Pelvic Radiotherapy Influences on Plasma Markers of Oxidative Stress and Plasma Endotoxin Level in Gynecologic Cancer Patients

Proceedings of the 53rd Annual ASTRO Meeting

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Pelvic Radiotherapy Alters Urine Levels of Calcitonin-Gene Related Peptide In Urine 1

A. Korcum , G. Aksu1, O. Duymus2, N. Ekinci2, N. Erin3 1

Akdeniz University, School of Medicine, Department of Radiation Oncology, Antalya, Turkey, 2Akdeniz University, Institute of Health Sciences, Antalya, Turkey, 3Akdeniz University, School of Medicine, Department of Pharmacology, Antalya, Turkey Purpose/Objective(s): Pelvic radiotherapy is widely used for the treatment of malignancies localized in the pelvis. Urinary complications are the major side effects of pelvic radiation. Etiopathogenesis of the radiation-induced bladder toxicity is not known. Calcitonin-Gene related peptide (CGRP) and Vasoactive intestinal peptide which are found in sensory neurons is important in both motor functions and local regulation of immune response in the urinary bladder. We previously observed that pelvic radiotherapy altered urinary SP levels which may have a role in acute and late toxicities of RT. There are, however no clinical studies examining the effects of pelvic radiotherapy on urine levels of sensory neuropeptides such as CGRP and VIP. Hence, the goal of this study was to determine the acute and sub acute effects of RT on CGRP and VIP levels in the urine. Materials/Methods: Ninety-four patients were enrolled in the study. Out of 94 patients 19 of them had endometrial, 24 of them had cervical, 22 of them had prostate and 29 of them had rectal carcinoma. Each patient received 2 Gy daily fractions and urine samples were obtained before first fraction, one hour after first, eighth and twenty-fifth fraction and twelve weeks after the completion of RT. Each patient was evaluated for urinary side effects weekly, according to RTOG toxicity criteria. SP levels were determined directly from urine samples by enzyme immune assay. Results: Time dependent increase in urinary side effects were reported such that in 76% of patients after 25th fraction developed side effects. Similarly there was significant and time dependent decrease in urinary CGRP levels which returned to control levels at the end of the 12 weeks. Patients who received (adjuvant or) concomitant chemotherapy, basal (Before RT) CGRP levels were significantly higher compared to untreated patients. CGRP levels were also time-dependently decreased following RT in patients who received chemotherapy. On the other hand basal CGRP level in patients who had previous pelvic surgery was significantly lower demonstrating that during pelvic surgery nerve fibers carrying sensory nerve endings were damaged. Urine VIP level was however not changed after RT. Similarly chemotherapy or previous pelvic surgery did not alter the urine VIP levels. This may reflect the non-neuronal origin of VIP found in urinary bladder. Conclusions: These results demonstrate that RT affects peptidergic neurons in the bladder and altered CGRP levels could partly play a role in acute and late toxicities of RT. Author Disclosure: A. Korcum: None. G. Aksu: None. O. Duymus: None. N. Ekinci: None. N. Erin: None.

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Hair-Sparing Whole Brain IMRT and Topical Tempol in Patients with Brain Metastases: A Prospective Phase II Trial for the Prevention of Iatrogenic Alopecia

