Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis

Sparber‐Sauer, Monika; Orbach, Daniel; Navid, Fariba; Hettmer, Simone; Skapek, Stephen X.; Corradini, Nadège; Casanova, Michela; Weiss, Aaron R.; Schwab, Matthias; Ferrari, Andrea

doi:10.1038/s41416-021-01320-1

Cited by 18 publications

(20 citation statements)

References 79 publications

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“…8,14,16 Tumor response, development of resistance or potential side effects influence the duration of treatment. [26][27][28][29] In our series, targeted therapy was indicated in one-third of patients (13/39 cases) in the neoadjuvant or adjuvant setting. Four patients received TKI (three of four after steroids) before a nonmutilating surgery, two patients after steroids and treated by only systemic treatment, two patients in second line of treatment after an incomplete resection, and five patients for the relapse therapy.…”

Section: Discussionmentioning

confidence: 79%

“…Several TKIs targeting ALK, ROS, and NTRK have demonstrated their efficacy in various diseases provided they harbor this molecular rearrangement 8,14,16 . Tumor response, development of resistance or potential side effects influence the duration of treatment 26–29 . In our series, targeted therapy was indicated in one‐third of patients (13/39 cases) in the neoadjuvant or adjuvant setting.…”

Section: Discussionmentioning

confidence: 93%

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Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

Pire

Orbach

Galmiche³

et al. 2021

Pediatric Blood & Cancer

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Background: Inflammatory myofibroblastic tumors (IMT) are rare, intermediate malignant tumors harboring frequent somatic molecular rearrangements. The management of IMT has not been standardized. Methods:A retrospective multicenter study was conducted on all pediatric patients treated for IMT between 2000 and 2019.Results: This series included 39 cases of IMT, with a median age at diagnosis of 7 years (range 20 days to 16 years). Tumor location included pelvis-abdomen (n = 16), thorax (n = 14), head and neck (n = 7), and limbs (n = 2). One patient had metastatic disease. Immunochemistry showed 21/39 (54%) anaplastic lymphoma kinase (ALK)positive tumors. Somatic tyrosine kinase rearrangement was present in 31/36 (86%) of the tumors analyzed: 21 ALK, five ROS1, and five NTRK. Immediate surgery was performed in 24 patients (62%), with adjuvant therapy for three patients. Delayed surgery after neoadjuvant therapy was possible in 10 cases. Exclusive systemic therapy was delivered to four patients; one patient with orbital IMT was managed by watchful waiting. After a median follow-up of 33 months (range 5-124), eight (20%) recurrences/progressions occurred after surgery (seven after primary surgery and one after delayed surgery), after a median interval of 7 months (range 2-21), all in thoracic locations. The 3-year overall and disease-free survivals were 96.8% (95% CI: 79.2%-94.0%) and 77.4% (95% CI: 59.6%-88.1%), respectively. Relapses/progressions were more common in patients with a thoracic primary (p < .001) or after incomplete surgery with no adjuvant therapy (p = .027). Conclusion:Surgery is effective in most cases of pediatric IMT. Systematic analysis of tyrosine kinase rearrangement is recommended. When the tumor is deemed only partially resectable to preserve organs and function, neoadjuvant therapy may be proposed to allow adequate conservative surgery.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 93%

Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

Pire

Orbach

Galmiche³

et al. 2021

Pediatric Blood & Cancer

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“…A prospective comparative trial in children or adults is needed to explore this further. 32 The TKI studies were recently published (publications between 2011 and 2019); 43 TKIs were approved by the Food and Drug Administration for oncological indications in 2019, but DTF is not yet one of them. 33 The toxicity profile of TKIs is manageable when analyzing the grade 3-4 adverse events, but relatively many grade 1-2 adverse events occur.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that DTF could be more aggressive in children. A prospective comparative trial in children or adults is needed to explore this further 32 …”

Section: Discussionmentioning

confidence: 99%

Clinical trials in desmoid‐type fibromatosis in children and adults: A systematic review

Maren

Noesel

Husson

et al. 2022

Pediatric Blood & Cancer

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Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm, which occurs in children and adults, with a peak incidence in young adults. For the majority of the patients, DTF is a chronic and symptomatic disease, which affects health-related quality of life. Systemic treatment regimens tend to differ for patients treated by pediatric oncologists compared to medical oncologists. This systematic review identified 14 clinical trials in children and adults with DTF. Tumor response and progression-free survival rates varied widely between studies and study populations.Treatment choices for patients with DTF are based on a paucity of (randomized) trials.Treatment principles of DTF are similar in pediatric and adult oncology, but the treatment itself is different. This seems mostly driven by a lack of tyrosine kinase inhibitor (TKI) accessibility in pediatric oncology. An insufficient number of studies examined patient-reported outcomes, which are extremely important for patients with a chronic disease like DTF.

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“…Although the exact mechanism(s) by which tyrosine kinase inhibitors (TKIs) act in DT has not been fully elucidated, 70 overexpression of platelet‐derived growth factor receptor β (PDGFRβ), which is inhibited by the TKI imatinib, has been postulated to drive DT development and growth 71 . Initial case reports suggested that imatinib had efficacy in patients with DT 72 .…”

Section: Systemic Control Strategiesmentioning

confidence: 99%

Evolving strategies for management of desmoid tumor

Riedel

Agulnik

2022

Cancer

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Desmoid tumors (DTs) are rare soft tissue mesenchymal neoplasms that may be associated with impairments, disfigurement, morbidity, and (rarely) mortality. DT disease course can be unpredictable. Most DTs are sporadic, harboring somatic mutations in the gene that encodes for βcatenin, whereas DTs occurring in patients with familial adenomatous polyposis have germline mutations in the APC gene, which encodes for a protein regulator of βcatenin. Pathology review by an expert soft tissue pathologist is critical in making a diagnosis. Magnetic resonance imaging is preferred for most anatomic locations. Surgery, once the standard of care for initial treatment of DT, is associated with a significant risk of recurrence as well as avoidable morbidity because spontaneous regressions are known to occur without treatment. Consequently, active surveillance in conjunction with pain management is now recommended for most patients. Systemic medical treatment of DT has evolved beyond the use of hormone therapy, which is no longer routinely recommended. Current options for medical management include tyrosine kinase inhibitors as well as more conventional cytotoxic chemotherapy (e.g., anthracyclinebased or methotrexate-based regimens). A newer class of agents, γsecretase inhibitors, appears promising, including in patients who fail other therapies, but confirmation in Phase 3 trials is needed. In summary, DTs present challenges to physicians in diagnosis and prognosis, as well as in determining treatment initiation, type, duration, and sequence. Accordingly, evaluation by a multidisciplinary team with expertise in DT and patient-tailored management are essential. As management strategies continue to evolve, further studies will help clarify these issues and optimize outcomes for patients.

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Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis

Cited by 18 publications

References 79 publications

Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents

Clinical trials in desmoid‐type fibromatosis in children and adults: A systematic review

Evolving strategies for management of desmoid tumor

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