Late Rectal Complications Research Articles

Safety and efficacy of salvage high-dose rate brachytherapy for prostate-bed recurrences following radical prostatectomy and external beam radiotherapy.

This retrospective study aims to evaluate the efficacy and safety of salvage HDR brachytherapy in second local recurrences of prostate cancer after applying radical prostatectomy (RP) and post-operative external beam radiotherapy (EBRT). Fifteen patients with locally recurrent prostate cancer after RP and EBRT were salvaged with HDR brachytherapy. Patients had no nodal or distant metastasis evidence on imaging findings, including whole body bone scan, CT scan, and MRI or PSMA PET scan. HDR brachytherapy was applied with 36Gy in four fractions, in two implantations with 1week apart. We followed the patients for a control visit every 3months for 2years, and every 6months thereafter. Fifteen patients with the mean age of 64years (ranged 51-79) underwent salvage HDR brachytherapy. The mean baseline level of PSA was calculated 2.26ng/ml (ranged from 0.21 to 9, SD = 2.33), which has been significantly decreased in all patients. Hence, two of our patients experienced a biochemical failure during the follow-up period. Our results showed that 86.6% (n = 13) of patients had never experienced a significant increment in PSA level after a median follow-up of 48months (ranging from 12 to 132months). Besides, salvage HDR brachytherapy did not induce any significant side effects such as acute or late rectal complications, despite causing urinary complication. HDR brachytherapy could be considered as a treatment in well-selected patients with the second recurrence in their prostatic bed after the former EBRT allowing for dose escalating to the second nodular recurrence.

High-dose external BEAM intensity-modulated radiotherapy (HD-IMRT) versus intensity-modulated radiotherapy plus HDR brachytherapy boost (LD-IMRT+HDR-B) dose escalation for intermediate- or high-risk prostate cancer

263 Background: To report early & late toxicity & biochemical outcome in a prospective series of 1,465 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-IMRT or with LD-IMRT+HDR-B. Methods: Between 12/1999 and 10/2011, 1,465 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-IMRT to the prostate in 38 fractions (group 1; 733 patients) or 46 Gy LD-IMRT followed by 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 732 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumor’s characteristics. Toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. Results: All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 or more rectal toxicity. 94 pts of group 1 (12.8%) and 20 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 49 pts in group 1 (6.7%) and 10 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). With a mean follow-up of 112 months, the 10-year free-from-failure survival was 90.7% and 98.3% (p<0.001) in group 1 and 2 respectively; free-from-metastases survival 93.9% and 97.8% (p<0,002)for group 1 and 2 respectively; and cause-specific survival 90.1% and 98.2% (p<0.001). No complications grade 2-4 were seen in either group. Conclusions: IMRT + HDR brachytherapy boost was a safe and extremely effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal complications were significantly reduced. Control rates were significantly better in the HDR-boosted patients as expected by higher effective-dose. Brachytherapy boost treated patients had a significant longer survival.

Re-irradiation with interstitial brachytherapy in uterine cancer patients with vaginal recurrence after post-operative pelvic irradiation.

PurposeThis study aimed to evaluate the outcomes and dose-volume parameters of re-irradiation with interstitial brachytherapy (ISBT) in uterine cancer patients with vaginal recurrence after post-operative pelvic irradiation.Material and methodsWe evaluated six uterine cancer patients who received re-irradiation with ISBT between January, 2012 and December, 2016. As an initial treatment, all patients received post-operative whole pelvic irradiation of 45-50.4 Gy in 25-28 fractions. For vaginal recurrence, all patients were treated with ISBT alone at a dose of 38-42 Gy in 6-7 fractions for clinical target volumes (CTVs) for 3-4 days.ResultsPost-operative pelvic irradiation was delivered to five and one patients, using a three-dimensional conformal technique and intensity-modulated radiotherapy, respectively. Median duration from surgery to vaginal recurrence was 25.7 months. Median tumor size just before ISBT was 3.3 cm. Median time from completion of pelvic irradiation to ISBT initiation was 24.1 months. Mean doses per fraction of ISBT for CTV D90 (the minimum dose received by 90% of CTV) and minimum dose received by 2cc (D2cc) for the bladder and for rectum were 6.1 Gy, 4.4 Gy, and 3.8 Gy, respectively. Mean total equivalent dose in 2 Gy fractions (EQD2), including external beam radiotherapy and ISBT, for D2cc for the bladder, sigmoid, and rectum were 92.1 Gy, 50.4 Gy, and 81.6 Gy, respectively. Median follow-up duration was 53.3 months. Local recurrence was observed in two patients, and four of the six patients were alive. Grade 2 late rectal complications occurred in two patients, and no late grade ≥ 3 complications were observed in four alive patients.ConclusionsRe-irradiation with ISBT may be an effective treatment strategy for gynecological cancer patients with vaginal recurrence after post-operative pelvic irradiation.

