- Email: [email protected]
Definitive Extended-Field Radiation Therapy for Cervical Cancer Patients With Para-Aortic Lymph Node Metastases
S202
International Journal of Radiation Oncology Biology Physics
1108
Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) has been applied as a radioablative modality to multiple disease sites, achieving local control rates proximate to those observed following surgery. However, very little experience with SBRT in the management of gynecologic cancers has been reported to date. For patients for whom brachytherapy or surgery are contraindicated, external beam radiation therapy (EBRT) alone offers historically poor disease control outcomes. To our knowledge, this prospective phase 2 study reports the largest cohort of endometrial and cervical cancer cases treated with curative intent using SBRT as a boost modality in place of brachytherapy. Materials/Methods: Protocol eligibility criteria included the following: (1) pathologically confirmed endometrial or cervical squamous cell carcinoma or adenocarcinoma (serous and clear cell histologies were excluded); (2) no radiographic evidence of extrapelvic disease; (3) technical or medical contraindication to surgical therapy and brachytherapy; and (4) primary gross tumor volume (GTV) of less than 125 cm3. All patients first received EBRT to a minimum dose of 45.0 Gy encompassing primary tumor and regional pelvic lymphatics. Boost treatment planning then followed, and SBRT GTV delineation was aided by coregistration of the boost planning computed tomography (CT) set to a positron emission tomography (PET)/CT scan. Prior to each SBRT fraction, target setup was verified by matching to organ-implanted radio-opaque fiducial markers and by assessing for deformations using cone beam CT imaging. A total radiation dose of 40.0 Gy was prescribed to the primary tumor and delivered over a 10-day schedule of 5 fractions of 8.0 Gy each. Disease control response was assessed pathologically by 3-month posttherapy biopsy and radiographically by biannual PET/CT imaging. Acute and chronic toxicities were assessed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3 toxicity scales. Quality of life assessment was determined using FACT-G measurements. Results: Forty patients with primary endometrial (n Z 12) or cervical (n Z 28) cancer have been treated since June 2007 and have been followed for a median of 51.0 months and a minimum of 24.0 months. Post-SBRT biopsy was negative for 33 of 40 patients, or 82.5% of all patients. At 2 years, post-SBRT PET/CT imaging demonstrated a radiographic complete response (SUVmax <2.5) at the SBRT treatment site for 77.5% of all patients. No grade 3 or greater urinary or bowel toxicities have been observed to date. Pre- and post-SBRT FACT-G scores were statistically similar in all studied domains: physical, social, emotional, and functional well-being. Conclusion: At a median follow-up greater than 4 years and with a minimum follow-up of 2 years, SBRT appears to offer an effective and welltolerated boost modality for the management of selected gynecologic cancer patients otherwise contraindicated for brachytherapy or surgery. Author Disclosure: C.A. Mantz: None. F. Abu Shahin: None. S. Sandadi: None. J. Orr: None.
