Nasal cavity reirradiation: a challenging case for comparison between proton therapy and volumetric modulated arc therapy



The aim of this case report is to report on a dosimetric comparison between volumetric modulated arc therapy (RapidArc technique and active scanning proton therapy (single-field (SFO) and multifield (MFO) techniques) in a case of nasal cavity cancer recurrence.

Case report

A 72-year-old man, who received adjuvant radiotherapy for a carcinoma of the nasal cavity, experienced an unresectable local recurrence in the previous surgical bed. Hence, the patient was evaluated for reirradiation by comparing different modalities, with a total prescribed dose of 50 Gy in standard fractionation. RA plan was revealed to be equivalent to the MFO plan in terms of target dose coverage and conformity index. SFO plan was not able to respect a maximum dose of 9 Gy to nervous structures, in contrast to RA and MFO plans.


In this challenging scenario, although a clear preference would be given to the MFO proton plan, the RA plan was revealed to be adequate for the clinical goal of target coverage and sparing of organs at risk.

Tumori 2016; 102(Suppl. 2): e12 - e15

Article Type: CASE REPORT



Ruggero Ruggieri, Francesco Dionisi, Rosario Mazzola, Francesco Fellin, Alba Fiorentino, Marco Schwarz, Francesco Ricchetti, Maurizio Amichetti, Filippo Alongi

Article History


Financial support: No grants or funding have been received for this study.
Conflict of interest: None of the authors has any financial interest related to this study to disclose.

This article is available as full text PDF.

Download any of the following attachments:


Although in locally advanced nasal cavity (NC) cancer, surgery followed by postoperative radiotherapy (RT) or radical RT with or without chemotherapy (CT) are generally recommended, a rate of locoregional recurrences of 30% is reported. In unresectable and resectable relapse, external reirradiation assures 10% and 20% disease control rates, respectively (1). Limiting issues are represented by the interval from previous RT, tumor volume, tolerance of surrounding organs at risk (OARs) and target volume dose coverage (2).

In cases of NC irradiation, volumetric modulated arc therapy, including the RapidArc technique (RA; Varian Inc., Palo Alto, CA, USA), assures adequate target dose coverage and homogeneity, with a high level of OAR dose sparing (3, 4). Proton therapy (PT), due to its dosimetric characteristics, can be an adequate option for NC reirradiation. The usefulness of PT for treating head and neck cancers (HNCs) near the spinal cord and the base of skull has already been demonstrated (5).

In the present report, a dosimetric comparison between RA and PT for NC cancer recurrence was made.

Case report

A 72-year-old man, with NC carcinoma, underwent to a left medial maxillectomy and resection of the nasal septum on May 2012. Histopathological examination confirmed a high-grade malignant intestinal adenocarcinoma, with negative margins. Adjuvant RT was performed in August 2012, by 7-field sliding window intensity modulated radiation therapy (IMRT) using a Trilogy linear accelerator (Varian Inc., Palo Alto, CA, USA), for a total dose of 60 Gy over 30 fractions.

In December 2014, the patient experienced a locoregional recurrence. At magnetic resonance imaging (MRI), the lesion occupied the previous surgical cavity strictly related to optic structures (Fig. 1). No visual deficit was referred to by the patient. The case was discussed at the multidisciplinary tumor board: due to the extension of the recurrence, the lesion was judged unresectable. Hence, the patient was a candidate for reirradiation, with a total prescribed dose (Dp) of at least 50 Gy in standard fractionation (d = 2 Gy/day).

Magnetic resonance imaging scan: transversal section of the recurrence of nasal cavity cancer.

Considering the previously irradiated site, the late-reacting OARs that were taken to be critical for reirradiation were the left and right optic nerves (RON and LON) and optic chiasm (OC). The 2 computed tomography (CT) datasets, used for planning at first occurrence and at recurrence of disease, were rigidly registered, including both translations and rotations, on the bone structures which confine the region of interest for tumor location. After registration, the plan used for the previous treatment was recomputed at an equal number of monitor units on the new CT dataset. As a result, the near-maximum (at 0.1 cm3) doses (D0.1cc) received during the previous treatment were estimated to be 53.5 Gy, 66.7 Gy and 59.5 Gy to the RON, LON and OC, respectively. Assuming a recovery of the nervous structures of around 10%-15% per year (6), a D0.1cc <9 Gy to the previous critical OARs for the present reirradiation was defined as the necessary criterion for planning approval. This approach, without any distinction between the 3 nervous structures, although with a different dose involvement from the previous treatment, was cautiously adopted to minimize the risk of blindness for both optic pathways.

