2195

Proceedings of the 48th Annual ASTRO Meeting

efficacy. The in situ gene therapy comprised of adenoviral vector mediated Herpes Simplex Virus-thymidine kinase (AdHSVtk) ⫹ valacyclovir (VCV). We are currently conducting clinical trials using this approach. This study explores long-term immune responses following combined radio-gene therapy compared to gene therapy as mono-therapy. Materials/Methods: The study design included two separate clinical trials in the Baylor Prostate Cancer SPORE Program: Trial A gene therapy in combination with IMRT for prostate cancer (31 patients) and Trial B gene therapy as monotherapy for local recurrent prostate cancer after failing initial radiotherapy (36 patients). Heparinized blood was collected at the time of vector injection and at selected intervals afterward until 12 months. Peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting (FACS) after the incubation with dual color labeled antibody pairs: CD45/CD14, CD3/CD19, CD3/CD8, CD3/CD4, CD8/HLA-DR, CD4/HLA-DR, CD3/HLA-DR, and CD3/CD56⫹CD16. Results: The pre-treatment mean percentage of activated CD8⫹ T cells (DR⫹CD8⫹ T cells) was 14.7% and 12.2% (Trials A and B, respectively). Two weeks after the vector injection, this increased to 31.7% and 21.9% (Trials A and B, respectively), and these increases were statistically significant (P ⬍ 0.0001 and P ⫽ 0.0188, respectively). Only in Trial A were significant increases seen at 4 weeks, 12 weeks, 4 months, 6 months, 8 months and 10 months (P ⬍ 0.0001, P ⫽ 0.0002, 0.0464, 0.0016, 0.0125 and 0.0354, respectively). In addition, activated CD4⫹ T cells were noted to increase significantly after the vector injection from 2 weeks till 12 months in Trial A only. (P ⫽ 0.0013 and 0.0069, respectively). Conclusions: This is the first report of long-term systemic immune responses following radio-gene therapy compared to genetherapy as mono-therapy. We present evidence showing long-term (up to 12 months) systemic T cell responses to two consecutive AdHSV-tk injections during combination in situ gene therapy and IMRT for prostate cancer. These results suggest the potential for sustained activation of cell-mediated immune responses and may have enhanced activities against cancer. This combined approach may maximize tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity. Author Disclosure: T. Fujita, None; B.S. Teh, None; W. Mai, None; T. Satoh, None; K. Tabata, None; E. Aguilar-Cordova, None; B.J. Miles, None; D. Kadmon, None; E.B. Butler, None; T.C. Thompson, None.

2194

Smoking and its Relationship to GU and GI Toxicity in Prostate Cancer Patients Treated With Radiation

N. H. Pahlajani, K. Ruth, E. M. Horwitz, M. B. Buyyounouski, D. Y. Chen, A. Pollack Fox Chase Cancer Center, Philadelphia, PA Background: Smoking is a cause of increased morbidity from cancer treatment. It is associated with an increased risk of radiation related toxicity in cancers of the head and neck, cervix, lung and breast. The impact of smoking on toxicity following radiation in prostate cancer patients, however, is not known. Purpose/Objective(s): The purpose of this study was to analyze the impact of smoking on gastrointestinal (GI) and genitourinary (GU) toxicity in patients with prostate cancer treated with definitive radiotherapy. Materials/Methods: 1398 patients were treated at Fox Chase Cancer Center for prostate cancer with 3D conformal radiation therapy alone between 1991 to 2001. Smoking information collected just prior to treatment included status as a current smoker, ex-smoker or non-smoker. Patients treated with androgen deprivation prior to or during treatment were excluded. The main endpoints examined in relation to smoking were acute and late GI and GU toxicity. Toxicity was defined by a modified RTOG scale, as described previously. Logistic regression and Cox proportional hazards models were used for univariate and multivariate analyses, and included RT dose, T-stage, Gleason score, and initial PSA, age, and history of diabetes mellitus. Results: Patients were treated to a median dose of 72 Gy. Median follow-up from the start of RT was 70.8 months. Smoking information was available for 1194 patients. Smoking was found to have a negative impact on acute GI toxicity. Compared to non-smokers, current smokers had more Grade 2 or higher acute GI toxicity on univariate analysis (p⫽0.002) and multivariate analysis (p⫽0.004) with an OR of 1.8 [1.2 to 2.8]. There was no difference in late GI toxicity in smokers. Smoking was found to have a negative impact on acute GU toxicity. Compared to non-smokers, current smokers had more grade 2 or higher acute GU toxicity on univariate analysis (p⫽0.001) and multivariate analysis (p⫽0.003), with an OR of 1.8 [95% CI of 1.3 to 2.8]. There was no difference in late GU toxicity by smoking status. Conclusion: In prostate cancer, current smokers treated with radiation are at increased risk of acute GI and GU toxicity. This finding correlates well with what has been described in other cancers. Since acute GU toxicity has been associated with late GU toxicity, longer follow-up may eventually demonstrate a relationship of smoking to late toxicity. These results underscore the importance of smoking cessation prior to RT. Author Disclosure: N.H. Pahlajani, None; K. Ruth, None; E.M. Horwitz, None; M.B. Buyyounouski, None; D.Y. Chen, None; A. Pollack, Varian, B. Research Grant; TAP Pharmaceuticals, D. Speakers Bureau/Honoraria; Astra Zeneca, D. Speakers Bureau/Honoraria.

