PD0332991 (Palbociclib) for treatment of pediatric intracranial growing teratoma syndrome

Schultz, Kris Ann P.; Petronio, Joseph; Bendel, Anne; Patterson, Richard J.; Vaughn, David J.

doi:10.1002/pbc.25338

Cited by 22 publications

(18 citation statements)

References 16 publications

(16 reference statements)

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“…Deregulation of the p16‐CDK4/6‐pRB‐E2F pathway has been described in other brain tumors, notably adult glioblastoma where therapeutic targeting of this pathway with CDK4/6 inhibitor palbociclib is being explored preclinically and clinically . Of relevance to potential treatment of iEPN‐PF, palbociclib was well tolerated and showed stabilization of tumor growth in pediatric intracranial growing teratoma syndrome . To our knowledge, however, no trials are ongoing for the use of palbociclib in EPNs of any type.…”

Section: Discussionmentioning

confidence: 99%

p16 Loss and E2F/cell cycle deregulation in infant posterior fossa ependymoma

Lummus

Donson

Gowan

et al. 2017

Pediatric Blood & Cancer

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Background Posterior fossa (PF) ependymomas (EPNs) in infants less than 1 year of age (iEPN-PF) have a poorer clinical outcome than EPNs in older children. While radiation therapy is the standard of care for the latter, it is withheld in infants to avoid neurotoxicity to immature brain. It is unknown whether the adverse outcome in iEPN-PFs is due to treatment differences or aggressive biology. We examined this question using molecular profiling. Methods Six anaplastic iEPN-PFs were subjected to transcriptomic analysis and FISH for p16 loss and gains of 1q, and compared with anaplastic PF EPNs from older children. Results were validated by immunohistochemistry (IHC). Results All six iEPN-PFs were grouped within EPN PF subgroup A (PFA). E2F targets and G2M checkpoint were identified as the most enriched gene sets in iEPN-PF, which was validated in a larger independent cohort. Accordingly, MIB-1 IHC demonstrated a higher mitotic rate in iEPN-PFs than noninfant anaplastic EPN PFA. Genetic and protein analyses demonstrated that p16 loss and low p16 protein expression is a hallmark of iEPN-PF, and that none harbored 1q gains. Kaplan–Meier analysis confirmed the poorer clinical outcome of the iEPN-PF cohort. Conclusions Biological differences, characterized by loss of p16 expression without gains of 1q in iEPN-PFs, as well as deregulated E2F target gene transcription, are indicative of deregulated p16-CDK4/6-pRB-E2F pathway activity. This may underlie the poor clinical outcome seen in this group of iEPN-PFs, rather than the withholding of radiation therapy. Results suggest a potential actionable therapy for iEPN-PF, namely cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.

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Section: Discussionmentioning

confidence: 99%

p16 Loss and E2F/cell cycle deregulation in infant posterior fossa ependymoma

Lummus

Donson

Gowan

et al. 2017

Pediatric Blood & Cancer

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“…Palbociclib, a CDK4/6 inhibitor (PD0332991), is reported that it can stabilize the vascularization of the tumor in pediatric patients with an intracranial teratoma [43]. It is a selective reversible inhibitor of cyclin-dependent kinases (CDK) 4 and 6.…”

Section: Discussionmentioning

confidence: 99%

“…It is a selective reversible inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Inhibition of CDK 4/6 blocks DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase [43]. The main side effect appears to be reversible neutropenia [44].…”

Section: Discussionmentioning

confidence: 99%

“…It has been especially effective in pRB-expressing teratomas (retinoblastoma protein) [45]. While further investigation of the use of Palbociclib in patients with GTS should be carried out [43], the number of major disease-related clinical events decreases with use of Palbociclib as did the median number of progression-free survival months for unresectable mature teratoma [46]. Inoperable metastases have been known to be treated with bevacizumab and cyclin-dependent kinase inhibitors [47], with tumor marker AFP usually returned to within the normal range [48, 49].…”

Section: Discussionmentioning

confidence: 99%

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Pediatric Ovarian Growing Teratoma Syndrome

