Surgical approaches to head and neck sarcomas –  current concepts and perspectives

Summary

Objective: Soft tissue sarcomas represent a unique form of malignancy within the head and neck region, characterized by low incidence. Despite being commonly regarded as rare tumors in adults by numerous authors, sarcomas constitute a subset of malignant diseases associated with poor prognoses across diverse age groups, including children, adolescents, and adults. Recent literature highlights the considerable number of sarcoma cases reported, suggesting that while they may be uncommon, they are not truly rare, with 27,908 cases reported in a seven-year period in Europe among a population of 500 million inhabitants. This emphasizes the importance of recognizing sarcomas as infrequent tumors, rather than being rare. Consequently, it is essential to have up-to-date knowledge and evidence-based recommendations to inform and guide the clinical practice in the management of these heterogeneous types of mesenchymal tumors. Methods: We conducted a literature review about head and neck sarcomas using the Web of Science database. The objective of our review was to identify relevant papers discussing various treatment modalities of sarcomas in the head and neck region. This study analyzed the diagnostic criteria for sarcomas and the therapeutic approach, focusing on the surgical approach for the management of head and neck sarcomas. Discussion: Soft tissue sarcomas of the head and neck are infrequent, with an estimated annual incidence of approximately 5 per 100,000 individuals. Recommendations are based on numerous factors, while directing the attention towards identifying markers implicated as risk factors for sarcomas is crucial. Pathological review coupled with the advancement of molecular techniques is essential for this inquiry. Diagnosis relies heavily on biopsy and histological findings, including immunohistochemistry and the detection of specific tumor markers. Recommended imaging methods include ultrasound, CT, HRCT, MRI, and PET/CT scans. To achieve precise classification and stratification, we must include a multidisciplinary oncological team constructed of pathologists, oncologists, surgeons, and radiologists. Treatment protocol and planning for head and neck sarcomas take into consideration factors such as size, localization, and biological behavior, as described in existing literature. The literature extensively analyzes data connected to fundamental treatment modalities in oncology, including surgery, radiotherapy, and chemotherapy. Radical surgery, ensuring R0 margins, is definite in the treatment approach.

Keywords:

diagnosis – therapy – treatment – recommendation – guidelines – head and neck sarcoma

Introduction

Soft tissue sarcomas account for a distinct form of malignancy within the head and neck region, characterized by relatively low incidence. Numerous authors have described this malignancy as a rare tumor in adults. However, sarcomas of the head and neck constitute a subgroup of malignant disease associated with poor prognosis in different age groups, including children, adolescents, and adults. Giannini et al. (2021) analysed 101 cases of Head and Neck Soft Tissue Sarcomas (HNSTS) [1].

The study of HNSTS examined the overall survival data in comparison with the TNM staging system, illustrating a negative prognostic association with tumor size (>5 cm) or infiltration depth (5 cm). Additionally, it was suggested that further multicentric cohort analyses are necessary to enhance the statistical strength of these findings. Stiller et al. (2013) described the incidence of sarcomas across 27 EU countries, reporting an incidence of 5.6 cases per 100,000 per year from 1995 to 2002, resulting in a total of 27,908 sarcoma cases across the entire body’s area, with 84% being soft tissue sarcomas and 14% being exclusively bone sarcomas [2]. Furthermore, Galy Bernadoy et al. (2016) published that the annual incidence of HNSTS was approximately 5 individuals per 100,000 per year [3].

