American Head & Neck Society

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

Published on by AHNS Office

Management of the cN0 neck for patients with cSCC parotid metastases

(from the AHNS Cutaneous Cancer Section)
by Yusuf Dundar, MD & A. Daniel Pinheiro, MD PhD

Metastatic squamous cell carcinoma from a cutaneous primary (cSCC) is the most common histology in patients with parotid gland metastasis. The standard treatment for cSCC with direct parotid gland invasion or intra-parotid lymph node metastasis is surgical excision and, in some cases, adjuvant radiotherapy +/- chemotherapy depending on presence of high-risk features. The extent of surgical intervention is controversial when there is no evidence of cervical lymph node metastasis.1 Since there are no prospective randomized trials regarding management of the cN0 neck in patients with parotid gland metastases, we have to rely on observational data from retrospective reviews (although in some the data were collected prospectively).

One area of controversy is the management of the deep lobe when there are cSCC metastases to the superficial lobe. Obviously, the minimum standard would include superficial parotidectomy with facial nerve dissection (SP). Some have proposed dissection of the deep lobe sparing the facial nerve (i.e., total conservative parotidectomy -TCP – as opposed to total radical parotidectomy) when there is disease in the superficial lobe. The reasons for additional surgery to remove the deep lobe are the fact that studies have shown occult metastatic disease to the deep parotid lobe2. In one retrospective single-institution series which included 42 patients with cSCC metastatic to the parotid, 26% of patients had occult metastases to the deep parotid lobe3. In that study, parotid bed local control was reported to be 93% for patients with cSCC3 and arguably local control might have been lower if the occult disease in the deep lobe had not been removed. However, since most of these patients have indications for adjuvant radiation, it is difficult to demonstrate if there is an additional benefit of TCP as opposed to just removing the parotid tissue lateral to the facial nerve, i.e., SP. For instance, in another retrospective review, Hirshoren et al.4 reported that 65 of 78 patients with cSCC metastatic to the parotid had SP instead of total parotidectomy. The parotid bed local control in those who received adjuvant radiation was 96.3% and they argued that more extensive parotid surgery might not be needed. However, the local control for those who did not receive radiation dropped to 73%. Therefore, there may be a role for TCP when the disease in the superficial lobe is limited without any a priori indications for adjuvant radiation. Even so, some would argue against TCP because of added dissection time, increased risk of facial nerve injury (at least transiently) and additional aesthetic deformity from loss of volume in pre-auricular area.

Occult nodal disease in cervical lymph nodes is considered a high-risk feature and poor prognostic factor, which requires appropriate treatment. Weiss et al. introduced a decision tree analysis in planning for elective neck dissection (END) for clinically N0 necks and proposed a 20% cut off to offer END for head and neck squamous cell cancers.5 There are variable data regarding occult cervical nodal metastasis in patients with clinically positive parotid metastasis, ranging from 14.7% to 45.2%.6,7 A recently published meta-analysis reported 22.5% occult cervical metastasis.8 Ebrahimi et al reported Level II is the most commonly involved compartment (35.6%), followed by level III (14.6%).9  Patients without any Level II or III nodal involvement did not display disease in level IV or Level V. O’Brien et al.  and Vauterin et al. reported similar results.1,10 Aggressive tumor histological features, advanced T stage, thick/deep primary tumors, immunosuppression, and pre-auricular primary tumor location were high risk features for having occult cervical node metastasis.

Cervical lymph node involvement is associated with poor survival outcomes. Five-year disease specific survival (DSS) and overall survival (OS) rates were reported ranging from 58% to 83% and from 48% to 80%, respectively in patients with cervical nodal metastasis. 8 However, there were no data available to compare survival rates in patients with occult metastasis relative to those with clinically positive nodes. There were very limited data on those treated by elective neck irradiation (ENI) versus END followed by adjuvant radiotherapy for patients with parotid metastasis. Herman et al compared recurrence rates following ENI versus END and adjuvant radiotherapy.11 The recurrence rates were reported as 1.5% and 2.4% in ENI and END + adjuvant radiotherapy arms respectively (p > 0.05). The recurrence rates were not statistically significant, and the study had many limitations including retrospective setting, high occult nodal metastasis in surgery arm (45.2%), and limited number of patients in study arms. The other limitation of elective neck irradiation is the inability to pathologically stage the neck. Additionally, there is a concern that the addition of neck dissection may increase complication rates, but literature is scant in this area.

