Munther Ajlouni

Image-guided and intensity-modulated radiosurgery for patients with spinal metastasis.

Radiosurgery can deliver a single, large radiation dose to a localized tumor using a stereotactic approach and hence, requires accurate and precise delivery of radiation to the target. Of the extracranial organ targets, the spine is considered a suitable site for radiosurgery, because there is minimal or no breathing‐related organ movement. The authors studied spinal radiosurgery in patients with spinal metastases to determine its accuracy and precision.

A technique of intensity-modulated radiosurgery (IMRS) for spinal tumors

This study is to demonstrate the feasibility of spinal radiosurgery using an image-guided intensity-modulated radiosurgical (IMRS) procedure. A dedicated Novalis shaped beam surgery unit equipped with a built-in micro-multileaf collimator (mMLC) with a single 6 MV photon beam was used. Each patient was simulated in the supine position using an AcQsim CT simulator with infrared sensitive markers for localization. A variety of different treatment plans were developed, but the most common plan was the use of seven coplanar intensity-modulated beams to minimize radiation to critical organs such as the spinal cord and kidneys. An automatic localization device based on infrared and video cameras was used to guide the initial patient setup. Two keV x-ray imaging systems were used to identify potential deviations from the planned isocenter. A total of 25 patients with spinal tumors have been treated using this procedure with a single prescription dose ranging from 6 to 12 Gy. The final verification images indicated that the average isocenter deviation from the planned isocenter was within 2 mm. The phantom verification of isocenter doses indicated that the average deviation of measured isocenter doses from the planned isocenter doses for all patients treated with intensity-modulated beams was less than 2%. Film dose measurement in a phantom study demonstrated good agreement of above 50% isodose lines between the planned and measured results. Preliminary experience shows that precision delivery of high dose radiation could be administered to the planned target volume while the dose to the critical organs is kept within tolerable limits.

Dosimetric study using different leaf‐width MLCs for treatment planning of dynamic conformal arcs and intensity‐modulated radiosurgery

This paper systematically studied the dosimetric difference between a 3 mm micro multileaf collimator (MLC), a 5 mm MLC, and a 10 mm MLC for stereotactic radiosurgery using the Brainscan treatment planning system. Thirty-four cases treated with the dynamic conformal arcs technique and 20 cases treated with the intensity modulated radiosurgery/fractionated radiotherapy (IMRS/ IMRT) technique were retrospectively studied. The conformity index, the percentage target coverage, and the dose-volume histogram (DVH) for organs-at-risk (OARs) were used for dosimetric analysis and comparison for different treatment techniques, target volumes, and treatment sites. For the dynamic conformal arcs technique, there were statistically significant differences in the conformity indices between different leaf-width MLCs. The ratio of the conformity indices between different MLCs depended on the target volume. The average conformity index ratios between the 5 mm MLC and the 3 mm MLC were 1.37+/-0.09, 1.12+/-0.04, 1.08+/-0.02 and 1.04+/-0.01, respectively, for patients with the target volume (V) in groups: (1) V< 1 cm3, (2) 1 cm3 < V< 8 cm3, (3) 8 cm3 < V< 27 cm3, and (4) V> 27 CC. The average conformity index ratios between the 10 and 3 mm MLCs were 2.00+/-0.33, 1.45+/-0.09, 1.28+/-0.09, and 1.18+/-0.05 for patients in these four volume groups, respectively. No statistically significant difference was found for the target coverage among different MLCs. For the IMRS/IMRT technique, the average conformity index and target coverage ratios were 1.01+/-0.05 and 1.00+/-0.02, respectively, between the 5 and 3 mm MLCs, and were 1.04+/-0.07 and 0.97+/-0.02, respectively, between the 10 and 3 mm MLCs. The 3 mm MLC showed slightly better overall OAR DVHs than the 5 and 10 mm MLCs, especially for the cranial site with small-volume OARs defined. The results suggest that for the dynamic conformal arcs technique, the narrower leaf-width MLC provides better dose conformity than the wider leaf-width MLCs. This advantage decreases when the target volume increases. For the IMRS/IMRT technique, the narrower leaf-width MLC could have better sparing of small OARs than the wider leaf-width MLC.

The correlation evaluation of a tumor tracking system using multiple external markers

The purpose of this study is to evaluate the correlations between external markers and internal targets for radiation therapy of lung cancer patients. Using an infrared camera system coupled with a clinical simulator, the simultaneous motions of multiple external markers and an internal target were obtained. The correlation between external and internal signals was analyzed using a cross-covariance function. A linear regression model was employed to generate a composite signal from multiple external markers in order to predict the internal target motion. The external and internal signals, and their correlations, demonstrated a wide range of variation with respect to marker location, motion dimension, and breathing pattern. The performance of the composite signal indicates that when more external signals were taken into account, the mean correlation between the composite signal and internal signal was improved. This implies that a combination of multiple external signals might be an improved way to predict internal target motion. Also, since the characteristics of respiratory signals can vary significantly, certain methods of preprocessing and external signal combination are necessary.