HNSTS represent a heterogeneous histological group comprising of 50 histological subtypes, each exhibiting distinct biological behavior, patterns, treatment, and prognosis. Various subtypes are considered to have a poor survival rate (5-year overall survival, approximately in 60% of cases) according to Galy-Bernadoy at al. (2016). Rapidis AD (2008) observed worse survival outcomes in head and neck sarcomas compared to sarcomas arising in extremities. Nodal metastases account for 3–10% of head and neck sarcomas. Rapidis highlights the potential benefit of chemotherapy, particularly for high-grade sarcomas, in achieving long-term survival and local control. Significant evidence has been described in molecular targeted therapies with tyrosine kinase inhibitors and antiangiogenic agents [4]. Peng et al. (2014) conducted an extensive analysis of 11,481 adult HNSTS and 1,244 pediatric HNSTS cases, reporting a 10-year survival rate in adults (61–76%) and in pediatric HNSTS cases (71–84%), dependent on their histological subtype. Survival outcomes depend on various factors, including tumor size, local tumor spread, histological subtype, and treatment radicality (margin status). Among pediatric cohorts, rhabdomyosarcoma, malignant fibrous histiocytoma, and osteosarcoma were described as the most common histological subtypes of sarcoma [5].

The literature highlights the significance of sarcoma, with noteworthy incidence of 27,908 cases reported over a seven-year period across Europe, within a population of 500 million inhabitants. Sarcomas are infrequent but their prevalence establishes their significance beyond rarity. Thus, it is imperative to integrate up-to-date knowledge and recommendation into clinical practice in order to effectively manage and treat the diverse spectrum of malignant mesenchymal tumors.

Coca-Pelaz et al. [6] conducted a meta-analysis consisting of 560 patients from 64 articles, focusing on radiotherapy-induced sarcomas. The analysis revealed a radio-induced sarcoma with a frequency of 0.15%, with the nasopharynx being the most common location. Among radio-induced sarcomas, the sinonasal region was the predominant site, with osteosarcoma being the primary sarcoma type, followed by fibrosarcoma. Mortality rate associated with radio-induced sarcoma reached 40.7% with a mean survival duration of 13.9 months. The majority of authors suggest that HNSTS represent a diverse collection of malignant mesenchymal tumors.

Andersen et al. (2019) conducted an analysis covering eight studies involving 1,120 patients from six countries, revealing the presence of 24 histological subtypes of sarcomas. Among these, 607 sarcomas (57%) were less than 5 cm in diameter, 745 sarcomas were grade 3, and 1,059 cases received surgical treatment [7]. The overall survival rate was 74%, with only a 56% disease-free interval observed over five years. Andersen at al. (2019) described the relatively poor prognosis associated with sarcomas, which constitute a high treatment variability. Thus, they recommend the implantation of treatment guidelines to enhance survival outcomes. Recurrence of sarcomas usually manifests locally [7]. The following authors have described the various biological behaviour or sarcomas with moderate prognosis [8, 9]. In the cited literature, the primary prognostic factors of sarcomas were identified, including tumor size, local extension, histologic grade, and margin status after surgical-intervention treatment [3–9].

The staging of sarcomas is usually performed according to the American Joint Committee on Cancer (AJCC) 2010 classification [10]. Despite this, various studies have mentioned and emphasized the absence of a standardized staging system for sarcomas, particularly concerning soft tissue sarcomas in the head and neck region [11, 12].

Baker introduced a staging system for sarcomas based on histological grading [12], while many other authors used the AJCC/UICC classification [13]. Current recommendations and targeted management guidelines for sarcomas are based on:

• surgical resection with negative margins;
• postoperative radiation therapy, which offers a prognostic advantage;
• effectiveness of chemotherapy is variable across histological types.

Sarcomas are divided into two subtypes for surgical treatment recommendation based on staging criteria [13, 14]:

• level 1: localized type – indicating surgery;
• level 2: metastatic type – suggesting no indication for surgery.

The objective of this paper is to gather relevant data regarding head and neck sarcomas, including their incidence, classification, and treatment recommendations for clinical practice derived from a meta-analysis of the literature.

