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Purpose Moderate hypofractionated radiation therapy (HypoRT) is an attractive alternative to conventionally fractionated radiation therapy for prostate cancer. However, most studies using HypoRT only included the prostate as the target volume. We report long-term outcomes of patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and HypoRT to the prostate and nodal areas with a simultaneous integrated boost technique. Methods and Materials Patients with localized, high-risk prostate cancer entered a prospective phase I/II study with a HypoRT regimen of 60 Gy/20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated radiation therapy with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT. Toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events v3. Outcomes rates were calculated by the actuarial method of Kaplan–Meier from the date of last radiation treatment until date of event. Results We report on the first 105 patients treated between October 2010 and February 2014. Median follow-up was 74 months, with 97% of patients followed for more than 36 months. Median ADT duration was 18 months. The worst grade 2 or higher late gastrointestinal or genitourinary toxicity was seen in 7% and 9%, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rates of grade ≥2 gastrointestinal or genitourinary toxicity were 2% and 3%, respectively, with no residual grade ≥3 toxicity. The 5- and 7-year actuarial overall survival and relapse free survival were 91% and 85% and 87% and 81%, respectively. Conclusions The longest follow-up report of moderate HypoRT (plus ADT) to the prostate and pelvic nodes shows that this approach is feasible, well tolerated, and effective. It is convenient for patients and the health system. A larger randomized trial using this approach is warranted.

300 Background: To determine the rate and time of testosterone (T) recovery to normal level in patients (pts) with prostate cancer treated with radiotherapy plus 6, 18 or 36 months of androgen deprivation therapy (ADT) and considered cured from their disease. Methods: We randomized 1230 pts with prostate cancer, into two phase III trials: 600 with intermediate risk and 630 with high-risk. We selected those considered cured to avoid subsequent T variations due to reintroduction of ADT for recurrence. We excluded the following pts: no ADT at all (126) or not receiving exactly 6, 18 or 36 months of ADT (69), survival less than one year (21), no T measured at baseline or during follow-up (75), biochemical failure (195) or evidence of metastatic/recurrent disease (137).T recovery rate was compared between baseline normal/abnormal T (values below biochemical normal range) and by ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed by including normal/abnormal T at baseline, age, Zubrod, comorbidities and ADT duration. A second model was performed by replacing ADT duration with baseline PSA, Gleason score and stage. The median time to T recovery was calculated only on pts who recovered normal T. Results: Results are reported with a median follow-up of 14 years. 607 pts fit the criteria and are available for analysis: 309 pts in the 6 months ADT schedule, 185 in the 18 and 113 in the 36. Overall, 76.7%, 54.6% and 45.1% pts recovered normal T on the 6, 18 or 36 months schedule, respectively (p

Purpose Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer. Methods The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from an 169 Yb source. Conventional HDR BT (10 Ci 192 Ir) and IMBT (18 Ci 169 Yb) plans were generated for 12 patients using an in-house column generation-based optimizer, coupled to a Geant4-based dose calculation engine, RapidBrachyMC. Treatment plans were normalized to match the same PTV D90 coverage as the clinical plan. Intershield attenuation effects were taken into account. A sensitivity analysis was performed to evaluate the dosimetric impact of systematic longitudinal source positioning errors ( ± 1 mm, ± 2 mm, and ± 3 mm) and rotational errors ( ± 5 ∘ , ± 10 ∘ , and ± 15 ∘ ) on clinically relevant parameters (PTV D90 and urethra D10 ). Results The platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV D90 coverage, the urethral D10 was reduced by 13.3% ± 4.7%, without change to other plan quality indices (PTV V100 , V150, V200 , bladder V75 , rectum V75 , HI, COIN). Delivery times for HDR BT and IMBT were 9.2 ± 1.6 min and 18.6 ± 4.0 min, respectively. In general, the PTV D90 was more sensitive to source positioning errors than rotational errors, while the urethral D10 was more sensitive to rotational errors than source positioning errors. For a typical range of positioning errors ( ± 1 mm, ± 5 ∘ ), the overall tolerance was Conclusions The AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.

Purpose This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss. Methods and materials The study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV1.5 cm). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT. Results For the purpose of this study, we considered an arbitrary 5 cm3 of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively. Conclusions The anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder.

Background Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with localized high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. Objective The aim of this superiority randomized trial was to compare outcomes of RT combined with either 36 or 18 mo of ADT. Design, setting and participants From October 2000 to January 2008, 630 patients with HRPC were randomized, 310 to pelvic and prostate RT combined with 36 mo (long arm) and 320 to the same RT with 18 mo (short arm) of ADT. Outcome measurements and statistical analysis Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results and limitations With a median follow-up of 9.4 yr, 290 patients had died (147 long arm vs 143 short arm). The 5-yr OS rates (95% confidence interval) were 91% for long arm (88–95%) and 86% for short arm (83–90%), p=0.07. QoL analysis showed a significant difference (p Conclusions In localized HRPC, our results support that 36 mo is not superior to 18 mo of ADT. ADT combined with RT can potentially be reduced to 18 mo in selected men without compromising survival or QoL. Thus, 18 mo of ADT appears to represent a valid option in HRPC. Patient summary In this study, we report outcomes from high-risk prostate cancer patients treated with radiotherapy and either 36 or 18 mo of androgen deprivation therapy. There was no difference in survival between the two groups, with the 18-mo group experiencing a better quality of life.