F. A. Gallant, M. Azoulay, D. Roberge McGill University Health Centre, Montreal, QC, Canada Purpose/Objective(s): Metastases are the most common malignant tumors affecting the brain–a standard treatment for which is whole brain radiotherapy (WBRT). This inevitably results in alopecia–an important source of distress in this population. Although alopecia can be reversible, recovery time often exceeds patient life expectancy. Our trial assessed alopecia severity using a novel combination of hair-sparing intensity-modulated WBRT (shown pre-clinically to reduce scalp dose by half), with concurrent topical Tempol, an anti-oxidant shown in a phase I trial to provide partial hair sparing. Materials/Methods: Ten patients with brain metastases were prospectively accrued. These patients could not to be planned for alopecia-inducing chemotherapy in the month following WBRT. The hair OAR volume was customized for each patient with the help of a wire marker at CT simulation. The CTV consisted of the entire brain and image-guided radiotherapy was used to ensure a PTV of no more than 2mm. Tempol (70 mg/ml) was applied to the scalp 30 minutes prior to irradiation, and washed off immediately after each fraction. The dose was 5 daily fractions of 4 Gy. Patients were assessed during treatment for toxicity and at multiple points post treatment for hair loss/regrowth. A subjective assessment of hair loss/regrowth on a 4-point scale was performed by both investigators and patients, with photographs taken at each visit. In-vivo dosimetry was performed in a standardized reference area. Results: The median patient age was 66 years (47 - 81) with a male:female ratio of 6:4. Treatment was delivered via helical tomotherapy (n = 6) or fixed-field image-guided IMRT (n = 4). The median measured skin dose per fraction was 193cGy (119 - 281), representing 48% of the prescribed dose. Investigators and patients subjectively rated hair loss as being minimal or moderate in 50% of cases, with severe to complete hair loss in the other 50%. All patients were seen in follow-up at least once in the first 6 weeks; for the 2 patients evaluable at 5 months, hair regrowth had taken place with a density similar to baseline. No significant side effects were reported. Conclusions: The combination of hair-sparing intensity modulated WBRT and concomitant topical Tempol is feasible, welltolerated by patients, and shows evidence of a reduction in radiation-induced alopecia in half of patients–an apparent improvement from the hair loss expected in patients receiving WBRT. Study challenges included assuring planned follow-up visits for these palliative patients, objective measurements of hair density, and a lack of good historical data. Future areas of investigation may include use of a control group, and inclusion of patients with primary intracranial tumors. Author Disclosure: F.A. Gallant: None. M. Azoulay: None. D. Roberge: None.

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Pelvic Radiotherapy Influences on Plasma Markers of Oxidative Stress and Plasma Endotoxin Level in Gynecologic Cancer Patients

H. Kim1, S Kang2 1 Seoul National University Hospital, Seoul, Korea, Republic of Korea, 2Medical Research Center, Seoul National University, Seoul, Korea, Republic of Korea

Purpose/Objective(s): The aims of this study were to assess the effect of pelvic radiotherapy on plasma markers of oxidative stress and plasma endotoxin level, and to examine their correlation with radiotherapy-related adverse events.

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I. J. Radiation Oncology d Biology d Physics

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Volume 81, Number 2, Supplement, 2011

Materials/Methods: Twelve gynecologic cancer patients who were treated by pelvic radiotherapy with or without concurrent chemotherapy were enrolled in this study. Plasma markers of oxidative stress such as glutathione (GSH), oxidized glutathione (GSSG) and total antioxidant capacity, and plasma endotoxin levels were measured weekly during treatment. Subjective symptoms were assessed using EORTC-QLQ-c30 at the baseline and 5th week of radiotherapy. Results: Plasma GSH was highly oxidized and thereby GSH/GSSG ratio was dramatically decreased. The mean plasma endotoxin in all patients tended to elevate and persisted during radiotherapy, and the number of patients who showed positive endotoxin (defined as above 0.005 EU/ml) also increased. In QoL, global health status was significantly decreased (baseline; 54.17 ± 4.81 and 5th week treatment; 37.5 ± 4.54, p = 0.049). Nausea/vomiting, appetite loss, and diarrhea were significant changed symptoms (p \0.05), but it could not be assessed whether changes in such symptoms are related with oxidative stress markers or endotoxin. Conclusions: Pelvic radiotherapy induced the changes of GSH/GSSG ratio and plasma endotoxin. Further investigations containing interventional and longitudinal studies will be required to find out the influence of the changes in oxidative stress markers and endotoxin on the radiotherapy-related adverse events. Author Disclosure: H. Kim: None. S. Kang: None.

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Prognostic Factors for Sexual Dysfunction among Endometrial Cancer Patients Treated with Simple Hysterectomy and Adjuvant Intravaginal Radiation Therapy

