Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric population. In 35% of cases, RMS develops in the head and neck (H&N) region, and only combined therapy is recognized as a curative treatment. However, recent advances in skull base and reconstructive surgery, along with microsurgery and endoscopic surgery, have strengthened the role of surgery as an important part of RMS treatment. In the present study, 36 pediatric RMS cases (24 males and 12 females) were analyzed after surgical treatment. The average age at diagnosis was 7 years. In total, 67% of tumors were localized in the parameningeal region. Alveolar RMS was the most common histopathological type. A total of 16 patients were treated due to disease recurrence or a previous non-radical surgical procedure, while 19 cases had inductive chemotherapy and/or radiotherapy preceding surgical treatment due to locally advanced disease. In 1 case, only diagnostic biopsy was performed. It is recommended that the management of H&N RMS is interdisciplinary from the beginning. Extensive surgical dissection in the H&N region for RMS may result in severe cosmetic defects and functional impairment; thus, these risks should be considered during treatment planning, and the surgical approach should be based on the individual characteristics of each patient.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, and represents 4.5% of all pediatric malignancies (
RMS develops from embryonic mesenchyme with the potential to differentiate into skeletal muscles (
Oncological advancements during the last decades have improved RMS treatment outcomes substantially (
Survival of children with RMS has improved significantly during the past 30 years (
In conjuction, chemotherapy is the backbone of therapy for RMS patients (
However, despite such advances in H&N RMS treatment, unfavorable prognostic factors such as parameningeal location or alveolar histopathological type reduce patient survival rates significantly (survival rates, 49 and 44%, respectively) (
Retrospective analysis was performed on a cohort of 36 pediatric patients diagnosed with H&N RMS who were treated at the Department of Otorhinolaryngology in the Faculty of Medicine and Dentistry of the Medical University of Warsaw (Warsaw, Poland) from January 2000 to December 2013. All patients underwent treatment with current therapy protocols for RMS, according to the guidelines of the Polish Pediatric Solid Tumors Group (
The patients' parameters included in the present analysis were age, gender, localization of the primary tumor, histopathological subtype, staging of the disease according to the tumor-node-metastasis (TNM) classification for RMS (
All patients or their families provided written consent to the proposed treatment. The medical data used in the present study are anonymous and are presented in the form of cumulative statistical analysis, without photos or personal information that could allow the identification of each individual.
From January 2000 to December 2013, 36 pediatric patients with H&N RMS underwent surgical treatment in the Department of Otorhinolaryngology at the Medical University of Warsaw. The cohort consisted mostly of males (67%) (
A total of 24 patients (67%) developed RMS in the parameningeal region. RMS primarily infiltrated the orbital region in 3 patients (8%). In 9 other cases (25%), the cancer was localized in different regions of the H&N (
The most commonly observed RMS histopathology was embryonal subtype (28 cases, 78%).
In 5 patients (14%) alveolar subtype of RMS was diagnosed, and in other 3 patients (8%), tumor tissue consisted of both alveolar and embryonal (mixed alveolar/embryonal RMS) (
Only 2 patients had their primary diagnostic biopsies performed in the Czerniakowski Hospital (Warsaw, Poland), while 16 patients were referred to the Department of Otorhinolaryngology at the Czerniakowski Hospital due to cancer relapse or previous non-radical surgical treatment. Of them, 75% had previously undergone surgery for RMS. A total of 18 patients were referred to the Czerniakowski Hospital for primary surgical treatment following induction chemotherapy, with radiotherapy if required.
In the analyzed cohort, the majority of patients presented with advanced disease. Among the patients referred to the Department of Otorhinolaryngology at the Czerniakowski Hospital for primary surgical treatment, 16 had stage III RMS disease according to TNM classification, 3 patients presented with lung metastasis, and 1 patient had bone marrow involvement.
Lateral, anterior, basal-through and combined surgical approaches were used depending on the localization and extent of disease progression. The most common localization was the skull base, and craniotomy was the most common surgical approach (20 cases). One patient had a concurrent nasal cavity surgical approach, while 2 others had a concurrent pharyngotomy. In 9 cases, access was achieved through rhinotomy with partial maxillectomy, if required; 2 cases involved a sublabial approach; 1 patient underwent petrosectomy; and 3 patients required lymphadenectomy due to disease stage. In other cases, different surgical procedures, including parotidectomy and resection of tumor of the parapharyngeal space or submandibular region, were performed if necessary.
