomy and significant donor site morbidity.The pectoralis major myofascial flap has become a mainstay in head and neck reconstruction for its ease of harvest and reliability but suffers from similar issues with donor site morbidity.The pedicled latissimus dorsi flap(PLDF)is another reliable option that has been used for multiple different ablative sites within the head and neck.The thin,pliable structure of the latissimus dorsi makes it a viable option for many defects,and recent reports also support its feasibility for use in an interdisciplinary two-team approach.Furthermore,the donor site morbidity of the PLDF is minimal compared to other similar myofascial options.In this article,we describe the surgical considerations and operative techniques for PLDF transfer along with a review of its associated donor site morbidity.展开更多
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
基金Heft Neal ME was supported in part by the NIH Grant(T32 DC005356).Brenner JC was supported in part by American Cancer Society Grant:132034-RSG-18-062-01-TBG.Brenner JC was supported by F31:DE-027600-01
文摘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.
基金Brenner JC received funding from NIH(U01-DE025184, P30-CA046592 and R01-CA194536)Brenner JC and Spector ME also received funding from the American Head and Neck Society
文摘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-na?ve 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.
基金supported by a 2022 AHNS CORE Grant Presidential Award.
文摘The incidence of human papillomavirus(HPV)-related oropharyngeal squamous cell carcinoma(OPSCC)will continue to rise in the United States over the next several decades.Thus,efforts to reduce treatment intensity,mitigate long-term physical and psychological sequelae of treatment,and simplify surveillance regimens for patients with HPV-related OPSCC are critical.Liquid biomarkers,namely plasma circulating tumor HPV DNA(ctDNA),have shown considerable promise for improvements in these domains by guiding personalized and adaptive treatment de-escalation paradigms and predicting disease recurrence in the survivorship period.Preliminary reports suggest an even broader impact of plasma HPV ctDNA assays for HPV-related OPSCC surveillance beyond the mere detection of cancer recurrence and metastasis.For instance,such assays may reduce the need for costly imaging studies,alleviate the financial toxicities of survivorship care,and improve care access and patient satisfaction.Currently,veterans and underserved populations are disproportionately affected by the financial burden of cancer surveillance and survivorship care.These disparities negatively impact oncologic outcomes,healthcare access,and utilization,specifically among veterans with HPV-related OPSCC.As such,we posit that HPV ctDNA monitoring may be of unique benefit and impact in the surveillance period for these patients specifically.Herein,we provide a narrative review of the current literature supporting the formal clinical evaluation of HPV ctDNA monitoring in veterans with HPV-related OPSCC.
文摘Aim:To describe a novel technique for the reconstruction of geometrically complex defects of the midface using an osteotomized folded scapular tip-free flap.Methods:Five patients underwent maxillectomy with defects disrupting two or more of the following facial axes:orbital,nasofacial,and palatal axes.Patients underwent primary reconstruction using an angular artery-based scapular tip-free flap with an osteotomy to fold the flap.Harvest techniques,including placement of osteotomies,folding and plating,surgical esthetic,and functional outcomes,are presented.Results:Osteotomies placed in the scapular tip-free flap allowed folding of the osseous flap and improved restoration of all three facial axes with a single flap.In one patient,the tip of the scapula was used to reconstruct the nasofacial axis,while the body and lateral border were used to reconstruct the palate.In four patients,the tip of the scapula was used to reconstruct the orbital axis,while the body and lateral border were used to reconstruct the nasofacial axis.Patients had successful oronasal separation,healed wounds withstanding adjuvant therapy,satisfactory orbital positioning and facial projection,preserved masticatory surfaces and opportunity for dental implants.Conclusion:The midface is geometrically complex and is one of the most challenging head and neck sites to reconstruct.Ablative defects in this area can disrupt facial axes resulting in poor esthetic and functional outcomes.This study demonstrates the reconstructive advantages of a novel osteotomized folded scapular tip-free flap.
文摘Free tissue transfer has become the gold standard for reconstruction within the head and neck.However,there are still many instances where pedicled locoregional flaps are the optimal reconstructive option.When myofascial tissue is needed,several options have been described throughout the literature.Various trapezius flaps have been used,although these have variable vascular anatomy and significant donor site morbidity.The pectoralis major myofascial flap has become a mainstay in head and neck reconstruction for its ease of harvest and reliability but suffers from similar issues with donor site morbidity.The pedicled latissimus dorsi flap(PLDF)is another reliable option that has been used for multiple different ablative sites within the head and neck.The thin,pliable structure of the latissimus dorsi makes it a viable option for many defects,and recent reports also support its feasibility for use in an interdisciplinary two-team approach.Furthermore,the donor site morbidity of the PLDF is minimal compared to other similar myofascial options.In this article,we describe the surgical considerations and operative techniques for PLDF transfer along with a review of its associated donor site morbidity.
