2024-03-1310:00
Ayşe ÖzkanBegül Yağcı KüpeliSerhan KüpeliGülay Sezginİbrahim Bayram
CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.
CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.
Childs Nerv Syst. 2024 Mar 13. doi: 10.1007/s00381-024-06329-4. Online ahead of print.
ABSTRACT
PURPOSE: Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens.
METHODS: After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed.
RESULTS: The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months.
CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.
PMID:38478066 | DOI:10.1007/s00381-024-06329-4
2024-03-1210:00
Ashley R TetensAllison M MartinAntje ArnoldOrlandi V NovakAdrian IdriziRakel TryggvadottirJordyn Craig-SchwartzAthanasia LiapodimitriKayleigh LunsfordMichael I BarbatoCharles G EberhartAdam C ResnickEric H RaabeMichael A Koldobskiy
CONCLUSIONS: This study provides a resource for understanding the epigenetic instability that underlies DIPG heterogeneity. It suggests the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells, as well as the use of decitabine in priming for immune-based therapies.
CONCLUSIONS: This study provides a resource for understanding the epigenetic instability that underlies DIPG heterogeneity. It suggests the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells, as well as the use of decitabine in priming for immune-based therapies.
Neurooncol Adv. 2024 Feb 19;6(1):vdae023. doi: 10.1093/noajnl/vdae023. eCollection 2024 Jan-Dec.
ABSTRACT
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a uniformly lethal brainstem tumor of childhood, driven by histone H3 K27M mutation and resultant epigenetic dysregulation. Epigenomic analyses of DIPG have shown global loss of repressive chromatin marks accompanied by DNA hypomethylation. However, studies providing a static view of the epigenome do not adequately capture the regulatory underpinnings of DIPG cellular heterogeneity and plasticity.
METHODS: To address this, we performed whole-genome bisulfite sequencing on a large panel of primary DIPG specimens and applied a novel framework for analysis of DNA methylation variability, permitting the derivation of comprehensive genome-wide DNA methylation potential energy landscapes that capture intrinsic epigenetic variation.
RESULTS: We show that DIPG has a markedly disordered epigenome with increasingly stochastic DNA methylation at genes regulating pluripotency and developmental identity, potentially enabling cells to sample diverse transcriptional programs and differentiation states. The DIPG epigenetic landscape was responsive to treatment with the hypomethylating agent decitabine, which produced genome-wide demethylation and reduced the stochasticity of DNA methylation at active enhancers and bivalent promoters. Decitabine treatment elicited changes in gene expression, including upregulation of immune signaling such as the interferon response, STING, and MHC class I expression, and sensitized cells to the effects of histone deacetylase inhibition.
CONCLUSIONS: This study provides a resource for understanding the epigenetic instability that underlies DIPG heterogeneity. It suggests the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells, as well as the use of decitabine in priming for immune-based therapies.
PMID:38468866 | PMC:PMC10926944 | DOI:10.1093/noajnl/vdae023
2024-03-0211:00
Nikhil P MankuzhyKathryn R TringaleIra J DunkelSameer Farouk SaitMark M SouweidaneYasmin KhakooMatthias A KarajannisSuzanne Wolden
CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.
CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.
Pediatr Blood Cancer. 2024 May;71(5):e30929. doi: 10.1002/pbc.30929. Epub 2024 Mar 2.
ABSTRACT
BACKGROUND: Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF).
METHODS: We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT.
RESULTS: Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30 Gy in 2-Gy fractions (n = 6) and 30-36 Gy in 3-Gy fractions (n = 14). Median age was 5 years (range: 3-14), median interval since initial RT was 8 months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18 months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5 months, respectively (p = .20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2 months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p = .4). No patients developed radionecrosis.
CONCLUSION: reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.
PMID:38430472 | DOI:10.1002/pbc.30929
2024-02-2411:00
Stuart L MarcusMark P de Souza
ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and...
ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and...
Cancers (Basel). 2024 Feb 10;16(4):740. doi: 10.3390/cancers16040740.
