SBRT to adrenal metastases provides high local control with minimal toxicity.

PURPOSE: The adrenal glands are a common site of metastases because of their rich blood supply. Previously, adrenal metastases were treated with systemic chemotherapy or, more rarely, with surgical resection or palliative radiation therapy. Stereotactic body radiation therapy (SBRT) has recently emerged as an attractive noninvasive approach to definitively treat these lesions. We present our experience in treating adrenal metastases using SBRT and review the current literature. METHODS AND MATERIALS: This is a single-institution retrospective review of patients who received SBRT to adrenal metastases originating from various primary malignancies. Patients who were eligible for SBRT included those with limited metastatic disease (≤5 sites) with otherwise controlled metastatic disease and uncontrolled adrenal metastases. RESULTS: Ten patients met the study's inclusion criteria and received SBRT doses of 30 to 48 Gy in 3 to 5 fractions. Acute sequelae of SBRT treatment included 4 patients with grades 1 or 2 nausea, 3 patients with grade 1 fatigue, and 1 with grade 1 diarrhea. The median follow-up was 6 months with a median overall survival of 9.9 months. One patient demonstrated progressive adrenal gland disease 18.8 months after SBRT treatment. Seven patients developed new distant metastases after treatment, with a median progression-free survival of 3.4 months. Three months after SBRT to the adrenal gland, 1 patient developed a gastrointestinal bleed. CONCLUSIONS: These results complement the limited existing body of literature by demonstrating that SBRT provides good control of treated adrenal gland metastasis; however, high-grade late toxicities may occur. More stringent dose constraint limits may prevent associated serious adverse events.

Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity in a pancreatic cancer xenograft model. However, patients with locally advanced NSCLC and pancreatic cancer receiving concurrent radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic diet and thus, poor tolerance.

Once Daily High-dose Radiation (≥60 Gy) Treatment in Limited Stage Small Cell Lung Cancer.

BACKGROUND: To investigate outcomes and prognostic factors in patients treated with once daily high-dose (≥60 Gy) radiation therapy (HDRT) and concurrent platinum-based chemotherapy in limited stage small cell lung cancer (LS-SCLC). While we await current phase III trials to determine optimal radiation dose fractionation schemes in LS-SCLC, we report our experience in LS-SCLC with once daily HDRT. We hypothesized that HDRT would achieve similar efficacy and tolerability as twice daily therapy. METHODS: We conducted a single institution retrospective review of all patients with LS-SCLC who underwent curative intent treatment from 2005-2013. Patients treated with HDRT (≥60 Gy) and concurrent chemotherapy (cisplatin or carboplatin and etoposide) were included in our analysis. Clinicopathologic variables assessed include gender, performance status, time to treatment, response to treatment, toxicity, volumetric tumor response at 3 months, and use of prophylactic cranial irradiation (PCI). RESULTS: 42 patients with LS-SCLC who initiated concurrent chemoradiation from 2005 to 2013 were included in the analysis. 38 patients (90%) completed definitive treatment to the lung; 16 (38%) also completed PCI. Median failure free survival (FFS) and overall survival (OS) were 11.9 and 23.1 months, respectively. Two-year and 5-year OS rates were 47% (CI=30-62%) and 21% (CI=7-38%), respectively. On univariate analysis, PCI was associated with improved FFS but this was not significant (p=0.18). Gender was the only co-variate significantly associated with statistical differences in FFS (p=0.03) and OS (p=0.02). Grade 3 and 4 esophagitis were 10.5% and 2.6%, respectively. Pre-HDRT tumor volume and 3-month post-treatment tumor volume were both associated with FFS (p<0.01) but not OS. CONCLUSIONS: In this single institution series, daily HDRT demonstrated a 2-year OS of 47% in LS-SCLC. This compares well to the historical survival of daily fractionation (47%) from INT 0096 reported by Turrisi et. al. Male gender was predictive of significantly worse FFS and OS. Once daily HDRT has similar OS to twice-daily radiation schemes; however, further studies assessing once daily HDRT for LS-SCLC are warranted.

Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients.

PURPOSE: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. METHODS AND MATERIALS: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. RESULTS: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). CONCLUSIONS: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.

Paddle-based rotating-shield brachytherapy.

PURPOSE: The authors present a novel paddle-based rotating-shield brachytherapy (P-RSBT) method, whose radiation-attenuating shields are formed with a multileaf collimator (MLC), consisting of retractable paddles, to achieve intensity modulation in high-dose-rate brachytherapy. METHODS: Five cervical cancer patients using an intrauterine tandem applicator were considered to assess the potential benefit of the P-RSBT method. The P-RSBT source used was a 50 kV electronic brachytherapy source (Xoft Axxent™). The paddles can be retracted independently to form multiple emission windows around the source for radiation delivery. The MLC was assumed to be rotatable. P-RSBT treatment plans were generated using the asymmetric dose-volume optimization with smoothness control method [Liu et al., Med. Phys. 41(11), 111709 (11pp.) (2014)] with a delivery time constraint, different paddle sizes, and different rotation strides. The number of treatment fractions (fx) was assumed to be five. As brachytherapy is delivered as a boost for cervical cancer, the dose distribution for each case includes the dose from external beam radiotherapy as well, which is 45 Gy in 25 fx. The high-risk clinical target volume (HR-CTV) doses were escalated until the minimum dose to the hottest 2 cm(3) (D(2cm(3)) of either the rectum, sigmoid colon, or bladder reached their tolerance doses of 75, 75, and 90 Gy3, respectively, expressed as equivalent doses in 2 Gy fractions (EQD2 with α/ß = 3 Gy). RESULTS: P-RSBT outperformed the two other RSBT delivery techniques, single-shield RSBT (S-RSBT) and dynamic-shield RSBT (D-RSBT), with a properly selected paddle size. If the paddle size was angled at 60°, the average D90 increases for the delivery plans by P-RSBT on the five cases, compared to S-RSBT, were 2.2, 8.3, 12.6, 11.9, and 9.1 Gy10, respectively, with delivery times of 10, 15, 20, 25, and 30 min/fx. The increases in HR-CTV D90, compared to D-RSBT, were 16.6, 12.9, 7.2, 3.7, and 1.7 Gy10, respectively. P-RSBT HR-CTV D90-values were insensitive to the paddle size for paddles angled at less than 60°. Increasing the paddle angle from 5° to 60° resulted in only a 0.6 Gy10 decrease in HR-CTV D90 on average for five cases when the delivery times were set to 15 min/fx. The HR-CTV D90 decreased to 2.5 and 11.9 Gy10 with paddle angles of 90° and 120°, respectively. CONCLUSIONS: P-RSBT produces treatment plans that are dosimetrically and temporally superior to those of S-RSBT and D-RSBT, although P-RSBT systems may be more mechanically challenging to develop than S-RSBT or D-RSBT. A P-RSBT implementation with 4-6 shield paddles would be sufficient to outperform S-RSBT and D-RSBT if delivery times are constrained to less than 15 min/fx.

Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.

Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2(•-)and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.

Comparison and consensus guidelines for delineation of clinical target volume for CT- and MR-based brachytherapy in locally advanced cervical cancer.

OBJECTIVE: To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. METHODS AND MATERIALS: Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. RESULTS: For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. CONCLUSION: In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx.

High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes.

PURPOSE: To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. MATERIAL AND METHODS: Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. RESULTS: Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach. CONCLUSIONS: MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator.

Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

PURPOSE: Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress. EXPERIMENTAL DESIGN: Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and γH2AX as indices of proliferation and DNA damage, respectively. RESULTS: The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA. CONCLUSIONS: These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress.

