Purpose
Intracranial growing teratoma syndrome (iGTS) is a rare phenomenon of paradoxical growth of a germ cell tumor (GCT) during treatment despite normalization of tumor markers. We sought to ...evaluate the frequency, clinical characteristics and outcome of iGTS in Western countries.
Methods
Pediatric patients from 22 North American and Australian institutions diagnosed with iGTS between 2000 and 2017 were retrospectively evaluated.
Results
From a total of 777 cases of central nervous system (CNS) GCT, 39 cases of iGTS were identified for an overall frequency of 5%. Pineal region was a more frequent location for iGTS as compared to cases of GCT without iGTS (p < 0.00001). In patients with an initial tissue diagnosis of GCT, immature teratoma was present in 50%. Serum AFP or ßhCG was detectable in 87% of patients (median values 66 ng/mL and 44 IU/L, respectively). iGTS occurred at a median of 2 months (range 0.5–32) from diagnosis, in the majority of patients. All patients underwent surgical resection, leading to gross total resection in 79%. Following surgery, all patients resumed adjuvant therapy or post treatment follow-up for GCT. At a median follow-up of 5.3 years (range 0.2–11.8), 37 (95%) of patients are alive, including 5 with stable residual mass.
Conclusion
iGTS occurs in 5% of patients with GCT in Western countries. Tumors of the pineal region and GCT containing immature teratoma appear to be associated with a higher risk of developing iGTS. Complete surgical resection is the mainstay of treatment. Overall survival of patients developing iGTS remains favorable.
Abstract only
9053
Background: Carboplatin based regimens are widely used in the treatment of unresectable pediatric LGG. Carboplatin hypersensitivity reaction (CHSR) represents a main limiting ...factor. Objective: To analyse the incidence, characteristics, management and impact on outcome of CHSR. Methods: National retrospective review of children diagnosed with LGG between 1988 and 2004. Inclusion criteria were age <18 years, pathology proven diagnosis of LGG except in NF1 patients, and no chemotherapy or radiotherapy prior to carboplatin chemotherapy. Results: 105 patients (61F/44M) from 10 Canadian centers were included in the study. Median age at diagnosis was 3.5y (0.3–16.8). 33 patients had NF1, 75 had diencephalic tumor. Carboplatin was given monthly or weekly respectively in 46 and 59 patients. 44 (41.9%) patients developed carboplatin HSR at a median time of 6.5 months (0.4–15.4), after a median number of 10.5 (3–39) injections. CHSR occurred significantly earlier with the weekly schedule (p=0.016). Cumulative incidence of CHSR increased with the number of injections with no plateau. Female had significant higher risk to develop CHSR (p=0.02) whereas age, NF1 status and schedule of administration were not significant risk factors. First allergic reaction was rated grade I, II in 36 patients (82%). 34 patients were reexposed to carboplatin with desensitization/premedication, allowing 14 patients (41.2%) to complete their treatment. But the majority (58.8%) had recurrent allergic reaction with a significant worsening of their symptoms (p=0.039). The median number of additional Carboplatin injections delivered was 4 (0.5–34). After Carboplatin discontinuation, 18 patients were switched to another chemotherapy regimen. 5 years PFS was not significantly different in allergic and non allergic patients (53.9% and 45.6%). Conclusions: In our experience, the incidence of CHSR is high (41.9%). Female have higher risk of CHSR. Desensitization/premedication has limited efficacy and does not prevent worsening of CHSR. CHSR did not impact the PFS. However many patients did switch to another chemotherapy regimen and the total duration of treatment was comparable in both groups.
No significant financial relationships to disclose.
Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. Up to 50% will be refractory to conventional chemotherapy. It is now known that the majority of PLGG have activation ...of the MAPK/ERK pathway. The same pathway is also activated in plexiform neurofibromas (PNs) which are low-grade tumors involving peripheral nerves in patients with neurofibromatosis type 1 (NF1). These lesions are known to be refractory to chemotherapy. Specific MEK inhibitors such as trametinib are now available and have been approved for other cancers harboring mutations in the MAPK/ERK pathway such as melanoma. We have observed significant responses to trametinib in patients with refractory PLGG in our institutions and results from the phase I study are promising. The treatment appears not only efficacious but is also usually well tolerated. We hypothesize that we will observe responses in the majority of refractory PLGG and PN treated with trametinib in this phase 2 study.