A Redefined Risk Stratification System for Patients With Stage I-II Myometrial Invasive Endometrioid Adenocarcinoma Z.S. Zumsteg, M.A. Kollmeier, G. Gardner, N.R. Abu-Rustum, and K.M. Alektiar; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): The lack of difference in outcome between the radiation therapy (RT) alone arm and the combined RT and chemotherapy (CT) arm in Gynecologic Oncology Group (GOG) 249 raises the question of whether patients designated as GOG high-intermediate risk (HIR) endometrioid adenocarcinoma, comprising the majority of patients enrolled in this trial, are in fact at high enough of a risk of relapse to justify the addition of CT to RT. We sought to determine whether such a subset of early-stage endometrioid adenocarcinoma patients at high risk of relapse could be identified. Materials/Methods: Patients with 1988 International Federation of Gynecology and Obstetrics stage IB-IIB endometrioid adenocarcinoma (GOG intermediate risk [IR]) treated at a single institution with definitive surgery without chemotherapy between 1992 and 2009 were analyzed. Unfavorable risk factors (URFs) were defined as statistically significant independent predictors of both relapse and death from endometrial cancer in Cox multivariate analyses. Results: Median follow-up was 5.4 years. Seven hundred and twenty-eight patients met the inclusion criteria for this study. Adjuvantly, 74.0% received intravaginal RT alone, 3.2% received pelvic RT alone, 7.7% received both, and 15.1% did not receive any RT. In multivariate analysis grade 3 (hazard ratio [HR]: 2.40, 95% confidence interval [CI]: 1.48-3.89; P < .001), age 60 years (HR: 2.55, 95% CI: 1.6-4; P < .001), and cervical stromal invasion (CSI; HR: 2.05, 95% CI: 1.16-3.62; P Z .13) were independent predictors for higher relapse, as well as death from endometrial cancer ([grade 3; HR: 2.94, 95% CI: 1.48-5.82; P Z .002], [age 60; HR: 2.50, 95% CI: 1.21-5.15; P Z .013], [CSI; HR: 4.00, 95% CI: 1.89-8.5; P < .001]). These factors were defined as URFs. Overall, 231 (32%), 421 (58%), and 76 (10%) patients had 0, 1, or 2 URFs. We dichotomized the cohort into those with 0 to 1 URF and those with 2 URFs. In comparison to patients with 0 to 1 URF, patients with 2 URFs had a markedly worse 5year outcome, as shown in Table 1. Similar results were seen even amongst the subgroup of 204 patients with GOG HIR disease, with the 48 (24%) patients with 2 URFs having significantly worse 5-year relapse (15.8% vs 40.8%, P < .001), death from endometrial cancer (5.8% vs 22.2%, P Z .016), distant relapse (10.1% vs 28.2%, P Z .008), and death from any causes (17.9% vs 32.7%, P Z .036) than those with 0 to 1 URF. Conclusion: Patients with 2 URFs (grade 3, age 60, and CSI) have significantly worse outcomes than those with 0 or 1 URF. However, this subset represented only 10% of patients in this study. This indicates that the vast majority of patients with GOG IR disease (90%), and even 76% of those classified as GOG HIR, have fewer than 2 URFs and are thus unlikely to benefit from adjuvant CT due to a low risk of relapse or death from endometrial cancer. ePoster Abstracts 1108; Table 1 5-year rates
0-1 RF
2 RF
P value
Distant relapse Any relapse Death from endometrial CA Death from any cause
5.2% 8.9% 3.5% 8.5%
28.8% 36.6% 20.0% 27.6%
<.001 <.001 <.001 <.001
Author Disclosure: Z.S. Zumsteg: None. M.A. Kollmeier: None. G. Gardner: None. N.R. Abu-Rustum: None. K.M. Alektiar: None.
1109 Stereotactic Body Radiation Therapy as a Boost Alternative to Brachytherapy for Primary Gynecologic Cancer: Disease Control and Quality of Life Outcomes From a Phase II Trial C.A. Mantz,1 F. Abu Shahin,2 S. Sandadi,2 and J. Orr2; 121st Century Oncology, Fort Myers, FL, 2Florida Gynecologic Oncology, Fort Myers, FL
1110 Definitive Extended-Field Radiation Therapy for Cervical Cancer Patients With Para-Aortic Lymph Node Metastases E.M. Osborne, A.H. Klopp, A. Jhingran, L. Meyer, and P.J. Eifel; MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Since 2000, innovations including chemoradiation, intensity modulated radiation therapy (IMRT), and positron emission tomography (PET) scans have transformed the treatment of locally advanced cervical cancer. Analysis of 88 patients with advanced cervical cancer involving the para-aortic lymph nodes (PANs) treated at our institution in the 1980s and 1990s revealed poor outcomes, with a 3year disease-specific survival (DSS) rate of 38%. In this single-institution study, we investigate outcomes of patients treated since 2000 with definitive radiation therapy (RT) for cervical cancer with PAN metastases. Materials/Methods: We reviewed the medical records of 102 cervical cancer patients with PAN metastases treated with curative intent at our institution between 2000 and 2014. All patients had pathologic or
