MSRO35-01 MSRO35-02 MSRO MSRO35 BOOST: Gynecology Integrated Science and Practice (ISP) Session. Participants. Sub-Events

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MSRO35 BOOST: Gynecology Integrated Science and Practice (ISP) Session Multisession Courses RO OI GU AMA PRA Category 1 Credits : 1.50 ARRT Category A+ Credits: 1.

1 MSRO35 BOOST: Gynecology Integrated Science and Practice (ISP) Session Multisession Courses RO OI GU AMA PRA Category 1 Credits : 1.50 ARRT Category A+ Credits: 1.50 Tue, Dec 2 10:30 AM - 12:00 PM Location: S103CD Participants Moderator Nina A. Mayr MD : Nothing to Disclose Moderator Tracy Michelle Sherertz MD : Nothing to Disclose Sub-Events MSRO35-01 Invited Speaker: Manjeet Chadha MD (Presenter): Nothing to Disclose MSRO35-02 Carbon-ion and Photon Radiation Effects on Human Papilloma Virus Positive and Negative Cervical Carcinoma Cells Katja Lindel (Presenter): Nothing to Disclose, Marco Vercruysse : Nothing to Disclose, Stefan Rieken : Nothing to Disclose, Sigrid Daffinger : Nothing to Disclose, Juergen Debus MD, PhD : Nothing to Disclose Purpose/Objective(s): To compare the effect of photon and carbon-ion radiation on four cell lines with different HPV-status regarding cell cycle regulation and HPV associated protein expression. Hypothesis is that carbon ion radiation might overcome radiation resistance of HPV-negative or HPV-integrated cells. Materials/Methods: W12 cell line was derived from a low grade cervical lesion by Stanley MA et al. 1989, and is unique among HPV16-containing cell lines in carrying its HPV 16 genome as a multicopy episome. W12 cells contain episomal HPV 16 genomes, whereas S12 cells, which derived from the W12 line, contain HPV DNA as integrated copies. Caski cells have their origin in epidermoid cell cervical cancer and are reported to contain an HPV 16 genome as well as sequences related to HPV-18. C33A is a HPV-negative human cervical cancer derived cell line. Cell cycle analyses were performed using flow cytometry (PI staining) 24 h and 48 h after RT with 2 and 7 Gy using photon RT and 2 GyE and 7 GyE carbon ion RT(C12). Expression of prb and p53 after irradiation with 2 and 7 Gy were analyzed by flow cytometry using intracellular staining comparing the mean fluorescence of gated cells. Results: C33A cells (HPV-negative) showed a minimal enhanced expression of prb after RT with photons or C12 (0 Gy=1.0, 2 Gy=1.09, 7 Gy=1. 4, 2 GyE= 1.3, 7 GyE=1.1). There was no effect of photon or C12 irradiation on p53 expression in C33A cells. Caski cells (HPV16/18 positive) showed increased expression after photon RT (2 Gy=1.3, 7 Gy=1.7). Irradiation with C12 induced a strong increase of prb expression (2 GyE=7.7, 7 GyE=8.3). There was a minimal change of p53 expression after RT (2 Gy=1.3; 7 Gy=1.2, 2 GyE=1.6, 7 GyE=1.5). S12 cells (HPV 16 integrated) showed a decrease of prb expression after RT with photons (2 Gy=0.47, 7 Gy=0.38). Irradiation with C12 enhanced the expression of prb positive cells (2 GyE= 1.8,7 GyE=1.94), but showed no significant expression of p53 in the control group. W12 cells (HPV 16 episomal) showed no change of prb expression in the control group or after RT. C12 RT induced an increase of prb expression (2 GyE=1.5, 7 Gy=2.9). There was no significant change of p53 expression in W12 and S12 cells after RT. C12-RT showed no effect on cell cycle distribution in W12/S12 and C33A cells. 48 h after irradiation with 7 Gy photons in C33A cells and 24 h after RT in S12 cells a G2/M-block was induced. Conclusions: The effect of carbon-ion-rt on protein expression seems to be dependent on HPV-status and type of protein with no effect on p53 or on HPV-negative cells, but a strong effect on prb expression in HPV-positive cells. The converse effect of carbon-ion-rt compared to photon-rt on HPV positive cell with integrated HPV regarding prb expression indicates that carbon-ion therapy might overcome HPV-integration induced radioresistance. MSRO35-03 CT Mapping of Metastatic Nodal Disease in Patients with Advanced Cervical Cancer in an Indigent US Population: Implications for Resource Utilization and Conformal Radiation (CRT) Planning April Alexander Bailey MD (Presenter): Nothing to Disclose, Lindsay Hwang BS : Nothing to Disclose, Yin Xi : Nothing to Disclose, Matthew McKeever BS : Nothing to Disclose, Kevin V. Albuquerque MD : Nothing to Disclose PURPOSE Geographically map lymph node metastases, using CT in advanced cervical cancer patients, and correlate with standard conformal radiation planning techniques.

