Continuous Medical Education Department of Neurosurgery, HKL 8 November 2006 Literature Review  of Management  of Pineal R...
OVERVIEW <ul><li>Pineal region tumors are derived from cells located in and around the pineal gland.  </li></ul><ul><li>In...
OVERVIEW <ul><li>Pineal region tumors make up 0.4-1.0% of intracranial tumors in adults and 3.0-8.0% of brain tumors in ch...
OVERVIEW <ul><li>Tumors of the pineal region have a varied histology that generally can be divided into  germ cell  and  n...
Revolution in Pineal Surgery <ul><li>In the early part of this century pineal region surgery had poor outcomes, with opera...
Revolution in Pineal Surgery <ul><li>Torkildsen in 1948 abandoning aggressive surgical resection in favor of cerebrospinal...
Revolution in Pineal Surgery <ul><li>Modification of this treatment strategy led to the radiation test by Japanese clinici...
Revolution in Pineal Surgery <ul><li>The advance of microsurgical techniques and stereotactic procedures has change the pr...
Pineal Tumour – Initial Management <ul><li>Initial management of patients with pineal region tumors should be directed at ...
Indication for Surgery <ul><li>Indications for neurosurgical intervention relate to the severity and chronicity of clinica...
Lab Studies <ul><li>Measurements of  serum and CSF tumor markers  are a valuable component of the preoperative evaluation....
Lab Studies <ul><li>Other biological markers for germ cell tumors include lactate dehydrogenase isoenzymes and placental a...
Lab Studies <ul><li>AFP  is a glycoprotein produced by fetal yolk sac elements and is produced by a wide range of cancers,...
Lab Studies <ul><li>BhCG  is a glycoprotein with a half-life of 15-20 hours and usually is produced by placental trophobla...
Lab Studies <ul><li>Significant variability in expression of tumor markers is such that the  absence of AFP or bhCG does n...
Lab Studies <ul><li>Pineal parenchymal cell tumor  markers are less well characterized than their germ cell counterparts a...
Intracranial Germ Cell Tumors Roger J. Packer, Bruce H. Cohen and Kathleen Cooney Oncologist  2000;5;312-320 <ul><li>Tumor...
Imaging Studies   <ul><li>High-resolution MRI with gadolinium  is necessary in the evaluation of pineal region lesions.  <...
Imaging Studies   <ul><li>Non–germ cell tumors  can derive from pineal parenchymal cells, as well as from surrounding tiss...
Imaging Studies   <ul><li>Astrocytomas , which can arise from the glial stroma of the pineal gland or surrounding tissue, ...
Imaging Studies <ul><li>Meningiomas  typically enhance homogenously and have smooth, distinct borders.  </li></ul><ul><li>...
Imaging Studies <ul><li>Germinomas  are isointense on T1-weighted MRI studies, are slightly hyperintense on T2, and have s...
Imaging Studies <ul><li>Teratomas are well-circumscribed benign tumors characterized by their heterogeneity, multilocularl...
Intracranial Germ Cell Tumors Roger J. Packer, Bruce H. Cohen and Kathleen Cooney Oncologist  2000;5;312-320 <ul><li>The n...
Imaging Studies <ul><li>In addition to MRI, angiography sometimes is used in cases of suspected  vascular anomalies .  </l...
Histologic Findings   <ul><li>Germ cell  tumors are the  most prevalent  neoplasms of the pineal region in  children  and ...
Histologic Findings <ul><li>Germinomas make up 60-70% of all pediatric germ cell tumors.  </li></ul><ul><li>Nongerminomato...
Histologic Findings <ul><li>Description and classification of a given lesion sometimes is confounded when  more than one t...
Histologic Findings <ul><li>The pineoblastoma is an aggressive tumor and resembles the medulloblastoma with respect to age...
Histologic Findings   <ul><li>Neoplasms derived from  glial cells  occur second most frequently in children with pineal re...
Staging   <ul><li>Currently, no formal staging designation is available for patients with pineal region tumors.  </li></ul...
Medical therapy: Radiation therapy   <ul><li>Current treatment protocols for patients older than 3 years who have malignan...
Medical therapy: Radiation therapy <ul><li>Potential complications include  hypothalamic and endocrine dysfunction , cereb...
Medical therapy: Radiation therapy <ul><li>Whole brain radiation  can cause significant  morbidity  in prepubescent patien...
Medical therapy: Radiation therapy <ul><li>Germinomas  are among the  most radiosensitive  tumors, with patient response r...
Intracranial Germ Cell Tumors Roger J. Packer, Bruce H. Cohen and Kathleen Cooney Oncologist  2000;5;312-320 <ul><li>In th...
Medical therapy: Radiation therapy <ul><li>The use of  prophylactic spinal irradiation  is controversial.  </li></ul><ul><...
Medical therapy: Radiation therapy <ul><li>The incidence of spinal metastasis for  germinomas  has been reported to be as ...
Medical therapy: Chemotherapy <ul><li>Chemotherapy  has evolved as an attractive means of minimizing the amount of radiati...
Medical therapy: Chemotherapy <ul><li>Patients with  intracranial nongerminomatous germ cell  tumors have demonstrated res...
Medical therapy: Chemotherapy <ul><li>Most clinicians currently advocate a derivative of the Einhorn regimen as an alterna...
Medical therapy: Chemotherapy <ul><li>Recently, high-dose cyclophosphamide has been advocated as a  single-agent protocol ...
Radiosurgery   <ul><li>Stereotactic radiation or radiosurgery  increasingly is being applied to patients with central nerv...
Reyns, N., M. Hayashi, et al. (2006). The role of Gamma Knife radiosurgery in the treatment of pineal parenchymal tumours....
Hasegawa, T., D. Kondziolka, et al. (2002). &quot;The role of radiosurgery for the treatment of pineal parenchymal tumors....
Radiosurgery <ul><li>In the pediatric population, radiosurgery is an attractive potential  first-line treatment  that meri...
Surgical therapy   <ul><li>The decision to perform a biopsy versus an open procedure for the pineal region tumor has been ...
Jeffrey N. Bruce, Alfred T. Ogden, Surgical Strategies for Treating Patients with Pineal Region Tumors, J Neurooncol, 69(1...
Jeffrey N. Bruce, Alfred T. Ogden, Surgical Strategies for Treating Patients with Pineal Region Tumors, J Neurooncol, 69(1...
Stereotactic biopsy   <ul><li>Stereotactic biopsy has been described as the  procedure of choice  for obtaining a tissue d...
Stereotactic biopsy <ul><li>In their 1996 series, Regis and colleagues revealed a mortality rate of 1.3% and a morbidity r...
(Reyns, Hayashi et al. 2006)Pineal region tumors and the role of stereotactic biopsy: review of the mortality, morbidity, ...
Popovic  EA ,  Kelly PJ .,  Stereotactic procedures for lesions of the pineal region.  , Mayo Clin Proc. 1993 Oct;68(10):9...
KRETH F. W.; SCHÄTZ C. R., Stereotactic management of lesions of the pineal region, Neurosurgery,1996, vol. 39, no2, pp. 2...
Open resection   <ul><li>Open resection carries the obvious advantage of  complete tumor resection.  </li></ul><ul><li>The...
Mahmoud H. Ragab, M.D., Mark G. Luciano, M.D., Ph.D.,  Pineal Region Tumors: Endoscopy versus Microsurgery  , Neurosurgery...
Tissue Biopsy <ul><li>Tissue diagnosis  is a vital part of management in most patients with pineal region tumors.  </li></...
Tissue Biopsy <ul><li>In their 1998 retrospective study, Kim and colleagues described the treatment of 107 patients with p...
Tissue Biopsy <ul><li>Twenty-nine patients treated with radiation and/or chemotherapy were studied retrospectively, includ...
Regueiro, C. A. (2003). &quot;[Treatment of intracranial germ cell tumours and other tumours of the pineal region].&quot; ...
Regueiro, C. A. (2003). &quot;[Treatment of intracranial germ cell tumours and other tumours of the pineal region].&quot; ...
Konovalov, A. N. and D. I. Pitskhelauri (2003). &quot;Principles of treatment of the pineal region tumors.&quot;  Surg Neu...