L’implantation du programme de formation Éthique et culture religieuse (Ministère de l’Éducation, du Loisir et du Sport, 2008) entraine un « changement profond » au regard de notre système d’enseignement (Conseil supérieur de l’éducation, 2008). Les perceptions des agents d’implantation par rapport à une innovation éducative peuvent affecter non seulement sa mise en oeuvre, mais ses résultats (Fullan, 2007). Afin de mieux comprendre les perceptions des enseignants du primaire face au programme d’ÉCR, une entrevue exploratoire semi-dirigée a permis d’explorer les perceptions des répondants par rapport au programme et à sa mise en oeuvre. Les résultats obtenus des thèmes émergents sont plutôt négatifs, et ce, peu importe le niveau d’expertise des enseignants par rapport à l’utilisation du programme., The implementation of the Ethics and Religious Culture program (Ministère de l’Éducation, du Loisir et du Sport, 2008) [ERC] leads to a “profound change” with regard to our educational system (Conseil supérieur de l’éducation, 2008). The perceptions of the implementation agents with regard to an educational innovation can affect not only its implementation process, but also its results (Fullan, 2007). In order to better understand primary school teachers’ perceptions of the ERC program, a semi-structured exploratory interview enabled an exploration of the interviewees’ perceptions with regard to the program and to its implementation. The results obtained from the emerging themes are somewhat negative, no matter what the teachers’ level of expertise with regard to using the program.

Purpose To report acute and late toxicity rates in patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and moderate hypofractionated radiation therapy (HypoRT) to the prostate and nodal areas. Methods and materials Patients with localized, high-risk prostate cancer were treated with a HypoRT regimen of 60 Gy in 20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated RT with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT and was given to all patients. Acute and late toxicity were prospectively assessed and graded according to the Common Terminology Criteria for Adverse Events, version 3. Results A total of 105 patients treated between September 2010 and November 2013 were reviewed. Median follow-up was 41 months, with 97% of patients followed for more than 26 months. Median ADT duration was 18 months. Acute grade 2 or higher gastrointestinal (GI) or genitourinary (GU) toxicity was seen in 18 (17%) and 19 (17%) patients, respectively, with only 1 and 3 patients experiencing either a GI or GU acute grade 3 toxicity. The worst grade 2 or higher late GI and GU toxicity were seen in 7 (7%) and 8 (8%) patients, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rate of grade 2 GI and GU toxicity was 5% and 3%, respectively, with no residual grade ≥3 toxicity. The 48-month actuarial progression free survival is 82%. Conclusions ADT with moderate HypoRT delivered with IMRT and an integrated simultaneous boost to the prostate (60 Gy) and pelvic nodes (44 Gy) in 20 fractions is feasible and well tolerated. This approach shortens treatment duration and is convenient for patients and the health system, and its results support a randomized trial.

Purpose Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. Methods and Materials Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). Results Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%–2% for prostate and 4%–7% for oral tongue). Dose differences were not clinically relevant ( Conclusions Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.

Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer.The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from anThe platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV DThe AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.

Purpose A preliminary report of patient reported outcomes (PROs) between men receiving high-dose radiation therapy (RT) on RTOG 0126, a phase III dose-escalation trial treated with either 3-dimensional conformal RT (3D-CRT) or intensity modulated RT (IMRT).

Purpose To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer. Patients and Methods One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up. Results There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen–based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively. Conclusion Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

Background Standard treatment for unresectable stage III non–small-cell lung cancer (NSCLC) is concurrent chemo-radiation (CRT). A regimen of induction carboplatin and gemcitabine followed by CRT was developed at the McGill University Health Centre to prevent delays in treatment initiation. We report the long-term outcomes with this regimen based on a pooled analysis of both protocol patients from a phase II study and nonprotocol patients. Methods and Materials Outcomes and toxicity data were retrieved for 142 patients with stage III NSCLC: 43 patients treated on protocol between January 2003 and November 2004, and 101 patients treated off-protocol between December 2004 and August 2013. Patients received 2 cycles of carboplatin with an area under the curve of 5 intravenously (IV) on day 1 and gemcitabine 1000 mg/m 2 IV on days 1 and 8 every 3 weeks, followed on day 50 by CRT, 60 Gy/30 over 6 weeks, concomitantly with 2 cycles of paclitaxel 50 mg/m 2 IV and gemcitabine 100 mg/m 2 IV on days 1 and 8 every 3 weeks. Results The median overall survival was 23.2 months. With a median follow-up of 23.8 months, the 3-, 4-, and 5-year overall survival was 38%, 30%, and 26%, respectively. The median and 5-year progression-free survival rates were 12.5 months and 25%, respectively. Rates of grade ≥ 3 hematologic, esophageal, and respiratory toxicity were 20%, 10%, and 10%, respectively. Forty-eight patients received further lines of chemotherapy. Conclusion The present analysis affirms the favorable toxicity profile of this novel induction chemotherapy, without apparent compromise in clinical outcomes, when compared with regimens using immediate concurrent CRT.

