Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 2, Num. 4, 2006, pp. 161-165

Journal of Cancer Research and Therapeutics, Vol. 2, No. 4, October-December, 2006, pp. 161-165

Original Article

Intensity modulated radiotherapy in abdominal malignancies: Our experience in reducing the dose to normal structures as compared to the gross tumor

Kataria Tejinder, Rawat Sheh, Sinha SN, Negi PS, Garg Charu, Bhalla NK, Munjal RK

Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi - 110 085
Correspondence Address:Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Center, Sector 5, New Delhi - 110 085, t_kataria@rediffmail.com

Code Number: cr06041

Abstract

Background and Purpose: A better understanding of appropriate sequencing and use of multimodality approach in the management and subsequent improvement in overall survival mandates a vigil on quality of life issues. Intensity modulated radiotherapy (IMRT) is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for abdominal malignancies.
Materials and Methods: During the period January 2002 to March 2004, 11 patients of various sites of malignancies in the abdominal region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms.
Results: An average dose reduction of the mean values by 50% to the liver, 57% to the right kidney, 56% to the left kidney, 66% to the cord and 27% to the bowel, with respect to the GTV could be achieved with IMRT. The two-year disease free survival was 79% and two-year overall survival was 88%. The average number of IMRT fields used was six.
Conclusion: IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs.

Keywords: Abdomen, intensity modulated radiotherapy

Introduction

Curative doses of radiation in many instances may lead to good disease control but cause radiation-induced chronic morbidities such as acute and late bowel toxicity, bladder ulcers, telengiectasia and contracted bladder and bone necrosis. These toxicities are dose-related and different structures have varying tolerance to radiation. The availability of data on tissue tolerances makes it imperative to respect the tolerance of critical structures such as the kidneys, liver, spinal cord, small bowel, rectum etc. and reduce associated morbidities while maintaining a good quality of life.

In most clinical situations, the radiation oncologist is compromised in prescription to treat to tolerance doses of normal tissues rather than to specific tumoricidal dose due to the vicinity of normal structures to the tumor. Intensity modulated radiotherapy (IMRT) has the potential to increase this therapeutic ratio. The use of IMRT as against conventional radiation allows one to sculpt the dose around a complex-shaped target and has the potential to deliver a higher biologically effective dose to the target. A number of studies have demonstrated the superiority of the physical dose distribution of IMRT compared to other modalities with application in brain tumors, head and neck cancers and prostate cancer treatments.[3],[14],[16],[21] As compared to conventional beams, the complexity of IMRT dose patterns makes the verification of the match between planned and delivered doses considerably more difficult. The accuracy of delivered doses is a critical issue for ongoing quality assurance in an IMRT program. Several different techniques have been described and used for clinical implementation of IMRT. These include the "step and shoot" auto sequence multileaf collimator (MLC), dynamic MLC and the physical intensity modulation. The "step and shoot" auto sequence MLC technique delivers an intensity modulated photon field by irradiating a sequence of static MLC ports. The dynamic MLC technique delivers an intensity modulated photon field by moving the collimator leaves during irradiation.[8] Physical intensity modulators are being used to deliver IMRT since the advent of inverse planning software.[13] Schulz[18] and Chang et al,[4] have shown in a comparative study between different techniques of IMRT, that the MLC technology requires considerably longer time (100-400%) to deliver the treatment as compared to PIM-based IMRT. They also found a better target volume dose uniformity with PIMs. Sherouse has elaborated that the solid filters are the gold standard and MLC can be an acceptable compromise.[20] He has described solid milled physical modulators as the technology of choice for implementing fluence modulation for IMRT. PIMs are more reliable as the photons are absorbed the same way every time by the PIM, whereas the initial validation measurement in MLC may vary a week later.[20] Hence a day-to-day quality assurance is required to maintain an MLC-based IMRT programme. The resolution of PIM is greater in one of the two dimensions because of the size of the MLC leaves, which is typically either 1 cm or 5 mm and the problem of time invariance arises with moving tissues. In dynamic MLC, if the target moves left while the right segment is being treated and weaves right while the left segment is treated, there is a potential of 100% error.[20]

We present our initial experience with the designing, implementation and dosimetric aspects of IMRT plans of 11 patients.

Materials and methods

Patients of abdominal malignancies form the study group. It is a heterogeneous population with postchemotherapy nonHodgkin′s lymphoma, postoperative cases of periampullary carcinoma, carcinoma stomach, caecum, colon, gall bladder and renal cell carcinoma referred for radiotherapy [Table - 1].