Jaishri O. Blakeley, MD and Stuart A. Grossman, MD ,  Management of Pineal Region Tumors  ,  Current Treatment Options in ...
Jaishri O. Blakeley, MD and Stuart A. Grossman, MD ,  Management of Pineal Region Tumors  ,  Current Treatment Options in ...
Nishioka, H., J. Haraoka, et al. (2006). &quot;Management of intracranial germ cell tumors presenting with rapid deteriora...
Preoperative details   <ul><li>Patients presenting with hydrocephalus and radiographic evidence of a malignant pineal regi...
Preoperative details <ul><li>A similar strategy may be employed for patients with marked symptomatic hydrocephalus and ben...
Preoperative details <ul><li>Improved endoscopic techniques have made third ventriculostomy an easy and reliable method to...
Cipri, S., A. Gangemi, et al. (2005). &quot;Neuroendoscopic management of hydrocephalus secondary to midline and pineal le...
Yamini, B., D. Refai, et al. (2004). &quot;Initial endoscopic management of pineal region tumors and associated hydrocepha...
Intraoperative details   <ul><li>In general, surgical approaches to the pineal region can be divided into supratentorial, ...
Koziarski, A., E. Skrobowska, et al. (2003). &quot;[Own experience in surgical treatment of the pineal region and midbrain...
Postoperative details   <ul><li>Once the physician makes a diagnosis of malignant tumor from tissue acquired intraoperativ...
Postoperative details   <ul><li>Equivocal findings on the initial postoperative scan warrant a repeat scan within 1-2 week...
Follow-up care   <ul><li>Life-long follow-up of children with pineal region tumors is required. These tumors can recur loc...
The Management of Pineal Area Tumors: A Recent Reappraisal PAUL H. CHAPMAN, MD,* AND RITA M. LINGGOOD, MDt,  Cancer  46:12...
OUTCOME AND PROGNOSIS   <ul><li>The prognosis for patients with pineal region tumors is dependent upon  tumor histology  a...
OUTCOME AND PROGNOSIS   <ul><li>Recurrent germ cell tumors have been shown to respond to chemotherapy, as have some pineal...
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Literature Review Of Management Of Pineal Region Tumour

  1. 1. Continuous Medical Education Department of Neurosurgery, HKL 8 November 2006 Literature Review of Management of Pineal Region Tumour
  2. 2. OVERVIEW <ul><li>Pineal region tumors are derived from cells located in and around the pineal gland. </li></ul><ul><li>In their 1954 pineal tumor study, Ringertz and colleagues defined the pineal region as being bound by the splenium of the corpus callosum and tela choroidea dorsally, the quadrigeminal plate and midbrain tectum ventrally, the posterior aspect of the third ventricle rostrally, and the cerebellar vermis caudally. </li></ul>
  3. 3. OVERVIEW <ul><li>Pineal region tumors make up 0.4-1.0% of intracranial tumors in adults and 3.0-8.0% of brain tumors in children. </li></ul><ul><li>Most children are aged 10-20 years at presentation, with the average age at presentation being 13 years. </li></ul><ul><li>Adults typically are older than 30 years at presentation. </li></ul><ul><li>A complete differential diagnosis for masses in the pineal region also should include vascular anomalies, as well as metastatic tumor. </li></ul>
  4. 4. OVERVIEW <ul><li>Tumors of the pineal region have a varied histology that generally can be divided into germ cell and non–germ cell derivatives . </li></ul><ul><li>Most tumors are a result of displaced embryonic tissue, malignant transformation of pineal parenchymal cells , or transformation of surrounding astroglia . </li></ul><ul><li>No specific genetic mutations have been associated with sporadic pineal region tumors. </li></ul>
  5. 5. Revolution in Pineal Surgery <ul><li>In the early part of this century pineal region surgery had poor outcomes, with operative mortality rates approaching 90%. </li></ul><ul><li>From Horsley's initial attempt at removing a pineal mass in 1910 and development of the lateral transventricular approach in 1931 by Van Wagenan, primitive anesthetic technique and the lack of an operating microscope hindered pineal region surgery. </li></ul>
  6. 6. Revolution in Pineal Surgery <ul><li>Torkildsen in 1948 abandoning aggressive surgical resection in favor of cerebrospinal fluid (CSF) diversion followed by empiric radiotherapy. </li></ul><ul><li>If the patient did not respond to radiation, a surgical procedure to remove radioresistant tumor was performed. </li></ul><ul><li>The algorithm of CSF diversion, radiation, and observation sometimes was successful; however, patients with benign lesions were exposed to unnecessary and ineffective radiation . </li></ul>
  7. 7. Revolution in Pineal Surgery <ul><li>Modification of this treatment strategy led to the radiation test by Japanese clinicians whose patient population had high percentage of radiosensitive germinomas. </li></ul><ul><li>According to this protocol, patients were administered with small doses of radiation, and their cases were followed radiologically. </li></ul><ul><li>If the pineal tumor decreased in size, it was presumed to be radiosensitive, and a full course of radiation was instituted. </li></ul><ul><li>Patients not responding to radiotherapy underwent surgical exploration. </li></ul><ul><li>Despite the low dose of radiation initially used, significant long-term morbidity remained associated with this strategy, particularly in children. </li></ul>
  8. 8. Revolution in Pineal Surgery <ul><li>The advance of microsurgical techniques and stereotactic procedures has change the practice of empiric radiotherapy without tissue diagnosis. </li></ul><ul><li>Therapeutic decision-making now is based on tumor histology rather than radiation responsiveness. </li></ul><ul><li>Currently, initial surgical management for tissue diagnosis, and possible resection , is the standard of care for most children with pineal region tumors </li></ul>
  9. 9. Pineal Tumour – Initial Management <ul><li>Initial management of patients with pineal region tumors should be directed at treating hydrocephalus and establishing a diagnosis. </li></ul><ul><li>Preoperative evaluation should include </li></ul><ul><ul><li>high-resolution MRI of the head with gadolinium; </li></ul></ul><ul><ul><li>measurement of serum and CSF markers , if available; </li></ul></ul><ul><ul><li>cytologic examination of CSF , if available; </li></ul></ul><ul><ul><li>evaluation of pituitary function if endocrine abnormalities are suspected; and </li></ul></ul><ul><ul><li>visual field examination if suprasellar extension of the tumor is noted on MRI. </li></ul></ul><ul><li>The ultimate management goal should be to refine adjuvant therapy based on tumor pathology. </li></ul>
  10. 10. Indication for Surgery <ul><li>Indications for neurosurgical intervention relate to the severity and chronicity of clinical presentation. </li></ul><ul><li>The symptoms of pineal region tumors can be as varied as their diverse histology. </li></ul><ul><li>Patients presenting with signs and symptoms of raised intracranial pressure must receive a head CT scan or an MRI to assess the need for emergent management. </li></ul><ul><li>Subsequent nonemergent workup of a patient with a pineal region tumor can be divided into radiologic and laboratory studies. </li></ul>
  11. 11. Lab Studies <ul><li>Measurements of serum and CSF tumor markers are a valuable component of the preoperative evaluation. </li></ul><ul><li>These results can be suggestive of tumor type but only occasionally provide the physician diagnostic information. </li></ul><ul><li>Markers have been most helpful in the workup of patients with germ cell tumors . </li></ul><ul><li>The expression of embryonic proteins, such as alpha-fetoprotein (AFP) and bhCG, are indicative of malignant germ cell elements. </li></ul>
  12. 12. Lab Studies <ul><li>Other biological markers for germ cell tumors include lactate dehydrogenase isoenzymes and placental alkaline phosphatase, although these are less specific. </li></ul><ul><li>Serum and CSF measurements can be used for diagnostic purposes and for monitoring a response to therapy. </li></ul><ul><li>In general, CSF measurements are more sensitive than serum measurements, and a CSF-to-serum gradient may be consistent with an intracranial lesion. </li></ul>
  13. 13. Lab Studies <ul><li>AFP is a glycoprotein produced by fetal yolk sac elements and is produced by a wide range of cancers, including gastric, liver, and colon adenocarcinoma, as well as extracranial germ cell tumors. </li></ul><ul><li>Serum levels of AFP are greatest in newborns and decline thereafter. </li></ul><ul><li>AFP is markedly elevated with endodermal sinus tumors and elevated to a lesser degree with embryonal cell carcinomas. </li></ul><ul><li>While teratomas do not secrete AFP, the less-differentiated immature teratomas can produce detectable amounts </li></ul>
