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Objectives: The first ASTRO guidelines on cervical cancer has recently been published recommending the use of modern radiation therapy. Furthermore, imaging has been incorporated in the new FIGO 2018 cervical cancer staging, which now re-categorizes nodal disease (IIIC). We sought to evaluate the outcomes and patterns of recurrence using FIGO 2018 staging in a cohort of patients treated in an era of high precision image-guided radiotherapy. Methods: A retrospective database review of 196 non-metastatic patients treated at a single institution from 2011 to 2018 was performed. All had pre-treatment MRI and PET scans and were treated with definitive concurrent chemoradiation using both intensity-modulated radiotherapy and 3D-image guided brachytherapy. Previously assigned 2009 FIGO staging and all imaging were reviewed for FIGO 2018 re-classification. Descriptive analyses and Kaplan-Meier survival curves were performed. Log-rank test was used to compare outcome between groups. Results: Five-year locoregional control rate, OS and DFS and were 82%, 79.6% and 70.1% respectively, with a median follow-up time of 51 months. Forty-eight patients experienced a recurrence, 80% of which included distant disease. In-field recurrence rate was 11.7%. Using the new FIGO staging, 48% of patients were upstaged to IIIC. Compared to FIGO 2009, OS and DFS were higher for all early 2018 FIGO stages, while stage III and IVA disease had poorer outcomes. Five-year OS was 91.6%, 72.8% and 61.7% for node-negative disease, IIIC1 and IIIC2 stages, respectively (p Conclusions: Integration of state-of-the-art imaging in cervical cancer staging as well as in radiotherapy and brachytherapy planning leads to excellent oncologic outcomes, however distant recurrence remains an important issue. FIGO 2018 staging better reflects patient prognosis, highlighting the need for new treatment strategies in stage IIIC cervical cancer.

BackgroundHistorically, radical hysterectomy followed by adjuvant radiotherapy has been offered to patients with endometrial cancer who have gross cervical involvement; however, this approach is known to carry considerable morbidity. Neoadjuvant radiotherapy followed by extra-fascial hysterectomy has been proposed as an alternative treatment but has been poorly studied to date.ObjectiveTo evaluate the locoregional control rate associated with neoadjuvant radiotherapy followed by extra-fascial hysterectomy.MethodsA retrospective cohort study of 30 patients with endometrial cancer with gross cervical involvement treated between May 2006 and January 2016 was performed. Eligible patients were those aged >18 years with non-metastatic endometrial adenocarcinoma and gross cervical disease treated with curative intent at the Centre hospitalier de l’Université de Montréal. Treatment protocol consisted of pelvic neoadjuvant radiotherapy and high-dose rate brachytherapy followed by extra-fascial hysterectomy. Kaplan-Meier curves were used for survival analysis.ResultsThe median age was 60 (range 37–82) and median body mass index was 32 kg/m2 (range 16–55). Twenty-four (80%) patients were diagnosed with a positive cervical/endocervical biopsy. Clinical staging confirmed 36.7% (n=11) as stage II, 20% (n=6) stage IIIB, 30% (n=9) stage IIIC1, and 13.3% (n=4) stage IIIC2. Seventy-seven per cent (n=23) of patients had an endometrioid histology. Locally advanced disease was identified by imaging alone in six patients. Rates of parametrial, adnexal, vaginal, and nodal invasion were 10% (n=3), 6.7% (n=2), 13.3% (n=4), and 43.3% (n=13) at diagnosis, respectively. All patients completed pelvic radiotherapy (13.3% extended field) and 90% received brachytherapy. Twenty per cent (n=6) of surgeries were performed using minimal invasive technique. On surgical specimen, 63.3% (n=19) had complete cervical response, 90% (n=27) had negative margins, and 10% (n=3) had residual nodal involvement. Median follow-up time was 62 months (range 1–120). Six recurrences were identified; all except one involved distant failure, and two with locoregional failure. Five-year locoregional control rate, disease-free, overall, and disease-specific survival were 90.5%, 78.5%, 92.6%, and 96.2%, respectively. Two patients (6.7%) had grade 3+ acute radiation-related complications (all grade 3). Grade 3+ post-operative morbidity was noted in 2 (6.7%) patients.ConclusionsNeoadjuvant radiotherapy followed by extra-fascial hysterectomy offers good locoregional control with low treatment-related morbidity in patients with endometrial cancer with overt cervical involvement.

