Definitive Twice Daily High-dose Rate Brachytherapy (HDRB), with or without Pelvic External Beam Radiotherapy (RT), for the Treatment of Medically Inoperable Stage I Uterus Cancer

I. J. Radiation Oncology d Biology d Physics

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Volume 75, Number 3, Supplement, 2009

Optimized Vaginal Apex Brachytherapy using the GynSite Intracavitary Balloon Applicator

D. A. Miller1, C. Bradfield2, C. Bertelsman2, S. Richardson1, P. W. Grigsby1 1

Washington University School of Medicine, St. Louis, MO, 2Barnes Jewish Hospital, St. Louis, MO

Purpose/Objective(s): Traditional postoperative HDR brachytherapy to irradiate the vaginal apex using nondeformable intracavitary cylinders delivers a reduced dose to the mucosal surface across air-surface interfaces. The 3D treatment planning facilitates development of modern applicators to account for variations in the size and shape of the vaginal apex in each patient and between implants. The purpose of this study is to describe the application and dosimetric parameters of the GynSite intracavitary balloon for postoperative endometrial cancer patients requiring vaginal apex brachytherapy. Materials/Methods: For this prospective study, informed consent was obtained from 29 consecutive patients with endometrial carcinoma. All patients underwent a hysterectomy and received adjuvant brachytherapy to treat the proximal third (3–4 cm) of the vagina. The HDR brachytherapy was administered in 6 weekly fractions using the GynSite intracavitary balloon (MammoSite, Hologic). Under direct visualization, the balloon was inserted to the vaginal apex and infused with a 5% Conray in normal saline solution. Optimal inflation was clinically determined to achieve complete balloon surface apposition with the vaginal mucosa and confirmed radiographically. Radiation dose was prescribed to the mucosal surface of the vagina and specified according to institutional policy for individual risk factors. A total of 17 patients also received external irradiation to the pelvis. The CT simulations were performed after each implant in all patients. The 3D brachytherapy treatment planning was executed with dose optimization to the vaginal mucosa. Results: A total of 164 insertions were performed. The mean volume of balloon inflation was 47.6 cc (range, 20.8–83.8 cc; ± 11.4 cc). The prescribed dose to the vaginal mucosa per patient ranged from 400 to 1,000 cGy. The mean dose from brachytherapy to the 2 cc volume of the bladder and rectum was 48.6% and 70.4% of the prescribed dose, respectively. Normalized to 100 cGy at the vaginal mucosal surface, the 2 cc bladder doses ranged from 26.7 to 73.4 cGy (mean 48.6 cGy, ± 9.0) and the 2cc rectal doses ranged from 32.6 to 92.1 cGy (mean 70.4 cGy, ± 9.8). The normalized rectal and bladder dose increased as a function of balloon volume and unaffected by prescription dose. Through dose volume histogram (DVH) analysis, 100% of the prescribed dose covered an average of 95.4% of the targeted vaginal apex. There were no acute complications or vaginal cuff recurrences at a mean follow-up of 8 months. Conclusions: Postoperative vaginal apex brachytherapy using the GynSite applicator eliminates air-surface interfaces and results in excellent coverage of the vaginal mucosa with acceptable doses to the bladder and rectum. The GynSite applicator provides a unique platform for optimized image guided intracavitary brachytherapy. Author Disclosure: D.A. Miller, None; C. Bradfield, None; C. Bertelsman, None; S. Richardson, None; P.W. Grigsby, None.

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Prospective Phase I/II Trial of Helical Tomotherapy, Intracavitary Brachytherapy, and Concurrent Chemotherapy in Patients with Cervical Cancer