Results of abdominoperineal resections for failures after combination chemotherapy and radiation therapy for anal canal cancers

Thirty patients treated with combination chemotherapy (CT) and radiation therapy (RT) for anal canal carcinoma were reviewed retrospectively to analyze the results of abdominoperineal resection (APR) for treatment failures. Mean follow-up was 34.9 months. Twenty-four patients had squamous carcinomas, and six had cloacogenic carcinomas. Twenty-five had negative inguinal lymph nodes, and five had positive inguinal lymph nodes. The group received 5-fluorouracil, mitomycin C, and 30 to 50 Gy of RT. Biopsy was obtained at six weeks posttherapy. Seventeen of 22 patients (77 percent) with primary tumors of less than 5 cm and negative nodes were disease free at 37 months post-CT-RT. None of the seven patients with primary tumors of greater than 5 cm or positive nodes were free of disease. APR was done for positive biopsy in eight patients and for local recurrence (disease detected after six months of treatment) in one patient. Eight of nine patients who had APR died of disease (mean, 20 months), and one of nine died of other causes. A review of published series, including our data, reveals 24 cases of APR post-CT-RT for positive biopsy, with 17 of 24 (71 percent) dead of disease within three years. APR for CT-RT failures has a poor prognosis. Future protocols may determine whether further CT-RT will improve survival. APR for palliation should always remain an option.

Image-guided radiosurgery of head and neck cancers

OBJECTIVES: Radiosurgery precisely delivers a single high dose or a few fractionated doses of radiation to a localized tumor via the stereotactic approach. Some head and neck sites are suitable for radiosurgery since there is minimal or no organ motion. The clinical studies were carried out to determine the accuracy of stereotactic radiosurgery and to demonstrate the effectiveness of radiosurgery in head and neck cancers. MATERIALS AND METHODS: Thirteen patients were treated with either single-dose or fractionated radio-surgery to the tumor. All patients except one with cancer of the lip had received prior treatments including surgery, radiotherapy, and chemotherapy for the primary cancers. The dose ranged 12 to 18 Gy for single-dose radiosurgery and 30 Gy in 5 or 6 fractions twice a week for fractionated radiosurgery. Tumor localization was achieved via the stereotactic approach. RESULTS: Accuracy of radiosurgery was within 1.5 mm. Despite the recurrent disease from previous heavy treatments, 9 patients (70%) showed a significant response (complete or >50% tumor reduction) to radiosurgery, and 3 patients had stable disease. Complete tumor response was achieved in 6 patients. All patients had excellent pain relief with functional and cosmetic preservation. There was no acute and subacute radiation toxicity detected clinically during the minimal follow-up of 6 months. CONCLUSION: Image-guided radiosurgery is effective in achieving the local tumor control and pain relief. Radiosurgery provided excellent functional and cosmetic preservation with minimal complication. The results indicate the potential of radiosurgery in the treatment of recurrent and selected primary head and neck cancers. (Otolaryngol Head Neck Surg 2004;130:690-7.)

Impact of fraction size on lung radiation toxicity: hypofractionation may be beneficial in dose escalation of radiotherapy for lung cancers.

PURPOSE To assess how fraction size impacts lung radiation toxicity and therapeutic ratio in treatment of lung cancers. METHODS AND MATERIALS The relative damaged volume (RDV) of lung was used as the endpoint in the comparison of various fractionation schemes with the same normalized total dose (NTD) to the tumor. The RDV was computed from the biologically corrected lung dose-volume histogram (DVH), with an alpha/beta ratio of 3 and 10 for lung and tumor, respectively. Two different (linear and S-shaped) local dose-effect models that incorporated the concept of a threshold dose effect with a single parameter D(L50) (dose at 50% local dose effect) were used to convert the DVH into the RDV. The comparison was conducted using four representative DVHs at different NTD and D(L50) values. RESULTS The RDV decreased with increasing dose/fraction when the NTD was larger than a critical dose (D(CR)) and increased when the NTD was less than D(CR). The D(CR) was 32-50 Gy and 58-87 Gy for a small tumor (11 cm(3)) for the linear and S-shaped local dose-effect models, respectively, when D(L50) was 20-30 Gy. The D(CR) was 66-97 Gy and 66-99 Gy, respectively, for a large tumor (266 cm(3)). Hypofractionation was preferred for small tumors and higher NTDs, and conventional fractionation was better for large tumors and lower NTDs. Hypofractionation might be beneficial for intermediate-sized tumors when NTD = 80-90 Gy, especially if the D(L50) is small (20 Gy). CONCLUSION This computational study demonstrated that hypofractionated stereotactic body radiotherapy is a better regimen than conventional fractionation in lung cancer patients with small tumors and high doses, because it generates lower RDV when the tumor NTD is kept unchanged.