The primary objective is to determine the objective response rate of trametinib as a single agent for treatment of progressing/refractory tumors with MAPK/ERK pathway activation. The TRAM-01 study is a phase II multicentric open-label basket trial including four groups. Group 1 includes NF1 patients with progressing/refractory glioma. Group 2 includes NF1 patients with plexiform neurofibroma. Group 3 includes patients with progressing/refractory glioma with KIAA1549-BRAF fusion. Group 4 includes other patients with progressing/refractory glioma with activation of the MAPK/ERK pathway. Eligible patients for a given study group will receive daily oral trametinib at full dose for a total of 18 cycles of 28 days. A total of 150 patients will be enrolled in seven Canadian centers. Secondary objectives include the assessment of progression-free survival, overall survival, safety and tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment.
Trametinib will allow us to target directly and specifically the MAPK/ERK pathway. We expect to observe a significant response in most patients. Following our study, trametinib could be integrated into standard treatment of PLGG and PN.
ClinicalTrials.gov Identifier: NCT03363217 December 6, 2017.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Clinical trials have failed to demonstrate a survival benefit of adjuvant chemotherapy in diffuse intrinsic pontine gliomas (DIPG). Radiation therapy (RT) is the only effective treatment ...thus far and reirradiation (rRT) has become an option at the time of progression. The aim of this study was to review the Canadian experience of DIPG rRT with a focus on the safety and possible efficacy of this approach.
Method
We retrospectively reviewed the demographic, clinical, and RT data of patients with DIPG treated in Canada with rRT.
Results
Since January 2011, we identified 16 patients with progressive DIPG who received rRT. Median time from diagnosis to progression was 10.5 months (range, 4–37 months). rRT was given focally in 14 patients at a dose ranging from 21.6 to 36 Gy. rRT was well tolerated by all children but one. All but three patients showed neurological improvement. With a median follow‐up from original diagnosis of 19.2 months, all patients died, with a median time from rRT to death of 6.48 months (range, 3.83–13.26 months). When compared to a historic cohort of 46 consecutive patients, the median time from progression to death was 92 days in the non‐reirradiated patients versus 218 days in the reirradiated ones (P = 0.0001).
Conclusion
In this limited experience, rRT was safe and feasible in patients with progressive DIPG, providing neurological improvement and a prolonged life span in most patients. Prospective Canadian rRT protocols are ongoing to further assess the benefit of this approach, including quality of life assessment.
Introduction
Atypical teratoid rhabdoid tumor (ATRT) is a rare, often lethal brain tumor of childhood characterized by a complex epigenetic landscape amongst a simple genetic background. Recent ...molecular studies have defined key biologic events that contribute to tumorigenesis and molecular subtypes of ATRT.
Methods
Seminal studies on ATRT are reviewed with an emphasis on molecular pathogenesis and its relevance to novel therapeutics.
Results
In this review, we summarize the key clinicopathologic and molecular features of ATRT, completed and ongoing clinical trials and outline the translational potential of novel insights into the molecular pathogenesis of this tumor.
Conclusions
SMARCB1 loss is the key genetic event in ATRT pathogenesis that leads to widespread epigenetic dysregulation and loss of lineage-specific enhancers. Current work is defining subtype-specific treatments that target underlying molecular derangements that drive tumorigenesis.
Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment ...with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible. Vinblastine was administered once per week at a dose of 6 mg/m
intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome. Results Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years). Most patients had chiasmatic/hypothalamic tumors (55.5%), and 13 patients (24.1%) had NF1. The most common histology was pilocytic astrocytoma (46.3%). Seventeen patients were diagnosed using radiologic criteria alone. Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%). Visual improvement was observed in 20% of patients with optic pathway glioma. Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort. Patients with NF1 had a significantly better PFS (85.1%; 95% CI, 68.0% to 100%) when compared with patients without NF1 (42.0%; 95% CI, 29.1% to 60.7%; P = .012). Age< 3 years or > 10 years was not associated with poor outcome. Treatment was well tolerated, and quality of life was not affected during treatment. In this trial, there was no correlation between BRAF alterations and outcome. Conclusion Vinblastine administered once per week is well tolerated in children with treatment naïve PLGG. Overall survival and PFS are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.
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