The dosimetric impact of vaginal balloon-packing on intracavitary high-dose-rate brachytherapy for gynecological cancer.

PURPOSE: We perform a clinical retrospective study to determine whether a vaginal balloon-packing system provides a dosimetric reduction to organs at risk (OARs) versus traditional gauze packing for gynecological high-dose-rate brachytherapy (HDR-BT). We also test various balloon filling materials for optimizing imaging quality. MATERIAL AND METHODS: Filling materials for balloon-packing were evaluated based on imaging quality with X-ray, computerized tomography, and magnetic resonance imaging modalities. We then retrospectively reviewed 45 HDR-BT plans of 18 patients performed with gauze packing and 39 plans of 16 patients performed with balloon-packing. Twelve patients received both gauze and balloon-packing. HDR-BT was delivered with an iridium-192 afterloader and a Fletcher-Suit-Declos-style T&O applicator. At each fraction, 3D imaging was obtained. The D2cc values of OARs were calculated, as well as ICRU-defined point doses. RESULTS: In the 84 HDR fractions reviewed, vaginal balloon-packing provides statistically equivalent doses to rectum, bladder, and sigmoid compared to gauze packing. On average balloon-packing produced average reductions of 3.3% and 6.9% in the rectal and sigmoid D2cc doses and an increase of 3.2% to the bladder D2cc dose (normalized to prescription dose), although none of these values were statistically significant for the twelve patients who received both gauze and balloon-packing (32 and 40 total fractions, respectively). CONCLUSIONS: In the 84 HDR fractions analyzed, vaginal balloon-packing is as effective as gauze packing for dose sparing to the rectum, bladder, and sigmoid. A 1: 1 solution of saline and contrast for filling material enables easy contouring for image-guided HDR with minimal artefacts.

Rotating-shield brachytherapy for cervical cancer.

In this treatment planning study, the potential benefits of a rotating shield brachytherapy (RSBT) technique based on a partially-shielded electronic brachytherapy source were assessed for treating cervical cancer. Conventional intracavitary brachytherapy (ICBT), intracavitary plus supplementary interstitial (IS+ICBT), and RSBT treatment plans for azimuthal emission angles of 180° (RSBT-180) and 45° (RSBT-45) were generated for five patients. For each patient, high-risk clinical target volume (HR-CTV) equivalent dose in 2 Gy fractions (EQD2) (α/ß = 10 Gy) was escalated until bladder, rectum, or sigmoid colon tolerance EQD2 values were reached. External beam radiotherapy dose (1.8 Gy × 25) was accounted for, and brachytherapy was assumed to have been delivered in 5 fractions. IS+ICBT provided a greater HR-CTV D90 (minimum EQD2 to the hottest 90%) than ICBT. D90 was greater for RSBT-45 than IS+ICBT for all five patients, and greater for RSBT-180 than IS+ICBT for two patients. When the RSBT-45/180 plan with the lowest HR-CTV D90 that was greater than the D90 the ICBT or IS+ICBT plan was selected, the average (range) of D90 increases for RSBT over ICBT and IS+ICBT were 16.2 (6.3-27.2)and 8.5 (0.03-20.16) Gy, respectively. The average (range) treatment time increase per fraction of RSBT was 34.56 (3.68-70.41) min over ICBT and 34.59 (3.57-70.13) min over IS+ICBT. RSBT can increase D90 over ICBT and IS+ICBT without compromising organ-at-risk sparing. The D90 and treatment time improvements from RSBT depend on the patient and shield emission angle.

Rapid emission angle selection for rotating-shield brachytherapy.