  14. 14. Lab Studies <ul><li>BhCG is a glycoprotein with a half-life of 15-20 hours and usually is produced by placental trophoblastic cells. </li></ul><ul><li>Choriocarcinomas secrete large amounts of bhCG, and lesser elevations can occur in patients with embryonal cell carcinomas. </li></ul><ul><li>The presence of syncytiotrophoblastic giant cells in mixed germinomas may result in detectable levels of bhCG, but the majority of germinomas are nonsecretory. </li></ul>
  15. 15. Lab Studies <ul><li>Significant variability in expression of tumor markers is such that the absence of AFP or bhCG does not rule out a mixed germ cell tumor . </li></ul><ul><li>Although recent studies suggest a less favorable prognosis for patients with germinomas secreting bhCG, no established prognostic significance of tumor markers exists. </li></ul><ul><li>Determination of AFP and bhCG levels prior to surgical resection is extremely important because it provides a reference point that can be used to assess recurrence during follow-up. </li></ul>
  16. 16. Lab Studies <ul><li>Pineal parenchymal cell tumor markers are less well characterized than their germ cell counterparts and include melatonin and the S antigen . </li></ul><ul><li>Neither of these proteins has proven valuable in the diagnosis of pineal parenchymal cell tumors. </li></ul><ul><li>Some authors have reported using melatonin levels in follow-up for patients with pineocytoma after surgical treatment. </li></ul>
  17. 17. Intracranial Germ Cell Tumors Roger J. Packer, Bruce H. Cohen and Kathleen Cooney Oncologist 2000;5;312-320 <ul><li>Tumor markers have been used to diagnose the specific type of tumor present. </li></ul><ul><li>When these markers are elevated, especially at high elevations, the diagnosis of a form of mixed germ cell tumor is essentially confirmed. </li></ul><ul><li>Similarly, isolated high elevations of β-HCG strongly suggest the presence of a choriocarcinoma . </li></ul><ul><li>Milder elevations of β-HCG are of less use, as they may be representative of a mixed germ cell tumor, choriocarcinoma, or possibly other forms of malignancy in the pineal region. </li></ul>
  18. 18. Imaging Studies <ul><li>High-resolution MRI with gadolinium is necessary in the evaluation of pineal region lesions. </li></ul><ul><li>Tumor characteristics, such as size, vascularity, and homogeneity, can be assessed, as well as the anatomic relationship with surrounding structures. </li></ul><ul><li>Irregular tumor borders can be suggestive of tumor invasiveness and associated histologic malignancy . </li></ul><ul><li>Although the type of tumor cannot be determined reliably from the radiographic characteristics alone, some patterns are associated with specific tumors. </li></ul>
  19. 19. Imaging Studies <ul><li>Non–germ cell tumors can derive from pineal parenchymal cells, as well as from surrounding tissue. </li></ul><ul><li>Pineocytomas and pineoblastomas typically are hypointense to isointense on T1-weighted images, have increased signal on T2, and demonstrate homogenous enhancement after administration of gadolinium. </li></ul><ul><li>Pineoblastomas can be distinguished by their irregular shape and large size (ie, some >4.0 cm). </li></ul>
  20. 20. Imaging Studies <ul><li>Astrocytomas , which can arise from the glial stroma of the pineal gland or surrounding tissue, also are hypointense on T1 and hyperintense on T2. </li></ul><ul><li>However, astrocytomas have variable enhancement patterns. </li></ul><ul><li>Calcium may be present in either pineal cell tumors or astrocytomas. </li></ul>
  21. 21. Imaging Studies <ul><li>Meningiomas typically enhance homogenously and have smooth, distinct borders. </li></ul><ul><li>Tentorial meningiomas can have an enhancing dural tail of origin and are anatomically distinguished by their dorsal location relative to the deep venous system. </li></ul>
  22. 22. Imaging Studies <ul><li>Germinomas are isointense on T1-weighted MRI studies, are slightly hyperintense on T2, and have strong homogenous enhancement. Germinomas can have evidence of calcification, which surrounds the pineal gland as the germinoma grows. </li></ul><ul><li>In contrast, pineocytomas commonly have intratumoral calcium. Intratumoral cysts can exist as well. </li></ul><ul><li>Unlike germinomas, teratomas typically have heterogenous MRI signals because they can contain tissue from all 3 germinal layers. </li></ul>
  23. 23. Imaging Studies <ul><li>Teratomas are well-circumscribed benign tumors characterized by their heterogeneity, multilocularly, and irregular enhancement. </li></ul><ul><li>These tumors also can demonstrate ring enhancement . In some cases, a well-circumscribed teratoma has areas of low attenuation that correlate with adipose tissue, which serves to further distinguish it from other pineal region tumors. </li></ul><ul><li>Malignant nongerminomatous germ cell tumors also can have a heterogeneous appearance due to a mixture of benign and malignant germ cell components. </li></ul><ul><li>Areas of intratumoral hemorrhage may distinguish specific subtypes, such as choriocarcinoma. </li></ul>
  24. 24. Intracranial Germ Cell Tumors Roger J. Packer, Bruce H. Cohen and Kathleen Cooney Oncologist 2000;5;312-320 <ul><li>The neuroimaging characteristics of germinomas and nongerminomatous germ cell tumors are similar enough to limit diagnostic certainty, and either tissue confirmation or the measurement of specific tumor markers are needed for diagnosis </li></ul><ul><li>In addition, in the pineal region, germ cell tumors cannot be definitively separated on basis of neuroimaging characteristics from other tumors, such as pineoblastomas, pineocytomas, or gliomas. </li></ul><ul><li>In the suprasellar region, germinomas may be difficult to separate from other lesions, including germinomas which infiltrate the surrounding brain mimicking gliomas and histiocytomas. </li></ul><ul><li>In general, mixed germ cell tumors tend to be more invasive than pure germinomas. </li></ul><ul><li>Pineal teratomas can often be differentiated based on more frequent areas of fat and large areas of calcification. </li></ul>
  25. 25. Imaging Studies <ul><li>In addition to MRI, angiography sometimes is used in cases of suspected vascular anomalies . </li></ul><ul><li>However, the anatomic and vascular information provided by MRI has largely circumvented the need for routine angiograms in the evaluation of pineal region neoplasms. </li></ul>
  26. 26. Histologic Findings <ul><li>Germ cell tumors are the most prevalent neoplasms of the pineal region in children and are histologically indistinguishable from those found at extracranial locations , including the mediastinum and gonads. </li></ul><ul><li>These extracranial locations most commonly are midline. </li></ul><ul><li>Intracranial germ cell tumors commonly are divided into 2 categories: germinomas and tumors derived from totipotential germ cells. </li></ul>
  27. 27. Histologic Findings <ul><li>Germinomas make up 60-70% of all pediatric germ cell tumors. </li></ul><ul><li>Nongerminomatous germ cell tumors fall along a spectrum of differentiation. </li></ul><ul><li>The least differentiated is the embryonal cell carcinoma , with further differentiation described as either embryonic or extraembryonic. </li></ul><ul><li>Immature and mature teratomas result from maturation along embryonic cell lines, whereas the endodermal sinus tumor or yolk sac tumor and the choriocarcinoma are a result of extraembryonic differentiation </li></ul>
  28. 28. Histologic Findings <ul><li>Description and classification of a given lesion sometimes is confounded when more than one type of germ cell component is found in a surgical specimen. </li></ul><ul><li>Mixed germ cell tumors are a result of simultaneous differentiation along more than one pathway such that, at presentation, 2 or more characterized components are recognized. </li></ul><ul><li>An example of this is the teratocarcinoma , an embryonal carcinoma containing elements of an immature teratoma. </li></ul>
  29. 29. Histologic Findings <ul><li>The pineoblastoma is an aggressive tumor and resembles the medulloblastoma with respect to age of presentation and its propensity to seed the subarachnoid space. </li></ul><ul><li>The pineocytoma is significantly less aggressive than the pineoblastoma. </li></ul><ul><li>It usually presents during adolescence and rarely seeds the subarachnoid space. </li></ul>
