|Year : 2015 | Volume
| Issue : 4 | Page : 830-834
Adult rhabdomyosarcoma: Clinical presentation, treatment, and outcome
Divya Khosla, Simit Sapkota, Rakesh Kapoor, Ritesh Kumar, Suresh C Sharma
Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||15-Feb-2016|
Senior Resident, Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Objective: Rhabdomyosarcoma (RMS) in adults is a rare malignancy. The objective of our study was to determine presentation, treatment, patterns of failure, and outcome in this disease.
Materials and Methods: A retrospective analysis of 25 patients of adult (>16 years) RMS who were treated at our institute from 2000 to 2009 was carried out. Tumors were classified according to the Intergroup Rhabdomyosarcoma Study (IRS) staging. All patients were treated with multimodality treatment except for three patients who received chemotherapy as the only modality.
Results: The median age was 19 years (range, 16-68 years). The most common site was head and neck (52%) followed by extremities (24%), genitourinary (20%), and retroperitoneal RMS (4%). Three out of 25 patients presented with distant metastasis. With a median follow-up of 45 months, the 5-year overall survival (OS) rate was 45%. The 5-year local control (LC) rate was 53%. IRS grouping and complete response after primary therapy were predictors of a better survival.
Conclusions: RMS in adults have poor prognosis as compared to childhood RMS. Adult RMS should therefore be treated aggressively with multidisciplinary approach comprising of surgery, radiation, and chemotherapy to achieve cure and prolonged survival.
Keywords: Adults, chemotherapy, prognosis, radiotherapy, rhabdomyosarcoma
|How to cite this article:|
Khosla D, Sapkota S, Kapoor R, Kumar R, Sharma SC. Adult rhabdomyosarcoma: Clinical presentation, treatment, and outcome. J Can Res Ther 2015;11:830-4
| > Introduction|| |
Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma, accounting for more than 50% of all soft tissue sarcomas. In contrast, RMS is exceedingly infrequent in adults. Soft tissue sarcomas constitute less than 1% of all adult malignancies, and RMS accounts for 3% of all soft tissue sarcomas. 
RMS arises from mesenchymal tissue and can occur at various sites in the body, but most common affected sites are head and neck (35%), genitourinary tract (22%) and extremities (18%).  Adult RMS differs from childhood RMS in terms of natural history, behavior, poor response to treatment, prognosis, and outcome. Risk-based treatment protocols are based on initial staging, grouping, and histology of tumor. The accepted treatment guidelines for childhood RMS include gross total resection with preservation of function, systemic chemotherapy for all and radiation therapy for all with the exception of those with group I embryonal tumors. ,,,
Due to the relative rarity of RMS in adults, most of the available data are derived from retrospective case series. ,,,,,,, Experience with adult RMS is limited and treatment modalities from childhood RMS are extrapolated widely to adults. Despite the use of multimodal therapy, various studies have substantiated poor outcomes in adult RMS. Age more than 10 years is identified as a poor prognostic feature in various pediatric studies. , Increased likelihood of poor prognostic features in adults such as unfavorable primary site and unfavorable histologic diagnosis have been attributed to difference in outcome between children and adults.  The goal of the present study was to determine clinical presentation, treatment and outcome of patients of adult RMS.
| > Materials and methods|| |
A retrospective analysis of 25 cases of adult RMS was carried at our institute from 2000 to 2009. The clinical case notes, surgical records, operation notes, histological slides, and treatment details of these patients were carefully reviewed. The diagnostic and staging work-up included a full history, physical examination, complete blood count, liver and renal function tests, chest imaging, abdominal ultrasound, and evaluation of local extent with computed tomography and/or magnetic resonance imaging. Location of tumor was divided into head and neck, genito-urinary, extremities, and others. Tumors of head and neck and genitourinary were further sub-classified into favorable (orbit, non-parameningeal head and neck, paratesticular) and unfavorable (parameningeal head and neck, bladder and prostate) sub-groups. Histological subtype was divided into embryonal, alveolar, pleomorphic, and undifferentiated subtype. The stage of disease was defined retrospectively according to both IRSG postsurgical grouping system and IRS pretreatment staging system.
Combination chemotherapy was given with VAC alternating with IE regimen every three weekly. VAC including vincristine, actinomycin and cyclophosphamide and IE included Ifosfamide and etoposide at standard doses. Radiation consisted of external beam therapy. Dose ranged from 36-54 Gy in 1.8-2 Gy per fraction with median dose of 45 Gy. Following treatment completion, patients were followed at 3 month intervals for the first 2 years, 6 months intervals for the next 3 years, and yearly afterwards.
