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PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

Purpose: Radical concurrent chemoradiotherapy with combined external beam radiotherapy (EBRT) and brachytherapy is used to treat locally advanced cervical cancer. Our institution has transitioned to high-dose-rate (HDR) intracavitary brachytherapy (ICBT) from low-dose-rate (LDR) brachytherapy in 2008, and a review was conducted on the effect of this change on patient outcomes. Methods and Materials: A single-arm retrospective chart review was performed on locally advanced (Fédération Internationale de Gynécologie et d’Obstétrique stage IB-IVA) patients with cervical cancer treated with combined external beam radiation therapy and HDR-ICBT with curative intent between 2008 and 2014. Clinical outcomes were evaluated, and multivariate analysis was performed to identify prognostic factors. Results: Of the 76 patients selected, median age was 47.9 years and median follow-up was 5.2 years. Thirteen patients (17.1%) developed locoregional recurrence and 23 patients (30.3%) patients developed distant recurrence. Five-year progression-free survival and overall survival were 63.7% and 69.3%, respectively. A significant survival difference was found between stages (P < .001). Multivariate analysis found nodal involvement was strongly associated with poorer survival (P = .007). Conclusions: Our experience with the transition to HDR-ICBT as part of concurrent chemoradiotherapy in treatment of locally advanced cervical cancer resulted in acceptable long-term outcomes and toxicity to that of LDR brachytherapy. Potential further improvement of treatment outcomes for patients may be possible with image guided brachytherapy and the addition of effective systemic therapy.

ObjectiveLymphovascular space invasion (LVSI) has been defined as a significant adverse prognostic factor in early-stage endometrial cancer, primarily because of its high association with nodal metastases. This study aimed to determine if LVSI provides any prognostic significance in pathologic node-negative surgically staged (T1N0) endometrial cancer patients.Methods/MaterialsThis retrospective cohort study included all patients with pathologic stage T1N0 endometrial carcinoma treated at The Ottawa Hospital Cancer Centre from 1998 to 2007. Patient demographics, pathologic findings, treatment, and outcome data were collected. Univariate and multivariate cox regression modeling was used to assess significance and adjust for demographic and histopathologic covariates. Kaplan-Meier curves were used to estimate the 5-year overall and recurrence-free survival.ResultsOur study included 400 pathologic stage T1N0 patients who received an initial total hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. The median age at diagnosis was 62 years, and the median follow-up was 66 months. Fifty-four patients (13.5%) had a positive LVSI status, and 346 (86.5%) had a negative LVSI status. The 5-year overall survival was 97.3% in patients without LVSI and 90.9% in those with LVSI (P < 0.001). The 5-year recurrence-free survival was 95.2% in patients without LVSI and 85.9% in those with LVSI (P = 0.006). Univariate analysis identified grade, stage, and LVSI as the covariates significantly associated with time to recurrence, and identified age, grade, stage, and LVSI to be significantly associated with overall survival. There were no significant covariates for recurrence-free survival by multivariate analysis, and only age and LVSI were significant for overall survival.ConclusionsLymphovascular space invasion is an overall poor prognostic factor in T1N0 endometrial cancer. After adjusting for other factors, LVSI remains an independent risk factor for worse overall survival. Therefore, estimation of overall survival in patients with early-stage, node-negative endometrial cancer should take into account LVSI status.

AimTo determine the outcome of patients with locally advanced cervix cancer treated with curative intent using external beam radiotherapy (EBRT), without brachytherapy.Materials and methodsA chart review was performed of all patients with cervix cancer who received EBRT alone at our centre from 2000 to 2010. Overall survival and local control were evaluated using Kaplan–Meier survival curves.ResultsIn total, 22 patients were identified. The median age and follow-up were 56 years and 65 months, respectively. The stage included IB to IVB. Main histology was squamous cell carcinoma (82%). Median tumour size was 5·5 cm. Majority treated with 3D conformal techniques and nine patients (41%) were treated with intensity-modulated radiation therapy (IMRT); 14 patients received doses of ≥65 Gy. Most patients (73%) received weekly concurrent cis-platinum. The major reason for not receiving brachytherapy was locally extensive tumour (59%). The 5-year relapse-free survival and overall survival rates were 57 and 50%, respectively. Seven patients (32%) had a component of loco-regional failure, mainly within the cervix. There was a better outcome among the nine patients treated with IMRT to a median dose of 66 Gy with a loco-regional control of 78%.ConclusionsPatients who cannot have brachytherapy may still achieve acceptable rates of loco-regional disease control if high radiation doses (>65 Gy) was delivered.

315 Background: Dose-escalated prostate radiotherapy (PRT) with androgen deprivation therapy (ADT) is a standard curative treatment for localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. We report the patient-reported health related quality of life (HR-QoL) outcomes from a phase III study exploring optimal sequencing of PRT with ADT in LPCa. Methods: Newly diagnosed LPCa patients with Gleason score ≤7, clinical stage T1b-T3a, and PSA < 30 ng/mL were randomized to receive PRT (76 Gy/38 fractions) with 6 months (mos) of ADT starting 4 mos prior to RT (NAHT arm) or concurrently with RT (CAHT arm). HR-QoL was assessed using EORTC QLQ-C30 and PR25 at baseline, q2 mos while on ADT, q4 mos for year 1 and 2 after ADT, q6 mos from year 3 to 5 and annually thereafter. Linear mixed modelling was applied to compare change in score (relative to baseline) over time. Wilcoxon rank-sum test was used to identify between-group difference in absolute scores, at 18, 36 and 60 mos. The statistical and clinical significance was set at p≤0.01 and 10-point threshold, respectively. Results: Overall 432 men were enrolled in the study and 393 (194 in NAHT and 199 in CAHT arm) were eligible for HR-QoL evaluation. There was a significant difference in the change in score of sleep disturbance due to urinary bother (least-squared mean: 3.9 vs. 7.6, P = 0.001) between the two arms. Although there were statistically significant differences in absolute scores of global QoL (18, 60 mos), cognitive (18, 60 mos), social and emotional functions (60 mo), sexual intimacy (18 mo) and fatigue (60 mo) favoring NAHT, the only clinically meaningful difference was noted in ejaculatory dysfunction at 18 (mean: 52.5 vs. 64.6), 36 (60.2 vs. 49.2) & 60 mos (61.4 vs. 50.9), respectively. Conclusions: We did not find any notable difference between the two arms with respect to score change over time in any of the HR-QoL metrics except sleep disturbance due to urinary bother. Clinically meaningful difference was noted only in the late absolute ejaculatory dysfunction score which favored the NAHT arm. Based on these findings, both NAHT and CAHT with PRT are reasonable standards of care for LPCa. Clinical trial information: DC-990-0082.

Purpose The in vivo dosimetry tool, RADPOS, has been modified to include a metal oxide–silicon semiconductor field effect transistor (MOSFET) array with an electromagnetic positioning sensor. This allows dose monitoring at five points rather than just at single dose point as in the other versions of the device. The detector has been used in a clinical trial, which is the first to measure both urethral dose and internal motion concurrently during permanent seed implantation for prostate brachytherapy using a single probe. Methods and Materials The RADPOS detector was secured inside a Foley catheter inside the patient's urethra. Spatial coordinates of the RADPOS detector were read every 0.5 s, and the timing of events such as needle insertion was noted. The MOSFET readings were taken over two 10-min periods; once all seeds had been implanted both before and after the transrectal ultrasound (TRUS), the probe was removed. Measurements were completed for 16 patients. Results Maximum integral dose in the prostatic urethral ranged from 89 to 195 Gy, and dose varied from −66% to 36% depending on the rectal probe position. The change in position of the RADPOS sensor owing to the removal of the TRUS probe ranged from 1.4 to 9.7 mm. Conclusions The modified RADPOS detector with MOSFET array is able to provide real-time dose information, which can be used to monitor dose rates while implantation is performed and to estimate the total integrated dose. Changes in position including those owing to the TRUS probe can be significant and should be quantified to evaluate the influence on dose distributions.

Purpose Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). Methods and Materials All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables, with the predictors of surgical treatment and adjuvant RT type. Results A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. Conclusion No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.