  30. 30. Histologic Findings <ul><li>Neoplasms derived from glial cells occur second most frequently in children with pineal region tumors, exceeded only by germinomas in 2 large series that include children with pineal region tumors. </li></ul><ul><li>The histologic and macroscopic appearances are similar to malignant glial neoplasms found in other areas of the CNS. </li></ul><ul><li>Glial-derived neoplasms in the pineal region can include low-grade and high-grade lesions. </li></ul>
  31. 31. Staging <ul><li>Currently, no formal staging designation is available for patients with pineal region tumors. </li></ul><ul><li>However, a postoperative MRI within 48 hours of surgery is an important means of assessing the degree of resection. </li></ul><ul><li>In addition, surveillance scans of the spine are used to assess the presence of drop metastasis. </li></ul>
  32. 32. Medical therapy: Radiation therapy <ul><li>Current treatment protocols for patients older than 3 years who have malignant pineal region tumors include radiotherapy . </li></ul><ul><li>Early clinical trials of patients treated with radiotherapy reported significant mortality . </li></ul><ul><li>Even low doses of radiation can have significant long-term effects upon a child's cognitive development . </li></ul><ul><li>Radiation-induced deficits are an important consideration because many children with pineal region tumors enjoy prolonged survival. </li></ul>
  33. 33. Medical therapy: Radiation therapy <ul><li>Potential complications include hypothalamic and endocrine dysfunction , cerebral necrosis, secondary tumorigenesis, and progression of disease. </li></ul><ul><li>Cases of radiation-induced meningioma have been reported in children after radiotherapy for pineal region tumors. </li></ul><ul><li>Standard radiotherapy protocols for children with malignant pineal cell tumors use 4000 cGy of whole brain radiation followed by 1500 cGy to the pineal region. </li></ul><ul><li>The dose is administered in 180-cGy daily fractions. </li></ul>
  34. 34. Medical therapy: Radiation therapy <ul><li>Whole brain radiation can cause significant morbidity in prepubescent patients, limiting the recommended initial extended field to 2500-3000 cGy. </li></ul><ul><li>An additional dose directed at the tumor bed can be administered subsequently. </li></ul><ul><li>Several studies demonstrate that patients receiving less than 5000 cGy are at risk for recurrence , strongly suggesting that this is the optimal total dose of radiation. </li></ul><ul><li>For children with malignant germ cell tumors, standard treatment is focal radiotherapy followed by radiation to the ventricular field . </li></ul><ul><li>The application of radiotherapy depends upon the histology of the tumor being treated. </li></ul>
  35. 35. Medical therapy: Radiation therapy <ul><li>Germinomas are among the most radiosensitive tumors, with patient response rates and long-term tumor-free survival rates greater than 90% in most published series. </li></ul><ul><li>Nongerminomatous malignant germ cell tumors are significantly less responsive to radiation, with a 5-year survival rate of 30-40% using this treatment alone. </li></ul><ul><li>Patients with low-grade pineocytomas can be observed cautiously after complete surgical resection without adjuvant radiation because no clear evidence shows that radiotherapy is beneficial. </li></ul><ul><li>These patients' cases should be followed carefully with serial MRIs to assess tumor recurrence or progression. </li></ul>
  36. 36. Intracranial Germ Cell Tumors Roger J. Packer, Bruce H. Cohen and Kathleen Cooney Oncologist 2000;5;312-320 <ul><li>In the past, a frequent means to determine the histological type of pineal region tumors, without surgery, was to diagnose the tumor on the basis of its response to radiotherapy </li></ul><ul><li>Patients with presumed germ cell tumors were given 2,000 cGy of radiation to the area of abnormality and if the tumor regressed after such treatment, a diagnosis of germinoma was made. </li></ul><ul><li>If there was minimal or no response, biopsy was recommended. </li></ul><ul><li>Although it is true that germinomas will respond to radiotherapy, other germ cell tumors will also respond, as will the pineoblastomas. </li></ul><ul><li>Given the differing types of treatment required for germ cell tumors, the use of responsiveness to radiotherapy as a diagnostic tool is not appropriate . </li></ul>
  37. 37. Medical therapy: Radiation therapy <ul><li>The use of prophylactic spinal irradiation is controversial. </li></ul><ul><li>Early recommendations for postoperative spinal irradiation have been preempted by reports showing the incidence of drop metastasis into the spine to be relatively low . </li></ul><ul><li>The propensity of a pineal region tumor to metastasize to the spine varies with tumor histology. </li></ul><ul><li>Estimates of the incidence of spinal seeding with pineal cell tumors are in the range of 10-20%, with significantly higher rates noted for pineoblastoma as compared to pineocytoma. </li></ul>
  38. 38. Medical therapy: Radiation therapy <ul><li>The incidence of spinal metastasis for germinomas has been reported to be as high as 11%, and, for endodermal sinus tumors , incidence is as high as 23%. </li></ul><ul><li>Craniospinal radiotherapy for nongerminomatous germ cell tumors is controversial but used routinely in some countries. </li></ul><ul><li>For patients with pineoblastomas , some authors suggest the use of preemptive spinal radiation therapy even if the results of the postoperative surveillance MRI are negative. </li></ul><ul><li>As modern improvements in surgical and adjuvant therapy are reflected in long-term survival, the rates of spinal metastasis likely will drop significantly, making the need for spinal irradiation obsolete. </li></ul><ul><li>Currently, a reasonable approach is to administer spinal irradiation only for documented seeding. </li></ul>
  39. 39. Medical therapy: Chemotherapy <ul><li>Chemotherapy has evolved as an attractive means of minimizing the amount of radiation needed to effectively treat children with pineal region tumors. </li></ul><ul><li>As with radiotherapy, the response to chemotherapy for patients with pineal region tumors varies according to tumor histology. </li></ul><ul><li>Germ cell tumors historically have been more sensitive to chemotherapy than pineal cell tumors. </li></ul><ul><li>Germinomas and nongerminomatous germ cell tumors have shown response rates ranging from 80-100% with platinum-based regimens. </li></ul><ul><li>Patients with extracranial nongerminomatous germ cell tumors respond well to treatment with a wide array of chemotherapeutic agents. </li></ul>
  40. 40. Medical therapy: Chemotherapy <ul><li>Patients with intracranial nongerminomatous germ cell tumors have demonstrated response rates as high as 78% with some regimens. </li></ul><ul><li>The Einhorn regimen , which includes cisplatin, vinblastine, and bleomycin, and later substituted VP-16 for vinblastine and bleomycin, has been used with some success. </li></ul><ul><li>Several ongoing studies are aimed at determining the optimal sequence of adjuvant therapy for children with nongerminomatous germ cell tumors. </li></ul><ul><li>Presently, these children undergo treatment with a course of chemotherapy prior to radiation. </li></ul><ul><li>The dramatic success of radiotherapy in treating children with germinomas has precluded extensive consideration of chemotherapy as a first-line treatment in older children. </li></ul><ul><li>Chemotherapy should be considered a first-line treatment only in very young children. </li></ul><ul><li>Some authors advocate treating children with chemotherapy prior to radiation in an effort to reduce radiation exposure and its associated morbidity. </li></ul>
  41. 41. Medical therapy: Chemotherapy <ul><li>Most clinicians currently advocate a derivative of the Einhorn regimen as an alternative treatment for patients with recurrent or metastatic germinomas . Some clinicians advocate the use of chemotherapy as well as radiotherapy after diagnosis of nongerminomatous germ cell tumors. The impetus for adding chemotherapy initially in these patients comes from the 5-year survival rate of 30-65% in children with nongerminomatous germ cell tumors treated with radiotherapy alone. </li></ul><ul><li>The reported effectiveness of chemotherapeutic regimens for children with pineal cell tumors is limited to anecdotal case reports and reported series involving small numbers of patients. No dominant agent has evolved as the drug of choice, and treatment regimens have included various combinations of vincristine, lomustine, cisplatin, etoposide, cyclophosphamide, actinomycin D, and methotrexate. </li></ul>