The patient was simulated with his head held in a thermoplastic immobilization device (Brainlab Inc., USA), in a supine position. Two-millimeter CT slices with contrast medium were obtained through the region of interest. The gross tumor volume (GTV) was defined as the extent of tumor on CT and MRI scans. GTV was not expanded to obtain a clinical target volume (CTV). Instead, an isotropic 3-mm margin was made from GTV to planning target volume (PTV). Planning at risk volumes (PRV), which were used in optimization only, were created for the OC, RON and LON with a 3-mm isotropic expansion. Both PTV and PRV margins were chosen equal to 3 mm as a result both of the rigidity of the adopted immobilization system (a frameless stereotactic cranial mask; BrainLab Inc.) and of the accuracy of the associated localization system (infrared and radiographic tracking by a 6D-robotic couch; ExacTrac, BrainLab Inc.).

Further, as reference structure for dose grid normalization, the PTV cropped by 1 mm (PTV1mm) from the RON, LON and OC was also derived.

The patient CT dataset was shared between the Radiation Oncology Department (Negrar-Verona, Italy) and the Proton Therapy Unit (Trento, Italy) for photon-proton planning comparison. The same dataset (CT data and structures) was used for both photon and proton planning.

Normalization of the optimized dose grids, for all of the compared plans, was fixed by requiring 95% Dp to 95% of the PTV1mm. For plan comparison purposes, PTV dose coverage was estimated in terms of near-maximum (D2%), near-minimum (D98%) and median dose (D50%), together with the fractional target volumes receiving at least 95% of Dp (VPTV95%Dp). From such parameters, the homogeneity index (HI) ([D98%−D2%]/D50%), which is equal to zero for the ideal plan, and the conformity index (CI) (VBody95%Dp/PTV), by assuming 95% as the reference isodose level, which is equal to 1 for the ideal plan, were also estimated.

RA, single-field (SFO) and multifield (MFO) plans were computed for Dp = 50-60 Gy (25-30 fractions). Finally, critical OAR dose involvement was estimated in terms of D0.1cc.

Photon planning

RA irradiation was based on a first pair of 280° arcs on a transverse plane, with a second pair of 160° arcs on a sagittal plane (90° couch rotation), both delivered with 10 MV flattening-filter-free (FFF) photon beam from a TrueBeam linear accelerator (Varian Inc., Palo Alto, CA, USA). To optimize the sparing of optic structures while pursuing target dose coverage, PRVs were also included in inverse optimization.

Optimization was performed by the PRO algorithm, and dose calculation was made with the AAA algorithm (version 10.0.28; Varian Inc., Palo Alto, CA, USA), using a dose calculation grid size equal to 2 mm and by including CT-based heterogeneity corrections.

Proton planning

Proton plans were generated using an XIO planning system (Xio Proton; Elekta AB, Stockholm, Sweden) using the beam model currently adopted at the Proton Therapy Unit of Trento, which has been treating patients since October 2014 using active scanned protons (energy range 70-230 MeV, spot sigma @ 32 g/cm2 ~ 2.65 mm) accelerated by a cyclotron and delivered by a 360° rotational gantry. SFO and MFO were tested for the present case. The former employs individually optimized PT fields that each deliver a homogeneous dose to the target volume, while MFO is analogous to IMRT and combines a number of nonuniform, nonhomogeneous fields to produce the desired dose distribution. A 4-field coplanar and noncoplanar beam arrangement (250° couch 0°, 110° couch 0°, 280° couch 90°, 240° couch 90°) was chosen for both SFO-MFO plans. No energy adsorber was employed. Spot spacing was set at 0.3 cm.