Volume 93 Number 3S Supplement 2015 radiographic confirmation of metastatic disease to the PANs. Patients received initial RT to the pelvis and PANs with fields extending proximally to at least the top of L2 (median dose 45 Gy in 25 fractions). Grossly involved PANs were boosted to a median total dose of 60 Gy. IMRT was used to treat PANs in 46 patients (45%), and 61 patients (60%) were staged with PET scans. Ninety-eight patients (96%) received concurrent chemotherapy. Median follow-up was 53 months. KaplanMeier and Cox proportional hazard models were used to determine survival outcomes. Results: The median age at diagnosis was 48 years. Patients often presented with locally advanced disease; 43 (42%) had stage III to IV disease and 53 (52%) had cervical tumors >6 cm. Most patients had extensive lymphadenopathy; 34 (33%) had nodal metastases >2 cm and 5 (5%) had biopsy-proven supraclavicular nodal metastases. The 3-year DSS rate was 54%, which was significantly improved over our historic controls (P Z .03); this improvement may in part reflect the addition of concurrent chemotherapy to radiation after 1999. However, for patients treated after 2000, factors associated with better DSS included staging with PET (P Z .02) and treatment of PANs with IMRT (P Z .009). The use of IMRT and PET scans became more routine after 2005. The 68 patients treated after 2005 had a 3-year DSS rate of 64% versus 35% for patients treated between 2000 and 2004 (P Z .004). After 2005, only 3 of 68 patients (4%) had a recurrence in PANs versus 6 of 34 patients (18%) treated in the earlier years. Most patients who had a recurrence had distant metastases (n Z 48, 47%). The rate of grade 3 or higher late toxicities was 17% and most frequently involved the gastrointestinal and genitourinary systems. Conclusion: Modern technological advances have led to improved outcomes for patients who have cervical cancer metastatic to PANs. Future studies should focus on ways to improve systemic treatments and reduce late toxicities without compromising local control. Author Disclosure: E.M. Osborne: None. A.H. Klopp: None. A. Jhingran: None. L. Meyer: None. P.J. Eifel: None.
1111 Real Time Dosimetry for Gynecologic Brachytherapy: Initial Results of a Prospective Clinical Trial Purpose/Objective(s): Clinical outcomes from brachytherapy are closely correlated with dose; however, there is currently no simple means of confirming the dose delivered to the target or organs at risk in real time. A nanoscintillator-based fiberoptic dosimeter (nanoFOD) was developed to allow for dose measurements for gynecologic brachytherapy in real time. With a cross-sectional diameter of <0.9 mm, this device allows for monitoring dose via adjacently placed brachytherapy catheters. A clinical trial was designed to prospectively test clinical feasibility in gynecologic high-dose-rate brachytherapy implants. Materials/Methods: An IRBeapproved prospective clinical trial was opened in 2014, enrolling women undergoing vaginal cylinder high-doserate brachytherapy. The first 15 fractions of a total planned 30 fractions will be the subject of this report. The nanoFOD device was attached to the side of vaginal cylinder at a fixed distance from the base with 2 thermoluminescent dosimeters (TLDs) placed at the same level for reference standards. Treatment was then delivered as per the standard of care, with real time dose rates continuously captured by the nanoFOD. The nanoFOD and TLD positions were then identified on the planning CT scan, and predicted doses were calculated by the treatment planning system (TPS) based on TG43 formalism. The ratios of the nanoFOD to TPS doses and TLD to TPS doses were then compared for consistency and accuracy with descriptive statistics. Results: Of 15 fractions, there were real time dose rates available in 14 of 15 treatments. There was a single device failure due to breakage of the fiberoptic cable. Of the remaining fractions, 12 were evaluable for TPS comparison at the time of analysis. The median ratio of nanoFOD/TPS dose was 0.99 (interquartile range [IQR] 0.97-1.03), with a TLD/TPS ratio of 1.01 (IQR 0.98-1.04). Nine of 12 nanoFOD measurements were within 5% of the TPS dose, 2 of 12 between 5% to 10% of the TPS dose, with
ePoster Sessions S203 the remaining one fraction with 18% variation from the TPS. In comparison, 18 of 20 TLD measurements were within 5% of the TPS dose, 1 of 20 were within 5% to 10% of the TPS dose, and the remaining fraction within 21% of the TPS dose. Conclusion: Initial results with a novel real time dosimeter for brachytherapy are encouraging, with minimal device failures, and good concordance in the majority of measurements in comparison to the TPS. There were outlying measurements with >10% variation from TPS calculations with both the nanoFOD and the TLD reference dosimeters, though were more common with the nanoFOD. Future efforts will be focused on more reliable identification of the nanoFOD position on planning CT, prevention of movement of the nanoFOD between planning and treatment, and translation into more complex treatments including tandem and ring/ovoid brachytherapy.