2 METHOD AND MATERIALS IRB-approved study of imaging, demographic and treatment data for patients with advanced cervical cancer referred for definitive radiation therapy between Pelvic (PLN) and paraaortic (PALN) lymph nodes were mapped on baseline CT examinations. PLN >8 mm and PALN >10 mm were considered abnormally enlarged and a surrogate for nodal metastatic disease. The anatomic location was recorded for PLN (common, internal, external iliac) and PALN (left paraaortic LPA, aortocaval AC, right paracaval RPC). Craniocaudal position and location with relation to the adjacent vertebral body for all PALN was recorded to create nodal maps. PET/CT was also obtained in 71.4% of this population; FDG-avid nodes were compared to the results of CT after primary analysis. RESULTS There were 77 patients included. PLN were identified in 74 of which 23 also had PALN. There were 3 additional patients with isolated PALN. Distribution of nodal disease in the pelvis was predominantly external iliac. The mean age of patients with and without PALN was different (55 v years, p=0.002). Higher FIGO stage (III or IV) also had a higher likelihood of PALN (p=0.0371). The most common PALN distribution was LPA (82.6%). No isolated RPC nodes were identified. Nearly all PALN (95.6%) were below the renal arteries. There was no correlation with type of PLN or presence of lower PALN to predict upper PALN indicating necessity to treat the entire infra-renal PALN chain with the presence of a single PALN. For the subset of patients with PET/CT evaluation, when a size threshold of >8 mm was used in the pelvis, no FDG-avid nodes were below detection, but if >10 mm was used in the pelvis, 13 out of 58 patients had metabolically active lymph nodes that would not have been identified. CONCLUSION Short axis PLN size of 8 mm on CT was a good surrogate for PET avidity which will assist resource poor locations. Geographic mapping of nodal size and patterns aid CRT planning by directing radiation port size and extent. CLINICAL RELEVANCE/APPLICATION Advanced cervical cancer treatment can be tailored by reviewing the common distribution patterns of pelvic and paraaortic lymphadenopathy on CT in an indigent US population. MSRO35-04 Prognosis and Survival of Women with Endometrial Carcinoma after Adjuvant Radiotherapy Robert Foerster (Presenter): Nothing to Disclose, Robert Kluck : Nothing to Disclose, Stefan Rieken : Nothing to Disclose, Juergen Debus MD, PhD : Nothing to Disclose, Katja Lindel : Nothing to Disclose Purpose/Objective(s): Endometrial cancer is the most common gynecologic malignancy. While therapy guidelines are widely established for endometrioid carcinomas, optimal treatment of subgroups with highly malignant histologies remains unclear. The purpose of this retrospective analysis was to determine the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors.materials/methods: 380 patients (pts) underwent adjuvant radiotherapy (RT) for endometrial carcinomas at the University Hospital Heidelberg, Germany, from 2004 until Median age at diagnosis was 66 years. The majority were early stage carcinomas (FIGO I 68.7%, FIGO II 13.6%, FIGO III 16.3%, FIGO IV 1.4%). 96.9% underwent lymphadenectomy (LNE) and 3.6% received additional adjuvant chemotherapy (ChT). 52.6% were treated with intravaginal brachytherapy (IVB) and 47.4% with IVB + external beam radiotherapy (EBRT). All pts were included in this retrospective cohort study and statistically evaluated (chi-square, LogRank test, Cox regression).results: Five year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 90%, 88.2% and 77.8% respectively. 