Local control (LC) and overall survival (OS) were calculated according to the Kaplan-Meier method. LC was calculated from the time of diagnosis to local progression or recurrence. OS was defined as the time from diagnosis to the date of death for any reason or to the last follow-up. The log rank test was used to compare the survival curves of the patient subgroups in a univariate analysis to ascertain the potential value of various prognostic factors.
| > Results|| |
Clinical and pathological characteristics
The patient and tumor characteristics are summarized in [Table 1]. The median age of patients was 19 years (range, 16-68 years). Fifteen patients (60%) were male and ten patients (40%) were females. Of the 25 patients, 22 patients had localized disease and 3 patients had metastasis at presentation. Undifferentiated RMS was the most common histology seen in 11 patients (44%) followed by alveolar in 9 (36%), embryonal subtype in 4 patients (16%), and pleomorphic in 1 patient (4%), respectively. The primary tumor site was head and neck in 13 (52%), extremity in 6 (24%), genito-urinary tract in 5 (20%), and trunk in 1 (4%). On classifying tumor by favorable or unfavorable prognostic sites, 13 patients (52%) have favorable sites and 12 patients (48%) had unfavorable sites. For the three patients who initially presented with distant metastasis, the sites of spread were pulmonary in two and pulmonary and bone in one patient. Two of them had primary as genito-urinary and one had limbs as primary site. Histopathology of the patients with distant metastases were alveolar (n = 1), embryonal (n = 1), and undifferentiated (n = 1). According to the IRSG postsurgical grouping system, the tumors were grouped as follows: Group I-3 patients (12%); group II-3 patients (12%); group III-16 patients (64%); group IV-3 patients (12%). IRS Stage distribution was as follows: Stage 1 in 11 (44%), Stage 2 in 4 (16%), Stage 3 in 7 (28%), and Stage 4 in 3 (12%).
Over a period of 10 years, patients were treated with a relatively uniform approach, which in most cases consisted of surgery, chemotherapy and radiotherapy. The aim was complete surgical resection with negative margins and preservation of both function and cosmesis wherever feasible. All patients were treated with multi-modality treatment except for three patients who had distant metastases at presentation were given chemotherapy as only modality. Fifteen patents underwent resection of which seven patients had complete resection, two patients had microscopic residual, and six patients had gross residual disease. The other ten patients had biopsy only. Out of 25 patients, seven underwent surgery, chemotherapy and radiotherapy; six underwent surgery and chemotherapy; seven patients had chemotherapy and radiotherapy; and two patients had surgery and radiotherapy.
Disease outcome and survival
Follow-up ranged from 7 months to 130 months with median follow-up of 45 months. The 5-year OS rate in this series was 45% [Figure 1]. The 5-year local control rate was 53%. IRS grouping (P = 0.007) and complete response after primary therapy (P = 0.024) were predictors of a better survival. There appeared to be an improved OS trend in female patients (P = 0.05) and those who had received radiation (P = 0.06). Histopathological subtype, favorable site and chemotherapy did not affect survival outcome. Out of 15 patients who have complete response after primary therapy, eight recurred. Median duration of recurrence was 18 months. Out of eight, three had local recurrence, two had nodal recurrence, and three had distant metastasis. Only two of the recurrences were successfully salvaged and both of them were local recurrences. Five patients developed distant metastasis during course of the disease and three patients presented with distant metastasis. Lung was the most common site of distant metastasis (50%) followed by brain (25%). Median survival after diagnosis of distant metastasis was 5 months.
All the local failures except for one occurred within first 15 months of primary therapy. One out of two group I patients, all three group III patients who didn't receive radiation developed local recurrence. Out of 16 patients of all groups who received radiation, five developed local recurrence. Local control according to use of radiotherapy is presented in [Table 2].
|Table 2: Local control according to use of radiotherapy to primary site |
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| > Discussion|| |
RMS is the most common soft tissue sarcoma in children. On the contrary, adult RMS is an uncommon neoplasm and, as a result, there is paucity of information regarding the management and prognosis of the patients. The current guidelines for treating adult RMS are nonetheless based on the multimodality approach conceived by the Intergroup Rhabdomyosarcoma Studies (IRS) which achieved striking improvements in long-term survival for children with RMS. ,,, In most of the studies, survival of adults with RMS has been lower than that of children. The 5-year OS in our series is lower than that reported in paediatric series ,, and slightly higher than the series of adults with RMS. ,,, The results of our study also shows disease outcome is considerably less favorable for adults than for children.
