Objectives Primary vaginal carcinomas are rare, accounting for 1–2% of gynaecological malignancies. This project aimed to describe a series of primary vaginal cancer cases at a single institution, identifying patient, tumour and treatment factors impacting outcomes. Methods A retrospective chart analysis was performed for all patients diagnosed with primary vaginal cancer from 2008 to 2018 at a single institution in Australia. For each case, data extracted included histopathology, staging, treatment received, socio-demographic information and patient outcomes. Overall, eight patients were eligible to be included in analysis. Results Average age at diagnosis was 59 years (34–75 years). 87.5% were in the most socially disadvantaged quintile of the Index of Socio-Economic Disadvantage. Overall, 75% of patients had squamous cell carcinoma and 25% had melanoma. Stage at presentation: FIGO stage one (n=3), stage two (n=2) and stage three (n=3). The average Body Mass Index was 26.2 kg/m2 and Charlson Comorbidity Score of 4.75. Treatment received included: surgery alone (n=2), primary chemo-radiotherapy (n=3), surgery and adjuvant radiation (n=1), surgery and adjuvant immunotherapy (n=1), and chemotherapy alone (n=1). With median 39 months follow-up (11–113 months), 2 of 6 patients with SCC have relapsed and 2 of 2 patients with melanoma have relapsed. Conclusions This study indicates that outcomes for vaginal cancers are poor, and that early presentation is essential to improve outcomes. Treatment is highly individualised based on extent of disease at presentation. Due to limited literature in this area, it is difficult to compare patient demographics, tumour factors and standard treatment.

Purpose or ObjectiveThe use of magnetic resonance imaging (MRI) is becoming more prevalent in cervical cancer external beam radiotherapy (RT).To our knowledge, no planning study has been conducted to evaluate the dosimetric implications of imaging modality for cervical cancer RT.

IntroductionThe purpose of this survey was to explore the current patterns of practice for brachytherapy in cervix cancer in Australia and New Zealand. The survey was also intended to explore clinician attitudes towards image-guided adaptive brachytherapy (IGABT) and identify barriers to the implementation of IGABT. MethodsElectronic surveys were sent to all radiotherapy centres in Australia and New Zealand under collaboration with Australia New Zealand Gynaecology and Oncology Group (ANZGOG), in order to identify patterns of radiotherapy practice. The survey was sent out in December 2013, with a reminder in February 2014. ResultsOf the 75 radiotherapy centres in Australia and New Zealand, 23 centres replied (31% response rate). Twenty-two responding departments treat cervix cancer with external beam radiation (EBRT) (22/23; 96%). Fourteen responses were from departments that also use intracavitary brachytherapy (14/22; 64%). The remaining eight departments who do not offer intracavitary brachytherapy referred their patients on to other centres for brachytherapy. Ultrasound was used by 86% for applicator guidance. CT and MRI were used by 79%, and 50% respectively for planning. Optimisation was based on organs at risk (93%) and target volumes (64%). ConclusionsBrachytherapy remains an integral component of definitive treatment for cervix cancer in Australia and New Zealand. There was increased use of soft tissue imaging modalities with emphasis on verification; high rates of volumetric planning, and adherence to a defined overall treatment period. Brachytherapy was not substituted with other EBRT modalities. Despite this, there remain barriers to implementation of image-guided brachytherapy.

Purpose:Breast cancers predominantly arise from Glandular Breast Tissue (GBT). If the GBT can be treated effectively post‐operatively utilising radiotherapy this may be adequate volumetric coverage for adjuvant breast radiotherapy. Adequate imaging of the GBT is necessary and will be assessed between MRI and CT modalities. GBT visualisation is acknowledged to be qualitatively superior on Magnetic Resonance Image (MRI) compared to Computed Tomography (CT), the current radiotherapy imaging standard, however this has not been quantitatively assessed. For radiotherapy purposes it is important that any treatment volume can be consistently defined between observers. This study investigates the consistency of CT and MRI GBT contours for potential radiotherapy planning.Methods:Ten experts (9 breast radiation oncologists and 1 radiologist) contoured the extent of the visible GBT for 33 patients on MRI and CT (both without contrast), which was performed according to a contouring guideline in supine and prone patient positions. The GBT volume was not a conventional whole breast radiotherapy planning volume, but rather the extent of GBT that was indicated from the CT or MR imaging. Volumes were compared utilizing the dice similarity coefficient (DSC), kappa statistic, and Hausdorff Distances (HDs) to ascertain the modality that was most consistently volumed.Results:The inter‐observer concordance was of substantial agreement (kappa above 0.6) for the CT supine, CT prone, MRI supine and MRI prone datasets. The MRI GBT volumes were larger than the CT GBT volumes (p<0.001). Inter‐observer conformity was higher for CT than MRI, although the magnitude of this difference was small (VOI<0.04). Conformity between modalities (CT and MRI) was in agreement for both prone and supine, DSC=0.75. Prone GBT volumes were larger than supine for both MRI and CT.Conclusion:MRI improves the extent of GBT delineation. The role of MRI guided, GBT‐targeted radiotherapy requires investigation in a clinical trial.This work was supported by a grant number APP1033237 from Cancer Australia and the National Breast Cancer Foundation.

