David N. Teguh

Local Anatomic Changes in Parotid and Submandibular Glands During Radiotherapy for Oropharynx Cancer and Correlation With Dose, Studied in Detail With Nonrigid Registration

PURPOSE To quantify the anatomic changes caused by external beam radiotherapy in head-and-neck cancer patients in full three dimensions and to relate the local anatomic changes to the planned mean dose. METHODS AND MATERIALS A nonrigid registration method was adapted for RT image registration. The method was applied in 10 head-and-neck cancer patients, who each underwent a planning and a repeat computed tomography scan. Contoured structures (parotid, submandibular glands, and tumor) were registered in a nonrigid manner. The accuracy of the transformation was determined. The transformation results were used to summarize the anatomic changes on a local scale for the irradiated and spared glands. The volume reduction of the glands was related to the planned mean dose. RESULTS Transformation was accurate with a mean error of 0.6 +/- 0.5 mm. The volume of all glands and the primary tumor decreased. The lateral regions of the irradiated parotid glands moved inward (average, 3 mm), and the medial regions tended to remain in the same position. The irradiated submandibular glands shrank and moved upward. The spared glands showed only a small deformation ( approximately 1 mm in most regions). Overall, the primary tumors shrank. The volume loss of the parotid glands correlated significantly with the planned mean dose (p <0.001). CONCLUSION General shrinkage and deformation of irradiated glands was seen. The spared glands showed few changes. These changes were assessed by a nonrigid registration method, which effectively described the local changes occurring in the head-and-neck region after external beam radiotherapy.

Atlas-Based Auto-segmentation of Head and Neck CT Images

Treatment planning for high precision radiotherapy of head and neck (H&N) cancer patients requires accurate delineation of many structures and lymph node regions. Manual contouring is tedious and suffers from large inter- and intra-rater variability. To reduce manual labor, we have developed a fully automated, atlas-based method for H&N CT image segmentation that employs a novel hierarchical atlas registration approach. This registration strategy makes use of object shape information in the atlas to help improve the registration efficiency and robustness while still being able to account for large inter-subject shape differences. Validation results showed that our method provides accurate segmentation for many structures despite difficulties presented by real clinical data. Comparison of two different atlas selection strategies is also reported.

Trismus in patients with oropharyngeal cancer: relationship with dose in structures of mastication apparatus.

Our aim was to assess the correlation between the radiation therapy (RT) dose to the mastication apparatus and trismus of oropharyngeal cancer patients.

Dose Uncertainties in IMPT for Oropharyngeal Cancer in the Presence of Anatomical, Range, and Setup Errors

PURPOSE Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions. METHODS AND MATERIALS We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation. RESULTS For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust. CONCLUSIONS For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive planning to improve adequate IMPT dose delivery.

Early Hyperbaric Oxygen Therapy for Reducing Radiotherapy Side Effects: Early Results of a Randomized Trial in Oropharyngeal and Nasopharyngeal Cancer

PURPOSE Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT). METHODS AND MATERIALS From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up. RESULTS On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001). CONCLUSIONS Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.

Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in the swallowing muscles after radiotherapy of cancer in the oropharynx

BACKGROUND AND PURPOSE Dysphagia is a serious complaint but frequently underreported. This paper assesses for oropharyngeal cancer (OPC) the relationship between the dose received by the swallowing structures, and the findings of a fiberoptic endoscopic evaluation of the swallowing process (FEES). MATERIALS AND METHODS Between 2000 and 2005, 60 of 67 OPC patients local-regionally NED for at least one year following treatment responded to three types of QoL questionnaires; i.e. Performance Status Scales, EORTC H&N35, and M.D. Anderson Dysphagia Inventory. Twenty-four patients agreed to the FEES procedure. The main swallowing muscles were delineated, with the mean dose per muscle calculated using the original 3D CT-based treatment plans. Regression analysis was performed between FEES variables and the doses in the different swallowing muscles and the dysphagia related questionnaires. RESULTS A significant relationship was found between the results of FEES and the mean dose in the superior constrictor muscle (SCM). Some of the subjective dysphagia complaints were significantly correlated with the FEES variables in this retrospectively study. CONCLUSION A higher dose in the SCM generally results in worsening of the findings obtained by the FEES examination.

Single vocal cord irradiation: A competitive treatment strategy in early glottic cancer

INTRODUCTION The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI). MATERIAL AND METHODS The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed. RESULTS A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved. CONCLUSIONS Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery.

Toxicity and outcome of intensity-modulated radiotherapy versus 3-dimensional conformal radiotherapy for oropharyngeal cancer: A matched-pair analysis

Because of the scarcity of randomized trials comparing toxicity and outcomes of intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) with 3D-conformal radiotherapy (3DCRT), we performed a matched-pair analysis from prospectively collected data from the Head and Neck Tumor Registry of our institution. In the absence of phase III trials, we believe this approach provides the highest quality data possible. Ninety-two patients treated with 3DCRT were matched (1:1) to 92 patients treated with IMRT for 9 potential predictive factors for toxicity and outcome: gender, age, T-stage, N-stage, tumor subsite, unilateral neck irradiation, chemotherapy, neck dissection and boost technique. Groups were compared for acute and late toxicity, locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analyses and toxicity was analyzed according to Common Terminology Criteria for Adverse Events v3.0. The overall incidence of grade 3 acute toxicity was significantly reduced by IMRT, compared to 3DCRT (45% vs. 70%, p = 0.001). The need for tube feeding was reduced from 50% to 37% (p = 0.04). The 3-year actuarial incidence of grade ≥2 late toxicity was also significantly reduced by IMRT, compared to 3DCRT (20% vs. 45%, respectively; p < 0.0001). The incidence of grade ≥2 late dysphagia and xerostomia for IMRT vs. 3DCRT were 10% vs. 31% for dysphagia, p = 0.004 and 13% vs. 37%, for xerostomia, respectively (p = 0.001). The 3-year Kaplan-Meier estimates of LRC, DFS, and OS for IMRT vs. 3DCRT were 90% vs. 82% (p = 0.1), 82% vs. 76% (p = 0.3), and 72% vs. 64% (p = 0.2), respectively. In conclusion, the presented nonrandomized comparative study of well-matched groups demonstrates the superiority of IMRT vs. 3DCRT for OPC by significantly reducing radiation-induced toxicity without jeopardizing outcomes. The improved therapeutic ratio achieved by the use of IMRT would allow dose escalation of radiotherapy to further improve outcomes of patients with OPC.

Intensity-modulated radiotherapy followed by a brachytherapy boost for oropharyngeal cancer.

The purpose of this study was to reduce the incidence of radiation‐induced toxicity in patients with early‐stage oropharyngeal cancer, using highly conformal radiation techniques.

Stereotactic Body Radiotherapy in Head and Neck Cancer

There is limited data regarding stereotactic radiotherapy (SRT) or stereotactic body radiotherapy (SBRT) for primary head and neck cancers, although it is feasible using SRT for primary HNC and its potential benefit in LC and organ preservation. The dose conformality by using SBRT and reduced CTV to PTV margins do seem to have a substantial effect on the dose received by the swallowing muscles and parotid glands as opposed to those treated with an IMRT or 3DCRT boost. Hypofractionated SRT may have the potential for curative or palliative treatment and could have a shorter duration of treatment, and a highly conformal dose distribution. However, severe late adverse reactions are anticipated with re-irradiation than with initial RT, partly because of the large doses per fraction used in most series. Compared with stereotactic radiosurgery using single fraction of high-dose irradiation, fractionated stereotactic radiotherapy may be superior in terms of tumor control and protection of normal tissues and organs surrounding the target.