Purpose The aim of this study was to compare early prostate-specific antigen (PSA) decline patterns and PSA nadirs between low-dose-rate seed prostate brachytherapy (LDR-PB) and different fractionations of external beam radiotherapy (EBRT) and their predictive importance for biochemical failure (bF). Methods and Materials Patients with D'Amico low- or intermediate-risk prostate cancer who underwent a single-modality treatment without androgen deprivation were included in this study. Three different treatment groups were compared: (1) normofractionation EBRT up to 70.2–79.2 Gy/1.8–2.0 Gy, (2) LDR-PB, and (3) EBRT with hypofractionation 60 Gy/3 Gy daily or 5–7.25 Gy once a week over 9–5 weeks, to a total dose of 45–36.25 Gy, respectively. The log-rank test, Cox regression analysis, and nonparametric tests were used. Results We analyzed 892 patients: the median followup for patients without bF was 84 months (interquartile range 60–102 months), with 12% of patients experiencing bF. The PSA decline within the first 15 months was generally exponential. LDR-PB showed a faster early exponential decline compared with EBRT treatments, but whether decline was fast or slow had no influence on recurrence. The only factors that were positive predictive factors in univariate and multivariate analyses were the time to nadir >48 months (median), PSA nadir Conclusions Although there are significant differences in early exponential PSA decline between different treatments, only the PSA nadir and longer time to nadir were predictive factors for bF.

INTRODUCTION AND OBJECTIVES:Salvage prostate bed radiotherapy (PBRT) results in about 70% 5 yr freedom from progression (FFP). A three arm randomized trial was designed to determine whether there a...

We tested different classification systems in order to separate intermediate-risk prostate cancers into prognostic groups. We then examined which groups were most suited for either prostate seed brachytherapy (PB) or external beam radiotherapy (EBRT).We selected patients with D'Amico intermediate-risk prostate cancer who were treated exclusively with either PB or EBRT. Patients were excluded if they had received androgen deprivation therapy in combination with EBRT or a follow up of30 months without recurrence. The Kaplan-Meier method was used to compare groups.Our sample consisted of 475 patients treated from July 2002-September 2013. Median follow up for patients without biochemical failure (BF) was 56 months (interquartile range 44-78); 222 patients (47%) were treated with PB exclusively (D90 interquartile range 145-176 Gy) and 253 (53%) with EBRT exclusively (dose interquartile range 76-80 Gy). The rate of BF was significantly lower in patients treated with PB (5.4%) than in patients treated with EBRT (14.2%) (p = 0.036, log-rank test). Upon univariate analysis, significant predictors of BF included the number of unfavorable intermediate-risk factors (0, 1, 2, 3) (p = 0.024) as well as the Cancer of the Prostate Risk Assessment (CAPRA) score (p = 0.002). After adjusting for the type of treatment, only the CAPRA score remained predictive (p = 0.025). For patients with a CAPRA score of 0-2, those with PB fared better than those treated with EBRT (p = 0.042). This difference disappeared in patients with a CAPRA score of 3-5 (p = 0.5).Using our current selection criteria for monotherapy, we found that PB or EBRT as monotherapy are equally effective treatment options for intermediate-risk prostate cancer.

To investigate the impact of 5‑alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer. We included 203 patients on a 5-ARI from our institutional database comprising over 2500 patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a 5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria: (a) progression of Gleason score or increase in cancer volume on biopsy, (b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and (c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. At a median follow-up of 38.2 months (standard deviation 22.2 months), 10 (4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) were significant predictive factors for BF, while Gleason progression (p = 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR, 5.7; 95% confidence interval, CI, 1.1–28.8; p = 0.04) and the number of cancer progression factors (HR 2.9, 95% CI 1.2–7.0, p = 0.02) remained adverse risk factors. PSA progression experienced during 5‑ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

Adenocarcinoma of the cervix constitutes only approximately 20% of all cervical carcinomas; therefore, specific Level 1 evidence to guide patient management is lacking. Most trials have included this histologic subtype but in insufficient numbers to do more than generate hypotheses from subset analyses. As a consequence, our understanding of the natural history and optimal management of adenocarcinoma of the cervix is limited. The optimal management of adenocarcinoma of the cervix continues to be a subject of debate among practitioners as to whether or not it should be different from squamous cell carcinoma and what would constitute this management. The purpose of this review was to give an overview of the current knowledge on adenocarcinoma of the cervix and its differences from squamous cell carcinoma with regard to risk factors, prognosis, survival rates, patterns of recurrence, and response to treatment. This article will focus on possible specific therapeutic directions to explore in the management of locally advanced adenocarcinomas.