Objectives Aborted cystectomy due to unresectable disease is not uncommon in patients with bladder cancer. Our aim was to review the outcome of these patients and evaluate various prognostic variables. Materials and methods Thirty-one bladder cancer patients who underwent aborted radical cystectomy due to unresectable disease from 1993 to 2007, and form the basis of this report. Survival was estimated by the Kaplan and Meier method, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied. Results Mean age of patients was 66 years with median follow-up of patients alive 10 months. The 2- and 5-year overall survival (OS) was 41% and 0%, respectively. Twenty patients had a pelvic lymph node dissection (PLND) and 11 patients did not. Twenty-three patients received postoperative therapy, of whom 8 received chemotherapy with the intent of surgical consolidation (only 2 were rendered resectable thereafter), and 15 received combined chemoradiation. OS was not significantly associated with hydronephrosis, concomitant CIS, performance status, history of superficial tumors, postoperative therapy, and salvage cystectomy. Patients with pN2-3 had similar overall survival compared with those with pT4b (13 vs. 17 months, P = 0.59). However, patients who underwent PLND trended towards improved OS compared with those who did not (24 vs. 10 months, P = 0.09). Conclusions Outcome of patients with unresectable disease is dismal. Patients who had an aborted cystectomy due to unresectable disease may benefit from PLND. Further refinements of clinical staging to better identify these patients preoperatively and offer them upfront chemotherapy are needed.

Purpose Since the recognition that prostate cancer probably has a low α/β ratio, hypofractionated radiotherapy has become an attractive treatment option for localized prostate cancer. However, there is little experience with the use of hypofractionation delivering a high biologically equivalent dose. We report our experience with high-dose hypofractionated radiotherapy. Material and Methods A total of 129 patients with favorable risk prostate cancer were treated with three-dimensional conformal radiotherapy treatment plans to the dose of 66 Gy in 22 fractions, prescribed at the isocenter. Planning target volume consisted of the prostate plus a uniform 7-mm margin, including the rectal margin. No patient received hormonal therapy. Toxicity was prospectively graded by the Common Toxicity Criteria version3. Biochemical relapse was defined as postradiotherapy nadir prostate-specific antigen + 2 ng/mL. Results With a median follow-up of 51 months, the 5-year actuarial biochemical control rate is 98%. The only 3 cases with biochemical failure did not have a clinical local relapse. More than 50% of patients did not develop acute toxicity. For late toxicity, the worst crude rate of Grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicity seen at any time during follow-up were 32% and 25%, respectively. There was no Grade 4 or 5 toxicity. At the last follow-up, persistent Grade ≥2 late GU and GI toxicity were 2% and 1.5%, respectively. Conclusions This hypofractionated regimen provides excellent biochemical control in favorable risk prostate cancer with an acceptable rate of late toxicity. Further studies exploring this hypofractionation regimen are warranted.

Purpose: To evaluate dose-volume histograms (DVHs) of bladder and rectum from the use of cone beam CT (CBCT)-based three-dimensional (3D) treatment planning in intracavitary high-dose-rate brachytherapy (HDRB) for cervical cancer patients and to compare these parameters with International Commission on Radiation Units and Measurements (ICRU) of rectal and bladder reference point dose measurements. Methods and Materials: Thirteen patients with cervical cancer underwent HDRB insertions. CT-compatible tandem and ovoid applicators were used to obtain intraoperative CBCT images. The use of a rectal tube and injection of bladder contrast before scanning facilitated contouring the rectum and bladder. All patients underwent intraoperative orthogonal x-ray filming, and treatments were prescribed using standard two-dimensional planning and dosimetry. DVHs for the bladder and rectum were constructed for each treatment. The minimum dose in the most irradiated 2.0-cm 3 volume of bladder (B D2v ) and rectum (R D2V ) were determined from DVHs and compared to ICRU reference point estimates of bladder (B ICRU ) and rectum (R ICRU ) doses. Results: Twenty-six CBCT-based plans were evaluated. The median B ICRU dose (347 cGy; range, 164-601 cGy) was significantly lower (p < 0.001) than the median B D2v (594 cGy; range, 260-969 cGy). The median R ICRU dose (405 cGy; range, 189-700 cGy) was also significantly lower (p = 0.037) than the median R D2V (488 cGy; range, 227-786 cGy). Conclusions: CBCT-based 3D planning can be used in HDRB for cervical cancer and is a convenient alternative to CT-based planning, with the advantage of minimizing applicator motion. Correlation with late effects will further define the role of CBCT-based 3D dosimetry in HDRB planning.