Purpose: To evaluate the feasibility of concurrent weekly Cis-platinum chemoradiation (CRT) in the curative treatment of primary vaginal cancer. Methods: A retrospective review was performed of all primary vaginal cancer patients treated with curative intent at the Ottawa Hospital Regional Cancer Centre between 1999 and 2004 using concurrent Cis-platinum CRT. Results: Twelve patients were treated with concurrent weekly CRT. The median age at diagnosis was 56 years (range, 34-69 years), and the median follow-up was 50 months (range, 11-75 months). Ten patients (83%) were diagnosed with squamous cell carcinoma and 2 patients (17%) with adenocarcinoma. The distribution according to stage was as follows: 6 (50%) Stage II, 4 (33%) Stage III, and 2 (17%) Stage IVA. All patients received pelvic external beam radiotherapy (EBRT) concurrently with weekly intravenous Cis-platinum chemotherapy (40 mg/m{sup 2}) followed by brachytherapy (BT). The median dose of EBRT was 4500 cGy given in 25 fractions over 5 weeks. Ten patients received interstitial BT, and 2 patients received intracavitary BT, with the median dose being 3000 cGy. The 5-year overall survival, progression-free survival, and locoregional progression-free survival rates were 66%, 75%, and 92%, respectively. Late toxicity requiring surgery occurred in 2 patients (17%). Conclusions: For the treatmentmore » of primary vaginal cancer, it is feasible to deliver concurrent weekly Cis-platinum chemotherapy with high-dose radiation, leading to excellent local control and an acceptable toxicity profile.« less

Background The role of radiotherapy for recurrent or residual granulosa cell tumor of the ovary (GCTO) is controversial. One reason for this controversy may be that most published studies on this topic have not utilized sectional imaging to assess response to radiotherapy. We report on three cases of recurrent or residual GCTO that were treated with radiotherapy for which pre- and post-treatment CT scans were available to assess response. Case reports Case #1: A 77-year-old woman with a 7×10-cm pelvic mass post-surgery was treated with radiotherapy to a dose of 45 Gy in 25 fractions followed by a boost of 10 Gy in 5 fractions. Post-treatment scans revealed a decrease in tumor size to 4×2.5 cm. The reduction in tumor volume was 86%, and the duration of response was 13 months. Case #2: A 73-year-old woman with multiple abdominal recurrences was treated with radiotherapy to a dose of 30 Gy in 20 fractions. The dominant mass shrank from 13×17 cm to 5.1×6.6 cm. The reduction in volume was 85%, and the duration of response has been 5 months. Her symptom of abdominal bloating and early satiety abated. Case #3: An 83-year-old woman with a 20×20×15-cm mass in the left abdomen was treated with radiotherapy to a dose of 45 Gy in 25 fractions. The mass decreased in size to 3.7×2.5 cm post-treatment. The duration of response has been 21 months. Her symptom of left leg swelling disappeared after therapy. Conclusion Radiotherapy is highly effective in treating recurrent or residual GCTO. In these three cases, the tumor volume decreased by 85 to 90%, and the duration of response has, up to now, been 5 to 21 months.

Purpose To assess the effect of treatment waiting time on clinical outcome for patients with cervix cancers treated with radical radiotherapy. Methods and materials A retrospective analysis was conducted on all cervix cancer patients treated with radical radiotherapy between 1990 and 2001 at the Ottawa Regional Cancer Centre. Analyses were performed according to the three following separate definitions of waiting times: interval from start of radiotherapy to ( 1 ) date of initial biopsy, ( 2 ) date of examination under anesthesia, and ( 3 ) date of radiation oncology consultation. Associations between waiting times and patient characteristics and disease control were investigated using t -tests, analyses of variance, and Cox regression analyses. Results A total of 195 patients were studied. The vast majority of patients were treated within 5, 6, and 8 weeks of their consultation (91%), examination under anesthesia (88%), and biopsy (81%), respectively. On average, delays between initial biopsy and treatment start were greater for older patients ( p = 0.025) (5.8 weeks for 70 years old) and those with smaller tumors ( p 4 cm vs. 6.3 weeks for ≤4 cm). Univariate analysis revealed no adverse effect of treatment delay on tumor control. Multivariate analysis, with the inclusion of multiple prognostic tumor and treatment parameters, revealed an adverse effect of treatment delay on survival outcomes. Conclusions Longer radiotherapy waiting times were found to be associated with diminished survival outcomes for patients treated radically for cervix cancer. The significance of this observed association requires further investigation.

