[en] Purpose: To identify dosimetric parameters predictive of a good prostate seed I¹²⁵ quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. Methods and Materials: We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I¹²⁵ brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of ≥90% and a D90 of ≥140 Gy on the basis of CT-D28 values. Results: On CT-D28, 72.4% of patients had a V100 of ≥90% and 74.8% had a D90 of ≥140 Gy. AUROC for a V100 of ≥90% was 0.665 (p = 0.004) on PRE-TRUS and 0.619 (p = 0.039) on POST-TRUS. AUROC for D90 of ≥140 Gy was 0.602 (p = 0.086) on PRE-TRUS and 0.614 (p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. Conclusions: Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography-based dosimetry

[en] Purpose: To assess the influence of fiducial marker (FM) migration on the matching quality in external beam radiation therapy (EBRT) for prostate cancer. Materials and methods: The position of FMs were identified using on-board kV imaging (OBI) and their 3-D position established using an in-house reconstruction algorithm for 31 patients with prostate adenocarcinoma. To carry out the match, the positions were overlaid on the digitally reconstructed radiographs (DRR) generated from the planning CT. The distance between each FM was calculated for seven treatments throughout the EBRT course. Four radiotherapy technologists were asked to independently perform and rate the match from OBI to DRR which was then correlated to the extent of FM migration. Results: All the matches were rated by at least three radiotherapy technologists as 'very easy' ('easy' subgroup) for 24 patients (77%), while the other seven patients had their match rated less than 'very easy' and considered the 'not easy' subgroup. The average daily FM migration was 0.93 ± 0.34 mm for the 'easy' subgroup vs. 1.82 ± 0.75 mm for the latter. An average migration >2 mm was seen in five/seven patients in the 'not easy' subgroup as compared to none in the 'easy' subgroup. There was a trend towards less FM migration and better matching if the planning CT was done later than the day of the FM implant (p = 0.093). Conclusions: FM migration >2 mm predicts for a more difficult matching process; PTV margins might have to be adjusted or the planning CT repeated.

[en] Purpose: To compare low (mean 0.44, SD ± 0.0163 mCi) with high source activity (0.61 ± 0.0178 mCi) in I¹²⁵ permanent seed brachytherapy regarding seed loss, dosimetric outcome, and toxicity. Methods and Materials: The study included 199 patients with prostate cancer treated by permanent seed brachytherapy alone: the first 105 with seeds of lower activity (first cohort), the following 94 with higher seed activity (second cohort). The V100, V150, V200, and D90 were analyzed on the CT scan 30 days after implantation (CTD30). The V100, V150, and D2 of the rectum were also calculated on CTD30. Seed loss was determined 30 days after implantation. Urinary toxicity was measured with the International Prostate Symptom Score (IPSS) questionnaire. Results: Lower seed activity was associated with lower V150 and V200 (p = 0.01 and p ≤ 0.001, respectively) on CTD30. More patients had a V100 <90% and D90 <140 Gy in the lower activity cohort (p = 0.098 for D90 and p = 0.029 for V100) on CTD30. There was no difference between cohorts in dose to the rectum (p = 0.325-0.516) or difference in patients' IPSS score from baseline (p = 0.0.117-0.618), although there was a trend toward more urinary toxicity at 4 and 8 months for high activity seeds. Seed loss as a percentage of implanted seeds was not different (p = 0.324). Conclusions: Higher seed activity (I¹²⁵ ≥ 0.6 mCi) results in at least equal V100 and D90 on CTD30. However, dose inhomogeneity and a trend toward more urinary toxicity at 4 and 8 months after treatment may lead to a higher long-term urinary complications.

[en] To evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT). From 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires. Five-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients. Short split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity

[en] Purpose: To report the toxicity outcome in patients with localized prostate cancer undergoing ¹²⁵I permanent-seed brachytherapy (BT) according to a urethra-sparing, intraoperative (IO), real-time planned conformal technique. Methods and Materials: Data were analyzed on 250 patients treated consecutively for low- or intermediate-risk prostate cancer between 2005 and 2009. The planned goal was urethral V₁₅₀ = 0. Acute and late genitourinary (GU), gastrointestinal (GI), and erectile toxicities were scored with the International Prostate Symptom Score (IPSS) questionnaire and Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time for patients with at least 2 years of follow-up (n = 130) was 34.4 months (range, 24–56.9 months). Results: Mean IO urethra V₁₅₀ was 0.018% ± 0.08%. Mean prostate D₉₀ and V₁₀₀ on day-30 computed tomography scan were 158.0 ± 27.0 Gy and 92.1% ± 7.2%, respectively. Mean IPSS peak was 9.5 ± 6.3 1 month after BT (mean difference from baseline IPSS, 5.3). No acute GI toxicity was observed in 86.8% of patients. The 3-year probability of Grade ≥2 late GU toxicity-free survival was 77.4% ± 4.0%, with Grade 3 late GU toxicity encountered in only 3 patients. Three-year Grade 1 late GI toxicity-free survival was 86.1% ± 3.2%. No patient presented Grade ≥2 late GI toxicity. Of patients with normal sexual status at baseline, 20.7% manifested Grade ≥2 erectile dysfunction after BT. On multivariate analysis, elevated baseline IPSS (p = 0.016) and high-activity sources (median 0.61 mCi) (p = 0.033) predicted increased Grade ≥2 late GU toxicity. Conclusions: Urethra-sparing IO BT results in low acute and late GU toxicity compared with the literature. High seed activity and elevated IPSS at baseline increased long-term GU toxicity.