Study Objective The aim of this study was to evaluate the use of vaginal misoprostol to decrease both the force required to dilate the cervix and the pain experienced during a hysteroscopy. Design Randomized clinical trial (RCT) (Canadian Task Force classification I). Setting University hospital gynecology clinic. Patients A total of 101 patients needing a diagnostic hysteroscopy. Fifty patients were randomized to the misoprostol group and 51 to the placebo group. Patient characteristics were similar in the 2 groups. Interventions Self-administration of 400 μg of vaginal misoprostol or vaginal placebo 12 to 24 hours before a hysteroscopy. Measurements and Main Results The force needed to dilate the cervix was assessed by a tonometer, and pain was measured by a visual analog scale. The force to dilate the cervix to 6 mm was significantly less in the misoprostol group (5.0 vs 7.5 N, p = .02). Pain-related measurements after dilatation of the cervix to 6 mm were significantly reduced in the misoprostol group (42.1 vs 57.2, p = .004). The main side effect reported with the use of the drug was pelvic cramping. Conclusion The use of 400 μg of vaginal misoprostol 12 to 24 hours before hysteroscopy reduces the pain and the force needed to dilate the cervix, with only mild side effects.

Objective The aim of this study was to assess and compare adjuvant chemotherapy followed by either high–dose-rate vaginal vault brachytherapy (VBT) alone or combined with pelvic external beam radiotherapy (EBRT) for International Federation of Gynaecology and Obstetrics stage 1 serous or clear cell (CC) endometrial cancer. Methods Between 2006 and 2012, 84 women with stage 1 serous or CC endometrial cancer were evaluated postoperatively for adjuvant treatment at our hospital. More than 80% of patients had pelvic lymphadenectomy. Patients declining or not completing adjuvant treatments were excluded. Twenty-five women received 4 to 6 cycles of carboplatin/paclitaxel followed by EBRT and VBT. Thirty-two women received 6 cycles of carboplatin/paclitaxel followed by VBT. Locoregional control and toxicities were assessed during follow-up. Results The 3-year disease-free survival and overall survival rates for the VBT group compared with the EBRT + VBT group were 88% versus 84%, P = 0.6, and 100% versus 94%, P = 0.6, respectively. Only 1 patient in the EBRT + VBT group developed a distant recurrence. One patient had grade 3 toxicity (chronic gastrointestinal [GI] toxicity) in the EBRT + VBT group. Acute grade 1-to-2 GI and grade 1 genitourinary (GU) toxicities were less frequent in the VBT group compared with the EBRT + VBT group (P = 0.008 and P = 0.019, respectively). Late GI and GU toxicities were comparable. Grade 1 vaginal toxicity was similar in both groups. No acute or late grade 2 GU or vaginal toxicities were reported. Conclusions According to this study, VBT alone seems to be as effective as EBRT and VBT for stage 1 serous and CC endometrial cancer treated with surgery and adjuvant chemotherapy. Furthermore, less acute GI and GU toxicities were seen in the VBT group.

Aims To report the long-term toxicities and sexual quality of life of a once-weekly hypofractionated radiation therapy schedule for low-risk prostate cancer. Materials and methods A multi-institutional phase II trial was conducted, using a three-dimensional conformal radiation therapy (3D-CRT) approach for low-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and prostate-specific antigen ≤ 10 ng/ml). Forty-five Gray (Gy) were delivered in nine fractions of 5 Gy given on a weekly basis. Acute and late genitourinary and gastrointestinal toxicities were graded according to the Radiation Therapy Oncology Group toxicity scale. Sexual function and sexual bother were assessed with the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Results Between March 2006 and August 2008, 80 patients were treated, with a median age of 69 years (interquartile range 64–72). The median follow-up was 83 months (interquartile range 73–85 months). At 7 years, overall survival was 88%. No patients died of prostate cancer. Cumulative grade ≥2 genitourinary and gastrointestinal late toxicity was reported for 31.3% and 30% of our patients, respectively. Cumulative grade ≥3 genitourinary and gastrointestinal late toxicity was seen in 3.8% and 12.5% of cases, respectively. Late genitourinary grade 2 toxicity was correlated with the occurrence of acute genitourinary grade 2 toxicity ( P = 0.006). The occurrence of late gastrointestinal toxicity was not correlated with acute gastrointestinal toxicity. Pre-treatment EPIC sexual function was low (37.5%) and the mean EPIC sexual function score at 7 years after treatment was 14%. On the other hand, pre-treatment EPIC sexual bother reached 80.5%, meaning little bother, and remained stable during follow-up. Conclusions Once-weekly 3D-CRT leads to excellent biochemical disease-free survival and acceptable toxicities. Pre-treatment EPIC sexual function dropped by 42% at 5 years of follow-up. This functional deficit did not bother patients, possibly due to the already low sexual function at baseline.

