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LETTER TO THE EDITOR
Year : 2015  |  Volume : 52  |  Issue : 1  |  Page : 25-26
 

Feasibility and efficacy of salvage radiotherapy with concurrent weekly topotecan in recurrent primitive neuroectodermal tumor


Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal, India

Date of Web Publication3-Feb-2016

Correspondence Address:
I Ghosh
Department of Medical Oncology, Tata Medical Center, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175587

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How to cite this article:
Ghosh I, Mallick I, Ray S. Feasibility and efficacy of salvage radiotherapy with concurrent weekly topotecan in recurrent primitive neuroectodermal tumor. Indian J Cancer 2015;52:25-6

How to cite this URL:
Ghosh I, Mallick I, Ray S. Feasibility and efficacy of salvage radiotherapy with concurrent weekly topotecan in recurrent primitive neuroectodermal tumor. Indian J Cancer [serial online] 2015 [cited 2019 Dec 11];52:25-6. Available from: http://www.indianjcancer.com/text.asp?2015/52/1/25/175587


Sir,

Peripheral primitive neuroectodermal tumor (PNET) is inherently sensitive to chemotherapy and radiation but prognosis of relapsed disease remains poor. We report a young adult with localized progressive disease while on treatment, salvaged with radiation and concurrent topotecan.

A 24-year-old medical internee presented with shortness of breath on exertion and heaviness in left chest since June 2011. A computed tomography (CT) scanthorax showed multiple nodular masses in left upper lobe. CT-guided biopsy revealed a malignant round-cell tumor, strongly positive for mic-2 and Fli-1, suggestive of PNET. A staging 18-fluourodeoxyglucose positron tomographic scan FDG-PET-CT showed extensive left pleural and chest wall mass with SUVmax 17.6. There was no evidence of disease outside the left hemithorax. He received 9 weeks of vincristine–ifosfamide–etoposide–adriamycin–cyclophosphamide chemotherapy. Post-chemotherapy (PET-CT) showed complete metabolic and significant morphological regression. He underwent left pleural decortication and tumor debulking (R2 resection).

External radiation to the primary tumor residual and margins covering the initial disease volumes was given using image-guided intensity-modulated radiotherapy (IG-IMRT). A limited planning PET-CT revealed a significant uptake over a large area of the left chest wall and the mediastinal pleura [Figure 1]a. Concurrent chemotherapy with vincristine–actinomycin D–cyclophosphamide was also administered and followed with continuation chemotherapy. A PET-CT done after 8 weeks of radiotherapy (RT) showed complete metabolic regression in the treated volume, but metabolically active disease involving parietal peritoneal deposit adjacent to the left lateral abdominal wall (SUVmax 5.3) [Figure 1]b and [Figure 1]c. Biopsy from the abdominal wall deposit showed round-cell tumor consistent with PNET. Decision was taken to irradiate the parietal deposit along with salvage chemotherapy. Accordingly, external radiation was given to the parietal deposit to a dose of 54 Gy in 27 fractions over 5.5 weeks with IG-IMRT. Five doses of concurrent weekly topotecan 3 mg/m 2 were given from day 1 of RT. Only toxicity was grade 1 thrombocytopenia. This was followed after 2 weeks by three cycles of topotecan (1.5 mg/m 2 D1-D3 IV) and cyclophosphamide (350 mg/m 2 D1-D3 IV) given every three weekly. There was no grade 3-4 toxicity. Following this, another PET-CT revealed non-FDG avid small loculated pleural effusion on the left side, whereas the previously FDG avid left parietal deposit had markedly regressed and become metabolically inert [Figure 1]d and [Figure 1]e. He has completed maintenance therapy with topotecan–cyclophosphamide for six cycles and clinically disease-free at the time of writing.
Figure 1: (a) Axial PET-CT image after induction chemotherapy and surgery, prior to chemoradiotherapy, showing residual disease in the chest; (b, c) axial PET-CT images after 8 weeks of completion of radiation, showing metabolic response in the chest but active disease on the left lateral abdominal wall (arrow); (d, e) axial PET-CT images after topotecan-based chemoradiotherapy showing complete resolution of metabolic activity and significant morphological regression of the parietal deposit (arrow)

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Topotecan–cyclophosphamide has shown encouraging response rates in relapsed PNET.[1],[2] Topotecan causes double strand DNA damage during DNA synthesis, by stabilizing the topoisomerase I-DNA complex. Thus, it can also act as a potential radiosensitizer. Topotecan concurrent with radiation has been tested for other solid tumors such as cervical cancer, lung cancer, brain metastases, and pediatric gliomas, but not PNET.[3] Most of these studies used a continuous infusional schedule of topotecan during irradiation. Weekly topotecan has been shown in ovarian cancer to be as effective but with lower toxicity as the more commonly employed 5-day schedule.[4] Hence, we used weekly topotecan concurrent with radiation in this patient. The relative contribution of radiation and topotecan to the response is difficult to ascertain in this patient. But PNET being essentially a systemic disease, the role of topotecan cannot be overemphasized here. Topotecan concurrent with radiation should be investigated further in prospective trials for PNET. We also want to highlight the role of PET-CT in the staging and response evaluation in this patient. Though it is still not a standard, sensitivity of 96% and specificity of 92% have been reported in a meta-analysis for FDG-PET-CT in Ewing sarcoma family of tumors.[5]

 
  References Top

1.
Saylors RL 3rd, Stine KC, Sullivan J, Kepner JL, Wall DA, Bernstein ML, et al. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: A pediatric oncology group phase II study. J Clin Oncol 2001;19:3463-9.  Back to cited text no. 1
    
2.
Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer 2006;47:795-800.  Back to cited text no. 2
    
3.
Neuhaus T, Ko Y, Muller RP, Grabenbauer GG, Hedde JP, Schueller H, et al. A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer. Br J Cancer 2009;100:291-7.  Back to cited text no. 3
    
4.
Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, et al. Topotecan weekly versus conventional 5-day schedule in patients with platinum-resistant ovarian cancer: A randomized multicenter phase II trial of the north-eastern German society of gynecological oncology ovarian cancer study group. J Clin Oncol 2011;29:242-8.  Back to cited text no. 4
    
5.
Treglia G, Salsano M, Stefanelli A, Mattoli MV, Giordano A, Bonomo L. Diagnostic accuracy of 18 F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumors: A systematic review and a meta-analysis. Skeletal Radiol 2012;41:249-56.  Back to cited text no. 5
    


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