Allen G. Meek

Video techniques for on-line portal imaging

The application of on-line portal imaging techniques to the verification of treatment precision is reviewed. The design parameters for a video portal imaging system are described, and the optimization of image quality is discussed with particular emphasis on photon noise. On-line images are presented for a head phantom imaged on a 4 MV linac, and compared with a conventional portal film. The relative advantages of an on-line system are compared with conventional portal film analysis.

A prospective study of prostate specific antigen levels in patients receiving radiotherapy for localized carcinoma of the prostate

Prostate Specific Antigen (PSA) is becoming the preferred tumor marker in the management of prostate cancer. Prostate Specific Antigen levels fall exponentially after radical prostatectomy with a half-life of between 2 and 3 days. Persistently elevated Prostate Specific Antigen levels beyond 7 half-lives suggest occult residual disease and may serve as an indication for post operative adjunctive therapy. The change in Prostate Specific Antigen levels during a course of radical external beam radiotherapy for prostate cancer has not been described. In this study of 81 patients receiving radiotherapy for primary prostate cancer, 47 had elevated Prostate Specific Antigen levels prior to therapy and 35 had serial measurement of Prostate Specific Antigen during their course of treatment. Working on an assumption that in patients with radioresponsive localized prostate cancer Prostate Specific Antigen levels will fall exponentially during the radiotherapy, a half-life of 43 +/- 11 days was derived. Prostate Specific Antigen half-life appears independent of stage, grade, or pretreatment Prostate Specific Antigen level and may be an independent prognostic indicator. A prolonged Prostate Specific Antigen half-life may suggest untreated or resistant disease and serve as an indication for adjuvant hormonal treatment in patients receiving radiotherapy for primary prostate cancer.

Intracarotid chemotherapy with etoposide and cisplatin for malignant brain tumors

Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood‐brain barrier permeability. The advantage of regional intra‐arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high‐grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra‐arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached.

INCREASED PLASMA LEVELS OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 IN LUNG AND BREAST CANCER ARE ALTERED DURING CHEST RADIOTHERAPY

PURPOSE Does the release of plasma matrix metalloproteinase-9 (MMP-9) by radiation-activated airway epithelial cells and infiltrating inflammatory cells play a role in the radiation damage or repair process in the lungs? We evaluated lung damage by ionizing radiation using plasma levels of MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and MMP-3 as biologic markers of tissue damage, and also their relationship to changes in pulmonary epithelial permeability, clinical signs and symptoms, and lung structural changes. METHODS AND MATERIALS Seven serial studies were conducted in each of 8 patients undergoing chest radiotherapy (RT) for lung or breast cancer, beginning before the first treatment (baseline) and then biweekly to approximately 100 days during and after RT. Chest radiographs were monitored for each patient. Sandwich enzyme-linked immunoassays (ELISA) were used to measure plasma MMP-3, MMP-9, and TIMP-1 levels. Lung permeability was evaluated by measuring the rate of epithelial clearance of approximately 150 microCi ( approximately 5.6 MBq) inhaled (99m)Tc diethylenetriamine pentaacetate aerosol (DTPA). RESULTS Lung and breast cancer resulted in very high plasma levels of MMP-9 (126-893 ng/mL) and TIMP-1 (496-8985 ng/mL) in all subjects studied before initiation of RT. This compares with plasma MMP-9 and TIMP-1 values in healthy volunteers of 29 +/- 11 ng/mL and 436 +/- 86 ng/mL, respectively. RT was followed by a sharp decrease in plasma MMP-9 within the first 2 weeks, but without a corresponding change in TIMP-1. In contrast, plasma MMP-3 levels, which are generally increased with inflammation, were elevated in only 1 of 5 subjects. CONCLUSION Lung and breast cancer are associated with high plasma levels of MMP-9 and TIMP-1. These high baseline plasma levels of MMP-9 were reduced in the first 2 weeks of RT in 7 of 8 subjects, and TIMP-1 plasma levels remained high in all subjects. The decrease in plasma MMP-9 after initiation of chest RT appears to reflect a suppressive effect on cancer-induced cellular responses rather than a primary role for MMP-9 in radiation-induced lung damage. Likewise, the lack of a rise in plasma MMP-3 levels does not support a role for MMP-3 in tissue injury or repair in the lung. It remains to be determined whether plasma MMP-9 measurements will serve as a useful parameter in predicting cancer relapse.

Investigation of a phase-only correlation technique for anatomical alignment of portal images in radiation therapy

A new image registration algorithm based on phase-only correlation is applied to portal images in radiation therapy to detect translational shift. The phase-only correlation shows a sharp peak in the correlation distribution as compared to the broad peak computed from conventional correlation using fast Fourier transform. In this paper, the algorithm of phase-only correlation is described and its applicability and robustness are tested when applied to portal images used in clinical radiation oncology. The results achieved give evidence that the phase-only correlation will deliver an alternative approach for image registration and image comparison, that may be applicable in routine clinical practice.

