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Endoluminal brachytherapy (EBT) has been shown to be an effective neoadjuvant monotherapy for rectal adenocarcinoma. Radiographic predictors of response are used to guide treatment in rectal cancer; however, no predictors of response to EBT have been identified. This is a single-institutional prospective study from 2010 to 2013. Analysis included 17 patients undergoing EBT and 13 patients undergoing conventional external beam chemoradiation (CRT). Clinical response to therapy was assessed with serial MRI and PET/CT variables. Pathological response to therapy was assessed using tumor regression grade (TRG) and compared with clinical response. EBT and CRT patients did not differ with respect to age, sex, race, carcinoembryonic antigen, or clinical stage of disease. There was a similar rate of pathologic complete response for both groups, with a trend towards more TRG 0 with EBT compared with CRT (35.3% vs. 7.7%, p = 0.08). Four days of EBT resulted in a significantly greater reduction in tumor volume on MRI than did CRT (92.7% vs. 63.1%, p = 0.004). Using receiver operating characteristic analysis, change in peak standardized uptake value was the best predictor for complete pathologic response in EBT patients (sensitivity 67%, specificity 82%). False-positive findings for nodal disease on MRI were seen in 59% of EBT patients and 23% of CRT patients. This study demonstrates that EBT is an effective alternative with similar response rates to CRT. However, the inability of MRI and PET/CT to discern reactive from malignant tumor and nodes may pose limitations in their use for guiding further therapy. Larger randomized studies are needed.

High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach. Proper administration of HDR-IORT requires institutional support and a joint effort among physics staff, oncologists, surgeons, anesthesiologists, and nurses. In order to determine the true efficacy of IORT for various malignancies, collaboration among institutions with established IORT programs is needed.

BACKGROUND Intraoperative radiotherapy (IORT) has advantages over external beam radiation therapy (EBRT). Few studies have described side effects associated with its addition. We evaluated our institution's experience with abdominopelvic IORT to assess safety by postoperative complication rates. METHODS Prospectively collected IRB-approved database of all patients receiving abdominopelvic IORT (via high dose rate brachytherapy) at Johns Hopkins Hospital between November 2006 and May 2014 was reviewed. Patients were discussed in multidisciplinary conferences. Those selected for IORT were patients for whom curative intent resection was planned for which IORT could improve margin-negative resection and optimize locoregional control. Perioperative complications were classified via Clavien-Dindo scale for postoperative surgical complications. RESULTS A total of 113 patients were evaluated. Most common diagnosis was sarcoma (50/113, 44%) followed by colorectal cancer (45/113, 40%), most of which were recurrent (84%). There were no perioperative deaths. A total of 57% of patients experienced a complication Grade II or higher: 24% (27/113) Grade II; 27% (30/113) Grade III; 7% (8/113) Grade IV. Wound complications were most common (38%), then gastrointestinal (25%). No radiotherapy variables were significantly associated with complications on uni/multi-variate analysis. CONCLUSIONS Our institution's experience with IORT demonstrated historically expected postoperative complication rates. IORT is safe, with acceptable perioperative morbidity.