Dose-volume findings, for both target dose coverage and OAR sparing are listed in Table I. Comparing the 3 computed plans for a Dp = 50 Gy, the SFO and MFO plans were associated with an improved D98% compared with the RA plan. A reduced D2% value was observed for SFO and MFO plans, as a consequence of a more homogeneous target dose distribution compared with the RA plan, as documented by the reduced HI values. A worst CI value was found for the SFO plan. The RA plan was revealed to be equivalent to the MFO proton plan in terms of target dose coverage and CI.

Dose-volume metrics for target dose coverage and dose involvement to critical organs at risk.

D2% D98% D50% HI CI VPTV95% DRON0.1cc DLON0.1cc DOC0.1cc
VMAT = Volumetric modulated Arc Therapy; SFO = Single field optimization; MFO = Multiple field optimization.
(Gy) (Gy) (Gy) (%) (Gy) (Gy) (Gy)
VMAT (Dp = 50 Gy) 57.5 34.8 52.6 0.43 1.08 90.8 6.6 8.6 5.8
SFO (Dp = 50 Gy) 54 38.9 52.3 0.29 1.2 91.2 12.2 14.1 5.1
MFO (Dp = 50 Gy) 51.3 38.1 49 0.27 1.11 91 4 4.5 2.3
MFO (Dp = 60 Gy) 61.6 45.7 58.8 0.27 1.11 91 4.8 5.4 2.8

Regarding the sparing of critical OARs, only the RA and MFO plans were able to respect the D0.1cc <9 Gy. This is illustrated both in Figure 2, where the dose distributions from the 3 plans are shown, and in Figure 3, where the cumulative dose-volume histograms (cDVH) for the 3 critical optic OARs (LON, RON and OC) are reported. Finally, if a Dp = 60 Gy had been prescribed, only the MFO plan would have been able to respect the D0.1cc <9 Gy to OARs criterion.

A snapshot of the dose distributions from the 3 plans compared (single-field optimization (SFO) on the left, RapidArc therapy (RA) in the middle, multifield optimization (MFO) in the right) with total prescribed dose (Dp) = 50 Gy, within the 9-47.5 Gy dose range. The contours depict the planning target volume (PTV) and the 3 critical optic organs at risk (OARs; right optic nerve (RON), left optic nerve (LON) and optic chiasm). Where the blue appears, the 9-Gy threshold dose to the critical optic OARs is reached, while where the red is saturated, the 95% of Dp = 50 Gy is assured for target dose coverage. At equivalent target dose coverage, the SFO plan enlarges the 9-Gy isodose level toward the 3 critical optic OARs compared with both the MFO and RA plans.

Dose-volume histograms for right optic nerve (RON), left optic nerve (LON) and optic chiasm (OC) from the 3 plans compared. MFO = multifield optimization; RA = RapidArc therapy; SFO = single-field optimization.


Recurrent HNC, in a previously irradiated area, poses a difficult therapeutic challenge for radiation oncologists. Although no phase III studies on dose escalation are available in the reirradiation setting, evidence from retrospective analyses suggest that higher radiation dose is associated with better local control. In fact, a dose ≥50 Gy seems to be related to a significantly better overall survival compared with a dose <50 Gy (7). In a phase II study (8), a total dose of 60 Gy was delivered. The 2- and 3-year locoregional control rates were 27% and 22%, respectively. Acute/late morbidity remained within acceptable limits.

NC reirradiation represents a hard clinical situation, often constrained by the tolerance of the optic apparatus. Considering the previous irradiation course, a precautionary D0.1cc <9 Gy constraint was chosen in the current case. In naive ­optic structures, the incidence of radiation-induced optic neuropathy is unusual for a maximum dose <55 Gy. This risk increases to around 7%-20% if a maximum dose >60 Gy is given. Limiting the OAR dose, it is not unusual to compromise the target ­coverage with a higher risk of locoregional failure (9). In case of reirradiation, the probability of late radiation-induced morbidity is higher and increases with larger volumes irradiated, thus, in the present case, GTV was not expanded to obtain CTV.

PT can be associated with better outcomes compared with photon therapy (5). The new IMRT techniques, such as RA, are able to reduce OAR doses in proximity to the NC (3). The results of the current report confirm that advanced PT techniques (spot size <5 mm sigma, intensity-modulated MFO techniques) are needed to create dose distributions superior to RA. Looking at dosimetric findings, a clear preference would be given to the MFO plan, in terms of higher Dp guaranteed with homogeneous target dose distribution and critical OAR sparing.