Dosimetric predictors of local control and complications in gynecologic transperineal implant patients: The medical college of wisconsin experience

Investigate the relationship between dosimetric parameters with local control (LC) and complications following transperineal high-dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic (GYN) malignancies. Between 2001 and 2016, 59 patients were treated for primary or recurrent GYN malignancies. Most patients received external beam irradiation, followed by transperineal ISBT via the Syed-Neblett applicator set with CT-based planning. Treatment plans were retrospectively reviewed to evaluate for an association among LC or toxicity with the equivalent dose at 2 Gy per fraction (EQD2) for the clinical target volume (CTV), 0.1 cc (D0.1cc), and 2 cc (D2cc) volumes of the organs at risk (OAR), low/high dose volumes for the OAR and CTV, and ratio of dose at the core vs. the implant periphery. The median follow-up among survivors was 24 months. 34% of patients had a component of local failure and in 12%, this was isolated. Late grade 3 (G3) toxicity occurred in 15% of patients. There were no G4-5 toxicities. Rectal D0.1cc > 75 Gy trended toward significance in predicting the development of non-fistula late G2-3 rectal complications. Bladder D0.1cc > 94 Gy significantly predicted for the development of late G2-3 vesicovaginal fistula formation. The ratio of the total dose at the vaginal surface to the needle periphery above 121% trended in predicting for any complication or fistula formation. HDR ISBT combined with EBRT achieved LC in 66% of patients with advanced or recurrent GYN cancers. Rectal and bladder D0.1cc doses may be predictive of complications as may the ratio of the implant dose at the core vs. periphery.

Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial

Intracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy. Between 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2-3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly. With a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages. HDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.

The Relationship Between Late Morbidity and Dose-Volume Parameter of Rectum in Combined Intracavitary/Interstitial Cervix Cancer Brachytherapy: A Mono-Institutional Experience.

PurposeTo establish a dose volume–effect relationship for predicting late rectal complication (LRC) in locally advanced cervical cancer patients treated with external beam radiotherapy (EBRT) followed by combined intracavitary/interstitial brachytherapy (IC/IS-BT).Materials and MethodsA retrospective analysis was performed in 110 patients with locally advanced cervical cancer who underwent definitive radiotherapy combined with IC/IS-BT from July 2010 to September 2018. We report the 90% of the target volume receiving the minimum dose for high risk clinical target volume (HR-CTV D90) and intermediate risk clinical target volume (IR-CTV D90), and the minimum doses to the most exposed 0.1, 1, and 2 cm³ doses at the International Commission on Radiation Units and Measurements (DICRU) for organs at risk (OARs). The total dose of EBRT plus brachytherapy was transformed to the biologically equivalent dose in 2 Gy fractions (EQD2) with α/β value of 10 Gy for target, 3 Gy for organs at risk using the linear quadratic model. The morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria. The Probit model was used to establish a prediction model on rectum between the organs at risk for dose and LRC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of dose volume parameters for LRC.ResultsThe median follow-up time was 72.3 months. The mean ( ± standard deviation) , and DICRU values of rectum were 64.72 ± 7.47 GyEQD2, 70.18 ± 5.92 GyEQD2, 79.32 ± 7.86 GyEQD2, and 67.22 ± 7.87 GyEQD2, respectively. The Probit model showed significant relationships between , and the probability of grade1–4, grade 2–4 rectal events at 1 year, and between and the probability of grade2–4 rectal events at 3 and 5 years. The dose values for 10% complication rates (ED10) of were 74.18 (70.42–76.71) GyEQD2, 67.80 (59.91, 71.08) GyEQD2, 66.37 (52.00, 70.27) GyEQD2 for grade 2–4 with rectal morbidity at 1, 3, and 5 years, respectively.ConclusionOur study proved that were considered as useful dosimetric parameters for predicting the risk of grade1–4 and grade2–4 LRC at 1-year, and might be an indicator for predicting grade2-4 LRC at 3/5years. The patients with rectal >66.37–74.18 GyEQD2 should be closely observed for grade2–4 LRC.