Importance Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences. Objective To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer. Design, Setting, and Participants The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008. Men with stage cT1b to T2b, Gleason score 2 to 6, and prostate-specific antigen (PSA) level of 10 or greater and less than 20 or Gleason score of 7 and PSA less than 15 received 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions. Main Outcomes and Measures Time to OS measured from randomization to death due to any cause. American Society for Therapeutic Radiology and Oncology (ASTRO)/Phoenix definitions were used for biochemical failure. Acute (≤90 days of treatment start) and late radiation therapy toxic effects (>90 days) were graded using the National Cancer Institute Common Toxicity Criteria, version 2.0, and the RTOG/European Organisation for the Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme, respectively. Results With a median follow-up of 8.4 (range, 0.02-13.0) years in 1499 patients (median [range] age, 71 [33-87] years; 70% had PSA P = .98). The 8-year cumulative rates of distant metastases were 4% for the 79.2-Gy arm and 6% for the 70.2-Gy arm (HR, 0.65; 95% CI, 0.42-1.01; P = .05). The ASTRO and Phoenix biochemical failure rates at 5 and 8 years were 31% and 20% with 79.2 Gy and 47% and 35% with 70.2 Gy, respectively (both P P = .006 [HR, 1.39; 95% CI, 1.10-1.77] and P = .003 [HR, 1.59; 95% CI, 1.17-2.16], respectively). Conclusions and Relevance Despite improvements in biochemical failure and distant metastases, dose escalation did not improve OS. High doses caused more late toxic effects but lower rates of salvage therapy. Trial Registration clinicaltrials.gov Identifier:NCT00033631

High-dose-rate brachytherapy is an important component of the curative treatment for cervical cancer. Some institutions use standardized template planning (STP), based on a precalculated table of dose rates, instead of computerized treatment planning (CTP), based on digitized orthogonal X-ray films. STP can be used as a backup check in case of computer hardware malfunction, and/or as a way to minimize treatment planning time. We performed a dosimetric comparison of STP and CTP to determine dose differences at point A and the International Commission on Radiation Units and Measurements Report 38 bladder and rectal reference points.We retrospectively reviewed the treatment plans of 62 patients (135 applications) treated with a tandem and two ovoids using the CTP method. For each of these plans, we calculated the dwell times required to deliver the same prescription dose had STP been used. We also used the planning computer to vary tandem and ovoid geometry and develop a table of dose rates based on geometric parameters.The mean dose at point A was 7.6 Gy using CTP, increasing to 8.4 Gy when the STP approach was used (p0.05). The mean doses at the International Commission on Radiation Units and Measurements Report 38 bladder and rectal points were both 4.5 Gy with CTP and increased to 4.9 and 5.0 Gy, respectively using STP (p0.05). Our table of dose rates showed significant dose rate dependency on the applicators geometry.Our study shows that if the STP approach had been used, a significantly higher dose would have been delivered, and that STP tables accounting for differences in implant geometry should be carefully considered.

Introduction The optimal combination of concomitant radiotherapy (RT) and chemotherapy in stage III unresectable non-small cell lung cancer (NSCLC) remains unclear. The role of induction chemotherapy with carboplatin/gemcitabine regimen has not been established in stage III NSCLC. Methods Forty-two stage III NSCLC patients, 41 assessable, with a median age of 60 years and good performance status, entered this trial between January 2003 and November 2004. They received carboplatin area under the curve 5 on day 1 and gemcitabine 1000 mg/m2 on days 1 + 8 every 3 weeks for two cycles, followed on day 50 by RT 60 Gy, concomitantly with paclitaxel 50 mg/m2 and gemcitabine 100 mg/m2 on days 1 + 8 every 3 weeks for two cycles. Results After induction, the partial response (PR) was 73.1% and stable disease was 24.4%. Disease progressed in one patient. After RT and paclitaxel/gemcitabine, 22% achieved a complete response and 73% a PR, and 5% had disease progression. The median survival was 25 months, the 1-year survival rate was 73.2%, and the 2-year survival rate was 50.5%. During concomitant RT and chemotherapy, grade 3 neutropenia, thrombocytopenia, and anemia occurred in eight, three, and three patients, respectively, and grade 4 neutropenia and thrombocytopenia in one patient each. One patient developed an esophageal fistula and died shortly after, which was considered a grade 5 toxicity; one patient developed grade 4 interstitial pneumonitis, and three patients developed grade 3 esophagitis. Conclusion This regimen appears to be effective and was well tolerated. Further studies using this approach are warranted in patients with stage III NSCLC.

The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT).Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set.Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set.Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.

