Volume 2, Issue 4 , Pages 243-249, December 2007
Para-meningeal rhabdomyosarcoma with critical airway compromise: Role of endoscopic debulking surgery
Article Outline
Summary
Paediatric para-meningeal rhabdomyosarcomas (RMSs) are treated with aggressive chemo-radiotherapy; so far, surgery has played a limited role in the management owing to the relative inaccessibility of lesion and the associated morbidity.
We present the management of two cases of para-meningeal embryonal RMS at our institution from 2005 to 2006, with critical airway compromise on presentation. Tumour stage and site were identical and both patients received chemo-radiotherapy based on the Malignant Mesenchymal Tumour Group MMT 953A protocol. In addition, one patient underwent debulking surgery to establish airway patency using trans-nasal endoscopic technique allowing a rapid return to normal activity. The second patient had higher morbidity and longer hospital stay due to prolonged intubation. We discuss the role of endoscopic surgery in the management of paediatric head and neck RMS.
Keywords: Rhabdomyosarcoma, Head and neck rhabdomyosarcoma, Paediatric, Para-meningeal, Endoscopic debulking
1. Introduction
Rhabdomyosarcomas (RMS) are the most common soft tissue sarcoma in the paediatric age group with an annual incidence of 4–7 per million in children age 15 years or younger [1]. RMS commonly involves the head and neck region (35%), genito-urinary tract and the extremities. Histologically, 60% of RMS is embryonal, 20% alveolar and the remainder undifferentiated [2]. A small percentage are botyroid.
Head and neck rhabdomyosarcoma (HNRMS) constitutes a distinct clinical entity as it tends to occur at a younger age, is more commonly of the embryonal subtype, and rarely metastasises to regional nodes [3]. HNRMS can be divided into three subsets on the basis of anatomical regions involved: orbital, para-meningeal (nasopharynx, nasal cavity, paranasal sinuses, infratemporal region, and middle ear) and non-para-meningeal (oral cavity, cheek, parotid, and neck).
The multi-modality treatment protocols for RMS have evolved from the work of large collaborative trials; both European and US based groups such as International Society of Paediatric Oncology (SIOP) and the Intergroup Rhabdomyosarcoma Study Group (IRS). Protocols from these trials have led to a significant improvement in the 5-year survival rate of patients with RMS from 25% to over 70% [4], [5]. Recommendations from both groups for the treatment of malignant mesenchymal tumor (MMT) as well as ongoing research aim to improve the survival rate and quality of life in patients with RMS. Whereas IRS therapies have focussed on the combination of radiation therapy and chemotherapy, European-based studies have attempted to reduce or limit radiation therapy by administration of higher doses of chemotherapy. Therapy is risk and response based with utilisation of up front chemotherapy, which aims to treat both the primary tumour as well as gross and microscopic metastatic disease. Use of radiation therapy is considered on the basis of the risk of local tumour recurrence and the extent of response. Second look surgery is also considered in order to achieve local disease control [6]. The staging systems used by the IRS and SIOP groups are distinct reflecting the difference in management and treatment philosophy (Table 1a, Table 1b, Table 2).