Dose rate in the highest irradiation area of the rectum correlates with late rectal complications in patients treated with high-dose-rate computed tomography-based image-guided brachytherapy for cervical cancer.

The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D0.1cc, >D2cc, and > D5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDRp). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD2). The associations between EDRp for D0.1cc, D2cc, and D5cc and the respective rectal EQD2 values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDRp for D0.1cc–5cc and had a greater EQD2 for D0.1cc–5cc. Multivariate analysis was performed using the mean EDRp for D2cc, EQD2 for D2cc, heavy smoking and BMI. Of these four variables, mean EDRp for D2cc (HR = 3.38, p = 0.004) and EQD2 for D2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDRp and EQD2 were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.

Dose-averaged linear energy transfer per se does not correlate with late rectal complications in carbon-ion radiotherapy

Background and purposeSeveral studies have focused on increasing the linear energy transfer (LET) within tumours to achieve higher biological effects in carbon-ion radiotherapy (C-ion RT). However, it remains unclear whether LET affects late complications. We assessed whether physical dose and LET distribution can be specific factors for late rectal complications in C-ion RT. Materials and methodsOverall, 134 patients with uterine carcinomas were registered and retrospectively analysed. Of 134 patients, 132 who were followed up for >6 months were enrolled. The correlations between the relative biological effectiveness (RBE)-weighted dose based on the Kanai model (the ostensible “clinical dose”), dose-averaged LET (LETd), or physical dose and rectal complications were evaluated. Rectal complications were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. ResultsNine patients developed grade 3 or 4 late rectal complications. Linear regression analysis found that D2cc in clinical dose was the sole risk factor for ≥grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting ≥grade 3 late rectal complications. Among 35 patients whose rectal D2cc was ≥60.2 Gy (RBE), no correlations were found between severe rectal toxicities and LETd alone or physical dose per se. ConclusionWe demonstrated that severe rectal toxicities were related to the rectal D2cc of the clinical dose in C-ion RT. However, no correlations were found between severe rectal toxicities and LETd alone or physical dose per se.

Outcomes analysis of pre-brachytherapy MRI in patients with locally advanced cervical cancer

IntroductionVarious brachytherapy options are available for treating cervical cancer. This study investigated whether pre-brachytherapy magnetic resonance imaging (MRI) findings could help identify the appropriate brachytherapy technique for cervical cancer.MethodsWe retrospectively...

The 2-year Results of Phase II Clinical Trial of Brachytherapy with Single-Channel Applicator For Cervical Carcinoma

To evaluate whether the patent single-channel applicator( China Patent number:200710050108.1), which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in the high-dose-rate brachytherapy for carcinoma of the cervix. This was a single blind, prospective, parallel randomized trial. This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR-TRC-12002321). All the eligible patients were randomized by random computer generation to 1 of 2 treatment groups: the Fletcher applicator group or the patent single-channel applicator group. Patients in both groups were treated with concurrent cisplatin chemotherapy and external beam radiotherapy(EBRT) followed by HDR brachytherapy (not includingⅡa1). Whole pelvis irradiation was given with 6-MV photons via a four-field box variants or anterior and posterior parallel fields. The standard prescribed dose was 46 to 50 Gy, consisting of 23 to 25 fractions 5 to 6 weeks apart. Five to six fractions with a dose of 7 Gy per fraction of intracavitary brachytherapy at point A once a week were designed for all patients after the third week of pelvic irradiation. This regimen gives a total equivalent dose in 2-Gy fractions (EQD2) of 80-90 Gy to Point A. Chemotherapy was given with intravenous cisplatin 40 mg/m2 once a week during the EBRT. The acute toxicities and the late toxicities were evaluated according to the RTOG grading scale. The Kaplan-Meier analysis was used to compare the overall survival (OS), the Progression-Free-Survival (PFS) and the locoregional failure-free survival (LRFFS). From December 1st 2011 to February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (FIGO 2009) stage Ⅰb2-Ⅳa carcinoma of the cervix were randomly assigned to the Fletcher applicator group(n=150) and the single-channel group (n=149). All but eight patients were treated with concurrent chemoradiotherapy. Up to February 2019, all the patients had achieved a minimum follow-up of 2 years. The 2-year OS, PFS and LRFSS was 81.4%, 77.7% and 79.5% for the Fletcher group, and for the single-channel group was 88.2%, 83.6% and 87.0%, respectively. The seriousness of acute treatment-related toxicities was similar in the two groups. The cumulative rate of late rectal complications for Grade 3-4 in the Fletcher group and the single-channel group was 4.0% and 5.4%, respectively. The cumulative rate of Grade 3-4 bladder complications was 1.3% for the Fletcher group and 0.7% for the single-channel group. The 2-year results of our study shows that the patent single-channel intracavitary applicator may be able to provide a protection for the rectum and bladder, and seems to have the same clinical efficacy as the standard Fletcher type three-channel applicator in the high-dose-rate brachytherapy for carcinoma of the cervix.

