Desmoid Tumor In Children Research Articles

The Role of Pharmacotherapeutic Agents in Children with Desmoid Tumors.

Desmoid tumors (DT) are rare fibroblastic, soft-tissue tumors that do not metastasize but can aggressively infiltrate tissues causing significant chronic discomfort and/or functional impairment. In the pediatric population, the incidence of DT is greatest during infancy and adolescence but can occur at any age. Dysregulated β-catenin, most commonly resulting from mutations in either CTNNB1 or germline APC (adenomatous polyposis coli) drives DT. Most cases are sporadic but some are associated with predisposition syndromes such as familial adenomatous polyposis (FAP). Historically, treatment has been surgery. However, the recurrence rate after surgery can be high. Various systemic cytotoxic chemotherapy regimens used in other soft-tissue sarcomas have been applied to DT with differing results. Given the chronic and rarely life-threatening nature of this disease and the potential short- and long-term toxicity of these regimens, especially in children, alternative non-cytotoxic interventions have been investigated. Molecularly targeted agents such as tyrosine kinase and gamma secretase inhibitors have shown activity against DT. Innovative local control therapies are being employed as alternatives to surgery and radiation. Periods of prolonged stability and spontaneous regression in the absence of therapy in some patients has prompted wider adoption of an upfront active surveillance approach in the appropriate setting. This review will briefly summarize the epidemiology, pathophysiology, and clinical presentation of DT in children, then focus on historical, current, and future pharmacotherapeutic management and finally, propose areas for future study.

КЛИНИЧЕСКАЯ, РЕНТГЕНОЛОГИЧЕСКАЯ И КОМПЬЮТЕРНО-ТОМОГРАФИЧЕСКАЯ КАРТИНА ДЕСМОПЛАСТИЧЕСКОЙ ФИБРОМЫ НИЖНЕЙ ЧЕЛЮСТИ У ДЕТЕЙ

The paper presents the results of a clinical observation of a 6-year-old female patient, who was admitted to the department of maxillofacial surgery of a multidisciplinary hospital under the compulsory health insurance system with a rare disease of the bone tissue of the lower jaw – desmoplastic fibroma. Desmoplastic fibroma of bone tissue (aggressive fibromatosis, desmoid fibroma) is a rare, locally aggressive, benign tumor localized in bone tissue, it is a mesenchymal fibroproliferative tumor with locally destructive growth, accounting for less than 0.03% of all human tumors. According to the literature, desmoplastic fibroma has a recurrence rate of 37% to 72%, resection of the affected bone is the preferred therapy, and, ideally, resection should be a single resection block. Wide excision is the method of choice for treating operable desmoid tumors in children. The article presents a dynamic observation within 1 year after surgical treatment. The article presents the clinical, radiological and computed tomographic picture of the disease and the results of instrumental and histological examination of a rare oncostomatological pathology. Purpose: clinical, radiological, 3D computed tomography observation of a child with desmoplastic fibroma of the lower jaw. Materials and methods: the results of a clinical examination, instrumental methods of X-ray diagnostics, stages of surgical treatment, a histological report and photographs of the patient's appearance are presented. Conclusion: Given the high regenerative capacity of bone tissue in children, it is necessary to perform surgical treatment of benign neoplasms by the type of marginal resection, that is, by the organ-preserving type, and to conduct dispensary observation of the patient during the first year.