S. Damast1, K. M. Alektiar1, S. Goldfarb1, A. Eaton1, S. Patil1, J. Mosenkis2, A. Bennett1, J. Carter1, E. Basch1 1 Memorial Sloan-Kettering Cancer Center, New York, NY, 2University of Chicago, Chicago, IL Purpose/Objective(s): Simple hysterectomy followed by intravaginal radiation therapy (IVRT) is a common treatment for early stage endometrial cancer (EC). Yet, there is little research on sexual functioning (SF) after such treatment. We investigated the prevalence of sexual dysfunction and factors associated with worse SF in EC patients followed routinely in a radiation oncology clinic. Materials/Methods: Patients with endometrioid adenocarcinoma (Stage I-II) who had received IVRT following simple hysterectomy between 01/03 - 10/09 were eligible to participate in this institutional review board approved, anonymous, cross-sectional study. Patients with recurrent disease, prior malignancy, or those who received external beam radiation or chemotherapy were excluded. Type of surgery was either minimally invasive (MIS, i.e., laparoscopic or robotic) or open. IVRT dose was 1800 2100cGy in 3 fractions, delivered with Ir-192, prescribed 0.5cm from the vaginal surface. Between 10/09- 05/10, patients received questionnaires either in clinic (n = 74) or by mail (n = 135). Questionnaire items included demographics, treatment information, and the Female Sexual Function Index (FSFI), a validated measure encompassing 6 domains of SF (desire, arousal, dryness, orgasm, satisfaction, pain). Multivariate regression was used with the FSFI as a continuous outcome variable (score range 1.2 - 35.4). Results: Of 209 questionnaires distributed, 159 (76%) were returned, with SF items completed in 104 (50%). Of these 104 cases, 61% were married, 80% were white, 74% were $ age 60, and 57% had $1 co-morbidity (diabetes, hypertension, depression). Type of surgery was MIS in 54%. Time interval from surgery was\6mo (24%); 6mo-2yr (24%); 2 - 5yr (32%); .5yr (19%). Posttreatment interventions for vaginal health included: dilator (76%), lubricant (35%), moisturizer (31%), and topical estrogen (8%). Sexual dysfunction, defined as FSFI score \26, was reported by 81% of respondents. In a model controlling for age, diabetes, time from surgery, type of surgery, and lubricant use, the factor with the largest observed negative effect on SF was having an open hysterectomy as opposed to MIS, which was associated with a 7-point drop in FSFI score (p \ 0.001). Effect of not using lubricant was also significant (p = 0.040). Effect of short time interval from surgery (\6 mo) was marginal (p = 0.059). Conclusions: Sexual dysfunction is prevalent in EC patients. Despite the advanced age and co-morbidities of this group, the factors most impacting SF appears to be modifiable, such as type of surgery and the use of lubricant. These findings may be useful when counseling patients about benefits of contemporary therapy and efficacy of post-treatment interventions which promote sexual health. Author Disclosure: S. Damast: None. K.M. Alektiar: None. S. Goldfarb: None. A. Eaton: None. S. Patil: None. J. Mosenkis: None. A. Bennett: None. J. Carter: None. E. Basch: None.

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Stereotactic Body Radiotherapy for Renal Cell Spinal Metastases is Optimal in Patients with Few Spinal Metastases

E. H. Balagamwala1, S. A. Koyfman2, C. A. Reddy2, T. Djemil2, G. K. Hunter2, L. Angelov3, J. H. Suh2, P. Xia2, S. T. Chao2 1 Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 2Cleveland Clinic Department of Radiation Oncology, Cleveland, OH, 3Cleveland Clinic Department of Neurological Surgery, Cleveland, OH

Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) has emerged as an important treatment option for patients with renal cell carcinoma (RCC) spinal metastases, as high prescription doses are thought to overcome inherent RCC radioresistance. We reviewed our outcomes in this patient population and identified factors associated with treatment failure. Materials/Methods: Fifty-eight patients (88 treatments) with RCC metastases received single fraction spine SBRT. The gross tumor and entire associated vertebral body(s) were included in the planning target volume (PTV) without additional margins. Toxicity was scored as per CTCAEv4.0 criteria. Pain relief was based on the Brief Pain Inventory and adjusted for narcotic use per RTOG 0631. Radiographic failure was defined as in-field or adjacent (within 1 vertebral body) failure on follow-up MRI. Multivariate analyses (MVA) were performed to correlate outcomes with the following variables: presence of epidural, paraspinal, or multilevel disease (2 - 5 sites); neural foramen involvement (NFI); vertebral body fracture prior to SBRT (VBF); PTV; SBRT dose; KPS; control of systemic disease; and prior radiotherapy (RT). Kaplan-Meier analysis and Cox proportional hazards modeling were utilized for statistical analysis. Results: Median age, KPS and follow-up were 58 yrs (range, 41 - 80), 80 (50 - 100) and 5.4 mo (0.3 - 38), respectively. At last follow-up, 19 (33%) patients were alive correlating with a median survival of 8.3 mo (1.5 - 38). Median actuarial time to