Methods

We conducted a literature review about head and neck sarcomas using the Web of Science database. Our analysis aimed to identify scientific papers which present and describe various treatment modalities within this anatomical region. The investigation examined various diagnostic criteria and treatment regimens specific to head and neck sarcomas. Our study focused exclusively on the Web of Science database to diminish citation duplicate citations, therefore ensuring the reliability of our findings. The key words utilized included “Sarcoma”, “Head”, “Neck area”, “Epidemiology”, “Incidence”, “Treatment results”, “Treatment protocol”, and “Classification”. The resulting resource evolution diagram is depicted in Scheme 1.

Our search criteria yielded a total of 17,775 papers (7,942 in WoS). Among these, papers which focused on head and neck sarcomas were identified as follows: larynx (417), pharynx (97), paranasal sinuses (285), orbit (500), jaw (450), maxillary sinus (326), ear (200), and nasopharynx (368). The exclusion criteria included case reports, meeting reports, and radio-induced sarcomas. Numerous publications were excluded due to incomplete data, lack of histological analysis, and the use of incomplete diagnostic methods (e. g., absence of imaging methods, molecular analysis). Additional papers were excluded for lacking analysis of surgical treatment outcomes (e. g., no margin description, metastatic presence, no proper description of treatment modalities). Some parameters were unavailable in certain studies. A representative selection of literature was included to discuss head and neck sarcoma treatment.

We reviewed 56 selected papers which met our inclusion criteria supplemented with additional literature about head and neck sarcoma treatment.

Discussion

Coca-Pelaz et al. (2012), suggested that the male-to-female ratio for head and neck sarcomas was 2: 1. The most frequent sarcomas were as follows: nasopharynx (65.7%), sinonasal region (3.7%), central nervous system (3.4%), eye (2.5%), and larynx (2.3%). The predominant histologies were osteosarcoma (35.5%) and fibrosarcoma (23%). The mean age at the time of primary treatment was 43.1 years old, ranging from 2 to 81 years [6].

Peng et al. (2014) conducted a study where 11,481 head and neck sarcoma cases across 18 registries from 1970 to 1990 were collected and analyzed. Survival rates were analyzed, revealing that for all types of sarcomas, 76% survived at 2 years, 66% at 5 years, and 61% at 10 years. Survival rate ranged between 30% to 90%. Rhabdomyosarcoma and osteosarcoma demonstrated the worst survival rates, whereas leiomyosarcoma, malignant fibrous histiocytoma, and chondrosarcoma exhibited the highest survival rate of 88–90%. The study concluded that surgery is the mainstay for treatment of head and neck sarcomas with adjuvant radiotherapy. Positive resection margins were identified as a major risk factor [5].

The recommendations for surgical treatment are based on several factors:

• soft tissue sarcomas are rare, yet they exhibit an aggressive behavior with an incidence of approximately 5 per 100,000 per year;
• sarcomas occurring in the head and neck regions are infrequent. Risk factors for sarcoma development include genetic predisposition and exposure to radiation;
• the 5-year overall survival rate is approximately 60%, with recurrence cases commonly occurring locally;
• thorough pathologic review and utilization of molecular techniques are therefore essential.

The classification of soft tissue sarcomas in the head and neck region was described in the literature [10–14]. The literature extensively analyzed the staging systems and validation nomograms of head and neck sarcomas. The work by the Shuman group is particularly notable, demonstrating oncological outcomes of patients with head and neck sarcomas, which can be accurately predicted using the AJCC and UICC staging systems, alongside individual prognostic information such as soft tissue sarcoma nomogram for clinical practice [15].

Scelsi et al. (2019) conducted a review of the diagnostic classifications of sarcomas, focusing on different imaging modalities, such as MRI, CT, and CTHR, according to the WHO head and neck sarcoma classification [16]. Vibhakar et al. (2021) presented data analysis regarding the positive results using PET/CT and whole-body MRI in sarcoma staging, highlighting the detection of soft tissue sarcoma and/or recurrence diagnosis. The new advancements of using artificial intelligence (AI) were also discussed [17].