Head and neck are most common sites in children accounting for 35% of cases of RMS. The incidence in adults is lower and orbital presentation is relatively uncommon. In our study, 13 patients were of head and neck which accounted for 52% of sites which is comparatively higher as compared to other adult RMS studies. ,, In our series, six patients had orbital presentation and three had non parameningeal head and neck presentation which are considered favorable sites. Relative lower median age of presentation may partly explain high number of head and neck location in our patients. Orbital RMS have favorable prognosis in children, as demonstrated in all four IRSG studies ,,, and all 6 patients of orbital RMS were disease free at last follow-up in our study.
Pediatric and adult RMS differ in terms of histopathological subtype also, with later having more frequent unfavorable subtypes. In IRS-IV, frequencies of the various tumor subtypes were embryonal/botryoid/spindle cell, 70%; alveolar, 20%; undifferentiated, 4%; and others, 6%.  Contrary to this, in our series, 44% were undifferentiated, 36% alveolar, 16% embryonal, and 4% pleomorphic. Predominance of unfavorable histological subtype may place adults at a disadvantage. In a study by Little et al.  patients with alveolar tumors experienced significantly poorer metastases-free rates than those with embryonal and pleomorphic tumors but this difference did not translate into significant disease-free survival. In another study of Hawkins et al.  no association was noted between survival and histologic subtype. In our study also, histological subtype did not affect survival outcome. Therefore, the prognostic significance of RMS subtype in adults still remains undefined.
RMS has high propensity of recurrence even after complete response. Distant metastasis is quite common and lung is the most common site of metastasis. All the 3 patients who presented with distant metastasis had lung metastasis (out of three, one had both lung and bone metastasis) and of the five patients who failed distantly, three had lung metastasis, one had brain metastasis and one had both brain and bone metastasis.
The use of chemotherapy and its combination had been major point of discussion in adult RMS. Hawkins et al.  concluded that there was no survival benefit with the use of chemotherapy in adult RMS. Few studies suggested that chemotherapy has same activity in adult and pediatric RMS, and when chemotherapy regimens are administered similarly to those used for treatment of pediatric patients, the outcomes for adults and children with RMS are comparable. ,, In a study by Ferrari et al.  the overall rate of response to chemotherapy was 85% and the authors emphasized that adults be treated on same lines as that of childhood RMS. In our series, patients were treated with multimodality therapy on lines of paediatric RMS thus explaining better survival and local control.
The dose, duration and timing of radiotherapy depends on the clinical group and the site of disease. The recommended dose for microscopic residual disease is 36 Gy - 41.4 Gy and for those with gross residual tumor it is 50.4 Gy.  In a randomized IRS-IV study of conventional fractionation radiotherapy (50.4 Gy/28 fractions given in 1.8 Gy daily fractions) versus hyperfractionated radiotherapy (59.4 Gy/54 fractions given in 1.1 Gy twice daily fractions) for group III RMS patients, the use of hyperfractionated radiotherapy did not improve local/regional control, failure free survival, or OS compared with conventional dose radiation.  Therefore, the standard of care for group III RMS remains conventional fractionation radiotherapy with chemotherapy. Breneman et al.  analyzed the effect of reduced-dose radiotherapy on local control in children with low-risk RMS treated on the Children's Oncology Group (COG) D9602 study. Most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide added for patient subsets with a higher risk of relapse in IRS Group III and IV studies. The authors concluded that for patients with microscopic tumor after surgical resection or with orbital primary tumors, reduced-dose radiotherapy does not compromise local control when cyclophosphamide is added to the treatment program.
Adult RMS though a rare disease is quite heterogenous. The biological behaviour and prognosis of adult RMS is still poorly understood. The limitations of our study are its retrospective nature and small number of patients treated over a long period of time. In our study, IRS grouping and complete response after primary therapy were predictors of a better survival. Distant metastasis have dismal prognosis. Localized RMS should therefore be treated aggressively with multidisciplinary approach comprising of surgery, radiation, and chemotherapy with primary aim of cure and maintaining quality of life with emphasis on preservation of function and cosmesis. Radiation therapy definitely improves local control but that did not transform into OS. Despite retrospective nature and small patient number, our findings are important, as there is sparsity of literature on RMS in adults.
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