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TREATMENT OF ADENOID CYSTIC CARCINOMA OF THE SALIVARY GLAND, A THREE-FIELD TECHNIQUE
SHARONM. HUMMEL, R.T.T.,C.M.D., THOMAS
GEORGEE.LARAMORE,M.D.,PH.D. University of Washington Cancer Center, 1959 N.E. Pacific Street, Seattle, Washington
98 195, U.S.A.
Abstract-Clinical trials have demonstrated that fast neutron radiotherapy is the treatment of choice for advanced inoperable salivary gland tumors. A three-field technique utilizing a medically dedicated cyclotron to produce fast neutrons is described for the treatment of adenoid cystic carcinoma of the parotid. This three-field technique utilizes the cyclotron’s multi-leaf collimator system to treat large asymmetric fields, which spare normal tissues otherwise treated with conventional wedged pair techniques. Field geometry, field weightings, and beam normalization will be discussed in relation to this three-dimensional treatment volume. Key Words: Adenoid
cystic carcinoma,Neutronradiotherapy,Muhikaf collimator,Treatmentpiarming.
nique it is difficult to avoid irradiating the contralatera1 eye, spare the contralateral parotid, and minimize the dose to normal brain tissue, yet treat the required target volume. Even with adequate field sizes, the success of treatment in the setting of gross disease with conventional photon irradiation has been suboptimal. In a randomized study directly comparing neutrons with photons in the treatment of inoperable salivary gland tumors, primary tumor and regional node clearance was achieved in only 33% of the photon patients. In contrast, the results when treated with fast neutrons show a tumor and regional node clearance of 85%.4 This is consistent with the radiobiological evidence that the relative biological effectiveness (RBE) of neutrons compared to cobalt beams for adenoid cystic carcinoma is 8.0 with fractionated treatment courses. For other tissues and tumors, the RBEs are in the range of 2.5 to 4.0.’ Hence, for a given level of normal tissue side effects, the biological effectiveness of neutrons should be approximately 2.5 times that of conventional photon irradiation. Patients with adenoid cystic carcinoma usually receive 2040 neutron cGy to the tumor volume and 1360 neutron cGy to regions at risk of containing microscopic disease. Compared to conventional photon irradiations, the dosages would be roughly equivalent to delivering 16,320 cGy and 10,880 cGy respectively, in terms of expected tumor responses. Furthermore, because of a lower neutron RBE in normal tissues, the risk of normal tissue side effects would be roughly equivalent to 6500 photon cGy. With these radiobiologic advantages matched with the superior clinical results achieved over conventional photon radiation, one can argue that fast neu-
Salivary gland tumors are quite rare, representing only 1 to 3% of the histology of the head and neck tumors6 The majority of salivary gland tumors occur in the parotid gland with adenoid cystic carcinoma representing 10% of malignant parotid tumors. Unlike other salivary gland malignancies, adenoid cystic carcinoma is known for its characteristic spread along nerve sheaths towards the cranial nuclei.2 This is a vital consideration in the treatment planning of adenoid cystic carcinomas of the parotid because, as seen in Fig. 1, the seventh cranial nerve penetrates the glandular tissue. Because of this intimate anatomic association of the seventh cranial nerve with the parotid gland, surgical resection of an advanced malignancy will often require a sacrifice of the facial nerve and leave the patient with an unacceptable cosmetic and functional defect. It should be noted that the auricular-temporal branch of the fifth nerve is also a risk for perineural tumor spread. This potential for perineural spread and patterns of lymphatic drainage are also important factors in radiotherapeutic treatment ofthese carcinomas. Radiation therapy treatment volumes need to be large, with field margins extending superiorly to the base of the skull to include the zygoma and two thirds of the ear; posteriorly to include the posterior cervical nodes and the mastoids; anteriorly to include the masseter muscle and two thirds of the cheek; and inferiorly to include the hyoid bone providing adequate coverage of potential submandibular nodal involvement.’ Because of these extended field sizes and areas at risk, we consider this three-field technique preferable for the initial treatment fields to the commonly used wedged pair combination.3 With a wedged pair tech99
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quate coverage of the tumor bed and potential areas at risk, while sparing a portion of the contralateral parotid gland to minimize the risk of permanent xerostomia. The technique utilizes patient immobilization, a treatment planning CT scan, fluoroscopic simulation, a three-dimensional treatment plan, and a cyclotron treatment machine equipped with a multileaf collimator system.
