American Head & Neck Society

Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.

  • About
    • Mission Statement and Purpose
    • Divisions & Services of the Society
      • Education
        • Scientific Program/Resident Courses
        • Surgical Videos
        • Journal Club
        • Journals
        • Global Outreach
        • Awards
          • Margaret F. Butler Award
      • Diversity, Equity and Inclusion Division
      • Patient Care
        • Cancer Survivorship
          • Patient Education on Post-Treatment Care
          • Interviews with Cancer Survivors
        • Cancer Prevention
          • SLIDE DECK: HPV-Related Oropharyngeal Cancer
        • Guidelines/Position Statements
        • Find-A-Physician
      • Research
        • Grant Information
        • Clinical Trial
        • Tissue Banks
      • Administrative Division
        • AHNS Process for Evaluating Projects Requiring Funding
    • Leadership
    • History
      • Society Background
      • AHNS History Interviews
      • Past Presidents
      • In Memory
    • AHNS Newsletter
    • Professionalism & Ethics
    • AHNS Policies and Procedures (P&P) Manual
    • AHNS Foundation
    • AHNS Bylaws
    • AHNS Staff
    • AHNS News and Announcements
    • COVID-19 Bulletin Board
  • Heads Up!
  • Post a Job
  • Meetings
    • AHNS Virtual Education Series
      • TORS Webinar Series
    • AHNS Meetings Info
    • AHNS Call For Abstracts
    • Past Meetings
    • Related Meetings
  • For Patients
  • For Trainees
    • Fellowship Curriculum for FY2024-2025
      • For Current AHNS Fellows
      • Certificate of Completion Request
    • Accredited Fellowships
      • Directory of Fellowships
      • AHNS Fellowship Match
      • Fellowship Curriculum
      • Fellowship Graduates
      • For Program Directors
    • AHNS Surgical Videos
    • Fellows’ Virtual Tumor Boards
    • Cutaneous Cancer
  • Sections
    • Endocrine Surgery
    • Skull Base Surgery Section
    • Reconstructive Head & Neck Surgery
      • Head and Neck Reconstruction- Information for Patients
    • Mucosal Malignancy Section
      • Mucosal Malignancy Section Patient Information
    • Salivary Gland Section
      • Salivary Gland Section Patient Education Handout: Parotidectomy
    • Cutaneous Cancer
  • Find-A-Physician
  • Member Central
    • Join AHNS
    • Find-A-Physician
    • Mailing List Order
  • Login
    • Password Reset
  • Donate

Published on June 27, 2022 by Andrew Nemechek

Systemic Therapy for Basal Cell Carcinoma of the Head and Neck

(from the AHNS Cutaneous Cancer Section)

Skin Cancer is the most common malignancy that affects humans. Malignancies develop in tissues native to the skin, basal cell carcinoma (BCCA) and squamous cell carcinoma (SCCA), and those embryologically derived elsewhere that come to reside in cutaneous structures: malignant melanoma (melanocytes from neural crest) and Merkel Cell carcinoma (neuroectoderm), among others. A variety of less-common cutaneous malignancies form from adnexal and sustentacular cells.

The most common skin malignancy is BCCA, named for the cells that reside in the basal layer (stratum germinativum) of the epidermis. These cells continually divide and populate more superficial layers closer to the skin’s surface. A majority of BCCA lesions remain locally in their primary site rarely metastasizing to regional lymph nodes or distant sites. Surgical excision with negative margins is the mainstay of treatment and curative for most patients. Other local maneuvers such as curettage, cryotherapy, topical agents and, occasionally, radiation therapy, are also employed for patients with local disease. However, some experience multiple recurrences or tumors that have the potential to significantly affect function and appearance. Surgical resection can be offered in these situations, coupled with complex reconstruction that leverages free-tissue transfer techniques if needed. Resection/reconstruction can be accompanied by significant morbidity that affects quality of life, especially in those with limited life expectancies. Alternately, radiation therapy can be offered in the adjuvant setting, especially for those with large tumors or positive resection margins. Tumor response is dose-dependent. Though effective in selective cases, radiation is not particularly efficient and precludes the opportunity for additional pathologic review if the patient has a complete response. Additional tumor analysis may prove to be important for risk stratification and to define potential targets of future therapeutics.