Purpose The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma. Methods and Materials An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours. Results Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer. Conclusions These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.

Purpose: To present the techniques and early clinical outcomes for MRI-based adaptive HDRB using 3T-image guidance and the EMBRACE protocol. Material and methods: From July 2010 to end-Dec 2014, 34 consecutive women (median age 51 yrs, range 31-77 yrs.) with carcinoma of the uterine cervix (FIGO Stage IA2-IVB, 76% SCC) were treated definitively with pelvis only (8/33, 24%) or extended field IMRT (26/33, 76%), and synchronous weekly cis-platinum chemotherapy. This was followed by 2 HDR brachytherapy (HDRB) insertions separated by 1 week. For each HDRB insertion, a utero-vaginal Vienna ring and tandem applicator set was inserted under general anaesthesia. The HDRB component delivered 4 fractions of 7 Gy to the high-risk CTV (HR_CTV). The weekly fraction pairs (i.e. Fx1 + 2 and Fx3 + 4) occurred on consecutive days, and required overnight in-patient admissions and multiple bed-couch transfers. In order to maintain the intra-insertional fidelity of the HDRB dosimetric process, we devised a novel applicator-patient immobilization system. Adaptive (4-D) contouring and planning were performed for each fraction utilizing images acquired on a networked 3T MR unit for each HDRB fraction. Using the BPS (Oncentra v.4.3, Nucletron Corporation), measurements were made of the distances between the sacral promontory and both the tandem tip (“Tandem Shift”) and the ring channel (“Ring Shift”) for each fraction pair to assess the magnitude of intra-insertional movement (drift) of the implant in 3-D. Changes in the anterior-posterior angulation of the implant described by the vectors denoting tandem and ring shift (“Angle Shift”) induced by multiple patient transfers and internal organ filling were also assessed. Finally, intra-insertional rotation shift (roll) of the implant within the fraction pairs was measured via the BPS extra-co-ordinate system (“ECS Shift”) in the patient’s y-plane as per ICRU 42 formalism. EMBRACE defined DVH objectives for CTV coverage and OAR restraints were recorded and correlated with local control and toxicity. Results: Median follow-up was 40 months (1-54 month). Detailed geometric outcomes (outlined below) and dosimetric data will be presented for 131 HDRB fractions and 333 patient couch-bed transfers. Insertion 1: Cut points for distance shift ± 4mm, or ECSS ± 4-degrees, (1) TS: No significant inter-fractional differences were detected for either HR-CTV or OAR dosing. (2) RS: No significant inter-fractional differences were detected for either HR-CTV or OAR dosing. (3) ECSS: No significant inter-fractional differences were detected for HR-CTV coverage but significant variation in both Rectal D1cc. and Rectal D0.1cc was noted due to subtle inter-fractional rectal filling differences. Insertion 2: Cut points for distance shift ± 3mm, or angle shift ± 5-degrees, (1) TS: No significant inter-fractional differences were detected for HR-CTV coverage but significant variation in Bladder D1cc due to minor filling variation. (2) AS: No significant inter-fractional differences were detected for HR-CTV coverage but significant variation in Rectal D1cc and Bladder D0.1cc due to minor inter-fractional filling variations. EMBRACE defined dosimetric objectives were easy to achieve and HR_CTV and IR_CTV were predictive for local cancer control. Conclusions: Pelvic and applicator immobilization during HDRB for cervical cancer can be achieved with excellent intra-insertional and paired inter-fractional geometric stability despite multiple patient transfers and external transport to the brachytherapy unit. OAR D1.0 and D0.1cc mean exposures were shown to be potentially sensitive to applicator re-construction in women with significant geometric uncertainties related to ECSS (Insertion 1), and for both TS and AS (Insertion 2). Minor over-night variations in organ filling were implicated. Overall local control was > 90% with minimal though important late radiation complications. Implementation of an afterloaded low-dose-rate brachytherapy technique for prostatic rhabdomyosarcoma Gemma Busuttil1, Joseph Bucci2, Emily Flower1, Komiti Enari2, Edgar Estoesta1, Andrew Howie2, Hang Nguyen1, Alicja Wach1, Dean Cutajar3, Linda Martin1, Verity Ahern1 1The Crown Princess Mary Cancer Centre, Westmead, 2St George Cancer Care Centre, 3The Centre for Medical Radiation Physics, University of Wollongong and St George Cancer Care Centre,

