-
JCO Global Oncology Apr 2023This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with...
PURPOSE
This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care.
PATIENTS AND METHODS
Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGβ levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease.
RESULTS
Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%.
CONCLUSION
The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.
Topics: Male; Humans; Child; Adolescent; Female; Prospective Studies; Brazil; Retrospective Studies; Brain Neoplasms; Germinoma; Biomarkers, Tumor
PubMed: 37075267
DOI: 10.1200/GO.22.00257 -
Neuro-oncology Advances 2023Germinomas are sensitive to radiation and chemotherapy, and their management distinctly differs from other kinds of pineal region tumors. The aim of this study was to...
BACKGROUND
Germinomas are sensitive to radiation and chemotherapy, and their management distinctly differs from other kinds of pineal region tumors. The aim of this study was to construct a prediction model based on clinical features and preoperative magnetic resonance (MR) manifestations to achieve noninvasive diagnosis of germinomas in pineal region.
METHODS
A total of 126 patients with pineal region tumors were enrolled, including 36 germinomas, 53 nongerminomatous germ cell tumors (NGGCTs), and 37 pineal parenchymal tumors (PPTs). They were divided into a training cohort ( = 90) and a validation cohort ( = 36). Features were extracted from clinical records and conventional MR images. Multivariate analysis was performed to screen for independent predictors to differentiate germ cell tumors (GCTs) and PPTs, germinomas, and NGGCTs, respectively. From this, a 2-step nomogram model was established, with model 1 for discriminating GCTs from PPTs and model 2 for identifying germinomas in GCTs. The model was tested in a validation cohort.
RESULTS
Both model 1 and model 2 yielded good predictive efficacy, with c-indexes of 0.967 and 0.896 for the diagnosis of GCT and germinoma, respectively. Calibration curve, decision curve, and clinical impact curve analysis further confirmed their predictive accuracy and clinical usefulness. The validation cohort achieved areas under the receiver operating curves of 0.885 and 0.926, respectively.
CONCLUSIONS
The 2-step model in this study can noninvasively differentiate GCTs from PPTs and further identify germinomas, thus holding potential to facilitate treatment decision-making for pineal region tumors.
PubMed: 37706201
DOI: 10.1093/noajnl/vdad094 -
Neuro-ophthalmology (Aeolus Press) 2022Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary...
Suprasellar germinomas can present with non-diagnostic, or even normal results on imaging. The spectrum of reported cases ranges from normal imaging, thickened pituitary stalks, to discrete tumour growths. This similar phenomenon is less commonly seen in the pineal region, or bifocal germinomas, and the literature is sparse with only a few case series or reports mentioning a similar presentation of signs and symptoms preceding radiological evidence of diagnosis. We report a case of pineal germinoma presenting with dorsal midbrain syndrome with no evidence of tumour growth on initial imaging despite symptoms. For patients presenting with this clinical radiological latent period, follow-up imaging is useful to identify interval development of germinomas. This applies to patients with dorsal midbrain syndrome, or even other unexplained ophthalmoplegia, as the initial sign of pineal region germinoma, despite normal imaging.
PubMed: 35859628
DOI: 10.1080/01658107.2022.2034890 -
Frontiers in Oncology 2022CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland.... (Review)
Review
CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland. Histopathologically, GCTs are broadly classified into germinomas and non-germinomatous GCTs (NGGCTs). In general, germinoma responds well to chemotherapy and radiation therapy, with a 10-year overall survival (OS) rate of approximately 90%. In contrast, NGGCTs have a less favorable prognosis, with a five-year OS of approximately 70%. Germinomas are typically treated with platinum-based chemotherapy and whole-ventricular radiation therapy, while mature teratomas can be surgically cured. Other NGGCTs require intensive chemotherapy with radiation therapy, including whole brain or craniospinal irradiation, depending on the dissemination status and protocols. Long-term treatment-related sequelae, including secondary neoplasms and cerebrovascular events, have been well recognized. These late effects have a tremendous impact in later life, especially since patients are mostly affected in childhood or young adults. Intending to minimize the treatment burden on patients, the identification of biomarkers for treatment stratification and evaluation of treatment response is of critical importance. Recently, tumor cell content in germinomas has been shown to be closely related to prognosis, suggesting that cases with low tumor cell content may be safely treated with a less intensive regimen. Among the copy number alterations, the 12p gain is the most prominent and has been shown to be a negative prognostic factor in NGGCTs. MicroRNA clusters (mir-371-373) were also revealed to be a hallmark of GCTs, demonstrating the potential for the application of liquid biopsy in the diagnosis and detection of recurrence. Recurrent mutations have been detected in the MAPK or PI3K pathways, most typically in and and low genome-wide methylation has been demonstrated in germinoma; this most likely reflects the cell-of-origin primordial germ cells for this tumor type. These alterations can also be leveraged for liquid biopsies of cell-free DNA and may potentially be targeted for treatment in the future. Advancements in basic research will be translated into clinical practice and can directly impact patient management. Additional understanding of the biology and pathogenesis of GCTs will lead to the development of better-stratified clinical trials, ultimately resulting in improved treatment outcomes and a reduction in long-term treatment-related adverse effects.