The literature supports that there is a high incidence of occult cervical nodal invasion (22.5%) in patients with clinically positive parotid metastasis who meet the criteria to offer END per the Weiss principle. However, this decision tree analysis is designed for purely clinically N0 necks. The patient population with clinically positive parotid metastasis has already demonstrated metastatic potential. Thus, it seems very reasonable to offer END as an addition to the Weiss principle. The extent of neck dissection should include at least level II and III, and typically, supraomohyoid (Level I, II and III) neck dissection is recommended. However, the location of the primary tumor may further inform the surgical plan (eg; posterior scalp, midface tumors, or primary unknown tumors).

Recently, the addition of neoadjuvant immunotherapy is being considered for cases with advanced parotid metastases based upon small, early studies. It is unclear how the consideration of elective neck dissection would be affected in this population. At this point, the use of neoadjuvant immunotherapy in these patients should be reserved to the clinical trial setting.

References:

  1. O’Brien CJ, McNeil EB, McMahon JD, Pathak I, Lauer CS, Jackson MA. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous cell carcinoma of the parotid gland. Head Neck. 2002;24(5):417-422.
  2. Pisani P, Ramponi A, Pia F. The deep parotid lymph nodes: an anatomical and oncological study. J Laryngol Otol. 1996 Feb;110(2):148-50. doi: 10.1017/s0022215100133006. PMID: 8729499.
  3. Thom JJ, Moore EJ, Price DL, Kasperbauer JL, Starkman SJ, Olsen KD. The Role of Total Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma and Malignant Melanoma. JAMA Otolaryngol Head Neck Surg. 2014 Jun;140(6):548-54. doi: 10.1001/jamaoto.2014.352. PMID: 24722863.
  4. Hirshoren N, Ruskin O, McDowell LJ, Magarey M, Kleid S, Dixon BJ. Management of Parotid Metastatic Cutaneous Squamous Cell Carcinoma: Regional Recurrence Rates and Survival. Otolaryngol Head Neck Surg. 2018 Aug;159(2):293-299. doi: 10.1177/0194599818764348. Epub 2018 Mar 13. PMID: 29533706.
  5. Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg. 1994;120:699-702.
  6. Palme CE, O’Brien CJ, Veness MJ, McNeil EB, Bron LP, Morgan GJ. 
Extent of parotid disease influences outcome in patients with metastatic cuta-neous squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2003; 129(7):750-753.
  7. Herman MP, Amdur RJ, Werning JW, Dziegielewski P, Morris CG, Mendenhall WM. Elective neck management for squamous cell carcinoma metastatic to the parotid area lymph nodes. Eur Arch Otorhinolaryngol. 2016;273:3875-3879.
  8. Rotman A, Kerr SJ, Giddings CEB. Elective neck dissection in metastatic cutaneous squamous cell carcinoma to the parotid gland: A systematic review and meta-analysis. Head Neck. 2019 Apr;41(4):1131-1139.
  9. Ebrahimi A, Moncrieff MD, Clark JR, et al. Predicting the pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck based on location of the primary. Head Neck. 2010;32:1288-1294.
  10. Vauterin TJ, Veness MJ, Morgan GJ, Poulsen MG, O’Brien CJ. Patterns of lymph node spread of cutaneous squamous cell carcinoma of the head and neck. Head Neck. 2006;28(9):785-791.
  11. Herman MP, Amdur RJ, Werning JW, Dziegielewski P, Morris CG, Mendenhall WM. Elective neck management for squamous cell carcinoma metastatic to the parotid area lymph nodes. Eur Arch Otorhinolaryngol. 2016;273:3875-3879.

 

Yusuf Dundar, MD – An Assistant Professor of Otolaryngology and Head&Neck Surgery at Texas Tech University (Lubbock/Texas). Dr. Dundar specializes in all aspects of head and neck oncology, including cutaneous malignancies, salivary gland cancers, thyroid cancers, mucosal head and neck cancers. He also performs complex microvascular reconstruction of the head and neck as well as transoral robotic surgery.

Daniel Pinheiro, MD PhD FACS – Daniel PInheiro is a head and neck surgeon at Mercy Clinic in Springfield, MO. He is the Director of Surgical Oncology at Mercy Clinic and has an interest in outcomes research. His clinical areas of expertise are in oropharynx cancer and endocrine head and neck surgery.