PURPOSE: Optimization of prostate brachytherapy is constrained by tissue deflection of needles and fixed spacing of template holes. We developed and clinically tested a robotic guide toward the goal of allowing greater freedom of needle placement. METHODS AND MATERIALS: The robot consists of a small tubular needle guide attached to a robotically controlled arm. The apparatus is mounted and calibrated to operate in the same coor- dinate frame as a standard template. Translation in x and y directions over the perineum � 40 mm are possible. Needle insertion is performed manually. RESULTS: Five patients were treated in an institutional review board-approved study. Confirma- tory measurements of robotic movements for initial 3 patients using infrared tracking showed mean error of 0.489 mm (standard deviation, 0.328 mm). Fine adjustments in needle positioning were possible when tissue deflection was encountered; adjustments were performed in 54 (30.2%) of 179 needles placed, with 36 (20.1%) of 179 adjustments ofO2 mm. Twenty-seven insertions were intentionally altered to positions between the standard template grid to improve the dosimetric plan or avoid structures such as pubic bone and blood vessels. CONCLUSIONS: Robotic needle positioning provided a means of compensating for needle deflections and the ability to intentionally place needles into areas between the standard template holes. To our knowledge, these results represent the first clinical testing of such a system. Future work will be incorporation of direct control of the robot by the physician, adding software algo- rithms to help avoid robot collisions with the ultrasound, and testing the angulation capability in the clinical setting. 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Since the Institute of Medicine's report, To Err is Human, was published, numerous interventions have been designed and implemented to correct the defects that lead to medical errors and adverse events; however, most efforts were largely reactive. Safety, communication, team performance, and efficiency are areas of care that attract a great deal of attention, especially regarding the introduction of new technologies, techniques, and procedures. We describe a multidisciplinary process that was implemented at our hospital to identify and mitigate hazards before the introduction of a new technique: high-dose-rate intraoperative radiation therapy, (HDR-IORT).A multidisciplinary team of surgeons, anesthesiologists, radiation oncologists, physicists, nurses, hospital risk managers, and equipment specialists used a structured process that included in situ clinical simulation to uncover concerns among care providers and to prospectively identify and mitigate defects for patients who would undergo surgery using the HDR-IORT technique.We identified and corrected 20 defects in the simulated patient care process before application to actual patients. Subsequently, eight patients underwent surgery using the HDR-IORT technique with no recurrence of simulation-identified or unanticipated defects.Multiple benefits were derived from the use of this systematic process to introduce the HDR-IORT technique; namely, the safety and efficiency of care for this select patient population was optimized, and this process mitigated harmful or adverse events before the inclusion of actual patients. Further work is needed, but the process outlined in this paper can be universally applied to the introduction of any new technologies, treatments, or procedures.

Since prehistoric times, elevated temperatures have been used to treat cancer in a variety of forms. In modern times (the last 40 years) efforts have concentrated on combining heat with other anti-tumour modalities, principally ionizing radiation and some chemotherapeutic drugs. Despite the emphasis on combined therapy, rodent data relating to heat sensitivity and thermal tolerance development assumed principal importance. These considerations suggested treating at 43°C as a target temperature and fractionation schemes emphasizing thermal tolerance avoidance. Concomitantly crucial data on heat-induced tumour reoxygenation and its temperature dependence were largely ignored. In reality these were unrealistic and undesirable goals. The preponderance of evidence now suggests that lower temperatures (40–42°C) administered more frequently, optimally immediately before and during each administration of ionizing radiation, are likely to yield optimal results. Factoring in trimodality therapy and other combinatio...

Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.

Purpose : A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low α/β ratio), more typical of the surrounding late-responding normal tissue. Methods and Materials : Earlier estimates of α/β for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, length of follow-up, and age. Results : The estimated value of α/β from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This α/β value is considerably less than typical values for tumors (≥8 Gy), and more comparable to values in surrounding late-responding normal tissues. Conclusions : This analysis provides strong supporting evidence that α/β values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced.

The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal). One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min), while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation.

Colorectal cancer is the third most common malignancy and the third leading cause of cancer-related death in the United States, with more than 40,000 rectal cancer cases diagnosed each year.1 Standard treatment for localized (ie, resectable) rectal cancer includes 5-fluorouracil (5-FU)-based chemoradiation therapy followed by surgery. Improved radiation technology including image-guided radiation therapy (RT) and brachytherapy (contact therapy) can allow for the delivery of higher doses of RT to the rectal tumor over a shorter time period. These treatments may result in improved outcomes; however, they require fiducial markers to allow better localization and targeting of the rectal tumor. In this retrospective study, we evaluated the role of gold fiducial markers in patients receiving neoadjuvant endorectal brachytherapy in patients with localized rectal tumors.