  42. 42. Medical therapy: Chemotherapy <ul><li>Recently, high-dose cyclophosphamide has been advocated as a single-agent protocol in the treatment of children with pineoblastomas . </li></ul><ul><li>In their 1996 study, Ashley and colleagues demonstrated that children treated with high-dose cyclophosphamide had stable or diminishing disease while on the protocol. Impaired pulmonary function and thrombocytopenia were notable adverse effects. </li></ul>
  43. 43. Radiosurgery <ul><li>Stereotactic radiation or radiosurgery increasingly is being applied to patients with central nervous system disease. </li></ul><ul><li>Currently, experience with radiosurgery in patients with pineal region tumors is limited; however, several small studies have shown safety and some efficacy in treating pineal region tumors over a range of histologies. </li></ul><ul><li>Review of these studies does show that radiosurgery is not a magic bullet for all pineal lesions with treatment failures occurring with more malignant lesions . </li></ul><ul><li>This demonstrates the importance of obtaining a histological diagnosis before embarking on a treatment plan and highlights the risk of treating a tumor of unknown histology with radiosurgery alone. </li></ul>
  44. 44. Reyns, N., M. Hayashi, et al. (2006). The role of Gamma Knife radiosurgery in the treatment of pineal parenchymal tumours. Acta Neurochir (Wien) . 148: 5-11; discussion 11. <ul><li>Retrospectively a series of 13 patients with PPT treated by Gamma Knife radiosurgery </li></ul><ul><li>8 patients had pineocytomas (61.5%) </li></ul><ul><li>5 had pineoblastomas (38.5%). </li></ul><ul><li>Radiosurgery was performed alone in 6 cases, </li></ul><ul><li>after partial microsurgical resection in 3 cases, </li></ul><ul><li>in association with chemotherapy in 3 cases and </li></ul><ul><li>following conventional fractionated radiotherapy in 1 case. </li></ul><ul><li>The marginal dose to these tumors ranged from 11 to 20 Gy (mean 15 Gy). </li></ul><ul><li>RESULTS : With a mean follow-up of 34 months (range 6 to 88), </li></ul><ul><li>all tumors responded to treatment and disappeared or ceased growing . </li></ul><ul><li>At the end of the follow-up period, 10 out of 12 patients were alive. </li></ul><ul><li>No mortality or major morbidity related to radiosurgery. </li></ul><ul><li>CONCLUSION : This study confirms that radiosurgery can be an effective and safe primary treatment modality for patients with pineocytomas . </li></ul><ul><li>It should have a role in multimodality therapy which includes microsurgical resection, fractionated radiotherapy and chemotherapy for the management of malignant pineal tumors. </li></ul>
  45. 45. Hasegawa, T., D. Kondziolka, et al. (2002). &quot;The role of radiosurgery for the treatment of pineal parenchymal tumors.&quot; Neurosurgery 51 (4): 880-9. <ul><li>Retrospectively evaluated 16 patients who had undergone radiosurgery as the primary or adjuvant treatment for pineal parenchymal tumors. </li></ul><ul><li>Ten patients (62.5%) had pineocytomas, two (12.5%) had mixed pineocytoma and pineoblastoma, and four (25%) had pineoblastomas. </li></ul><ul><li>RESULTS : The overall 2- and 5-year survival rates after diagnosis were 75.0 and 66.7%, respectively. In 14 patients who were evaluated with imaging, 4 (29%) demonstrated complete remission , 8 (57%) had partial remission, 2 (14%) had no change, and no patient had local progression. The local tumor control rate (complete remission, partial remission, or no change) was 100%. Five patients died during follow-up. One patient with a pineocytoma and three patients with pineoblastomas died secondary to leptomeningeal or extracranial spread tumor. No cause of death was established for one patient. Two patients developed adverse radiation effects after radiosurgery. </li></ul><ul><li>CONCLUSION : Stereotactic radiosurgery is a valuable primary management modality for patients with pineocytomas . </li></ul><ul><ul><li>As adjuvant therapy , radiosurgery may be used to boost local tumor dose during multimodality management of malignant pineal parenchymal tumors. </li></ul></ul>
  46. 46. Radiosurgery <ul><li>In the pediatric population, radiosurgery is an attractive potential first-line treatment that merits further investigation. </li></ul><ul><li>Some authors have proposed using radiosurgery in place of conventional radiotherapy in an effort to reduce or eliminate the long-term sequelae of radiotherapy in children. </li></ul><ul><li>Radiosurgery is optimized for targets 3 cm or less, which precludes treatment of some patients with larger pineal region tumors. </li></ul>
  47. 47. Surgical therapy <ul><li>The decision to perform a biopsy versus an open procedure for the pineal region tumor has been debated extensively in the literature. </li></ul><ul><li>While the ultimate choice of procedure is based to some extent upon the surgeon's personal bias and experience, some distinct advantages and disadvantages exist for each of these procedures. </li></ul>
  48. 48. Jeffrey N. Bruce, Alfred T. Ogden, Surgical Strategies for Treating Patients with Pineal Region Tumors, J Neurooncol, 69(1):221-236, Aug-Sept 2004 <ul><li>Optimal management of pineal region tumors depends on securing an accurate histologic diagnosis to facilitate management customized to the nuances of specific pathologies.  </li></ul><ul><li>As an initial step, surgical intervention by either stereotactic biopsy or open surgery is necessary to obtain tissue for pathologic examination.  </li></ul><ul><li>Stereotactic biopsy has the benefit of relative ease and minimal morbidity but is associated with greater likelihood of diagnostic inaccuracy compared to open surgery where more extensive tissue sampling is possible. </li></ul><ul><li>The role of surgical debulking in the management of pineal tumors is clearly defined for some tumors but is less evident for others.  </li></ul><ul><li>Among the one third of pineal tumors that are benign or low grade , complete surgical resection is achievable and constitutes optimal management with excellent long-term recurrence-free survival.  </li></ul>
  49. 49. Jeffrey N. Bruce, Alfred T. Ogden, Surgical Strategies for Treating Patients with Pineal Region Tumors, J Neurooncol, 69(1):221-236, Aug-Sept 2004 <ul><li>The benefits of aggressive surgical resection among malignant tumors are less clear but several studies have correlated degree of tumor removal with improved outcome. </li></ul><ul><li>Advances in technology, surgical technique, and post-operative care have minimized surgical complications, however all surgical procedures in the pineal region, including both stereotactic biopsy and open surgery, are potentially hazardous.  </li></ul><ul><li>Advanced judgment, experience, and expertise are necessary to achieve rates of success sufficient to justify aggressive management.  </li></ul><ul><li>Management strategies using stereotactic biopsy, endoscopy, and radiosurgery can also provide favorable outcomes in some cases.  </li></ul><ul><li>Selective incorporation of these innovations can be expected to improve the already highly favorable outcome for all pineal region tumors. </li></ul>
  50. 50. Stereotactic biopsy <ul><li>Stereotactic biopsy has been described as the procedure of choice for obtaining a tissue diagnosis in certain situations such as widely disseminated disease, clearly invasive malignant tumor, or patients with multiple medical problems. </li></ul><ul><li>Early experience with stereotactic biopsies resulted in morbidity and mortality specifically related to targeting periventricular structures adjacent to the deep venous system. </li></ul><ul><li>More recent studies, however, have shown stereotactic biopsy to be a safe and efficient means of obtaining a tissue diagnosis. </li></ul>
  51. 51. Stereotactic biopsy <ul><li>In their 1996 series, Regis and colleagues revealed a mortality rate of 1.3% and a morbidity rate of less than 1.0% in 370 patients with stereotactic biopsies of pineal region tumors. The study included data from 15 French neurosurgical centers and documented statistical homogeneity among the different centers. </li></ul><ul><li>In a similar study, Kreth and colleagues (1996) retrospectively evaluated the risk profile, diagnostic accuracy, and the therapeutic relevance of the stereotactic approach in 106 patients. They showed a morbidity rate of 2 out of 106 patients, a mortality rate of 9 out of 106 patients , and a definitive tissue diagnostic rate of 103 out of 106 patients . While stereotactic biopsy clearly can be performed safely and effectively at centers familiar with the technique, it is disadvantageous to patients who would benefit from complete or near-complete resection of tumor. </li></ul>
  52. 52. (Reyns, Hayashi et al. 2006)Pineal region tumors and the role of stereotactic biopsy: review of the mortality, morbidity, and diagnostic rates in 370 cases.[Neurosurgery. 1998] <ul><li>370 stereotactic biopsies of pineal region tumors were reviewed, from 15 French neurosurgical centers. </li></ul><ul><li>RESULTS : The mortality rate was 1.3% (5 patients of 370), and 3 patients suffered severe neurological complications. </li></ul><ul><li>This study is the first to clearly demonstrate that the mortality, morbidity, and diagnostic rates for stereotactic biopsies are not different in the pineal region. </li></ul><ul><li>CONCLUSION : Our conclusion is that stereotactic biopsy must remain a main diagnostic modality for tumors of the pineal region. </li></ul>
  53. 53. Popovic EA , Kelly PJ ., Stereotactic procedures for lesions of the pineal region. , Mayo Clin Proc. 1993 Oct;68(10):965-70 <ul><li>During the 7-year period between June 1985 and May 1992, 34 patients with pineal lesions underwent 66 stereotactic procedures (37 biopsies, 19 third ventriculostomies, 6 cyst aspirations, 3 instillations of 32P into cysts, and 1 insertion of an Ommaya reservoir into a cyst) at the Mayo Clinic. </li></ul><ul><li>RESULT: No mortality or permanent morbidity was associated with the 66 stereotactic procedures; 2 patients had temporary complications--1 neurologic (transient diplopia) and 1 nonneurologic (pulmonary embolism). </li></ul><ul><li>Diagnostic tissue was obtained in 33 of the 34 patients . </li></ul><ul><li>CONCLUSION :We conclude that stereotactic biopsy of pineal lesions can be performed safely , has a high diagnostic yield , and facilitates rational planning of treatment. </li></ul>
  54. 54. KRETH F. W.; SCHÄTZ C. R., Stereotactic management of lesions of the pineal region, Neurosurgery,1996, vol. 39, no2, pp. 280-291 (53 ref.) <ul><li>OBJECTIVE : The relevance of the computed tomography-guided stereotactic approach for the management of lesions of the pineal region is analyzed. </li></ul><ul><li>METHODS : Retrospective analysis conducted between 1985 and 1993, of the stereotactic approach in 106 patients was studied. </li></ul><ul><li>RESULTS : A histological diagnosis was obtained in 103 of the 106 patients . </li></ul><ul><ul><li>In three patients, a conclusive diagnosis could not be established because of intraoperative complications. </li></ul></ul><ul><ul><li>One lesion was misdiagnosed as a pineocytoma instead of a pineoblastoma. </li></ul></ul><ul><ul><li>Two of the 106 patients died ; </li></ul></ul><ul><ul><li>9 patients experienced perioperative morbidity. </li></ul></ul><ul><ul><li>In 38 patients, the stereotactic approach was also useful for therapy . </li></ul></ul><ul><ul><li>Cyst aspiration and/or internal drainage was performed in 18 patients with symptomatic cystic lesions. </li></ul></ul><ul><ul><li>In 12 patients, the obtained tissue diagnosis was the basis for deferring additional therapy. </li></ul></ul><ul><ul><li>In 43 patients with germ-cell tumors, pineoblastomas, or malignant gliomas, a stereotactic biopsy was the starting point for additional radiotherapy/chemotherapy. </li></ul></ul><ul><li>CONCLUSION : The stereotactic approach to the pineal region is a relatively safe procedure in experienced hands. </li></ul><ul><li>The diagnosis obtained by computed tomography-guided stereotactic biopsy is a valid basis for treatment decisions . Long-term follow-up observation of the benign lesions is necessary for a definite confirmation of diagnostic accuracy. </li></ul>
  55. 55. Open resection <ul><li>Open resection carries the obvious advantage of complete tumor resection. </li></ul><ul><li>The long-term benefits of complete tumor resection are best surmised by tumor type and histology. </li></ul><ul><li>For patients with benign lesions, the surgical resection can be curative . </li></ul><ul><li>In patients with malignant tumor components, evidence suggests that surgical debulking may improve the response to postoperative adjuvant therapy . </li></ul><ul><li>Gross total tumor resection also provides ample tissue specimen to the neuropathologist for diagnosis. </li></ul><ul><li>This circumvents the potential problems of sampling error and erroneous diagnosis associated with the small volume of tissue provided by stereotactic biopsy. </li></ul>
  56. 56. Mahmoud H. Ragab, M.D., Mark G. Luciano, M.D., Ph.D., Pineal Region Tumors: Endoscopy versus Microsurgery , Neurosurgery Online, Volume 53(2), August 2003, pp 520-521 <ul><li>Between 1995 and 2001, 31 patients underwent surgery for the management of their pineal region tumors. Twenty-two endoscopic procedures and nine craniotomies were performed. A combined biopsy and third ventriculostomy was performed in 19 of 22 endoscopic cases with biopsy only in 3 cases. </li></ul><ul><li>RESULTS : Endoscopic treatment was possible in 22 (71%) of 31 of presented pineal region tumors. A combined biopsy and third ventriculostomy was possible in 18 (82%) of the 22 cases. </li></ul><ul><ul><li>Tumor diagnosis based on endoscopic biopsy was adequate in 18 (82%) of 22 cases. Hydrocephalus was adequately treated in 17 (89%) of 19 cases. </li></ul></ul><ul><ul><li>Craniotomy was required in 9 (29%) of 31 cases secondary to ventricular or tumor anatomy. </li></ul></ul><ul><ul><li>A pathological diagnosis was adequate in 9 (100%) of 9 cases; however, hydrocephalus required further treatment in 3 (33%) of 9 cases, and the complication rate (4 [44%] of 9 cases) was higher. </li></ul></ul><ul><li>CONCLUSION : A combined endoscopic biopsy and third ventriculostomy was possible and successful in treatment and diagnosis of pineal region tumors with low morbidity. </li></ul>
  57. 57. Tissue Biopsy <ul><li>Tissue diagnosis is a vital part of management in most patients with pineal region tumors. </li></ul><ul><li>However, nonoperative management of patients with positive tumor markers is a reasonable option for some patients. </li></ul><ul><li>A markedly elevated level of AFP and bhCG is pathognomonic for germ cell tumors with malignant components. </li></ul><ul><li>New strategies currently under study have been aimed at minimizing surgical intervention prior to ascertaining whether a tumor is responsive to radiation and/or chemotherapy. </li></ul>
  58. 58. Tissue Biopsy <ul><li>In their 1998 retrospective study, Kim and colleagues described the treatment of 107 patients with primary intracranial germ cell tumors. This included 60 patients with tumors in the pineal region. Thirty of these patients were treated without surgery based on radiological findings and tumor markers. </li></ul><ul><li>Univariant analysis of a response to trial radiation and chemotherapy was shown to be correlative with outcome, justifying the administration of trial chemotherapy or radiotherapy without tissue biopsy in the subgroup of patients with positive germ cell markers. These findings corroborate the results of a 1997 study by Sawamura and colleagues evaluating the necessity of radical resection in patients with intracranial germinomas. </li></ul>
  59. 59. Tissue Biopsy <ul><li>Twenty-nine patients treated with radiation and/or chemotherapy were studied retrospectively, including 10 with solitary pineal region masses. </li></ul><ul><li>The results showed no significant difference in outcome related to extent of surgical resection and an overall tumor-free survival rate of 100% over a follow-up period of 42 months. </li></ul><ul><li>This retrospective evidence is quite compelling in favor of withholding surgical treatment of children with pineal region tumors and positive serum or CSF markers. </li></ul>
