Comparative dosimetric evaluation of the simultaneous integrated boost with photon intensity modulation in head and neck cancer patients
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.
Section snippets
Patient selection
A cohort of five patients presenting with stage III–IV squamous cell carcinomas of head and neck region (T4N1 of the larynx, T2N1 and T4N3 of the oropharynx, T4N2 of the pharynx, T2N1 of the base of tongue), and already treated in our institute with a conformal technique [14], was selected for the planning study.
CT data were acquired with a slice spacing of 5 mm, thickness of 3 mm, over the entire treatment area and extending at least 6 cm beyond the elective target volume in both directions.
Dose prescription
The physical dose prescriptions that have to be foreseen in the three fractionation strategies are reported in Table 2, together with the dose per fraction and the total number of fractions. Those dose levels are the physical doses biologically equivalent to 50 Gy to PTVII and 80 Gy to PTVI given in conventional sequential regime at 2 Gy per fraction, one fraction per day.
Plan intercomparison
The results of the comparison of the three fractionation schemes (with dose prescriptions as in Table 2) are reported in Table 3
Discussion
The SIB concept developed by Mohan et al. [23], and already clinically introduced in their institute to accelerate and dose-escalate treatments in head and neck patients has been investigated in the present study, together with accelerating the boost in the last period of treatment [3], [17]. The aim of our analysis was the investigation of dosimetric properties of the conventional sequential regime compared to the SIB and to a modified SIB regime (SEQ/SIB), where the concomitant integrated
Conclusion
A critical appraisal of three different fractionation regimes, sequential, SIB and modified SIB (SEQ/SIB) was carried out, as a comparative analysis of treatment plans, for advanced head and neck cancer. Treatment plans were based on IMRT with photon for all regimes. The modified fractionation strategy proposed was intended to allow an escalation of tumour dose that would not jeopardise the quality of life in terms of the acute complications, compared with standard SIB regime. Total dose to the
Acknowledgements
The present work was partially sponsored by TERA Foundation, Novara, Italy and by Onco-Suisse Foundation, Bern, Switzerland. The authors are deeply grateful to Varian MS AG, Zug, Switzerland, who provided logistic support and free access to the Cadplan-Helios treatment planning system to perform our studies.
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