Early complications manifested as 1 case of hematoma in the postoperative site, which required surgical intervention, and 1 case of cutaneous flap necrosis. Among the late complications, there were 3 cases of trismus after orbitozygomatic craniotomy; rehabilitation relieved symptoms in 2 of these patients, while 1 patient required surgical treatment. Hypernasal speech developed in 2 other cases, caused by losses of soft palate tissue. Salivary fistula ending in the external acoustic meatus formed in 1 patient. The majority of children suffered from various grade cosmetic defects, which depended on the extent of surgical resection. In total, 4 patients had to undergo orbital exenteration due to tumor infiltration of the orbit and eyeball. In 2 cases, the orbital content, including the bony structures, was removed, and microvascular flap reconstruction was performed to close the postoperative site. One patient underwent reconstructive surgery to enable the usage of oculi prosthesis. In 1 case, reconstructive surgery in the orbital region was postponed until achieving complete clinical remission.
Out of 20 patients treated with primary surgical resection, 10 patients succumbed to disease, 8 of them due to a disease relapse, while 2 others did not achieve clinical remission. Of the remaining patients, 2 were lost on follow-up, and 7 patients are currently free of disease with relapse-free survival at 6–13 years post-diagnosis. At present, 1 patient is treated due to a disease relapse. The 5-year OS for patients treated with primary surgical resection was estimated to be 50% (
The treatment strategies for children with H&N RMS have changed drastically over the last 30 years (
The signs and symptoms of pediatric H&N RMS vary widely with these sites of involvement (
Children with localized H&N RMS are able to undergo complete surgical resection with low long-term surgical morbidity (
According to the IRS III, >1/2 of patients with localized disease had previously undergone only subtotal resection or biopsy as a surgical treatment (
Since survival rates in patients with RMS have improved with more effective treatment regimens, more long-term treatment-associated complications have been described (
A limited number of studies in the literature comment on the surgical treatment of pediatric H&N RMS. The majority of publications concern population studies, epidemiological analyses or multinational collaborations summarizing the efficacy of combined therapy treatment according to differing treatment protocols (
Moretti
In the current study, a heterogenous patient cohort that was treated at Department of Otorhinolaryngology at the Czerniakowski Hospital is presented. Among these patients, ~1/2 of them were referred due to previous treatment failure for salvage surgery. A significant number of tumors were parameningeal, which is an anatomical space difficult for surgical access and correlated with an unfavorable long-term prognosis. Out of 12 patients with a favorable prognosis due to tumor localization, 10 were operated in the Department of Otorhinolaryngology at the Czerniakowski Hospital due to cancer relapse, 9 of whom had previously undergone surgical treatment in different medical centers. The majority of patients (18 in total) had locally advanced cancer after induction chemotherapy and, possibly, radiotherapy. In the majority of cases, residual tumor was localized in the surrounding area of the infratemporal and pterygopalatine fossa; thus, the preferable surgical approach orbitozygomatic craniotomy. Skin incision was performed in line with the coronal suture, and subsequently lengthened longitudinally down along the anterior border of the auricle. This minimized postoperative scarring. Revelation of skin, fascial layer, temporal muscle and zygomatic arch excision provided excellent access to the infratemporal fossa, which allowed the identification and occasional preservation of the trigeminal nerve and maxillary artery. Furthermore, it eased complete resection of the pterygoid muscles with their bone insertion (pterygoid processes, temporomandibular joint and part of the mandibular ramus) in cases of muscle infiltration. The unilateral resection of the temporomandibular joint caused minor face asymmetry, and led to trismus in 3 cases, 1 of who required surgical correction while 2 others only underwent rehabilitation.
In 9 patients with RMS localized in the limits of the nasopharynx and/or maxillo-ethmoidal complex, the preferred surgical approach was lateral rhinotomy with partial maxillectomy. This approach allowed access into the nasal cavity structures, and following excision of the medial part of the maxilla with frontal process, it enabled the revision of the entire maxillary sinus. Furthermore, acceptable exposition of the ethmoid bone granted insight into possible infiltration towards the base of the anterior crania fossa.