Table 1a. IRS Clinical Groups and Risk Classification scheme
| Group I | Localised disease completely excised (N0) |
| (a) Confined to organ/muscle of origin | |
| (b) Infiltrating outside organ/muscle of origin | |
| Group II | Loco-regional disease with gross tumour resection |
| (a) Grossly resected tumour with microscopic residual disease | |
| (b) Completely resected regional disease and involved nodes and/or tumour extension into adjacent organ | |
| (c) Grossly resected regional disease and involved nodes with evidence of microscopic disease | |
| Group III | Incomplete tumour resection or biopsy with gross residual disease |
| Group IV | Distant metastasis present at diagnosis |
| Low risk | Embryonal RMS at favourable site |
| Embryonal RMS at favourable site with complete resection/microscopic residual disease | |
| Intermediate risk | Embryonal RMS at unfavourable site with gross residual disease |
Metastatic embryonal RMS in children <10 years | |
| Alveolar RMS at any site | |
| High risk | Patients with metastatic RMS at presentation except embryonal RMS in children<10 years |
Table 1b. TNM and pre-treatment staging system for rhabdomyosarcoma (IRS-IV)
| T-tumour | Favourable sites |
| T1 tumour confined to anatomical site of origin | •Orbit, head and neck excluding para-meningeal |
| T2 tumour fixed and/or extending to surrounding tissue | •Genito-urinary excluding prostate and bladder |
| a ≤5cm in diameter | |
| b >5cm in diameter | |
| N-regional nodes | Unfavourable sites |
| N0 not clinically involved | •Para-meningeal/cranial |
| N1 clinically involved | •Extremity |
| Nx unknown | •Trunk/retro-peritoneal |
| •Bladder/prostate | |
| M-Distant metastasis | |
| M0 no metastasis | |
| M1 metastasis present | |
| Stage | Site | T | T size | N | M |
|---|---|---|---|---|---|
| 1 | Favourable | T1 or T2 | a or b | N0, N1, Nx | M0 |
| 2 | Unfavourable | T1 or T2 | a | N0 or Nx | M0 |
| 3 | Unfavourable | T1 or T2 | a | N1 | M0 |
| T1 or T2 | b | N0, N1, Nx | M0 | ||
| 4 | All sites | T1 or T2 | a or b | N0 or N1 | M1 |
Table 2. TNM and pre-treatment staging system for rhabdomyosarcoma (SIOP)a
| Stage | Sites | Tb | Sizec | Nd | Me |
|---|---|---|---|---|---|
| 1 | Orbit | T1 or T2 | a or b | N0 or N1 or Nx | M0 |
| Head and neck (excluding para-meningeal) | |||||
| GU–non-bladder/non-prostate | |||||
| Biliary tract | |||||
| 2 | Bladder/prostate | T1 or T2 | a | N0 or Nx | M0 |
| Extremity, cranial para-meningeal | |||||
| Other (trunk, retroperitoneum, etc.) | |||||
| Except Biliary tract | |||||
| 3 | Bladder/prostate | T1 or T2 | a | N1 | M0 |
| Extremity, cranial para-meningeal | b | N0 or N1 or Nx | |||
| Other (trunk, retroperitoneum, etc.) | |||||
| Except Biliary tract | |||||
| 4 | All | T1 or T2 | a or b | N0 or N1 | M1 |
aInternational Society of Paediatric Oncology Malignant Mesenchymal Tumour study. |
bSite-T1-confined to anatomic site of origin; T2-extension and/or fixative to surrounding tissue. |
cSize-a ≤5 |
dRegional nodes-N0 regional nodes not clinically involved; N1 regional nodes clinically involved by neoplasm; Nx clinical status of regional nodes unknown (especially sites that preclude lymph node evaluation). |
eMetastasis-M0 no distant metastasis; M1 metastasis present. |
The role of surgery is to obtain tissue samples for histological diagnosis and resection of tumour in anatomically accessible regions. Current recommendations for resection are to completely excise the tumour with a margin of at least 0.5cm [1]. The aim in this situation is to achieve local control without use of adjuvant radiotherapy. This is difficult to achieve in the head and neck region without possible disfigurement and damage to vital structures.
Outcome of therapies for HNRMS vary considerably depending on factors such as site and stage of disease. In general, orbital RMS has the highest survival and the para-meningeal RMS patients are on the opposite end of the spectrum. Due to ease of surgical access, the role of complete resection in non-para-meningeal HNRMS is well established. Orbital RMS constitutes a unique category as it responds well to organ preserving modalities and thus the role of surgery is limited [7], [8], [9].
For para-meningeal RMS, radical surgery is hazardous due to the inaccessible location of the tumour and risk of incomplete excision. Therefore, the management rests predominantly with combination chemotherapy and radiotherapy [10].
Although it has been argued that debulking the para-meningeal tumour improves survival and reduces morbidity, evidence in support of debulking is lacking [11]. Our aim is to demonstrate that surgical debulking does play a role in certain para-meningeal HNRMS as a tool to reduce morbidity.
