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.
Background
To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy.
Methods
This ...study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy.
Results
Out of 65 patients with a median age at diagnosis of 8.7 years (0.6–20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty‐eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow‐up of 78.6 months, 5‐year overall and event‐free survivals (EFS) were 90.1% (95% confidence interval CI: 79.2–95.5) and 89.1% (95% CI: 78.4–94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline‐based chemotherapy (p = .1181) were not correlated with EFS.
Conclusions
Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.
Background
Previous studies have shown that neutrophil‐to‐lymphocyte (NLR) ratio at diagnosis and early lymphocytes recovery on doxorubicin‐based chemotherapy, may impact the outcome in patients with ...osteosarcoma (OST). This study aimed to evaluate the prognostic value of hemogram parameters in patients with OST treated with high‐dose methotrexate and etoposide/ifosfamide (M‐EI) chemotherapy.
Materials and methods
We retrospectively analyzed the prognostic value of various hemogram parameters at diagnosis and during therapy in a large consecutive cohort of patients with OST included in the French OS2006 trial and treated with M‐EI chemotherapy.
Results
A total of 164 patients were analyzed. The median age was 14.7 years (interquartile range IQR: 11.7–17). Median follow‐up was 5.6 years (IQR: 3.3–7.7 years). Three‐year event‐free survival (EFS) and overall survival (OS) were 71.5% (95% confidence interval CI: 64%–78%) and 86.4% (95% CI: 80%–91%), respectively. In univariate analysis, blood count parameters at diagnosis and early lymphocyte recovery at Day 14 were not found prognostic of survival outcomes. By contrast, an increase of NLR ratio at Day 1 of the first EI chemotherapy (NLR‐W4) was associated with reduced OS in univariate (p = .0044) and multivariate analysis (hazards ratio HR = 1.3, 95% CI: 1.1–1.5; p = .002), although not with EFS. After adjustment on histological response and metastatic status, an increase of the ratio NLR‐W4 of 1 was associated with an increased risk of death of 30%.
Conclusions
We identified NLR‐W4 as a potential early biomarker for survival in patients with OST treated with M‐EI chemotherapy. Further studies are required to confirm the prognostic value of NLR and better identify immune mechanisms involved in disease surveillance.
Alveolar rhabdomyosarcoma (ARMS) is associated with PAX3/PAX7‐FOXO1 fusion, which confers specific clinic and biologic characteristics with inferior outcomes. A minority of tumors ...still histologically classified as “true” ARMS lack the canonical PAX‐FOXO1 fusion but have new molecular alterations. We present the first case of PAX3‐NCOA1 ARMS with clinical data and follow‐up in a two‐year‐old girl with ARMS of the tongue and nodal extension, treated with chemotherapy, hemi glossectomy, lymph node dissection, and brachytherapy to conserve oral function and limit long‐term sequelae. Given the rarity of such variant fusion in ARMS, international collaboration is required to evaluate its prognostic value.
Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress ...has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse.
In anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALK+ ALCL), positive minimal residual disease (MRD+) after the first chemotherapy course was proven of strong prognostic ...significance. We aimed to validate these results in 138 French patients. Eighty‐seven patients had a detectable minimal disseminated disease at diagnosis (MDD+). Early MRD assessment was performed in 33 of 87 patients and was positive in 18 and negative in 15 (MRD−). Three‐year progression‐free survival was significantly correlated with the MDD/MRD status: 81.1% in MDD−, 69.6% in MDD+/MRD−, and 15.2% in MDD+/MRD+ patients. In conclusion, we confirmed on an independent cohort that the MDD/MRD status has strong prognosis significance in ALK+ ALCL.
Despite considerable recent advances in understanding and treating many other cancers, malignant brain tumors remain associated with low survival or severe long-term sequelae. Limited progress, ...including development of immunotherapies, relates in part to difficulties in accurately reproducing brain microenvironment with current preclinical models. The cellular interactions among resident microglia, recruited tumor-associated macrophages, stromal cells, glial cells, neurons, and cancer cells and how they affect tumor growth or behavior are emerging, yet many questions remain. The role of the blood-brain barrier, extracellular matrix components, and heterogeneity among tumor types and within different regions of a single tumor further complicate the matter. Here, we focus on brain microenvironment features impacted by tumor biology. We also discuss limits of current preclinical models and how complementary models, such as humanized animals and organoids, will allow deeper mechanistic insights on cancer biology, allowing for more efficient testing of therapeutic strategies, including immunotherapy, for brain cancers.
In this review, Pasqualini et al. describe the tumor microenvironment in brain cancers and its impact on tumor behavior. They discuss how, compared to current preclinical models, humanized animals and organoids will allow more accurate evaluations of these complex interactions.
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