A. J. Chang, J. K. Schwarz, P. W. Grigsby Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): The objective of this prospective trial was to investigate the acute and chronic toxicity, response to therapy, and survival outcome of patients with cervical cancer treated with Helical Tomotherapy (HT) and concurrent chemotherapy. Materials/Methods: There were 15 patients with a new diagnosis of cervical cancer enrolled in this study from April 2006 to December 2006. The clinical stages of their disease was Ib1 in 3, Ib2 in 3, IIa in 2, IIb in 4, IIIb in 2, and IVa in 1. FDG PET/CT simulation was performed in all patients. All patients received HT to the pelvis (50.4 Gy PTV, 20 Gy MTV Cervix), concurrent HDR brachytherapy (650 cGy to point A weekly for 6 weeks) and concurrent weekly cisplatin chemotherapy (40mg/m2) for 6 weeks. All patients underwent pre-treatment and 3-month post-treatment whole body FDG PET/CT. Clinical follow-up was performed every 3 months. Patients were monitored for acute and chronic toxicity using the CTC 3.0 criteria. Survival estimates were performed using the Kaplan-Meier Method. Results: One patient died of intercurrent disease during therapy and the remaining 14 completed HT and HDR brachytherapy as planned. The median overall treatment time was 54 days (range, 46 to 72 days). Chemotherapy was given for 6 cycles in 12 patients and 3 patients refused chemotherapy. The acute Grades 3 and 4 hematologic toxicities were 27% and 13%. The acute Grades 3 and 4 GI toxicities were 13% and 0%. The acute Grades 3 and 4 GU toxicities were 7% and 0%. Grade 4 chronic GI toxicity occurred in 1 (1/15; 7%). There were no Grades 3 or 4 chronic GU toxicities. The 3-month post-therapy FDG-PET/CT demonstrated a complete metabolic response in 13/14 (93%) and a partial metabolic response in 1/14 (7%) The median follow-up time for those alive at last follow-up was 28 months. The 3-year cause-specific and progression-free survivals were 92 and 77%. Conclusions: External irradiation delivered with HT in combination with concurrent HDR brachytherapy and weekly cisplatin is feasible with acceptable acute and chronic toxicity. Author Disclosure: A.J. Chang, None; J.K. Schwarz, None; P.W. Grigsby, None.

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Definitive Twice Daily High-dose Rate Brachytherapy (HDRB), with or without Pelvic External Beam Radiotherapy (RT), for the Treatment of Medically Inoperable Stage I Uterus Cancer

S. Koyfman1, V. V. Thakkar2, J. J. Juliano1, D. A. Wilkinson1, C. A. Reddy1, P. A. Fleming1 1

Cleveland Clinic, Cleveland, OH, 2Southeast Radiation Oncology Group, Charlotte, NC

Purpose/Objective(s): To review outcomes of medically inoperable patients with Stage I uterus cancer treated with definitive radiotherapy. Materials/Methods: We retrospectively reviewed patients treated at the Cleveland Clinic between 1997 and 2006 for this IRB approved study. Patient, disease and treatment characteristics were abstracted from the medical record, including age, race, body mass

Proceedings of the 51st Annual ASTRO Meeting index (BMI), Charleson comorbidity score (unadjusted and age adjusted), smoking status, stage, grade, histology, brachytherapy dose and fractionation, and the use of external beam. Local control (LC) cause specific survival (CSS) and overall survival (OS) rates were calculated using the actuarial method. Prognostic factors were assessed using a Cox proportional hazards model. Results: From 1996–2006, 48 patients with Stage I uterine adenocarcinoma were treated with definitive radiotherapy and followed for a median time of 26.6 months. Median age was 67.5, BMI was 40.1, Charleson score was 2, and the median age adjusted Charleson score was 5. Forty-five patients (93.8%) had endometrioid histology and the other three (6.3%) had papillary serous type histology. Twenty-seven (56.3%), 15 (31.3%), and 6 (12.5%) patients had FIGO Grades 1, 2, or 3 disease, respectively. Pre-treatment MRI was obtained in only 15 patients (31%). Depth of myometrial invasion was unknown in 68% of patients. All patients were treated with twice-daily HDRB, with a 1–2 week mid-treatment break for patients receiving more than 4 fractions. Median HDRB dose was 46.24Gy in 8 fractions, with a median dose per fraction of 5.78Gy. Most often, either a double tandem (Rotte-Y) applicator (58%), or a tandem and ring applicator (18%) was used. All patients were planned using 2D imaging. Eleven patients (23%) received supplemental RT (median dose 45Gy). One patient (2%) experienced Grade 4 rectal bleeding requiring a permanent colostomy. Actuarial 5 year LC, CSS and OS were 71.5%, 80.9%, and 24.5%, respectively. Of the 9 patients (18.8%) who failed locally, 5 underwent salvage hysterectomy, and 2 of these patients remain free of disease. Multivariate analysis revealed that older age (p = 0.0015) and Grade 3 disease (p = 0.0126) were the only features that were significantly associated with worse overall survival. No patient, disease, or treatment characteristics were found to be associated with improved LC. Conclusions: Definitive twice daily HDRB is an effective treatment for Stage I uterine cancer. Routine pretreatment MRI may help guide the use of supplemental whole pelvic radiotherapy. 3D planning may help ensure accurate disease targeting. While CSS remains excellent, OS in this patient cohort is poor, likely due to significant co-morbidities. Author Disclosure: S. Koyfman, None; V.V. Thakkar, None; J.J. Juliano, None; D.A. Wilkinson, None; C.A. Reddy, None; P.A. Fleming, None.

