Radiation Induced Sarcomas of the Head and Neck

European Journal of Clinical Oncology

ISSN - 2732-2654

Research Article - (2019) Volume 1, Issue 1

Radiation Induced Sarcomas of the Head and Neck

Liuzzi Juan F*, DaCunha Maribel, Siso Saul and Salas Daniuska
*Correspondence: Liuzzi Juan F, Attending Head and Neck Surgeon of the Head and Neck Department, Oncology Hospital of the Venezuelan Institute of Social Security, Caracas 1040, Venezuela, Email:

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Background: Head and neck sarcomas are uncommon clinical entities and radiation-induced sarcomas of the head and neck (RISHN) even more. They comprise a very serious long-term complication of radiation therapy. Patients and methods: We reviewed the medical records of all patients with diagnosis of head and neck sarcomas evaluated and treated in our Hospital from 2005 to 2015, and selected those who had sarcomas related to the use of external beam radiotherapy. Results: The incidence of RISHN was 17.5% among all head and neck sarcomas evaluated. Most patients had sarcomas located at the maxillary sinus. Leiomyosarcoma was the most common histological type. The latency period average between time of initial radiation therapy and time of diagnosis of RIHNS was 18.4 years. Patients received single or combined treatment modalities, including surgery, chemotherapy and/or radiation therapy, according to the criteria for tumor resectability. The average follow-up was 24.42 months and the disease free-survival rate at the end of the study was 28.6%. Conclusions: The overall prognosis of RISHN is poor regardless the modality of treatment received. Despite the difficulties to perform a surgical procedure in a radiated field, we consider surgery the best option to treat RISHN, over chemotherapy and radiation therapy.


Head and neck, radiation-induced sarcomas.


Radiotherapy is a common modality of treatment for some types of head and neck cancers. It could be used as a definitive treatment or as an adjuvant therapy as well. Sometimes radiotherapy induces the development of other tumors, such as squamous cell carcinomas and sarcomas. These tumors are known as radiationinduced second malignancies. In particular, radiation-induced sarcomas (RIS) are probably the most devastating of the late complications of radiotherapy [1].

RIS represent less than 5% of all sarcomas and account approximately 12% of all radiation-induced second malignancies, being the second most common after radiation-induced squamous cell carcinoma [2].

Radiation-induced sarcomas of the head and neck (RISHN) have been related with poor prognosis, when compared to de novo sarcomas located in the same areas. Probably, the main reason is that the diagnosis is more difficult due to the radiation-associated tissues changes that occur in the radiation field. Another important reason is the difficulty to perform surgery or to give more radiation within a previous irradiated area [3].

The purpose of this case series report is to describe all the clinical aspects of the patient with diagnosis of RISHN treated in our Hospital and to make a review of the literature.

Patients and Methods

The study was focused on patients with head and neck sarcomas evaluated and treated from 2005 to 2015 at the Head and Neck Department of the Oncology Hospital of the Venezuelan Institute of Social Security (Figures 1-3). We selected those patients with sarcomas that met the criteria for radiation-induced sarcomas proposed by Cahan et al. [4] in 1948 and modified by Arlen et al. [5] in 1971. The criteria are the following:


Figure 1. MRI showing a leiomyosarcoma arising from the left maxillary sinus in a 16-year old male patient with history of retinoblastoma treated with radiation therapy at age of 2-year old, this tumor was considered unresectable and was treated with chemotherapy and EBRT.


Figure 2. CT scan with a high-grade osteoblastic osteosarcoma of the right maxillary sinus in a 21-year old male patient with history of oropharyngeal rhabdomyosarcoma treated with chemotherapy and radiation therapy at age of 10-year old. This patient underwent chemotherapy and EBRT.


Figure 3. 63-year old female patient with a rhabdomyosarcoma of the posterior neck (a) With history of a posterior fossa meningioma treated with surgery and radiation therapy at age of 42-year old (b) This patient underwent surgery with wide resection of the tumor and reconstruction.

• The sarcoma must arise in an irradiated field.

• The patient must have a documented history of previous radiotherapy in the head and neck area.

• The sarcoma must be histologically different from the original tumor.

• The latency period must be more than 3 years (defined as the interval from the initiation of the first radiation therapy to the onset of the RIS).

After review the clinical records of each eligible patient, we obtained data including epidemiological characteristics, details of primary disease and the treatment received, latency period for the second malignancy, treatment of the RISHN, follow-up and outcome.