1112 Correlation Between Vaginal Stenosis (VS), Vaginal Packing (VP) Volume, and Vaginal Dose in Cervical Cancer High-Dose-Rate Brachytherapy M. Federico, A. Tornero, S. Torres Pozas, B. Pinar, D. Rey Baltar Oramas, P. Lara, and R. Martin Oliva; HUGC Dr. Negrin, Las Palmas, Spain Purpose/Objective(s): Three-dimensional (3D) BT for CC shows outstanding results in terms of tumor control and morbidity. Nevertheless, vaginal morbidity is an unsolved problem, and no dose constraints have been published so far. The aim of this study is to identify a threshold level for VP volume and a dose response curve for VS. Materials/Methods: One hundred twenty-four consecutive CC patients (median age 52 years) treated between 2008 and 2014 were considered. All patients received 3D RCT and T-O HDR BT (overall 554 fractions). Fifty-eight patients (group A) received CT-based BT (5 fractions of 5.5 Gy), 66 patients (group B) received MR-based BT (4 fractions of 7 Gy). Group A patients had a treatment slightly optimized to organs at risk (OARs). Group B patients had a treatment optimized to OARs and HRCTV according GEC ESTRO recommendations. All patients entered prospective follow-up. Morbidity was scored according to Common Terminology Criteria for Adverse Events version 3.0 VP was contoured from a plane tangential to lower border of pubic bone up above ovoids surface. Vaginal walls were delineated as a 2-mm expansion of VP subtracted of VP volume. To compare dose distributions of applications of different dose size, the optimized plans of group A patients were reescalated to 7 Gy. For all patients a standard 7-Gy point A plan was calculated. The influence of VP volume on BT dose distribution to vagina for optimized and standard plans was analyzed plotting vagina DVH parameters against VP volume. Furthermore, out of 124 patients, 85 who were alive at the time of analysis with controlled disease and a follow-up time >1 year were analyzed. To assess the relationship between VS, VP, and vaginal dose, a median VP volume (VPm) among the 5 (group A) or 4 (group B) applications each patient received was calculated. Moreover the cumulative BT EQD2 dose to the vagina that each patient received was calculated. A Logistic model (LM) was used to analyze data Results: Average VP volume was 80.4 44.8 cm3. In 554 applications a double exponential fit was noticed between vagina D80, D65, D50, D30, and VP volume, with a fast growing exponential part (minimal variations in VP volume corresponding to huge variations in vaginal dose), and a slow growing exponential part (variation in VP volume having a modest impact on dose). VP volume cutoff values dividing the 2 parts of the curve for standard and optimized plans and for all considered vagina DVH parameters were encompassed between 70 and 80 mL. LM showed good correlation (R2 Z 0.82 and 0.76, respectively) between VPm and G2 and G3 VS. Risk of VS G3 or G2 was less than 5% when a VPm volume >75 or 110 mL was obtained. A dose response curve was found for VS greater than G1 and vaginal EQD2 D80 (R2 Z 0.96), D65 (R2 Z 0.82), D50 (R2 Z 0.68), and D30 (R2 Z 0.89) with a risk of G2-3 VS lower of 5% when EQD2 dose to respective DVH parameters was lower than 2.16 Gy, 10.89 Gy, 9.76 Gy, and 25.18 Gy.