Sporadic desmoid tumors in the pediatric population: A single center experience and review of the literature

Background/PurposeWe present our long experience with desmoid tumors in children. MethodsData were retrospectively collected from 17 children/adolescents treated for sporadic desmoid tumors at a tertiary pediatric hospital in 1988–2016. There were 10 girls and 7 boys aged 1–17years. Tumor sites included head and neck, trunk, extremity, and groin. Eight patients underwent radical resection, with complete remission in 7 and local relapse in one which was treated with chemotherapy. Four patients underwent incomplete surgical resection, three with adjuvant chemotherapy. Five patients underwent biopsy only and chemotherapy. Two of the 9 chemotherapy-treated patients also had intraarterial chemoembolization. Chemotherapy usually consisted of vincristine and actinomycin-D with or without cyclophosphamide or low-dose vinblastine and methotrexate. Two patients also received tamoxifen. ResultsAfter a median follow-up of 3.3years, 10 patients were alive in complete remission, 5 had stable disease, and 2 had reduced tumor size. Five-year overall survival was 100%, and event-free survival, 87.5%. Ten were screened for CTNNB1 mutations. CTNNB1 gene sequencing yielded mutations in 5/10 samples tested: 3 T41A, 2 S45F. There was no association of CTNNB1 mutation with clinical outcome or prognosis. ConclusionPediatric desmoid tumors are rare, with variable biologic behavior and morbidity. Treatment requires a multidisciplinary approach. Level of evidenceLEVEL IV, treatment study.

Is Wide Resection Obsolete for Desmoid Tumors in Children and Adolescents? Evaluation of Histological Margins, Immunohistochemical Markers, and Review of Literature

Desmoid fibromatosis is a benign fibroblastic neoplasm with high recurrence rates predominantly observed in pediatric and adolescent patients. The use of wide resection margins has been discussed controversially in literature. In addition, data on non-surgical treatment is limited as phase III studies are still missing. Nineteen patients under the age of 18 years were identified. Tumor location, surgical treatment for primary or recurrent tumors, resection margins, medical neo-/adjuvant treatment, time to recurrence as well as immunohistochemical markers (estrogen receptor, ER α and β, progesterone and androgen receptors, somatostatin, Ki-67, c-kit, platelet-derived growth factor receptors, PDGFRs, α and β, β-catenin) were evaluated. The mean age at diagnosis was 6.6 years, with a mean follow-up of 114 months. Recurrences were detected in four out of nineteen patients. Surprisingly, the recurrence rate was not influenced by type of resection used (R0, R1/2). All samples were tested negative for ER α, somatostatin, and progesterone receptor. In contrast, a majority of tumors showed positive results for PDGFR α and β and β-catenin. No correlation between positive immunohistochemical markers and tumor recurrences was detectable. In conclusion, recurrence rates are not depending on resection type and immunohistochemical markers seem to behave differently in children and adolescents in contrast to adult patients.

Erratum to “Desmoid Fibromatosis in Pediatric Patients: Management Based on a Retrospective Analysis of 59 Patients and a Review of the Literature”

Background. Only limited data are available concerning desmoid tumor in children. Methods. Fifty-nine children and adolescents with desmoid tumor treated in 2 French cancer centers with a very long followup were retrospectively reviewed. Results. Median age was 6 years (range, 0–15). Tumors mainly involved the limbs (42%). Five cases occurred in a context of genetic disorder. Surgery was first-line treatment in 80% of cases. Resection was microscopically complete in 3 patients (pts), with a microscopic residue in 19 pts and a macroscopic residue in 35 cases. Various adjuvant therapies were used. Overall response to all systemic therapies was 33%. Thirty-eight patients developed one or more recurrences or progressions. After a median followup of 8.5 years, 34 patients were alive in complete remission (CR), including 16 first CR. Seven patients died, 6 from refractory disease and 1 from colorectal carcinoma in a genetic context. Ten-year progression-free survival (PFS) and overall survival were 31% and 88%, respectively. In univariate analysis, age less than 10 years and head-neck site were favorable prognostic factors for PFS. Conclusions. When surgery is required, surgical margins must be negative. Low-dose chemotherapy can be proposed as adjuvant therapy. Prospective trials must be developed to evaluate long-term response and side effects.

Safety and efficacy of high‐dose tamoxifen and sulindac for desmoid tumor in children: Results of a Children's Oncology Group (COG) Phase II Study

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT. Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates.