Purpose: The purpose of this study was to assess variability in contouring the gross tumor volume (GTV) and clinical target volume (CTV) of 3 clinical cervix cancer cases by a cohort of international experts in the field in preparation for the development of an online teaching atlas.Methods and materials: Twelve international experts participated. Three clinical scenarios: node positivity (PLN), retroverted uterus (RV), and parametrial invasion (PI) were used. Sagittal and axial magnetic resonance images of the clinical cases were downloaded to participants' treatment planning systems for contouring. The GTV/cervix/uterus/parametria/vagina and nodal CTV were contoured. Contour consensus was assessed for sensitivity/specificity using an expectation maximization algorithm called Simultaneous Truth and Performance Level Estimation and experts' overall agreement was summarized by kappa statistics.Results: Agreement for GTV in the 3 clinical cases was high (Simultaneous Truth and Performance Level Estimation sensitivity, 0.54-0.92; specificity, 0.97-0.98; and kappa measure for PLN, RV, and PI was 0.86, 0.76, and 0.42; P < .0001). Moderate to substantial agreement was seen for nodal CTV (kappa statistics for PLN, RV, and PI was 0.65, 0.58, and 0.62; P < .0001), uterus (kappa for PLN, RV, and PI was 0.45, 0.74, and 0.77; P < .0001), and parametria (kappa for PLN, RV, and PI was 0.49, 0.62, and 0.50; P < .0001). Contouring heterogeneity was greatest for the cervix (kappa measure for PLN, RV, and PI was 0.15, 0.4, and 0.24; P < .0001) and vagina (kappa for PLN, RV, and PI was 0.47, 0.36 and 0.46; P < .0001), reflecting difficulties in determining the interface between GTV and these tissues.Conclusion: Kappa statistics of the different CTV components generally demonstrated moderate to substantial agreement among international experts in the field of gynecological radiation therapy. Further planning target volume margins accounting for organ motion and setup errors are a necessary addition to the CTV. (C) 2015 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.

Aims: Increasingly complex imaging techniques, such as computed tomography, magnetic resonance imaging and positron emission tomography/computed tomography scans are being used by radiation oncologists to improve the accuracy of their radiotherapy planning contours, despite limited formal training in diagnostic imaging. This study aimed to assess whether the availability of an 'in-house' radiologist would be beneficial in enhancing the interpretation of oncological imaging and accuracy of contouring.Materials and methods: A radiology/oncology fellow was based in the oncology department, providing radiological advice on diagnostic and planning images, for two sessions per week over a 9 month period. Oncology staff were able to book a time slot with the radiologist on a MOSAIQ cancer database and record the reason for the consultation and its outcome. The radiologist also reviewed the accuracy of the patient's contours for the weekly quality assurance audit meetings.Results: The radiologist reviewed 56 scans during the 49 consultation sessions. Advice over diagnostic images and target volume delineation were the main reasons for the consultations, which resulted in a change of practice in 45% of cases, ranging from changing target volumes (25%) to carrying out further imaging (20%). For the quality assurance audit meetings, the radiologist's review of 99 patients' planning contours resulted in a significant change in management in 6% of cases.Conclusions: This is the first study to attempt to formally quantify the clinical benefit of having a dedicated 'in-house' radiologist within a radiation oncology department, clearly showing the valuable impact of such a role. Crown Copyright (C) 2014 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.

