Intracavitary Radiation for Cystic Craniopharyngiomas

15   Intracavitary Radiation for Cystic Craniopharyngiomas


L. Dade Lunsford, Ajay Niranjan, Hideyuki Kano, Peter Kang, and Douglas Kondziolka




Despite the major advances of skull base microsurgical techniques, as well as expanded endoscopic techniques, craniopharyngiomas continue to be difficult to remove totally with acceptable morbidity. Ideally, surgical techniques result in total removal, maintenance of visual function, sparing of endocrinologic loss, and absence of delayed recurrence. Even when feasible, radical resection continues to be associated with unsatisfactory long-term outcomes, often because of residual neurobehavioral disorders, cognitive impairment, the long-term need for replacement hormone therapy, and hypothalamic obesity.


Realizing the morbidity of surgical techniques for craniopharyngioma in the early 1950s, both Leksell et al and Wycis et al proposed the implantation of a β-emitting isotope into cystic craniopharyngiomas.1,2 Isotope implantation was designed to lead to slow involution of the cyst wall by delivery of a tumoricidal dose to the thin epithelial layer of the cyst. Since that time, selected pioneers in Europe have continued to apply the instillation of radioactive isotopes into craniopharyngioma cysts. Efforts in Europe, especially in Stockholm under the direction of Erik-Olof Backlund, demonstrated that intracavitary irradiation provides an effective and safe technique in the management of cystic craniopharyngiomas.35 Leksell and Backlund used both radioactive phosphorus 32 (in colloidal chromic solution) and yttrium 90.1,3 In the United States, the unavailability of 90Y has led to the primary use of 32P. Stereotactic insertion of the isotope with fine-needle technique is critical.


images Rationale for Intracavitary Irradiation


The treatment of cystic brain tumors using radioactive isotopes is based on the concept that continued cyst enlargement is the result of secretion from the thin epithelial cyst layer. Most craniopharyngiomas in fact have solid components, and subsequently develop cystic changes over the course of time. The cyst gradually enlarges like a bubble blown off a piece of bubblegum. By the time of clinical presentation, the cyst may range in volumes as small as 1 mL to as large as 126 mL. Depending upon its location and volume, the enlarging cyst results in endocrine loss, progressive visual dysfunction, and neurocognitive and intellectual deficits.


Intracavitary irradiation uses stereotactic precision to puncture the cyst and instill the isotope volume designed to deliver 180 to 250 Gy of radiation over five half-lives of the isotope.68 Because the half-life of 32P is 14 days, it takes ~70 days to deliver the full isotope effect. As a pure β emitter, the falloff of radiation from the decay of the isotope is very steep. The radiation dose falls off in accordance with the inverse square law, which refers to the fact that reduction in activity is proportional to 1 divided by the square of the distance from the source. The half-value tissue penetrance of 32P is 0.9 mm, indicating that most of the radiation effect by far is delivered within several millimeters of the cyst wall. Implantation of the isotope leads to a “coating out” of the internal cyst wall and slow delivery of the radiobiological effect of the 32P decay. This dose range appears to be sufficient to lead to cyst involution in the vast majority of cases. Long-term outcome studies from multiple centers are now available to demonstrate the benefit of intracavitary management of cystic craniopharyngiomas. Because current magnetic resonance imaging (MRI) confirms that most patients have solid and cystic tumors, many will require multimodality management. Successful strategies require cyst control, solid tumor management by microsurgery or endoscopic surgery, and stereotactic radiosurgery.9,10 A combination of such techniques may be best to achieve the best outcomes for patients with these strategically located tumors capable of producing visual, endocrinologic, and cognitive dysfunction.


