Current Cancer Therapy Reviews - Volume 10, Issue 4, 2014

Radiotherapy plays a critical role in the nodal management of patients with head and neck cancer. The indications, dose fractionation schedules, and results of postoperative radiation therapy (PORT) and elective nodal management (ENI) in various head and neck cancers are reviewed and summarized with common themes identified.

Radiation therapy has been a major modality employed in the treatment of head and neck (H&N) cancer for decades. In that time, radiation technology has evolved considerably. Thirty years ago radiation therapy for H&N cancer consisted of two-dimensional techniques using plain field radiographs, bony anatomy, and hand drawn blocks [1]. Beam set ups were generally quite simple and plans generally consisted of opposed lateral fields matched to an anteroposterior supraclavicular field. Nearly a decade later, several technologic developments combined to catapult radiation therapy into a new era. Three-dimensional imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) were integrated with radiation planning technologies creating three-dimensional conformal radiation therapy (3DCRT). The CT simulator rapidly came to replace the x-ray simulator. With CT simulation, the radiation oncologist could now take into account axial anatomy; thereby more accurately identify tumor volumes and institute more complex beam arrangements in treatment planning [2]. During the decade that followed, the cerrobend block was replaced by the multileaf collimator and advances in computer optimization algorithms gave birth to intensity modulated radiation therapy (IMRT). This technological improvement allowed us to modulate the number of radiation fields and the intensity of radiation within each field. Instead of the physician choosing the beam angle, block, and weighting, computer optimization techniques would create a distribution of beamlets based on dose parameters to contoured structures (a process referred as inverse planning) [3, 4]. IMRT changed the practice of radiation oncology by providing the user unprecedented ability to sculpt the radiation dose. Since the advent of IMRT there have been several “technological advances.” Image guided radiation therapy (IGRT), adaptive radiation therapy (ART), and now proton therapy (PRT) represent new technologies that are either actively used or being incorporated into the treatment of H&N cancer. The H&N region is an ideal site to examine a new radiation treatment paradigm. The tissues in the H&N are exquisitely sensitive to the acute and late effects of radiation treatment. Even in the present day, toxicities such as mucositis, dermatitis, soft tissue fibrosis, and xerostomia commonly arise from irradiation of the H&N [5-7]. Head and neck cancer patients historically face long-term difficulties with eating, speaking, tasting, dry mouth, decreased range of motion, and wound healing [8, 9]. Radiation treatment of H&N cancer bears a high toxicity burden. Therefore, technological advances that improve conformity and precision of radiation delivery have been employed to decrease side effects in this patient population. The questions that bear asking are “what have we gained from these advancements in the last 30 years and what are the next steps?”

Technological advancements in robotics, imaging and stereotactic localization have made extracranial radiosurgery possible. Stereotactic body radiation therapy (SBRT) utilizes specially modified linear accelerators to deliver radiation to precisely defined anatomic targets. Radiation is delivered in one to five fractions at high doses per fraction compared to conventional radiation therapy techniques. SBRT was first utilized to treat lesions of the lungs, liver, pancreas and spine but in recent years, there has been a growing body of literature describing the use of this technique in head and neck cancer amongst others. These studies indicate that the treatment is well-tolerated by patients, and in the setting of recurrent head and neck cancer is similar in efficacy to other non-surgical salvage strategies. Optimization of treatment parameters has led to improvements in tumor control while reducing the already low rates of severe chronic toxicities. The promising results to date suggest that SBRT may play an increasing role in the therapeutic armamentarium in head and neck cancer.

Purposes: To improve normal tissue sparing for head-and-neck (H&N) image-guided radiotherapy (IGRT) by employing treatment plans with tighter margins for CTV 2 and 3, and documenting the delivered dose throughout the entire treatment course. Methods: Ten H&N cases treated with simultaneous integrated boost on a TomoTherapy unit (Accuray Inc.) were analyzed. Dose-limiting critical structures included brainstem, spinal cord, cochleae, parotid glands and mandible. The targets include the PTV1 (gross disease volume), PTV2 (next echelon nodal regions) and PTV3 (areas harboring subclinical disease). The standard margin plans (plan_ref) were generated using the standard margin of 3 mm to CTV1-3. Reduced margin plans (plan_0margin) using the CTV-to-PTV margin of zero for CTV2 and 3 were compared with plan_ref. All patients went through daily pre-treatment megavoltage CT (MVCT) and weekly kilovoltage CT (kVCT) scans. A GPU-based 3D image deformation/ visualization tool was developed to register the weekly kVCT scans with the planning CT scan. The deformation of each contoured structures was computed to account for non-rigid change in the patient setup. Calculation of the dose accumulation was performed to determine the delivered mean/minimum/maximum dose, dose volume histograms (DVHs), etc. Results: The averaged planned cord maximum doses in Plan_0margin were 7.6% lower, and the parotid mean doses were 18.9% lower than plan_Ref. No significant changes in D95 and D90 for the CTV2/3 cumulative doses in both reference and Plan_0margin were observed during the planning stage. Under kVCT guidance on TomoTherapy, for the reference plans, the averaged cumulative mean dose ratios during the entire treatment course were consistent within 5% and 1.5% of the planned mean doses for PTVs and CTVs, respectively. Interfraction anatomical changes introduced variations in delivered target doses that reduced the improved normal structure sparing observed in plan_0margin during the planning stage. For the tighter margin plans, the cumulative mean dose ratios were consistent within 4.3% and 2.3% of the planned mean doses for CTV2 and CTV3, respectively. Similar dose variations of the delivered dose were seen for the reference and tighter margin plans. However, the delivered maximum and mean doses for the cord were 20% and 10% higher than the planned doses; a 3.6% higher cumulative mean dose for the parotids was also observed for the delivered dose than the planned doses in both plans. Conclusions: The GPU-based image framework enables real-time dose verification, accumulation and documentation. By imposing tighter CTV margins for level 2 and 3 targets for H&N irradiation, acceptable cumulative doses were achievable when coupled with weekly kVCT guidance while improving normal structure sparing.

