Biochemical control and toxicity after intensity-modulated radiation therapy for prostate cancer.

Intensity modulated radiation therapy (IMRT) has achieved widespread use for prostate cancer; however, in relation to this use, outcomes studies are still relatively sparse. We report a single-institutional experience in outcomes analysis with the use of IMRT for the primary management of prostate cancer. One hundred thirty consecutive patients with adenocarcinoma of the prostate were treated at a single institution using IMRT with curative intent. Thirty-six (28%) patients were classified as low-risk, 69 (53%) as intermediate-risk, and 25 (19%) as high-risk. The median dose prescription was 76 Gy to the planning target volume. Sixty-five (50%) patients received androgen deprivation therapy (ADT) for a median 4 months, starting 2 months prior to IMRT. Biochemical failure was defined as PSA < post-treatment nadir+2. Gastrointestinal (GI) and Genitourinary (GU) toxicity were defined by RTOG criteria. Median follow-up was 53 months. By NCCN risk category, 4-year biochemical control was 97%, 94%, and 87% for low, intermediate, and high-risk patients, respectively. Among disease factors, multivariable analysis demonstrated the strongest association between biochemical control and Gleason score < or =6 (p=0.0371). Therapy was well tolerated with no Grade 4 toxicity and limited grade 3 GI or GU toxicity. Acute Grade 3+ GI and GU toxicity rates were 0% and 2%, and maximal late Grade 3+ GI and GU toxicity rates were 5% and 6%, respectively. Late rectal toxicity was associated with higher volumes of RT to the rectum. By last follow-up late Grade 3+ toxicity was 2% for both GI and GU systems. In conclusion, patients treated with IMRT for prostate cancer have excellent rates of biochemical control and low rates of severe toxicity of treatment.

The dosimetric effects of tissue heterogeneities in intensity-modulated radiation therapy (IMRT) of the head and neck.

The dosimetric effects of bone and air heterogeneities in head and neck IMRT treatments were quantified. An anthropomorphic RANDO phantom was CT-scanned with 16 thermoluminescent dosimeter (TLD) chips placed in and around the target volume. A standard IMRT plan generated with CORVUS was used to irradiate the phantom five times. On average, measured dose was 5.1% higher than calculated dose. Measurements were higher by 7.1% near the heterogeneities and by 2.6% in tissue. The dose difference between measurement and calculation was outside the 95% measurement confidence interval for six TLDs. Using CORVUS' heterogeneity correction algorithm, the average difference between measured and calculated doses decreased by 1.8% near the heterogeneities and by 0.7% in tissue. Furthermore, dose differences lying outside the 95% confidence interval were eliminated for five of the six TLDs. TLD doses recalculated by Pinnacle3's convolution/superposition algorithm were consistently higher than CORVUS doses, a trend that matched our measured results. These results indicate that the dosimetric effects of air cavities are larger than those of bone heterogeneities, thereby leading to a higher delivered dose compared to CORVUS calculations. More sophisticated algorithms such as convolution/superposition or Monte Carlo should be used for accurate tailoring of IMRT dose in head and neck tumours.

MRI measurements correctly predict the relative effects of tumor oxygenating agents on hypoxic fraction in rodent BA1112 tumors.

PURPOSE: We evaluate whether magnetic resonance imaging (MRI) with blood oxygenation level-dependent (BOLD) contrast correctly predicts the relative effects of tumor-oxygenating agents on hypoxic fraction in BA1112 rhabdomyosarcomas in WAG/Rij rats. METHODS AND MATERIALS: The response of ten tumors to carbogen (95% O(2)/5% CO(2)), a perfluorocarbon emulsion (PFC), and the combination of PFC + carbogen was studied with high spectral and spatial resolution MR imaging of the water resonance at 4.7 Tesla. Decreases in MR signal linewidth indicate increases in tumor blood oxygen levels. RESULTS: Average MR signal linewidth was decreased 2.0% by carbogen, 2.5% by PFC + air, and 4.9% by PFC + carbogen. PFC + carbogen caused a larger linewidth decrease than either treatment alone (p < 0.04 by ANOVA). Maps of pixels responding to treatment indicate that combining PFC with carbogen significantly enlarges the area of the tumor in which oxygen levels are increased (p < 0.01 by ANOVA). CONCLUSION: MRI predicts that PFC + carbogen will increase radiosensitivity more than either treatment alone; this agrees with the known effects of these treatments on hypoxic fraction. Utilizing MRI to choose the treatment that maximizes the size and extent of increases in tumor oxygenation could reduce hypoxic fraction.

Uptake of a superparamagnetic contrast agent imaged by MR with high spectral and spatial resolution.

Conventional MRI implicitly treats the proton signal as a single, narrow Lorentzian. However, water signals in vivo are often in homogeneously broadened and have multiple resolvable components. These components represent discrete populations of water molecules within each pixel which are affected differently by physiology and contrast agents. Accurate measurement of each component of the water resonance can improve anatomic and functional MR images and provide insight into the structure and dynamics of subpixelar microenvironments. This report describes high spectral and spatial resolution (HiSS) MR imaging of rodent prostate tumors before and after injection of a superparamagnetic contrast agent. HiSS datasets were used to synthesize images in which intensity is proportional to peak height, peak frequency, and linewidth. These images showed anatomic features which were not clearly delineated in conventional T(2) and gradient echo images. HiSS images obtained after injection of the contrast agent showed T *(2) and T(1) changes which were not seen in conventional images. These changes are associated with microvessel density and permeability. The results suggest HiSS with superparamagnetic contrast agents has the potential to improve characterization of tumors.

