Late Gastrointestinal Complications Research Articles

Late gastroenterological complications in children after allogeneic hematopoietic stem cell transplantation: A retrospective cohort study and a case series of children treated with Kampo medicines

AbstractAimThis study aimed to describe children developing late gastrointestinal (GI) complications after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), focusing on Kampo medicine.MethodsAt the Nagoya University Hospital Department of Pediatrics, 179 consecutive patients underwent allo‐HSCT over five years, of whom 167 achieved engraftment and survived at least 100 days post transplant and therefore were included in the study.ResultsThirteen patients (7.8%) developed late GI symptoms. Among these, three had upper GI symptoms, three had lower GI symptoms, while seven had upper/lower GI symptoms. Total parenteral nutrition was administered in 10 (77%) patients for a median of 81 days (range: 20–303). Four (31%) had histologically proven graft‐versus‐host‐disease (GVHD), two (15%) had adverse drug reactions, and one (8%) had a viral infection. All three patients with lower GI symptoms responded to Kampo formulas' warming interior [TM1]. Two patients with upper GI symptoms had epigastric rigidity and responded to Aurantii Fructus Immaturus‐based formulas. One patient developed severe cachexia, which was successfully reversed with Kampo medicines. There were no adverse effects due to Kampo medicines.ConclusionsLate GI complications may be a burden on children after allo‐HSCT. Kampo medicines may provide a safe and promising therapy to resolve GI symptoms not otherwise specified.

MP48-09 TOXICITY PROFILE OF IMMEDIATE POST-PROSTATECTOMY RADIATION THERAPY: RESULTS FROM A LARGE MULTI-INSTITUTIONAL SERIES

MP48-09 TOXICITY PROFILE OF IMMEDIATE POST-PROSTATECTOMY RADIATION THERAPY: RESULTS FROM A LARGE MULTI-INSTITUTIONAL SERIES

Association of Incidence of Acid-related Upper Gastrointestinal Disorders With Glycated Hemoglobin Level.

Previous cross-sectional studies show diabetes and higher levels of plasma hemoglobin A1c (HbA1c) are associated with a higher prevalence of gastrointestinal (GI) complications. However, whether the glycemic status is associated with incident acid-related upper GI disorders remains unclear. We aimed to determine the effect of hyperglycemia per se, in terms of HbA1c, on the incidence of acid-related disorders. We analyzed consecutive subjects who had undergone repeated upper endoscopies as part of the health examinations at the National Taiwan University Hospital from 2005 to 2011. Acid-related endoscopic abnormalities were defined as erosive esophagitis (EE), Barrett's esophagus (BE), and peptic ulcer disease (PUD), which included gastric ulcers (GUs) and duodenal ulcers (DUs). All subjects were categorized by 3 tertiles of HbA1c levels. We analyzed the occurrence of respective acid-related disorders during the follow-up period. A total of 11 391 participants (mean HbA1c level 5.6 ± 0.7%) were enrolled in this longitudinal study. During the 38 426.3 person-years of follow-up (mean duration 3.37 ± 1.59 years), the incidence of EE, BE, GU, DU, PUD, and any acid-related disorders were 22.1%, 0.5%, 4.5%, 8.6%, 12.3%, and 30.3%, respectively. The higher HbA1c level was associated with higher risk of disease incidents, except BE, during the follow-up (all log-rank P < .001). In the Cox regression analyses with confounding factors fully adjusted, the hazard ratios for EE, GU, DU, PUD, and acid-related disorders were 1.174, 1.339, 1.24, 1.24, and 1.186, respectively, for the third tertile of HbA1c (all P < .05). Higher HbA1c level was associated with a higher risk of acid-related upper GI endoscopic abnormalities. Efforts toward better glycemic control may help to prevent the development of late GI complications.

Dosimetric Predictors of Toxicity in Patients With Early-Stage Prostate Cancer Treated With Moderately Hypofractionated IMRT or PBT: A Multi-Institutional Analysis