PURPOSE: The authors present a rapid emission angle selection (REAS) method that enables the efficient selection of the azimuthal shield angle for rotating shield brachytherapy (RSBT). The REAS method produces a Pareto curve from which a potential RSBT user can select a treatment plan that balances the tradeoff between delivery time and tumor dose conformity. METHODS: Two cervical cancer patients were considered as test cases for the REAS method. The RSBT source considered was a Xoft Axxent(TM) electronic brachytherapy source, partially shielded with 0.5 mm of tungsten, which traveled inside a tandem intrauterine applicator. Three anchor RSBT plans were generated for each case using dose-volume optimization, with azimuthal shield emission angles of 90°, 180°, and 270°. The REAS method converts the anchor plans to treatment plans for all possible emission angles by combining neighboring beamlets to form beamlets for larger emission angles. Treatment plans based on exhaustive dose-volume optimization (ERVO) and exhaustive surface optimization (ERSO) were also generated for both cases. Uniform dwell-time scaling was applied to all plans such that that high-risk clinical target volume D90 was maximized without violating the D2cc tolerances of the rectum, bladder, and sigmoid colon. RESULTS: By choosing three azimuthal emission angles out of 32 potential angles, the REAS method performs about 10 times faster than the ERVO method. By setting D90 to 85-100 Gy10, the delivery times used by REAS generated plans are 21.0% and 19.5% less than exhaustive surface optimized plans used by the two clinical cases. By setting the delivery time budget to 5-25 and 10-30 min∕fx, respectively, for two the cases, the D90 contributions for REAS are improved by 5.8% and 5.1% compared to the ERSO plans. The ranges used in this comparison were selected in order to keep both D90 and the delivery time within acceptable limits. CONCLUSIONS: The REAS method enables efficient RSBT treatment planning and delivery and provides treatment plans with comparable quality to those generated by exhaustive replanning with dose-volume optimization.

Dosimetric impacts of applicator displacements and applicator reconstruction-uncertainties on 3D image-guided brachytherapy for cervical cancer.

PURPOSE: To quantify the dosimetric impact of applicator displacements and applicator reconstruction-uncertainties through simulated planning studies of virtual applicator shifts. MATERIAL AND METHODS: Twenty randomly selected high-dose-rate (HDR) titanium tandem-and-ovoid (T&O) plans were retrospectively studied. MRI-guided, conformal brachytherapy (MRIG-CBT) plans were retrospectively generated. To simulate T&O displacement, the whole T&O set was virtually shifted on treatment planning system in the cranial (+) and the caudal (-) direction after each dose calculation. Each shifted plan was compared to an unshifted plan. To simulate T&O reconstruction-uncertainties, each tandem and ovoid was separately shifted along its axis before performing the dose calculation. After the dose calculation, the calculated isodose lines and T&O were moved back to unshifted T&O position. Shifted and shifted-back plan were compared. RESULTS: Regarding the dosimetric impact of the simulated T&O displacements, rectal D2cc values were observed as being the most sensitive to change due to T&O displacement among all dosimetric metrics regardless of point A (p < 0.013) or MRIG-CBT plans (p < 0.0277). To avoid more than 10% change, ± 1.5 mm T&O displacements were accommodated for both point A and MRIG-CBT plans. The dosimetric impact of T&O displacements on sigmoid (p < 0.0005), bladder (p < 0.0001), HR-CTV (p < 0.0036), and point A (p < 0.0015) were significantly larger in the MRIG-CBT plans than point A plans. Regarding the dosimetric impact of T&O reconstruction-uncertainties, less than ± 3.0 mm reconstruction-uncertainties were also required in order to avoid more than 10% dosimetric change in either the point A or MRIG-CBT plans. CONCLUSIONS: The dosimetric impact of simulated T&O displacements was significantly larger in the MRIG-CBT plans than in the point A plans. Either ± 3 mm T&O displacement or a ± 4.5 mm T&O reconstruction-uncertainty could cause greater than 10% dosimetric change for both point A plans and MRIG-CBT plans.

Target volume changes through high-dose-rate brachytherapy for cervical cancer when evaluated on high resolution (3.0 Tesla) magnetic resonance imaging.