Forty patients with diagnosis of head and neck sarcomas were evaluated and treated from 2005 to 2015 at the Head and Neck Department of the Oncology Hospital of the Venezuelan Institute of Social Security. Seven patients matched with the criteria for RIS (17.5%). Table 1 summarizes all the data of these patients. Incidence of RISHN was higher in males than females (male 2.5:1 female). The average age was 36.9 years (range from 16 to 64 years). Retinoblastoma and rhabdomyosarcoma were the most common tumors considered as primary diseases for which patients received radiation therapy. Five patients had their primary disease when they were at a pediatric age. The average latency period from irradiation of the primary disease to the diagnosis of RIS was 18.4 years (range from 11 to 32 years). The average radiation dose for the primary condition was 50 Gy (30-60 Gy).

S.No. Age/Sex Primary disease Rad dose Latency Localization Histological type Treatment Outcome (Months)
1 24/M RMS of Eyelid 55 Gy 17 years Ethmoid sinus LMS Surgery plus EBRT Died of disease 34 m
2 63/F Posterior fossa Meningioma 60 Gy 21 years Neck UPS Surgery plus EBRT Free of disease 60 m
3 16/M Retinoblastoma 35 Gy 14 years Maxillary sinus LMS Chemotherapy Died of disease 21 m
4 64/M Larymgeal SCC 60 Gy 15 years Neck EHE EBRT Died of disease 14 m
5 34/M Retinoblastoma Unknown 32 years Maxillary sinus LMS Surgery plus EBRT Free of disease 8 m
6 29/M Oropharyngeal RMS 30 Gy 19 years Maxillary sinus Osteoblastic osteosarcoma Chemotherapy Died of disease 23 m
7 28/F Oropharyngeal Adenocarcinoma 60 Gy 11 years Maxillary sinus Fibrosarcoma Chemotherapy Died of disease 11 m

Table 1: Summary of radiation-induced sarcomas of head and neck.

Histological types of RIS were diverse, being leiomyosarcoma the most common. Five RIS had high grade of differentiation (71.43%). Five tumors were located in the paranasal sinus region, mainly at the maxillary sinus. No patients had regional lymph nodes or distant metastasis at the time of diagnosis. All the patients received treatment. Three patients underwent surgical treatment with wide local resection followed by external beam radiation therapy. The rest of the patients had unresectable tumors and received chemotherapy and/or external beam radiotherapy.

The average follow-up was 24.42 months (range from 8 to 60 months). During the follow-up, one of the three patients that underwent surgery plus radiotherapy had distant relapse and died of disease 34 months after surgery; the other two patients were free of disease at the end of their follow-up. No one of these three patients developed local failure. The other four patients that underwent chemotherapy and/or radiotherapy, developed disease progression under treatment and died of distant metastasis.

In summary, at the end of the follow-up, two patients were alive with no evidence of disease, and five patients had died of disease. The disease free-survival at the end of the study was 28.57% and mortality was 71.42%.


The incidence of radiation-induced tumors has been rising in the last decades. This phenomenon has been occurring due to the increase in the use of radiotherapy for treat a wide spectrum of malignant tumors, in addition to the longer life expectancy of patients after receiving treatment [6] According to Brady et al. [2], the incidence of RIS is less than 5%; however, the incidence in our research was higher, reaching 17.5%.

Although radiation therapy is used to treat malignant tumors, its potential carcinogenic effect has been recognized for many years. Second malignancies, usually squamous cell carcinomas and sarcomas, are known to arise within or at the edge of radiation fields after a period of several years after the initial radiation exposure [7].

The precise pathogenic mechanism for the development of radiation-induced tumors is poorly understood. The paradigm focuses on radiation-induced DNA damage leading to mutations in susceptible cells [1]. In this regard, p53 mutations and genetic aberrations in the Rb gene have been implicated. Other studies have demonstrated that changes in microenvironments promote genomic injury in stem cells, playing an important role in tumorigenesis [8]. Lately, the “bystander effect” phenomenon, in which non-irradiated cells exhibit effects as a result of signals received from nearby irradiated cells, has been implicated as well [9-11].

In 1948, Cahan et al. [4] described the conditions to establish a relation between radiation and sarcoma genesis. These statements were modified in 1971 by Arlen et al. [5] and are currently in use.

On regards to the best interval to establish if a sarcoma of head and neck is considered a RIS, continues to be a subject of debate. The original lapse for this latent period was 5 years. Subsequent modifications have intended decrease the interval inclusive to 6 month [12-14]. For RISHN, arbitrary periods of 3-4 years have been used as cutoffs, based on a consensus that this was a sufficient gap for radiation carcinogenesis to occur [15,16]. In our study, we observed a latency period with a range of 11 to 32 years with a median latency period of 18.43 years; all patients had more than 5 years of latency.

