|Ahead of print publication
Pediatric extremity rhabdomyosarcoma treated with re-brachytherapy in recurrent setting
Ankita Rungta Kapoor1, Manish Chandra1, Rajendra Bhalavat1, Chetna Bakshi2, Chetan Anchan3, Pratibha Bauskar4, Saurabh Markana1
1 Department of Radiation Oncology, Jupiter Hospital, Thane, Maharashtra, India
2 Department of Medical Oncology, Jupiter Hospital, Thane, Maharashtra, India
3 Department of Bone and Soft Tissue Oncosurgery, Jupiter Hospital, Thane, Maharashtra, India
4 Department of Medical Physics, Jupiter Hospital, Thane, Maharashtra, India
|Date of Submission||25-May-2020|
|Date of Decision||16-Jul-2020|
|Date of Acceptance||14-Oct-2020|
|Date of Web Publication||22-Jun-2022|
Ankita Rungta Kapoor,
Jupiter Hospital, Off Eastern Express Highway, Thane - 400 601, Maharashtra
Source of Support: None, Conflict of Interest: None
Rhabdomyosarcomas (RMS) are pediatric soft-tissue sarcomas arising from immature mesenchymal cells that are intended to form striated skeletal muscles. Brachytherapy delivers high-dose of precised radiation to the target tissue with high conformity, sparing the nearby normal tissues, hence allowing dose escalation and reducing the likelihood of normal tissue toxicity. There is a scarcity of reports on the use of brachytherapy for extremity RMS. We report the case of pediatric extremity RMS treated with re-brachytherapy in recurrent setting. A 4-year-old boy diagnosed with RMS of right upper arm underwent local excision of the lesion. Postoperative magnetic resonance imaging showed suspicious residual lesion. Revision surgery followed by brachytherapy with 30 Gy in 10 fractions twice a day over 5 days was delivered. The child developed local recurrence after 12 months. Reexcision and re-irradiation with brachytherapy were done delivering 27 Gy in 9 fractions twice a day over 5 days. The child is disease-free 18 months posttreatment with no significant disparity in limb length suggestive of successful preservation of growth epiphysis. Re-irradiation with interstitial brachytherapy can be considered as an option for the treatment of recurrent pediatric extremity rhabdomyosarcoma, in conjunction with surgery and chemotherapy, despite treated previously with brachytherapy.
Keywords: Brachytherapy, case report, extremity rhabdomyosarcoma, pediatric
|How to cite this URL:|
Kapoor AR, Chandra M, Bhalavat R, Bakshi C, Anchan C, Bauskar P, Markana S. Pediatric extremity rhabdomyosarcoma treated with re-brachytherapy in recurrent setting. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 2]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=347792
| > Introduction|| |
Rhabdomyosarcomas (RMS) are pediatric soft-tissue sarcomas arising from the immature mesenchymal cells that are intended to form striated skeletal muscles. They are seen in children of age 2–6 years or 15–19 years with two-third cases under the age of 6 years. Most cases are sporadic but can be inherited as a part of syndromes such as neurofibromatosis and Li-Fraumeni. They can originate from any anatomic location most commonly para-meningeal and nonpara-meningeal head and neck, genitourinary, extremity, and trunk in the descending order. Major histologies include embryonal (classic, spindle cell, and bortryoid), alveolar, pleomorphic, and undifferentiated. Extremity RMS is usually alveolar histology. The tumor appears as a small round blue cell tumor morphologically. Evaluation of suspected cases of RMS requires an assessment of the extent of primary disease as well as metastatic workup. Radiological evaluation can be done by a plain radiograph or a computed tomography (CT) scan of the primary. Although metastatic disease at presentation has a worse prognosis, yet metastases from genitourinary sites have better outcome as compared to other primary sites. Treatment is selected according to a risk-based algorithm that combines histologic classification with presurgical stage and postsurgical clinical group. Large international groups such as Intergroup Rhabdomyosarcoma Study Group have developed multimodality treatment protocols leading to improved cure rates over the past several decades. Complete resection followed by local radiation with brachytherapy with or without external-beam radiation therapy (EBRT) enhances local control in almost all patients, particularly in patients with residual microscopic or gross residual disease.,, Brachytherapy delivers high-dose of conformal radiation to the target tissue sparing the critical organs-at-risk, hence escalating the dose and eliminating the possibility of normal tissue toxicities. The most frequent tumor sites where brachytherapy has been used are gynecological RMS, and prostate/bladder RMS. In small series from two institutions, it was found to be associated with good survival rates with retention of organ function in most of the pediatric patients with gynecological RMS., There is a scarcity of reports on the use of brachytherapy for extremity RMS. We report a case of pediatric extremity RMS treated with re-brachytherapy in recurrent setting, previously treated with interstitial implant.