22.2% died, 8.9% had a local recurrence and 8.9% developed distant metastases.better LRFS was associated with lower FIGO stage (p=.002), smaller tumor size (p<.001), N0 (p<.001), L0 (p<.001), V0 (p=.003), R0 (p<.001) and after LNE (p<.016).dmfs was prolonged with age <66 (p=.005), lower FIGO stage (p=.006), smaller tumor size (p<.001), N0 (p=.001), lower grading (p=.039), endometrioid histology (p=.043), L0 (p<.001), V0 (p<.001) and after LNE (p=.006).os was improved with age <66 years (p=.014), lower FIGO stage (p<.001), smaller tumor size (p<.001), N0 (p<.001), lower grading (p<.001), endometrioid histology (p<.001), L0 (p<.001), V0 (p<.001), R0 (p<.001) and after LNE (p=.004).in stage I there were no statistically significant survival differences for Grading in LRFS, DMFS or OS.In multivariate analysis for OS age (p=.019), grading (p=.014), histology (p=.001) and blood vessel infiltration (p<.001) remained as prognostic factors. For DMFS only blood vessel infiltration (p<.001) remained and for LRFS lymph vessel infiltration showed a tendency towards statistical significance (n.s.). Conclusions: RT ensures good local control rates in carcinomas of the uterus. However, carcinomas with non-endometrioid histology or advanced stages with high grading have a substantially worse prognosis and these pts are in need of a combined local and systemic therapy approach. For endometrioid carcinomas vessel infiltration might be the best predictive factor for a benefit from systemic therapy. MSRO35-05 Does the Apparent Diffusion Coefficient Value Predict Disease Recurrence in Patients with Locally Advanced Cervical Cancer Treated with Radical Chemoradiation? Adam Gladwish MD, MSc (Presenter): Nothing to Disclose, Michael Milosevic : Nothing to Disclose, Anthony Fyles : Nothing to Disclose, Warren D. Foltz PhD : Nothing to Disclose, Nathan Becker PhD : Nothing to Disclose, Haiyan Jiang : Nothing to Disclose, Wilfred Levin MD : Nothing to Disclose, Lee Manchul MD : Nothing to Disclose, Kathy Han MD : Nothing to Disclose PURPOSE To investigate whether pre-treatment apparent diffusion coefficient (ADC) from diffusion-weighted MRI is predictive of disease recurrence in women with locally advanced cervical cancer treated with radical

3 chemoradiation. METHOD AND MATERIALS Eighty-five women with stage IB-IVA cervical cancer treated with radical chemoradiation from had staging MRI, including T2-weighted (T2W) and DWI series at either 1.5 or 3.0T (b-value ). T2W images and ADC maps were co-registered in Pinnacle, and the tumor was delineated on the ADC maps with the aid of T2W images. The mean, median, 75th, 90th and 95th percentile ADC of the tumor were extracted using Matlab, and normalized to each patient's mean urine ADC to reduce variability (reported as dimensionless quantitates: nadc mean, nadc median, nadc 75, nadc 90, nadc 95, respectively). The primary outcome was disease-free survival (DFS). Information about recurrence and survival was recorded prospectively. Uni- and multivariate Cox regression analyses evaluated the predictive value of ADC parameters and relevant clinical variables (age, histology, stage, nodal status, baseline hemoglobin, tumor size) for DFS. RESULTS Of the 85 women included, 62 were disease free at last follow-up (FU). Median FU was 2.2 years. FIGO stage was IB in 45 patients, II in 33, and III/IVA in 7 patients. Median tumor diameter was 4.8 cm. Thirty-two women had pelvic nodal involvement, and 11 had paraaortic nodal involvement on staging CT/MR. The median nadc 95 was 0.58 (range ). Significant variables on univariate analysis included tumor size (HR 1.45, p = 0.01), paraaortic nodal involvement (HR 4.25, p=0.002), and all nadc parameters (HR ranged from per 0.01 increase in nadc, p < 0.04). nadc 75, nadc 90, and nadc 95 were highly correlated, and therefore only nadc 95 (lowest HR and p value) was