Homan Dehnad

Clinical feasibility study for the use of implanted gold seeds in the prostate as reliable positioning markers during megavoltage irradiation

BACKGROUND AND PURPOSE The aim of this study was to assess the feasibility of using gold seed implants in the prostate for position verification, using an a-Si flat panel imager as a detector during megavoltage irradiation of prostate carcinoma. This is a study to guarantee positioning accuracy in intensity-modulated radiotherapy. METHODS AND MATERIALS Ten patients with localized prostate carcinoma (T2-3) received between one and three fiducial gold markers in the prostate. All patients were treated with 3-D conformal radiotherapy with an anterior-posterior (AP) and two lateral wedge fields. The acute gastrointestinal (GI) and genitourinary (GU) toxicities were scored using common toxicity criteria scales (CTC). Using three consecutive CT scans and portal images obtained during the treatment we have studied the occurrence of any change in prostate shape (deformation), seed migration and the magnitude of translations and rotations of the prostate. RESULTS We observed no acute major complications for prostate irradiation regarding the seed implantation. The maximum acute GU toxicity grade 2 (dysuria and frequency) was observed in seven patients during the treatment. The maximum grade 2 (diarrhoea) was scored in two patients regarding the acute GI toxicities. No significant prostate deformation could be detected in the consecutive CT scans. It appeared that the distances between the markers only slightly changed during treatment (S.D. 0.5 mm). Random prostate translations were (1 S.D.) 2.1, 3.2 and 2.2 mm in the lateral (LR), AP and cranial-caudal (CC) directions, respectively, whereas systematic translations were 3.3, 4.8 and 3.5 mm in the LR, AP and CC directions, respectively. Random prostate rotations were (1 S.D.) 3.6, 1.7 and 1.9 degrees around the LR, AP and CC axis, respectively, whereas systematic rotations were 4.7, 2.0 and 2.7 degrees around the LR, AP and CC axis, respectively. CONCLUSIONS We found that the fiducial gold seeds are a safe and appropriate device to verify and correct the position of prostate during megavoltage irradiation. The amount of seed migration and prostate deformation is far below our present tumour delineation accuracy.

Measurements and clinical consequences of prostate motion during a radiotherapy fraction.

PURPOSE Here we study the magnitude of prostate motion during the delivery of a radiotherapy fraction. These motions have clinical consequences for on-line position verification and the choice of margins around the target volume. METHODS AND MATERIALS We studied the motion of the prostate for 10 patients during 251 radiotherapy treatment fractions by assessing the position of implanted gold markers. Gold markers of 1 mm diameter and 5 mm length were implanted in the prostate before the start of the radiotherapy. We obtained movies during each fraction using an a-Si flat-panel imager. The markers could be detected in separate frames using a marker extraction kernel. RESULTS Marker displacements as large as 9.5 mm were detected in one fraction. The motion of the prostate is greatest in the caudal-cranial and the anterior-posterior directions. Within a time window of 2 to 3 min, deviations from the initial marker position, averaged over all patients, are 0.3 +/- 0.5 mm and -0.4 +/- 0.7 mm in the anterior-posterior and caudal-cranial directions, respectively. CONCLUSIONS It appeared that on average, the intrafraction prostate motions did not result in margins larger than 1 mm, provided that the position verification is performed at time intervals of 2 to 3 min. Only for some patients performing more frequent position verification or adding extra margins of 2 to 3 mm is required to account for intrafraction prostate motions.

Comparison of megavoltage position verification for prostate irradiation based on bony anatomy and implanted fiducials.

PURPOSE The patient position during radiotherapy treatment of prostate cancer can be verified with the help of portal images acquired during treatment. In this study we quantify the clinical consequences of the use of image-based verification based on the bony anatomy and the prostate target itself. PATIENTS AND METHODS We analysed 2025 portal images and 23 computed tomography (CT) scans from 23 patients with prostate cancer. In all patients gold markers were implanted prior to CT scanning. Statistical data for both random and systematic errors were calculated for displacements of bones and markers and we investigated the effectiveness of an off-line correction protocol. RESULTS Standard deviations for systematic marker displacement are 2.4 mm in the lateral (LR) direction, 4.4 mm in the anterior-posterior (AP) direction and 3.7 mm in the caudal-cranial direction (CC). Application of off-line position verification based on the marker positions results in a shrinkage of the systematic error to well below 1 mm. Position verification based on the bony anatomy reduces the systematic target uncertainty to 50% in the AP direction and in the LR direction. No reduction was observed in the CC direction. For six out of 23 patients we found an increase of the systematic error after application of bony anatomy-based position verification. CONCLUSIONS We show that even if correction based on the bony anatomy is applied, considerable margins have to be set to account for organ motion. Our study highlights that for individual patients the systematic error can increase after application of bony anatomy-based position verification, whereas the population standard deviation will decrease. Off-line target-based position verification effectively reduces the systematic error to well below 1 mm, thus enabling significant margin reduction.

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients.

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

The dose to the parotid glands with IMRT for oropharyngeal tumors: the effect of reduction of positioning margins.