Purpose To evaluate the displacement of the pelvic lymph node (PLN) target when using cone beam computed tomography (CBCT) for localization of the prostate in patients treated with simultaneous integrated boost. Methods and materials High-risk prostate cancer patients treated with image guided intensity modulated radiation therapy with simultaneous integrated boost receiving 60 Gy in 20 fractions to the prostate and proximal seminal vesicles (PTV60) and 44 Gy in the same 20 fractions to the PLN (PTV44) were studied. Two hundred weekly CBCTs of 50 patients were retrospectively reviewed to assess the displacement of the iliac vessels compared with the simulation computed tomography. For each CBCT, possible displacements were analyzed at 3 levels of PTV44: a superior, middle, and inferior slice, making a total of 600 slices reviewed. Geographical miss (GM) was defined when any part of the iliac vessels on the CBCT was outside of the PTV44 contour. Results GM was found in 7 of the 600 CBCT slices, all in different patients. All GMs were of ≤5 mm. Four GMs occurred on the middle slice and 3 on the superior slice. In 3 cases, the GM was related to shifts ≥7 mm applied to the prostate. Conclusions Our review suggests that for high-risk prostate cancer, the chance of not appropriately covering the PLN target after adjusting the prostate is low. GM was uncommon and in the order of only a few millimeters when it occurred.

We explore techniques for the evaluation and visualization of radiogenomic data-driven models in an effort to investigate the integration of genetic variations (single nucleotide polymorphisms [SNPs] and copy number variations [CNVs]) with dosimetric and clinical variables in modeling radiation-induced rectal bleeding (RB).

Objective: To evaluate a possible deleterious effect of waiting time to radiotherapy on the biochemical relapse (BR) of patients with localized prostate cancer. Patients and Methods: Patients included in this retrospective study had localized prostate adenocarcinoma treated with external-beam irradiation alone. Waiting time was defined as the interval between the first consultation and the first radiation treatment. BR was defined as 3 consecutive rises of prostatic specific antigen (PSA). Patients were split into 3 groups of waiting time: group A were treated within 40 days; group B waited 41 to 80 days; group C waited >80 days to receive radiotherapy. The effect of waiting on BR was estimated by the Kaplan-Meier method. Multivariate Cox proportional hazards modeling was adjusted for known prognostic factors. Results: There were 289 patients who participated in the analysis. Median follow-up time was 6.1 year. Overall BR rate was 44% at 5 years. The median waiting time increased over the study period from 26 days in 1992 to 123 days in 2000. In adjusted multivariate analysis there was a nonsignificant higher risk of BR with waiting for 41 to 80 days (hazard ratio [HR] = 0.8; 95% confidence interval [Cl] = 0.3-1.6) and for >80 days (HR = 0.6; 95% CI = 0.2-1.5) when compared with patients treated within 40 days after consultation. Conclusion: Delaying the start of radiotherapy showed little effect on the rate of BR in the group of 288 prostate cancer patients analyzed in this study.

Hypoxia, an important mechanism of radioresistance, is a strong stimulus for erythropoietin (EPO) production. The stimulatory effects of EPO are mediated through the activation of its receptors, EPO receptors (EPORs). The objective of this study is to determine whether EPORs are expressed in biopsy specimens of patients with squamous cell carcinoma of the cervix. Eighteen biopsy specimens were studied after obtaining Institutional Review Board-approved consent. Standard immunohistochemistry techniques were utilized. Expression of EPORs was present in 16 out of 18 (88.9%) specimens. The intensity (qualitative) and the frequency (semiquantitative) of EPORs expression showed a statistically significant correlation (P= 0.00379). Statistical analysis was performed to determine whether EPORs expression is related to other parameters such as age, FIGO stage, histologic grade, and hemoglobin levels. Only age showed a statistically significant correlation with EPORs frequency of expression (P= 0.00878). Currently, work is in progress in our laboratory to study the radiobiologic effects of EPO on the radiation response of cultured cancer cell lines in vitro.