Purpose: To evaluate the efficacy of on-line MR guided radiotherapy for cervix cancer patients. MR guidance was simulated in order to optimize the fractional dose to the on-line targets. Methods: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. In the previous retrospective adaptive planning study using 3 mm PTV margin, 5 over 33 patient cases were identified and enrolled in this study in which the coverage of GTV/CTVs was not acceptable with single IMRT adaptation with bone matching. MR guidance was simulated in order to maximize online high risk CTV (HRCTV) volume to be within 95% of the prescription dose (95p). Fractional dose after the image guidance was calculated, and was deformed back to the reference (planning) image for dose accumulation. Accumulated dose of the proposed technique was compared with that of current standard image guidance technique, bone matching in terms of the target coverage (cervix, GTV, HRCTV, lower uterus, parametria, and upper vagina) and OAR sparing (bladder, bowl, rectum, and sigmoid). Target coverage was considered acceptable if 95p dose or more was delivered to 98% of the target volume. OAR sparing was evaluated with accumulated V45 and D2cc. Results: On line MR based soft tissue guidance proposed in this study achieved the acceptance of target coverage to 97% from 53% (bone matching). Dose delivery to HRCTV and lower uterus was significantly improved (p<0.001, paired t-test). The mean D2cc and V45 were reduced in bladder, rectum and sigmoid compared to bone matching. Conclusions: The retrospective study revealed that the on-line MR based soft-tissue image guidance is very effective for cervix cancer treatment. The technique significantly and successfully improved target coverage for the most difficult patient group identified from the previous study. Statistically significant improvement in OAR sparing was also noted. Anna Lundin and Henrik Rehbinder are both employees and shareholders of RaySearch Laboratories AB. All other authors have no conflicts to report.

The study aimed to evaluate how effectively the 'Consensus guidelines for the delineation of clinical target volume (CTV) for intensity modulated pelvic radiation therapy (IMRT) for the definitive treatment of cervical cancer' could be applied in clinical practice, without specific training. The CTV for four cervical cancer patients undergoing radiation therapy, were independently contoured by two radiation oncologists and two radiologists. The consensus guidelines, patient's clinical summaries and MRI reports were used as a guide to aid the observers in contouring the GTV (gross tumor volume), parametrium, uterus and vagina on planning MRI images. Subsequently the observers agreed upon consensus contours, creating a gold standard CTV for each patient. The mean absolute surface distance (MASD), the Dice similarity co-efficient (DSC) and tissue volume were calculated and used to compare each observers' contour with the consensus gold standard by evaluating the distance between the contoured surfaces and the difference in over/ underlap of the contoured volumes. The inter-observer variation and the consistency between radiologists' and radiation oncologists' contours were also compared. Although a wide ranging result for the gross tumor volume was demonstrated (MASD 2.0 to 9.2mm, mean DSC = 0.39 to 0.66) for all observers when compared to the consensus, all the contours were still within the recommended planning target volume (PTV) margin of 20mm. There was much less inter-observer variation between the contours for the vagina, parametrium and uterus. For the inter-group variation, the radiation oncologists had a significantly less inter-group variation for DSC (p < 0.01) and MASD (p < 0.05), compared with the radiologists. Their contours also varied significantly less from the gold standard consensus contours, for all of the metrics DSC, MASD and Volume (p < 0.01 for all). Whilst all contoured GTVs were within the associated PTV, large variations in contours were seen between observers. Steep learning curves affecting the radiation oncologists with interpretation of MRI images and for the radiologists in the use of contouring software, should be considered in future studies and additional specific training may be necessary in the application of the of consensus guidelines.