PURPOSE The aim of this paper is to quantify the importance of the reduction of positioning margins applied to the clinical target volume (CTV) on the dose distribution of the parotid gland for different intensity-modulated radiotherapy (IMRT) strategies for the treatment of oropharyngeal cancer. METHODS AND MATERIALS CTVs and organs at risk were delineated in the planning computed tomographic (CT) scans of three patients. Margins of 0, 3, 6 and 9mm were applied to the CTVs in order to obtain the planning target volumes (PTVs). Three IMRT strategies were used to optimize the dose distribution. RESULTS The analysis of the three IMRT strategies resulted in: (1) an optimal dose distribution in the PTV; (2) optimal dose distribution in the PTV while sparing the parotid gland and (3) more parotid gland sparing but at expense of the dose homogeneity in the PTV. The mean parotid dose increased linearly with increasing margin by approximately 1.3Gy per mm. As a result, the normal complication probability (NTCP) for xerostomia decreased when smaller margins were applied. Reducing the margin from 6 to 3mm resulted in an NTCP reduction of approximately 20%. CONCLUSION Reducing the CTV-PTV margin by improving the patient position accuracy may lead to a significant reduction of NTCP for the IMRT treatment of the oropharyngeal tumors and lymph nodes level II.

Level II lymph nodes and radiation-induced xerostomia

PURPOSE To investigate the influence of the cranial border of electively irradiated Level II lymph nodes on xerostomia in patients with oropharyngeal cancer using three-dimensional conformal and intensity-modulated radiotherapy (3D-CRT and IMRT). METHODS AND MATERIALS The target volumes and organs at risk were delineated on the planning CT scans of 12 patients. Two elective target volumes were delineated. The first had the transverse process of the C1 atlas and the second had the transverse process of the C2 axis as cranial border of the Level II lymph nodes. 3D-CRT and IMRT planning were performed for both elective volumes, resulting in two plans per patient and technique, called the C1 and C2 plans, respectively. Irradiation of the ipsilateral elective volume up to C1 and the contralateral up to C2 was also performed for IMRT. The normal tissue complication probability (NTCP) for xerostomia 1 year after RT was calculated using the parotid mean dose. RESULTS The average mean dose +/- standard deviation (SD) to the contralateral parotid gland was reduced from 33 +/- 5 Gy for the IMRT C1 plans to 26 +/- 4 Gy for the IMRT C2 plans and from 51 +/- 6 Gy to 49 +/- 7 Gy for the 3D-CRT C1 and C2 plans, respectively. The associated NTCP +/- SD for xerostomia was 38% +/- 10% for IMRT C1 plans and 24% +/- 6% for IMRT up to C2 on the contralateral side, regardless of which cranial border was irradiated on the ipsilateral side. For the 3D-CRT C1 and C2 plans, an NTCP value of 74% +/- 12% and 71% +/- 15% was obtained, respectively. The NTCP for xerostomia of the ipsilateral parotid gland was 53% +/- 17% and 45% +/- 20% for the IMRT C1 and C2 plans and 89% +/- 11% and 87% +/- 12% for the 3D-CRT C1 and C2 plans, respectively. CONCLUSION Lowering the cranial border of the Level II lymph nodes from C1 to C2, in the case of bilateral elective neck irradiation, could be considered on the contralateral side when the risk of metastasis on that side is very low. This is especially true when IMRT is used, because the relative reduction of NTCP for xerostomia 1 year after RT could be up to 68% compared with conventional conformal RT up to C1.

Response to motexafin gadolinium and ionizing radiation of experimental rat prostate and lung tumors

PURPOSE To investigate the responses of two experimental rat tumors to single and fractionated X-ray doses whether or not combined with Motexafin gadolinium (MGd), and the distribution of MGd in R3327-MATLyLu (MLL) tumors using MRI. METHODS L44 lung tumor in BN rats and MLL prostate tumor in Copenhagen rats were grown subcutaneously. MGd at concentrations of 8.7 to 25.1 micro mol/kg was administered 2 h before or just before treatments with single and fractionated X-ray doses. Tumor volume growth delay was the endpoint used. The two-dimensional distribution of the MGd concentration in time was analyzed simultaneously in slices through the center of MLL tumors using MRI. Directly after the MRI experiments, tumor sections were stained for cytoplasm, nuclei, and microvessel endothelium. RESULTS MGd at different concentrations administered a few minutes or 2 h before X-ray doses produced no radiation enhancement in the two tumor models. The MGd concentration as determined by MRI was maximal 5 min after injection and decreased slowly thereafter. In a representative section at the center of the MLL tumor, the microvessel density is nearly homogeneous and correlates with a nearly homogeneous MGd distribution. Hardly any MGd is taken up in underlying muscle tissue. CONCLUSION No radiosensitization was observed for the different irradiation regimens. The distribution of MGd is nearly homogeneous in the MLL tumor and hardly any MGd is taken up in underlying muscles. Our negative results on radiosensitivity in our two tumor models raise questions about the efficacy of MGd as a general radiosensitizing agent.