Adolescent–adult nonmetastatic Ewing sarcoma—Experience from a large developing country

Abstract

Background: Outcome and toxicity data in adolescent-adult Ewing sarcoma (AA-ES) patients are sparse and merits exploration. Methods: Histopathologically confirmed, nonmetastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (Ewing's family of tumors-2001 [EFT-2001]) comprising of ifosfamide plus etoposide and vincristine, doxorubicin plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS), and overall survival (OS). Results: There were 235 patients (primary safety cohort [PSC]) with median age of 23 (15-61) years; 159 (67.7%) were males, 155 (65.9%) had skeletal primary and 114(48.5%) had extremity tumors. One hundred ninety-six (83.4%) were treatment naïve (primary efficacy cohort [PEC]) and of these 119 (60.7%) had surgery. In PEC, at a median follow-up of 36.4 (interquartile range [IQR] 20-55) months, estimated 3-year EFS and OS were 67.3% (95% CI 60.3-75.1%) and 91.1% (95% CI 86.7-95.7%), respectively. Of these, 158 (80.6%) complying with intended treatment, at a median followup of 39 (IQR 26-57) months had an estimated 3-year EFS of 68.2% (95% CI 60.3-76.1%). In multivariable analysis, good prognostic factors included longer symptom(s) duration (HR 0.93, 95% CI 0.86-0.994), ≥99% necrosis (HR 0.30, 95% CI 0.11-0.77), and treatment completion (HR 0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile neutropenia (119, 50.6%), anemia (130, 55.3%), peripheral neuropathy (37, 15.7%), with three (1.3%) chemo-toxic deaths. Conclusions:The outcomes of AA nonmetastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen can be considered a standard of care in AA-ES.

Outcomes of Ewing sarcoma in adults over 40 years of age from a low-middle income country

“…Our finding of inferior survival in older adults is in concurrence with many studies [ 15 , 30 , 36 , 50 – 52 ], including our data of non-metastatic AA ES [ 43 ]. The worse outcome can be explained by less physiological reserve and more comorbidity in this group leading to more treatment-related toxicity, with even some curative patients not being considered for intensive chemotherapy owing to these reasons.…”

“…In this cohort vincristine was the chemotherapeutic drug which was most commonly modified/omitted. In our earlier study of adolescent-adult (AA) non-metastatic ES patients [ 43 ], we have noted that the permanent dose modifications for the entire regimen were required predominantly for haematological toxicities in 34 (14.5%) cases. There were transient or permanent alterations in vincristine doses and/or frequency of administration in additional 83 (35.3%) cases due to peripheral neuropathy (grade ≥2).…”

“…There were transient or permanent alterations in vincristine doses and/or frequency of administration in additional 83 (35.3%) cases due to peripheral neuropathy (grade ≥2). Few studies also show that delivery of chemotherapy to elderly patients remains a challenge compared to younger patients [ 44 , 45 ] in view of toxicity and lesser dose intensity achieved in older patients [ 38 , 43 , 46 ]. Cardiac toxicity comparison of older patients with paediatric and AA cohort reveals a higher incidence of cardiac toxicity for children [ 43 , 47 ] as they are more sensitive to anthracyclines [ 48 ].…”

The Survival Outcomes, Prognostic Factors and Adverse Events following Systemic Chemotherapy Treatment in Bone Sarcomas: A Retrospective Observational Study from the Experience of the Cancer Referral Center in Northern Thailand

“…Although chemotherapy is one of the most effective modalities for bone sarcomas, there have been a few reports on the experience of such treatment modalities in developing countries [ 47 , 48 , 49 , 50 ]. For osteosarcoma, the most common regimen for neoadjuvant, adjuvant, and palliative chemotherapy in our setting was Cisplatin plus Doxorubicin, followed by Ifosfamide plus Doxorubicin, and its combination with Cisplatin or Methotrexate.…”

Prognostic Modeling for Bone Sarcomas based on a Large Prospective Cohort from a Tertiary Care Cancer Centre in India

“…In our published data on patients with Ewing's sarcoma at our institute treated with the "EFT-2001" protocol, statistically significant prognostic factors included longer symptom duration, >= 99% necrosis, and protocol completion. [10] There are unique challenges with rare cancers like bone sarcomas globally and a prognostic model with wide applicability including for the patients in LMIC wherein including social challenges also play a role is an unmet need. Special challenges in LMIC include lack of awareness among patients and primary health care providers with resultant delayed presentation, upstaging and high tumor burden.…”