The last decade has seen a rapid rise in the use of systemic therapies for locally advanced, recurrent, and metastatic malignancies involving the head and neck. Both cemiplimab and pembrolizumab have FDA approval for treatment of cutaneous SCCA. Cytotoxic platinum-based chemotherapy and others have been used for many years preceding these recent approvals. Cytotoxic therapies have demonstrated mixed local efficacy in the treatment of BCCA, especially when combined with taxanes and ifosfamide, though survival benefits have not been shown. As such, efforts to elucidate other targets for systemic therapies were undertaken. In 1980, the Hedgehog (Hh) signaling pathway was described in the Drosophila melanogaster model and was shown to play a critical role in normal stem cell differentiation. This pathway is normally not active after embryogenesis. Ligand-independent aberrant signaling was subsequently described in patients with Basal Cell Nevus Syndrome. BCCA was the first malignancy shown to exhibit abnormal Hh signaling, and is observed in 95% of patients with sporadic BCCA. Dysregulation in this pathway results in uncontrolled proliferation of basal cells. Several agents have been developed to block this aberrant pathway via the Smoothened (SMO) G-protein-coupled receptor. Cyclopamine was the first, but demonstrated limited in vivo activity. Several synthetic small molecule inhibitors of SMO have been evaluated. Vismodegib (Erivedge) received FDA approval in January 2012. Indications for its use include treatment of locally advanced BCCA in those who are not surgical candidates or who have failed radiation or have technically unresectable disease. Vismodegib is an oral agent taken once daily. Its side effects include fatigue, anorexia and weight loss, and muscle spasms. Patients may be able to tolerate treatment for many months and then need to take breaks from therapy as these side effects can be cumulative and significantly reduce quality of life in these patients seeking long-term palliation. Partial response rates range between 40% and 70%. Aggressive tumor regrowth following discontinuation of the drug has been reported. The optimal length of therapy is not known. Recent work has defined a possible role for Hh inhibition in the neoadjuvant setting, allowing for smaller resections, smaller radiation fields, or de-escalation of radiation dose

Sonidegib (Odomzo), also an oral therapeutic, is another small molecule inhibitor of the Hh pathway with observed rates approaching 60%. It was approved for use in July 2015. It has a similar side-effect profile to vismodegib. The monthly cost for these Hh inhibitor therapies can approach $13,000.00.

Most recently, cemiplimab (Libtayo) was approved for patients with advanced BCCA previously treated with Hh inhibitors or if Hh inhibitor therapy is contraindicated. It is delivered intravenously. The efficacy study leading to its approval reported a 29% response rate durable to approximately 6 months. Its cost approaches $10,000.00 monthly.