Fig. 1. The location of the seventh cranial nerve relative to the parotid gland.
tron radiation therapy is the treatment of choice for advanced salivary gland malignancies.6 2. METHODS
At the University of Washington Cancer Center, we have formulated a three-field technique for irradiating salivary gland tumors with fast neutrons. The technique was developed in an attempt to provide ade-
Fig. 2. Immobilization
2.1. Immobilization Patient immobilization is extremely important for patients receiving neutron therapy because of the length of time required for treatment and setup. Using the three-field technique, each treatment and setup takes approximately 30 minutes. Because it is impossible for any patient to remain perfectly still for this period of time, a thermoplastic mask, as shown in Fig. 2, is used to immobilize each patient during the treatment planning CT, the simulation, and the treatment. Prior to the patient’s treatment planning CT scan, an immobilization mask is made in the simulator room. A thermoplastic sheet glued to a wooden frame is placed in a waterbath heated to 60°C. When the thermoplastic sheet becomes transparent from the heat of the water, it is quickly placed on the patient’s face and is carefully shaped around the patient’s nose and chin. Upon cooling, the mouth, the eyes and the nostril areas are cut out and cut edges are covered with paper tape for the patient’s comfort. During use,
mask used during treatment planning CT, simulation, and treatment. The patient is shown here lying on the cyclotron treatment table immobilized in the mask.
Treatment of carcinoma of the salivary gland 0 SHARONM. HUMMEL et al.
the mask is bolted to a plexiglass frame measuring 4 I X 41 centimeters. The inferior portion of the plexiglass lies under the patient’s shoulders. The additional weight of the patient’s shoulders as well as the bolting of the mask to the frame makes this masking system an effective immobilizer. Plastic bolts are used rather than metal bolts for CT compatability. 2.2. Treatment planning CT scan Following the immobilization process the patient receives a treatment planning CT scan. The patient’s head is immobilized in the thermoplastic mask with the head in treatment position. The scan includes all potential treatment areas from base of the skull to thoracic inlet. Following scanning, the radiologist uses the GE CT Correlate program’ to delineate the tumor volume on anterior and lateral scouts generated by the CT scan. The radiation oncologist uses this information during simulation to define the target volume, and again during the dosimetry process. 2.3. Simulation With the patient’s head immobilized in the mask, fluoroscopy assists the midline placement of the treatment fields’ isocenter and determines the field parameters. Subsequently, the superior and inferior field borders of the treatment fields are defined. These borders, as described earlier, include the base of the brain superiorly and the hyoid bone inferiorly. The anterior and posterior borders are then defined to
Fig. 3. The lateral simulator
include the masseter muscle and two thirds of the cheek anteriorly: and the posterior cervical nodes and the mastoids posteriorly. All lateral treatment fields may be drawn using only one lateral simulator film. This is because the patient’s head is straight within the mask and the isocenter is at the patient’s midline, thereby assuring that the patient’s anatomy would not be projected differently were an opposing lateral film to be taken. Using the projection of the ceiling and wall mounted lasers, three points are marked on the mask, which correspond to the isocenter location. Two simulator films, an anterior and a lateral, are taken. The anterior film simply documents isocenter location from left to right relative to the patient’s midline. On the lateral film, the three treatment fields are drawn, as shown in Fig. 3. The patient whose films are shown is a 76-yearold man who presented with an adenoid cystic carcinoma of his left parotid gland. The large left lateral field includes his primary tumor, posterior cervical nodes, and submandibular nodes. The superior border of the large field includes the base cf his skull, but is carefully shielded using the multileaf collimator system to avoid treating the optic nerves, the optic chiasm and the cranial contents. A smaller left lateral field matches all parameters of the large lateral field, but does not include the submandibular nodes and anterior-inferior neck. The submandibular nodes and anterior neck are treated with an opposing right lateral field. The contralateral anterior neck opposed
film with three treatment