Background. Several recent studies have suggested radiosensitizing effects of paclitaxel, a microtubular inhibitor. To test the universality of this finding, the interaction between paclitaxel and radiation treatment of cell lines derived from three common human carcinomas MCF-7 (breast cancer) ; DUT-145 (prostate cancer) ; and HT-29 (colon cancer) was evaluated. The study focused on the ability of paclitaxel to block cells at the G2-M phase of the cell cycle and potentially enhance the radiation sensitivity of the cells. Methods. All cell lines were exposed to three different clinically achievable paclitaxel concentrations ranging from 2 nM to 25 nM. Paclitaxel pretreatment for 12 and 24 hours before radiation was tested in all three cell lines. The radiation dose ranged from 0 to 8 Gy delivered in a single fraction. Cellular survival after treatment with paclitaxel and/or radiation was determined by clonogenic assay. Cell cycle distribution as determined by flow cytometry was performed after various dose-time combinations of paclitaxel. Results. Cytotoxicity studies with paclitaxel alone demonstrated a time-dependent and dose-dependent survival relationship for all three cell lines. Resultant surviving fractions were in the range of 5 to 90% after 24-hour exposure to paclitaxel alone. The interaction between paclitaxel and radiation was primarily additive in each of the three cell lines for all paclitaxel dose-time combinations studied. Flow cytometric analysis failed to reveal a prominent G2-M block in all three cell lines after paclitaxel treatment for 24 hours. Conclusions. Paclitaxel lacked a radiosensitizing effect on MCF-7, DUT-145, and HT-29 cells in this study. These results should be considered when designing clinical trials that use paclitaxel as a potential radiosensitizer of certain human carcinomas. Cancer 1995 ; 75 :2262-8.

Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT).Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls.Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P<0.001). There was a trend towards higher rate of pathologic CR for EBT (P=0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P=0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions.Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.

1. 1.|We investigated the relationship between heat-induced perturbation of cell cycle progression and cytotoxicity at low temperature hyperthermia in three human cell lines human breast carcinoma cells (MCF-7) and human prostatic adenocarcinoma cells (DUT-145 and PC-3). 2. 2.|MCF-7 cells which were resistant to mild hyperthermia exhibited a G 1 block during heating at 41°C. In contrast, DUT-145 and PC-3 cells which were sensitive to mild hyperthermia failed to accumulate in G 1 -phase. Both DUT-145 and PC-3 cells progressed through S-phase and accumulated in the G 2 /M-phase. These results rule out any species-based generalization for heat sensitivity. 3. 3.|Electron micrographs and gel electrophoresis data show the accumulation of mitotic-like cells and DNA fragmentation during mild hyperthermia in prostatic carcinoma cells. 4. 4.|These results suggest that cell death is associated, at least partly with DNA fragmentation, perhaps apoptosis in prostatic carcinoma cells.

Clinical application of long duration hyperthermia at temperatures42 degrees C has traditionally been avoided because of the possibility of chronic thermotolerance development, such as is observed with rodent cells. In support of long duration hyperthermia, both rodent and human cells have been shown to be sensitized to low dose-rate irradiation by simultaneous heating at 40 or 41 degrees C. The relationship between these supposed contradictory responses to hyperthermia were investigated in rat 9L gliosarcoma cells in vitro. Thermotolerance developed during 41 degrees C heating with or without concurrent low dose-rate irradiation. Thermotolerance reached a maximum within 6 h during 41 degrees C heating and remained stable for at least 24 h. When cells were returned to 37 degrees C after heating at 41 degrees C for 6 h, thermotolerance remained stable for at least 12 h. The time course of thermotolerance development correlated with that of induction of 41 degrees C radiation sensitization. Radiation sensitization, on the other hand, was shown to be independent of thermotolerance because the protein synthesis inhibitor cycloheximide prevented thermotolerance induction but had no effect on radiation sensitization. We conclude that thermotolerance development during concurrent clinical application of long duration mild temperature hyperthermia and low dose-rate irradiation should not be a factor in altering treatment outcome.