ABSTRACT
ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and has the potential to achieve clinical success in the treatment of both intracranial and extracranial cancers. This review describes the creation and evolution of ALA PDT, from the treatment of skin cancers to PDD and PDT of malignant brain tumors and, most recently, into a noninvasive form of PDT, ALA SDT. Current clinical trials of ALA SDT for recurrent glioblastoma and high-grade gliomas in adults, and the first pediatric ALA SDT clinical trial for a lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described.
PMID:38398131 | PMC:PMC10886505 | DOI:10.3390/cancers16040740
2024-02-2411:00
Yazmin OdiaCarl KoschmannNicholas A VitanzaPeter de BlankDolly AguileraJeffrey AllenDoured DaghistaniMatthew HallZiad KhatibCassie KlineTobey MacDonaldSabine MuellerShamia L FaisonJoshua E AllenOdin J NadererSamuel C RamageRohinton S TaraporeSusan Lynne McGovernSoumen KhatuaWafik ZakySharon L Gardner
CONCLUSIONS: ONC201 given D1D2 was well-tolerated at all DLs and associated with greater AUC0-48.
CONCLUSIONS: ONC201 given D1D2 was well-tolerated at all DLs and associated with greater AUC0-48.
Neuro Oncol. 2024 Feb 24:noae001. doi: 10.1093/neuonc/noae001. Online ahead of print.
ABSTRACT
BACKGROUND: This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma.
METHODS: This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at three dose levels (DLs; -1, 1, and 2). Actual administered dose within DLs was dependent on weight. Safety was assessed in all DLs; PK analysis was conducted in DL2. Patients receiving once-weekly ONC201 (D1) served as a PK comparator.1.
RESULTS: Twelve patients received D1D2 ONC201 (DL-1, n=3; DL1, n=3; DL2, n=6); no dose-limiting toxicities or grade ≥3 treatment-related adverse events occurred. PK analyses at DL2 (D1-250mg, n=3; D1-625mg, n=3; D1D2-250mg, n=2; D1D2-625mg, n=2) demonstrated variability in Cmax, AUC0-24, and AUC0-48, with comparable exposures across weight groups. No accumulation occurred with D1D2 dosing; the majority of ONC201 cleared before administration of the second dose. Cmax was variable between groups but did not appear to increase with D1D2 dosing. AUC0-48 was greater with D1D2 than once-weekly.
CONCLUSIONS: ONC201 given D1D2 was well-tolerated at all DLs and associated with greater AUC0-48.
PMID:38400780 | DOI:10.1093/neuonc/noae001
2024-02-2011:00
Danai PapangelopoulouBrigitte BisonLars BehrensSimon BaileyMarc AnsariKaroline EhlertOfelia Cruz MartinezChristof M KrammAndres Morales La MadridAndre O von Bueren
CONCLUSIONS: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management.
CONCLUSIONS: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management.
Childs Nerv Syst. 2024 Apr;40(4):1053-1064. doi: 10.1007/s00381-023-06272-w. Epub 2024 Feb 20.
ABSTRACT
PURPOSE: Brain stem tumors in children < 3 months at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management.
METHODS: This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers, including patients with a brainstem tumor diagnosed between 2009 and 2020 and aged < 3 months at diagnosis. Clinical data were collected, and imaging characteristics were analyzed blindly and independently by two neuroradiologists.
RESULTS: Five cases were identified. No patient received any therapy. The epicenter of two tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in three. For patients with tumor in equal parts in the medulla oblongata and the pons (n = 3), the extension at diagnosis involved the spinal cord; for the two patients with the tumor epicenter in the medulla oblongata alone (n = 2), the extension at diagnosis included the pons (n = 2) and the spinal cord (n = 1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died. In one patient, autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n = 2) or stable disease (n = 1). Survivors were followed up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma.
CONCLUSIONS: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management.
PMID:38376530 | DOI:10.1007/s00381-023-06272-w