Clinical investigation: head and neck
Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system

Accepted for poster discussion presentation at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Salt Lake City, UT, October 19–23, 2003.
https://doi.org/10.1016/j.ijrobp.2003.12.024Get rights and content

Abstract

Purpose

Many patients receiving fractionated radiotherapy (RT) for head-and-neck cancer have marked anatomic changes during their course of treatment, including shrinking of the primary tumor or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss. We conducted a pilot study to quantify the magnitude of these anatomic changes with systematic CT imaging.

Methods and materials

Fourteen assessable patients were enrolled in this pilot study. Eligible patients had to have a pathologic diagnosis of head-and-neck cancer, be treated with definitive external beam RT, and had have gross primary and/or cervical nodal disease measuring at least 4 cm in maximal diameter. All patients were treated using a new commercial integrated CT-linear accelerator system (EXaCT) that allows CT imaging at the daily RT sessions while the patient remains immobilized in the treatment position. CT scans were acquired three times weekly during the entire course of RT, and both gross tumor volumes (GTVs: primary tumor and involved lymph nodes) and normal tissues (parotid glands, spinal canal, mandible, and external contour) were manually contoured on every axial slice. Volumetric and positional changes relative to a central bony reference (the center of mass of the C2 vertebral body) were determined for each structure.

Results

Gross tumor volumes decreased throughout the course of fractionated RT, at a median rate of 0.2 cm3 per treatment day (range, 0.01–1.95 cm3/d). In terms of the percentage of the initial volume, the GTVs decreased at a median rate of 1.8%/treatment day (range, 0.2–3.1%/d). On the last day of treatment, this corresponded to a median total relative loss of 69.5% of the initial GTV (range, 9.9–91.9%). In addition, the center of the mass of shrinking tumors changed position with time, indicating that GTV loss was frequently asymmetric. At treatment completion, the median center of the mass displacement (after corrections for daily setup variation) was 3.3 mm (range, 0–17.3 mm). Parotid glands also decreased in volume (median, 0.19 cm3/d range, 0.04–0.84 cm3/d), and generally shifted medially (median, 3.1 mm; range, 0–9.9 mm) with time. This medial displacement of the parotid glands correlated highly with the weight loss that occurred during treatment.

Conclusion

Measurable anatomic changes occurred throughout fractionated external beam RT for head-and-neck cancers. These changes in the external contour, shape, and location of the target and critical structures appeared to be significant during the second half of treatment (after 3–4 weeks of treatment) and could have potential dosimetric impact when highly conformal treatment techniques are used. These data may, therefore, be useful in the development of an adaptive RT scheme (periodic adjustment of the conformal treatment plan) that takes into account such treatment-related anatomic changes. In theory, such a strategy would maximize the therapeutic ratio of RT.

Introduction

Radiotherapy (RT) has been used in the treatment of patients with head-and-neck cancer for several decades. However, whether RT is used definitively in an organ-preserving strategy or postoperatively to enhance locoregional control, it is fundamental that an adequate radiation dose be accurately delivered to the desired target volume throughout the treatment course. The clinical consequences for inaccuracy include both potential underdosage of the target volumes (with a resultant increased risk of tumor recurrence) and potential overdosage of normal tissues (with a resultant increased risk of complications).

Recent advances in image-based treatment planning have improved the clinician's ability to design conformal treatment plans that maximize both tumor coverage and normal tissue sparing 1, 2, 3, 4, 5. However, several variables could theoretically cause deviations in radiation dose delivery from the thoughtful initial treatment plan. Aside from variations in the initial target volume and normal tissue delineation, these uncertainties include external daily setup variations and internal geometric and volumetric changes occurring throughout the 6–7-week RT course.

It has long been recognized that some patients receiving RT to the head-and-neck will have significant anatomic changes during their treatment course, including shrinking primary tumors or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss 6, 7, 8, 9. An example of such a case is shown in Fig. 1. However, the methods available for quantification of such changes have been rather crude. The studies of radiation effect on the gross tumor volume (GTV) and position, for instance, have been limited to recording the gross disease characteristics by methodical physical examinations before, during, and at the completion of RT 6, 7, 8, 9. These studies did not adequately describe the ongoing geometric changes in tumors and normal tissues during a several-week course of treatment.

Despite this limited understanding of the anatomic changes occurring during RT, clinicians have nonetheless recognized these changes as clinically significant. For example, ongoing weight loss can cause imprecise daily repositioning if an immobilization device loosens over time; this could potentially result in underdosage of the tumor/target tissues (persistence/recurrence risk) or overdosage of normal tissues (toxicity risk). Although at times these are clinically relevant even with conventional RT techniques, concern is heightened that geometric changes have even greater significance when using the more modern, highly conformal RT delivery methods.

Currently, RT is planned on the basis of the acquisition of a single set of CT scans before the start of treatment. This treatment plan includes a margin for potential microscopic spread (i.e., clinical target volume), along with the anticipated uncertainties related to daily setup variation and intrafractional organ motion (i.e., planning target volume) 10, 11. This margin does not specifically address ongoing alterations in anatomy during the next 6–7 weeks of therapy. It is our hypothesis that anatomic changes throughout fractionated RT could have significant dosimetric effects in the setting of highly conformal treatment approaches, such as intensity-modulated RT (IMRT). We, therefore, conducted a pilot study to investigate this question with frequent CT imaging throughout the RT course. With the recent availability of in-room CT scanners or integrated CT/linear accelerator combinations, patient position and internal anatomy can be imaged frequently with the patient in the treatment position 12, 13, 14, 15. In this investigation, we concentrated on quantifying these geometric and volumetric changes during the course of RT.

Section snippets

Patient eligibility

We designed a pilot study, approved by the institutional review board (IDO2-617), to enroll 15 patients at The University of Texas M.D. Anderson Cancer Center. Eligible patients were newly diagnosed with head-and-neck cancer and had gross primary and/or cervical nodal disease measuring at least 4 cm in maximal dimension that was visible by CT. Patients were treated with definitive external beam RT using either conventional or conformal treatment techniques. The use of concurrent chemotherapy

Patient accrual and clinical characteristics

Between December 31, 2002 and March 3, 2003, 15 patients were enrolled in a pilot study at The University of Texas M.D. Anderson Cancer Center. The patient characteristics are shown in Table 1. The planned CT scans could not be acquired in 1 patient because the body habitus was incompatible with the bore of the treatment CT scanner. The remaining 14 patients were treated with definitive RT or chemoradiotherapy and successfully underwent additional CT scanning according to the protocol. Most

Discussion

In this study, we attempted to specifically quantify the progressive geometric/anatomic changes occurring in patients treated with RT for head-and-neck cancer. In this study, we used high-definition imaging studies throughout the treatment course to quantify the magnitudes and rates of three-dimensional anatomic changes occurring gradually over time. Significant volumetric and positional changes occurred for gross disease in these patients with locally advanced head-and-neck carcinoma. Over

Conclusion

In this investigation, we quantified the geometric and volumetric changes in anatomy for 14 patients who underwent fractionated external beam RT for head-and-neck cancer. Measurable anatomic changes occurred throughout the course of treatment. For both primary tumor and involved lymph nodes, the rate of volume regression was approximately 1.8%/d, relative to the initially defined volume. The parotid volume also reduced at a rate of approximately 0.6%/d. These changes in anatomy resulted in

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