Presenter: Lei Dong, PhD Presenter's Affiliation: Division of Radiation Oncology, the University of Texas M.D. Anderson Cancer Center Type of Session: Scientific
Despite continued efforts of behalf of the oncology community, prognosis for patients with locally advanced non-small cell lung cancer (NSCLC) remains poor.
Radiotherapy dosing is limited by the proximity of lung cancer tumors to other vital structures including the heart, spinal cord, and esophagus.
Treatment volumes in locally advanced NSCLC remain quite controversial; although dose escalation is likely more possible with smaller treatment volumes and may lead to improved outcomes (Rengan, 2004), these tumors have a high propensity for nodal and subclinical metastasis, and risk of marginally recurrent disease may be increased with smaller treatment volumes.
Several radiotherapy techniques have been employed in attempt to deliver adequate dose to regions of known and subclinical disease, including three-dimensional conformal radiotherapy, intensity modulated radiotherapy, and photon-based stereotactic radiosurgery.
Simultanous in-field boost (SIB) has been utilized with photons in attempt to deliver higher dose to regions of known disease (Gross Tumor Volume, or GTV) and lower doses to regions concerning for subclinical disease (Clinical Target Volume, or CTV) by delivering larger fractions to GTV regions.
This study was carried out in order to evaluate the possibility of delivering SIB using proton beam radiotherapy, and to evaluate potential benefits of this technique in treatment of locally advanced, stage III, NSCLC.
Materials and Methods
The cases of 14 patients with stage III NSCLC were considered as part of this dosimetric study.
GTV was delineated based on tumor visualization through CT scans as well as PET/ CT.
CTV was defined as an 8 mm expansion of the GTV, specifically including areas of suspected microscopic extension. CTV was reduced in certain circumstances in which the expanded volume was noted to cross other organ compartments.
For the cases considered, GTV volumes ranged from 81 – 310 cc, and CTV volumes ranged from 231 – 789 cc. The average CTV:GTV ratio was 2.7.
For each patient considered, 5 treatment plans were created. In all treatment plans, the CTV was prescribed to receive 60 CGE. Plans were created to provide 60, 66, 72, 78, and 84 CGE to the GTV using proton SIB. All treatment was planned to be delivered over 30 fractions.
For all plans, CTV and GTV were planned to receive 95% of their prescribed doses, respectively.
All plans were based on treatment delivery via 250 MeV passively scattered proton beams.
The authors describe making use of properties specific to proton radiotherapy in order to deliver desired doses. Specifically, they note that creating a smaller volume to receive the highest total dose (ie GTV versus CTV) permits use of a smaller spread-out Bragg peak (SOBP). Furthermore, a smaller SOBP is associated with decreased entrance dose, allowing maintenance of low peripheral dose, with increase of the dose to the smaller, GTV, target.
In all treatment plans for the patients evaluated, the CTV received the same dose coverage of 60 CGE to 95% of the volume.
Additionally, in all treatment plans, 95% of the GTV received the prescribed dose (60, 66, 72, 78, or 84 CGE).
The authors describe that plans delivering 60 CGE to both the CTV and GTV demonstrated large penumbras, with dose spread covering the heart and spinal cord, as well as the treatment volumes. In contrast, they note that plans delivering 60 CGE to the CGE and 84 CGE to the GTV had more narrow penumbras. Dose distribution was noted to be heterogenous, and this was associated with decreased dose to the spinal cord and heart.
Specific organ dosing was as follows:
The mean dose to the heart was noted to decrease in all cases when GTV dose was increased from 60 CGE to 84 CGE.
Mean heart doses were 7.4, 15.8, 4.2 and 12.6 CGE for patients 1-4 when GTV was prescribed to 60 CGE, and 5.5, 12.4, 2.4, and 10.9 CGE, respectively, when GTV was prescribed to 84 CGE.
The volume of the heart receiving 40 CGE was also noted to decrease as GTV dose was increased.
The mean dose to the total lung volume was noted to stay approximately constant with GTV dosing to 66 and 72 CGE when compared to 60 CGE, and to increase very slightly with dosing to 78 and 84 CGE (by 0.7 and 1.6 CGE, respectively).
Total lung volume receiving 5 CGE (V5) and 10 CGE (V10) was noted to decrease with escalation of GTV dose.
The authors made special note that these volumes reflected total lung dose, not volume of lung with CTV volume subtracted.
The volume of esophagus receiving at least 50 CGE was noted to decrease with increased dosing to the GTV.
The mean total body dose was noted to decrease with GTV dose to 66, 72, and 78 CGE. Mean total body dose increased by approximately 4 CGE with GTV dose to 84 CGE.
The authors conclude that the proton SIB technique is feasible with passively scattered proton therapy, and that dose to normal tissues is essentially unchanged with GTV boost to 84 CGE when compared to GTV dose to 60 CGE.
They note that this method takes advantage of a slowly-falling proximal SOBP dose distribution that allows creation of a non-uniform dose gradient between the GTV and the CTV, creating a heterogenous dose distribution.
Radiotherapeutic treatment of NSCLC remains controversial with regards to treatment volumes and planned doses. Regardless of technique, this treatment is complicated by the risk of damage to vital structures such as the heart, lung, and spinal cord.
The dosimetric data presented here raises the interesting concept that proton radiotherapy may be used to deliver simultaneous in-field boost to the GTV with little increased dose to normal tissues.
The clinical implications of this technique are yet to be investigated; however, this technique may be an appropriate addition to the armory of techniques available for treatment of NSCLC.
Stable or decreased dose to normal tissues would be expected to allow increased dose to known tumor volumes, potentially without increased risk of radiation-induced cardiac, lung, and neurologic toxicity that may be seen with dose-escalation in the setting of photon radiotherapy.
Use of the technique described here will likely be limited in the immediate setting by our limited understanding of proton dose and trajectory in lung tissue (Widescott, 2008).
Although the technique presented here is theoretically quite appealing, clinical benfits have not at this time been investigated. Further trials examining the use of the technique in the clinical setting would certainly be of interest.