Comparative dosimetric evaluation of the simultaneous integrated boost with photon intensity modulation in head and neck cancer patients

Abstract

Background and purpose

The objective of this study is to evaluate, at planning and dosimetric level, the potential benefits of the simultaneous integrated boost (SIB) concept with intensity-modulated radiation therapy (IMRT), using a comparative analysis on physical dose distributions corrected for radiobiological models. The concept of SIB at the end of the treatment has been analysed as an alternative acceleration scheme.

Patients and methods

Physical dose distributions were computed on a commercial planning system (Varian Cadplan-Helios) for five patients presenting with advanced head and neck carcinomas. Treatment plans were designed using five IMRT beams. Three fractionation strategies were compared in the study: the standard sequential irradiation SEQ of elective and boost volumes, the pure SIB, and a modified SIB (SEQ/SIB), where the actual SIB follows a first phase of conventional fractionation to the elective volume. All physical dose distributions were corrected using a linear quadratic biological model, taking into account also repopulation and time at repopulation onset. Objective quantities, derived from biological dose volume histograms, were used for the analysis.

Results

Physical doses equivalent to 50 and 80 Gy (in fractions of 2 Gy) to elective volume and boost were calculated for the SIB and SEQ/SIB regimes. With SIB 54 and 72 Gy dose levels have to be delivered in 30 fractions, while in the SEQ/SIB scheme 36 Gy are delivered in 20 sessions to the elective volume, and further 18 and 35.5 Gy during the last 10 fractions are delivered to elective volume and boost, respectively (for a total physical dose of 71.5 Gy). The comparison showed: (1) the boost target homogeneity resulted in generally acceptable and comparable among sequential and modified SIB schemes, while it was statistically worse for the pure SIB approach; (2) the fraction of elective target volume not included in the boost volume was characterised by a higher level of dose heterogeneity; (3) the spinal cord never reached tolerance levels and maximum point dose was on average below 38 Gy (biologically corrected to 2 Gy/fraction); and (4) sparing of parotid glands strongly depends on their eventual inclusion in the target volumes: for glands not included or only partially included, it was possible on average to keep the dose to 2/3 of the volume below 29 Gy for all regimes (32 Gy as physical dose).

Conclusions

Feasibility of SIB techniques and in particular of the modified SIB appears to be dosimetrically proven and the results reported here justify the activation of a phase I protocol to verify clinically their impact using IMRT photon-based techniques.

Introduction

Loco-regional failures remain a major concern following irradiation of locally advanced head and neck cancers; this has led radiation oncologists to investigate novel approaches that might offer better therapeutic indexes. It is now generally accepted that the modification of dose fractionation schedules can improve the therapeutic outcome by using accelerated or hyperfractionated regimes for fast growing tumours [1], [2], [3], [4], [16], [17]. Different strategies of hyperfractionation [1], [2] proved that an increase of 10–15% in the total dose is consistently associated with a 10–15% increase in local control rates without appreciable increase of late complications. Among acceleration, available data [1], [2] reveal that an acceleration of 1–2 weeks in the total treatment time, without total dose reduction, yielded approximately an increase of 15% over the control rate, still without worsening the late complication rates. In the concomitant boost schemes, a variation of the accelerated models, a second daily dose is delivered to a reduced target volume (at high risk of recurrence) during the course of conventionally fractionated radiotherapy. This might result in a decreased incidence in severe mucositis, which is among the most important dose-limiting acute effects during accelerated/hyperfractionated regimes. In 1990, Ang et al. [3] published results on three different ways to deliver concomitant boost: during the whole treatment of 5–6 weeks, or during the first 2–2.5 weeks, or during the last 2–2.5 weeks of the treatment. The tumour control rate of the third schedule appeared to be superior to the other arms. This was confirmed in 1997, when the same group published data showing that oropharyngeal patients receiving the boost in the last part of the treatment had a higher rate of local disease control (P=0.06) than did those who received the other sequences [17].