PubMed: 36132131
DOI: 10.3389/fonc.2022.982608 -
Cureus Oct 2022Pineal gland tumours are reported rarely in Malayasia and early diagnosis and intervention promise a better prognosis for patients. We report a rare case of pineal gland...
Pineal gland tumours are reported rarely in Malayasia and early diagnosis and intervention promise a better prognosis for patients. We report a rare case of pineal gland tumour with drop metastases in the fourth ventricle in a 20-year-old young male with Parinaud syndrome. The patient, who had no underlying medical illnesses, presented with neurological symptoms and limb weakness associated with tremors and blurring of vision which worsened over a span of four months. The patient was having difficulty in ambulating with reduced power over the lower limbs with tremors as well as Parinaud syndrome indicated through the limitation of upward gaze, light-near dissociation of the pupils and convergence nystagmus. An MRI showed the presence of a pineal gland tumour with drop metastases in the fourth ventricle with calcification. The patient underwent an endoscopic third ventriculostomy and tumour biopsy. The biopsy indicated a pineal gland tumour with a germinoma subset and the patient was subjected to radiotherapy. Latency of diagnosis is an important prognostic factor as it reduces the survival rate for these patients hence the following discussion on the pineal gland tumour and its diagnostic dilemma.
PubMed: 36204259
DOI: 10.7759/cureus.29855 -
Frontiers in Oncology 2024Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs...
BACKGROUND
Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas.
MATERIAL AND METHODS
A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance.
RESULTS
Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors [ = 17; pineoblastoma ( = 13) and pineal parenchymal tumors of intermediate differentiation ( = 4)] and others [ = 10; low-grade glioma ( = 6) and atypical teratoid rhabdoid tumor ( = 4)]. Using an adjusted -value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted = 0.0058, = 0.0478, and = 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%, < 0.001) with a sensitivity of 25% and a specificity of 100%.
CONCLUSION
Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications.
PubMed: 38665953
DOI: 10.3389/fonc.2024.1219796 -
The American Journal of Case Reports Nov 2022BACKGROUND Pineal gland tumors are rare central nervous system tumors, and while neck pain and headaches may be common among those who have had these tumors removed,...
BACKGROUND Pineal gland tumors are rare central nervous system tumors, and while neck pain and headaches may be common among those who have had these tumors removed, there is little research regarding management of these symptoms. CASE REPORT A 45-year-old man with a history of pineal germinoma treated with pinealectomy, chemotherapy, radiation therapy, and ventriculoperitoneal shunt placement at age 21 presented with chronic neck pain and headaches, which initially improved following his surgery and concurrent therapies, yet progressively worsened over the following years. He required thyroid and testosterone medication because of radiation-induced hypopituitarism, yet was employed, and until recently, active with playing tennis. He had previously seen his primary care provider, orthopedist, and neurologist, and had been cleared of severe pathology via brain magnetic resonance imaging and was referred to the chiropractor. On examination, the patient had severely limited passive cervical spine range of motion, yet hat no neurologic deficits, and radiographs showed mild cervical spondylosis and cervicothoracic scoliosis. His history and presentation were suggestive of radiation-induced fibrosis. The patient's neck pain, headaches, and quality of life improved with multimodal treatments including spinal and soft-tissue manipulation, stretches, and yoga. CONCLUSIONS This case illustrates long-term sequelae of a pineal gland tumor and its treatment, including neck pain and headache, and improvement with multimodal chiropractic therapies. Despite the success in this case, these results are not broadly generalizable. Further research is needed to understand the natural history of symptoms and effectiveness of multimodal therapies among patients who have had pineal tumor surgery.
Topics: Male; Humans; Young Adult; Adult; Middle Aged; Neck Pain; Pinealectomy; Chiropractic; Quality of Life; Headache; Combined Modality Therapy
PubMed: 36401511
DOI: 10.12659/AJCR.937906 -
Cureus Jul 2023Convergence-retraction nystagmus alongside behavioral changes can be rare manifestations of a potentially life-threatening midbrain lesion. After experiencing headaches...