 

 

Published on by AHNS Webmaster

TODAY: AHNS Educational Series: Presented by AHNS In Partnership with the Head and Neck Alliance “HPV-Related Oropharyngeal Cancer: The Importance of Early Detection & Prevention

AHNS Educational Series: Presented by the AHNS Cancer Prevention and Survivorship/Supportive Care/Rehabilitation Services
In Partnership with the Head and Neck Cancer Alliance

“HPV-Related Oropharyngeal Cancer: The Importance of Early Detection and Prevention”

The AHNS gratefully acknowledges the generous educational grant in support of this activity from Roche.

Wednesday, July 20, 2022 at 7:00 PM Eastern
This session is one hour and complimentary to all!

Moderator:
Ann Gillenwater, MD – AHNS Cancer Prevention Service Vice-Chair

Panelists:
Laura Dooley, MD – AHNS Cancer Prevention Service Member
Warren Swegal, MD – AHNS Survivorship/Supportive Care/Rehabilitation Service Member
Kristin Oliver, MD – Pediatrician
Michael Murphy – Survivor, Head and Neck Cancer Alliance Ambassador

At the end of this webinar, participants will be able to:

  • Identify the current trends in the epidemiology of HPV-related oropharyngeal cancer
  • Recognize the common clinical presentation of HPV-related oropharyngeal cancer
  • Distinguish the short and long-term side effects that come with head and neck cancer treatment
  • Articulate current barriers to population-based screening for HPV-related oropharyngeal cancer, thus emphasizing the importance of primary prevention
  • Outline the current indications for HPV-vaccination and the role it plays in prevention of HPV-related cancers.


Published on by AHNS Webmaster

AHNS Educational Series: Presented by AHNS In Partnership with the Head and Neck Alliance “HPV-Related Oropharyngeal Cancer: The Importance of Early Detection & Prevention

AHNS Educational Series: Presented by the AHNS Cancer Prevention and Survivorship/Supportive Care/Rehabilitation Services
In Partnership with the Head and Neck Cancer Alliance

“HPV-Related Oropharyngeal Cancer: The Importance of Early Detection and Prevention”

The AHNS gratefully acknowledges the generous educational grant in support of this activity from Roche.

Wednesday, July 20, 2022 at 7:00 PM Eastern
This session is one hour and complimentary to all!

Moderator:
Ann Gillenwater, MD – AHNS Cancer Prevention Service Vice-Chair

Panelists:
Laura Dooley, MD – AHNS Cancer Prevention Service Member
Warren Swegal, MD – AHNS Survivorship/Supportive Care/Rehabilitation Service Member
Kristin Oliver, MD – Pediatrician
Michael Murphy – Survivor, Head and Neck Cancer Alliance Ambassador

At the end of this webinar, participants will be able to:

  • Identify the current trends in the epidemiology of HPV-related oropharyngeal cancer
  • Recognize the common clinical presentation of HPV-related oropharyngeal cancer
  • Distinguish the short and long-term side effects that come with head and neck cancer treatment
  • Articulate current barriers to population-based screening for HPV-related oropharyngeal cancer, thus emphasizing the importance of primary prevention
  • Outline the current indications for HPV-vaccination and the role it plays in prevention of HPV-related cancers.


Published on 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.
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

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Published on by AHNS Webmaster

AHNS Educational Series: Presented by the AHNS Cancer Prevention and Survivorship/Supportive Care/Rehabilitation Services

HPV-Related Oropharyngeal Cancer: The Importance of Early Detection &  Prevention

AHNS Educational Series: Presented by the AHNS Cancer Prevention and Survivorship/Supportive Care/Rehabilitation Services In Partnership with the Head and Neck Cancer Alliance

Wednesday July, 20, 2022 at 7:00 PM EST
This session is an hour and complimentary for all!

The AHNS gratefully acknowledges the generous educational grant in support of this activity from Roche.

Moderator:
Ann Gillenwater, MD– AHNS Cancer Prevention Service Vice-Chair

Panelists:
Laura Dooley, MD – AHNS Cancer Prevention Service Member
Warren Swegal, MD – AHNS Survivorship/Supportive Care/Rehabilitation Service Member
Kristin Oliver, MD– Pediatrician
Michael Murphy –Survivor, Head and Neck Cancer Alliance Ambassador

At the end of this one-hour webinar, participants will be able to:
1. Identify the current trends in the epidemiology of HPV-related oropharyngeal cancer
2. Recognize the common clinical presentation of HPV-related oropharyngeal cancer
3. Distinguish the short and long-term side effects that come with head and neck cancer treatment
4. Articulate current barriers to population-based screening for HPV-related oropharyngeal cancer, thus emphasizing the importance of primary prevention
5. Outline the current indications for HPV-vaccination and the role it plays in prevention of HPV-related cancers.

Register Here Now!