We met one of our favorite older patients having been treated for multiply recurrent BCCA of the left auricular/post-auricular skin. He had multiple comorbidities. He had undergone treatment by multiple clinicians including general dermatology, Mohs surgeons, general otolaryngologists, neurotologists, and radiation oncology. His treatment included multiple surgeries, topical agents (imiquamod) and radiation (60Gy). He had significant pain, especially near the temporomandibular joint, recurrent infection requiring frequent systemic antibiotics, and spontaneous bleeding that was robust. At our evaluation, dense, friable tumor measuring 8.2cm was present involving the auricular remnant and surrounding skin, including the upper neck, and middle ear. There was no purulence or bleeding. No lymph nodes were palpable. His cranial nerve exam was normal other than subjective hearing loss. A contrast enhanced CT scan confirmed a peri-auricular tumor mass involving the lateral temporal bone structures and lateral aspect of the TMJ. His previous pathology specimens were re-examined to confirm a diagnosis of BCCA and rule out attendant squamous cell carcinoma. Our radiation and medical oncology colleagues were consulted and he was discussed during our interdisciplinary head and neck tumor conference. Resection and free-tissue transfer for reconstruction were offered. A series of long discussions with him shed light on his goals of therapy: controlling pain and reducing the frequency of bleeding episodes and infection (improving cleanliness). He did not want to undergo surgery. Vismodegib therapy was instituted. Within three weeks of initiation, his pain improved, especially around his TMJ, and bleeding from his tumor stopped. He cancelled a planned CT scan at 8 weeks; satisfied that he was improving symptomatically. After 4 months of therapy, with excellent compliance, he decided to discontinue therapy because of increasing and profound fatigue and anorexia. He also was quite concerned about the monthly copays that he was required to pay for his treatment. His pain, bleeding, and purulent discharge returned again about 3 weeks later. He restarted therapy again approximately five weeks later. His pain and bleeding again quickly abated.

Our patient repeated this on-treatment/off-treatment cycle 3 more times over the next two years. When he was off treatment, he required home nursing to help him with his difficult wound. He eventually elected not to restart therapy and died a month later supported by home hospice staff of unsupported anemia and infection. Our experience with him illustrates the significant positive and negative impact targeted agents potentially have and, as such, the role they can play in the long-term palliation of patients with locally advanced BCC involving critical head and neck structures.

The preceding discussion may prompt some salient discussion points:

  1. There are multiple systemic treatment strategies available to treat these challenging patients. Each has its own unique risk/benefit (and significant cost) profile.
  2. There is heightened need to understand the molecular underpinnings of the carcinogenesis of cutaneous basal cells. Future discovery will positively affect millions of people worldwide. More importantly, are there “upstream” targets for prevention of this widespread disease?
  3. Many types of clinicians with diverse training backgrounds could potentially treat patients with advanced BCCA with therapies that have complicated risk profiles. Robust, peer-reviewed interdisciplinary team discussion, so valued in the delivery of care of other head and neck cancer patients, is now requisite for patients with cutaneous malignancy, including those with BCCA. Decision-making and treatment not informed by such a process will prove to be dated and dangerous.

References:

  1. Pellegrini, C.; Maturo, M.G.; Di Nardo, L.; Ciciarelli, V.; Gutiérrez García-Rodrigo, C.; Fargnoli, M.C. Understanding the Molecular Genetics of Basal Cell Carcinoma.  J. Mol. Sci.2017, 18, 2485.
  2. Koelblinger P, Lang R. New developments in the treatment of basal cell carcinoma: update on current and emerging treatment options with a focus on vismodegib. Onco Targets Ther. 2018;11:8327-8340. 
  3. Sekulic A, Migden MR, Basset-Seguin N et al. . Correction to: Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer2019; 19: 366. 
  4. Chen L, Aria AB, Silapunt S, et al. Treatment of advanced basal cell carcinoma with sonidegib: perspective from the 30-month update of the BOLT trial. Future Oncology 2017;16(6):515-525.
  5. Enrico Zelin, Iris Zalaudek, Marina Agozzino, Caterina Dianzani, Arianna Dri, Nicola Di Meo, Roberta Giuffrida, Giovanni Francesco Marangi, Nicoleta Neagu, Paolo Persichetti, Ludovica Toffoli, Claudio Conforti Curr Treat Options Oncol. 2021; 22(4): 35. Published online 2021 Mar 16. doi: 10.1007/s11864-021-00826-3.
  • Bio
  • Latest Posts
Andrew Nemechek