Objectives. A reference range of prostate-specific antigen (PSA) values compatible with cure following radiotherapy (RT) for prostate cancer (PCa) has yet to be established. Various thresholds, as low as 0.5 ng/mL, have been used to define biochemical disease-free status. We report PSA profiles in 118 patients who were systematically biopsied following standard RT, with a minimum 4-year follow-up. Methods. One hundred eighteen patients were treated with standard external beam RT from May 1987 to October 1991, and were followed prospectively with transrectal ultrasound (TRUS)-guided biopsies and measurement of serum PSA levels. Stage distribution was as follows: T1b: 25 patients, T2a: 27 patients, T2b/c: 42 patients, T3: 23 patients, T4: 1 patient. Median follow-up for patients without clinical failure is 68 months (range 48 to 108). Treatment failures were categorized as biochemical (biochemical failure [chemF]: PSA level of 2.0 ng/mL or more and greater than 1 ng/mL over nadir), local (local failure [LF]: positive biopsy and PSA level greater than 2.0), and distant failure (DF). Results. PCa recurred in 55% of patients: 38% LF (n = 45; 30 isolated and 15 with DF), 25% DF (n = 30; 15 isolated and 15 with LF), and 4% chemF (n = 5). Mean PSA nadir was 0.4 for patients with no evidence of disease (NED) and occurred at 33 months, 3.2 for LF at 17 months, 7.7 for DF at 12 months, and 1.4 for chemF at 24 months. After reaching the nadir, PSA in patients with recurrence followed first-order kinetics, rising exponentially over time. The mean PSA doubling time was 12.6 months for LF, 5.2 months for DF, and 21.8 months for chemF (P = 0.004). At last follow-up, the median PSA for patients without evidence of disease is 0.5 ng/mL. Four such patients had PSA values that rose to between 1 and 2 ng/mL for 5 to 38 months, but these eventually fell again to less than 1 ng/mL. Three patients had PSA values between 2 and 3 ng/mL, but 2 now have decreasing levels and the third has a rising level. All patients whose PSA levels rose to greater than 3 ng/mL exhibited a persistently rising pattern and ultimate tumor recurrence. Conclusions. There is a range of PSA values following RT for PCa that is compatible with cure. A definition of biochemical disease-free status at any absolute threshold of PSA level less than 3 ng/mL will overdiagnose failure in a significant proportion of patients. Patients with a PSA level between 1.5 and 3 ng/mL should be observed until there is unequivocal evidence of disease recurrence. In the absence of known biopsy status, PSA doubling time can be a useful indicator of whether failure is local or distant.

Purpose To determine if there is an association between the degree of prostate trauma during prostate brachytherapy and development of acute urinary toxicity. Methods and materials In a consecutive prospective cohort of permanent 125 I prostate brachytherapy patients, the number of times each needle was repositioned was tracked, and the dosimetry plans were used to determine the number of times needles within 1 cm of the urethra were manipulated. Additionally, prostate volume, total number of needles, number of needles/prostate volume, and the number of periurethral needle manipulations/prostate volume were determined. The need for catheterization beyond 24 hours and the Radiation Therapy Oncology Group (RTOG) urinary toxicity score at 4 weeks were recorded. The independent samples t test was used to search for a correlation between these parameters and the recorded toxicity scores. Results Twenty-eight consecutive implant patients were evaluated in the study. Median (range) values were as follows: prostate volume 35 cc ( range, 15–51 cc), number of needles per patient 32 (range, 21–41), number of needle manipulations per patient 94.5 ( range, 55–147), and number of periurethral needle manipulations 42 (range, 17–65). The only significant association between urinary toxicity and these variables was for the number of periurethral needle manipulations ( p = 0.025). Conclusions These data provide evidence that needle prostate trauma during brachytherapy contributes to acute urinary toxicity.

