We developed an IMRT planning “algorithm” for early glottic cancer with limited beams and segments that reliably reduces carotid artery dose as compared with traditional lateral beam arrangements. This simplified planning has limited impact on resource use, and our early clinical experience is excellent. Despite the limited clinical experience and follow-up currently available, we believe that the important survivorship implications for carotid-sparing IMRT for early glottic cancer warrants introducing this new treatment approach now for academic discussion and further evaluation.
Intensity-modulated RT for T2 glottic cancer has previously been reported by Penagaricano et al
) in a pilot series of 3 patients showing reduction in dose to soft tissue and spinal cord. However, there are no previously published data on the effect of IMRT specifically for carotid dose reduction. The optimized 3D wedged oblique technique presented by Hardie et al
) to reduce arytenoids dose also reduces carotid dose; however, each carotid is at least in the path of the contralateral exit beam, leading to much higher carotid dose than can be achieved with IMRT, approximately half that of the dose prescribed to the CTV. Conceivably, there are additional strategies that might potentially reduce carotid dose without IMRT implementation. Radiation effects on the carotid arteries begin rather quickly after therapy and typically require several years to progress to clinical symptoms. Head-and-neck cancer RT patients in a small prospective series had a 21-fold increase in the thickness of the carotid wall at 1 year after therapy as compared with epidemiologically matched control cohorts (42
). Cheng et al
) observed that the annualized progression rate from <50% to ≥50% stenosis in irradiated arteries was 15.4%, compared 4.8% in nonirradiated vessels, and noted time from RT (>6 years) as a significant risk factor. Relative conditional survival profiling for early glottic cancers demonstrates that laryngeal cancers, as a cohort, demonstrate a plateau in projected disease-specific mortality approximately 2 years after diagnosis (43
Consequently, in early-stage larynx patients with expected disease-specific survival of >5 years, competing causes of mortality (including stroke and second cancers) will typically supersede the rate of recurrence for the index cancer.
Vascular event-probability modification is especially difficult given the typical concurrent health issues facing HNC patients, such as lifetime smoking history (7
). Smoking cessation may reduce risks for vascular disease, as well as second primary cancers, and should be pursued with all patients. A dose–response relationship for carotid arterial effects raises the impetus to consider carotid artery radiation dose reduction when feasible (36
). Surveillance vascular imaging has been recommended to detect and intervene for carotid lesions before clinical progression (13
Given the tissue-sparing effects, IMRT has been increasingly adopted, especially for HNC (46
). It is not infrequent for new technologies to be embraced for a variety of reasons before a benefit is proven, and sometimes the complexities of implementing new technology may undermine the potential gains as compared with more traditional techniques (47
). To date, IMRT has been shown to increase recovery of parotid flow in patients with nasopharyngeal cancer in two randomized clinical trials (48
) and to be cost-effective only for prostate cancer (50
Intensity-modulated RT planning for the vast majority of HNC is highly complex. It requires detailed knowledge of patterns of contiguous and lymphatic spread and the corresponding anatomy of tissue structures, dedicated time to delineate various target volumes (GTV, proper subclinical margins, draining nodal regions, all critical tissues to be spared), and logical specification of dose constraints to individual organs along with fractionation schemes with and without concurrent chemotherapy. Therefore, the professional component of the reimbursement is substantially undervalued despite the addition of special treatment procedure elements. An exception is the IMRT technique for the treatment of T1–2 glottic carcinoma as presented in this article, in which the workload is similar to that of conformal therapy and for which we do not bill differently.
Some have argued against the use of IMRT for early glottic cancer because there would be no practical way to prove benefit over standard therapy. Local control rates exceed 90% (51
), and reported catastrophic complication rates are <1% (6
). We espouse IMRT as a way to safely reduce the risk for late carotid events despite escalation of fractional dose (2 Gy to 2.25 Gy). There is also potential for using IMRT to reduce the dose to the arytenoids, cricopharyngeal inlet, and thyroid gland. A tradeoff, however, would be a small increase in dose to the spinal cord. There have been previous attempts to reduce potential acute treatment toxicity for early glottic cancer, primarily focusing on the reduction in arytenoid dose (52
), and although this is also an important aim, there is not any published documented benefit to date.
Our clinical experience shows that IMRT optimization compensates for dosimetric shortcomings of 6-MV X-rays as compared with 60Co. Intensity-modulated RT planning gives the ability to direct more segments where required, which helps to reduce the penumbra effect to confine the effective field length to 4 cm for T1 cancers and may reduce the requirement for bolus for anteriorly located tumors, though dose modeling in the build-up region may require careful evaluation. Intensity-modulated RT additionally gives the potential for lateralizing therapy more precisely than lateral beam weighting. There is the potential for further dose escalation in the case of T2 tumors, for which control rates are still not optimal, but this notion requires further testing.
We launched a pilot trial based on the favorable outcome of the virtual dosimetry study, which confirmed the simplicity of planning and treatment delivery. The overall time in the treatment room is decreased, thereby improving patient throughput. We will continue to carefully monitor the incidence of cerebrovascular events in these patients. Our current approach treats the entire larynx, similar to the lateral technique. Future studies might serve to reduce dose further when appropriate to the arytenoids, the uninvolved contralateral cord, the cricopharyngeal inlet, and portions of the thyroid gland. Already, four-dimensional CT data have been reported from an investigation of the feasibility of single vocal cord radiation in early glottic cancer (55
). Additional safe and effective small-volume dose escalation could reduce treatment duration. These refinements should be done in centers with excellent physics, dosimetry, and technical support and have implemented stringent quality control procedures.
In summary, limited-field and segmental IMRT techniques for the treatment of early glottic cancer significantly reduce unnecessary dose to the carotid arteries. The development of a template within the planning system allows plans to be generated, optimized, and delivered quickly. Given the high cure rate for early glottic cancer, these dosimetric advantages may be especially important for younger patients, those with extant carotid artery pathology, and those at risk for subsequent development of a metachronous second HNC. On the basis of these data, we are planning a prospective study to compare the conventional and IMRT radiation delivery approaches, specifically investigating posttreatment formation of carotid artery atherosclerotic plaques and clinical outcomes.