Purpose To evaluate a prototypical system of dynamic intraoperative dosimetry for prostate brachytherapy using registered ultrasound and fluoroscopy (RUF) with a nonisocentric C-arm (GE OEC, Salt Lake City, UT) and to compare intraoperative dosimetry of RUF as well as ultrasound-based seed localization (USD) with Day 0 CT dosimetry. Methods Seed positions were independently determined using RUF and USD. RUF uses a radio-opaque fiducial for registration to ultrasound and 3-dimensional reconstruction of seeds relative to prostate using nonisocentric C-arm fluoroscopy. Postimplant CT was performed on Day 0. Squared differences between dosimetric measures for RUF vs. CT and USD vs. CT were calculated and mean squared differences evaluated. Paired t test was used to evaluate which method was more closely aligned with CT. Accuracies of USD and RUF compared with CT were estimated using a nonparametric approach. Results Six patients were treated and compared with USD. RUF identified areas of underdosage intraoperatively in all patients and median 5 additional seeds were placed. In 40 of 42 measures, RUF was equally or more closely correlated with CT than USD. USD showed statistically significant variation from CT for 6 of 7 parameters compared with 1 of 7 parameters for RUF. Mean squared differences from CT were significantly smaller for RUF in 4 of 7 parameters compared with USD. Conclusions Dynamic intraoperative dosimetry is possible with a conventional nonisocentric C-arm. Compared with an USD method, RUF-based intraoperative dosimetry was more closely aligned with immediate postimplant CT. RUF identified areas of underdosage, which were not detected using USD.

Brachytherapy (radioactive seed insertion) has emerged as one of the most effective treatment options for patients with prostate cancer, with the added benefit of a convenient outpatient procedure. The main limitation in contemporary brachytherapy is faulty seed placement, predominantly due to the presence of intra-operative edema (tissue expansion). Though currently not available, the capability to intra-operatively monitor the seed distribution, can make a significant improvement in cancer control. We present such a system here.Intra-operative measurement of edema in prostate brachytherapy requires localization of inserted radioactive seeds relative to the prostate. Seeds were reconstructed using a typical non-isocentric C-arm, and exported to a commercial brachytherapy treatment planning system. Technical obstacles for 3D reconstruction on a non-isocentric C-arm include pose-dependent C-arm calibration; distortion correction; pose estimation of C-arm images; seed reconstruction; and C-arm to TRUS registration.In precision-machined hard phantoms with 40-100 seeds and soft tissue phantoms with 45-87 seeds, we correctly reconstructed the seed implant shape with an average 3D precision of 0.35 mm and 0.24 mm, respectively. In a DoD Phase-1 clinical trial on six patients with 48-82 planned seeds, we achieved intra-operative monitoring of seed distribution and dosimetry, correcting for dose inhomogeneities by inserting an average of over four additional seeds in the six enrolled patients (minimum 1; maximum 9). Additionally, in each patient, the system automatically detected intra-operative seed migration induced due to edema (mean 3.84 mm, STD 2.13 mm, Max 16.19 mm).The proposed system is the first of a kind that makes intra-operative detection of edema (and subsequent re-optimization) possible on any typical non-isocentric C-arm, at negligible additional cost to the existing clinical installation. It achieves a significantly more homogeneous seed distribution, and has the potential to affect a paradigm shift in clinical practice. Large scale studies and commercialization are currently underway.

Intra-operative guidance in Transrectal Ultrasound (TRUS) guided prostate brachytherapy requires localization of inserted radioactive seeds relative to the prostate. Seeds were reconstructed using a typical C-arm, and exported to a commercial brachytherapy system for dosimetry analysis. Technical obstacles for 3D reconstruction on a non-isocentric C-arm included pose-dependent C-arm calibration; distortion correction; pose estimation of C-arm images; seed reconstruction; and C-arm to TRUS registration. In precision-machined hard phantoms with 40-100 seeds, we correctly reconstructed 99.8% seeds with a mean 3D accuracy of 0.68 mm. In soft tissue phantoms with 45-87 seeds and clinically realistic 15° C-arm motion, we correctly reconstructed 100% seeds with an accuracy of 1.3 mm. The reconstructed 3D seed positions were then registered to the prostate segmented from TRUS. In a Phase-1 clinical trial, so far on 4 patients with 66-84 seeds, we achieved intraoperative monitoring of seed distribution and dosimetry. We optimized the 100% prescribed iso-dose contour by inserting an average of 3.75 additional seeds, making intra-operative dosimetry possible on a typical C-arm, at negligible additional cost to the existing clinical installation.

Purpose Ultrasound tracking of target motion relies on visibility of vascular and/or anatomical landmark. However this is challenging when the target is located far from vascular structures or in organs that lack ultrasound landmark structure, such as in the case of pancreas cancer. The purpose of this study is to evaluate visibility, artifacts and distortions of fusion coils and solid gold markers in ultrasound, CT, CBCT and kV images to identify markers suitable for real-time ultrasound tracking of tumor motion in SBRT pancreas treatment. Methods Two fusion coils (1mm × 5mm and 1mm × 10 mm) and a solid gold marker (0.8mm × 10mm) were embedded in a tissue–like ultrasound phantom. The phantom (5cm × 12cm × 20cm) was prepared using water, gelatin and psyllium-hydrophilic-mucilloid fiber. Psylliumhydrophilic mucilloid acts as scattering medium to produce echo texture that simulates sonographic appearance of human tissue in ultrasound images while maintaining electron density close to that of water in CT images. Ultrasound images were acquired using 3D-ultrasound system with markers embedded at 5, 10 and 15mm depth from phantom surface. CT images were acquired using Philips Big Bore CT while CBCT and kV images were acquired with XVI-system (Elexta). Visual analysis was performedmore » to compare visibility of the markers and visibility score (1 to 3) were assigned. Results All markers embedded at various depths are clearly visible (score of 3) in ultrasound images. Good visibility of all markers is observed in CT, CBCT and kV images. The degree of artifact produced by the markers in CT and CBCT images are indistinguishable. No distortion is observed in images from any modalities. Conclusion All markers are visible in images across all modalities in this homogenous tissue-like phantom. Human subject data is necessary to confirm the marker type suitable for real-time ultrasound tracking of tumor motion in SBRT pancreas treatment.« less

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50 –11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >10.0 ng/mL, Gleason score >7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p

Purpose: Immobilization devices combine rigid patient fixation as well as comfort and play a key role providing the stability required for accurate radiation delivery. In the setup step, couch re-positioning needed to align the patient is derived via registration of acquired versus reference image. For subsequent fractions, replicating the initial setup should yield identical alignment errors when compared to the reference. This is not always the case and further couch re-positioning can be needed. An important quality assurance measure is to set couch tolerances beyond which additional investigations are needed. The purpose of this work was to study the inter-fraction couch changes needed to re-align the patient and the intra-fraction stability of the alignment as a guide to establish the couch tolerances. Methods: Data from twelve patients treated on the Accuray CyberKnife (CK) system for fractionated intracranial radiotherapy and immobilized with Aquaplast RT, U-frame, F-Head-Support (Qfix, PA, USA) was used. Each fraction involved image acquisitions and registration with the reference to re-align the patient. The absolute couch position corresponding to the approved setup alignment was recorded per fraction. Intra-fraction set-up corrections were recorded throughout the treatment. Results: The average approved setup alignment was 0.03±0.28mm, 0.15±0.22mm, 0.06±0.31mm in the L/R, A/P, S/I directions respectively and 0.00±0.35degrees, 0.03±0.32degrees, 0.08±0.45degrees for roll, pitch and yaw respectively. The inter-fraction reproducibility of the couch position was 6.65mm, 10.55mm, and 4.77mm in the L/R, A/P and S/I directions respectively and 0.82degrees, 0.71degrees for roll and pitch respectively. Intra-fraction monitoring showed small average errors of 0.21±0.21mm, 0.00±0.08mm, 0.23±0.22mm in the L/R, A/P, S/I directions respectively and 0.03±0.12degrees, 0.04±0.25degrees, and 0.13±0.15degrees in the roll, pitch and yaw respectively. Conclusion: The inter-fraction reproducibility should serve as a guide to couch tolerances, specific to a site and immobilization. More patients need to be included to make general conclusions.