Numerous authors have described treatment recommendations, including the surgical approach and prognosis analyses based on the biological behavior of sarcomas. These analyses revealed that sarcomas can be categorized into tumors with good, moderate, and poor prognoses and/or survival outcomes [16–18].

Accurate diagnosis is based upon histological, immunobiological, and molecular analyses of tissue specimens.

Clinical practice is further supported by a selection of key representative papers [19–36], summarized in Tab. 1.

The table has been constructed using data extracted from literature sources [19–36], taking into consideration the scarcity of data on rare diseases and cohort studies. Note that for various types of sarcomas, there is a lack of cohort studies and case series analyses.

Rapidis (2008) described the low incidence of metastasis in sarcomas (3–10%) [4]. Sarcomas demonstrate a spectrum of biological behavior, ranging from relatively slow-growing lesions to locally aggressive malignant tumors. Yanzon et al. (2021) conducted a sizable cohort study of 48 head and neck sarcoma patients finding an overall 5-year survival rate of 68%. The radio-induced sarcomas exhibit lower survival rate of only 58%. Their analysis revealed that positive and/or close resection margins as an independent negative prognostic factor [39]. Sturgis and Potter (2003) noted that sarcomas represent less than 1% of malignant tumors in the United States, with only 5–15% occurring in the head and neck region. Adjuvant chemotherapy is utilized for high-grade sarcomas and adjuvant therapy is aimed to control disease progression. The primary management of sarcoma remains surgery [40].

Various authors have advocated radiotherapy for sarcoma treatment. Orton et al. (2016) published a case report describing radiotherapy treatment for high-grade pleiomorphic sarcoma, supporting the concept of the recommended protocol based on radical surgery treatment whenever possible, with adjuvant or neoadjuvant radiotherapy or chemotherapy [41]. Vazques et al. (2022) described the pencil mean proton therapy [42]. The choice of the type of proton beam therapy depends on the histological type and location of the sarcoma, as described by Astl et al. (2022) [43]. In the last decade, biological agents have been used in the treatment of soft tissue sarcomas. Becquart et al. (2018) described the therapy with bevacizumab and paclitaxel. Comprehensive data about regular soft tissue sarcoma therapy requires an extensive analysis in the future [44].

In most soft tissue sarcomas of the head and neck series, the grade of the tumor and margin status are important for local control of the tumor. Distant metastasis findings are often described as the most influential determinant of the overall survival in this heterogeneous tumor group.

Various histological types and TNM classifications may also influence the prognosis of soft tissue sarcomas. Having said that, chondrosarcoma is usually well-differentiated pathologically and often has better prognosis [3]. A comprehensive analysis conducted by Dietz and Frerich (2009) validated the necessity for large biopsies for accurate diagnosis, and recommended an interdisciplinary treatment approach [45]. Dietz et al. (2022) recommended therapy standards for soft tissue sarcomas in the head and neck region [46]. von Mehren et al. (2022) based the therapy of head and neck sarcomas on NCCN Clinical Practice Guidelines (Oncology version 2.2022) and German Guidelines [47, 48].

In general, the overall survival rate of head and neck sarcomas tends to be poorer compared to those found in the extremities. Upon reviewing the literature, 5-year survival rates for patients with soft tissue sarcomas of the head and neck ranged from 32 to 75%.

Park et al. (2015) conducted an analysis of 122 cases of head and neck sarcomas, identifying age, tumor size, nodal metastasis, and stage of the disease as significant prognostic factors [49].

Across all publications, it was concluded that the important positive prognostic factors include tumor-free resection margins and choice of therapy (radical surgery and irradiation), while some suggest chemotherapy alone. It was concluded by all the analyses that due to the rare incidence of head and neck sarcomas, there was limited information and choice of treatment modalities presented in many papers, and it is necessary to focus on clinical multicenter studies [50]

Specific sarcomas are radio-induced tumors. Cannon et al. (2019) documented the improved disease-free interval survival with adjuvant radiation therapy for positive sarcoma tumor margins [51]. Surgery is frequently the treatment of choice in various protocols, guidelines, and studies for head and neck sarcomas [52]. Surgery remains the treatment of choice for many types of head and neck sarcomas, with radical surgery showing effectiveness for moderate and high-trade sarcomas and moderate surgery for low--grade sarcomas. Mahmoud et al. (2016) concluded that adjuvant therapy (radiation and/or chemotherapy) improved the survival rate for high-grade sarcomas [53].