Radiation therapy aims to deliver high radiation dose to tumor target with minimal exposure to surrounding normal tissue. However, he physics of energy decomposition and mechanical limitations restrict the achievable dose distribution, necessitating tradeoffs between target coverage and normal tissue sparing. Treatment planning is the process of obtaining control parameters to yield such a dose pattern. Dose volume histograms (DVHs) are common tools in radiation therapy treatment planning to characterize plan quality and used as objective functions. Despite their efficacy as a compact statistical summary of dose pattern, DVHs provides limited spatial information as a report quantity and insufficient control as optimization objectives. This limitation is particularly severe for treatment site with complex geometry, as in the case of head and neck, with the presence of multi-level target volumes and various adjacent organs at risk (OARs). This paper discussed a method for dose carving, by modifying the optimization objective in the treatment planning system. Motivated by the emergent compressive sensing techniques, we introduce an objective function whose minimization leads to more direct tradeoff between target coverage and OAR sparing, sharper dose dropoff and better target dose homogeneity, achieving a better “carving” in the dose distribution. This principle, though generally applicable to all sites, is particularly beneficial for cases with complex geometry, such as head and neck planning.

Purpose: For patients with early stage lateralized head and neck cancer, unilateral radiotherapy has been shown a superior treatment than bilateral radiotherapy. Unilateral treatment not only maintains the same level of tumor control, it reduces treatment related toxicity. To take the advantage of treating a lateralized and smaller volume, radiotherapy has experienced evolution from mixed photon/electron fields, to wedge pair and IMRT treatment. The recent available proton treatment can offer further contralateral organ sparing but at a significantly higher financial cost, in addition to its technical complexities and limited accessibility. A new non-coplanar radiotherapy technique that is deliverable on existing C-arm linacs, term 4π, is in traduced in this article. Methods: Two patients with unilateral head and neck cancer were included in the planning study. The first patient was a post-surgical head-and-neck patient with a tumor involving posterior right maxillary sinus. The second patient had a primary parotid tumor. A single-level 60 Gy was prescribed to the PTV. Three treatment plans were developed including volumetric modulated arc therapy (VMAT, clinically used) using 2 partial arcs, 4π plans using 6 MV non-coplanar beams, and a non-intensity-modulated 3-field proton plan. The 4π plans were created using an in-house optimization program. Both VMAT and the proton plans were generated on Eclipse (Varian). Results: All photon plans achieved 95% coverage of the PTV and less than 10% hot spots in the PTV. The proton plan showed greater dose heterogeneity in the PTV and greater high dose spillage to the surrounding normal tissue. For the first patient, comparison of the maximum doses between VMAT, 6 MV 4π and proton plans shows that for the contralateral cochlea, it was reduced from 15.6 to 4.6 and 0 Gy; the chiasm, it was from 31 to 10.6 and 7.2 Gy; for the contralateral lens, it was reduced from 6.2 to 1 and 1 Gy; for the contralateral optical nerve, it was reduced from 31.5 to 16.4 and 10.9 Gy; for the brain stem, it was reduced from 28.6 to 14.5 and 14.2 Gy. For the second patient, the same comparison shows that the spinal cord dose was reduced from 35.7 to 21.7 and 5 Gy, contralateral optical nerve dose was reduced from 35.1 to 16.3 and 8.7 Gy, contralateral eye dose was reduced from 12.1 to 7.5 and 0.1 Gy, contralateral lens dose was reduced from 5.5 to 3.1 and 0.1 Gy, contralateral cochlea dose was reduced from 24.6 to 8.52 and 0.05 Gy and contralateral parotid dose was reduced from 14.5 to 5.11 and 0.15 Gy. Conclusion: The 4π plan’s capacity to spare normal organs is benchmarked against the state of the art partial arc VMAT and proton plans. For well lateralized target in the case study, 4π plans showed remarkable potentials to further reduce distant organ doses compared to VMAT. While the level of distant organ sparing is not equivalent to proton therapy, 4π was able to attain the majority of the gains from using the proton therapy at the same time achieving superior PTV coverage and proximal organ sparing.

It is now well-established that human papillomavirus (HPV)-associated squamous cell carcinoma, which comprises an increasing proportion of all oropharyngeal cancers, represents a unique entity with distinct clinical and molecular characteristics. Data also has emerged demonstrating that patients with HPVpositive head and neck cancer have an improved prognosis compared to their HPV-negative counterparts, with several series showing that patients with HPV-related tumors arising from the oropharynx have at least half the risk of death. However, these studies have been complicated by such factors as the limited quality of data, small sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. Although the exact reason for the improved survival among HPV-positive patients is unclear, many investigators have proposed that HPV-related head and neck cancer is more sensitive to the effects of radiation therapy than HPVnegative tumors arising in the setting of traditional environmental exposures. Despite the attractiveness of this hypothesis, the data focusing on possible de-intensification approaches remains preliminary, and treatment paradigms will likely continue to evolve as findings from innovative clinical trials yield answers to many provocative questions.