Dose escalation with high-dose-3D-conformal/IMRT (HD-3D-CRT/IMRT) compared with low-dose 3D-conformal/IMRT plus HDR brachytherapy (LD-3D-CRT/IMRT+HDR-B) for intermediate- or high-risk prostate cancer: Disease control, survival, and toxicity.

169 Background: To report early and late toxicity and biochemical outcome in a prospective series of 1,465 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-3D-CRT/IMRT or with LD-3D-CRT/IMRT+HDR-B. Methods: Between 12/1999 and 10/2011, 1,465 pts (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-3D-CRT or IMRT to the prostate in 38 fractions (group 1; 733 pts) or 46 Gy LD-3D-CRT or IMRT followed by 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 732 pts), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. Results: All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 or more rectal toxicity. 94 pts of group 1 (12.8%) and 20 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 49 pts in group 1 (6.7%) and 10 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). With a mean follow-up of 102 months, the 10-year free-from-failure survival was 90.7% and 98.3% (p<0.002) in group 1 and 2 respectively; free-from-metastases survival 95.9% and 97.8% (p<0,006)for group 1 and 2 respectively; and cause-specific survival 97.1% and 98.2% (p<0.08). Conclusions: High-dose 3D-EBRT + HDR brachytherapy was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal complications were significantly reduced with the combined treatment, compared with what was observed with high-dose conventional, 3D-conformal radiotherapy. Control rates were significantly better with in the HDR-boosted patients as expected by higher effective-dose.

Interim MRI Provides Accurate Information of Brachytherapy for Patients with Locally Advanced Cervical Cancer

To investigate the impact of interim MRI on outcome of cervical cancer patients treated with radical radiotherapy including series of high-dose-rate (HDR) brachytherapy (BT). We retrospectively analyzed consecutive 146 patients with locally advanced cervical cancer treated with radical radiotherapy between December 2009 and September 2015. The median dose of pelvic irradiation was 30.6 Gy (range, 30.6-39.6 Gy); further treatment used 10.8-19.8 Gy with a midline block. For all pts, the tumor size and location was diagnosed by interim MRI within 7 days before first HDR-BT. The standard intracavitary brachytherapy (ICBT) was principally administered for patients with 4 cm or smaller mass and symmetrical location on interim MRI. The selection criteria of individualized BT, which included interstitial brachytherapy (IBT), hybrid brachytherapy (HBT) and dose escalating ICBT to the high risk (HR) CTV D90, was diagnosed with interim MRI, namely 1) the width larger than 4 cm and asymmetrical tumor location, 2) the tumor with a vaginal invasion thicker than 5mm and 3) the bulky barrel shaped tumor. In case of ICBT, dose of 20-24 Gy/4 fractions were prescribed to point A or HRCTV D90. And in case of IBT, the dose of 24-30 Gy/4-5 fractions/2-3 days were prescribed to HRCTV D90. The patient characteristics were followings, median age was 57 years old (range 27-80 years old). Six pts were in FIGO stage Ib2, 67 in II, 64 in III and 9 in IVA. A total of 124 pts had squamous cell carcinoma, and 22 had adenosquamous cell carcinoma or adenocarcinoma. Median tumor size measured by initial pretreatment MRI was 52 mm (range 17-132 mm). At the time of initial pretreatment, 19 pts had severe vaginal invasion, 21 had asymmetrical tumor and 39 had corpus invasion. Median tumor size measured by interim MRI was 30 mm (range 0-78 mm). Finally, 119 pts were treated with standard ICT, 8 with dose escalated ICT, 4 with HBT and 15 with IBT. Median follow up period was 37.6 months (range 2.5-84.5 months). Complete response was obtained 139 pts (95.2%). Three-year overall survival (OS), disease free survival, local control (LC) and distant metastasis free survival were 84.2%, 75.6%, 90.1% and 81.8%, respectively. The grade 2 or 3 late rectal complications were recorded in 6 pts (4.2%). On univariate and multivariate analysis, there was no significant difference between LC and tumor characteristics such as large tumor, tumor with severe vaginal invasion, asymmetrical tumor and tumor with corpus invasion. On multivariate analysis, small tumor and local control after radiotherapy were significantly related to excellent OS (p=0.001 and <0.001, respectively). Interim MRI provides accurate radiological information to select appropriate brachytherapy method individually for patients with locally advanced cervical cancer and leads to excellent LC and OS.