OBJETIVO: Relatar os resultados de tratamento de pacientes com câncer de pulmão de pequenas células com doença limitada (CPPC-DL), num período de dez anos, numa única instituição, para controle de qualidade e comparação com dados de literatura. MATERIAIS E MÉTODOS: Entre janeiro de 1992 e dezembro de 2002, 101 pacientes portadores de CPPC-DL completaram tratamento em nossa instituição. Seus resultados foram revistos e incluíram quimioterapia, radioterapia, a seqüência dos dois tratamentos e o uso de irradiação profilática cerebral (PCI). A radiação foi administrada com dose mediana de 45 Gy em 1,8 a 2 Gy por fração. A dose mediana de PCI foi de 25 Gy em dez frações. RESULTADOS: O seguimento mediano foi de 50,6 meses e a idade mediana dos pacientes foi de 63 anos. Houve 85 mortes confirmadas, 5 pacientes foram perdidos de seguimento e 11 estavam vivos. O tempo de sobrevida mediano foi de 11 meses, a sobrevida global em dois e cinco anos foi de 25,5% e 10%, respectivamente. Não houve diferença significante na sobrevida global em dois ou cinco anos segundo a idade e sexo dos pacientes. Também não houve diferença significante na sobrevida global entre os pacientes que realizaram PCI ou não, ou foram tratados em dois períodos diferentes (1997-2002 vs. 1992-1996). CONCLUSÃO: Os resultados de tratamento dos pacientes portadores de CPPC-DL na nossa instituição refletem as constantes mudanças no manuseio do CPPC. Nossa sobrevida global em dois anos de 25,5% é semelhante a outros resultados uni-institucionais publicados, mas menor que os resultados de 47% a 54% recentemente publicados por grupos cooperativos.OBJECTIVE: To report the results of the treatment of patients with small-cell lung cancer with limited disease (SCLC-LD) in a single institution during a 10-year period, for quality assurance and comparison with data from the literature. MATERIALS AND METHODS: Between January 1992 and December 2002, 101 patients with SCLC-LD completed treatment at our institution. The outcomes were reviewed and included chemotherapy, radiotherapy, the sequence of the two treatments, and the use of prophylactic cranial irradiation. Radiation was delivered with a median dose of 45 Gy in 1.8 to 2 Gy per fraction. The median dose of the prophylactic cranial irradiation was 25 Gy in 10 fractions. RESULTS: Average follow-up was of 50.6 months and the average age of the patients was 63 years. There were 85 confirmed deaths, 5 patients were lost to follow up and 11 patients were alive. The median survival time was 11 months, the overall survival at 2 and 5 years was 25.5% and 10% respectively. There were no significant difference in overall survival at 2 or 5 years according to the age and sex of the patients. In addition, there were no statistical difference in overall survival among patients who had prophylactic cranial irradiation or not, or who were treated in two different periods (1997-2002 vs. 1992-1996). CONCLUSION: The results of the treatment of SCLC-LD patients in our institution reflect the constant changes in the management of SCLC. The 2-year's 25.5% overall survival seen in our institution is similar to reports published from other single institution, but lower than the 47% to 54% recently published results from cooperative groups.

Objectives The treatment of patients with asymptomatic prostate cancer with biochemical failure (BF) remains controversial. The early introduction of hormonal therapy causes important secondary effects and increases costs. Our general policy has been to follow-up patients with low prostate-specific antigen (PSA) levels and a long PSA doubling time without therapy. We report our experience using such an approach. Methods Between 1992 and 2000, 676 patients with localized prostate cancer were treated with radical radiotherapy, with or without adjuvant hormonal therapy at our institution. Asymptomatic patients with BF, no clinical evidence of metastatic disease, a low PSA level, and long PSA doubling time were considered for follow-up without immediate hormonal therapy. The prognostic factors such as stage and Gleason score were not considered when electing follow-up without additional therapy. The follow-up included at least two annual visits with physical examination and PSA determination. Results With a median follow-up of 85 months, 285 patients (42%) had BF. In 178 of these men, the rising PSA level was the only abnormality. Of these, 113 were followed up without additional therapy and 65 received hormonal therapy. Of the 113 patients in the untreated group, 101 (89%) were alive and asymptomatic at the last follow-up visit and 12 (11%) had died of causes other than prostate cancer. The long-term outcomes were similar in both groups. Conclusions Expectant management, without initial hormonal therapy, may be a reasonable option for selected patients with prostate cancer who present with BF without metastatic disease after radical external beam radiotherapy. This decision is important because the early introduction of hormonal therapy is associated with side effects and is expensive.

Objectives. To evaluate the long-term treatment outcome of patients with carcinoma of the cervix treated with high dose rate brachytherapy (HDRB) using a small number of fractions. Methods. Between 1984 and 1997, 282 patients with cervix cancer (stages IB to IVA) were treated with external beam radiotherapy to the whole pelvis (median dose of 45 Gy) and HDRB (median dose of 24 Gy at point A in 3 insertions given weekly). Endpoints assessed were survival, patterns of failure and complications. Multivariate analysis was performed to identify variables predictive for overall survival and local control. Variables investigated were stage, age, overall duration of treatment, HDRB scheduling and total dose to point A. Results. At a median follow-up of 86.3 months for patients at risk, the 5-, 10- and 15-year overall survival rates are 57%, 52% and 47%, respectively. On multivariate analysis, only stage and age correlated with improved survival. Treatment duration beyond 47 days was associated with poorer overall survival, although it did not reach statistical significance ( P = 0.10). Brachytherapy scheduling and BED to point A had no impact on overall survival. Stage and age significantly correlated with pelvic disease control. Duration of therapy, scheduling of the brachytherapy and BED at point A were not individual predictors for overall local control. Overall, gastrointestinal and genitourinary actuarial complication rates were 15% and 8%, respectively. Conclusions. In our experience, HDRB using 3 insertions is well tolerated and the results are comparable to HDRB using larger number of fractions and to low dose rate brachytherapy.