2. Materials and method
We present two cases of para-meningeal nasopharyngeal RMS in paediatric patients of similar age, histological diagnosis and clinical stage. These patients underwent treatment at the Women's and Children's Hospital, Adelaide, Australia in 2005–2006.
At the time of presentation both patients had significant airway compromise secondary to large tumour mass in the post-nasal space. Diagnostic workup included CT scan (head, neck, chest and abdomen), MRI-head, histopathology, PET scan and bone marrow biopsy. Based on these results combined chemo-radiotherapy was commenced as per the Malignant Mesenchymal Tumour Group MMT953A protocol (chemotherapy includes Ifosfamide, Vincristine and Dactinomycin). Tumour staging was done as per the SIOP protocols (Table 2, Table 3).
Table 3. Patient summary
| Age/sex | Site | Histology | Group | TNM stage | Risk | Treatment | Chemo | Radiation | Response (MRI 9/52 after commencing treatment) | Follow-up/status |
|---|---|---|---|---|---|---|---|---|---|---|
| 5.3/F | Nasopharynx | Embryonal | III | T1N0M0 stage 2 | Intermediate | CTa, RTb, debulking | MMT 953A protocol | External (Wk 9-14) 54Gy 30 Fractionsc | PRd | 15 months/complete remission |
| 3.10/M | Nasopharynx | Embryonal | III | T1N0M0 stage 2 | Intermediate | CT, RT | MMT 953A protocol | External (Wk 9-17) 59.4Gy 28 fractions | PR | 12 months/complete remission |
aChemotherapy. |
bRadiotherapy. |
cGray. |
dCR-complete response (complete disappearance of disease); PR-partial response (≥50% reduction in size of tumour); MR-minor response (<50% reduction in size of tumour); NR-no response (stable disease OR |
2.1. Case reports
2.1.1. Case 1A 3 years 10-month-old boy presented to the emergency department with an 8-month history of upper respiratory tract infection treated unsuccessfully with multiple courses of oral antibiotics. Additional history of inability to eat solids and progressive snoring with witnessed apnoeic episodes was obtained. Significant past history included multiple presentations with croup.
On assessment, the patient was febrile, stertorous, and tachycardic with notable mouth breathing. Oral cavity examination demonstrated a nasopharyngeal mass visible behind the soft palate. Airway obstruction with intermittent desaturations necessitated elective endotracheal intubation with an oral tube, as nasopharyngeal intubation was not possible. The patient was admitted to the intensive care unit and commenced on intravenous steroids and antibiotics.
CT and MRI scan of the head revealed a complex solid lesion in post-nasal space extending into both nasal cavities and inferiorly to the free edge of the soft palate. No intracranial extension was detected and a cleavage plane was evident between the tumour and prevertebral tissues. Biopsy confirmed the diagnosis of embryonal rhabdomyosarcoma. Further investigations including bone marrow biopsy showed no evidence of metastatic disease, thus he was classified as stage 2 (T1N0M0).
The patient commenced chemotherapy based on the MMT953A protocol and a decision was made to leave the endotracheal tube until the tumour shrunk sufficiently to allow safe extubation. Nasogastric feeds were poorly tolerated due to vomiting and were supplemented with parenteral nutrition.
Two days later, the endotracheal tube was accidentally displaced, resulting in airway compromise with oxygen desaturation and bradycardia. Reintubation proved difficult due to subglottic oedema and a CPAP mask was utilized with success to stabilise the vitals, following which the airway was secured with a smaller oral endotracheal tube. Examination under anaesthesia was repeated and reduction in tumour mass was evident. Mucosal tears were noted in vocal cords (due to multiple attempts at intubation) with mild subglottic oedema. A nasal endotracheal tube was placed and the patient was successfully extubated 3 days later, transferred to the oncology ward and continued on chemotherapy as per the protocol.