Feasibility of Gynecologic High Dose Rate Brachytherapy Despite Uterine Perforation or False Passage Creation: Not Throwing Out the Baby With the Bathwater

The reported incidence of uterine perforation in tandem & ovoid brachytherapy ranges from 2 to 10%. Perforation not only potentially increases short term infection risk but treating a tandem in extrauterine or in a false myometrial passage may increase the risk of late rectal or sigmoid complications. When identified at the time of simulation, the brachytherapy may be cancelled, the apparatus removed, and antibiotics started with a subsequent low risk of infection. However, with modern HDR plan optimization, another option may be to treat before device removal if satisfactory dosimetry is achievable since the patient has already accrued the risks of a perforation. Between 2009-2016, 407 tandem & ovoid and 3 tandem & interstitial procedures were performed in 103 patients with cervical cancer. Procedures where the tandem perforated the uterus or created a false passage were identified from the simulation CT scans. HR-CTVs were retrospectively contoured in order to compare V100, D100, D90, rectal Dmax, and sigmoid Dmax doses between insertions with or without perforations and for patients with tandem false passages. Uterine perforations were identified in 12 insertions (2.9%) of which 9 (in 6 pts) were treated before removal. Tandem myometrial false passages without perforation were identified in 20 insertions (5%) in 4 pts all of whom were treated. Median follow up for all patients was 18 months (5 – 69). No acute complications and only 2 late GI toxicities occurred (1, Gr 2 and 1, Gr 3, both from false passage cases). At last follow up, there was 1 pt (10%) with local failure, 1 pt (10%) dead of metastases, 1 (10%) alive with metastases, and 7 (70%) alive without disease. For the 6 patients who had insertions with (9) and without (13) perforations, dosimetry for perforation vs. non-perforation insertions was: V100 74.5% (54 – 97) vs. 86.7% (66 – 100), D100 2.9 Gy (1.8 – 3.4) vs. 3.9 Gy (2.7 – 6.1), D90 4.7 Gy (3.1 – 6.1) vs. 6.2 Gy (3.8 – 9.6), rectal Dmax 3.7 Gy (1.6 – 6.6) vs. 3.8 Gy (2.4 – 5.1), and sigmoid Dmax 9.5 Gy (5 – 14) vs. 9.3 Gy (5.1 – 22). There were no statistically significant differences between the V100, D100, D90, rectal, and sigmoid doses between the insertions with and without perforations. For the false passage insertions (20 in 4 patients): V100 84.4% (66 – 99), D100 3.4 Gy (2.2 – 5.4), D90 5.6 Gy (3.8 – 8.8), rectum Dmax 3.7 Gy (2.1 – 4), and sigmoid Dmax 7.2 Gy (5.4 – 10). Routine abandonment of malpositioned tandem and ovoid brachytherapy insertions may not be necessary. Acute toxicity following uterine perforation is low. Moreover, in selected cases, optimized dosimetry may make possible comparable target volume coverage and normal tissue sparing despite perforating or malpositioned tandems.

Early Interim Results of a Phase 2Clinical Trial of Brachytherapy With Single-Channel Applicator for Cervical Carcinoma

