Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer

doi:10.1016/j.radonc.2005.10.017

Radiotherapy and Oncology

Volume 77, Issue 3, December 2005, Pages 247-253

https://doi.org/10.1016/j.radonc.2005.10.017 Get rights and content

Abstract

Background and purpose

To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT) can be used to reduce doses to normal lung than three-dimensional conformal radiotherapy (3DCRT) in treating distal esophageal malignancies.

Patients and methods

Ten patient cases with cancer of the distal esophagus were selected for a retrospective treatment-planning study. IMRT plans using four, seven, and nine beams (4B, 7B, and 9B) were developed for each patient and compared with the 3DCRT plan used clinically. IMRT and 3DCRT plans were evaluated with respect to PTV coverage and dose–volumes to irradiated normal structures, with statistical comparison made between the two types of plans using the Wilcoxon matched-pair signed-rank test.

Results

IMRT plans (4B, 7B, 9B) reduced total lung volume treated above 10 Gy (V₁₀), 20 Gy (V₂₀), mean lung dose (MLD), biological effective volume (V_eff), and lung integral dose (P<0.05). The median absolute improvement with IMRT over 3DCRT was approximately 10% for V₁₀, 5% for V₂₀, and 2.5 Gy for MLD. IMRT improved the PTV heterogeneity (P<0.05), yet conformity was better with 7B–9B IMRT plans. No clinically meaningful differences were observed with respect to the irradiated volumes of spinal cord, heart, liver, or total body integral doses.

Conclusions

Dose–volume of exposed normal lung can be reduced with IMRT, though clinical investigations are warranted to assess IMRT treatment outcome of esophagus cancers.

Section snippets

Patients and methods

Ten patients who underwent treatment for esophageal cancer were selected from our existing patient population. Because the anatomy of distal esophageal cancers only varies slightly from patient to patient, these 10 cases were sufficient to represent typical anatomies for this group of patients. The patient identifiers were removed in accordance with an Institutional Review Board-approved retrospective study protocol. All of the patients had tumors involving the distal esophagus and

Results

Isodose distributions of 3DCRT plan and three IMRT plans for one of the typical esophagus cases studied in this work are presented in Fig. 1. In the 3DCRT plan, two AP–PA parallel opposed beams and two posterior oblique beams were used to create the dose distribution. In the 4B-IMRT plan, even though identical beam angles were used, intensity modulation has helped to push the 10 and 20 Gy isodose lines away from the normal lung and reduced the corresponding lung volumes treated as a result. In

Discussion

Clinical studies have shown that chemoradiation used alone or preoperatively to treat esophageal cancer can result in severe complications [1], [2], [3]. Besides good clinical rationale, evidence exists that suggests that minimization of the volume of lung irradiated to low doses could results in fewer pulmonary complications [4]. Our study addressed whether IMRT for esophageal cancer can be used to reduce the volume of lung irradiated even at low doses of 10–20 Gy. This goal was achieved with

Acknowledgments

This work was partially supported by grants NCI-CA74043 from the National Institute of Health, USA.

References (17)

H. Lee et al.
Postoperative pulmonary complications after preoperative chemoradiation
Int J Radiat Oncol Biol Phys
(2003)
J. Bedford et al.
A quantitative treatment planning study evaluating the potential of dose escalation in conformal radiotherapy of the oesophagus
Radiother Oncol
(2000)
C. Nutting et al.
A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy
Radiother Oncol
(2001)
S.L. Kwa et al.
Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients
Int J Radiat Oncol Biol Phys
(1998)
M. Graham et al.
Clinical dose–volume histogram analysis for pneumonitis after 3D treatment
Int J Radiat Oncol Biol Phys
(1999)
E. Yorke et al.
Dose–volume factors contributing to the incidence of radiation pneumonitis
Int J Radiat Oncol Biol Phys
(2002)
G. Kutcher et al.
Histogram reduction method for calculating complication probabilities for non-uniform normal tissue irradiation: the effective volume method
Int J Radiat Oncol Biol Phys
(1991)
C. Burman et al.
Fitting of normal tissue tolerance data to an analytic function
Int J Radiat Oncol Biol Phys
(1991)

There are more references available in the full text version of this article.

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Objectives: Compare the efficacy and safety of high vs standard radiation dose of definitive concurrent chemoradiotherapy (dCCRT) for esophageal cancer (EC).
Methods and materials: This meta-analysis is registered in PROSPERO, and it was followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Eligible randomized clinical trials (RCTs) comparing high dose (HD;≥59.4 Gy/1.8 Gy) and standard doses (SD; 50 Gy/2Gy or 50.4 Gy/1.8 Gy) were identified on electronic databases. STATA16.0 was used for statistical analysis. A meta-analysis was performed to compare treatment effect and toxicity.
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Conclusion: SD-RT had similar treatment effect but lower Grade ≥ 3 treatment-related toxicities rates compared with the HD-RT. Therefore, SD (50 Gy/2Gy or 50.4 Gy/1.8 Gy) should be considered as the recommended dose in dCCRT for EC. Further RCTs are needed to verify our conclusions.
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Citation Excerpt :
In the literature, several studies revealed a correlation between the radiation dose to organs at risk (OAR) and the incidence of complications [6–9]. The implementation of modern radiation delivery techniques, such as intensity modulated radiation therapy (IMRT) and proton therapy, allows to better sculpt the dose to the target volume and to reduce the dose to the OAR [10–14]. Uncertainties in tumour delineation and in inter- and intra-fractional position variation, however, lead to substantial irradiated volumes.
To prospectively evaluate the feasibility of solid gold marker placement in oesophageal cancer patients and to quantify inter-fractional and intra-fractional (baseline shift) marker motion during radiation treatment. Radiotherapy target margins and matching strategies were investigated.
Thirty-four markers were implanted by echo-endoscopy in 10 patients. Patients received a planning 4D CT, daily pre-treatment cone-beam CT (CBCT) and a post-treatment CBCT for at least five fractions. For fractions with both pre- and post-treatment CBCT, marker displacement between planning CT and pre-treatment CBCT (inter-fractional) and between pre-treatment and post-treatment CBCT (intra-fractional; only for fractions without rotational treatment couch correction) were calculated in left–right (LR), cranio-caudal (CC) and anterior-posterior (AP) direction after bony-anatomy and soft-tissue matching. Systematic/random setup errors were estimated; treatment margins were calculated.
No serious adverse events occurred. Twenty-three (67.6%) markers were visible during radiotherapy (n = 3 middle oesophagus, n = 16 distal oesophagus, n = 4 proximal stomach). Margins for inter-fractional displacement after bony-anatomy match depended on the localisation of the primary tumour and were 11.2 mm (LR), 16.4 mm (CC) and 8.2 mm (AP) for distal markers. Soft-tissue matching reduced the CC margin for these markers (16.4 mm to 10.5 mm). The mean intra-fractional shift of 12 distal markers was 0.4 mm (LR), 2.3 mm (CC) and 0.7 mm (AP). Inclusion of this shift resulted in treatment margins for distal markers of 12.8 mm (LR), 17.3 mm (CC) and 10.4 mm (AP) after bony-anatomy matching and 12.4 mm (LR), 11.4 mm (CC) and 9.7 mm (AP) after soft-tissue matching.
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Oesophagus IMRTFeasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer

Abstract

Background and purpose

Patients and methods

Results

Conclusions

Section snippets

Patients and methods

Results

Discussion

Acknowledgments

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Oesophagus IMRT
Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer