Daniel J. Buchholz

Preoperative infusional chemoradiation therapy for Stage T3 rectal cancer

PURPOSE To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. METHODS AND MATERIALS Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m2/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. RESULTS Posttreatment tumor stages were T1-2, N0 in 35%, T3 N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. CONCLUSIONS Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further.

A Prospective Pilot Study of Curative-intent Stereotactic Body Radiation Therapy in Patients With 5 or Fewer Oligometastatic Lesions

It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection.

Preoperative chemoradiation for adenocarcinoma of the pancreas : excessive toxicity of prophylactic hepatic irradiation

PURPOSE In an effort to reduce relapse in the liver and improve survival in patients with potentially resectable adenocarcinoma of the pancreatic head, we combined whole-liver irradiation with our standard preoperative chemoradiation regimen. METHODS AND MATERIALS Eleven patients with biopsy-proven, potentially resectable adenocarcinoma of the pancreatic head were treated with 50.4 Gy of external beam irradiation to the pancreas (1.8 Gy/day, 5 days/week) and concurrent continuous infusion 5-fluorouracil (300 mg/m2 per day). The liver was treated with 23.4 Gy on Days 8 through 21 (13 fractions; 1.8 Gy/fraction). Patients, who upon restaging with radiography and computed tomography were considered to have resectable tumors, were subsequently taken to surgery. If, at surgery, tumors were resectable, pancreaticoduodenectomy was performed, and 10 Gy of intraoperative electron-beam radiation therapy was delivered to the bed of the resected pancreas. RESULTS All 11 patients completed chemoradiation. Two treatment-related deaths occurred following chemoradiation, prompting premature termination of the study. Of seven patients taken to surgery, four underwent resection. Seven patients have died of disease, five with liver metastases. CONCLUSIONS Prophylactic hepatic chemoradiation, as given in this study, was associated with two treatment-related deaths and a higher than expected incidence of subsequent liver metastases. Our data do not support the use of this treatment program in patients with adenocarcinoma of the pancreas.

Clinical evaluation of interfractional variations for whole breast radiotherapy using 3-dimensional surface imaging.

PURPOSE To evaluate the impact of 3-dimensional (3D) surface imaging on daily patient setup for breast radiotherapy. MATERIALS AND METHODS Fifty patients undergoing treatment for whole breast radiotherapy were setup daily using an AlignRT system (VisionRT, London, UK) for 3D surface-based alignment. Daily alignments were performed against a reference surface topogram and shifts from skin marks were recorded daily. This investigation evaluated the following: (1) the performance of the surface-based imaging system for daily breast alignment; (2) the absolute displacements between setup with skin marks and setup with the surface-based imaging system; and (3) the dosimetric effect of daily alignments with skin marks versus surface-based alignments. RESULTS Displacements from 1258 treatment fractions were analyzed. Sixty percent of those fractions (749) were reviewed against MV portal imaging in order to assess the performance of the AlignRT system. Daily setup errors were given as absolute displacements, comparing setup marks against shifts determined using the surface-based imaging system. Averaged over all patients, the mean displacements were 4.1 ± 2.6 mm, 2.7 ± 1.4 mm, and 2.6 ± 1.2 mm in the anteroposterior (AP), superoinferior (S/I), and left-right (L/R) directions, respectively. Furthermore, the standard deviation of the random error (σ) was 3.2 mm, 2.2 mm, and 2.2 mm in the A/P, S/I, and L/R directions, respectively. CONCLUSIONS Daily alignment with 3D surface imaging was found to be valuable for reducing setup errors when comparing with patient alignment from skin marks. The result of the surface-based alignments specifically showed that alignment with skin marks was noticeably poor in the anteroposterior directions. The overall dosimetric effect of the interfractional variations was small, but these variations showed a potential for increased dose deposition to both the heart and lung tissues. Although these interfractional variations would not negatively affect the quality of patient care for whole breast radiotherapy, it may require an increase in PTV margin, especially in cases of partial breast irradiation.