Andrew Nemechek

Dr. Nemechek earned his medical degree from the Tulane University School of Medicine, where he also completed his otolaryngology residency training. He received fellowship training in advanced head and neck oncologic surgery at the University of Texas MD Anderson Cancer Center. Dr. Nemechek earned his Master of Science degree in healthcare delivery from the Tuck School of Business at Dartmouth College. He serves as the national medical director of the Head and Neck Tumor Program for the Sarah Cannon Research Institute, the cancer and research arm of HCA Healthcare. He also serves as the chairman of the surgery department at Swedish Medical Center in Colorado. In addition to his clinical responsibilities, Dr. Nemechek has a specific interest in designing healthcare delivery systems that shape system-wide policies vital to improving the health and wellness of at-risk populations.
Andrew Nemechek

Latest posts by Andrew Nemechek (see all)

  • Systemic Therapy for Basal Cell Carcinoma of the Head and Neck - June 27, 2022
  • Service and Leadership - December 5, 2019

Published on December 5, 2019 by Andrew Nemechek

Service and Leadership

American Head and Neck Society – The Cancer Prevention Service

Image: Admiral William McRaven

November was declared National Veteran and Military Families Month. In November, we celebrate Veterans Day, a commemoration of the hundreds of thousands of men and women who have dedicated their lives and spirit leading in the defense of our country. At this Spring’s American Society of Head and Neck Surgery meeting in Austin, many of us listened to Admiral William McRaven with deep admiration as he described the many struggles, and successes, effective leaders experience in the course of a prescribed mission. He poignantly offered that the success of that mission, be it military, surgical, program-building, or overcoming life’s traumas depend on our vigilant attention to (seemingly) little things. His conclusion: every day, you must Make Your Bed. 

We all have the experience of participating in administrative discussions that focus on the “high-level view”, implying somehow that being in “the weeds” is too difficult, too dense, and that work in the weeds is better suited for foot soldiers than those that possess more stars and more years. I’m curious whether the current of endless meetings and their inefficiencies could be slowed if leaders spent more time in the weeds, making sure “the nail” is in place, so that the shoe, horse, soldier, battle, and war are not lost. Doubtless, teams can become bogged down in their detail-oriented efforts. How, then, do leaders provide the necessary balance that maintains and revisits the overall direction of a project and guides the day-to-day execution of its vision?

Our recent experience starting a service and outreach project might help to provide insight into such challenges. Similar to many other teams, we were fortunate to win support from the AHNS for our project that provides screening and clinical support services to the homeless in the Greater Denver area. We partner with a well-established shelter that helps many of its clients on a daily basis which has strengthened our efforts with follow-up in this highly transient population. In the past 18 months, we have evaluated more than 200 clients. From inception to the present, our team has led each other to meet predictable (and many unpredictable!) challenges. The following five points have helped achieve some of our successes and have guided our responses to our failures. Each is dependent on and independent of the other.

1. Invest in Human Capital: Successful leaders cast a wide net when building teams. Diversity is welcomed. Differences are discussed and celebrated. Commonalities among members are discovered and nurtured. Small, dedicated teams are formed that embrace a singular purpose. If practical, co-location is encouraged. Leaders make participation (volunteerism) easy, and recognize the importance of staff wellness. Our outreach team has experienced an overall improvement in regular job satisfaction (the fourth pillar of the Quadruple Aim in Healthcare.) Effective leaders consistently ask, “Who can best amplify change?” and amplify them.

2. Creatively Partner: Seemingly disparate groups when brought together offer unique experiences and resources that combine to create powerful synergies benefitting all involved. Our team partners with Father Woody’s (support organization for the homeless), App-based transportation services, the Colorado Coalition for the Homeless, multiple dental practices, our hospital system, our colleagues in multiple medical specialties, area schools, and others. Each of these organizations, in turn, leverages their resources to gain knowledge that informs their specific operational goals.  An excellent example of this process is Rush University Hospital in Chicago. That organization and its leaders have been recognized for their ability to understand the impact of social determinants of health has in their community and to partner with local and regional groups to create inclusive, sustainable, and culturally-competent investment opportunities that directly benefit at-risk populations. This process has been termed Place-Based Investing. A robust scale-up process has resulted in participation by a network 41 hospitals nationwide that purchase $50B worth of goods from their local communities and hold $150B in assets. Therefore, innovative leaders that recognize the potential of being service-oriented do so by consistently creating value directed towards advancing the social good.