655 Background: Rectal cancer affects over 40,000 patients in the US per year. The current standard of care for patients with localized rectal cancer is neoadjuvant radiation therapy with concurrent chemotherapy (NCRT) followed by surgery; however, it has shown no proven survival benefit for locally advanced rectal cancer patients. Preliminary results show that a short course of radiation therapy, using high-dose rate endorectal brachytherapy (Endo-HDR), may be as effective with less toxicity and delay to time of surgery. This requires the placement of fiducial markers, using an endoscopic ultrasound guided method (EUS), into the tumor for accurate source placement and treatment. Our aim is to compare three different types of fiducials in terms of visibility and migration. Methods: 12 patients with locally advanced rectal cancer that received Endo-HDR and EUS guided fiducial placement were retrospectively evaluated at JHH. Results: 12 patients underwent EUS guided placement of 42 fiducials. For 11 of our 12 patients, the mean number of fiducials placed per patient was 3.63 (SD 1.03) using a 19-gauge needle. One patient received 2 fiducials using a 22- gauge needle. Of the 12 patients that received fiducials, 3 received traditional fiducials (TF), 8 received segmented fiducials (SF) and 1 received foldable fiducials. All fiducials were clearly visible. The mean number of fiducials that detached from implanted site before surgery for patients with TFs was 0.667, and for patients with SFs was 0.875 (p=0.744). The median migration distance, as measured by interfiduciary distance, for segmented fiducials was significantly larger when compared to traditional fiducials (0.45 cm for SF compared to 0.1 cm for TF; p=0.049) Conclusions: SFs appear to be less stable, with regards to migration, in the rectum when compared to traditional fiducials in our patient population. These differences could be due to placement difficulty or operator dependent differences. Improvement in fiducial structure is required in order to help decrease migration and detachment and maximize visualization, which will lead to more accurate administration of Endo-HDR.

261 Background: High-dose-rate endorectal brachytherapy (Endo-HDR) is a promising technique using a short course of radiation therapy in the neoadjuvant setting for rectal cancer. While clinical exam and standard imaging (CT and MRI) suggest outstanding radiation response in these patients, they cannot reliably predict pathologic complete response (pCR) or high tumor regression grade (TRG). In this study, we investigate the utility of PERCIST criteria to predict pathologic change. Methods: We treated nine patients on a prospective clinical trial investigating Endo-HDR as a single agent neoadjuvant therapy (6.5 Gy x 4 fractions, total dose of 26 Gy) for stage II-III rectal cancer patients. A pre-radiation PET/CT scan was compared to a post-treatment PET/CT scan performed one month following the completion of radiation. All nine patients proceeded to surgical resection with the pathologic specimen analyzed for residual disease. TRG (Mandard et al.) was used to quantify response to treatment. A 50% decrease in SUVpeak by PERCIST criteria was correlated with a TRG 1 or 2 (none or minimal residual cancer cells on the final pathologic specimen). Results: As demonstrated in our table, 3/5 (60%) of patients achieving a TRG 1 or 2 had a SUVpeak that decreased by 50% or more; contrarily, zero of 4 (0%) of patients without a TRG 1 or 2 had a SUVpeak of 50% or more. Despite a trend, the small patient sample limited statistical significance (p=0.17). A minimum decrease of 50% in SUVpeak resulted in a positive predictive value of 100%, a negative predictive value of 67%, a specificity of 100%, and a sensitivity of 60% for predicting TRG 1 or 2. Conclusions: Our results demonstrate the first report of utilizing PERCIST criteria in rectal cancer treated with neoadjuvant Endo-HDR. Reliable clinical predictors following Endo-HDR for excellent pathologic response may identify patients in whom a non-operative rectal cancer treatment is possible. [Table: see text]

Purpose: To determine the feasibility of using [ 11 C ] ‐PK11195‐based PETimaging to study radiation‐induced pulmonary inflammation in vivo and to validate the molecular imaging results by histology. Method and Materials: Female adult C57BL/6J mice were used. The lower portion of the right mouse lung (RLL) was locally irradiated with a 5mm‐diameter customized collimator in a 137 Cs gamma‐ray irradiator. Radiographicimaging was employed for irradiation collimation alignment. The radiationdoses were measured using Gafchromic EBT film. The irradiated mouse was imaged at 7 days after local irradiation. PETimaging was performed in a dedicated small animal PET scanner. Each mouse received 0.3 mCi of [ 11 C ] ‐PK11195 via injection through the tail vein. A dynamic imaging protocol was used for each scan with a total duration of 30 minutes. Raw images were reconstructed and analyzed by 3D OSEM. Immediately after imaging, the mouse was euthanized and the lung was inflated and fixed in 10% formalin for 48 hours before paraffin embedding. 5 μm thick slices were cut for hematoxylin & eosin staining and histological images were acquired with a Zeiss light microscope. Results: The average dose in the locally irradiated lung region was 19.2Gy, while the total body dose was 3.9 Gy due to gamma ray leakage through the collimator. Tomographic slices in coronal and transaxial sections of the mouse lung showed significant PK11195 accumulation in RLL, while the other regions remained normal. Histologic images from different lung portions demonstrated that only RLL showed significant infiltration of macrophages and neutrophils, which agrees with the noninvasive imaging data. Conclusion: This study demonstrates the noninvasive evaluation of early radiation‐induced pulmonary injury in a mouse model. Since [ 11 C ] ‐PK11195 is approved for clinical use, this technique may see potential applications in monitoring early molecular events of radiation‐induced pulmonary injury and assessing the efficacy of new treatment strategies.