The following developments complicated further stay in hospital:
Radiotherapy to 59.4Gy in 28 fractions was commenced in week 9 as per protocol; however the treatment was interrupted due to severe mucositis leading to significant delay. The remainder of the treatment was completed without any major complication. The patient was still in remission 15 months following treatment.
A 5-year-old girl presented to the emergency department with a 4-week history of blocked nose and greenish nasal discharge, disturbed sleep and witnessed obstructive apnoeic episodes. There were no constitutional symptoms. Her local doctor had commenced her on oral antibiotics, but no improvement was noted. Past history was unremarkable except for mild laryngomalacia during infancy.
On assessment, the patient was lethargic, afebrile and tachycardic with noticeably hyponasal speech and stertor. ENT examination revealed enlarged tonsils and a bulging soft palate suggestive of a space-occupying lesion in the nasopharynx (Photo 1 and 2). CT scan demonstrated a heterogenous post-nasal space mass with rim enhancement and without bony erosion. The patient was admitted to the paediatric intensive care unit (PICU) and underwent MRI scan on the following day. The lesion was found to be continuous with lymphoid tissue in the left fossa of Rosenmüller.
Photo 1.
Rigid nasendoscopy in case 2: tumour extending into the R nasal cavity and post-nasal space.
Examination under anaesthesia, biopsy and endoscopic powered debulking of tumour was undertaken. Tumour was seen to arise from a small pedicle in the left fossa of Rosenmüller. Following the procedure, the patient was electively ventilated overnight and extubated on the following day without complications.
Histopathology confirmed the lesion to be embryonal rhabdomyosarcoma. Further investigations were undertaken for staging and included chromosomal studies, PET scan, bone marrow biopsy, MRI head and CT chest and abdomen. There was no evidence of metastatic disease. The patient was referred to the oncology department and classified as stage 2 (T1N0M0) disease based on cranial para-meningeal site classification.
Further treatment included chemotherapy based on the MMT953A protocol with Radiotherapy (54Gy in 30 fractions) from weeks 9 through 14. The patient was in remission 12 months after completing the treatment.
3. Discussion
Although HNRMS is an infrequently encountered tumour, RMS itself constitutes one of the most common solid tissue malignancies in the paediatric population. Despite advances made in the field of cancer diagnosis and treatment, the 5-year-survival rates have plateaued in the vicinity of 80%. Early diagnosis is paramount to a successful outcome and RMS should be included in the differential diagnosis of all paediatric head and neck masses. CT and MRI imaging are paramount for an early diagnosis [2], [12].
A multi-disciplinary approach coordinated by a paediatric oncology unit, and supported by various other specialties is essential. The regimen is tailored to the specific disease subset and is determined by factors such as anatomic location and stage of disease.
Chemotherapy regimens including Cyclophosphamide (C), Vincristine (V) and Actinomycin-D (A) have been the gold standard for treating RMS. Ifosfamide (I), anthracyclines and Etoposide (E) have been tried with success as well [13], [14]. Radiation doses of 40–45Gy for microscopic residual disease and 45–50Gy for gross residual tumour are considered adequate [3]. Hyper-fractionation is believed to lower local relapse rate and the long-term adverse effects [15]. Brachytherapy has a site-specific application in management of HNRMS [16].
On initial presentation, surgical treatment is often limited to diagnostic biopsy. Over the last three decades, radical surgery has been replaced with a more conservative approach. Primary excision with adjuvant chemo-radiotherapy, or salvage surgery for chemotherapy failure is preferred for accessible tumours of non-para-meningeal type.
The AMORE protocol (Ablative surgery, Moulage with afterloading brachytherapy and Reconstruction) provides an alternative treatment strategy [17], [18]. The role of lymph node sampling and sentinel lymph node mapping is yet undefined in the HNRMS.
Para-meningeal RMS has an unfavourable outlook owing to location with associated delay in diagnosis, inaccessibility, proximity to the CNS and morbidity associated with high dose radiation. Up to 25–30% patients may have CNS involvement at the time of diagnosis [19].
