Impactos ambientales y medidas de protección

• _{Medical management to suppress pituitary hyperfunction with drugs such as}

bromocriptine (a dopamine agonist), cyproheptadine hydrochloride (Periactin),

mitotane (Lysodren), and octreotide acetate (Sandostatin) is used as primary therapy, and provides temporary control or remission while awaiting the slower but permanent response of irradiation.

Surgical Management

• _{Transsphenoidal microsurgery, effective in selective removal of microadenomas, also}

is used for adenomas extending outside the sella.

• _{Contraindications include dumbbell-shaped adenomas with constriction at}

diaphragma sellae, lateral suprasellar extension, massive suprasellar tumor, and incompletely pneumatized sphenoid.

• _{Delayed surgical complications may occur.}

• Anterior pituitary function may be affected with nonfunctioning adenomas.

• Excellent vision improvement occurs with surgery alone.

• _{Recurrence may be delayed by many years in larger tumors, but the recurrence rate}

is high with surgery alone.

Radiation Therapy

• Radiation therapy is effective in controlling hypersecretion and neoplastic or mass

effects of large or recurrent tumors (9,11,17–19).

• _{External irradiation controls hypersecretion in approximately 80% of patients with}

acromegaly, 50% to 80% of those with Cushing's disease, and one-third of those with hyperprolactinemia (1).

• _{Normalization of circulating hormone levels requires anywhere from a few months to}

several years for acromegaly, and approximately 3 months to 1 year for Cushing's disease.

• Primary radiation therapy is often effective to control mass effects of larger tumors, but in general, it is preferable to perform a biopsy, decompress the optic chiasm, and irradiate postoperatively to prevent recurrence.

• External irradiation is used to treat tumors that are recurrent after primary surgery

(10).

• _{Reirradiation is sometimes used for recurrences (13).}

• _{In contrast to conventional irradiation, proton and} α_{-particle irradiation and}

implantation of radioactive sources (yttrium 90 or gold 198) deliver very large doses to highly restricted volumes within the pituitary gland; thus, their application is limited to small, essentially intrasellar tumors.

• _{Stereotactic radiosurgery has been used on a limited basis (16).}

• In acromegaly, posttreatment GH values of less than 10 ng per ml indicate a successful response to therapy. GH levels should be followed to predict tumor recurrence.

• _{With prolactin-secreting tumors, the objective is to lower the prolactin level to the}

normal range.

• Plasma and urine steroids and plasma adrenocorticotrophic hormone levels measure

evaluation of the response to therapy in Cushing's disease.

• _{For all patients treated for pituitary tumors, periodic assessment of gonadal, thyroid,}

and adrenal function is necessary because hypopituitarism may occur as a result of irradiation or surgery. Patients treated with irradiation may develop hypopituitarism a number of years after treatment.

Radiation Therapy Techniques

• _{All diagnostic evidence, including that from tomograms, arteriograms, and magnetic}

resonance imaging and computed tomography scanning, as well as clinical and surgical findings, should be combined to define the tumor volume.

• Computed tomography simulation helps define the treatment volume, which should

be slightly larger to include a margin for error in estimation of tumor volume and variation in daily setup.

• For well-defined adenomas, the uncertainty of margin is small; with invasive tumors,

there is greater uncertainty. This must be considered in determining the volume to be included, whether the extension is into the sphenoid, or into intracranial structures.

• _{Variability of setup should be no more than 2 or 3 mm. To ensure accuracy and}

reproducibility, the patient's head must be fixed. Use of three localizing light or laser beams permits easy repositioning.

• _{Both lateral and sagittal beam-check films must be obtained at the beginning of}

therapy and periodically thereafter.

• The technique should be designed to restrict the high-dose region to the treatment

volume.

• _{Special care must be taken to avoid exposure to the eyes; this requires observation}

of the actual setup on the treatment machine by the radiation oncologist. Radiopaque markers, placed on the contralateral eye when field verification films are taken, document the location of the eye with respect to the radiation beam. The eye is approximately 25 mm in length, and the lens lies in the anterior 1 cm.

• _{Volume treated includes the pituitary fossa and adjacent tissues, as determined by}

evaluation of extent of the adenoma.

• _{In general, portals 5 × 5 cm to 6 × 6 cm, or shaped fields 5 to 6 cm in diameter, are}

used. Parallel-opposed lateral portals are used.