International Journal of Radiation Oncology Biology Physics
1108
Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) has been applied as a radioablative modality to multiple disease sites, achieving local control rates proximate to those observed following surgery. However, very little experience with SBRT in the management of gynecologic cancers has been reported to date. For patients for whom brachytherapy or surgery are contraindicated, external beam radiation therapy (EBRT) alone offers historically poor disease control outcomes. To our knowledge, this prospective phase 2 study reports the largest cohort of endometrial and cervical cancer cases treated with curative intent using SBRT as a boost modality in place of brachytherapy. Materials/Methods: Protocol eligibility criteria included the following: (1) pathologically confirmed endometrial or cervical squamous cell carcinoma or adenocarcinoma (serous and clear cell histologies were excluded); (2) no radiographic evidence of extrapelvic disease; (3) technical or medical contraindication to surgical therapy and brachytherapy; and (4) primary gross tumor volume (GTV) of less than 125 cm3. All patients first received EBRT to a minimum dose of 45.0 Gy encompassing primary tumor and regional pelvic lymphatics. Boost treatment planning then followed, and SBRT GTV delineation was aided by coregistration of the boost planning computed tomography (CT) set to a positron emission tomography (PET)/CT scan. Prior to each SBRT fraction, target setup was verified by matching to organ-implanted radio-opaque fiducial markers and by assessing for deformations using cone beam CT imaging. A total radiation dose of 40.0 Gy was prescribed to the primary tumor and delivered over a 10-day schedule of 5 fractions of 8.0 Gy each. Disease control response was assessed pathologically by 3-month posttherapy biopsy and radiographically by biannual PET/CT imaging. Acute and chronic toxicities were assessed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3 toxicity scales. Quality of life assessment was determined using FACT-G measurements. Results: Forty patients with primary endometrial (n Z 12) or cervical (n Z 28) cancer have been treated since June 2007 and have been followed for a median of 51.0 months and a minimum of 24.0 months. Post-SBRT biopsy was negative for 33 of 40 patients, or 82.5% of all patients. At 2 years, post-SBRT PET/CT imaging demonstrated a radiographic complete response (SUVmax <2.5) at the SBRT treatment site for 77.5% of all patients. No grade 3 or greater urinary or bowel toxicities have been observed to date. Pre- and post-SBRT FACT-G scores were statistically similar in all studied domains: physical, social, emotional, and functional well-being. Conclusion: At a median follow-up greater than 4 years and with a minimum follow-up of 2 years, SBRT appears to offer an effective and welltolerated boost modality for the management of selected gynecologic cancer patients otherwise contraindicated for brachytherapy or surgery. Author Disclosure: C.A. Mantz: None. F. Abu Shahin: None. S. Sandadi: None. J. Orr: None.