To evaluate whether a single-channel intracavitary applicator ( China Patent number:200710050108.1) which transformed from a traditional tandem applicator with a oval-shaped shield maded of high density alloy has the same clinical efficacy and safety as the standard Fletcher-type applicator in the high-dose-rate(HDR) brachytherapy for carcinoma of the cervix. From December 1st 2011 to December 1st 2014, 112 patients with cervix cancer were randomly assigned to the Patent applicator group (n=54) and the Fletcher applicator group(n=58). All but seven patients with early stage were treated with concurrent cisplatin chemotherapy and external beam radiotherapy (EBRT) followed by HDR brachytherapy. Whole pelvis irradiation was given with 6-MV photons via a four-field box variants or anterior and posterior parallel fields. The standard prescribed dose was 46 to 50 Gy, consisting of 23 to 25 fractions 5 to 6 weeks apart. Five to six fractions with a dose of 7 Gy per fraction of intracavitary brachytherapy at point A once a week were designed for all patients after the third week of pelvic irradiation.This regimen gives a total equivalent dose in 2-Gy fractions (EQD2) of 80-90 Gy to Point A. Chemotherapy was given with intravenous cisplatin 40 mg/m2 once a week during the EBRT. The acute toxicities and the late toxicities were evaluated according to the RTOG grading scale. The Kaplan-Meier analysis was used to compare the overall survival (OS), the progression-Free-Survival (PFS) and the local control (LC). The 2-year OS rate in the two groups was 72.4% in the Fletcher group and 83.2% in the Patent group, respectively. The 2-year PFS rate was 69.0% in the Fletcher group and 79.4% in the Patent group. The 2-year LC rate was 72.4% in the Fletcher group and 79.4% in the Patent group. The seriousness of acute treatment-related toxicities was similar in the two groups. 34 (58.6%) patients in the Fletcher group and 29 (53.7%) in the Patent group had Grade 3–4 hematologic toxicity. No Grade 4 nonhematologic toxicity was observed in the two groups. 5 (8.6%) patients in the Fletcher group and 10 (18.5%) in the Patent group had Grade 3 acute gastrointestinal toxicity. Grade 3 acute rectal reaction and genitourinary effect for the Fletcher group was both 1.7%, and for the Patent group was both 1.9%. The cumulative rate of late rectal complications for Grade 3–4 in the Fletcher group and the Patent group was 5.2% and 1.9%, respectively. The bladder late complications rate of Grade 3–4 was 1.7% for the Fletcher group, and no patients in the Patent group had serious bladder late complications． The early interim results of our study have shown that the patent single-channel intracavitary applicator may be able to provide a protection for the rectum and bladder, and has the same clinical efficacy as the standard Fletcher type three-channel applicator in the HDR brachytherapy for carcinoma of the cervix. Further studies are needed to assess long-term outcomes and associated toxicities.

Palliative radiation therapy of bladder cancer

Introduction. One of the problems of urologic oncology is that patients with bladder cancer (BC) show up late for appointments, which leads to increased numbers of patients with advanced cancer stages accompanied by symptoms considerably reducing their quality of life. In most similar cases, external beam radiation therapy (EBRT) may be given with palliative intent to lessen or relieve the local symptoms of disease and to deliver the highest possible dose of radiation to bladder tumor. Objective : to assess the efficacy and toxicity of palliative EBRT in patients with BC. Materials and methods . Outcomes of palliative EBRT that had been given to 103 patients with BC were analyzed. Poor somatic health status of these patients caused by underlying disease or accompanying pathology made radical treatment impossible. Results. During EBRT treatment, hematuria was stopped in 56 (72.7 %) and reduced in 21 (27.3 %) patients. After completing EBRT, bladder pain syndrome was relieved in 13 (76.5 %) of 17 patients, but in 1 patient the pain got worse, and in 3 (17.6 %) patients no changes in this symptom occurred. Acute bladder reactions were observed in 37 (35.9 %) patients: grade I–II (RTOG) in 32 (31.1 %) patients and grade III–IV in 5 (4.8 %) patients. Acute grade I–II rectitis was noted in 10 (9.7 %) patients. Late grade I–II bladder complications (RTOG/EORTC) occurred in 16 (15.5 %) patients, and late rectal complications in 2 (1.9 %) patients. Due to relief of local symptoms and improvement of somatic health status in 16 (15.5 %) patients, it was possible to perform radical treatment for BC. At 12 months after treatment, objective tumor response was achieved in 34 (33.0 %) and stable disease in 14 (13.6 %) BC patients. Conclusion . Radiation therapy is an effective method of palliative care of patients with advanced BC and marked local symptoms. In most cases, EBRT can help stop or reduce hematuria and pain as well as improve quality of patient life. Therefore, it is necessary to develop methods of effective palliative care for patients with complicated advanced BC. A personalized approach to optimize programs palliative treatment of BC is a promising direction for further research.