Purpose Adjuvant postoperative para-aortic lymph nodal irradiation is an acceptable alternative to para-aortic and ipsilateral pelvic irradiation postorchiectomy for patients with Stage I seminoma of the testis. In this article, we report the long-term results of our prospective evaluation of para-aortic irradiation only for such patients. Methods and materials Between March 1991 and September 2000, 71 patients with Stage I seminoma were treated with adjuvant irradiation to the para-aortic region only after radical inguinal orchiectomy. Radiotherapy was delivered using parallel-opposed fields extending from T11 to L5. A total dose of 25 Gy in 15 fractions was prescribed to midpoint. Follow-up was performed every 3 months for the first year, every 4 months for the second and third years, every 6 months for the fourth and fifth years, and annually thereafter. Chest X-ray, tumor markers, and computed tomography scan of the pelvis were performed routinely as part of the follow-up investigation. Results At a median follow-up of 75 months, 68 of 71 patients are alive and free of relapse. Only 1 patient (1.4%) experienced failure in the ipsilateral inguinal nodal region. Two patients (2.8%) died of unrelated causes. The actuarial 10-year relapse free survival is 98.5% and the actuarial 10-year overall survival is 92%. No late toxicity has been encountered. Conclusion Patients with Stage I seminoma of the testis may be safely treated with para-aortic radiotherapy only. Risk of pelvic failure is very low and treatment toxicity minimal.

Purpose Recent studies have identified and proposed gamma emitting radionuclides (75Se, 169Yb, 153Gd) with intermediate energy (50 keV Materials and methods Post implant treatment plans were simulated with a Geant4-based Monte Carlo dose calculation engine, BrachySource, coupled to a column-generation based optimizer, for a prostate brachytherapy case. The patient was treated with a brachytherapy boost with a dose of 15 Gy in a single fraction. Simulations were performed using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active cores of the source. The plans were independently approved by two radiation oncologists. Two MC calculation protocols were performed for each radionuclide: (1) dose calculations for which patient anatomy is modelled as unit density water and (2) dose calculations for which patient anatomy is modelled with accurate chemical composition of tissues and densities are obtained using the HU values from CT scan. Results With 90% of the planning target volume (PTV) receiving over 15 Gy, plans can reduce the PTV V150 to 19.8%, 18.0%, 18.5%, 13.7% and 11.6% for 60Co, 192Ir, 75Se, 169Yb, and 153Gd, respectively, without sacrificing the urethral D10, the bladder V75 and the rectum V75. In general, dose homogeneity within the PTV increased with decreasing average photon energy. The inclusion of tissue composition and density corrections resulted in a reduction of the PTV D90 (urethral D10) by 0.0% (0.0%), 0.8% (0.7%), 1.8% (1.6%), 3.0% (4.7%) and 4.5% (4.1%) for 60Co, 192Ir, 75Se, 169Yb, and 153Gd, respectively. Conclusion Intermediate-energy sources have the potential to increase dose homogeneity within the PTV while reducing hot spots in the urethra, bladder, and rectum. This work shows the importance of accurate MC-based treatment planning engine, which can account for tissue composition and heterogeneities, for the dosimetry of intermediate-energy sources.

5008 Background: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. The aim of this randomized trial (Clinical Trials.gov, #NCT00223171) was to compare outcomes of RT combined with either 36 or 18 months of ADT. Methods: Patients with HRPC were randomized to pelvic and prostate RT combined with 36 (arm 1) or 18 months (arm 2) of ADT. Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results: 630 patients were randomized, 310 to arm 1 and 320 to arm 2. With a median follow-up of 9.4 years, 290 patients had died (147 arm 1 vs. 143 arm 2). The 10-year OS rate was 62.4% (95% confidence interval [CI] 56.4%, 67.8%) for arm 1 and 62.0% (95% CI 56.1%, 67.3%) for arm 2 (p = 0.8412) with a global hazard ratio (HR) of 1.024 (95% CI 0.813-1.289, p = 0.8411). QoL analysis showed a significant difference (p < 0.001) in 6 scales and 13 items favoring 18 months ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. Conclusions: In HRPC, ADT combined with RT can be safely reduced from 36 to 18 months without compromising outcomes or QoL. 18 months of ADT represents a new standard of care in HRPC. Funded by AstraZeneca Pharmaceuticals Clinical trial information: NCT00223171.

47 Background: Two recent large randomized trials confirm that 60Gy in 20 fractions is an effective regimen compared to conventionally fractionated escalated doses in localized prostate cancer. However, in these two trials the prostate was the only target volume irradiated. The purpose of this study is to report acute and late toxicity in patients with high-risk prostate cancer treated with the same moderate hypofractionated radiotherapy (HypoRT) to two target volumes at the same time: prostate and pelvic nodes. Methods: High-risk prostate cancer patients received 60Gy/20 fractions (4 weeks) to the prostate while the pelvic-nodes received 44Gy delivered with intensity modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) during the same 20 fractions. ADT started 2-3 months before HypoRT. Acute and late toxicity were prospectively assessed according to CTCAE.v3. Results: 105 patients treated between September/2010 and November/2013 were reviewed. Median follow up is 41 months. Median ADT duration was 18 months. Acute grade > 2 gastrointestinal (GI) or genitourinary (GU) toxicity was seen in 17% and 17% respectively, with only 1 and 3 patients experiencing GI and GU acute grade 3 toxicity, respectively. The worst grade > 2 late GI and GU toxicity was seen in 7% and 8% of patients, respectively. There was no grade 4-5 toxicity. At the last follow-up, the rates of grade = 2 GI and GU toxicity were 5% and 3%, respectively with no residual grade > 3 toxicity. The 48-month actuarial progression free survival is 82%. We found only 8 publications on this topic, all delivered the HypoRT in 25-28 fractions, but only one has long-term toxicity. Conclusions: ADT with HypoRT delivered with IMRT and SIB to the prostate (60Gy) and pelvic nodes (44Gy) in 20 fractions is feasible and well tolerated after 41months of median follow-up. Our approach shortens treatment duration, is convenient and its results support a needed randomized trial. Clinical trial information: NCT02107287.