A Redefined Risk Stratification System for Patients With Stage I-II Myometrial Invasive Endometrioid Adenocarcinoma Z.S. Zumsteg, M.A. Kollmeier, G. Gardner, N.R. Abu-Rustum, and K.M. Alektiar; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): The lack of difference in outcome between the radiation therapy (RT) alone arm and the combined RT and chemotherapy (CT) arm in Gynecologic Oncology Group (GOG) 249 raises the question of whether patients designated as GOG high-intermediate risk (HIR) endometrioid adenocarcinoma, comprising the majority of patients enrolled in this trial, are in fact at high enough of a risk of relapse to justify the addition of CT to RT. We sought to determine whether such a subset of early-stage endometrioid adenocarcinoma patients at high risk of relapse could be identified. Materials/Methods: Patients with 1988 International Federation of Gynecology and Obstetrics stage IB-IIB endometrioid adenocarcinoma (GOG intermediate risk [IR]) treated at a single institution with definitive surgery without chemotherapy between 1992 and 2009 were analyzed. Unfavorable risk factors (URFs) were defined as statistically significant independent predictors of both relapse and death from endometrial cancer in Cox multivariate analyses. Results: Median follow-up was 5.4 years. Seven hundred and twenty-eight patients met the inclusion criteria for this study. Adjuvantly, 74.0% received intravaginal RT alone, 3.2% received pelvic RT alone, 7.7% received both, and 15.1% did not receive any RT. In multivariate analysis grade 3 (hazard ratio [HR]: 2.40, 95% confidence interval [CI]: 1.48-3.89; P < .001), age 60 years (HR: 2.55, 95% CI: 1.6-4; P < .001), and cervical stromal invasion (CSI; HR: 2.05, 95% CI: 1.16-3.62; P Z .13) were independent predictors for higher relapse, as well as death from endometrial cancer ([grade 3; HR: 2.94, 95% CI: 1.48-5.82; P Z .002], [age 60; HR: 2.50, 95% CI: 1.21-5.15; P Z .013], [CSI; HR: 4.00, 95% CI: 1.89-8.5; P < .001]). These factors were defined as URFs. Overall, 231 (32%), 421 (58%), and 76 (10%) patients had 0, 1, or 2 URFs. We dichotomized the cohort into those with 0 to 1 URF and those with 2 URFs. In comparison to patients with 0 to 1 URF, patients with 2 URFs had a markedly worse 5year outcome, as shown in Table 1. Similar results were seen even amongst the subgroup of 204 patients with GOG HIR disease, with the 48 (24%) patients with 2 URFs having significantly worse 5-year relapse (15.8% vs 40.8%, P < .001), death from endometrial cancer (5.8% vs 22.2%, P Z .016), distant relapse (10.1% vs 28.2%, P Z .008), and death from any causes (17.9% vs 32.7%, P Z .036) than those with 0 to 1 URF. Conclusion: Patients with 2 URFs (grade 3, age 60, and CSI) have significantly worse outcomes than those with 0 or 1 URF. However, this subset represented only 10% of patients in this study. This indicates that the vast majority of patients with GOG IR disease (90%), and even 76% of those classified as GOG HIR, have fewer than 2 URFs and are thus unlikely to benefit from adjuvant CT due to a low risk of relapse or death from endometrial cancer. ePoster Abstracts 1108; Table 1 5-year rates
0-1 RF
2 RF
P value
Distant relapse Any relapse Death from endometrial CA Death from any cause
5.2% 8.9% 3.5% 8.5%
28.8% 36.6% 20.0% 27.6%
<.001 <.001 <.001 <.001
Author Disclosure: Z.S. Zumsteg: None. M.A. Kollmeier: None. G. Gardner: None. N.R. Abu-Rustum: None. K.M. Alektiar: None.
1109 Stereotactic Body Radiation Therapy as a Boost Alternative to Brachytherapy for Primary Gynecologic Cancer: Disease Control and Quality of Life Outcomes From a Phase II Trial C.A. Mantz,1 F. Abu Shahin,2 S. Sandadi,2 and J. Orr2; 121st Century Oncology, Fort Myers, FL, 2Florida Gynecologic Oncology, Fort Myers, FL
1110 Definitive Extended-Field Radiation Therapy for Cervical Cancer Patients With Para-Aortic Lymph Node Metastases E.M. Osborne, A.H. Klopp, A. Jhingran, L. Meyer, and P.J. Eifel; MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Since 2000, innovations including chemoradiation, intensity modulated radiation therapy (IMRT), and positron emission tomography (PET) scans have transformed the treatment of locally advanced cervical cancer. Analysis of 88 patients with advanced cervical cancer involving the para-aortic lymph nodes (PANs) treated at our institution in the 1980s and 1990s revealed poor outcomes, with a 3year disease-specific survival (DSS) rate of 38%. In this single-institution study, we investigate outcomes of patients treated since 2000 with definitive radiation therapy (RT) for cervical cancer with PAN metastases. Materials/Methods: We reviewed the medical records of 102 cervical cancer patients with PAN metastases treated with curative intent at our institution between 2000 and 2014. All patients had pathologic or