field is arranged so its superior border adequately covers the submandibular nodal groups, while sparing a portion of the contralateral parotid gland. This field is also placed anterior to the spinal cord to permit maximum doses to the tumor bed and areas at risk before the spinal cord tolerance of 1000 neutron cGy is reached. The posterior contralateral neck nodes are not treated because they are felt to be at low risk for potential disease in most patient cases. The diagram in Fig. 4 shows the three-field geometry relative to the involved parotid gland. The solid line represents the large ipsilateral field; the broken line represents the reduced ipsilateral field, and the dotted line represents the contralateral neck field, which treats the submandibular nodes. The region of the diagonal lines represents the area blocked by the cyclotron’s variable collimators. Treatment fields generally match along the central axis, that is, the contralateral neck field’s superior and posterior borders fall along the central axis as shown in Fig. 3. As shown in Fig. 4, treatment fields may match within the region of the target volume because of the need to include the submandibular nodes with the opposing field. The match line is not moved during the treatment of the three-field technique. When the submandibular nodes have received 1360 neutron cGy, the inferior borders of the treatment fields used to treat the parotid gland target volume will include the inferior portion of the parotid originally included within the submandibular field margins. 2.4. Dosimetry Following simulation, the process of dosimetry begins. Treatment planning is accomplished using the
Fig. 4. The geometry of the three-field technique relative to the parotid gland.
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three-dimensional treatment planning software system developed in our department called UWPLAN.5 A commercial version of the system is used in many radiation therapy centers.’ The treatment planning CT is loaded onto UWPLAN via magnetic tape. Generally three to four CT slices are utilized for the planning of the three-field technique. Only three CT slices were needed to plan this described case. On the CT slices, dose calculation points are digitized to represent the contralateral parotid gland, the spinal cord, the brain stem, and the midplane inferior neck field. The CT slices used to plan this patient’s case were through the level of the superior target volume, the mid inferior neck, and the central axis, which is also frequently the mid target volume. Dose distributions through the superior target volume and the mid inferior neck are shown in Figs. 6 and 7. Historically, with conventional radiation therapy, lateral electron fields or an ipsilateral wedged pair might be used to treat the tumor volume and spare the contralateral parotid gland, which is not at risk, and avoid xerostomia. The three-field technique also achieves this goal. To minimize the tumor dose to the contralateral parotid gland, the two ipsilateral fields are normalized to the medial tumor volume, and not to the isocenter at the patient’s midline. Normalizing this way gives the prescribed dose, 170 neutron cGy per day to the target volume, while minimizing the dose to normal structures. The dose to the contralateral parotid gland is limited to less than 35% of the total tumor dose (700 neutron cGy of a prescribed 2040 neutron cGy total dose). With the exception of scattered radiation from the boost fields, the only dose to the contralateral parotid will be from this three-field technique. Each of the ipsilateral fields delivers 85 neutron cGy to the target volume per fraction. The contralatera1 neck field must also receive 170 neutron cGy per day. To achieve this, first the left ipsilateral fields are normalized to the medial parotid bed. Only the large left ipsilateral field is contributing dose from its primary beam to the midplane of the contralateral neck field. In this case, the dose from the large left lateral field was 72 neutron cGy of the 85 neutron cGy delivered to the parotid bed. The reduced left lateral field contributed scattered radiation of 10 neutron cGy. So, to deliver 170 neutron cGy to the inferior neck and submandibular nodes, the contralateral neck field must deliver 88 neutron cGy to an inferior midplane point within its field parameters. The intent is to deliver as much of the prescribed 1800-2040 neutron cGy with this treatment technique, while limiting the cord dose to less than 1000 neutron cGy. The remaining fractions will treat only the primary tumor volume in the parotid bed using common treatment techniques, such as an ipsilateral wedged pair. It will be necessary to deliver two additional fractions to the
Treatment of carcinoma of the salivary gland ??SHARON
Fig. 5. The cyclotron’s multileaf collimator system.