  60. 60. Regueiro, C. A. (2003). &quot;[Treatment of intracranial germ cell tumours and other tumours of the pineal region].&quot; Neurocirugia (Astur) 14 (2): 127-39. <ul><li>The management of patients with central nervous system germ-cell tumours is evolving, and a definitive standard has not been achieved . </li></ul><ul><li>A large amount of data indicate that radiotherapy alone results in long-term relapse free survival rates of about 90% in patients with germinoma. </li></ul><ul><li>Various prospective trials evaluated the results of combinations of chemotherapy and reduced dose and/or volume radiotherapy. </li></ul><ul><li>The survival rates of combined treatment approaches were similar to the rates achieved with craniospinal radiotherapy alone . </li></ul><ul><li>Nevertheless, the relapse rates were probably higher due to the significant number of relapses that arouse outside the volume treated with radiotherapy. Additional studies are necessary to determine the appropriate radiotherapy volumes and the role of combined treatments. </li></ul><ul><li>Chemotherapy alone results in high relapse rates and can not be recommended. </li></ul><ul><li>Mature teratomas are benign germ cell tumours that can be controlled with complete surgical resection in over 90% of cases. </li></ul>
  61. 61. Regueiro, C. A. (2003). &quot;[Treatment of intracranial germ cell tumours and other tumours of the pineal region].&quot; Neurocirugia (Astur) 14 (2): 127-39. <ul><li>Non-germinoma germ cell tumours are a heterogeneous group of tumours that includes very aggressive tumours such as mixed and pure choriocarcinomas, yolk sac tumours, and embryonal carcinomas; and tumours with intermediate aggressiveness such as mixed tumours with germinoma and teratoma, immature teratomas and teratomas with malignant transformation. </li></ul><ul><li>Both radiotherapy alone and chemotherapy alone result in quite low rates of tumour control and current treatment approaches include chemotherapy and radiotherapy , with surgical removal of the tumour in some patients. </li></ul><ul><li>Pineocytomas are benign tumours that are controlled in most cases by complete surgical resection or partial surgical resection and local field irradiation . </li></ul><ul><li>Current treatment approaches for pineoblastomas include surgery, chemotherapy, and craniospinal irradiation with a local boost. </li></ul><ul><li>Chemotherapy alone was used to delay irradiation in infants with very little success. </li></ul>
  62. 62. Konovalov, A. N. and D. I. Pitskhelauri (2003). &quot;Principles of treatment of the pineal region tumors.&quot; Surg Neurol 59 (4): 250-68. <ul><li>From 1976 to 1999 about 700 patients with tumors of the pineal region and posterior third ventricle were managed ,In more than 330 cases the tumor was removed. </li></ul><ul><li>There are four main groups of tumors: </li></ul><ul><ul><li>the germ cell tumors-87 (31%); </li></ul></ul><ul><ul><li>the pineal parenchymal tumors-75 (27%); </li></ul></ul><ul><ul><li>the glial tumors-77 (27%); and miscellaneous-43 (15%). </li></ul></ul><ul><li>Radiation therapy was administered in 145 (51%) and chemotherapy in 16 patients. </li></ul><ul><li>RESULTS : </li></ul><ul><ul><li>A total tumor removal was achieved in 148 operations (58%), subtotal in 74 (29%) and partial in 33 (13%). </li></ul></ul><ul><ul><li>The projected 5-year and 10-year survival rates for patients with malignant pineal tumors, who received irradiation after tumor resection or underwent radiation therapy alone, were: 95% and 88% for pure germinomas, 80% and 50% for high grade gliomas, 44% and 0% for malignant pineal parenchymal tumors, and 20% and 0% for malignant germ cell tumors, respectively. </li></ul></ul><ul><li>CONCLUSIONS : Benign pineal tumors should be cured with surgery alone . Malignant tumors should be treated with aggressive resection followed with irradiation and chemotherapy . Pure germinomas , which are exquisitely radiosensitive, can be cured by conventional radiation therapy alone. </li></ul>
  63. 63. Jaishri O. Blakeley, MD and Stuart A. Grossman, MD , Management of Pineal Region Tumors , Current Treatment Options in Oncology 2006, 7 :505-516 <ul><li>Accurate histologic diagnosis important to allow rational therapeutic planning. </li></ul><ul><li>Evaluation of a pineal lesion should begin with craniospinal MRI and analysis of the cerebrospinal fluid (CSF). </li></ul><ul><li>Certainty of the histologic diagnosis is now a requirement for treatment in Western nations , some Asian centers continue to recommend a test dose of radiation therapy based on the high incidence of germinoma in those countries. </li></ul><ul><li>If there is high clinical suspicion of a germinoma or tectal glioma, stereotactic or endoscopic biopsy may be pursued. </li></ul><ul><li>All other lesions should be referred for open biopsy with microsurgical techniques. This approach provides adequate tissue for diagnosis, may be curative in low-grade tumors, and may substantially improve survival in patients with malignant tumors. </li></ul>
  64. 64. Jaishri O. Blakeley, MD and Stuart A. Grossman, MD , Management of Pineal Region Tumors , Current Treatment Options in Oncology 2006, 7 :505-516 <ul><li>If open surgery is not desired by the patient or practitioner, stereotactic or endoscopic biopsy may be followed by radiosurgery for localized, well-demarcated tumors. </li></ul><ul><li>Radiation therapy is the first-line therapy for germinomas . </li></ul><ul><li>Evidence of  CSF seeding requires craniospinal radiation and adjuvant chemotherapy regardless of tumor type . </li></ul><ul><li>Diagnosis of any of the malignant tumors (non-germ cell tumors, pineoblastomas, and parenchymal tumors of intermediate determination) also requires craniospinal radiation (with local tumor doses of at least 50 Gy) and adjuvant chemotherapy (generally platinum based). </li></ul><ul><li>Patients with tectal gliomas may undergo excision with or without postoperative radiation; however, they also may be observed with vigilant follow-up alone. </li></ul>
  65. 65. Nishioka, H., J. Haraoka, et al. (2006). &quot;Management of intracranial germ cell tumors presenting with rapid deterioration of consciousness.&quot; Minim Invasive Neurosurg 49 (2): 116-9. <ul><li>Three patients who presented with rapid deterioration of consciousness but resulted in complete remission of the tumor after emergency surgery for both diagnostic (biopsy) and therapeutic (for hydrocephalus) purposes followed by prompt initiation of radiochemotherapy. </li></ul><ul><li>CONCLUSION : </li></ul><ul><ul><li>For management of these rapidly deteriorating patients, immediate histological verification and avoidance of delay in the induction of radiochemotherapy are essential. </li></ul></ul><ul><ul><li>Thus, emergency surgery with a less invasive procedure is the first choice of treatment, i. e., endoscopic surgery for pineal region tumor and CT-guided biopsy for basal ganglia tumor. </li></ul></ul>
  66. 66. Preoperative details <ul><li>Patients presenting with hydrocephalus and radiographic evidence of a malignant pineal region tumor may have their hydrocephalus treated with third ventriculostomy or ventriculoperitoneal (VP) shunt prior to biopsy or resection. </li></ul><ul><li>The staged procedure allows for definitive control of the hydrocephalus prior to surgical resection of lesions suspicious for being malignant. </li></ul>
  67. 67. Preoperative details <ul><li>A similar strategy may be employed for patients with marked symptomatic hydrocephalus and benign-appearing lesions. </li></ul><ul><li>The timing of the second procedure can vary according to the surgeon's preference. </li></ul><ul><li>Peritoneal seeding with shunting is a rare, but well-documented, complication in these patients. </li></ul><ul><li>However, the use of a filter to decrease the incidence of seeding has been associated with frequent shunt malfunctions and generally is not recommended, particularly because third ventriculostomy is a better option </li></ul>
  68. 68. Preoperative details <ul><li>Improved endoscopic techniques have made third ventriculostomy an easy and reliable method to divert CSF. </li></ul><ul><li>As with all CSF diversion procedures, CSF may be acquired and sent for cytologic and biochemical analysis during the case. Third ventriculostomy has the added advantage of potentially allowing for a biopsy during the procedure by endoscopic guidance. </li></ul><ul><li>This provides the opportunity to make an intraoperative diagnosis with subsequent tailoring of further therapy. </li></ul>