| > Case Report|| |
A 4-year-old boy with no family history presented with a lump in the right upper arm in January 2017, progressively increased in size and not associated with pain. Local ultrasonography revealed heterogeneous well-defined irregular mass of size 3.5 cm × 2 cm with low-to-medium echogenicity. Core biopsy from the lump showed a spindle cell RMS. Immunohistochemistry (IHC) was positive for desmin, myoglobin, surface membrane antigen, and negative for S100, CD34, cytokeratin, epithelial membrane antigen, and CD99. He underwent wide local excision; histopathology showed specimen size 5 cm × 4 cm × 3 cm, partly encapsulated and microscopy confirmed it to be spindle cell RMS; the margins were negative. He was classified as RMS Group 1, low risk. Magnetic resonance imaging (MRI) of the right shoulder showed postoperative changes in the lateral aspect of the right arm, fluid collection 1.5 cm × 1.2 cm × 2.7 cm at operative site suggestive of operative debris. He received three cycles of adjuvant chemotherapy with vincristine, ifosfamide, and etoposide, then defaulted further treatment. Parents came with a complaint of a feeling of nodularity at the previous surgical site in august 2017. MRI of the right arm showed sub cm suspicious lesion at the site of previous surgical scar in the lateral aspect of the right arm. Revision surgery was done with frozen section, which confirmed malignancy. In the same sitting, ten interstitial brachytherapy catheters were placed in the tumor bed. Final histopathology showed residual spindle cell RMS of size 0.3 cm × 0.2 cm, and all margins were free. CT-based planning was done, and the plan that delivered a good dose to the clinical target volume (CTV) and acceptable doses to nearly normal tissue was selected for the treatment. The dose to skin, entry and exit points of catheters were kept within an acceptable range. A total dose of 30 Gy in 10 fractions twice a day over 5 days was delivered keeping a gap of at least 6 h between the fractions. The equivalent dose in 2 Gy per fraction (EQD2) of this regimen was 33 Gy which is close to recommended dose of 36 Gy with EBRT. The child was cooperative throughout the treatment course and tolerated the treatment fairly well. He completed 5 cycles of maintenance chemotherapy, last dose in November 2017. Positron emission tomography-computed tomography (PET-CT) done in February 2018 showed no evidence of disease. [Figure 1] depicts the flowchart of events of the reported case.
In August 2018, he complained of pain around the right shoulder and parents noticed thickening under the surgical scar. On examination, there was thickening of mid-segment of the surgical scar with local tenderness, with a preserved range of movements. MRI right shoulder and upper arm showed a recurrent lesion of size 1.5 cm × 1.3 cm × 0.9 cm at the operated site in the anterolateral aspect involving underlying deltoid muscle. Restaging PET-CT showed 0.9 cm × 0.8 cm × 0.9 cm well-defined intramuscular-enhancing lesion involving lateral end of right triceps brachii muscle (maximum standardized uptake value 11.18) and ill-defined patchy enhancing intramuscular lesion along the incision site of right deltoid muscle showing low-grade uptake. There was no evidence of distant metastasis. He underwent re-excision in September 2018 with the placement of five interstitial catheters in a single plane covering the tumor bed. Histopathology report showed a 1.5 cm × 1.5 cm × 2 cm hard nodule on grossing, microscopy confirmed spindle cell RMS without necrosis and mitotic activity of 2/hpf. All margins were free. He was diagnosed as recurrent RMS. The patient's parents were not ready for long duration of treatment as with external-beam radiotherapy (EBRT), thus, option of repeat brachytherapy was given. Interstitial catheters were placed intra-operatively covering the tumor bed under general anesthesia. Intra-operative pictures of interstitial implant and planning are shown in [Figure 2] and [Figure 3]. A highly conformal High Dose Rate (HDR) brachytherapy plan was generated preserving the nearby bone (humerus) from high-dose radiation. He received 27 Gy in 9 fractions over 5 days two fractions per day keeping minimum 6 h gap between the two fractions. Dosimetry of CTV and humerus is given in [Table 1] and [Table 2]. In the residual setting, V100, V150, V200 for CTV was 95%, 33.7%, and 13.9%, respectively, and for the humerus, Dmax was 3.67 Gy, D50 was 43% and D2 was 86%. In the recurrent setting, V100, V150, and V200 for CTV was 90%, 18%, and 8.6%, respectively, and for the humerus, Dmax was 1.74 Gy, D50 was 21.5%, and D2 was 44.5%.