Volume 93 Number 3S Supplement 2015 radiographic confirmation of metastatic disease to the PANs. Patients received initial RT to the pelvis and PANs with fields extending proximally to at least the top of L2 (median dose 45 Gy in 25 fractions). Grossly involved PANs were boosted to a median total dose of 60 Gy. IMRT was used to treat PANs in 46 patients (45%), and 61 patients (60%) were staged with PET scans. Ninety-eight patients (96%) received concurrent chemotherapy. Median follow-up was 53 months. KaplanMeier and Cox proportional hazard models were used to determine survival outcomes. Results: The median age at diagnosis was 48 years. Patients often presented with locally advanced disease; 43 (42%) had stage III to IV disease and 53 (52%) had cervical tumors >6 cm. Most patients had extensive lymphadenopathy; 34 (33%) had nodal metastases >2 cm and 5 (5%) had biopsy-proven supraclavicular nodal metastases. The 3-year DSS rate was 54%, which was significantly improved over our historic controls (P Z .03); this improvement may in part reflect the addition of concurrent chemotherapy to radiation after 1999. However, for patients treated after 2000, factors associated with better DSS included staging with PET (P Z .02) and treatment of PANs with IMRT (P Z .009). The use of IMRT and PET scans became more routine after 2005. The 68 patients treated after 2005 had a 3-year DSS rate of 64% versus 35% for patients treated between 2000 and 2004 (P Z .004). After 2005, only 3 of 68 patients (4%) had a recurrence in PANs versus 6 of 34 patients (18%) treated in the earlier years. Most patients who had a recurrence had distant metastases (n Z 48, 47%). The rate of grade 3 or higher late toxicities was 17% and most frequently involved the gastrointestinal and genitourinary systems. Conclusion: Modern technological advances have led to improved outcomes for patients who have cervical cancer metastatic to PANs. Future studies should focus on ways to improve systemic treatments and reduce late toxicities without compromising local control. Author Disclosure: E.M. Osborne: None. A.H. Klopp: None. A. Jhingran: None. L. Meyer: None. P.J. Eifel: None.
1111 Real Time Dosimetry for Gynecologic Brachytherapy: Initial Results of a Prospective Clinical Trial Purpose/Objective(s): Clinical outcomes from brachytherapy are closely correlated with dose; however, there is currently no simple means of confirming the dose delivered to the target or organs at risk in real time. A nanoscintillator-based fiberoptic dosimeter (nanoFOD) was developed to allow for dose measurements for gynecologic brachytherapy in real time. With a cross-sectional diameter of <0.9 mm, this device allows for monitoring dose via adjacently placed brachytherapy catheters. A clinical trial was designed to prospectively test clinical feasibility in gynecologic high-dose-rate brachytherapy implants. Materials/Methods: An IRBeapproved prospective clinical trial was opened in 2014, enrolling women undergoing vaginal cylinder high-doserate brachytherapy. The first 15 fractions of a total planned 30 fractions will be the subject of this report. The nanoFOD device was attached to the side of vaginal cylinder at a fixed distance from the base with 2 thermoluminescent dosimeters (TLDs) placed at the same level for reference standards. Treatment was then delivered as per the standard of care, with real time dose rates continuously captured by the nanoFOD. The nanoFOD and TLD positions were then identified on the planning CT scan, and predicted doses were calculated by the treatment planning system (TPS) based on TG43 formalism. The ratios of the nanoFOD to TPS doses and TLD to TPS doses were then compared for consistency and accuracy with descriptive statistics. Results: Of 15 fractions, there were real time dose rates available in 14 of 15 treatments. There was a single device failure due to breakage of the fiberoptic cable. Of the remaining fractions, 12 were evaluable for TPS comparison at the time of analysis. The median ratio of nanoFOD/TPS dose was 0.99 (interquartile range [IQR] 0.97-1.03), with a TLD/TPS ratio of 1.01 (IQR 0.98-1.04). Nine of 12 nanoFOD measurements were within 5% of the TPS dose, 2 of 12 between 5% to 10% of the TPS dose, with
ePoster Sessions S203 the remaining one fraction with 18% variation from the TPS. In comparison, 18 of 20 TLD measurements were within 5% of the TPS dose, 1 of 20 were within 5% to 10% of the TPS dose, and the remaining fraction within 21% of the TPS dose. Conclusion: Initial results with a novel real time dosimeter for brachytherapy are encouraging, with minimal device failures, and good concordance in the majority of measurements in comparison to the TPS. There were outlying measurements with >10% variation from TPS calculations with both the nanoFOD and the TLD reference dosimeters, though were more common with the nanoFOD. Future efforts will be focused on more reliable identification of the nanoFOD position on planning CT, prevention of movement of the nanoFOD between planning and treatment, and translation into more complex treatments including tandem and ring/ovoid brachytherapy.