The adoption of IMRT to treat gynecologic malignancies has been limited by the potential for target underdosing caused by anatomic motion and tumor regression. This research evaluated the effectiveness of dosimetrically evaluating treatment progress and replanning based on errors in target dosimetry. Thirty-three patients with Stage IB–IVA cervix cancer underwent baseline CT/MRI and weekly MRI scans during standard radiotherapy treatment. Target volumes (GTV and CTV) and organs-at-risk (rectum, sigmoid, bladder, and bowel) were contoured on the fused MR-CT baseline images and on the subsequent weekly scans. The CTV was defined to be the union of the GTV, cervix, parametria, 2 cm of vagina inferior to the GTV, and 2 cm of uterus superior to the GTV. The contours were converted to surface meshes and an in-house deformable registration algorithm (MORFEUS) was used to derive an anatomic deformation model. This model mapped patient anatomy at each fraction to the baseline anatomy allowing the dosimetric impact of interfraction motion to be assessed through specialized software (ORBIT Workstation, Research Laboratories). A 3 mm PTV margin IMRT plan was created from DVH optimization criteria to prescribe a dose to 98% volume (D98) of 50 Gy, 49 Gy, and 47.5 Gy to the GTV, CTV, and PTV, respectively. The accumulated dose (dose delivered to the patient accounting for target and organ motion) was compared to the planned dose after each weekly MRI scan. If the accumulated D98 to the GTV or CTV fell below 49 Gy or 47.5 Gy, respectively, an automated replan was performed by applying the baseline optimization criteria to the updated patient geometry. Of the 33 patients, 17 (52%) triggered at least one replan and the number of patients requiring 1, 2, and 3 replan(s) were 11, 4, and 2, respectively. All patients met the desired GTV D98 of 49 Gy and CTV D98 of 47.5 Gy at treatment completion, while 8 patients would have failed at least one criterion if replanning was not performed. The OAR dose sparing was maintained as measured by the volume of each OAR receiving 45 Gy or more, with the exception of the sigmoid. The average volume of this organ receiving 45 Gy was 57.8% under the replanning approach and 54.0% without replanning (p = 0.036). The average baseline CTV volume for patients who did not trigger any replans was larger than that of patients who triggered at least one replan (284 cc and 196 cc; p = 0.029). Adaptive replanning is a feasible strategy to ensure target coverage for small margin IMRT treatments in the presence of organ motion and tumor regression. Automated replanning based on errors in target dosimetry during treatment is a practical approach that minimizes both the number of replans and the workload to implement a replan.

Purpose: Palliative Radiotherapy (PRT) plays an important role in the relief of neurologic symptoms in patients with brain metastases; however, little is known about the use of PRT on a population level. The purpose of this study was to describe temporal trends in the use of PRT for brain metastases in Ontario. Methods: The Ontario Cancer Registry was used to gather information on all cancer deaths in Ontario between the years 1984-2004. The proportion of these cases receiving at least one course of PRT for bone metastases within the last two years of life was described over time and by disease site. Results: There were 435,055 cancer deaths in Ontario during the study period. Of these cases, 4.0% received at least one course of PRT for brain mets within the last two years of life. The rate of PRT varied significantly by primary site (e.g. lung8.7%, breast-6.4%, kidney-5.0%, prostate-0.6%) (p<0.001). Over time, the proportion of cases receiving PRT for brain mets increased from 2.1% to 5.0% (p<0.001). This increasing trend remained significant after taking into account primary site, age, sex, and time from diagnosis till death (p<0.001). The rate over time also varied by primary site (e.g. lung5.3% to 11.2%, breast3.7% to 8.8%, kidney2.2% to 6.0%, prostate0 to 0.9%) (p<0.001). Conclusion: The rate of PRT for brain metastases in Ontario has significantly increased over time. Explanations for these trends will be discussed.

Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group.Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines fir IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants.Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate.Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting. (C) 2011 Elsevier Inc.

Inter-fractional organ motion adversely affects the coverage of the clinical target volume (CTV) for cervix cancer patients. Planning target volumes (PTV) using a convex hull (CH) around combined CTV volumes have shown excellent target coverage for patients whose bladder filling is variable over the course of radiation treatment, at the expense of high dose to the rectum. A modified CH (mCH) technique is proposed in this study to reduce rectal dose without compromising target coverage. Nine cervix cancer patients with large changes in bladder filling during treatment were selected from a larger planning study. MRI scans were acquired for planning and weekly during treatment. Images were fused to a planning CT scan using bony alignment and CTV and organs at risk (OAR) contoured. The two image-sets with largest and smallest bladder were identified. The union of the CTVs from these image sets was constructed and a CH applied to the resulting volume. The CH was then modified by subtracting the rectal volume and adding a 3mm margin posteriorly (mCH PTV). IMRT plans were generated to cover 98% mCH PTV with 49 Gy. Contours were converted to 3D surface meshes for deformation analysis. Accumulated dose on the deformed organs were simulated using dose accumulation software (ORBIT Workstation, RaySearch Laboratories). The average volume of mCH PTV was only 14% larger than a conventional 5mm PTV margin. The delivered dose using mCH showed excellent CTV coverage (D98% of 49.3 Gy on average) except for one patient (D98% of 47.3 Gy) whose rectum was full at the time of planning. Dose reduction to the rectum (average dose and V45 Gy) was statistically significant (t<0.1) when compared to the unmodified CH PTV plans. A non-uniform margin around combined CTV volumes using the mCH PTV technique was shown to successfully characterize patient-specific CTV motion and deformation for most patients. IMRT plans using mCH PTV demonstrate good target coverage and rectal saving for cervix cancer patients with variable bladder filling.