|Figure 2: Intraoperative picture (a) showing ten interstitial catheters in treatment of residual disease; (b) showing computed tomography planning in coronal plane, red color denotes 200%, pink 100%, yellow 90%, and cyan 80% dose (c) showing cosmetic outcome at 10 months postsurgery and brachytherapy|
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|Figure 3: Intraoperative picture (a) showing five interstitial catheters in recurrence; (b) and (c) showing computed tomography planning in coronal and sagittal planes, respectively. Red color denotes 200%, pink 100%, cyan 90%, and yellow 80% dose|
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|Table 1: Dosimetry parameters per fraction for clinical target volume after interstitial brachytherapy in residual and recurrent settings|
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|Table 2: Dosimetry parameters per fraction for humerus as organ-at-risk after interstitial|
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Adjuvant chemotherapy was advised; however, the parents refused further treatment as the child had already received eight cycles of chemotherapy previously and were very anxious about the acute toxicities. PET-CT was performed 2 months postcompletion of brachytherapy which showed no evidence of disease. He remains disease-free at his last follow-up in July 2020, local MRI showed no evidence of disease. Written informed consent was obtained from the parents for the publication of this case report and accompanying images.
| > Discussion|| |
Interstitial brachytherapy has been tried in recurrent pediatric RMS in orbit, soft palate, gluteal and anal mass, but there is a dearth of evidence for its use in extremity. Brachytherapy allows the escalation of dose to the target with normal tissue sparing which makes it a preferred modality for tumors with nearby critical organs. Children of age ≤36 months with RMS are difficult to treat in view of a high probability of morbidity associated with the treatment. Even in patients with Stage I disease if the radiation is excluded from the multimodality treatment, there is an increased probability of local recurrence reinforcing the necessity of radiation therapy. In extremity RMS, primary re-excision before initiation of chemotherapy is considered appropriate in patients with microscopic disease in initial surgery which can be resected by a second surgery without cosmesis or functional loss. In our patient, re-irradiation with brachytherapy was done in the recurrent setting, previously treated with interstitial implant, with a disease-free interval of 1 year. Recurrence was limited locally with no nodal or distant metastases. The site of disease was at the upper third of humerus so brachytherapy was considered as a good option for delivering adjuvant radiation to spare the growth epiphysis. The critical dose to growth epiphysis is 25 Gy below which significant growth abnormalities are rare., The dose of brachytherapy in the second recurrence was reduced to meet this constraint. Single plane interstitial implant was found to be yielding adequate coverage as the child's muscle mass was very low. It is important to note that although the limb may be spared with the use of radiotherapy, the limb is at risk of shortening, pathologic fracture, and atrophy. Such morbidities are actually dose-dependent and can lead to survivorship issues in later life. Despite these late adverse effects, the parents should be counseled to make them understand that residual arm-length discrepancy still offers significantly better function as compared to amputation. The child in our case has no significant disparity in arm's length as compared to the other arm; however, longer follow-up time is needed to comment upon the same. Brachytherapy has the additional advantage of shorter duration of the treatment which is especially beneficial for pediatric patients.
| > Conclusions|| |
Re-irradiation with interstitial brachytherapy can be considered as an option for the treatment of recurrent pediatric extremity rhabdomyosarcoma, in conjunction with surgery and chemotherapy, despite treated previously with brachytherapy. Longer follow-up is needed to comment upon late effects of brachytherapy in this setting.