In our report, we observed that five of seven patients received radiation therapy at a pediatric age, mostly under 10 years old. A younger age at initial diagnosis has been considered an important risk factor for the development of secondary sarcomas. There are some reasons for the susceptibility of younger patients to develop RIS. First, young people have higher number of stem cells with high proliferative rates, which makes them more sensitive to have tumorigenic changes when they are exposed to radiation. Second, radiotherapy usually inhibits proliferation of irradiated cells; but this could be less effective in some organs during youth. Finally, many types of childhood cancers involve a germline mutation, increasing the sensitivity to radiation-induced cancer. Retinoblastoma, the most common primary intraocular cancer in children, has been related with germline mutations [1,17]. Two of our patients had this condition as their primary disease.

Regarding the location, there is no subsite predilection; they can arise in any irradiated tissue of mesenchymal origin [1,18]. In some recently published series with patients who lived at the Southeast of Asia, where nasopharyngeal carcinoma is endemic, the most common subsites were the nose and paranasal sinus region [19-21]. In our research, the most common site for RISHN was the paranasal sinus region, mainly the maxillary sinus. This was the most common location due to the majority of initial tumors was close to the paranasal sinus (eye and oropharynx).

RISHN can include osseous and soft tissue sarcomas; the vast majority of them are high-grade differentiated. The most common histologic subtype of RIS in many reported series is sarcoma NOS (formerly referred to as malignant fibrous histiocytoma). Other usual tumors include osteosarcoma, chondrosarcoma, fibrosarcoma, angiosarcoma and rhabdomyosarcoma (particularly in children) [16,18,19,22,23]. Leiomyosarcoma is not known as a common RISHN [24,25], however we report three of seven patients with this type of tumor. There is no specific histopathological criteria for determining differences between RIS and de novo sarcomas, however, some changes in the morphology of adjacent tissues may be suggestive of RIS: e.g. the form of dense cellular fibrosis plaques, presence of atypical fibroblasts, alteration of the vascular architecture and abundant fibrous stroma in the dermis adjacent to the sarcoma [26].

Management of these tumors is complex and challenging. Patients should be treated according to the same principles of de novo sarcoma patients, however, there are some limitations given by the previous therapy. Surgical resection with clear margins appears to offer the best chance for cure, but surgery in irradiated tissue is a limited tool, and even more in head and neck due to the proximity to critical neurovascular structures [18]. Bjerkehagen et al. [27] reported a high percentage of positive margins and local recurrence in those patients with RIS who underwent surgery, concluding that local control is difficult to achieve in this type of tumors. Patient with unresectable criteria could be treated with chemotherapy and/or radiotherapy, which is difficult when the sarcomas are arising in a previous irradiated field [1,28].

A great number of de novo sarcomas receive adjuvant radiotherapy [29], but in RIS the role of adjuvant radiation therapy remains unclear. The major limitation is the amount of prior radiation delivered in the same field. Factors that need to be considered include: previous volume and dose fractionation schedule, critical tissues, organs at risk and the time elapsed since the first treatment.

Outcome of RISHN has been estimated worse than de novo sarcomas. Some of the explanations are the following:

• Delay in making a diagnosis.

• Close or positive surgical margins, due to proximity of the tumor to critical structures.

• Limited of treatment options in a radiated field.

• Poor tumor sensitivity to chemotherapy.

• The majority of RISHN are high-grade tumors [3,30,31].

Disease free-survival at the end of the study was 28.57% and mortality rate was 71.42%. These data support that the overall prognosis for patients with RISHN is poor.


In conclusion, RISHN are one of the most serious long-term complication of radiation therapy. Management of these tumors is difficult due to the delay in making an early diagnosis and the challenging to achieve a definitive curative treatment. Overall prognosis is poor even receiving any of the treatment modalities usually given to de novo sarcomas. We consider that surgery with clear margins is the best option in resectable tumors with similar local control than other sarcomas, in spite of the difficulties to perform a surgical procedure in a radiated field.


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Author Info

Liuzzi Juan F*, DaCunha Maribel, Siso Saul and Salas Daniuska
Head and Neck Department, Oncology Hospital of the Venezuelan Institute of Social Security, Caracas 1040, Venezuela

Received: 30-Aug-2019 Published: 19-Sep-2019

Copyright: © 2019 Liuzzi Juan F, et al. This is an open access paper distributed under the Creative Commons Attribution License. European Journal of Clinical Oncology is published by Lexis Publisher.