The present experience reflects a challenging clinical scenario, where the high risk of treatment-related toxicity could hamper the delivery of an adequate dose for local control. Photon-proton planning comparison studies can help in choosing the proper treatment strategy. However, their limitations should not be underestimated: (i) the PTV concept to account for geometrical uncertainties is commonly accepted in the photon world, while it can not be adequate to account for PT, especially for MFO plans (10); (ii) robustness analysis (i.e., evaluation of the offset between the planned and the delivered dose distribution) for both techniques was not performed in this case. In this context, the complex interaction between setup errors and anatomical uncertainties (i.e., anatomical changes during the treatment course) can result in a degradation of quality between planned dose and delivered dose (11). The potential impact of such variations is greater in PT than in photon therapy, due to the finite range of protons. The development of robustness tools (i.e., protocols for reimaging and plan adaptation during treatment) to ensure the delivery of high-quality plans is essential, especially when nonuniform, nonhomogeneous fields are used as in MFO planning. To date, the clinical implementation of MFO in Trento is ongoing.

Finally, for a Dp of 50 Gy, the RA plan was not less appropriate than the SFO plan for several reasons: (a) it satisfied an OAR D0.1cc <9 Gy; (b) it obtained a target dose coverage and CI better than the SFO and equivalent to MFO. For the second reason, the MFO was the only one capable of ensuring adequate target coverage and OAR sparing for the highest dose prescription (60 Gy).

In conclusion, we have quite good reasons to believe that the beam model used for this treatment comparison can be a satisfactory description of the beam in actual use in patient treatment.


Financial support: No grants or funding have been received for this study.
Conflict of interest: None of the authors has any financial interest related to this study to disclose.
  • 1. Forastiere A Koch W Trotti A Sidransky D Head and neck cancer. N Engl J Med 2001 345 26 1890 1900 Google Scholar
  • 2. Cacicedo J Navarro A Alongi F et al. The role of re-irradiation of secondary and recurrent head and neck carcinomas: is it a potentially curative treatment? A practical approach. Cancer Treat Rev 2014 40 1 178 189 Google Scholar
  • 3. Jeong Y Lee SW Kwak J et al. A dosimetric comparison of volumetric modulated arc therapy (VMAT) and non-coplanar intensity modulated radiotherapy (IMRT) for nasal cavity and paranasal sinus cancer. Radiat Oncol 2014 9 193 Google Scholar
  • 4. Mazzola R Ricchetti F Fiorentino A et al. Dose-volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment. Br J Radiol 2014 87 1044 20140543 Google Scholar
  • 5. Patel SH Wang Z Wong WW et al. Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis. Lancet Oncol 2014 15 9 1027 1038 Google Scholar
  • 6. Steel GG Basic clinical radiobiology. 3th ed 2002 Great Britain Hodder Arnold Google Scholar
  • 7. Sher DJ Haddad RI Norris CM Jr, et al. Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer. Cancer 2010 116 20 4761 4768 Google Scholar
  • 8. Langendijk JA Kasperts N Leemans CR Doornaert P Slotman BJ A phase II study of primary reirradiation in squamous cell carcinoma of head and neck. Radiother Oncol 2006 78 3 306 312 Google Scholar
  • 9. Mayo C Martel MK Marks LB Flickinger J Nam J Kirkpatrick J Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys 2010 76 3)(Suppl S28 S35 Google Scholar
  • 10. Cianchetti M Amichetti M Sinonasal malignancies and charged particle radiation treatment: a systematic literature review. Int J Otolaryngol 2012 2012 325891 Google Scholar
  • 11. Fukumitsu N Ishikawa H Ohnishi K et al. Dose distribution resulting from changes in aeration of nasal cavity or paranasal sinus cancer in the proton therapy. Radiother Oncol 2014 113 1 72 76 Google Scholar



  • Department of Radiation Oncology, Sacro Cuore Don Calabria Hospital, Negrar (Verona) - Italy
  • Proton Therapy Unit, Department of Oncology, Azienda Provinciale per i Servizi Sanitari (APSS), Trento - Italy
  • Radiation Oncology School, Palermo - Italy

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.