96 Background: To investigate the impact of 5-alpha-reductase inhibitors (5-ARIs) usage on radiotherapy outcomes for localized prostate cancer. Methods: From our institutional database of over 2500 patients, we identified 203 patients on a 5-ARI. They were all treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients receiving a 5-ARI were analyzed according to the following prostate cancer progression criteria: a) progression of Gleason score or increase in cancer volume on the biopsy, b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. Results: At a median follow-up of 36 months (interquartile range [IQR] 22-52 months), 10 (4.9%) patients experienced BF. 52% of men demonstrated none of the progression criteria, 37% showed only one prostate cancer progression criteria and 11% showed two. Using a univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) but not Gleason progression (p = 0.3) were a significant predictive factor of BF. With separate multivariate analysis adjusted for the CAPRA score (HR 1.7, 95% CI 1.2-2.3, p = 0.003), a rising PSA (HR 5.7, 95% CI 1.1-28.8, p = 0.04) and the number of cancer progression factors (HR 2.9, 95%CI 1.2-7.0, p = 0.02) remained adverse risk factors. Both Gleason score progression (p = 0.4) and first biopsy positive for cancer (p = 0.13) failed to remain significant. Age and obesity were not significant factors in univariate or multivariate analysis. Conclusions: A PSA progression experienced while under 5-ARI treatment before EBRT or brachytherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

Background The aim of this study was to assess the management of cervical necrosis (CN) following radiotherapy (RT) and the impact of smoking status. This rare complication mimics a neoplastic recurrence, and causes concern among attending physicians. Methods Between July 2008 and March 2013, 5 women on 285 with localized cervical cancer had a CN following RT. Patients were treated with concomitant chemoradiation. The medical records were reviewed to abstract demographic and clinical information until March 2013. Results 1.75% (95% confidence interval: 0.23 to 3.28%) developed CN. All patients were smokers with a mean of 19.5 pack-years (range: 7.5-45 pack-years). All patients were treated with weekly Cisplatin chemotherapy and external beam radiation to the pelvis, 45 Gy in 25 fractions. Four patients received an extra boost with a median dose of 7.2 Gy (range: 5.4-10 Gy). All patients had intracavitary brachytherapy (range: 27.9 to 30 Gy). Clinical presentation was similar for all the cases: vaginal discharge associated with pain. Mean time for time post-radiation therapy to necrosis was 9.3 months (range: 2.2-20.5 months). Standard workup was done to exclude cancer recurrence: biopsies and radiologic imaging. Conservative treatment was performed with excellent results. Resolution of the necrosis was complete after a few months (range: 1 to 4 months). Median follow-up until March 2013 was 19 months. All the patients were alive with no clinical evidence of disease. Conclusions This study, the largest to date, shows that conservative management of CN after RT is effective, and should be attempted. This complication is more common in smokers, and counseling intervention should result in fewer complications of CN.

The purpose of this work was to assess the stability of fiducial markers in the prostate bed and compared their use to surgical clips.In this study, 3-4 gold fiducial markers were transrectally implanted in the prostate bed of 14 patients. The stability of the fiducial markers position (fiducial markers fixity) over an EBRT course was assessed. Furthermore, the advantages of the fiducial markers compared to the surgical clips were assessed and the interobserver variation between the two technologies was compared.The mean fiducial marker migration during a course of EBRT was small with 1.2 mm (SD ± 0.8 mm). Compared to fiducial markers, the matches with surgical clips were mismatched ≥ 2 mm in 68% of treatments. This discrepancy of 2 mm was on average 3.7 ± 1.3 mm. There was less interobserver variability for matching of fiducial markers (0.8 ± 0.7 mm) than for surgical clips (2.0 ± 1.6 mm).Fiducial markers showed less interobserver variability in matching and less variation in position than surgical clips. Fiducial markers could ultimately help in reducing treatment margins.

Purpose To determine the extent of gold fiducial marker (FM) migration in patients treated for prostate cancer with concurrent androgen deprivation and external-beam radiation therapy (EBRT). Methods and Materials Three or 4 gold FMs were implanted in 37 patients with prostate adenocarcinoma receiving androgen deprivation therapy (ADT) in conjunction with 70-78 Gy. Androgen deprivation therapy was started a median of 3.9 months before EBRT (range, 0.3-12.5 months). To establish the extent of FM migration, the distance between each FM was calculated for 5-8 treatments once per week throughout the EBRT course. For each treatment, the distance between FMs was compared with the distance from the digitally reconstructed radiographs generated from the planning CT. A total of 281 treatments were analyzed. Results The average daily migration was 0.8 ± 0.3 mm, with distances ranging from 0.2 mm-2.6 mm. Two of the 281 assessed treatments (0.7%) showed migrations >2 mm. No correlation between FM migration and patient weight or time delay between ADT and start of EBRT was found. There was no correlation between the extent of FM migration and prostate volume. Conclusion This is the largest report of implanted FM migration in patients receiving concomitant ADT. Only 0.7% of the 281 treatments studied had significant marker migrations (>2 mm) throughout the course of EBRT. Consequently, the use of implanted FMs in these patients enables accurate monitoring of prostate gland position during treatment.

Background Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. Materials and Methods We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Results Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Conclusions Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.