Callagaro et al. (2017) developed and described a new nomogram for the follow-up of head and neck sarcomas into clinical practice [54], providing valuable insights for making decisions regarding adjuvant therapy for soft tissue sarcomas in the head and neck region.

In contrast, Williams et al. (2018) gathered data about radiation-induced sarcomas, modifying the treatment approach and protocols, in addition to influencing the decision-making in personalized oncological therapy recommendations [55]. Based on data from de Bree et al.’s study (2006) [56], it is clear that due to the relatively low frequency and rare incidence of head and neck sarcomas, along with numerous treatment modalities and protocols, clinical multicenter studies are crucial for the establishment of standardized protocols and deeper understanding of head and neck sarcoma management.

Despite available data and analyses of head and neck sarcomas, we propose the following recommendation for clinical practice. In contrast, we utilize the insights and experience gathered from our institutions [57–60].

These facts and analysis of literature suggest the next recommendations for today’s clinical practice for the treatment of head and neck sarcomas:

Diagnosis is based on:

a)
Biopsy and histology, which includes immunohistochemistry and the detection of specific tumor markers.

b)
General investigation of tumor signs.

c)
Recommended imagining methods include ultrasound, CT, HRCT, MRI, PET-scan (PET-CT scan) included.

d)
Genetic analysis is necessary for precise diagnosis in the future.

The exact classification and stratification must be done by an oncological team composed of pathologists, oncologists, surgeons, and radiologists.

General guidance for the surgical treatment protocol and planning for head and neck sarcomas relies on several factors such as tumor size, location, and biological behavior, as noted in the literature. The literature proves data analyses of basic treatment modalities in oncology, including surgery, radiotherapy, and chemotherapy. At present, there is limited available data about immunotherapy.

Surgical treatment focuses on addressing the primary tumor and management of metastatic disease. The primary goal of surgery is achieving complete resection with negative margins (R0 status).

Various types of surgeries, either total or partial, are described in the literature depending on the size of the tumor. Whenever possible, an endoscopic approach may be used for tumors located in the larynx or nasal cavity, while large tumors with evident infiltration to an extensive area may require a total tumor resection approach. In contrast, for certain histological types like chondrosarcoma, it is possible to use a more conservative surgical approach like de-escalated surgery and/or organ preservation protocol.

The main goal of surgery is complete resection with negative margins (R0 status).

The literature indicates that 10–12% of soft tissue sarcomas of the head and neck develop early neck metastasis. In our cohort data of surgically treated patients, nodal or distant metastases were generally absent, likely due to early diagnosis followed by radical surgical treatment. Various authors described that fibrosarcoma, the more frequent type encountered, exhibits metastasis in less than 25% of patients, even in the poorly differentiated cases. Thus, elective neck dissection is generally not necessary. In our series, one surgically-treated patient presented with a neck mass (enlarged lymph node was evident on ultrasound, CT, and MR imaging), leading to neck dissection (10%) which confirmed the presence of neck metastasis. Once again, the surgical goal is to achieve complete resection with negative tumor presence (R0 status).

The role of RT in the treatment of head and neck sarcomas has undergone significant changes over the past three decades. Literature suggests that sarcomas demonstrate considerable resistance to radiotherapy. However, numerous authors have noted the importance of radiotherapy as a critical adjunct in soft tissue sarcoma treatment, aimed to reduce the incidence of local recurrence.