Improved Late Rectal and Urinary Toxicity With High-Dose Intensity Modulated Radiation Therapy Using Intraprostate Fiducial Markers for Localized Prostate Cancer

To evaluate the impact of intensity modulated radiation therapy (IMRT) with intraprostate fiducial markers on the incidence of late urinary and rectal toxicity compared to 3D conformal radiation therapy (3DCRT) for patients with prostate cancer (PC) treated in a dose-escalation protocol. The hypothesis is that IMRT with image guided radiation therapy (IGRT) allows increasing dose with less toxicity than 3DCRT. Between 1995 and 2015, 1022 consecutive patients with localized PC were treated with dose-escalation radiation therapy (RT) of which 733 patients were enrolled in this study. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up >23 months. The study included 438 patients treated with 3DCRT and 295 treated with IMRT using intraprostate gold fiducial markers IGRT. The median ICRU radiation dose was 79.8 Gy (range, 72.1-87.1), 78.7 Gy and 80.7 Gy for 3DCRT and IMRT/IGRT respectively (P<0.001). Acute and late toxicities were assessed using the EORTC/RTOG and CTCAEs v4.0 definition. A logistic regression analysis was performed to identify clinical and dosimetric prognostic factors affecting the risk of late urinary and rectal complications. Statistical analyses were carried out using statistical analysis software. The mean follow-up for the entire cohort was 75 months (range, 24-204 months). The incidence of late grade ≥ 2 urinary complications was 5.4% and 13.0% for IMRT/IGRT and 3DCRT respectively (P = 0.001) and the incidence for grade ≥ 2 rectal toxicity was 3.7% and 9.4% for IMRT/IGRT and 3DCRT respectively (P = 0.004). On multivariate analysis, the use of IMRT/IGRT (odds ratio [OR] = 0.374, P = 0.001) and the antecedent of prior transurethral resection of the prostate (OR = 2.452, P = 0.005), were the only independent factors correlated with late grade ≥2 urinary complications. Other factors like the presence of acute urinary symptoms during RT (OR = 1.780, P = 0.060) and the use of hormone therapy (OR = 0.596, P = 0.069) were of borderline statistical significance but with potential clinical relevance. The use of IMRT/IGRT (OR = 0.378, P = 0.014), the antecedent of colon diverticula (OR = 3.515, P<0.001) and the patient age (OR = 0.941, P = 0.040) were significantly correlated with late grade ≥ 2 rectal toxicity. High-dose IMRT/IGRT with intraprostatic fiducial markers is associated with a significantly lower rate of rectal and urinary side effects compared to 3DCRT in spite of higher radiation dose. Further follow up is needed to confirm the protective effect of hormone therapy on late urinary complications.

Treatment results of brachytherapy vs. external beam radiation therapy for intermediate-risk prostate cancer with 10-year followup

PurposeTo compare 10-year treatment outcomes of brachytherapy vs. external beam radiation therapy for patients with intermediate-risk prostate cancer (IRPC). Methods and MaterialsBetween 2004 and 2007, 93 IRPC patients underwent brachytherapy using iodine-125 to a dose of 145 Gy without supplemental external radiation. A retrospective comparison was performed to a contemporary cohort of 597 patients treated with external beam radiation therapy to a median dose of 75.3 Gy using a propensity score-matched analysis. ResultsMedian followup was 7.8 years. With brachytherapy, 51.6% had Gleason score 7 vs. 72.0% for external radiation (p < 0.001). Median initial prostate-specific antigen was 8.3 for brachytherapy vs. 9.4 for external radiation (p = 0.01). Neoadjuvant androgen deprivation therapy was given in 59.5% of external radiation vs. 10.8% of brachytherapy patients (p < 0.001). The 10-year freedom from biochemical failure (FFBF) for brachytherapy was 81.7% vs. 54.5% for external radiation (p = 0.002). Unfavorable intermediate-risk patients experienced borderline significant improved FFBF with brachytherapy (p = 0.08). The 10-year freedom from salvage therapy for brachytherapy was 93.2% vs. 72.2% for external radiation (p = 0.006). There were no significant differences in distant metastases-free survival, prostate cancer-specific survival, or overall survival after adjusting for age. Multivariate analysis with propensity score matching showed that brachytherapy remained an independent predictor for improved FFBF (p = 0.007). Grade 1 and 2 late rectal complication rate was 6.5% for brachytherapy vs. 15.2% for external radiation (p = 0.02). ConclusionsBrachytherapy using iodine-125 without supplemental external radiation is a reasonable treatment option for selected IRPC patients.