• _{Fifteen-degree wedges, with the heel placed anteriorly, assist in obtaining a more}

homogeneous dose distribution and in decreasing the dose delivered to the optic chiasma.

• _{With photon energies below 10 MV, it is strongly recommended that a vertex field be}

used to decrease the irradiation dose to the temporal lobes. To localize this portal, the patient is placed in the supine position, with head flexed and chin close to the lower neck. A beam entering through the vertex of the head, at approximately the midline of the hairline, is directed posteriorly to pass approximately 1 cm behind the posterior clinoid processes (Fig. 16-2). Even with higher-energy photons, the vertex portal is recommended to optimize the dose distribution.

• _{Daily dose is 1.8 to 2.0 Gy; total dose is 45 to 50 Gy. For masses larger than 2 cm,}

we administer 54 Gy.

• _{Guidelines for treatment are shown in Table 16-2.}

• Isodose curves for 4- and 18-MV photons using bilateral fixed wedges and a vertex

field are shown in Figure 16-3.

• _{Use of two fixed parallel-opposed fields yields poor isodose distributions and should}

be avoided.

• Other techniques include bilateral coaxial wedge fields plus a coronal field, moving

• With very large tumors, two bilateral coaxial fields occasionally may be used;

however, this technique generally is discouraged because it delivers an unnecessarily high irradiation dose to the temporal lobes.

View Figure

View Figure

Fig. 16-2: A: Lateral simulation film illustrates portal used for external irradiation of pituitary adenoma.

Arrow indicates plane of rotation. B: Localization film on therapy machine. C: Lateral view of head illustrates position and angle of beam for frontal/vertex portal, similar to radiographic Towne's

projection. (From Paris DQ. Craniographic positioning with comparison studies. Philadelphia: FA Davis Co, 1983.) D: Simulation film of anteroposterior vertex portal (similar to Towne's projection in

diagnostic radiology) that can be used to deliver a portion of the dose without irradiating temporal lobes. E: Portal verification film of frontal/vertex portal illustrates path of beam. Film is obtained by placing it in a cassette on the side of the patient's head and exposing the film with a few monitor units; the patient is removed from the linear accelerator couch, and the couch is positioned so that the cassette is in the central axis of the frontal/vertex field beam. A second exposure with a few monitor units is obtained, and the film is processed. (From Grigsby PW. Pituitary. In: Perez CA, Brady LW, eds.

Principles and practice of radiation oncology, 3rd ed. Philadelphia: Lippincott–Raven, 1998:829–848,

View Figure

Fig. 16-3: Three-portal arrangement with open vertex and two lateral 15-degree wedged fields using 4-MV (A) or 18-MV (B) photons. SAD, source-axis-distance. (From Grigsby PW. Pituitary. In: Perez CA, Brady LW, eds. Principles and practice of radiation

oncology, 3rd ed. Philadelphia: Lippincott–Raven, 1998:829–848, with permission.) Postoperative Radiation Therapy

• Radiation therapy after transsphenoidal resection is effective for primary therapy of

acromegaly.

• _{When selective resection is possible, the surgical procedure has the advantage of a}

rapid response and a low rate of hypopituitarism.

Stereotactic Radiosurgery

• Stereotactic radiosurgery with the gamma knife delivers focused radiation from a

cobalt-60 source to a pituitary tumor in a single session, with minimal radiation to the adjacent normal brain tissue. Approximately 16 Gy and 30 Gy can be delivered to nonfunctioning tumors and functioning tumors, respectively. Tumor control is near 100%. The radiation dose to the optic chiasm should be limited to less than 10 Gy. The neuronal and vascular structures running in the cavernous sinus are much less

radiosensitive, allowing an ablative dose to be administered to tumors showing lateral invasion and impinging on cranial nerves III, IV, V, and VI (7,14).

Table 16-2: Guidelines for treatment at Radiation Oncology Center, Mallinckrodt Institute of Radiology

Irradiation alonea

Cushing's disease 45–50 Gy

Microadenomas 50 Gy (or transsphenoidal resection)

Macroadenomas 50–54 Gy (medically operable)

Postoperative irradiationa

Invasive disease 50 Gy

Incomplete resection 54 Gy

a

1.8 Gy per day.

From Grigsby PW. Pituitary. In: Perez CA, Brady LW, eds. Principles and practice of radiation

oncology, 3rd ed. Philadelphia: Lippincott–Raven, 1998:829–848, with permission.