Planning- A thermoplastic cast was made in the treatment position on the simulator using laser beam alignment and fiducial markers were placed on the thermoplastic cast. A planning computed tomography (CT) scan with contrast at cross sections of 3 mm was performed after aligning the external fiducial markers to lasers. The CT images were then transferred to the treatment-planning computer through direct cable network.

Contouring of the tumor and critical normal structures was done by the radiation oncologist with the assistance of a radiologist on every CT slice. Gross tumor volume (GTV) is taken as the gross extent of the tumor as shown by imaging studies coupled with the findings on physical examination in lymphoma cases and clinical target volume (CTV) was defined at 10 mm from the GTV. In postoperative cases, the CTV for every case was individualized according to the drainage areas, information regarding the tumor bed as per surgical notes and knowledge regarding organ motion. The uniformity of margin was not kept if some highly sensitive structure was in the proximity. PTV was placed at 3-5 mm outside the CTV and the beam edge to PTV was placed at 3-4 mm by the medical physicist. Prescription of dose to the target and defining dose constraints for the critical normal structure such as the liver, cord, kidneys, bowel etc. was done keeping in mind the partial tolerances from the published literature[5] [Table - 2]. This patient data facilitated virtual reconstruction of patient anatomy with tumor and organs at risk.

A photon fluence pattern of each individual beam was generated that met the defined dose constraints on the three-dimensional treatment planning system (3-D TPS - Plato, Nucletron International) with inverse planning and optimization software. The fluence patterns were used to design and cut special Necupur templates on computerized numerically controlled 3-D milling machine (Autimo system, Hek Medizintechnik). These templates were subsequently used to mould physical intensity modulators (PIMs) of cerro bend.[13]

Resimulation was done for verification of isocenter and each angle of beam entry as per optimized plan with the help of previously placed fiducial markers under the supervision of medical physicist. Photon fluence pattern from film dosimetry (Vidar scanner) as well as by portal imaging were matched with that of optimized fluence maps from treatment planning system for each beam.

Percentage PTV receiving 100% of prescribed dose (V100), percentage PTV receiving less than 93% dose (V93) and percentage PTV receiving more than 110% of prescribed dose (V110) were evaluated as per Collaborative Working Group (CWG) recommendations.[3] The homogeneity index (H.I.) was calculated by evaluating the percentage variation between 95% and 10% volume of the PTV using the following formula H.I. = D ₁₀ /D ₉₅ where D ₁₀ is the dose received by 10% PTV and D ₉₅ is the dose received by 95% of the PTV.[9],[11]

Statistical analysis was done using SPSS software version 10. Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan Meier method. The DFS was calculated from the date of completion of the planned treatment and OS was calculated from the date of commencement of treatment. For calculating DFS, "disease recurrence", "residual disease" and "lost to follow-up with disease" were taken as events while for calculating the OS, "cause specific death", "lost to follow-up with disease" and "alive with disease" were considered as events.

Results

The median age was 51 (31-74) years. The median follow-up was 15 months. Eight out of 11 patients achieved a complete response (C.R.), one had partial response (P.R.), one had progressive disease and both these patients were lost to follow-up. One patient had a relapse and is undergoing salvage chemotherapy. Both incomplete responses were at the local site. The average number of IMRT fields was six (range 5-11). For PTV, V100 was 90.3% (70-98%), V93 was 2.4% (0-5%) and V110 was 10% (2-23%). For GTV, V100 was 90.3% (70-98%), V93 was 2.3% (0-4%) and V110 was 11.2% (2-30%). The homogeneity index (H.I.) calculated by evaluating the percentage variation between 95% and 10% volume of the PTV was 1.1 (1.1-1.3) and 95% and 10%volume of the GTV was 1.1 [Table - 3]. It is important to note that the maximum dose described by the international commission on radiation units and measurements report 50 is the region that is encompassed by 1.5 cm ³.[7]

With IMRT plans we were able to achieve an average reduction in mean doses by 50% to the entire liver, 51% to 2/3rd and 42% to 1/3rd liver; 57% to the entire right kidney, 59% to 2/3rd and 54% to 1/3rd right kidney; 56% to entire left kidney, 58% to 2/3rd and 50% to 1/3rd of the left kidney; 66% to the cord and 27% to the bowel, with respect to the GTV [Table - 4].