Correlation of magnetic resonance and oxygen microelectrode measurements of carbogen-induced changes in tumor oxygenation.

PURPOSE: The aim of this work was to test the hypothesis that decreases in the linewidth of magnetic resonance (MR) water signals in tumors caused by oxygenating treatments are due to increases in capillary and venous oxygen saturation of hemoglobin, which are tightly coupled to increases in extravascular oxygen tension (pO2). To establish this link, changes measured by MR were compared to changes in tissue pO2 measured directly by oxygen microelectrodes during carbogen (95% O2/5% CO2) inhalation. METHODS AND MATERIALS: Mammary adenocarcinomas (R3230AC) in nine rats were imaged at 4.7 Tesla. T1-weighted (TR = 200 ms, flip angle = 45 degrees) spectroscopic images of the water resonance in a single slice through each tumor were acquired with spectral resolution of 3.9 Hz and bandwidth of +/-1000 Hz. In the same slices in these tumors, microelectrode measurements were made using a non-Clark style oxygen electrode with a 350-micron tip. MR and microelectrode measurements were made during alternating periods of air and carbogen inhalation. RESULTS: Water resonance linewidth decreased significantly during carbogen-induced hyperoxia. Paired Student's t-test analysis of microelectrode data indicated that pO2 was significantly (p < 0.05) increased as a result of carbogen inhalation. MR and microelectrode data averaged over each tumor demonstrated that decreased MR water signal linewidth is strongly correlated (r = 0.92, p < 0.05) with increased tumor pO2 levels. CONCLUSION: Although tumor oxygenating agents increase response to radiation in rodent tumors, clinical studies have shown only marginal effects on the radiosensitivity of human tumors. This may be, in part, because the effects of tumor oxygenating treatments are highly heterogeneous both within each tumor and among a population of tumors. The noninvasive, high-resolution MR methods that are validated by the present work could guide the design of new and more effective tumor oxygenating agents and optimize treatments for individual patients.

Fast spectroscopic imaging of water and fat resonances to improve the quality of MR images.

RATIONALE AND OBJECTIVES: The authors evaluated whether fast spectroscopic imaging of water and fat resonances can produce high-quality anatomic magnetic resonance (MR) images of rodent tumors and human breast. MATERIALS AND METHODS: Fast MR spectroscopic images of eight rats with mammary tumors were acquired by using a 4.7-T MR unit equipped with self-shielded gradient coils. MR spectroscopic images of four human breasts were acquired with a 1.5-T MR unit. RESULTS: Artifacts due to eddy currents were minimal. Images synthesized from MR spectroscopic data, in which intensity was proportional to water signal peak height, were similar to T2-weighted MR images. Boundaries of rodent mammary tumors are similar but not identical on peak height-weighted and T2-weighted images. MR spectroscopic images of human breast showed improved detail compared to gradient-echo MR images. CONCLUSION: Preliminary results suggest that incorporation of fast MR spectroscopic imaging methods into many standard clinical MR imaging procedures may substantially improve image quality.

Spectroscopic imaging of the water resonance with short repetition time to study tumor response to hyperoxia.

A variety of treatments that modulate tumor oxygen tension are used clinically to improve the outcome of radiotherapy. High resolution, noninvasive measurements of the effects of these treatments would greatly facilitate the development of improved therapies and could guide treatment of cancer patients. Previous work demonstrated that magnetic resonance (MR) gradient echo imaging of the water proton resonance detects changes in T2* and T1 in tumors during hyperoxia that may reflect increased tumor oxygenation. This report describes the use of high resolution MR spectroscopic imaging with short repetition time (TR = 0.2 s) to improve the accuracy with which changes in T2* and T1 are measured. Mammary adenocarcinomas grown in the hind limbs of rats were studied. Carbogen inhalation was used to induce hyperoxia. A single 2-mm slice through the center of tumors and underlying muscle was imaged at 4.7 Tesla with in-plane resolution of approximately 1.2 mm and frequency resolution of 5.8 Hz. The peak integral increased by an average of 6% in tumors during carbogen inhalation suggesting a decrease in T1 (n = 8, P < 0.001). Peak height increased by an average of 15% in tumors during carbogen inhalation (n = 8, P < 0.001). The large difference between increases in peak height and peak integral demonstrates that the width of the water resonance decreased. Assuming a Lorentzian lineshape, an average increase of 12% in T2* was observed in tumors. In muscle, peak integral and peak height increased slightly (about 1.2% and 3%, respectively; P < 0.02) during carbogen inhalation but no significant change in T2* was observed. Spectroscopic imaging detects changes in the water proton resonance in tumors during hyperoxia accurately and reproducibly with high signal-to-noise ratio and allows clear separation of T1 and T2* effects. Increases in T2* may be due to decreased deoxyhemoglobin in tumor blood vessels (i.e., the BOLD effect) and may provide a clinically useful index of increases in tumor oxygenation.