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1 Clinical Pharmacologist, HCG Cancer centre, Health Care Global Enterprises, Kalburgi, Karnataka-585102, India;
2 Cancer Research Centre, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran;
3 Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;
4 Department of Pharmacy Practice, Jaya College of Paramedical Sciences, College of Pharmacy, Thiruninravur, Chennai-602024, India;
5 Department of Pharmacy Practice, C.L Baid Metha College of Pharmacy, Thorapakkam, Chennai-600097, India
Corresponding Author: John Thomas Palathingal, Clinical Pharmacologist, HCG Cancer centre, Health Care Global Enterprises, Kalburgi, Karnataka-585102, India. Mobile Number: +919791140261; E-mail: johnpt1993@gmail.com.
Running title: A Case report on Relapsed Ewings Sarcoma
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ABSTRACT |
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INTRODUCTION |
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CASE REPORT |
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DISCUSSION |
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CONCLUSION |
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ACKNOWLEDGEMENT |
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ABBREVIATIONS |
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ETHICAL APPROVAL |
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REFERENCES |
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ABSTRACT
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Ewing’s Sarcoma has increased chances of relapsing and metastases with deposits of lesions in other bones and organs. Its peak occurrence is between the age group of 10 to 20 years affecting the elderly too. We present a case on Relapsing of Ewing's Sarcoma in the right finger and metastases to the left knee joint. The PET CT initially revealed a small metabolically active lesion in the lateral aspect of the base of the right ring finger. With recurrence of chief complaint, PET CT image, MRI scan, and other confirmative procedures he was confirmed with RES. He was followed by a chemotherapy protocol of VAC/IE in 17 cycles, radiation therapy and additional therapy. Our patient showed improvement in his side effects with immunotherapy for his hair loss. He did not undergo any surgical procedures. Appropriate patient counselling and discharge medications with time to time reviewing were carried out in the patient. This case elaborates the benefits of combination therapy in an RES when compared to chemotherapy alone..
KEY WORDS: Bone lesion; Chemotherapy; Ewing's sarcoma; PET CT|
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INTRODUCTION |
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Ewing’s sarcoma is a very rare type of cancerous tumour occurring in bones or the soft tissues surrounding the bones, such as cartilage or the nerves. It is a small round blue cell tumour belonging to the Ewing Sarcoma Family of Tumour (1, 3, 28). It has equal incidence of occurrence in Axial and Appendicular region. It is the second common type of sarcoma found next to osteosarcoma in children’s. It usually affects people from the age of 10 to 20 years at peak. It is slightly more common in males than in females with a male/female ratio of 1.5:1. Its presenting symptoms may include swelling, fever and pain at site and fever which makes it most commonly misdiagnosed as Osteomyelitis. Thus complete differentiated diagnosis would be required in order to confirm it. It mostly occurs in Caucasians than the Afro -Americans or Asians (6, 8, 27). Chances of tendency towards recurrence and proclivity to haematogenous metastases to bones and lungs have been known. Etiological factors associated with Ewings or its risk factors are not completely known. About 90% of tumours have their translocation at t(11:22)(q24:q12) and the rest 10% at t(21:12)(22:12) (1, 2). Here we present as case on 26 year old male with RES in his right ring finger and metastases towards the left knee on Chemotherapy, Radiation and Immunotherapy (11-14).
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CASE REPORT |
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A 26 year old Indian male patient came to Oncology department of the hospital with chief complaints of inflammation, swelling and pain on the right ring finger for the past 5 months. He was a known case of Ewing's Sarcoma since more than a year ago with no family history of Malignancy. He was initially diagnosed with Ewing’s sarcoma confirmed through biopsy reports, following which he had undergone 3 courses of chemotherapy with VAC/IE. PET CT showed disease free after the therapy and he was defaulted from chemotherapy for 10 months. After 5 months he had been experiencing pain and inflammation at the same site. Past medical history, signs and symptoms along with PET CT indicated, a recurrence of Ewing’s sarcoma (Figure 1). His PET CT image showed small metabolically active lesion in the lateral aspects of the base of the right ring finger which was not noted in the earlier one. His immunohistochemistry report showed malignant round cell tumor suggestive of Ewing's sarcoma primitive neuroectodermal tumor, Biopsy from mass right finger proximal phalanx (Figure 2). MRI scan showed hyperintense lesion, the soft tissues of the proximal phalanx of the 4th finger, the lesion in hyperintense on PDFs images and GRE images and heterogeneous signal intensity on T2W. Lesion is isointense on T1W images, it measures about 3 × 3 cm on coronal image, No obvious calcification and fat within the lesion. There was increased 99 mTc-MDP uptake along the proximal phalanx of the right 4th finger with no obvious erosion/Lytic changes.