The full right kidney dose was 22.4 Gy (10 Gy -38 Gy), 2/3rd kidney was less than 21.7 Gy (12 Gy -38 Gy) while 1/3rd right kidney received less than 26.4 Gy (18 Gy - 37 Gy).The full left kidney dose was 21.3 Gy (10 Gy -35 Gy), 2/3rd left kidney was less than 20.2 Gy (11 Gy -33 Gy) while 1/3rd left kidney received less than 24.1 Gy (15 Gy - 40 Gy).

Two-year DFS was 79% with a mean of 31.26 months [95% C.I.: 19.57, 42.96] and two-year OS was 88% with a mean of 39.69 months [95% C.I.: 31.51, 47.87].

Discussion

There is paucity of data regarding the practice of IMRT in abdominal malignancies in literature using physical intensity modulators. We have presented the initial observations and results using PIMs; and this is the only study highlighting daily reproducibility, accuracy and outcomes using this technique so far available in literature [Table - 5].

The only technical advantage of MLC in present time seems to be that it does not involve manufacturing of a physical modulator which is time-consuming and that the technologist does not have to go in the treatment room again and again to change the PIM.

The TD 5/5 of 23 Gy for whole organ irradiation of kidneys, 30 Gy for 2/3rd kidney and 36 Gy for 1/3rd kidney have been reported by Rubin, Sell and Withers,[17],[19],[23] Willett,[22] Birkhead.[1] In our series, the average full renal dose was 21.8 Gy, 2/3rd of the kidney received less than 21.9 Gy and 1/3rd organ received less than 25.25 Gy.

The TD 5/5 of 30 Gy for whole liver, 35 Gy for 2/3rd liver and 50 Gy for 1/3rd liver has been accepted, the end point being hepatitis or liver failure.[5] In our series, the entire liver received a dose of 25 Gy (12 Gy - 41 Gy), 2/3rd received a dose of 24.2 Gy (15 Gy - 32 Gy) and 1/3rd liver received a dose of 30 Gy (16 Gy - 45 Gy).

Landry et al[12] have reported on treatment of 10 cases of pancreatic cancer with IMRT and described 1/3rd of small bowel receiving 30.2±12.9Gy. The median volume of small bowel receiving 50 Gy was 19.2±11.2%. The median volume of small bowel that received greater than 60 Gy was 12.5±4.8%. Using Lyman Kutcher model, they predicted small bowel complication probability of 9.3±6% with IMRT.

Portelance et al, in a dosimetric analysis have shown the small bowel to receive 11.01±5.67% of prescribed dose by 4-field IMRT plan. Similarly the doses to the rectum and bladder have also been reduced drastically.[15] In our series, we were able to limit the dose to 24 Gy (19 Gy-36 Gy) to the entire bowel, 25 Gy (18 Gy-32 Gy) to 2/3rd bowel and 32 Gy (22 Gy-39 Gy) to 1/3rd bowel.

However, there are some areas of concern in planning and delivery of IMRT. Although parameters such as organ movements and daily patient set-up variation are accounted for to some extent in the concept of PTV, there is no provision for the shrinkage of the gross tumor and subsequent change in geometry over the course of radiotherapy.

In view of the fact that IMRT introduces steep gradients near the perimeter of both the target volume and normal structures, IMRT can be "less forgiving" than conventional radiation in regard to the effects resulting from such geometric uncertainties.

Conclusion

IMRT treatment planning uses advanced imaging techniques for tumor and normal tissue segmentation and computer-aided optimization to generate treatment plans that conform the prescription dose to the tumor, with maximum exclusion of the adjacent normal organs. Patient immobilization and computer driven beam shaping devices as well as portal imaging are used to decrease treatment uncertainties and assure the quality of treatment delivery. The reduced volume of normal tissues receiving radiation should hypothetically decrease the radiation morbidity, permitting escalation of tumor dose, thereby yielding higher rates of tumor control.

In our series, it was possible to achieve an average reduction in the mean dose by 50 % to the liver, 57 % to the right kidney, 56% to left kidney, 66 % to the cord and 27 % to the bowel, with respect to the GTV.

IMRT will open up new vistas in cases of reirradiation wherein critical structures have already received near tolerance doses of radiation.

References

Copyright 2006 - Journal of Cancer Research and Therapeutics

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