imagesInitial Experience


After the primary author returned from his Van Wagenen–sponsored fellowship at the Karolinska Institute in 1981, an initial, cautious trial of the role of intracavitary radiosurgery was pursued at the University of Pittsburgh Center for Image-Guided Neurosurgery. In the 28-year interval from 1980 to 2003, 61 patients with craniopharyngioma (33 males and 28 females) underwent intracavitary radiation after the initial diagnosis or recognition of a recurrent craniopharyngioma.6 All patients had their tumor confirmed initially (before 1991) with computed tomography (CT) and with magnetic resonance imaging (MRI) afterward. The ages of the patients in this initial experience ranged from 4 to 74 years (mean, 28 years), and the calculated cyst volumes ranged from 1.8 to 126 mL. All patients underwent preoperative endocrinologic assessment, visual acuity and formal visual field examinations, and overall neurologic assessment. The majority of the patients had undergone multiple prior surgical procedures, including one or more craniotomies and transsphenoidal resection, and seven patients had had ventriculoperitoneal shunts placed for hydrocephalus management. Fractionated external beam radiation therapy, the role of which has declined over the last 10 years, had been previously administered to 11 patients.


imagesStereotactic Technique for Intracavitary Irradiation


We select patients with monocystic or multicystic craniopharyngiomas. After review of the preoperative CT scan or MRI, we can estimate the cyst volume for the nuclear pharmacist. Using a simple calculation, π/6× (X × Y × Z), we determine the volume of an oblate spheroid. X, Y, and Z are the diameters of the lesion in the three cardinal planes; × denotes multiplication. The nuclear pharmacist orders colloidal chromic phosphate 32P in a stock solution dose. This is assayed on the day of delivery and reassayed on the day of the operation. If the cyst volume is less than 20 cm3, the suspension is usually diluted with a 30% glucose solution to facilitate delivery of the isotope.


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Fig. 15.1 In the transfrontal stereotactic approach to a suprasellar cystic craniopharyngioma, the twist drill craniostomy is placed near the coronal suture, and fine-needle technique (0.9-mm outerdiamenter needle) is used to puncture the cyst (as depicted in a drawing by Erik-Olof Backlund, a pioneer in stereotactic techniques and disciple of Lars Leksell).


All patients are brought to the operating room for the surgical procedure, which is done under mild conscious sedation. The Leksell Model G stereotactic head frame (Elekta Instruments, Stockholm, Sweden) is attached to the patient’s head with the use of local anesthesia. Highresolution axial CT (2.5-mm configured axial slices, 512 × 512 matrix) is performed with a dedicated intraoperative CT scanner in our image-guided operating room suite. The cyst area in square centimeters is calculated on each slice by tracing the cyst volume after intravenous iodinated contrast is administered. The sum of each slice is then multiplied by the slice thickness (2.5 mm) to calculate the cystic tumor volume in cubic centimeters. The calculated cyst volume is called to the nuclear pharmacist, who prepares the isotope and calculates the volume of P32 necessary to provide a dose of 180 to 250 Gy over five half-lives (~70 days).


The patient is advanced through the opening of the CT scanner, and the head is prepared with alcohol and draped. A frontal coronal suture twist drill craniostomy is performed with the arc attached at the chosen X, Y, and Z coordinates for a central puncture of the cyst. The trajectory is plotted in advance to reduce the number of pial transgressions and, when feasible, the ventricular entry. The target point is usually 7 to 10 mm inferior to the dorsal margin of the cyst, as it is sometimes necessary to puncture the cyst sharply and depress the cyst briefly before the 0.9-mmouter-diameter sharp-tipped needle is inserted into the center of the cyst (Fig. 15.1). The 0.9-mm sharp-tipped needle is passed through a 15-cm stabilizing cannula after closed-skull percutaneous twist drill craniostomy and puncture of the dura. Once the target is reached, the stylet is removed and a three-way stopcock is attached (Fig. 15.2). Using a tuberculin syringe, we generally withdraw 1 mL of cyst fluid. A neuropathologist examines the fluid with polarized light microscopy to detect cholesterol crystals. Two tuberculin syringes are attached to the three-way stopcock (Fig. 15.3). The nuclear pharmacist and the radiation safety officer deliver the calculated volume of 32P, usually in the range of 0.6 to 0.8 mL. The isotope contained in the syringe is injected through the stopcock into the cyst, and a barbotage method is used to ensure mixture. After this, the residual isotope is flushed out of the needle with 0.2 mL of sterile saline.