included in multivariate analysis. On multivariate analysis, paraaortic nodal involvement and nadc 95 remained predictive of DFS (HR 3.12, p=0.02; and HR 0.92, p=0.005, respectively). CONCLUSION ADC may be a useful imaging biomarker for predicting treatment failure in patients with locally advanced cervical cancer treated with chemoradiation. CLINICAL RELEVANCE/APPLICATION Identification of patients with locally advanced cervical cancer at higher risk of recurrence based on the pre-treatment apparent diffusion coefficient will enable personalized treatment approach. MSRO35-06 Radiation Treatment Toxicities in Elderly Patients with Gynecological Cancers Arun George Paul MD, PhD (Presenter): Nothing to Disclose Purpose/Objective(s): A patient's age can be associated with co-morbidities and illnesses and is associated with poor outcomes in terms of patterns of failure and recurrence in many gynecological malignancies such as endometrial cancer. In this study, we retrospectively reviewed the toxicity profile of elderly (age >= 69 years) patients (pts) treated with radiation therapy (RT) for various gynecological malignancies.materials/methods: Elderly gynecological cancer pts receiving RT with or without surgery and/or chemotherapy from 04/2009 till 10/2013 at a single institution were retrospectively reviewed for treatment related toxicities. Pts were prospectively assessed weekly during the course of RT for toxicities such as fatigue, radiation dermatitis, vaginal bleeding, vaginal discharges, dysuria, diarrhea, nausea, and vomiting. The RT techniques and modalities used and the duration of RT were reviewed.results: 50 pts were treated with RT during the study period and 29 pts with detailed weekly documentation of treatment related toxicities were reviewed. The median age was 75 (69-90). 24 pts were treated for endometrial cancer, 2 for vaginal, 1 each for vulvar, cervical, and ovarian cancers. 15 pts were treated with surgery and adjuvant chemotherapy and radiation, 8 were treated with surgery and adjuvant radiation, 3 were treated with chemotherapy and radiation, and 3 with radiation alone. 14 pts with endometrial cancer underwent TAH-BSO with pelvic and peri-aortic nodal dissection, 3 had TAH-BSO with pelvic nodal dissection, and 3 had TAH-BSO alone. RT consisted of EBRT alone (n = 13), HDR alone (n = 9) or a combination of EBRT and HDR (n = 7). The techniques used for EBRT (n = 20) were IMRT (n = 14), 4-field (n =2), and 2 field (n = 4) and for HDR (n = 16) were vaginal cylinders (n = 13), ring/tandem (n = 2) and ovoid/tandem (n = 1). Median durations of treatment for patients receiving EBRT with HDR, EBRT alone, and HDR alone were 51 days (41-102), 36 days (34-60), and 7 days (6-14), respectively.4%, 48.2%, and 26.9% of the pts reported genitourinary (GU) side effects such as vaginal bleeding, vaginal discharges, and dysuria and 11.5%, 19.2%, and 64.3% reported gastrointestinal (GI) side effects such as vomiting, nausea, and diarrhea, respectively. 43.5% of the pts reported fatigue and 12.5 % and 16.7% of the pts had grade 1 and grade 4 radiation dermatitis of treated area, respectively. Conclusions: Overall, our data suggests that elderly (age >= 69 years) gynecological cancer pts treated with RT have satisfactory toxicity outcomes. To delineate the factors underlying the various GI and GU side effects we observed, we are currently analyzing the co-morbidities and RT parameters such as: a) the total dose received by the rectum, sigmoid, bowel, and bladder, b) the types of RT technique/modalities used, and c) duration of RT treatment. MSRO35-07 Clinical Outcome of Adjuvant Radiation Therapy in Early Stage Uterine Cervical Cancer Hyunju Kim (Presenter): Nothing to Disclose Purpose/Objective(s):To evaluate the outcome of adjuvant radiotherapy (RT) in FIGO IB-IIA uterine cervical cancer.materials/methods:we retrospectively reviewed the medical records of 197 patients with FIGO IB-IIA uterine cervical cancer who had undergone curative surgery followed by adjuvant RT in Yonsei Cancer Center between June 1997 and December The patient's median age was 48 years (range, 28-80yrs). Pelvic lymph node dissection and