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose escalating conformal HDR prostate brachytherapy was performed. We are reporting the outcomes. MaterialsM the high dose was 85% p = 0.001. There was improvement in cause-specific survival in favor of the brachytherapy high dose level p = 0.016. On multivariate analysis, a low dose level, higher Gleason score, shorter time to nadir and higher nadir value were associated with increased biochemical failure. RTOG grade 3 GI/GU complications ranged 0.5–9%. Actuarial 5 yr impotency rate was 52%. Conclusion: EBRT interdigitated with HDR prostate brachytherapy boost is a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on BC and cause-specific survival with higher doses. These results coupled with the low risk of complications and advantage of not being radioactive post-implant defines a new standard for treatment.

Ultrasonic systems were developed for the treatment of superficial human tumors, generating local tumor hyperthermia at tumor center temperatures ranging from 43 degrees to 50 degrees. Twenty-eight patients with disease of varying histology were evaluable for response, and demonstrated an overall response rate of 57% with a complete response rate of 18%. In 11 patients who had received definitive radiation therapy to the heat treated area, the response rate was 81%; there were no toxicities other than those noted for the overall study. As temperature was escalated a marked increase was observed both in response rates (from 53% (43-44 degrees C) to 83% (48-50 degrees C) and in duration of response (from 29 to 250 days for the same temperatures). Toxicities were minimal, consisting of superficial blistering in four patients and pain in six patients. Pain was usually associated with tumor involvement in the periostium.

Clinical hyperthermia has been practised at The University of Texas System Cancer Center for nearly a decade at the time of writing. In 1977 we began with the use of systemic hyperthermia affected by circulating hot water through blankets surrounding the patient (Barlogie et al. 1979). The following year we began the development of systems for inducing local and regional hyperthermia to attain higher intratumoural temperatures, achieve greater antitumour activity and yet circumvent the toxicities associated with systemic hyperthermia above 42 degrees Celsius. The systems described below were the result of this effort, and, at the time that this contract was awarded in 1981, an active program was underway using ultrasound and magnetic induction as the two principal methods for external non-invasive tumour temperature elevation. Needle implant techniques were also in use as invasive methods for direct ohmic heating of tumours by the conduction of electric currents between arrays of implanted stainless steel...

Rat 13762NF mammary adenocarcinoma cells (clone MTC) were heated to 42 degrees C either in vivo as a subcutaneous tumour in the rat mammary fat pad or in vitro as attached cells. Labelling in vivo or in vitro detected very similar heat-stress proteins (hsp) at 160, 112, 90, 70 and 56 kDa. Syngeneic rat endothelial and macrophage cells synthesized several cellular proteins in vitro differently than did the tumour cells in vitro, but both types of normal cells were similar to tumour cells in the hsp synthesized. Although the quantitative aspects of induction and repression of hsp may depend on cell type and microenvironment, the major tumour hsp being studied for function in vitro were qualitatively similar to those produced and labelled in vivo in response to a similar heat dose. Hsp were similar in both normal cells and tumour cells from the same host. These observations support the concept that hsp function in fundamental processes in the different microenvironmental and metabolic conditions found in vivo and in vitro. In addition, these observations suggest that prediction of tumour thermal response by measuring hsp levels may be influenced by host cell components.