1112 Correlation Between Vaginal Stenosis (VS), Vaginal Packing (VP) Volume, and Vaginal Dose in Cervical Cancer High-Dose-Rate Brachytherapy M. Federico, A. Tornero, S. Torres Pozas, B. Pinar, D. Rey Baltar Oramas, P. Lara, and R. Martin Oliva; HUGC Dr. Negrin, Las Palmas, Spain Purpose/Objective(s): Three-dimensional (3D) BT for CC shows outstanding results in terms of tumor control and morbidity. Nevertheless, vaginal morbidity is an unsolved problem, and no dose constraints have been published so far. The aim of this study is to identify a threshold level for VP volume and a dose response curve for VS. Materials/Methods: One hundred twenty-four consecutive CC patients (median age 52 years) treated between 2008 and 2014 were considered. All patients received 3D RCT and T-O HDR BT (overall 554 fractions). Fifty-eight patients (group A) received CT-based BT (5 fractions of 5.5 Gy), 66 patients (group B) received MR-based BT (4 fractions of 7 Gy). Group A patients had a treatment slightly optimized to organs at risk (OARs). Group B patients had a treatment optimized to OARs and HRCTV according GEC ESTRO recommendations. All patients entered prospective follow-up. Morbidity was scored according to Common Terminology Criteria for Adverse Events version 3.0 VP was contoured from a plane tangential to lower border of pubic bone up above ovoids surface. Vaginal walls were delineated as a 2-mm expansion of VP subtracted of VP volume. To compare dose distributions of applications of different dose size, the optimized plans of group A patients were reescalated to 7 Gy. For all patients a standard 7-Gy point A plan was calculated. The influence of VP volume on BT dose distribution to vagina for optimized and standard plans was analyzed plotting vagina DVH parameters against VP volume. Furthermore, out of 124 patients, 85 who were alive at the time of analysis with controlled disease and a follow-up time >1 year were analyzed. To assess the relationship between VS, VP, and vaginal dose, a median VP volume (VPm) among the 5 (group A) or 4 (group B) applications each patient received was calculated. Moreover the cumulative BT EQD2 dose to the vagina that each patient received was calculated. A Logistic model (LM) was used to analyze data Results: Average VP volume was 80.4 44.8 cm3. In 554 applications a double exponential fit was noticed between vagina D80, D65, D50, D30, and VP volume, with a fast growing exponential part (minimal variations in VP volume corresponding to huge variations in vaginal dose), and a slow growing exponential part (variation in VP volume having a modest impact on dose). VP volume cutoff values dividing the 2 parts of the curve for standard and optimized plans and for all considered vagina DVH parameters were encompassed between 70 and 80 mL. LM showed good correlation (R2 Z 0.82 and 0.76, respectively) between VPm and G2 and G3 VS. Risk of VS G3 or G2 was less than 5% when a VPm volume >75 or 110 mL was obtained. A dose response curve was found for VS greater than G1 and vaginal EQD2 D80 (R2 Z 0.96), D65 (R2 Z 0.82), D50 (R2 Z 0.68), and D30 (R2 Z 0.89) with a risk of G2-3 VS lower of 5% when EQD2 dose to respective DVH parameters was lower than 2.16 Gy, 10.89 Gy, 9.76 Gy, and 25.18 Gy.