A rapid colour stabilization technique for radiochromic film dosimetry

Various forms of GAFChromic film have been used for several years as radiographic media for measuring dose distributions of brachytherapy sources and small radiation fields. Upon irradiation the film changes colour and darkens with time post-irradiation. The darkening is most rapid in the first 24 h, and it has been suggested that for accurate dosimetry a waiting period of 24 h should occur before any optical density (OD) measurements are taken. A more rapid colour stabilization (RCS) procedure has been developed and is evaluated. The procedure consists of heating the film post-irradiation for a period of 2 h at 45 degrees C. The RCS procedure is compared with a control group and the dose response is tested for linearity, stability and reproducibility using two densitometers with light sources at different wavelengths (632.8 nm and 671 nm). The rise in net optical density (NOD) for the period 3-168 h is less than 3% for the RCS group as compared with 12% for the controls. In the first 24 h, the increase in NOD for the RCS samples is less than 0.5%, as opposed to 6% for the control group.

Clinical use of a wing field with transmission block for the treatment of the pelvis including the inguinal node

Treatment planning of photon and electron beams to include the pelvis and the groin poses a technical difficulty of positioning beams, and a dosimetric problem of abutting fields at the groin. We have analyzed a simpler AP/PA method using a central transmission block. The posterior portal is smaller and opposes only the pelvic portion of the anterior portal under the transmission block, while the anterior extended portion (hence the wing) is unattenuated to treat the inguinal region. By calculating the attenuation thickness according to the patients separation and the beam quality, the dose distribution is tailored to yield the proper dose to the pelvic mid-plane and the inguinal nodes while minimizing the dose to the femora. Measured dose distribution (6MV) using film dosimetry in a tissue-equivalent phantom indicates that a 30% hot spot is created by the posterior portal diverging into the wings of the anterior field. Therefore, the pelvic attenuator is tapered at its lateral edges, thereby significantly reduced the dose inhomogeneity (5%) at the groin. Clinical methods are outlined for the verification of the patient portal films against possible mismatch in beam divergence.

Evaluation of the eclipse electron Monte Carlo dose calculation for small fields

Varian Medical Systems (Palo Alto, CA) has implemented the Monte Carlo electron dose calculation algorithm (eMC) in the Eclipse treatment planning system. Previous algorithms for electron treatment planning were limited in their calculation ability for small field depth doses and monitor units. An old rule of thumb to approximate the limiting cutout size for an electron field was determined by the lateral scatter equilibrium and approximated by E (MeV)/2.5 in centimeters of water. In this study, we compared eMC calculations and measurements of depth doses, isodose distributions, and monitor units for several different energy and small field cutout size combinations at different SSDs. Measurements were made using EBT film (International Specialty Products, Wayne, NJ) and a PinPoint ion chamber (PTW‐New York Corp., Hicksville, NY). Our results indicate that the eMC algorithm can accurately predict depth doses, isodose distributions, and monitor units (within 2.5%) for field sizes as small as 3.0 cm diameter for energies in the 6 to 20 MeV range at 100 cm SSD. Therefore, the previous energy dependent rule of thumb does not apply to the Eclipse electron Monte Carlo code. However, at extended SSDs (105–110 cm), the results show good agreement (within 4%) only for higher energies (12, 16, and 20 MeV) for a field size of 3 cm. PACS number: 87.53.Hv

Glucose metabolic changes in nontumoral brain tissue of patients with brain tumor following radiotherapy : A preliminary study

PURPOSE Our goal was to measure the effect of radiotherapy on the brain glucose metabolism of tumoral and nontumoral tissue of patients with brain malignancies. METHOD Fifteen patients with primary or metastatic brain tumors were studied with 2-deoxy-2-[18F]fluoro-D-glucose and PET prior to radiotherapy, and nine of them were rescanned 1 week after completing radiotherapy. RESULTS Brain metabolism in patients (all brain regions except for tumoral and edematous tissue) was lower than that of matched controls (34.0 +/- 8.3 vs. 46.5 +/- 6.4 mumol/100 g/min; p < or = 0.0001). Five of the nine patients retested after radiotherapy showed decrements in tumor metabolism (47 +/- 10%; p < or = 0.05) and increases in brain metabolism (10 +/- 4%; p < or = 0.004), and the other four showed no changes in tumor or in brain metabolism. Radiotherapy-induced changes in tumor metabolism were negatively correlated with changes in brain metabolism (r = 0.85, p < or = 0.004), but not with changes in tumor volume (assessed with MR images). CONCLUSION The study indicates that radiotherapy-induced increases in metabolism of nontumoral tissue are secondary to decreased tumor metabolic activity and not just due to volume reduction.

Unified dosimetry index (UDI): a figure of merit for ranking treatment plans

We have formulated a unified dosimetry index (UDI) that computes, for any given treatment plan, its deviations in terms of dose coverage, conformity, homogeneity, and dose gradient vis‐à‐vis an ideal plan (which we define as a dosimetry plan of perfect dose coverage, conformity, homogeneity, and step‐wise fall‐off to zero dose outside the planning target volume). In order to validate the UDI scoring system, 21 stereotactic cranial radiosurgery cases were evaluated retrospectively. The cases were planned on the BrainSCAN treatment planning system (BrainLAB, Feldkirchen, Germany) using 6 to 8 non‐coplanar static beams collimated with the micro multi‐leaf collimator (mMLC). We suggest a technique for creating a ranking system that can be utilized for plan evaluation and comparison between multiple plans. Under this system treatment plans are classified as “excellent”, “good”, “average”, or “poor”. The proposed ranking system can be utilized as a general guide for generating an optimal dosimetry plan for external beam radiation therapy.