The authors acknowledge the work and support of the nursing staff: Mrs. Uma Ambekar, Mrs. Sunu John and Mrs. Dayana Jain.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the parents have given their consent for images and other clinical information to be reported in the journal. The parents understand that names and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Skapek SX, Ferrari A, Gupta AA, Lupo PJ, Butler E, Shipley J, et al
. Rhabdomyosarcoma. Nat Rev Dis Primers 2019;5:1.
Dagher R, Helman L. Rhabdomyosarcoma: An overview. Oncologist 1999;4:34-44.
Sultan I, Ferrari A. Selecting multimodal therapy for rhabdomyosarcoma. Expert Rev Anticancer Ther 2010;10:1285-301.
Shiu MH, Hilaris BS, Harrison LB, Brennan MF. Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb. Int J Radiat Oncol Biol Phys 1991;21:1485-92.
Harrison LB, Franzese F, Gaynor JJ, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in the management of completely resected soft tissue sarcomas of the extremity and superficial trunk. Int J Radiat Oncol Biol Phys 1993;27:259-65.
Chaudhary AJ, Laskar S, Badhwar R. Interstitial brachytherapy in soft tissue sarcomas. The Tata Memorial Hospital experience. Strahlenther Onkol 1998;174:522-8.
Manir KS, Basu A, Choudhury KB, Basu S, Ghosh K, Gangopadhyay S. Interstitial brachytherapy in soft tissue sarcoma: A 5 years institutional experience with Cobalt 60-based high-dose-rate brachytherapy system. J Contemp Brachytherapy 2018;10:431-8.
Flamant F, Gerbaulet A, Nihoul-Fekete C, Valteau-Couanet D, Chassagne D, Lemerle J. Long-term sequelae of conservative treatment by surgery, brachytherapy, and chemotherapy for vulval and vaginal rhabdomyosarcoma in children. J Clin Oncol 1990;8:1847-53.
Magné N, Oberlin O, Martelli H, Gerbaulet A, Chassagne D, Haie-Meder C. Vulval and vaginal rhabdomyosarcoma in children: Update and reappraisal of Institut Gustave Roussy brachytherapy experience. Int J Radiat Oncol Biol Phys 2008;72:878-83.
Pötter R, Knocke TH, Kovacs G, Schmilowski GM, Haverkamp U, Hawliczek R, et al
. Brachytherapy in the combined modality treatment of pediatric malignancies. Principles and preliminary experience with treatment of soft tissue sarcoma (recurrence) and Ewing's sarcoma. Klin Padiatr 1995;207:164-73.
Haie-Meder C, Mazeron R, Martelli H, Oberlin O. Role of brachytherapy in pediatric rhabdomyosarcomas. Cancer Radiother 2013;17:155-8.
Breneman J, Meza J, Donaldson SS, Raney RB, Wolden S, Michalski J, et al
. Local control with reduced-dose radiotherapy for low-risk rhabdomyosarcoma: A report from the Children's Oncology Group D9602 study. Int J Radiat Oncol Biol Phys 2012;83:720-6.
Walterhouse DO, Pappo AS, Meza JL, Breneman JC, Hayes-Jordan AA, Parham DM, et al
. Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 2014;32:3547-52.
Hays DM, Lawrence W Jr, Wharam M, Newton W Jr, Ruymann FB, Beltangady M, et al
. Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites. J Pediatr Surg 1989;24:5-10.
Paulino AC. Late effects of radiotherapy for pediatric extremity sarcomas. Int J Radiat Oncol Biol Phys 2004;60:265-74.
Eifel PJ, Donaldson SS, Thomas PR. Response of growing bone to irradiation: A proposed late effects scoring system. Int J Radiat Oncol Biol Phys 1995;31:1301-7.
Lewis RJ, Marcove RC, Rosen G. Ewing's sarcoma -- functional effects of radiation therapy. J Bone Joint Surg Am 1977;59:325-31.
Rao AD, Ladra M, Dunn E, Kumar R, Rao SS, Sehgal S, et al
. A road map for important centers of growth in the pediatric skeleton to consider during radiation therapy and associated clinical correlates of radiation-induced growth toxicity. Int J Radiat Oncol Biol Phys 2019;103:669-79.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]