5-Fluorouracil-radiation interactions in human colon adenocarcinoma cells

PURPOSE To determine the effect of cellular proliferation and cell cycle stage on the ability of postirradiation 5-fluorouracil (5-FU) to radiosensitize cultured human colon adenocarcinoma Clone A cells. METHODS AND MATERIALS Cell survival curves were generated for irradiated: (a) log- and plateau-phase Clone A cells; and (b) Clone A cells separated by centrifugal elutriation into the various phases of the cell cycle; with and without postirradiation treatment with 100 micrograms/ml 5-FU. RESULTS Postirradiation treatment with 5-FU sensitized proliferating cells to a greater degree than it sensitized cells growing in plateau phase. The beta component of cell kill in log-phase cells was increased by a factor of 1.5 with a sensitizer enhancement ratio of 1.21 at the 0.01 survival level. Plateau-phase cells showed less radiosensitization (sensitizer enhancement ratio of 1.13 at the 0.01 survival level); however, there was a mild increase in both alpha and beta kill in plateau-phase cells. Elutriated G1 cells were the most radiosensitive, independent of treatment with 5-FU. The phase of the cell cycle had little effect on the ability of fluorouracil to radiosensitize Clone A cells. CONCLUSION Proliferating cells are more susceptible to radiosensitization with 5-FU than plateau-phase cells are, but this effect appears to be independent of the phase of the cell cycle.

SU‐DD‐A3‐03: Evaluation of An Infrared Camera and X‐Ray System for Gated Radiation Therapy

Purpose: To determine the clinical feasibility of a gated treatmentdelivery system from BrainLab™. Method and Materials: The Exactrac from BrainLab™ is a localization system that uses both infrared cameras and x‐rays. In gated mode, target location is determined by implanted fiducials. Breathing patterns are determined by infrared reflectors attached to the patients surface. The User selects an x‐ray trigger point and radiotherapy beam‐on window relative to the breathing cycle. Multiple trigger levels may be selected to simulate a fluoroscopic mode to measure organ motion. Prior to clinical use feasibility tests including localization accuracy, gating window accuracy, and beam‐on accuracy were performed. Patients with small lung lesions were selected for treatment and implanted with a 20 by 0.7 mm gold fiducial. Treatment planning CT scans were taken at expiration breath hold with internal and external fiducials present. Results:_Localization accuracy was within 3mm when using 20% of the breathing cycle for beam on. To date, five patients with lung lesions were treated.Treatment times were approximately twenty minutes (standard dose fractionations). Implanted fiducials were well localizable in all patients. Target motion was on the order of 5mm average. Repeat CT scans showed implants did not migrate. The primary limitations with the system were related to breathing signal due to placement of external fiducials. Conclusion: Gating treatment technique from Exactrac™ has been used to treatlung lesions. This initial evaluation of the system verified the accuracy of the localization system under Gated mode. Implanted fiducials are localizable in patients, and gating is possible. The benefit of this system is the potential to decrease treatment margins and improve targeting. Continued evaluation of this system would help to define patient specific dose margins and beam‐on windows for treatment.

SU‐FF‐T‐06: Megavoltage CT Imaging Enables CT‐Based Low‐Doserate Brachytherapy Planning Without CT‐Compatible Applicators

Purpose: To determine feasibility of megavoltage computed tomography (MVCT) imaging for low dose rate (LDR) brachytherapy for cervical carcinoma.Method and Materials: A helical tomotherapy treatment unit (Tomotherapy HiArt ,Tomotherapy Inc., Madison, WI) using a nominal 3.5 MV x‐ray beam was used to image a dosimetry phantom containing standard, non‐CT compatible Fletcher‐Suit applicators and dummy Cs‐137 tube sources (3M Model 6500). The phantom contained several small steel BB markers which were used as dose points. The MVCT images were transferred to a commercially available treatment planning system (CMS XiO 4.2, Computerized Medical Systems, St. Louis, MO). Digitally reconstructed radiographs (DRRs) were generated from the MVCT data set, and doses(dose rates) were calculated at the phantom dose points using standard 2D, film‐based dosimetry methods. Doses were also calculated using a CT‐based, 3D dosimetry technique in which the brachytherapy source tips and ends were localized directly on MVCT images. Separate experiments were performed to verify the spatial accuracy of the MVCT image reconstruction in‐phantom. Results: In‐phantom localization accuracy was 0.6 ± 0.3 mm, slightly less than the size of an axial MVCT image pixel and less than half of the MVCT slice thickness. Point doses in‐phantom calculated by 2D and by 3D methods agreed within an average of 1.5%. The techniques developed for successful MVCT imaging in‐phantom can be used to calculate 3D dose distributions in a human patient undergoing a traditional (non‐CT compatible) Fletcher‐Suit implant. Conclusion: MVCT imaging allows CT‐based dosimetry planning without the use of special, “CT‐compatible” applicators.