Comparative Treatment Planning Between Proton and X-Ray Therapy in Esophageal Cancer

doi:10.1016/S0360-3016(98)00047-9

International Journal of Radiation OncologyBiologyPhysics

Volume 41, Issue 2, 1 May 1998, Pages 441-450

https://doi.org/10.1016/S0360-3016(98)00047-9 Get rights and content

Abstract

Purpose: Conformal treatment planning with megavoltage x-rays and protons for five patients with esophageal cancer has been studied in an attempt to determine if there are advantages of using protons instead of x-rays.

Methods and Materials: For each of the five patients, two different proton plans, one x-ray plan, and one mixed plan with x-rays and protons were made. A three-dimensional treatment planning system, TMS™, was used. The evaluation of the different plans was made by applying the tumor control probability (TCP) model proposed by Nahum and Webb and the normal tissue complication (NTCP) model proposed by Lyman on the dose distributions in terms of dose–volume histograms (DVHs).

Results: The comparison shows advantages of using protons instead of x-rays for all five patients. The dose-limiting organs at risk are the spinal cord, the lungs, and the heart, but the proton plans also spare the kidneys better than the x-ray plan does. At 5% NTCP in any risk organ, the calculated mean TCP value for the five patients is increased by an average of 20%-units (from 2 to 23%-units) with the best proton plan compared with x-rays only. However, if we assume maximally a 1% risk in the spinal cord and a total NTCP for the two lungs of 100%, the mean TCP value for the five patients is increased from 6 to 49% with the best proton plan compared with x-rays only. The corresponding figure for the mixed plan is 27%. These gains are relatively insensitive to variations within reasonable limits in the biological parameters.

Conclusions: Protons appear to have clear therapeutic advantages over conventional external radiotherapy when treating esophageal carcinoma.

Introduction

Esophageal cancer is a substantial cause of mortality in the Western world and recent data indicate that the incidence is increasing (1). Surgery, although potentially curative in only a small subset of patients, is usually the main treatment option. In addition to surgery, radiotherapy and chemotherapy are increasingly used with the aim of improving the dismal prognosis (2). Radiotherapy is also used alone, or in combination with chemotherapy in primarily inextirpable esophageal cancer in order to get a down-staging permitting subsequent surgery (3). Finally, apart from palliative purposes, radiotherapy has also been tried in patients who are not medically fit for curative surgery or who refuse such surgery (4). In small, usually superficial tumors, various intracavitary techniques, alone or in combination with external radiotherapy, have often given satisfactory palliative results (5). The results with radiotherapy alone have, however, been disappointing 2., 6..

In order to obtain higher tumor control rates without increased normal tissue complication rates, a precise dose delivery to the target volumes is important. This can be achieved in several ways. The technical development of conventional radiotherapy, such as multileaf collimators, compensation filters, and 3-D treatment planning, has allowed the dose delivery to be more conformed with the target volume. Protons have a finite range of penetration in tissues and an increased dose delivery at the end of the range (7). Range modulated protons are thus in this context an interesting alternative to conventional x-rays and electron beams. Clinical gains with protons have already been observed in the treatment of uveal melanomas, and sarcomas of the base of the skull or of the paravertebral region (8). Protons have also been tried in a number of other tumors, including those from the esophagus (6), with preliminarily favorable results (9).

The potential advantages for protons over conventional x-ray therapy have also been demonstrated in model treatment planning studies for a number of tumors (10., 11., and references quoted therein). These studies have usually been performed on a single patient; the proton treatment plans have been compared with the present conventional radiotherapy and the evaluation has been limited to comparing the absorbed dose distributions. In order to gain the desired precise knowledge about the potential advantages of protons, so that decisions about future investments will be improved, several typical patients must be planned and the evaluation should also include estimates of the probability distribution of the treatment outcome, based on biological models. This approach has previously been used in two studies, one including patients with prostatic carcinoma (11) and one with locally advanced rectal cancer (10). In both studies, the tumor control probability increased using protons, although the difference was only marginal in prostatic carcinoma.

The same approach is used in the present study which explores the potential benefits of proton therapy over conventional external x-ray therapy in the treatment of patients with a primary carcinoma of the esophagus.

Section snippets

Patients

Comparative treatment planning was performed for five patients (2 women and 3 men, median age 63 years, range 51–76) with a primary squamous cell carcinoma of the esophagus. The patients were treated within a prospective study to 40 Gy in 2-Gy daily fractions to the primary tumor and adjacent lymph nodes at risk to contain tumor cells, followed by surgery. In addition, the patients received chemotherapy with cisplatinum and 5-fluorouracil. No correlations with the outcome of the individual

Optimization of the x-ray plan

For the two patients where different energies and techniques were tested by experienced treatment planners, it was found that the 4-beam technique using 21-MV photons was not significantly inferior to the others (data not shown). The “optimized” techniques could lower the dose in a particular risk organ, such as the heart, or one of the lungs, which may be of relevance in an individual patient, but it did not increase the TCP significantly above what could be achieved with an optimized 4-beam

Discussion

This study indicates that radiotherapy with protons used either as the sole modality or as a boost after conventional x-rays may have potential advantages over external conventional x-rays when treating patients with an esophageal carcinoma. This advantage was evident in all five patients, both when examining the absorbed dose distributions and using the biological models. The magnitude of the advantage, i.e., how many more patients will be (locally) cured, is, however, difficult to estimate

Conclusions

Proton beam therapy has potential advantages over conventional external x-ray therapy when treating inoperable patients with esophageal carcinoma. The study thus provides support for proposals about proton therapy facilities that have the capacity to prove the potential benefits in large randomized studies. Model studies, like the present one, the study in prostatic carcinoma patients (11), and the study in medically inoperable rectal cancer patients (10) are then needed to identify tumor

Acknowledgements

This study was supported by grants from the Swedish Cancer Society and from the Lion’s Cancer Foundation at Uppsala University Hospital. The authors thank all personnel at the Department of Hospital Physics at Uppsala University Hospital and especially Charles Widström for constructive and interesting discussions. Valuable help from Dr. Gunnar Wagenius and Marie-Ann Emamjomeh is gratefully acknowledged.

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Physics ContributionsComparative Treatment Planning Between Proton and X-Ray Therapy in Esophageal Cancer

Abstract

Introduction

Section snippets

Patients

Optimization of the x-ray plan

Discussion

Conclusions

Acknowledgements

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Radiother. Oncol.

Radiother. Oncol.

Comp. Meth. Prog. Biom.

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.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Oesophageal carcinomaThe need for screening

Eur. J. Cancer Prev.

Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery

J. Clin. Oncol.

Downstaging of esophageal cancer after preoperative radiation and chemotherapy

Ann. Surg.

101 oesophageal cancersA surgeon uses radiotherapy

Ann. R. Coll. Surg. Engl.

High dose rate brachytherapy before external beam irradiation in inoperable oesophageal cancer

Br. J. Ca.

Physics Contributions
Comparative Treatment Planning Between Proton and X-Ray Therapy in Esophageal Cancer