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Fig. 15.2 Once the target is reached, the fine-needle stylet is removed and a three-way stopcock is attached to the needle hub. A tuberculin syringe is used to withdraw generally 1 mL of cyst fluid, which is sent to neuropathology to assess for the presence of cholesterol crystals under polarized light microscopy.


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Fig. 15.3 Phosphorus 32 is injected into the cyst after attachment of a tuberculin syringe containing the predetermined amount of isotope, designed to deliver 250 Gy to the internal cyst wall over five half-lives of isotope decay (70 days). The isotope and cyst fluid are mixed by a barbotage method of withdrawal and the injection repeated five or more times. After this, 0.2 mL of sterile saline is injected via the other stopcock port to clear the needle of remaining isotope. The needle and stopcock are cleared of the isotope by the radiation safety officer, and that activity is subtracted from the calculated amount delivered to provide a final isotope volume.


The goal is to restore the cyst volume to that of the original calculation. Collapse of the cyst induces a potential for internal wrinkling, which may suboptimally cause areas of the wrinkled cyst wall to receive an insufficient therapeutic dose of the β-emitting isotope. After the final isotope injection, the residual activity of 32P (as well as all instruments and supplies used) is assayed by the nuclear pharmacist. Any activity is subtracted from the dose administered to the patient. Using our intraoperative CT, we do an immediate postoperative head scan and usually observe a small air bubble at the anterior margin of the cyst (the patients are supine on the CT scanner table). All patients are kept in the hospital for a one-night stay. In our experience, the mean radiation dose delivered is 224 Gy (range, 189–250 Gy to the cyst wall). The median cyst volume is 7.0 cm3 (range, 2.0–20 cm3).


imagesFollow-up


Clinical follow-up and imaging are obtained from each patient and the referring physicians. When possible, patients are contacted by telephone to determine their long-term outcomes. CT or MRI studies are normally performed at 3 months after the procedure and at quarterly intervals during the first year. In the next 5 years, they are requested annually. Formal neuro-ophthalmologic evaluations, as well as periodic endocrinologic assessments, are also performed.


imagesResults


In this review of 61 patients treated before 2008, 12 of the 61 patients eventually died as a result of tumor progression and eight were lost to follow-up (Table 15.1). The mean follow-up interval after diagnosis was 82 ± 14 months (47 ± 8 months after intracavitary irradiation). Actuarial survival rates after diagnosis were 90% at 5 years and 80% at 10 years. We noted a trend toward increased survival in children younger than 16 years of age. Among 53 patients who had long-term follow-up, treatment with 32P intracavitary irradiation was considered to have failed in eight. The results of cyst response after intracavitary irradiation are shown in Table 15.2. In 15 patients with predominantly mono- or multicystic tumors, 80% of the tumors became smaller after treatment. In 37 patients with mixed solid and cystic tumors, 65% of the tumors became smaller after treatment. Cystic control was not associated with the patient’s sex or age, tumor type (ie, mono- or multicystic tumor, mixed tumor with solid components), primary versus adjuvant treatment, cyst volume, radiation dose, preoperative visual acuity or field, or preoperative pituitary function. During follow-up, six patients developed new cystic tumors. Illustrative cases of tumor reduction are shown (Figs. 15.4 and 15.5).


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imagesAdditional Treatment


Among the 53 patients with long-term follow-up, treatment with intracavitary radiation failed in eight. Seventeen patients (32%) required additional cyst aspiration after intracavitary irradiation because of persistent symptoms related to larger cyst volume (Fig. 15.6). The median interval between intracavitary irradiation and additional cyst aspiration was 0.5 months (range, 0.2–18 months). Early cyst decompression is especially important in patients with progressive optic neuropathy. Although spontaneous cyst regression is the rule, it may take several months. Early cyst aspiration at 2 to 6 weeks after implantation may be necessary to achieve the best early response. In such patients, the procedure is repeated with stereotactic technique. After cyst puncture with fine-needle technique, we gently aspirate approximately one-half of the calculated volume. We assay the fluid to make sure that no significant isotope has been removed. Even if planned reaspiration is performed within 2 weeks of the 32P instillation, a relatively small percentage of isotope can be recovered as it presumably adheres to the internal cyst wall.


imagesClinical Response


Among our patients who underwent primary management with intracavitary irradiation for a monocystic craniopharyngioma, 48% had improved visual acuity and 52% had improved visual fields. Among patients who were treated as part of a multimodality strategy (intracavitary irradiation was an adjuvant strategy), 28% had improved visual acuity and 25% had improved visual fields (Tables 15.3 and 15.4). Three patients developed the new onset of visual abnormalities despite documented tumor regression. One of these patients underwent stereotactic radiosurgery to the solid component of the residual tumor. In these patients, visual dysfunction was thought to be related to a potentially adverse effect of 32P irradiation.


imagesEndocrinologic Response


Among patients treated with primary monocystic intracavitary irradiation, 52% continue to have normal pituitary function, but 48% have had one or more axes of pituitary function loss. In the adjuvant treatment group, only 19% of patients had preserved endocrine function before the procedure, and 81% had documented loss of pituitary function in one or more axes. Three patients developed pituitary dysfunction as a consequence of cystic recurrence. Four patients developed diabetes insipidus after treatment with 32P intracavitary radiation.


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Fig. 15.4 Coronal gadolinium-enhanced MRI obtained in a 14-year-old boy with a cystic craniopharyngioma, intrasellar and suprasellar in location, compressing the overlying optic apparatus at the time of stereotactic P32 intracavitary irradiation as initial treatment (left). Coronal gadolinium-enhanced MRI obtained three months after stereotactic P32 irradiation, revealing reduction in the cystic tumor (center). Coronal gadolinium-enhanced MRI obtained three years after P32 irradiation, revealing complete cyst regression (right).


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Fig. 15.5 Sagittal and coronal gadolinium-enhanced MRI obtained in a 5-year-old boy with a mixed solid and cystic craniopharyngioma, intrasellar and suprasellar in location, compressing the overlying optic apparatus at the time of stereotactic intracavitary irradiation as an initial treatment (top). Sagittal and coronal gadolinium-enhanced MRI obtained 2 years after stereotactic irradiation, revealing marked reduction in the cystic portion of the tumor (bottom).


imagesOther Complications


In our total 28-year experience, only one patient developed an early postoperative complication. A patient with a mixed multicystic and solid craniopharyngioma underwent multiple endoscopic skull base procedures but developed a tumor cyst of the third ventricle. Before the planned procedure, the cyst spontaneously ruptured into the ventricle and decompressed. However, within a matter of months, the cyst reformed, and intracavitary stereotactic irradiation was performed. Several days after this procedure, the patient was readmitted with headache, low-grade fever, stiff neck, and cerebrospinal fluid (CSF) pleocytosis. No radioactivity was confirmed in the CSF. The patient had an aseptic meningitic reaction that resolved with corticosteroids. This patient has undergone additional surgical procedures followed by gamma knife stereotactic radiosurgery.9,10


imagesDiscussion


Patients who are eligible for radical gross total resection of a craniopharyngioma may have the best long-term response in terms of tumor control.1119 However, such patients often pay a significant price that may include endocrinologic, cognitive, behavioral, and visual difficulties.20,21 Craniopharyngiomas remain one of the most difficult tumors for neurosurgeons to manage. For patients, the side effects of surgery are often significant. Because of the attachment of these tumors to critical neurovascular, endocrine, and visual structures, patients are often unable to undergo radical resection with an acceptable morbidity. For most of these patients, multimodality management, administered over the course of years, is frequently necessary.10,22 The options for craniopharyngioma management include fractionated radiation therapy,22 cyst management with intracavitary irradiation, intracystic chemotherapy with bleomycin,2328 endoscopic resection, and, more recently, phase I trials with interferon.


