Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma

• Published in: Pediatric blood & cancer Vol. 62; no. 1; pp. 16 - 23
• Main Authors: Dantonello, Tobias M., Stark, Monika, Timmermann, Beate, Fuchs, Jörg, Selle, Barbara, Linderkamp, Christin, Handgretinger, Rupert, Hagen, Rudolf, Feuchtgruber, Simone, Kube, Stefanie, Kosztyla, Daniel, Kazanowska, Bernarda, Ladenstein, Ruth, Niggli, Felix, Ljungman, Gustaf, Bielack, Stefan S., Klingebiel, Thomas, Koscielniak, Ewa
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-01-2015; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chemotherapy; Child; Child, Preschool; embryonal rhabdomyosarcoma; Female; Follow-Up Studies; Hematology; Humans; Infant; Infant, Newborn; Lymphatic Metastasis; Male; Multivariate analysis; Neoadjuvant Therapy; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Oncology; Ovarian cancer; Pediatrics; Prognosis; response; Retrospective Studies; Rhabdomyosarcoma, Embryonal - drug therapy; Rhabdomyosarcoma, Embryonal - mortality; Rhabdomyosarcoma, Embryonal - pathology; Survival Rate; Tumor Burden; Young Adult; chemotherapy; embryonal rhabdomyosarcoma; response
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.25207

Background
Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG‐III) embryonal rhabdomyosarcoma (RME) in consecutive CWS‐trials. To evaluate its actual impact we studied response‐related treatment and outcomes.
Procedure
Patients with IRSG‐III RME <21 years and non‐response (NR, <33% volume reduction) in five consecutive CWS‐trials were analysed and compared with partial responders (PAR, ≥33% reduction). The NR was reviewed and sub‐classified as Objective Response (OR, <0%–33% reduction) or Stable/Progressive Disease (SPD).
Results
Fifty‐nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk‐factors including age, tumour size, and TN‐classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk‐factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN‐classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty‐two non‐responders were irradiated, and the tumours were completely resected in n = 20. After a median follow‐up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease‐related deaths were locoregional. The five‐year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001).
Conclusion
Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control. Pediatr Blood Cancer 2015;62:16–23. © 2014 Wiley Periodicals, Inc.