Elsevier

Medical Dosimetry

Volume 27, Issue 2, Summer 2002, Pages 121-129
Medical Dosimetry

Treatment of pancreatic cancer tumors with intensity-modulated radiation therapy (IMRT) using the volume at risk approach (VARA): Employing dose-volume histogram (DVH) and normal tissue complication probability (NTCP) to evaluate small bowel toxicity

https://doi.org/10.1016/S0958-3947(02)00094-8Get rights and content

Abstract

The emergent use of a combined modality approach (chemotherapy and radiation) in pancreatic cancer is associated with increased gastrointestinal toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the tumor volume while decreasing the dose to critical structures such as the small bowel. We evaluated the influence of IMRT with inverse treatment planning on the dose-volume histograms (DVHs) of normal tissue compared to standard 3-dimensional conformal radiation treatment (3D-CRT) in patients with pancreatic cancer. Between July 1999 and May 2001, 10 randomly selected patients with adenocarcinoma of the pancreatic head were planned simultaneously with 3D-CRT and inverse-planned IMRT using the volume at risk approach (VaRA) and compared for various dosimetric parameters. DVH and normal tissue complication probability (NTCP) were calculated using IMRT and 3D-CRT plans. The aim of the treatment plan was to deliver 61.2 Gy to the gross tumor volume (GTV) and 45 Gy to the clinical treatment volume (CTV) while maintaining critical normal tissues to below specified tolerances. IMRT plans were more conformal than 3D-CRT plans. The average dose delivered to one third of the small bowel was lower with the IMRT plan compared to 3D-CRT. The IMRT plan resulted in one third of the small bowel receiving 30.2 ± 12.9 Gy vs. 38.5 ± 14.2 Gy with 3D-CRT (p = 0.006). The median volume of small bowel that received greater than either 50 or 60 Gy was reduced with IMRT. The median volume of small bowel exceeding 50 Gy was 19.2 ± 11.2% (range 3% to 45%) compared to 31.4 ± 21.3 (range 7% to 70%) for 3D-CRT (p = 0.048). The median volume of small bowel that received greater than 60 Gy was 12.5 ± 4.8% for IMRT compared to 19.8 ± 18.6% for 3D-CRT (p = 0.034). The VaRA approach employing IMRT techniques resulted in a lower dose per volume of small bowel that exceeded 60 Gy. We used the Lyman-Kutcher models to compare the probability of small bowel injury employing IMRT compared to 3D-CRT. The BIOPLAN model predicted a small bowel complication probability of 9.3 ± 6% with IMRT compared to 24.4 ± 18.9% with 3D-CRT delivery of dose (p = 0.021). IMRT with an inverse treatment plan has the potential to significantly improve radiation therapy of pancreatic cancers by reducing normal tissue dose, and simultaneously allow escalation of dose to further enhance locoregional control.

Introduction

Intensity-modulated radiation therapy (IMRT) is an emerging technology that allows physicians and physicists to be more precise in the delivery of radiation to tumors. It gives a high degree of conformality of isodose to the tumor volume while at the same time minimizes the dose to surrounding structures. The dose to critical structures can be further minimized with the use of an inverse treatment planning system. It allows oncologists and physicists to set dose constraints for both normal tissues and tumors. This ability to set dose constraints to normal tissue before defining field arrangements is a powerful treatment planning tool. Although the process involves a trial and error approach to designing treatment fields, it gives the advantage of truly determining the limits of a particular field arrangement when dose constraints are set a priori.

Portelance et al.1 evaluated the impact of IMRT on reducing the dose to the small bowel in patients treated for cervical cancer compared to conventional techniques. IMRT was delivered by 4-, 7-, and 9-field arrangements. This was compared to 2- and 4-field arrangements for conventional therapy. IMRT resulted in a decrease in the amount of small bowel that received 45 Gy. With a 4-field IMRT technique, the volume of small bowel treated to 45 Gy was 11% compared to 34% for 4-field conventional treatment.1 In respect to prostate cancer, Zelefsky et al.,2 employing a 5-field arrangement with IMRT and inverse treatment planning, showed a decrease in grade 2 rectal complications compared to treating patients with non-IMRT fields. They reported a grade 2 complication rate of 3% with IMRT compared to 16% for 3-dimensional conformal therapy (3D-CRT). The aforementioned is an example of how IMRT can be employed to minimize the dose to critical organs, such as the rectum.