Evaluation of residual patient position variation for spinal radiosurgery using the Novalis image guided system

PURPOSE The Novalis system has been demonstrated to achieve accurate target localization on anthropomorphic phantoms. However, other factors, such as rotational deviation, patient intrafraction motion, and image fusion uncertainty due to patient body deformation, could contribute additional position uncertainty for actual patients. This study evaluates such position uncertainty for spinal radiosurgery patients. MATERIALS AND METHODS Fifty-two consecutive spinal radiosurgery patients were included in the study. Rotational deviation was evaluated from 6-deg of freedom (6D) fusion results for all patients. The combined uncertainty of patient motion and image fusion was determined from fusion results of additional kV x-ray images acquired before, during, and after treatment for 25 of the 52 patients. The uncertainty of image fusion was also evaluated by performing 6D fusion ten different times with various regions of interest in the images selected for fusion. This was performed for two patients with L3 and T2 lesions, respectively, for comparison. RESULTS The mean rotational deviation was 0.7 +/- 1.8, 0.7 +/- 1.5, and 0.7 +/- 1.6 deg along the yaw, roll, and pitch directions, respectively. The combined uncertainty from patient motion and image fusion was 0.1 +/- 0.9, 0.2 +/- 1.2, and 0.2 +/- 1.0 mm in the anteroposterior (AP), longitudinal, and lateral directions, respectively. The uncertainty (standard deviation) due to image fusion was less than 0.28 mm in any direction for the L3 lesion and 0.8 mm in the AP direction for the T2 lesion. CONCLUSION Overall position uncertainty for spinal radiosurgery patients has been evaluated. Rotational deviation and patient motion were the main factors contributed to position uncertainty for actual patient treatment.

Investigation of the location effect of external markers in respiratory‐gated radiotherapy

In 7 lung and breast cancer patients, we investigated the location effect of external markers on the correlation between the motions of external markers and of an internal target under various breathing patterns. Our department developed a tumor tracking system consisting of two infrared cameras and a medical simulator. Using the system, we monitored the simultaneous motions of tumor and external markers placed at various locations on a patients skin and saved the results for offline analysis. We then used a cross‐covariance approach to analyze the correlation between the motions of individual markers and of the tumor. Based on the additive model, we evaluated the predictability of tumor motion from the motions of the external markers. The effect of marker location on the correlation between the motions of the tumor and of the external markers varied widely from patient to patient. At no specific marker location did the surrogate signal consistently present superior correlation with tumor motion in 3 breathing sessions with 7 patients. When the composite external signal generated from multiple external motion signals was correlated with tumor motion, the quality of the correlation improved significantly. In most cases, the composite signal provided the best surrogate signal for correlating with tumor motion. Correlation between the motions of external markers and of a tumor may be affected by several factors, including patient characteristics, marker locations, and breathing pattern. A single external marker cannot provide sufficient and reliable tracking information for tumor motion. A composite signal generated from the motions of multiple external makers provides an excellent surrogate signal, which in this study demonstrated superior correlation with tumor motion as compared with the signal provided by an individual marker. A composite signal would be a more reliable way to track tumor motion during respiratory‐gated radiotherapy. PACS numbers: 87.53.Jw

Adaptive prediction of internal target motion using external marker motion: a technical study

An adaptive prediction approach was developed to infer internal target position by external marker positions. First, a prediction model (or adaptive neural network) is developed to infer target position from its former positions. For both internal target and external marker motion, two networks with the same type are created. Next, a linear model is established to correlate the prediction errors of both neural networks. Based on this, the prediction error of an internal target position can be reconstructed by the linear combination of the prediction errors of the external markers. Finally, the next position of the internal target is estimated by the network and subsequently corrected by the reconstructed prediction error. In a similar way, future positions are inferred as their previous positions are predicted and corrected. This method was examined by clinical data. The results demonstrated that an improvement (10% on average) of correlation between predicted signal and real internal motion was achieved, in comparison with the correlation between external markers and internal target motion. Based on the clinical data (with correlation coefficient 0.75 on average) observed between external marker and internal target motions, a prediction error (23% on average) of internal target position was achieved. The preliminary results indicated that this method is helpful to improve the predictability of internal target motion with the additional information of external marker signals. A consistent correlation between external and internal signals is important for prediction accuracy.