Because craniopharyngiomas frequently are detected in childhood, we generally try to withhold conventional fractionated radiation therapy, even when it can be administered with modern techniques of image-guided radiation therapy.22 Intracavitary irradiation with 32P is an additional tool for treating patients with cystic craniopharyngiomas. Using modern imaging techniques, we find that most patients have a solid, small tumor component with one or more cysts arising from it. Intracavitary irradiation provides symptomatic cyst control in a high percentage of patients, but it does not solve the ultimate progression of the solid component of the tumor. It also does not prevent the formation of new tumor cysts. In such patients, repeat surgery or stereotactic radiosurgery may be necessary.9,10


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Fig. 15.6 Surgical procedures before and after P32 intracavitary irradiation in patients with cystic craniopharyngioma. In a comparison of the numbers of procedures performed before and after intracavitary radiation, the number of additional procedures tended to decrease after intracavitary radiation.


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The continuing goals for the management of craniopharyngioma include preservation of visual and endocrine function and reduction in the risk for delayed cognitive dysfunction. Intracavitary irradiation with 32P has more than a 60-year history and remains a valuable tool. The use of this tool requires training and expertise, as emphasized by Leksell et al1 and Backlund.3 Access to pure β emitters is critical to the successful continued management of tumor cysts when they develop. The need for delayed stereotactic aspiration with precise frame-based imaging guidance, especially when tumors are wrapped around critical vascular and optic nerve structures, is critical.


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imagesConclusion


Stereotactic 32P intracavitary irradiation has a relatively low risk. It is an effective strategy for the primary treatment of monocystic craniopharyngiomas and for the adjuvant management of the cystic component of multicystic or mixed solid craniopharyngiomas. Craniopharyngiomas are one of the most difficult tumors that neurosurgeons encounter. Efforts to minimize morbidity from the tumor or from its treatment can reduce the significant dysfunction that patients with cranopharyngioma experience. Minimally invasive treatment strategies that pursue the goals of cognitive, endocrine, and vision preservation remain critical to the long-term successful management of these patients.