Primary indications for postoperative radiotherapy, as recommended in the literature, include high-grade lesions, positive surgical margins, large tumors (>5 cm), and recurrent lesions.

Statistical documentation of chemotherapy’s effect on various sarcomas remains insufficient. We acknowledge that neoadjuvant chemotherapy and radiotherapy have been described solely for rhabdomyosarcoma. Immunotherapy and biological therapy are not often utilized, and we found no studies which support their use.

Modified treatment protocol recommendations

a)
Surgery: surgical intervention must be radical. Surgical margins have a crucial importance for sarcoma grading. The primary aim must be R0 margin status.

b)
Radiotherapy: the choice of beam therapy depends on oncological protocol, which includes staging, grading, histological type of sarcoma, and radicality of the prior surgery, if performed.

c)
Chemotherapy: aggressive histological subtypes of sarcomas require chemotherapy treatment, which includes a combination of vincristine, doxorubicin, cyclophosphamide/iphosphamide, mensa, and etoposide. Other chemotherapy regimens depend on the histological type and biological activity of the sarcomas. However, in many cases the effect of chemotherapy did not have a significant influence on survival outcomes.

Surgery indications in clinical practice:

• T1 tumor with a diameter less than 2 cm – limited organ preservation procedures and/or partial organ resections if necessary;
• T2 tumor with a diameter greater than 2 cm and less than 4 cm – partial or total organ resections if possible;
• T3 tumor with a diameter greater than 4 cm localised type – total organ resection;
• N0 – no evidence of nodal metastases – no block lymph node dissection;
• N1 – evidence of lymph node metastases – block (radical) neck lymph node dissection;
• M0 – no evidence of distant and organ metastases.

The following findings suggest no surgery indication:

• T4a – tumor of the brain layers, brain, orbit, masticatory muscles, and face skeleton;
• T4b – tumor growing into the brain, surrounding the carotid, and infiltrating the prevertebral space or central nervous system through perineurial growth;
• N any;
• M any.

Postoperative adjuvant radiotherapy is exclusively reserved for high-grade tumors with positive surgical margins. Neoadjuvant chemotherapy and/or radiotherapy is recommended for rhabdomyosarcoma only.

The treatment steps for head and neck sarcomas in clinical practice are based on the analysis results:

• surgery if possible;
• neoadjuvant chemoradiotherapy if the reduction of the tumor can improve the surgical outcome;
• adjuvant chemoradiotherapy should be adjusted according to the cellular types of sarcomas and the presence of any receptors and/or mutation types;
• biological therapy if applicable.
• Follow-up for sarcoma involves:
• appointment to exclude local recurrence and general manifestations of sarcoma presence. Recommended methods for the head and neck area include endoscopy and ultrasound every 2–4 months for the first year after radical surgery and/or adjuvant radiotherapy or chemotherapy;
• narrow-band imaging (NBI) endoscopy as needed;
• yearly MRI, CT, HRCT, and/or PET-scan;
• monitoring of tumor markers, if applicable.

Conclusion

Diagnosing head and neck sarcomas relies on biopsy and histology, including immunohistochemistry and the identification of specific tumor markers.

The treatment approach of head and neck sarcomas depends on various factors such as size, localization, and biological behavior of the tumor.

The primary goal of the surgical approach is complete resection of the tumor with negative surgical margins (R0 status).

Postoperative adjuvant radiotherapy is exclusively reserved for high-grade tumors with positive surgical margins. Neoadjuvant chemotherapy and/or radiotherapy is recommended solely for rhabdomyosarcoma.

Funding

This work was supported by the Project MO 1012 of the Ministry of Defence of the Czech Republic and by the Cooperation Program, research area SURG, Charles University, Czech Republic.

Conflict of interest statement

The author of the article declares that he has no conflict of interests in connection with the topic, creation and publication of this article, and that neither the creation nor the publication of the article was supported by any pharmaceutical company. This statement also applies to all co-authors.