submandibular nodes with opposing fields, matching their superior field margin to the inferior border of the parotid fields. Dose distributions in two transverse planes using the three-field technique are shown in Figs. 6 and 7. These distributions are displayed on a high resolution graphic monitor. The parotid target volume in this plan measures three centimeters long. 1020 neutron cGy is normalized to a mid target point at 3 centime-
Fig. 6. Dose distributions
ters deep. This delivers 1200 neutron cGy to the supe-
rior target volume as shown in Fig. 6. A wedged pair boost of an additional 840 neutron cGy will be required to deliver a total of 2040 cGy to the target volume. Fig. 7 shows the dose distribution through the region of the submandibular nodes. An additional 340 neutron cGy will be delivered via opposing lateral fields to a total of 1360 neutron cGy to the submandibular nodes at risk.
through the superior portion of the parotid target volume.
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Fig. 7. Dose distributions through the submandibular nodes within the three-dimensional treatment volume.
2.5. Treatment In the University Cancer Center at the University of Washington Medical Center, a medically dedicated cyclotron generates a 24 MeV fast neutron beam from a 50 Mev p + Be reaction. The dose distributions from the neutron beam are similar to those of a photon beam produced by a 6 MeV linear accelerator. The neutron fields are collimated by the multileaf collimator system, which can produce an irregularly shaped field size as shown in Fig. 5. Patients receive 12 fractions in four weeks. Patients are treated three times weekly, with 1800-2040 neutron cGy being prescribed to the target boost volume. 3. RESULTS We have treated six patients with adenoid cystic carcinomas of the parotid and submandibular salivary glands using this technique. Doses to the primary target volume have ranged between 1800-2040 neutron cGy, while the doses to the contralateral parotid region have been restricted to between 550-900 neutron cGy. In most cases adequate salivary function has returned in approximately six to nine months. However, in the case of the patient who received 900 neutron cGy to the contralateral parotid, it took approximately two years for this to take place. Only one patient exhibited a “marginal” failure at the superior border of the field; all other patients continue to exhibit local/regional control. This technique has been
applied to two patients with mucoepidermoid tumors of the major salivary glands with similar results. 4. SUMMARY In summary, we note that the three-field technique is a highly effective method of treating the large, eccentrically-shaped risk volume for adenoid cystic carcinomas of the parotid and submandibular salivary glands. The same technique has been adapted to the treatment of squamous cell metastases to the parotid bed from skin cancers of the forehead and temporal region. However, in these cases photons are used for the large ipsilateral and small contralateral fields, while electrons are used for the eccentric smaller, ipsilateral field. Our results obtain excellent local/regional control, sparing the patient the morbidity of permanent xerostomia by minimizing the radiation dose to the contralateral parotid. (There will be some transient xerostomia starting towards the end of radiotherapy and continuing for several months thereafter.) While we do not have sufficient information to establish a dose-response curve for return of salivary gland function, it does appear that higher radiation doses to the contralateral parotid are associated with longer recovery times. REFERENCES 1. Battermann.J.I.; Brew, K.: Hart, G.A.M.; Van Pepperzeal, H.A. Observations of pulmonary metastases in patients after single doses and multiple fractions of fast neutrons and cobalt60 gamma rays. European Journal t$ Cancer 11539-548; I98 1.
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