Convergence-retraction nystagmus alongside behavioral changes can be rare manifestations of a potentially life-threatening midbrain lesion. After experiencing headaches for three months, a 13-year-old boy was diagnosed with depression due to exhibiting reduced speech, hypersomnia, and psychomotor slowing for three weeks. It was preceded by headache for three months. Examination revealed visual acuity of 6/6 bilaterally, convergence-retraction nystagmus worst on upgaze, limited bilateral ocular motility in upgaze, and light-near dissociation on pupil examination, all of which point towards Parinaud's syndrome. However, there was no lid retraction to suggest Collier's sign. Fundus examination revealed papilledema. Magnetic resonance imaging showed a large pineal mass extending to both thalami, dilated ventricles due to obstructive hydrocephalus, and cerebral edema. An urgent external ventricular drain was inserted, and biopsy revealed pineal gland germinoma. Chemotherapy and radiotherapy resulted in adequate tumor shrinkage. This case report highlights that subacute behavioral changes may mask a potentially life-threatening intracranial tumor, especially when associated with abnormal eye movement.
PubMed: 37637548
DOI: 10.7759/cureus.42497 -
Child's Nervous System : ChNS :... Sep 2023Resecting pineal region tumors in children is often challenging. Several approaches have been proposed and practiced. A personal series of pediatric pineal region tumors...
PURPOSE
Resecting pineal region tumors in children is often challenging. Several approaches have been proposed and practiced. A personal series of pediatric pineal region tumors resected through craniotomy with posterior interhemispheric occipital transtentorial (OT) approach are reviewed. We present the surgical techniques, pitfalls, and their results.
MATERIAL AND METHODS
Eighty patients ranging in age from 3 months to 21 years old, and treated over 3 decades were reviewed. Hydrocephalus caused the main presenting symptoms and was noted in 74 patients. It was treated prior to the craniotomy for tumor resection with endoscopic third ventriculostomy (ETV) in 33, external ventricular drainage in 26, and precraniotomy shunt in 15. Nine patients had ETV together with endoscopic biopsy. All patients had a parieto-occipital craniotomy in a prone position. Through a tentorial section, a gross total resection of the tumor was attempted except for germinomas.
RESULTS
The tumor pathology showed 32 germ cell tumors (GCT), 22 benign astrocytomas, 13 pineal parenchymal tumors, 5 ATRTs, 3 papillary tumors, and 5 others. Of GCTs, 18 were teratomas. The extent of resection consisted of 55 gross total resections, 13 subtotal resections, 10 partial, and 2 biopsies with one postoperative death. Hemiparesis in 2, cerebellar ataxia in another 2, and hemiballismus in 1 were transient and improved over time. One had permanent hemisensory loss and another patient had bilateral oculomotor palsy. Postoperative homonymous hemianopia occurred in 2 patients but subsided over a short period of time. Parinaud's sign was noted in 24 patients, of which 16 were transient.
CONCLUSION
The posterior interhemispheric OT approach provides a safe route and comfortable access to the pineal region in children. A great majority of postoperative neurological complications are the results of direct manipulations of the midbrain at tumor resection. Identification and preservation of the tumor-brain interface are of paramount importance. GCTs other than teratomas are treated with neoadjuvant chemotherapy and may eliminate the need for craniotomy. Exophytic midbrain JPAs are amenable to resection.
Topics: Child; Humans; Pinealoma; Retrospective Studies; Brain Neoplasms; Pineal Gland; Postoperative Complications; Teratoma
PubMed: 35821434
DOI: 10.1007/s00381-022-05595-4 -
Computers in Biology and Medicine Jan 2023Pineal region tumors (PRTs) are highly histologically heterogeneous. Germinoma is the most common PRT and is treatable with radiotherapy and chemotherapy. A non-invasive...
BACKGROUND
Pineal region tumors (PRTs) are highly histologically heterogeneous. Germinoma is the most common PRT and is treatable with radiotherapy and chemotherapy. A non-invasive system that helps identify germinoma in the pineal region could reduce lab exams and traumatic therapies.
METHODS
In this retrospective study, 122 patients with histologically confirmed PRTs and pre-operative multi-modal MR images were included. Radiomics features were extracted from different ROIs and image sequences separately. A computational framework that combines a few classification and feature selection algorithms were used to predict histology with radiomics features and demographics. We systemically benchmarked performance of models with feature matrices from all possible combinations of ROIs and image sequences. The Area under the ROC Curve (AUC) was then used to evaluate model performance.
RESULTS
Models with demographics and radiomics features outperform radiomics-only or demographics-only models. The best demographical-radiomics model reached the highest AUC of 0.88 (CI95%: 0.81-0.96). Through the comprehensive evaluation of possible sequence combinations in the differential diagnosis of pineal tumor, T1 and T2 emerged as the most informative sequences for the task. There is imbalanced usage of feature classes as we analyze their proportion in all models.
CONCLUSIONS
The demographical-radiomics model can accurately and efficiently identify germinomas in the pineal region. The preference for MRI sequences, radiomics feature classes, features selection and classification algorithms provide a valuable reference for future attempts at developing classifiers on medical images.
Topics: Humans; Retrospective Studies; ROC Curve; Magnetic Resonance Imaging; Machine Learning; Germinoma
PubMed: 36470145
DOI: 10.1016/j.compbiomed.2022.106366