Rentea

Varghese

Ahmed

et al. 2017

Case Reports in Surgery

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Ovarian immature teratoma is a germ cell tumor that comprises less than 1% of ovarian cancers and is treated with surgical debulking and chemotherapy depending on stage. Growing teratoma syndrome (GTS) is the phenomenon of the growth of mature teratoma elements with normal tumor markers during or following chemotherapy for treatment of a malignant germ cell tumor. These tumors are associated with significant morbidity and mortality due to invasive and compressive growth as well as potential for malignant transformation. Current treatment modality is surgical resection. We discuss a 12-year-old female who presented following resection of a pure ovarian immature teratoma (grade 3, FIGO stage IIIC). Following chemotherapy and resection of a pelvic/liver recurrence demonstrating mature teratoma, she underwent molecular genetics based chemotherapeutic treatment. No standardized management protocol has been established for the treatment of GTS. The effect of chemotherapeutic agents for decreasing the volume of and prevention of expansion is unknown. We review in detail the history, diagnostic algorithm, and previous reported pediatric cases as well as treatment options for pediatric patients with GTS.

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“…Palbociclib (PD0332991) is reported that it can stabilize the vascularization of the tumor in pediatric patients with an intracranial teratoma. 19 But further investigation of the use of Palbociclib in patients with growing teratoma syndrome should be carried out. 19 From these literatures, tumor markers AFP usually returned to within the normal range, with the exception of 2 cases reported by Pendlebury et al and Lorusso et al 18,20 …”

Section: Discussionmentioning

confidence: 99%

Growing Teratoma Syndrome Secondary to Ovarian Giant Immature Teratoma in an Adolescent Girl

Liu

Dong

et al. 2016

Medicine

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Growing teratoma syndrome (GTS) is a rare clinical entity first described by Logothetis et al in 1982. Although it is unusual for GTS to be located in the ovary, this report is of a case of an adolescent girl who underwent a complete surgical resection of the mass. Histopathology confirmed only an immature teratoma had originated from the ovary and so she received adjuvant chemotherapy with blemycin, etopside, and cisplatin over 4 cycles. Results from an abdominal enhanced CT (computed tomography) 9 years later revealed a giant mass had compressed adjacent tissues and organs. Laparotomy was performed and a postoperative histopathology showed the presence of a mature teratoma, and so the diagnosis of ovarian GTS was made. One hundred one cases of ovarian GTS from English literature published between 1977 and 2015 were collected and respectively analyzed in large samples for the first time.The median age of diagnosis with primary immature teratoma was 22 years (range 4–48 years, n = 56). GTS originating from the right ovary accounted for 57% (27/47, n = 47) whereas the left contained 43% (20/47, n = 47). Median primary tumor size was 18.7 cm (range 6–45 cm, n = 28) and median subsequent tumor size was 8.6 cm (range 1–25 cm, n = 25). From the primary treatment to the diagnosis of ovarian GTS, median tumor growth speed was 0.94 cm/month (range 0.3–4.3 cm/month, n = 21). Median time interval was 26.6 months (range 1–264 months, n = 41). According to these findings, 5 patients did have a pregnancy during the time interval between primary disease and GTS, making our patient the first case of having a pregnancy following the diagnosis of ovarian GTS. Because of its high recurrence and insensitiveness to chemotherapy, complete surgical resection is the preferred treatment and fertility-sparing surgery should be considered for women of child-bearing age.Anyhow GTS of the ovary has an excellent prognosis. Patients with GTS had no evidence of recurrence or were found to be disease free during a 40.3-month (range 1–216 months, n = 48) median follow-up. Moreover, regular follow-ups with imaging and serum tumor markers are important and must not be neglected.

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PD0332991 (Palbociclib) for treatment of pediatric intracranial growing teratoma syndrome

Cited by 22 publications

References 16 publications

p16 Loss and E2F/cell cycle deregulation in infant posterior fossa ependymoma

p16 Loss and E2F/cell cycle deregulation in infant posterior fossa ependymoma

Pediatric Ovarian Growing Teratoma Syndrome

Growing Teratoma Syndrome Secondary to Ovarian Giant Immature Teratoma in an Adolescent Girl

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