Of the two recent cases we presented, one patient underwent endoscopic powered debulking of the tumour to restore the airway. This resulted in a short hospital stay and a complete and rapid resolution of symptoms. The other patient was electively intubated until the tumour mass shrunk with treatment. Although these tumours often respond rapidly to treatment, intubation was required for several days, and this resulted in greater morbidity and longer hospital stay for this patient. In addition, tumour site necessitated an oral cuffless endotracheal tube, which is inherently less stable and more prone to displacement than nasal tubes. Such displacement can be effectively avoided by restoring the normal airway by removing tumour bulk.
Significant advances have been made in the field of endoscopic sinus surgery (ESS) with the availability of powered instruments and smaller diameter fiberoptic telescopes. ENT surgeons experienced in the techniques of ESS not infrequently undertake endoscopic-assisted excision of various sino-nasal neoplasms. Our experience thus far has been consistent with the reports in the literature that patients with para-meningeal RMS stand to benefit from debulking of tumour [20]. Airway patency can be rapidly restored in this group of patients. This allows much shorter stay in the hospital and prompt return to normal activity. Whether tumour debulking improves response to chemoradiation is uncertain. The relative rarity of the disorder makes scientific evaluation of this point difficult. With current endoscopic techniques, however, it would be feasible to use endoscopic-assisted techniques for complete excision of grossly visible tumour, thus converting Clinical Group III to Group II disease (Table 1a).
References
- . Childhood rhabdomyosarcoma. Semin. Pediatr. Surg. 2006;15(1):57–62
- Orofacial rhabdomyosarcoma in neonates and young children: a review of literature and management of four cases. Oral Oncol. 2002;38(5):508–515
- . Rhabdomyosarcoma: an overview. Oncologist. 1999;4(1):34–44
- Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J. Clin. Oncol. 2001;19(12):3091–3102
- Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life. J. Pediatr. Hematol. Oncol. 2001;23(4):215–220
- . Rhabdomyosarcoma: many similarities, a few philosophical differences. J. Clin. Oncol. 2005;23(12):2586–2587
- . Head and neck rhabdomyosarcoma. Semin. Pediatr. Surg. 1994;3:203–206
- . Rhabdomyosarcoma of the head and neck in children. Oral Oncol. 2002;38(5):450–459
- . Prognostic factors in head and neck rhabdomyosarcoma. Head Neck. 2002;24(5):468–473
- Rhabdomyosarcoma of the head and neck region: experience at the pediatric unit of the Istituto Nazionale Tumori. Milan J. Otolaryngol. 2006;35(1):53–59
- . Pediatric rhabdomyosarcoma of the head and neck: is there a place for surgical management?. Arch. Otolaryngol. Head Neck Surg. 2000;126(4):468–472
- . Nasal mass in a pediatric patient. Head Neck. 1992;14(5):415–418
- . Clinical trials and soft tissue sarcomas. Surg. Oncol. Clin. N. Am. 2003;12(2):485–497
- Rhabdomyosarcoma in infants younger than 1-year-old. Cancer. 2003;97(10):2597–2604
- Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma—a report from the IRSG. Int. J. Radiat. Oncol. Biol. Phys. 2001;51(3):718–728
- A 10-year experience of pediatric brachytherapy. Int. J. Radiat. Oncol. Biol. Phys. 1995;32(2):451–455
- New combined treatment of surgery, radiotherapy, and reconstruction in head and neck rhabdomyosarcoma in children: the AMORE protocol. Head Neck. 1998;20(4):283–292
- AMORE protocol in pediatric head and neck rhabdomyosarcoma: descriptive analysis of failure patterns. Head Neck. 2005;27(5):390–396
- . Advances in the surgical management of sarcomas in children. Am. J. Surg. 2002;184(6):484–491
- . Pediatric rhabdomyosarcoma of the head and neck. Curr. Treat. Options Oncol. 2006;7(1):13–22
PII: S1871-4048(07)00063-9
doi:10.1016/j.pedex.2007.07.003
Crown Copyright © 2007. Published by Elsevier Inc. All rights reserved.
Volume 2, Issue 4 , Pages 243-249, December 2007