Purpose:Radiotherapy with concurrent cisplatinum-based chemotherapy became a standard recommendation for the management of advanced cervical cancer in 1999. We reviewed our experience with this approach to determine the impact on patient outcomes.Methods:A retrospective review of all cervical cancer patients treated with curative intent using radical radiotherapy ± chemotherapy from 1992 to 2005 was performed. Survival and relapse rates were analyzed using the Kaplan-Meier method and were compared using the log-rank test.Results:During this period, 224 treated patients were identified: 153 (68%) were treated between 1992 and 1999 (group 1) and 71 (32%) were treated after 1999 (group 2). The median age was 53 and 55 years with a median follow-up of 49 and 34 months for groups 1 and 2, respectively. Stage classification and histological diagnosis were similar for both groups. Treatment usually consisted of external beam pelvic radiotherapy (40-45 Gy in 20-25 fractions) followed by low-dose rate brachytherapy (35-40 Gy to point A). Chemotherapy consisted of weekly intravenous cisplatinum (40 mg/m2) given concurrently with pelvic radiation. The proportion of patients receiving chemotherapy increased significantly after 1999, 12% in group 1 compared with 79% in group 2 (P < 0.01). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 53% and 54% for group 1 and 64% and 67% for group 2. The improvement in PFS for group 2 approached statistical significance (P = 0.06), but the difference in OS did not.Conclusions:There has been a significant increase in the use of concurrent chemoradiation for cervical cancer treatment after 1999, and this seems to have led to higher rates of PFS and OS, although these have yet to achieve statistical significance.

Purpose To investigate the feasibility of using new micro-MOSFET detectors for QA and in vivo dosimetry of the urethra during transperineal interstitial permanent prostate implants (TIPPB). Methods and materials This study involves measurements for several patients who have undergone the implant procedure with iodine-125 seeds. A new micro-MOSFET detector is used as a tool for in vivo measurement of the initial dose rate within the urethra. MOSFETs are calibrated using a single special order calibration seed. The angular response is investigated in a 100 kVp X-ray beam. Results micro-MOSFETs are found to have a calibration factor of 0.03 cGy/mV for low energy X-rays and a high isotropic response (within 2.5%). Prostate volume and shape changes during TIPPB due to edema caused by the trauma of needle insertion, making it difficult to achieve the planned implant geometry and hence the desired dose distribution. MOSFET measurements help us to evaluate the overall quality of the implant, by analyzing the maximum dose received by urethra, the prostate base coverage, the length of the prostatic urethra that is irradiated, and the apex coverage. Conclusions We demonstrate that ease of use, quick calibration and the instantaneous reading of accumulated dose make micro-MOSFETs feasible for in vivo dosimetry during TIPPB.

Objective. To evaluate the efficacy of radiotherapy (RT) for symptomatic recurrent or residual ovarian cancer. Methods. A review was conducted on patients (pts) treated with palliative RT for symptomatic ovarian cancer at The Ottawa Hospital Regional Cancer Centre between 1990 and 2003. Patient demographics, tumor factors, treatment variables, and clinical outcome were entered into a database. Symptom response was defined as complete (CR), partial (PR), or none. Results. 62 courses of RT were delivered to 53 pts. The symptoms treated were: bleeding (40%), pain (37%), and ‘others' (23%). The most common dose fractionation scheme was 30 Gy in 10 fractions (f) (range: 5 Gy/1 f to 52.5 Gy/20 f). The overall response rate was 100%, with 68% achieving a CR. The CR rates were 88, 65, and 36% for the symptoms of bleeding, pain, and ‘others', respectively ( P = 0.003). The median duration of response was 4.8 months (range: 1–71 months). In multivariate analysis, the only factors that were found to be significant positive predictors of symptom control were: the symptom bleeding ( P = 0.015) and stage III/IV disease at presentation ( P = 0.01). The most commonly reported toxicities were grades 1 and 2 nausea/vomiting and diarrhea. There were no grade 3/4 toxicities reported. Conclusions. Radiotherapy is highly effective in palliating symptomatic ovarian cancer. Excellent results are achieved for patients presenting with bleeding or pain. Symptomatic patients should be strongly considered for palliative radiotherapy. Higher doses of radiotherapy should be considered for those with symptoms other than bleeding or pain and those with longer life expectancies.

Disease control rates and toxicity were evaluated among 28 primary vaginal cancer patients treated with curative intent using radiotherapy. At 5 years, the majority (60%) of patients were disease-free and local control was 73% when a combination of external beam radiotherapy and brachytherapy were used. Serious late toxicity was seen in 11% of patients.