PURPOSE: To evaluate tumor volume changes that occurred during courses of high-dose-rate brachytherapy (HDR) using high resolution (3.0 Tesla) magnetic resonance imaging (MRI), along with the regression after external beam radiation therapy (EBRT). METHODS AND MATERIALS: Fourteen patients with International Federation of Gynecology and Obstetrics stage IB1-IV cervical cancer were studied retrospectively. All patients underwent EBRT with concurrent chemotherapy followed by HDR brachytherapy. Gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV) were contoured on a 3.0 Tesla MRI on the day of the HDR and on diagnostic MRI (1.5 Tesla) prior to EBRT. Two physicians independently contoured the GTV and HR-CTV on a total of 46 MRI data sets for the HDR plans. The percent volume changes of GTV and HR-CTV were quantified after EBRT and again after each HDR. The conformity indices (CIs) of the 2 contours were assessed. RESULTS: GTV and HR-CTV considerably regressed after the first ( --31.7% ± 19.3% and --26.4% ± 6.9%, respectively) and the second (--26.8% ± 14.3% and --23.8% ± 11.0%) fraction of HDR while relatively small regressions were observed after the third (--16.3% ± 14.2% and --10.6% ± 13.4%) and the fourth (--8.0% ± 3.4% and --9.0% ± 8.0%) fractions. The lymph node-positive on positron emission tomography (PET) and stage III or IV group showed, on average, more than 200% larger GTV and HR-CTV before EBRT than those of the other patients. The GTV and HR-CTV for the group were larger on average more than 150% after EBRT and before the first HDR fraction than the other group. Interobserver CI did not vary significantly (0.75 ± 0.11) for HR-CTV, although a smaller CI (0.56 ± 0.21) was found for GTV. CONCLUSIONS: Larger tumor regressions were observed after the first and second fractions of HDR than after all subsequent fractions. The PET-identified lymph node-positive patient group and stage III or higher tumors showed larger tumor volumes before and after EBRT than other cases.

Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system.

PURPOSE: To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd(2)O(2)S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si) flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL produces a greater fluence of keV-range photons than the TBL, to which the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB. METHODS: A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVision(TM) image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head- and pelvis-sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast-to-noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data. RESULTS: For head and neck and pelvis-sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10(- 8)), 1.64 (p < 10(- 13)), 2.66 (p < 10(- 9)), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head- and pelvis-sized phantoms. CONCLUSIONS: Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose.

Analysis of interfraction prostate motion using megavoltage cone beam computed tomography.

PURPOSE: Determine the degree of interfraction prostate motion and its components measured by using daily megavoltage (MV) cone beam computed tomography (CBCT) imaging. METHODS AND MATERIALS: A total of 984 daily MV CBCT images from 24 patients undergoing definitive intensity-modulated radiotherapy for localized prostate cancer were analyzed retrospectively. Pretreatment couch shifts, based on physician registration of MV CBCT to planning CT data sets, were used as a measure of daily interfraction motion. Off-line bony registration was performed to separate bony misalignment from internal organ motion. Interobserver and intraobserver variation studies were performed on 20 MV CBCT images. RESULTS: Mean interfraction prostate motion was 6.7 mm, with the greatest single-axis deviation in the anterior-posterior (AP) direction. The largest positional inaccuracy was accounted for by systematic deviations in bony misalignment, whereas random deviations occurred from bony misalignment and internal prostate motion. In the aggregate, AP motion did not correlate with days elapsed since beginning therapy or on average with rectal size at treatment planning. Interobserver variation was greatest in the AP direction, decreased in experienced observers, and further decreased in intraobserver studies. Mean interfraction motion during the first 6 days of therapy, when used as a subsequent offset, reduced acceptable AP planning target volume margins by 50%. CONCLUSION: The MV CBCT is a practical direct method of daily localization that shows significant interfraction motion with respect to conventional three-dimensional conformal and intensity-modulated radiotherapy margins, similar to that measured in other modalities.