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Evaluation Of External Beam Parametrial Boost In Locally Advanced Cervix Cancer–An Interim Report

A. Gangopadhyay S. Saha Medical College Hospitals, Kolkata 700049, India Purpose/Objective(s): Parametrial boost (PMB) in locally advanced cervix cancer (FIGO IIB and IIIB) is one of the under-explored areas in cervix cancer radiotherapy. This prospective randomized single institute pilot study aims to evaluate the outcome of PMB with individually customized central shield; based on dose distribution data derived from CT based HDR brachytherapy planning. Tumor response, recurrence pattern, disease free survival, and OAR toxicity are the study endpoints. Materials/Methods: From February 2006 to January 2008, 59 histopathologically proven patients of squamous cell carcinoma of cervix of Stages IIB or IIIB were randomly assigned after informed consent, on completion of conventional whole pelvic concomitant chemoradiotherapy (50 Gy in 25 fractions in 5 weeks by four field box with Cobalt60 plus concomitant weekly CDDP 30 mg/ m2) and CT based HDR intracavitary brachytherapy (18 Gy in 2 fractions over 2 weeks) into two arms - receiving additional external beam PMB (The Study Arm; n = 26) and no PMB (The Control Arm; n = 33). PMB was delivered to a dose of 9 Gy/5 fractions/1 week through AP-PA fields. Individual planning of parametrial boost fields accounted for width of brachytherapy reference isodose - midline shield was customized accordingly. Individualized CT based planning was done for each insertion of brachytherapy. Width of reference isodose and pelvic wall dose were recorded in each, as also, dose received by 0.1cc, 1cc, 2cc and 5cc volume of rectum, bladder and sigmoid from cDVH analysis of OARs. The entire treatment was completed within 8 weeks. Results: Median duration of follow-up was only 24 months. Complete response was in all patients in the Study Arm and in 32/33 of the Control Arm. Among complete responders, 3/26 in the Study Arm and 18/32 of the Control Arm suffered local recurrence in 24 months (p = 0.0008) - median time to treatment failure was 14 months. Parametrial failure (confirmed by MRI scan with contrast) was in none of the Study Arm (all 3 had central recurrence) and 14 of the Control Arm (p = 0.0001). One each in both arms had distant failure. Two-year DFS was 22/26 (84.6%) with PMB (the Study Arm) and 13/33 (39.4%) without PMB (p = 0.0005). An RTOG Grade 3 rectal toxicity was in 1 the Study Arm and none in the Control Arm. Grade 3 bladder toxicity was encountered in none of either arm. Conclusions: There was hardly any work in world literature to analyze the impact of parametrial boost with individually customized central shield in locally advanced cervix cancer. The initial results of this study - possibly the first one of its kind, justify this dose escalation in parametrial tissue as it significantly reduces incidence of parametrial failure and improves DFS without increased toxicity, provided the central shielding is designed individually on the basis of reference isodose width of CT based brachytherapy. Author Disclosure: A. Gangopadhyay, None; S. Saha, None.

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Effect of Chemoirradiation on Levels of Insulin-like Growth Factor-I (IGF I) and Insulin-Like Growth Factor-II (IGF II) in Patients with Stage IIIB Cancer of Uterine Cervix

P. K. Nandwani, R. K. Vyas, D. C. Bhavsar, M. J. Mehta, P. V. Iyer Gujarat Cancer & Research Institute, Ahmedabad Gujarat, India Purpose/Objective(s): This study was aimed to study the effect of chemoirradiation on levels of insulin like growth factor (IGF I) and insulin like growth factor (IGF II) in patients with Stage IIIB cancer of uterine cervix. Materials/Methods: In our study, we included 50 patients of histopathologically proven squamous cell carcinoma of Stage IIIB cancer of uterine cervix from May 2008 to August 2008. The age of patients ranged from 35 to 62 years. Along with the routine investigations pretreatment serum levels of IGF I & IGF II were done by ELISA kits. The serum level of IGF I was 250.9 + 68.5 ng/ mL and IGF II was 1,600 + 345 ng/mL. All patients were given concurrent cisplatin (30 mg/m2) weekly along with radiation (50 Gy/25#) with conventional portals followed by two sittings of intracavitary radiotherapy (7.5Gy each) on mHDR. All these patients were kept on regular follow-up with the serum levels of IGF I & IGF II done regularly at one, three and six months post treatment. Results: The mean serum levels of IGF I & IGF II in patients who achieved complete response (40%) returned to normal whereas the mean serum levels of IGF I & IGF II in patients who achieved partial response (50%) was 140 ng/mL and 850 ng/mL,

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