Emerging Applications of Stereotactic Body Radiation Therapy for Head and Neck Cancer

Farzan Siddiqui; David Raben; Jiade J Lu; John C Grecula; Simon S Lo; Zhibin Huang; Nina A Mayr; Bin S Teh; Min Yao

Expert Rev Anticancer Ther. 2011;11(9):1429-1436.

Image Verification & Treatment Devices

Image-guided radiation therapy encompasses a wide range of techniques and equipment options to visualize the target and organs at risk before and sometimes during the delivery of radiation therapy. This includes, but is not limited to, port films, cone-beam computed tomography (CT) scans and fiducial tracking.

The development of image-guided radiation therapy has allowed the delivery of high doses of radiation per fraction with increased confidence and safety in the form of SBRT. There has been a gradual move from more conventional methods such as port films of treatment fields to more sophisticated and complex methods.

Various image verification systems are currently utilized for SBRT treatments. The CT-on-rails set-up involves a CT scanner placed in the same room as the linear accelerator. The CT system is placed on rails and can be moved to allow CT imaging of patient anatomy in the treatment position, image verification and treatment delivery without the need to move the patient off the treatment couch.

In-room orthogonal systems utilize two floor- or ceiling-mounted x-ray sources with opposing amorphous silicon flat-panel detectors. After the patient is placed in the treatment position, orthogonal films are obtained and digitally reconstructed for verification of isocenter placement based on bony anatomy. An example of such a system is the ExacTrac® (BrainLAB, Feldkirchen, Germany) system. This uses floor mounted x-ray sources with detectors in the ceiling. In addition, an infrared camera system is also combined with this to allow optical tracking of the patient's surface anatomy.

Cone-beam CT (CBCT) scans are now being increasingly employed for set-up verification. It is being provided as an option by most linear accelerator manufacturers nowadays and can be either kilovoltage CBCT (Varian Trilogy, Novalis TX and Elekta Synergy) or megavoltage CBCT (Siemens Oncor). To obtain cone-beam images, the x-ray source is turned on as the gantry rotates 180 degrees or more around the patient in the treatment position. Multiple planar projection images are acquired and 3D images reconstructed using a filtered back-projection algorithm.^[26,27] Unlike a conventional helical CT scanner where the images are obtained by longitudinal translation of the patient through a narrow x-beam being generated by a rotating x-ray source, CBCT uses a broad beam of x-ray with a 2D detector array to provide a larger field of view. Megavoltage CBCTs use the linear accelerator as the source of x-rays. The gantry can rotate 200° in 45 s with one image per degree being captured on the electronic portal imaging device.^[28] The 3D images are again reconstructed using the filtered back-projection algorithm.

Helical megavoltage CT or 'slice therapy' was first proposed by Mackie et al. in 1993.^[29] The concept was further developed for commercial use and is now available as the Hi-Art® treatment system (TomoTherapy Inc., WI, USA). In this design, the megavoltage linear accelerator is mounted on a CT-like gantry. As with the acquisition of helical CT scan, the patient is translated through the rotating gantry to produce images in the treatment position. These images can be matched and compared with the treatment-planning CT. If shifts are required, couch adjustments are made prior to treatment. After a proper match, the patient is treated on the same couch and gantry without any need for moving the patient.

A fair amount of head and neck SBRT experience across various centers has been gained using the CyberKnife system. The Accuray CyberKnife® Robotic Radiosurgery (Accuray Inc., CA, USA) system consists of a compact x-band linear accelerator mounted on an industrial robotic manipulator arm.^[30] The manipulator arm is configured to direct the radiation beams to the region of beam intersection of two orthogonal x-ray imaging systems integrated to provide image guidance for the treatment process. The patient under treatment is positioned on an automated robotic couch (RoboCouch™) such that the lesion to be treated is located within this radiation beam-accessible region. The Cyberknife and Gamma Knife systems are used only for radiosurgery or stereotactic radiation therapy purposes. By contrast, the linear accelerator and tomotherapy machines are more versatile and can be used for both stereotactic and regular external beam radiation treatments.

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Table 1. Review of current literature for stereotactic body radiation therapy in head and neck cancers.
Patients (n)	Sites	Dose	Technique	Med FU (m)	Response (%)		Local control		Survival	Late toxicity	Ref.
34	Orbit, LNs, Npx, Opx, others	19.5–42 Gy in 3–8 fr	CyberKnife	16	CR: 32.4 PR: 38.6				OS₁: 70.6% OS₂: 58.3%	n = 6 in re-RT, hemorrhage	[50]
22	Tongue, mandible, PNS, Opx, LNs	20–42 Gy/2–5 fr	CyberKnife	24	CR: 64.3 PR: 7.1 Stable: 7.1 PD: 21.4		LRC₂: 57.8% (40–50 Gy) LRC₂: 31.7% (15–36 Gy)		OS₂: 12.5% (+LNs) OS₂: 78.6% (-LNs)	n = 3-grade 3 osteo-radionecrosis	[55]
96		15–50 Gy Dose escalation	CyberKnife, Varian Trilogy	14	CR: 20–50, depending on dose		LRC₂: 30.7%		OS₁: 58.9% OS₂: 28.4%	No grade 4/5 toxicity	[52]
70 (35: SBRT alone; 35: SBRT + cetuximab)	Larynx, Npx oral cav, Opx	20–44 Gy/5 fr	CyberKnife, Varian Trilogy	21.3	SBRT onlyCR: 34.3 PR: 28.6 Stable: 17.1 PD: 20	SBRT + cetCR: 45.7 PR: 31.4 Stable: 14.3 PD: 8.6	SBRT only1 year: 53.8% 2 year: 33.6%	SBRT +cet1 year: 78.6% 2 year: 49.2%		No grade 4/5 toxicity	[49]
46	Npx oral cav, Hpx, Larynx	18–35 Gy in 1–5 fr	CyberKnife	7	CR: 27 PR: 29.8 Stable: 10				Med OS: 11.9 months OS₁: 46%	n = 8: carotid blowout; 7/8: fatal	[56]
65	Opx, Npx, Hpx, PNS, LNs	21–35 Gy in 2–5 fr	CyberKnife	16	CR: 54 PR: 27 Stable: 20		2 year: 30%		Med OS: 12 months	n = 7 (11%); 1/7: fatal	[57]
44	Opx, eyelid, lip orbit, Hpx, mandible, LNs	13–18 Gy in 1 fr; 36–48 Gy in 5–8 fr	BrainLab	36	CR: 31 PR: 46 Stable: 16 PD: 3		1 year: 83.3% primary, 60.6% recurrent, 75% metastatic groups,		OS₁: primary- 70%; OS₁: recc.: 38.1%	n = 7, necrosis and fistulae	[48]
36	Npx, PNS, LNs, Skull base, nasal cav. orbit	18–40 Gy in 3–5 fr	CyberKnife	17.3	CR: 42.9 PR: 37.1 Stable: 8.6 PD: 11.4		LRC₁: 61% LRC₂: 52.2%		OS₁: 52.1% OS₂: 30.9%	n = 3, bone and soft tissue necrosis	[58]
22	LNs, Npx, Opx, PNS	10–36 Gy in 1–8 fr	CyberKnife	19			2 year: 26%		Med OS: 12 months	No Gr 4/5	[53]

Cet: Cetuximab; CR: Complete response; Hpx: Hypopharynx; LN: Lymph node; LRC: Loco-regional control; Med: Median; Npx: Nasopharynx; Opx: Oropharynx; OS: Overall survival; PD: Progressive disease; PNS: Paranasal sinus; PR: Partial response; SBRT: Stereotactic body radiation therapy.

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