Independently from the surgical approach, macroscopic assessment of the tumor infiltration margins was difficult, and intraoperative histopathological examination of the surgical margins previously altered by radiochemotherapy was not always evident. Due to those limitations, the scope of operation relied mainly on the result from imaging studies (CT and MRI). Adequate assessment of tissue material acquired during surgery required specific experience and often involved immunohistochemical staining; thus, the reference center evaluated and verified every histopathological result. After surgery was performed at the Department of Otorhinolaryngology at the Czerniakowski Hospital, patients continued therapy according to treatment protocols at their respective referring oncology centers. Patients were postoperatively monitored, due to collaboration between the Department of Otorhinolaryngology of the Faculty of Medicine and Dentistry of the Medical University of Warsaw and the aforementioned oncology centers providing subsequent therapy. However, not all patients reported for follow-up, mainly due to the distance from their place of residence and ongoing systemic therapy. The relatively low survival rate in the group of patients operated at the primary treatment stage may result from the advanced stage of the disease at the moment of diagnosis (95% of patients exhibited stage ≥3) and unfavorable tumor localization (86% of the group). In the group operated due to a disease relapse, the tumor was localized mainly in a favorable site, thus resulting in a relatively good survival rate.
It should be emphasized that management of H&N RMS must be interdisciplinary at the time of diagnosis. The surgical approach should be based on the individual characteristics of each patient. It is important to explain the possible complications of surgery, such as functional losses, cosmetic defects and permanent limitations, to parents and to the child, if necessary. In case of parameningeal RMS, obtaining negative surgical margins is often impossible; therefore, subsequent adjuvant therapy is indispensable. Experienced pathologists should examine both tumor
The present study was supported by the Medical University of Warsaw (Warsaw, Poland) statutory funding and the Military Institute of Medicine (Warsaw, Poland) statutory funding. Treatment costs were covered by the Polish National Health Fund (Warsaw, Poland). A.M.C. was supported by a SONATA grant from the National Science Centre (NCN; Warsaw, Poland; grant no. UMO-2012/05/D/NZ5/01844) and a WIM intramural grant from the Military Institute of Medicine [grant no. 1/8863 (355)]. A.M.C and C.S. were supported by an OPUS grant from the NCN (grant no. UMO-2011/01/B/NZ5/02822).
Distribution of patients according to gender.
Distribution of patients according to age.
Distribution of patients according to the primary tumor site.
Distribution of patients according to histological subtype.
Kaplan-Meier survival curve showing the 5-year overall survival probability in the group of patients subjected to primary surgical treatment.
Kaplan-Meier survival curve showing the 5-year overall survival probability in the group of patients operated due to a disease relapse.
Patients' characteristics and outcome.
Pt no. | Age at diagnosis (years) | Pre-treatment TNM staging | Localization | Histological subtype | Clinical course | Survival |
---|---|---|---|---|---|---|
1 | 10 | 3 | Parameningeal | ARMS | Local recurrence | Died 33 months post-ID |
2 | 3 | 4 | Parameningeal | ERMS/ARMS | Alive 11 years post-ID | |
3 | 4 | 3 | Other H&N | ERMS | Local recurrence | Died 20 months post-ID |
4 | 2 | 3 | Parameningeal | ERMS | Alive 6 years post-ID | |
5 | 3 | 4 | Parameningeal | ERMS | No clinical remission | Died 24 months post-ID |
6 | 4 | 3 | Parameningeal | ERMS | Alive 8 years post-ID | |
7 | 8 | 3 | Parameningeal | ERMS/ARMS | Alive 11 years post-ID | |
8 | 13 | 3 | Parameningeal | ERMS | Local recurrence | Alive 6 years post-ID |
9 | 9 | 3 | Parameningeal | ERMS | Alive 9 years post-ID | |
10 | 7 | 3 | Parameningeal | ERMS | Local recurrence | Died 33 months post-ID |
11 | 6 | 3 | Parameningeal | ERMS | Local recurrence | Died 31 months post-ID |
12 | 4 | 3 | Parameningeal | ERMS | Alive 13 years post-ID | |
13 | 22 | 3 | Parameningeal | ERMS | Local recurrence | Died 31 months post-ID |
14 | 1 | 3 | Parameningeal | ERMS | Local recurrence | Died 37 months post-ID |
15 | 10 | 3 | Parameningeal | ERMS | Alive 7 years post-ID | |
16 | 2 | 1 | Other H&N | ARMS | Local recurrence | Alive 8 years post-ID |
17 | 7 | 3 | Parameningeal | ERMS | Alive 12 years post-ID | |
18 | 4 | 3 | Parameningeal | ERMS | Local recurrence | Died 27 months post-ID |
19 | 5 | 4 | Parameningeal | ARMS | Local recurrence | Died 42 months post-ID |
20 | 4 | 3 | Parameningeal | ERMS/ARMS | No clinical remission | Died 11 months post-ID |
Pt no, patient number; TNM, tumor-node-metastasis; H&N, head and neck; ARMS, alveolar rhabdomyosarcoma; ERMS, embryonal rhabdomyosarcoma; ID, initial diagnosis.