4 para-aortic lymphnode dissection were performed in 138 (70.1%) and 92 (46.7%) patients, respectively. Adjuvant radiotherapy was delivered to whole pelvis field or extended field with or without brachytherapy up to total dose 50.4 Gy (range, Gy). Eighty-eight patients were high risk group and 109 patients were low-intermediate risk group. Of whole patients, 71 patients (36%) received adjuvant chemotherapy concurrently or sequentially. Results:The median follow-up period was 54.5 months. Loco-regional recurrence alone was occurred in 6 patients, distant metastasis was in 15 patients, and simultaneous regional and distant metastasis was in 2 patients. For all patients, 5 year locoregional recurrence free survival (LRFS) and 5 year distant metastasis free survival (DMFS) were 95.8% and 89.3%, respectively. Tumor size and non-squamous histology were the significant prognostic factors associated with LRFS (p=0.049) and DMFS (p=0.047), respectively in multivariate analysis.conclusions: Our results indicate that high loco-regional control rate was achieved by adjuvant RT for early cervical cancer. But, new systemic treatment is needed to be considered to reduce distant metastasis. MSRO35-08 Feasibility of Cervical Brachytherapy with a Novel 50 kv Electronic Brachytherapy Source J. Spencer Thompson MD (Presenter): Nothing to Disclose Purpose/Objectives To explore the feasibility of using a 50 kv electronic source for delivery of brachytherapy treatment in cervical cancer. Materials/Methods Two patients have been treated using the electronic source, with instruments provided by the manufacturer (tandem and colpostats). Both patients received 45 Gy to the pelvis at 1.8 Gy per fraction with weekly cisplatinum at 40 mg/m 2. A parametrial boost was then given to 50.4 Gy for the first patient and to 54 Gy for the second. After 36 Gy, both patients were implanted under general anesthesia and dilation of the cervical os to sufficient width in order to permit tandem insertion under ultrasound guidance with a cervical stopper attached to the tandem at the distance from the tip of the tandem to correspond the sounded depth of the uterus. Brachytherapy was performed weekly while external beam treatment was still occurring and then twice weekly to complete treatment within 8 weeks. Colpostat covers were chosen to provide maximum lateral displacement of the vaginal mucosa. CT-based three dimensional planning with non-contrast images was utilized after fixation of the instruments and packing of the vagina to push the bladder and rectum as far away as possible. Dose was prescribed to point A using 5.5 Gy per fraction for one patient and 6 Gy per fraction for the second patient (who had a larger tumor with initial clinical stage IIIB disease). Five fractions were performed for each patient. Results The implantation procedure, treatment planning, treatment delivery and post-anesthesia recovery took over 6 hours in the first insertion attempt, but the total required time had dropped to approximately 3 hours once all staff became familiar with the instruments and software. There were no observed complications from treatment and both patients tolerated anesthesia and brachytherapy well. Mean dose to point A was 5.57 Gy for patient 1 and 5.68 Gy for patient 2. Corresponding doses for points