On general examination the patient was found to be conscious, oriented and afebrile. Patient was anaemic and Thrombocytopeniaic with varying values in complete blood count. His Chemotherapy was Vincristine/Doxorubicin/Cyclophosphamide and Ifosfamide based protocol. He was started on treatment with Cap. Aprepitant 125 Mg OD,Inj. Palonestron 0.25 mg IV OD, Inj. Etoposide 220 mg in 500 ml NS over 1 hour OD,Inj. Mesna (Mercaptoethanesulfonate) 540 mg in 5% dextrose 100 ml over 15 min OD, Inj.Ifosfamide 3960 mg in 500 ml NS over 1 hour OD, Inj. Ranitidine 50 mg OD and Inj. Dexamethasone 8mg with 100 mL/NS over 10 mins OD, Inj. Vincristine 2 mg IV stat, Inj. Cyclophosphamide 2640 mg with 500 ml over 2 hours, Inj. Actinomycin D 2.6 mg IV stat, Inj. Colistin 300 mcg SC 24 hours after chemotherapy. Patient was regular to his treatment, completing 17 cycles of chemotherapy along with 17 cycles of radiation therapy.Radiation therapy included Photon energy by IMRT technique on linear accelerator varian machine with a dose of 45 Gy125fr©180cGy/fr.His discharge medications included T.Ondansetron 8 mg TID, T. Pantoprazole 20 mg BID, T. Ascorbic acid OD, T. Ferrous Fumarate/Folic acid BID, T.Acetaminophen TID. The condition of the patient has improved and he was discharged with proper counselling. His PET CT scan reports during his next visit to the hospital showed resolution of metabolic activity of the lesion in his right ring finger (Figure 3). At the time of discharge he was found to have inflammation on the right knee which was non-cancerous in nature. Recent PET CT scan indicated a persistent metabolic activity in the left knee joint, left upper tibio-fibular joint. MRI of left knee joint showed enhancing lesions in posterior intercondylar region and lateral to lateral tibial plateau possibly metastatic deposit. Inflammation likePost anterior ligament reconstruction status in right knee with increased metabolic activity along operative tract was seen.There was no evidence of abnormal increased FDG accumulation in any other visceral organs or elsewhere in the body (Figure 4). Thus further continuation of Immunotherapy was the choice applied in the patient.
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DISCUSSION |
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There is no established standard chemotherapy regimen for relapsed Ewing’s sarcoma. Currently Ewing’s Sarcoma is treated with Chemotherapy, Radiation therapy, Surgery, targeted therapy, High-dose chemotherapy with stem cell rescue (16-19). New types of treatment are being tested in clinical trials-Chimeric antigen receptor (CAR) T-cell therapy (1). In this Case patient was anaemic, leukopenic, thrombocytopenic and immunocompromised after the first cycle of chemotherapy. After the completion of 4th chemotherapy cycle, patient experienced hair loss. Patient was managed with IV fluids along with chemotherapy. After 24 hours of each chemotherapy, the patient was treated with Inj. Colistin 300 mcg subcutaneously for increasing total count. Patient was informed about the side effects of treatment that can occur during the course of chemotherapy. After 17 cycles of chemotherapy along with 17 cycles of Radiation Therapy, patient’s condition improved. Recombinant Human Interleukin-7 was used to boost the immune system.
In our patient combination therapy was involved for the treatment of relapsed Ewing’s sarcoma. The treatment regimen involved the use of various chemotherapeutic agents, combined with radiation therapy, immunotherapy which gave better outcome. This finding disagrees with the study conducted by Tenneti et al., where even with HDCT/ASCT treatment, PET scan revealed progression of the disease (1, 15, 20).The study conducted by A. Tong et al., demonstrated that natural killer cells are effective against pulmonary ES making immunotherapy a better option to fight cancer which supports our study (4). In our study, the patient’s condition got improved after 17 cycles of chemotherapy and radiotherapy. In contrast, study conducted by Khan SJ et al., using 13 patients with pelvic ES, the treatment given was radiotherapy and chemotherapy following EuroEwing-99 protocol. The result revealed poor local control and overall survival of ES patient (2, 5, 10). Prominent chemotherapeutic agents made use of in patients with ES were Vincristine, Ifosfamide, Cyclophosphamide, Doxorubicin, Etoposide, Dactinomycin etc. These neoadjuvant chemotherapeutic agents have reduced the need for limb-salvages, thus increasing the functional activity of the patients without the need for surgery. Ewing’s sarcoma is highly radiosensitive and thus making use of chemotherapy along with radiation therapy has more chances for reducing mortality and obtaining complete cure.
Combined multimodal therapy that included chemotherapy, radiotherapy, and surgery was used as a treatment option in patients with ES of the head and neck in the study conducted by Olson MD et al. The study revealed that the use of combined multimodal therapy resulted in 5 year overall survival and recurrence free survival of 87% and 75% respectively which agrees with our study that combined therapy can be a better option to prevent relapse Ewing’s sarcoma (3, 4).
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CONCLUSION |
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Health education is a paramount to control cancer in its early stages. Regular monitoring is required to control the recurrence of cancer(Ewing’s Sarcoma).Chemotherapy has many side effects like hair loss, decreased immunity etc which can be managed through immunotherapy and Radiation Therapy. Therefore, combination therapy is found to be a better option in the treatment of cancer. Initially treating with chemotherapy along with Radiation Therapy in severe stages followed by immunotherapy gives a better outcome.
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ACKNOWLEDGEMENT |
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We thank the patient for giving his consent towards publication of his case report and other healthcare members of the hospital.
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ABBREVIATIONS |
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PET CT: Positron Emission Tomography-Computed Tomography
CAR: Chimeric antigen receptor
99mTC-MDP: Technetium Medronic acid
MRI: Magnetic Resonance Imaging
GRE: Gradient Recalled Echo
HDCT/ASCT: High Dose Chemotherapy with Autologous Stem Cell Transplantation
RES: Relapsed Ewings Sarcoma
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ETHICAL APPROVAL |
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Permission from the hospital was obtained in order to publish the case report. Informed consent was duly signed by the patient and the care taker for its publication.
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REFERENCES |
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