Background and purpose We explore analytical and data-driven approaches to investigate the integration of genetic variations (single nucleotide polymorphisms [SNPs] and copy number variations [CNVs]) with dosimetric and clinical variables in modeling radiation-induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients. Materials and methods Sixty-two patients who underwent curative hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 and 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Fifty-four patients had full dosimetric profiles. Two parallel modeling approaches were compared to assess the risk of severe RB (Grade ⩾3) and ED (Grade ⩾1); Maximum likelihood estimated generalized Lyman–Kutcher–Burman (LKB) and logistic regression. Statistical resampling based on cross-validation was used to evaluate model predictive power and generalizability to unseen data. Results Integration of biological variables xrcc1 CNV and SNP improved the fit of the RB and ED analytical and data-driven models. Cross-validation of the generalized LKB models yielded increases in classification performance of 27.4% for RB and 14.6% for ED when xrcc1 CNV and SNP were included, respectively. Biological variables added to logistic regression modeling improved classification performance over standard dosimetric models by 33.5% for RB and 21.2% for ED models. Conclusion As a proof-of-concept, we demonstrated that the combination of genetic and dosimetric variables can provide significant improvement in NTCP prediction using analytical and data-driven approaches. The improvement in prediction performance was more pronounced in the data driven approaches. Moreover, we have shown that CNVs, in addition to SNPs, may be useful structural genetic variants in predicting radiation toxicities.

Purpose To report the frequency, timing, and magnitude of prostate-specific antigen (PSA) bounce (PB) in patients who received high-dose-rate (HDR) brachytherapy (HDRB) plus hypofractionated external beam radiation therapy (HypoRT) and to assess a possible correlation between PB and biochemical failure (BF). Methods and Materials Patients with intermediate-risk prostate cancer received 10 Gy single-fraction 192Ir HDRB followed by 50 Gy in 20 daily fractions of HypoRT without androgen deprivation therapy. All patients had a minimum 2-year followup. The PB was defined as PSA elevation higher than 0.2 ng/mL from previous measurement with subsequent drop to pre-bounce level. The BF was defined as PSA nadir + 2 ng/mL. Results A total of 114 patients treated between 2001 and 2009 were eligible for analysis. At a median followup of 66 months, the PB was found in 45 (39%) patients with a median time to bounce of 16 months (range, 3–76 months). The median time to PSA normalization after a PB was 9 months (range, 2–40 months). The median magnitude of PB was 0.45 ng/mL (range, 0.2–6.62). The BF occurred in 12 (10.5%) patients of whom three had a PB. Median time to BF was 52.5 months. Four patients (3.5%) in the PB group fit the criteria for BF. Conclusions The PB is common after HDRB and HypoRT and can occur up to 76 months after treatment. It can rarely fit the criteria for BF. The time to PB is shorter than the time to BF. There is a lower incidence of BF in patients with a PB. An acknowledgment of this phenomenon should be made when interpreting PSA results during followup to prevent unnecessary interventions.

PURPOSE: To assess the impact of intravesical contrast during computed tomography (CT) simulation on prostate tumor volume definition and dose distribution. METHODS AND MATERIALS: Sixteen patients with localized adenocarcinoma of the prostate underwent CT-based virtual simulation in preparation for definitive radiotherapy. Patients were immobilized with a foam cradle and an initial CT was performed after oral but without intravesical contrast (noncontrast scan). A second scan was performed following administration of intravesical contrast (contrast scan). Beam apertures were designed on the noncontrast scans and digitized into the contrast scan file. Beam apertures were also designed on the contrast scans. Isodose plans were generated for several beam apertures and arrangements. RESULTS: There was enhanced visualization of the prostate at the cephalad portion of the field for 15 of the 16 cases. The mean differences between the noncontrast and contrast volumes was significant (p = 0.0001). The mean percent underdosage to the prostate ranged from 3.9% to 18.6%, depending upon the target volume and beam arrangement. CONCLUSION: This study demonstrates the necessity of using intravesical contrast for defining the location of the prostate during CT simulation. The underestimation of the extent of the prostate when omitting intravesical contrast leads to significant underdosage. The value of intravesical contrast is most evident when small (prostate only) conformal fields are used.