B and H were 1.26 Gy and 1.28 Gy; and 4.59 Gy and 5.68 Gy, respectively. Mean dose to the bladder was 1.37 Gy for patient 1 and 1.61 Gy for patient 2. The dose (D 5 ) received by 5% of bladder volume was 3.64 Gy for patient 1 and 4.49 Gy for patient 2. Mean rectum doses were 1.97 Gy and 1.13 Gy and rectum D 5 was 2.37 Gy and 2.95 Gy for patients 1 and 2, respectively. Conclusions To our knowledge, this represents the first report of electronic-source brachytherapy for cervical cancer and was accomplished with acceptable dosimetry and clinical tolerability. MSRO35-09 Clinical Outcomes of Post-Operative Endometrial Cancer Patients Treated with Vaginal Brachytherapy Alone Katarina Petras (Presenter): Nothing to Disclose Purpose/Objective: To assess the clinical outcomes of post-operative endometrial cancer patients undergoing adjuvant vaginal brachytherapy (VBT). Materials and Methods: The records of all endometrial cancer patients treated with adjuvant VBT alone following total abdominal hysterectomy and bilateral saphingo-oophorectomy (TAH/BSO) at our institution between 2006 and 2010 were retrospectively reviewed. VBT was delivered with vaginal cylinders using high-dose-rate (HDR) iridium-192 radiation. All relevant clinical and brachytherapy plan dosimetric data were collected. For the purpose of this study, patients were restaged according to FIGO 2009 classification. Any short-term or long-term treatment related toxicity, as well as the incidence of local, regional, and distant failure was recorded. Results: A total of forty-five patients were examined. The median age was 67 years (range 37-86). Median follow-up from the date of the last VBT fraction was 39.2 months (range ). All patients but one received 22 Gy in 4 fx prescribed to 0.5 cm depth (one patient received 21 Gy in 3 fx). Thirty-six percent of patients received concurrent chemotherapy (most frequently with carboplatin and taxol). The number of stage IA, IB, II, and IIIA patients were 20, 13, 11, and 1, respectively. Twenty-nine had endometrioid-type adenocarcinoma (64.4%), 12 were papillary serous (26.7%), 3 were clear cell (6.7%), and 1 was a mixed mesenchymal tumor (2.2%). The median cylinder apex point dose, as a percentage of total prescription dose, was 100% (range %). The median treatment length was 3.1 cm (range cm). Treatment was well tolerated as no patients experienced any on-treatment or long-term toxicity (fatigue, GI, GU, or skin) greater than grade 1. Two patients failed locally (1 adenocarcinoma, 1 clear cell), 5 patients failed regionally (1 adenocarcinoma, 4 papillary serous), and the mixed mesenchymal tumor patient failed distally. Median time to recurrence was 12.2 months from the date of the last VBT fraction (range ). One local failure occurred at the vaginal cuff (adenocarcinoma, grade 2, stage IA) while the other occurred in the vagina location NOS (clear cell, grade 3, stage IA). Of the four papillary serous regional recurrences, 2 were stage IA, 1 was stage IB, and 1 was stage II; all 4 patients received concurrent chemotherapy. Conclusion: Satisfactory local control (96%) was achieved in our patient population with minimal toxicity. Since most of our regional failures were of papillary serous histology, consideration should be given to pelvic nodal irradiation in addition to, or in lieu of, VBT in this particular subset of patients.

PORTEC-4. Patient seqnr. Age at inclusion (years) Hospital:

PORTEC-4. Patient seqnr. Age at inclusion (years) Hospital: May 2016 Randomisation Checklist Form 1, page 1 of 2 Patient seqnr. Age at inclusion (years) Hospital: Eligible patients should be registered and randomised via the Internet at : https://prod.tenalea.net/fs4/dm/delogin.aspx?refererpath=dehome.aspx