[en] The split-course schedule of chemo-radiation for anal cancer is controversial. Eighty-four patients with invasive anal cancer treated with definitive external beam radiotherapy (RT) with a mandatory split of 12 days (52 patients, Montreal, Canada) or without an intended split (32 patients, Zurich, Switzerland) were reviewed. Total RT doses were 52 Gy (Montreal) or 59.4 Gy (Zurich) given concurrently with 5-FU/MMC. After a mean follow-up of 40 ± 27 months, overall survival and local tumor control at 5 years were 57% and 78% (Zurich) compared to 67% and 82% (Montreal), respectively. Split duration of patients with or without local relapse was 15 ± 7 d vs. 14 ± 7 d (Montreal, NS) and 11 ± 11 d vs. 5 ± 7 d (Zurich; P < 0.001). Patients from Zurich with prolonged treatment interruption (≥ 7 d) had impaired cancer-specific survival compared with patients with only minor interruption (<7 d) (P = 0.06). Bowel toxicity was associated with prolonged RT (P = 0.03) duration as well as increased relapse probability (P = 0.05). Skin toxicity correlated with institution and was found in 79% (Montreal) and 28% (Zurich) (P < 0.0001). The study design did not allow demonstrating a clear difference in efficacy between the treatment regimens with or without short mandatory split. Cause-specific outcome appears to be impaired by unplanned prolonged interruption

[en] Purpose: To determine the incidence of pseudoprogression (PP) after spine stereotactic body radiation therapy based on a detailed and quantitative assessment of magnetic resonance imaging (MRI) morphologic tumor alterations, and to identify predictive factors distinguishing PP from local recurrence (LR). Methods and Materials: A retrospective analysis of 35 patients with 49 spinal segments treated with spine stereotactic body radiation therapy, from 2009 to 2014, was conducted. The median number of follow-up MRI studies was 4 (range, 2-7). The gross tumor volumes (GTVs) within each of the 49 spinal segments were contoured on the pretreatment and each subsequent follow-up T1- and T2-weighted MRI sagittal sequence. T2 signal intensity was reported as the mean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargement on ≥2 serial MRI studies for ≥6 months or on pathologic confirmation. PP was defined as a GTV enlargement followed by stability or regression on subsequent imaging within 6 months. Kaplan-Meier analysis was used for estimation of actuarial local control, disease-free survival, and overall survival. Results: The median follow-up was 23 months (range, 1-39 months). PP was identified in 18% of treated segments (9 of 49) and LR in 29% (14 of 49). Earlier volume enlargement (5 months for PP vs 15 months for LR, P=.005), greater GTV to reference nonirradiated vertebral body T2 intensity ratio (+30% for PP vs −10% for LR, P=.005), and growth confined to 80% of the prescription isodose line (80% IDL) (8 of 9 PP cases vs 1 of 14 LR cases, P=.002) were associated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to volume enlargement and growth within the 80% IDL as significant predictors of PP. LR involved the epidural space in all but 1 lesion, whereas PP was confined to the vertebral body in 7 of 9 cases. Conclusions: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement were predictive for PP.

[en] Purpose: To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. Methods and Materials: Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. Results: With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. Conclusion: In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities.

[en] Purpose: The optimal chemotherapy regimen remains undefined in the treatment of locally advanced oropharyngeal cancer by concomitant chemoradiation. This article compares two platinum-based chemotherapy regimens. Methods and Materials: In this retrospective study, we reviewed all consecutive patients treated for Stage III or IVA-B oropharyngeal cancer using either a combination of carboplatin and 5-fluorouracil (5FU) every 3 weeks or high-dose cisplatin every 3 weeks concomitant with definitive radiation therapy. Results: A total of 200 patients were treated with carboplatin-5FU and 53 patients with cisplatin. Median potential follow-up was 43 months. The 3-year overall survival rates for carboplatin-5FU and cisplatin respectively were 79.1% and 74.9% (p = 0.628), the 3-year disease-free survival rates were 76.0% and 71.3% (p = 0.799), and the 3-year locoregional control rates were 88.4% and 94.2% (p = 0.244). Conclusions: We could not demonstrate differences between these two regimens, which both proved efficacious. Polychemotherapy and monochemotherapy therefore seem comparable in this retrospective analysis.

[en] Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.