Dose Escalation with High-Dose-3D-Conformal/IMRT (HD-3D-CRT/IMRT) Compared with Low-Dose 3D-Conformal/IMRT Plus HDR Brachytherapy (LD-3D-CRT/IMRT+HDR-B) for Intermediate- or High-Risk Prostate Cancer: Higher Disease Control and Survival with Lower Toxicity

To report early and late toxicity and biochemical outcome in a prospective series of 1343 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-3D-CRT/IMRT or with LD-3D-CRT/IMRT+HDR-B. Between 12/1999 and 10/2010, 1343 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-3D-CRT or IMRT to the prostate in 38 fractions (group 1; 673 patients) or 46 Gy LD-3D-CRT or IMRT followed by 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 672 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 or more rectal toxicity. 86 pts of group 1 (12.8%) and 18 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 45 pts in group 1 (6.7%) and 9 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). With a mean follow-up of 102 months, the 10-year free-from-failure survival was 90.7% and 98.3% (p<0.002) in group 1 and 2 respectively; free-from-metastases survival 95.9% and 97.8% (p<0,006)for group 1 and 2 respectively; and cause-specific survival 97.1% and 98.2% (p<0.08). High-dose 3D-EBRT + HDR brachytherapy was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal complications were significantly reduced with the combined treatment, compared with what was observed with high-dose conventional, 3D-conformal radiotherapy. Control rates were significantly better with in the HDR-boosted patients as expected by higher effective-dose.

Estimation of late rectal normal tissue complication probability parameters in carbon ion therapy for prostate cancer

PurposeThe aim of this study was to estimate normal tissue complication probability (NTCP) parameters for late rectal complications after carbon ion radiotherapy (C-ion RT) for prostate cancer. Methods and materialsA total of 163 patients were used to derive NTCP parameters. These patients were treated with relative biological effectiveness (RBE)-weighted dose ranging from 57.6Gy (RBE) up to 72Gy (RBE) and included in dose escalation trials. The Lyman–Kutcher–Burman (LKB) model was used and the model parameters were fit to the relation between dose and complication observed after C-ion RT. ResultsThe resulting NTCP parameters were the volume effect parameter; n=0.035 (95% CI: 0.024–0.047), the steepness of the NTCP curve; m=0.10 (0.084–0.13), the tolerance dose associated with 50% probability of complication; TD50=63.6Gy (RBE) (61.8–65.4Gy (RBE)) for Grade⩾1, n=0.012 (0.0050–0.023), m=0.046 (0.033–0.062), TD50=69.1Gy (RBE) (67.6–70.9Gy (RBE)) for Grade⩾2. ConclusionA new set of rectal NTCP parameters in C-ion RT was determined. The rather small n values suggest that the rectum was consistent with being strictly serial organ. The new derived parameter values facilitate estimation of rectal NTCP in C-ion RT.

SU‐E‐T‐803: Verification of QUANTEC Lyman Kutcher Burman (LKB) Model for Grade&gt;=2(2+) Late Rectal Complication Rates Using a Database of 79 Prostate Patients Treated with IMRT

Purpose:QUANTEC review of best parameters for the LKB NTCP model of rectal complications is based exclusively on datasets obtained with 3D conformal techniques. The report suggests that inherent differences in rectal dose distributions obtained with IMRT techniques could require modification of the parameters which provide the best fit to clinical data.Methods:We compiled a database of 79 prostate patients who were treated with an IMRT technique to a dose of 77.4 Gy, 1.8Gy/fx, with an integrated boost to 81–83Gy in a sub‐volume of a prostate which was identified on a pre‐treatment MRI study. Rectal toxicities were graded according to CTCAE v4 by a physician who retrospectively reviewed patient's medical records. Late grade 2+ toxicities were defined as toxicities occurring later than 90 days following the end of treatment. We defined the model in terms of parameters, m,n and TD_50, as recommended in the Quantec report. We converted the dose to 2Gy equivalent dose using linear‐quadratic model with alpha over beta of 3Gy. We applied QUANTEC model to our data and compared results to our own fit of LKB model using two sample t‐test.Results:Grade 2+ late rectal toxicity occurred in 4% (3/79 patients). The best fit of LKB model to data was obtained for n = 0.26, m = 0.25, and TD_50 = 81.53Gy. The two sample t‐test yielded p value of 0.67. Average NTCP predicted by our parametrization is 3.8% while average NTCP predicted by QUANTEC parametrization is 3.5%.Conclusion:Predictions of late rectal toxicities in IMRT patients using LKB model with parameters from QUANTEC report match observed toxicity rates. Independent fit of LKB model to IMRT data produces somewhat different parameter set, but two parametrizations are equivalent within statistical uncertainties.