References


  1. Leksell L, Backlund EO, Johansson L. Treatment of craniopharyngiomas. Acta Chir Scand 1967;133(5):345–350
  2. Wycis HT, Robbins R, Spiegeladolf M, Meszaros J, Spiegel EA. Studies in stereoencephalotomy III; treatment of a cystic craniopharyngioma by injection of radioactive P32. Confin Neurol 1954;14(4):193–202
  3. Backlund EO. Studies on craniopharyngiomas. 3. Stereotaxic treatment with intracystic yttrium-90. Acta Chir Scand 1973;139(3):237–247
  4. Van den Berge JH, Blaauw G, Breeman WA, Rahmy A, Wijngaarde R. Intracavitary brachytherapy of cystic craniopharyngiomas. J Neurosurg 1992;77(4):545–550
  5. Voges J, Sturm V, Lehrke R, Treuer H, Gauss C, Berthold F. Cystic craniopharyngioma: long-term results after intracavitary irradiation with stereotactically applied colloidal beta-emitting radioactive sources. Neurosurgery 1997;40(2):263–269, discussion 269–270
  6. Hasegawa T, Kondziolka D, Hadjipanayis CG, Lunsford LD. Management of cystic craniopharyngiomas with phosphorus-32 intracavitary irradiation. Neurosurgery 2004;54(4):813–820, discussion 820–822
  7. Lunsford LD, Pollock BE, Kondziolka DS, Levine G, Flickinger JC. Stereotactic options in the management of craniopharyngioma. Pediatr Neurosurg 1994;21(Suppl 1):90–97
  8. Pollock BE, Lunsford LD, Kondziolka D, Levine G, Flickinger JC. Phosphorus-32 intracavitary irradiation of cystic craniopharyngiomas: current technique and long-term results. Int J Radiat Oncol Biol Phys 1995;33(2):437–446
  9. Chiou SM, Lunsford LD, Niranjan A, Kondziolka D, Flickinger JC. Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after surgery, with or without radiation therapy. Neurooncol 2001;3(3):159–166
  10. Niranjan A, Kano H, Mathieu D, Kondziolka D, Flickinger JC, Lunsford LD. Radiosurgery for craniopharyngioma. Int J Radiat Oncol Biol Phys 2010;78(1):64–71
  11. Abe T, Lüdecke DK. Transnasal surgery for infradiaphragmatic craniopharyngiomas in pediatric patients. Neurosurgery 1999;44(5):957–964, discussion 964–966
  12. Duff JM, Meyer FB, Ilstrup DM, Laws ERJ, Schleck CD, Scheithauer BW. Long-term outcomes for surgically resected craniopharyngiomas. Neurosurgery 2000;46(2):291–302, discussion 302–305
  13. Fahlbusch R, Honegger J, Paulus W, Huk W, Buchfelder M. Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 1999;90(2):237–250
  14. Honegger J, Buchfelder M, Fahlbusch R. Surgical treatment of craniopharyngiomas: endocrinological results. J Neurosurg 1999;90(2):251–257
  15. Isaac MA, Hahn SS, Kim JA, Bogart JA, Chung CT. Management of craniopharyngioma. Cancer J 2001;7(6):516–520
  16. Kalapurakal JA, Goldman S, Hsieh YC, Tomita T, Marymont MH. Clinical outcome in children with recurrent craniopharyngioma after primary surgery. Cancer J 2000;6(6):388–393
  17. Khafaga Y, Jenkin D, Kanaan I, Hassounah M, Al Shabanah M, Gray A. Craniopharyngioma in children. Int J Radiat Oncol Biol Phys 1998;42(3):601–606
  18. Kim SK, Wang KC, Shin SH, Choe G, Chi JG, Cho BK. Radical excision of pediatric craniopharyngioma: recurrence pattern and prognostic factors. Childs Nerv Syst 2001;17(9):531–536, discussion 537
  19. Wang KC, Kim SK, Choe G, Chi JG, Cho BK. Growth patterns of craniopharyngioma in children: role of the diaphragm sellae and its surgical implication. Surg Neurol 2002;57(1):25–33
  20. Caldarelli M, di Rocco C, Papacci F, Colosimo C Jr. Management of recurrent craniopharyngioma. Acta Neurochir (Wien) 1998;140(5):447–454
  21. Fisher PG, Jenab J, Goldthwaite PT, et al. Outcomes and failure patterns in childhood craniopharyngiomas. Childs Nerv Syst 1998;14(10):558–563
  22. Habrand JL, Ganry O, Couanet D, et al. The role of radiation therapy in the management of craniopharyngioma: a 25-year experience and review of the literature. Int J Radiat Oncol Biol Phys 1999;44(2):255–263
  23. Cavalheiro S, Sparapani FV, Franco JO, da Silva MC, Braga FM. Use of bleomycin in intratumoral chemotherapy for cystic craniopharyngioma. Case report. J Neurosurg 1996;84(1):124–126
  24. Hader WJ, Steinbok P, Hukin J, Fryer C. Intratumoral therapy with bleomycin for cystic craniopharyngiomas in children. Pediatr Neurosurg 2000;33(4):211–218
  25. Haisa T, Ueki K, Yoshida S. Toxic effects of bleomycin on the hypothalamus following its administration into a cystic craniopharyngioma. Br J Neurosurg 1994;8(6):747–750
  26. Hetelekidis S, Barnes PD, Tao ML, et al. 20-year experience in childhood craniopharyngioma. Int J Radiat Oncol Biol Phys 1993;27(2):189–195
  27. Jiang R, Liu Z, Zhu C. Preliminary exploration of the clinical effect of bleomycin on craniopharyngiomas. Stereotact Funct Neurosurg 2002;78(2):84–94
  28. Savas A, Arasil E, Batay F, Selcuki M, Kanpolat Y. Intracavitary chemotherapy of polycystic craniopharyngioma with bleomycin. Acta Neurochir (Wien) 1999;141(5):547–548, discussion 549

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Feb 8, 2017 | Posted by in NEUROSURGERY | Comments Off on Intracavitary Radiation for Cystic Craniopharyngiomas

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