Prospective trial in 3D PDR brachytherapy
Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: Results of the French STIC prospective study

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Abstract

Purpose

In 2005 a French multicentric non randomized prospective study was initiated to compare two groups of patients treated for cervix carcinoma according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric planning method was chosen for each patient in each center according to the availability of the technique. This study describes the results for 705 out of 801 patients available for analysis.

Patients and methods

For the 2D arm, dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly CT) and performed with PDR BT. Each center could follow the dosimetric method they were used to, according to the chosen radioelement and applicator. Manual or graphical optimization was allowed.

Three treatment regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76; 3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D arm: 118; 3D arm: 117).

The DVH parameters for CTVs (High Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent doses in 2 Gy fractions (EQD2). Side effects were prospectively assessed using the CTCAEv3.0.

Results

The 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT doses and volumes were comparable between the 2D and 3D arms in terms of dose to point A, isodose 60 Gy volume, dose to ICRU rectal points, and TRAK.

Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High Risk CTV (HR CTV D90) was respectively, 81.2 Gyα/β10, 63.2 Gyα/β10 and 73.1 Gyα/β10 for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5 Gyα/β10, 57.3 Gyα/β10 and 61.7 Gyα/β10 for groups 1, 2 and 3. For the OARs, doses delivered to D2 cc ranged 60–70 Gyα/β3 for the bladder, 33–61 Gyα/β3 for the rectum, and 44–58 Gyα/β3 for the sigmoid according to the regimen.

At 24 months, local relapse-free survival was 91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3; grade 3–4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2, and 22.7% and 2.6% in group 3 for 2D and 3D arm.

Conclusion

This multicentric study has shown that 3D BT is feasible and safe in routine practice. It has improved local control with half the toxicity observed with 2D dosimetry. The combined treatment with radiotherapy and surgery was more toxic than definitive radiotherapy. For patients with advanced tumors, it is necessary to improve coverage of target volumes without raising toxicity.

Section snippets

Material and methods

From March 2005 to June 2007, twenty centers participated in the study. BT could be associated with EBRT/chemotherapy and/or surgery according to the stage of the disease. For IB1 tumors, patients were treated with BT followed by surgery 6 weeks later. For higher stages or in case of nodal involvement, treatment started with EBRT associated with chemotherapy in the absence of contra indication, followed by BT; surgery could be proposed according to each center protocol, for limited stages. The

Results

The study was completed in June 2007 after 801 patients were enrolled. By September 1st 2009, 705 patients were available for analysis and are reported here. The 96 remaining patients were excluded from the analysis as we were not able to retrieve any data about them.

The 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, chemotherapy and EBRT (Table 1). The most frequent applicator used was the Fletcher’s, followed by the mold applicator (Table 2). In the 2D arm, PDR,

Discussion

During the last decades, the introduction of the afterloading miniaturized sources have led to improvements in BT by allowing for variation of the stepping time of the source (HDR or PDR BT) and additionally, the ability to visualize 3D dosimetry on cross-sectional images. The clinical impact of optimization of BT dose has been recently clearly demonstrated [21], [22]. 3D BT is now considered as a standard, although a number of questions remain to be clarified [23].

In 2004, our study was

Conclusion

This multicenter prospective study including 20 centers has shown that 3D BT is feasible and safe in routine practice. We also showed that even without complex procedures of optimization, 3D BT has improved the outcome of cervix carcinoma: it allowed for lower grade 3–4 toxicity by a factor 2 while improving local control, compared to 2D BT, although longer follow up is needed to confirm these results. Therefore, we propose conversion of 2D cervix BT to 3D dosimetry and optimization in all

Conflict of interest

None declared.

Acknowledgments

We wish to thank Astrid de Leeuw for the material support for the calculation of the radiobiologically equivalent dose of PDR BT.

The following radiation oncologists and physicists are being acknowledged for their contribution to the STIC PDR study:

P. Magnenet, N. Allières, T. Lacornerie, Y. Kirova, J. Bonnet, J. Coulot, P. Romestaing, M.-P. Sotton, P. Lang, G. Boisserie, S. Racadot, C. Malet, A. Chemin, D.Williaume, J. Bellec, C. Krzisch, K. Peignaux, J.-P. Brenier, A. Cussac, A. Lisbona, M.-H.

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