2195

Correction to Target (PTV) Underdose and Rectal Overdose_Review of 1762 CT Scans Obtained During Image- Guided Radiation Therapy Using an In Room CT-on-Rail With a Linear Accelerator for the Treatment of Prostate Cancer

J. R. Wong1, M. Uematsu2, T. Chen1, S. Merrick1, N. P. Machernis1, C. Cheng1 Morristown Memorial Hospital, Morristown, NJ, 2Keio University, Tokyo, Japan

1

Background: Interfractional movements of organs between radiation deliveries of prostate cancer can be problematic. Depending on the margins, the posterior movements of the PTV (potential target volume) may lead to under dosage of the PTV and thus potential decreasing the local control, whereas the anterior movements of the rectum may lead to over dosage and thus increasing rectal complications. Because the anterior, superior, inferior and lateral margins of the PTV can be more generous, such organ movements may not lead to under or over dosage of the PTV or rectum. Purpose/Objective(s): Using in room CT scans obtained just prior to the radiation treatments, interfractional organ movements can be measured and corrected. We investigated the frequency and magnitude of the movements of prostate and rectum.

S317

S318

I. J. Radiation Oncology

● Biology ● Physics

Volume 66, Number 3, Supplement, 2006

Materials/Methods: The treatment records of 308 prostate patients from 5/2000 to 8/2005 with a total of 1762 in room CT scans obtained just prior to radiation treatments were reviewed. These patients had either primary prostate cancer or rising PSA after radical prostatectomy. 5–10 CT scans were obtained consecutively either during the last part of a cone down treatment or during the initial part of the radiation course as adaptive radiation therapy delivery. CT scannings were obtained using a CT-on-rail sharing the same table couch as the linac. The methodology of our image guided radiation therapy (IGRT) will be presented. Results: Of the 1762 CT scans reviewed, 51% required no isocenter adjustments in the AP-PA direction (if isocenter movement is ⬍3 mm, no adjustment is performed), 17% had shifts of 3–5 mm, 24% had shifts of 6 –10mm, and 8% had shifts ⬎10mm. In the superoinferior direction, 80% had no shift of isocenter (ie, ⬍3mm movement), 11% had shifts of 3–5mm, 7% had shifts of 6 –10mm, and 2% had shifts ⬎10mm. In the lateral directions, 73% had no shifts of isocenter, 11% had shifts of 3–5 mm, 13% had shifts of 6 –10mm, and 3% had shifts ⬎10mm. Furthermore, a total of 1222 CT scan data were analyzed from a subgroup of 200 patients with specific regards to AP vs. PA movements. Significant PA movements of the target may lead to under dosage of the PTV, and can be corrected by PA isocenter shifts. The incidence of PA shifts were_21% required shifts ⬎4mm, 12% ⬎6mm, and 3% ⬎10mm. Significant AP movements of the target (usually secondary to rectal filling/movement, which will be explained and presented) may lead to over dosage of the rectum, and can be corrected by AP isocenter shifts. The incidence of AP shifts of isocenters were_27% required shifts ⬎4mm, 13% required shifts ⬎6mm, and 3% required shifts ⬎10mm. Dosimetric evaluations will be presented. Conclusions: This is one of the largest and longest series of prostate patients clinically treated with IGRT. The AP and PA shifts as shown in our data have important implications regarding_a) the potential under dosage of the target, and thus increasing the local failure rate, and b) the potential over dosage of the rectum, and thus increasing the incidence of rectal complications, when prostate patients are not treated with IGRT. Author Disclosure: J.R. Wong, None; M. Uematsu, None; T. Chen, None; S. Merrick, None; N.P. Machernis, None; C. Cheng, None.

2196

Comparison of Two Types of Biochemical Failures Within the ASTRO and Phoenix Consensus Definitions in Patients Treated on RTOG 92– 02 and 94 –13

C. C. Pan1, K. Bae2, G. E. Hanks3, W. U. Shipley4, M. Roach5, H. M. Sandler1 University of Michigan, Ann Arbor, MI, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3Fox Chase Cancer Center, Philadelphia, PA, 4Massachusetts General Hospital, Boston, MA, 5University of California, San Francisco, CA

1

Purpose/Objective(s): A small, but significant population of prostate cancer patients treated with external beam radiation that are classified as biochemical failures by the ASTRO Consensus Definition or the new Phoenix Consensus Definition may be those patients who were deemed failures due to the “start of any salvage hormonal therapy.” Some of these patients’ PSA patterns following radiation are clinically obvious to be immediately considered failures, while other patients’ non-PSA clinical data may induce the start of hormonal therapy. “Start of hormonal therapy” failure patients may have a different prognosis compared to those patients who were deemed failures due to “three consecutive rising PSAs.” Additionally, this group may provide some insight into extreme PSA patterns. With current work on an updated Consensus definition progressing, this group should be explored. The next Consensus definition should be able to identify these patients in addition to the mainstream patients. We conducted this study to determine the differences in outcome between those patients who failed due to “start of any salvage hormonal therapy” and those patients who failed due to ASTRO or Phoenix PSA criteria. Materials/Methods: 2,800 patients from RTOG 92– 02 (1,521) and 94 –13 (1,279) were analyzed. The ASTRO consensus definition defines biochemical failure as occurring after three consecutive PSA rises following a nadir (A1), or any non-A1 event that prompted the initiation of salvage therapy (A2) after the end of radiation therapy. The date of failure is defined as the point half way between the nadir date and the first rise for A1, or the start date of salvage hormone therapy before the three consecutive rises for A2. The Phoenix definition defines biochemical failure as occurring when PSA is greater than nadir ⫹ 2 ng/ml (P1), or any non-P1 event that prompted the initiation of salvage therapy (P2) after the end of radiation therapy. The date of failure was defined to be the date that PSA is greater than nadir ⫹ 2 ng/ml for P1, or the start date of salvage hormone therapy before PSA is greater than nadir ⫹ 2 ng/ml for P2. Time to biochemical failure is measured from the randomization date to the date of failure. Results: The median time to biochemical failure for all patients, by biochemical failure type, was 24.0 months for A1, 21.5 months for A2, 34.5 months for P1, and 24.9 months for P2. Patients classified as A2 failures had a trend of earlier median time to failure compared to A1, and patients classified as P2 failures had a significantly earlier median time to failure in all arms of both studies than those classified as P1. 81 of 291 (27.8%) patients originally classified as A2 were captured as biochemical failure by PSA rise (P1). Overall survival, disease specific survival, and PSA kinetics for A1, A2, P1, and P2 will be reported. Conclusions: Patients deemed biochemical failures by A2 or P2 may have biologically more aggressive disease. Further investigation of this group’s PSA kinetics is warranted. While the Phoenix consensus definition can capture additional patients previously not deemed A1 failures by the previous ASTRO consensus definition, a large portion of A2 are still not captured with the nadir ⫹ 2ng/ml used in P1. Future use of Phoenix consensus definition should report the P2 group outcomes separately. Author Disclosure: C.C. Pan, None; K. Bae, None; G.E. Hanks, None; W.U. Shipley, None; M. Roach, None; H.M. Sandler, None.

2197

Comparison of Second Cancer Risk in Prostate Cancer Patients Treated With Neutron/Photon Irradiation, Photon Irradiation, or Prostatectomy

L. A. McGee, C. H. Bock, D. Perry, S. Bolton, C. Orton, J. D. Forman Karmanos Cancer Institute, Detroit, MI Purpose/Objective(s): Data from the atomic bomb survivors indicated that irradiation induced malignancies and neutron irradiation was approximately 20 fold more carcinogenic. In addition, high energy linear accelerators also emit neutrons at