A large phase III randomised clinical study was conducted by RTOG whose first report was published in 2000 [16]. Patients were assigned to four groups, standard fractionation, hyperfractionation, accelerated fractionation and accelerated fractionation with concomitant boost for the last 12 sessions. More than 1000 patients were analysed for outcome with a median follow-up of 23 months. Patients with hyperfractionation and accelerated fractionation with concomitant boost had significantly increased loco-regional control with respect to the conventional fractionation. All three altered fractionations increased significantly the acute complication rates, however no significant increase was observed for late effects.

The recent clinical diffusion of intensity-modulated radiation therapy (IMRT) has added new interest in the field of concomitant boost irradiation [3], [4], [10], [20]. Given the promising superiority of IMRT techniques with respect to conventional and conformal techniques [11] to deliver more conformal doses to targets sparing the organs at risk, it could then be justified to combine IMRT with dose escalation, until now hardly applicable to head and neck irradiation with conventional techniques due to excessive toxicity. Moreover the IMRT technique allows the planning and irradiation of different targets at different dose levels in a single treatment session, instead of two treatment plans in two daily sessions.

Among the institutions which developed the application of IMRT techniques to acceleration and concomitant boost in head and neck cancer management, the Baylor College of Medicine in Houston, USA, proposed the simultaneous modulated accelerated radiation therapy (SMART), whilst the Medical College of Virginia in Richmond, USA introduced the simultaneous integrated boost (SIB) technique. In 1999, the former group reported that 20 patients were treated, using the SMART [6], between 1996 and 1997, with doses of 60 and 50 Gy in 25 sessions to the gross tumour site and to the regions at risk for microscopic disease, respectively. With a median follow-up of 15 months, the group reported satisfying results in terms of xerostomia (the highest degree was moderate in 46% of the cases with major relief within 6 months), with good data in terms of treatment outcome (19/20 patients with complete response with only 2/19 recurrences between 10 and 15 months.) The latter group published, starting from 2000, several reports describing the SIB technique [23], [24], [30], [31]. To start off, they designed their fractionation strategies based on radiobiological principles with the aim of allowing an escalation of tumour dose and an adequate sparing of normal tissues outside the target volume. Since, with the SIB technique, physical dose plans are characterised by quite unconventional fractionations even within the same ‘volumes’, the Richmond group developed methods to convert nominal dose distributions back to normalised total doses, using iso-effective formulas based on the linear quadratic model. A dosimetric study (on physical dose distributions) was carried out, in four patients, for SIB in comparison with conventional non-IMRT techniques. Of the planning target volumes, 98% received 70 Gy with the IMRT plans and 73 Gy with the conformal plans. Target coverage was considered clinically satisfactory in both schemes. The major differences were expected for parotids where, with conventional irradiation, almost 95% of the gland volume received at least 46 Gy, sufficient to induce severe xerostomia. With IMRT, 50% of the same volumes received only 28 Gy, with a low probability to induce severe complications. The clinical feasibility and impact of the SIB was the subject of further investigation and, at the end of 2001, the first two groups of 14 patients (mainly oropharyngeal) completed the described treatment [31]. The SIB design included three dose levels: 68 Gy (or 71 or 74 Gy) for gross tumour volumes (the first two groups are completed), 60 Gy for subclinical tumour extensions and 54 Gy for elective nodal irradiation. From preliminary data analysis, the dosimetric objective to irradiate GTV with at least 98% of the prescribed dose was generally met with a significant sparing of parotids (on average 26 Gy to the contralateral and 41.2 Gy to the omolateral glands).

The two concepts of the concomitant boost delivered at the treatment proposed by Ang [3] and the SIB–IMRT have been combined together in the present work. The aim is to evaluate through a comparative treatment plan analysis, the dosimetric and radiobiological aspects of different IMRT fractionation schemes applied to head and neck carcinoma. Two different fractionation approaches, the pure SIB or the SIB in the last part of the treatment, are studied and compared to the conventional sequential regime, with a particular emphasis on radiobiological differences between the approaches.

The rationale are: (i) to have an acceleration to reduce the probability for tumour cells to regenerate during the treatment; (ii) to accelerate the last part of the treatment to increase local control and facilitate the compliance with rather short overall treatment time; (iii) to deliver the accelerated part on rather small volumes with IMRT that allows the planning to two different dose levels, and, by improving the sparing of parotid glands, should reduce severe xerostomia.