In head-and-neck tumors, IMRT techniques are well matched to the complexity of head-and-neck cancer management. Studies from University of California-San Francisco and Washington University3, 4 showed that IMRT allowed minimization of the dose to the parotid gland with resultant significant decrease of xerostomia. With a median follow-up of 21.8 months, Sultanem et al.4 reported 50% of patients had grade 1, and none had grade 2 xerostomia. They also showed that there were no local-regional failures with and without chemotherapy in the treatment of nasopharyngeal carcinoma with IMRT.4

Clinical applications of these treatment strategies may allow us to minimize serious long-term complications while increasing cure probability in cancer patients. For pancreatic cancers, combined chemotherapy and radiation with new agents such as Gemcitibine has resulted in increased gastrointestinal toxicity (ECOG Phase I pancreatic trial, personal communication, Mark Talamonti, July 2001). In treating pancreatic cancer with radiotherapy, radiation dose given to the target volume is largely limited by the tolerance of the surrounding normal tissue in close proximity to the tumor site, including small bowel, kidneys, and spinal cord. To decrease the risk for a marginal miss, generous treatment margins are frequently added to the target volume, which extends into the adjacent dose-sensitive structures. Most investigators who use IMRT techniques employ this modality primarily for boosting tumors after conventional treatments, and are delivering high radiation doses to small tumor volumes. Although this strategy has merit, the use of IMRT technology from the beginning of treatment would allow one to start the process earlier of minimizing dose to normal tissues. This strategy may give the oncologist and physicist greater freedom to push the radiation dose because critical structure doses are minimized from the onset. At our institution, we are investigating the use of IMRT with inverse treatment planning techniques from the beginning of treatment. To execute such a strategy requires drawing not only critical normal structures but also the areas at risk for tumor spread. When the areas at risk are identified and outlined on high-quality CT images with volumetric margins, it becomes possible to minimize irradiation of the normal tissue volume.

Organ motion is also considered in setting 3D margins. Data from Massachusetts Hospital5 indicate that the pancreas moves with respiration. In a volumetric analysis of abdominal organ motion using clip coordinates and CT scans during various phases of the respiratory cycle, the authors documented pancreas movement of 16 to <5 mm cranial to caudal, 5 to 7 mm anterior to posterior, and 2 to 3 mm medial to lateral. An extra 1 cm of margin is built into our planning treatment volume (PTV) margin to account for the gross tumor volume (GTV) movement with respiration.

We defined this 3D process of outlining the clinical tumor volume as well as the nodal and soft tissue volumes as the volume at risk approach, or VaRA. We plan to use the VaRa approach with IMRT to minimize the dose to the small intestines when treating patients with pancreatic cancer. The literature6, 7, 8 supports the fact that small bowel obstruction increases when radiation doses above 45 to 50 Gy are delivered. Because the small bowel loops around the pancreatic head, it is difficult to deliver doses to the pancreas above 50 Gy with radiation techniques such as 3D-CRT without exceeding small bowel tolerance. Thus, the ability to increase the radiation dose to the pancreas is limited because of anatomical constraints. In this paper, we analyzed the potential benefits of IMRT in minimizing the dose of radiation delivered to various volumes of small bowel when treating patients with pancreatic cancer. To further validate the IMRT approach, the dose-volume histograms (DVHs) of patients planned with IMRT to 61.2 Gy were compared with the 3D-CRT approach to the same dose level. The possible clinical relevance of these results was studied using radiobiological models.

Section snippets

Patients and methods

Between July 1999 and May 2001, 10 randomly selected patients with adenocarcinoma of the pancreatic head were planned simultaneously with 3D-CRT and IMRT using the VaRA approach and compared for various dosimetric parameters. To assure accurate visualization of the small bowel, all patients were given 3 or 4 glasses of radiopaque gastrograffin oral contrast, and were placed supine on a rigid foam cradle (Fig. 1). Approximately 30 minutes after drinking the oral contrast, treatment planning

Results

The beam’s-eye view, radiation field arrangements, and isodose comparisons between 3D-CRT and IMRT is illustrated in Fig. 4, Fig. 5, Fig. 6, Fig. 7. Further analysis of the difference between 3D-CRT and IMRT was evaluated using DVHs. The comparisons are illustrated in Fig. 8, Fig. 9.

We evaluated the IMRT and 3D-CRT DVHs for 10 patients with an emphasis on evaluating the difference in the radiation dose to various volumes of small bowel. Table 2 is an illustration of this comparison.

The

Discussion

IMRT with inverse treatment planning is a powerful tool to use in decreasing the dose to critical structures. As illustrated in the literature for treating cancers of the cervix, head and neck, and prostate—to list a few—IMRT has resulted in significant decrease in dose to the small bowel, parotid, and rectum. We have demonstrated that IMRT has the same power to minimize dose to the small bowel in patients undergoing radiation for pancreatic cancer. Although 3D-CRT techniques have been used to

Conclusions

With IMRT and inverse treatment planning, we decreased the volume of small bowel that received radiation doses of 50 Gy or higher. This minimization could potentially allow one to increase the dose delivered to the pancreatic tumor as well as decrease small bowel-related side effects such as nausea. Analysis of DVH and NTCP of small bowel showed that IMRT has the potential to significantly improve radiotherapy of pancreatic cancers by reducing normal tissue dose and simultaneously allowing

Acknowledgements

The authors thank Ms. Diane Cassels for her capable assistance in preparing the manuscript. Drs. Beatriz Sanchez-Nieto and Alan Nahum kindly provided the BIOPLAN software.

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