External‐beam radiotherapy for pediatric and young adult desmoid tumors

To report long-term outcomes following radiotherapy for desmoid tumors in children and young adults and identify variables impacting local-regional control and treatment complications. From 1978 to 2008, 30 patients <30 years old were treated with radiotherapy for a pathologically confirmed desmoid tumor. The median age at radiotherapy was 23.7 years old (range, 10.3-29.9). Fifteen patients underwent definitive radiotherapy, 14 received radiotherapy after gross total resection, and 1 received preoperative radiotherapy. Sixteen patients received 1.8 Gy once daily and 14 received 1.2 Gy twice daily. Variables analyzed for prognostic value included gender, age at diagnosis, primary or recurrent presentation, age at radiotherapy, tumor site, tumor size, extent of resection, fractionation schedule, and radiotherapy dose. The actuarial 15-year overall survival and local-regional control rates were 96% and 55%, respectively. Local-regional control in patients <18 years old at the time of radiotherapy was 20% versus 63% in those 18-30 years old (P = 0.08). Local-regional control rates for tumors receiving ≥ 55 Gy and < 55 Gy were 79% and 30%, respectively (P = 0.02). No other factors had a statistically significant association with local-regional control by univariate analysis. Twelve of 30 patients experienced grade 3-4 complications, including pathologic fractures, impaired range of motion, pain, and in-field skin cancers. The role of radiotherapy in managing young patients with desmoid tumors remains unclear. Younger patient age is associated with inferior local-regional control following RT. In children and young adults, doses ≥55 Gy were associated with improved tumor control, but also lead to increased risk of complications.

MRI and Biologic Behavior of Desmoid Tumors in Children

The outcome of desmoid tumor in children cannot be reliably predicted on the basis of histologic findings. We sought to determine whether the postoperative presence of residual or recurrent tumor can be predicted on the basis of demographic variables and baseline MRI features of the tumor. We also aimed to determine how imaging features change during adjuvant treatment and how the imaging features relate to the histologic features. Two radiologists retrospectively reviewed images from 281 MRI examinations performed at baseline and during postoperative therapy for desmoid tumor. The examinations had been performed on 17 children treated between September 1991 and March 2003. Tumor volume; distinctness of margins; involvement of bone and neurovascular bundle; and T1-weighted, T2-weighted, and STIR signal intensity and contrast enhancement pattern were recorded. Baseline imaging and demographic features were correlated with the postoperative presence of residual or recurrent tumor. Imaging changes during follow-up were compared with treatment response and outcome. The imaging features of eight tumors were compared with percentage cellularity and collagen deposition in biopsy samples obtained within 30 days of imaging. Baseline involvement of the neurovascular bundle approached significance as a predictor of the presence of residual or recurrent tumor (p = 0.08). Other baseline imaging and demographic features were not predictive (p > or = 0.4). Changes in imaging features were variable during follow-up. T2-weighted and STIR signal intensity may be correlated with percentage cellularity and collagen deposition. MRI has limited value in prediction of the postoperative presence of residual or recurrent desmoid tumor in children. It is useful, however, for detecting disease and monitoring postoperative adjuvant therapy.

DESMOID TUMORS IN CHILDHOOD

Eight cases of extraabdominal desmoid tumors in children are reviewed. Seven were located in the pelvis or forearm, and the most common presenting complaint was a slowly enlarging mass. In all cases, diagnosis was established by open biopsy, and initial treatment was by surgical excision. At follow-up (average, 5.8 years), six patients were tumor free. Desmoids are benign tumors that usually carry a good prognosis. There is no difference between the tumor behavior in children and adults. The treatment of choice is wide local excision. If vital structures are involved, it may be more appropriate to preserve function by performing partial tumor excision. For quiescent recurrent tumors, observation is appropriate management, but if further treatment is required, reexcision or radiotherapy may be tried.

The clinical behavior of desmoid tumors in children

The clinical behavior of desmoid tumors in children