3. Revisit “Mission” Frequently: It is easy for organizations to embrace “new” initiatives. Our culture frequently becomes enamored by the latest and greatest, dedicating its energy and resources to projects with short investment horizons. This results in many pilot projects being developed but that are not allowed to fully realize their potential. By revisiting one’s mission frequently, and messaging and living it effectively, service-oriented leaders help their teams create and maintain focus. Being agile within this focus, trying new things is important and challenging; creativity sparks innovation and productive disruption, but each new idea or experiment forwarded by the team must past the litmus test of being closely aligned with the original mission.

4. Anticipate Barriers: What are our blindspots? At times, our team has made the wrong assumption that others share the same ethos as we do about the project, especially because such projects are grounded in an effort to improve conditions for the marginalized. External political and economic forces reveal and forward their agendas which frequently aren’t aligned with ours. Good leaders search for alignment. Introspection reveals that we are all products of our personal history and are guided and biased by this narrative. The present state of instant digital connectedness skews our perception of time urgency: not every issue constitutes a burning platform. As such, our sense of patience has been lost. With respect to outreach and the advancement of social and healthcare equity, sustainable change truly depends on our honest answer to the question: Do we want to be Hero or Helper? We are reminded that policy does not happen to us; it happens through us, and that we must shape policy accordingly. Change psychology repeatedly demonstrates to us that impactful change can only move at the speed of trust.

5. Foster and Promote a Deep Sense of Gratitude: We lead clinical and administrative teams every day. Deadlines, inefficiencies, and crises demand our attention and take a heavy toll on our collective ability to recognize goodness even in the course of battle. However, we can choose to lead teams during these times with conspicuous gratefulness. Gratitude strengthens our posture and decision-making. Our team achieves a clarity of purpose that enables them to discern its purpose, weather overwhelming fatigue, understand loss, and to discover the vital resiliency needed to serve others. Apropos for this season of Thanksgiving, through gratitude, we are able to profoundly meet others in their story and humbly walk in their shoes.

The preceding discussion offers a few thoughts by one person that may serve to encourage ongoing dialogue regarding the relationship between leadership and service. The AHNS is certainly fortunate to have countless members engaged in impactful projects that forward its mission of mentorship and research leading to the contemporary, innovative, and vigilant care of our patients. The Cancer Prevention Service of the AHNS welcomes all comments from Society members regarding their individual experiences that could positively direct the Society’s efforts to design and implement initiatives that improve the health and wellness of our local and global communities.

For information on National Veteran and Military Families Month click here  or https://www.militaryfamily.org/november-is-military-family-appreciation-month/

 

  • Bio
  • Latest Posts
Andrew Nemechek

Andrew Nemechek

Dr. Nemechek earned his medical degree from the Tulane University School of Medicine, where he also completed his otolaryngology residency training. He received fellowship training in advanced head and neck oncologic surgery at the University of Texas MD Anderson Cancer Center. Dr. Nemechek earned his Master of Science degree in healthcare delivery from the Tuck School of Business at Dartmouth College. He serves as the national medical director of the Head and Neck Tumor Program for the Sarah Cannon Research Institute, the cancer and research arm of HCA Healthcare. He also serves as the chairman of the surgery department at Swedish Medical Center in Colorado. In addition to his clinical responsibilities, Dr. Nemechek has a specific interest in designing healthcare delivery systems that shape system-wide policies vital to improving the health and wellness of at-risk populations.
Andrew Nemechek

Latest posts by Andrew Nemechek (see all)

  • Systemic Therapy for Basal Cell Carcinoma of the Head and Neck - June 27, 2022
  • Service and Leadership - December 5, 2019

 

© 2002–2025 American Head and Neck Society · Privacy and Return Policy
· Managed by BSC Management, Inc