  69. 69. Cipri, S., A. Gangemi, et al. (2005). &quot;Neuroendoscopic management of hydrocephalus secondary to midline and pineal lesions.&quot; J Neurosurg Sci 49 (3): 97-106 <ul><li>In 14 select cases, hydrocephalus was secondary to midline and pineal lesions, with a follow-up ranged from 3 months to 5 years after discharge. </li></ul><ul><li>In 9 cases the endoscopic procedure represented the only surgical treatment. </li></ul><ul><li>In 5 cases, microsurgical removal of the lesions and/or ventriculo-peritoneal shunts placement were performed, as additional treatment, </li></ul><ul><li>while adjuvant radiotherapy was utilized in 4 cases; high dose chemotherapy followed by bone marrow transplantation was performed in 3 cases. </li></ul><ul><li>RESULTS : obstructive hydrocephalus secondary to midline and pineal lesions, was successful treated by neuroendoscopic approach alone in 9 cases, with an unremarkable course and good outcome, except in 1 case. </li></ul><ul><li>CONCLUSIONS : Neuroendoscopic approach affords a minimally invasive way to obtain 4 objectives by one-step surgical approach, </li></ul><ul><ul><li>such as resolution of obstructive hydrocephalus by endoscopic third ventriculostomy (ETV), </li></ul></ul><ul><ul><li>cerebrospinal fluid sample to detect tumor markers and to perform cytological analysis, </li></ul></ul><ul><ul><li>biopsy specimens and tissue diagnosis, </li></ul></ul><ul><ul><li>associated to absence of shunt-related complications. </li></ul></ul><ul><li>Therefore, in experienced hands, ETV should be the treatment of first choice, in cases of hydrocephalus secondary to lesions of the pineal gland. </li></ul>
  70. 70. Yamini, B., D. Refai, et al. (2004). &quot;Initial endoscopic management of pineal region tumors and associated hydrocephalus: clinical series and literature review.&quot; J Neurosurg 100 (5 Suppl Pediatrics): 437-41. <ul><li>In six patients with pineal tumors and associated hydrocephalus who underwent an endoscopic biopsy procedure and third ventriculocisternostomy (ETVC) in a single sitting. </li></ul><ul><li>RESULT : The ETVC was successfully performed without complication in all patients; however, a ventriculoperitoneal shunt was eventually required in four. </li></ul><ul><ul><li>Histological diagnosis was successfully established in four patients. </li></ul></ul><ul><li>The authors also reviewed the literature to assess reports involving ETVC and tumor biopsy sampling in patients with pineal tumors and hydrocephalus. </li></ul><ul><ul><li>A total of 54 cases, including those in this study, have been reported. </li></ul></ul><ul><ul><li>Fifteen percent of the patients eventually required placement of a ventricular shunt. </li></ul></ul><ul><ul><li>The transient complication rate was 15% with no death. A positive tissue diagnosis was established in 89% of the cases overall. </li></ul></ul><ul><li>CONCLUSIONS : The authors conclude that the endoscopic management of patients with pineal region masses and hydrocephalus may be a preferred initial strategy. </li></ul>
  71. 71. Intraoperative details <ul><li>In general, surgical approaches to the pineal region can be divided into supratentorial, infratentorial, and a combined supratentorial-infratentorial approach. </li></ul><ul><li>Supratentorial approaches include the parietal-interhemispheric approach described by Dandy (1936) and the occipital-transtentorial approach originally described by Horrax, later modified by Poppen. </li></ul>
  72. 72. Koziarski, A., E. Skrobowska, et al. (2003). &quot;[Own experience in surgical treatment of the pineal region and midbrain tumors via the infratentorial approach].&quot; Neurol Neurochir Pol 37 (2): 473-84. <ul><li>Nine cases of tumours located in the pineal and midbrain region in adults operated on between November 1998 and July 2002 </li></ul><ul><li>The histopathological examination revealed </li></ul><ul><ul><li>anaplastic pinealoma in 2 cases, </li></ul></ul><ul><ul><li>and pineocytoma, pineal cyst, mesencephalic glial cyst, protoplasmatic astrocytoma, epidermoid cyst, unclear glial scar, and papillary ependymoma in single cases. </li></ul></ul><ul><li>Occipito-suboccipital osteoplastic craniotomy was performed in each case and tumours were totally removed microsurgically via the infratentorial epicerebellar approach. </li></ul><ul><li>All the patients improved significantly and resumed their previous life activities. </li></ul><ul><li>Three patients with pineal tumours and one with a small postoperative ependymoma recurrence were irradiated after the surgery. </li></ul><ul><li>CONCLUSION : Very good results of the surgical treatment of tumours in this area suggest that such patients should be referred earlier to one stage surgical management , as the procedure is easier to perform and shunt implantation may be avoided. </li></ul>
  73. 73. Postoperative details <ul><li>Once the physician makes a diagnosis of malignant tumor from tissue acquired intraoperatively, the surgeon is obligated to evaluate the patient for spinal metastasis. </li></ul><ul><li>Prior to widespread use of the MRI, patients' disease was staged postoperatively with CT myelogram. </li></ul><ul><li>Currently, the most sensitive radiographic modality for screening is a complete spinal MRI with and without gadolinium. </li></ul><ul><li>The first MRI scan should be timed at least 2 weeks after surgery because spinal canal enhancement can occur in the early postoperative period. </li></ul>
  74. 74. Postoperative details <ul><li>Equivocal findings on the initial postoperative scan warrant a repeat scan within 1-2 weeks. </li></ul><ul><li>Radiographic artifacts secondary to surgery regress while drop metastasis remain stable or increase in size over time. </li></ul><ul><li>The role for postoperative lumbar puncture and subsequent CSF analysis for cytology is questionable. </li></ul><ul><li>The presence of abnormal cells postoperatively does not correlate well with spinal metastasis due to spillage during surgery . </li></ul>
  75. 75. Follow-up care <ul><li>Life-long follow-up of children with pineal region tumors is required. These tumors can recur locally or appear distally as late as 5 years after diagnosis. In addition, patients can present later in life with new tumor formation (eg, meningioma). </li></ul><ul><li>MRI scans should be obtained on a periodic basis as determined by tumor histology of original diagnosis, extent of resection, and presence of metastasis at time of diagnosis. </li></ul><ul><li>Tumor marker studies for patients with germ cell tumors should be performed also on a periodic basis, even if markers were not abnormal at diagnosis. </li></ul>
  76. 76. The Management of Pineal Area Tumors: A Recent Reappraisal PAUL H. CHAPMAN, MD,* AND RITA M. LINGGOOD, MDt, Cancer 46:1253-1257, 1980. <ul><li>22 patients with pineal area tumors from 1972 through 1977. </li></ul><ul><li>Eleven identified tumors included: three gliomas, three pineoblastomas, two endodermal sinus tumors, one germinoma, one epidermoid, and one metastasis. Three others were presumptively germinomas. </li></ul><ul><li>Twelve cases were treated by means of radiation and shunting if necessary. </li></ul><ul><li>Eight patients underwent direct surgery and then radiotherapy if appropriate. </li></ul><ul><li>There were 6 deaths from recurrence. </li></ul><ul><li>Death occurred in spite of radiologic evidence of radiation response. </li></ul><ul><li>Cerebrospinal fluid (CSF) cytology was positive in 2 of 7 cases involving potentially disseminating tumors and negative in 2 cases involving spinal metastases. </li></ul><ul><li>CONCLUSION: Radiation response and CSF cytology are insufficient to determine optimum treatment. </li></ul><ul><li>Direct operations, which were got associated with mortality or serious morbidity were most useful for providing a tissue diagnosis. </li></ul>
  77. 77. OUTCOME AND PROGNOSIS <ul><li>The prognosis for patients with pineal region tumors is dependent upon tumor histology and is subject to change as more effective adjuvant therapy is developed. </li></ul><ul><li>In general, patients with intracranial germinomas have an excellent prognosis because of the radiosensitivity of these tumors. </li></ul><ul><li>Children with nongerminomatous germ cell tumors have a significantly worse prognosis than do children with germinomas or pineal cell tumors. </li></ul><ul><li>No conventional approach is designed for managing recurrence . Chemotherapy, radiotherapy, or radiosurgery can be applied if maximal doses have not already been administered. </li></ul><ul><li>A second surgical procedure generally is reserved for patients with benign lesions who demonstrate recurrence several years later. </li></ul>
  78. 78. OUTCOME AND PROGNOSIS <ul><li>Recurrent germ cell tumors have been shown to respond to chemotherapy, as have some pineal cell tumors, although to a lesser degree. </li></ul><ul><li>Radiosurgery may be a consideration for all recurrences less than 3 cm in diameter. </li></ul>
  79. 79. Thank You

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