<h3>Purpose/Objective(s)</h3> Limited published data address modifiable risk factors for significant toxicity complicating moderately hypofractionated schedules of intensity-modulated radiation therapy (IMRT) and proton-beam therapy (PBT) in patients with early-stage prostate cancer (PC). This study explored dosimetric predictors of Grade 3+ gastrointestinal (GI) and genitourinary (GU) toxicity following IMRT or PBT in this patient population. <h3>Materials/Methods</h3> The study population included patients from five tertiary referral centers treated from 2002-2018 for low- or intermediate-risk biopsy-proven prostate adenocarcinoma. All patients were treated with moderately hypofractionated radiation defined as 250–300 cGY per daily fraction given over 4-6 weeks. Primary outcomes were late GI and GU toxicity as defined by CTCAE v4.0. Dosimetric variables included PTV max dose, PTV volume, bladder V31 Gy, bladder V50 Gy, bladder V70 Gy, bladder max dose, rectum V31 Gy, rectum V50 Gy, rectum V70 Gy, rectum max dose, penile bulb V10 Gy, penile bulb V15 Gy, and the left and right femoral head V40 Gy. The association of dosimetric variables with treatment toxicity was assessed with the Wilcoxon signed-rank test. <h3>Results</h3> Dosimetric data were obtained for 1139 patients, including 667 treated with IMRT and 472 treated with PBT. Median follow-up for the two groups was 46.0 and 48.5 months, respectively. Late toxicity rates for the total population were 4.7% for Grade 3+ GU toxicity and 1.5% for Grade 3+ GI toxicity. Grade 3+ GU toxicity was associated with prostate volume, bladder V31 Gy and bladder V50 Gy (<i>P</i> = 0.016, <i>P</i> = 0.018, <i>P</i> = 0.028), but not with bladder V70 Gy or maximum dose to the bladder. Grade 3+ GI toxicity was not associated with any of the dosimetric variables. When analyzed by treatment group, Grade 3+ GU toxicity was observed in 3% of the IMRT cohort and 1.7% of the PBT cohort. Grade 3+ GI toxicity was seen only in PBT and was observed in 1.5% of patients. Proton plans were associated with less radiation exposure of rectum and bladder at lower doses (rectum V31 Gy: 13% vs 16%, <i>P</i> < 0.001; bladder V31 Gy: 18% vs 26%, <i>P</i> < 0.001), while IMRT was associated with less radiation exposure of rectum and bladder at higher doses (rectum V70 Gy: 0.4% vs 2%, <i>P</i> < 0.001; bladder V70 Gy: 1% vs 3%, <i>P</i> < 0.001). Photon plans yielded superior V40 Gy to the femoral heads, and superior V10 Gy and V15 Gy to the penile bulb (<i>P</i> < 0.001, <i>P</i> < 0.003, <i>P</i> < 0.002). <h3>Conclusion</h3> In this multi-institutional analysis of 1139 early-stage PC patients treated with moderately hypofractionated IMRT or PBT, risk of serious late GU and GI complications was low for both treatment groups. Analysis of the dosimetric variables identified an association of Grade 3+ GU toxicity with low-dose radiation exposure of the bladder. Grade 3+ GI toxicity was unrelated to dosimetric variables. PBT plans yielded less exposure of non-target organs to lower-dose radiation while IMRT plans yielded less exposure of non-target organs to higher-dose radiation.

Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy

Background We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). Material and methods The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS). Results Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade ≥2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, p=.004). However, no significant difference grade ≥2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; p=.15). Acute grade ≥2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade ≥2 GI toxicity. Estimated 3-year late grade ≥3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (p= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis. Conclusion In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.

Five-year results of combined radiation therapy for high-risk prostate cancer

The purpose of the study is to assess the effectiveness and toxicity of the treatment of prostate cancer (PCa) with combined radiation therapy (CRT), where high dose rate brachytherapy (HDR-BT) "boost".&#x0D; Materials and methods: CRT was carried out in 98 patients of high-risk and extremely high-risk PCa. External part of treatment (conformal external radiation therapy) provided total dose 46-50 Gy with a single focal dose (SFD) 2 Gy to the prostate gland (PG), seminal vesicles and regional lymphatic zones. Two regimes of "boost" to the PG and seminal vesicles were used: in the first group – two fractions of 10 Gy (81 patients), in the second - 15 Gy (17 patients).&#x0D; Results: median follow-up equals: I group - 57.5 months, II group - 55.2. Three- and five-year survival without biochemical progression in group I - 75.4% and 69.0%, II group - 76.4% and 52.9%, respectively. Similar indicators regardless of the CRT regime in groups of different risk of relapse were equal: high risk - 84.6% and 75.9%, extremely high risk - 69.4% and 60.7%, respectively (p=0.05).&#x0D; There were no late radiation genitourinary and gastrointestinal complications of 4-5 degrees. The most significant variants of late disorders were the formation of urethra stricture (one patient of the I group) and stenosis of the rectum (one patient of the II group). Late genitourinary radiation toxicity (L-GURT) was mainly represented by changes that can be characterized as 1 degree (RTOG/CTCAE): I group - from 40.6% to 53.2%, II - 18.8% to 35.3%.&#x0D; Conclusions: the studied CRT regimes showed perfectly acceptable survival rates with no signs of biochemical progression and radiation toxicity during the five-year period of follow-up.

Hypofractionated sequential radiotherapy boost: a promising strategy in inoperable locally advanced pancreatic cancer patients.

To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints. Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up. Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20Gy in 5 fr (N: 6; 19.4%), 20Gy in 4 fr (N: 5; 16.2%), 25Gy in 5 fr (N: 18; 58.0%) and 30Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19months (range 1-156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28months; range 2-139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18months (range 1-139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%. Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages.

Postoperative pelvic intensity-modulated radiation therapy reduced the incidence of late gastrointestinal complications for uterine cervical cancer patients.

The aim of the study was to compare incidences of late gastrointestinal adverse events and clinical outcomes between 3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) after radical hysterectomy for cervical cancer patients. Between March 2007 and May 2014, 73 cervical cancer patients with high-risk prognostic factors (pelvic lymph node metastasis and/or parametrial invasion) underwent postoperative pelvic radiation therapy (RT) after radical hysterectomy. Of these patients, 33 (45%) and 40 (55%) received 3DCRT and IMRT, respectively. Because the gastrointestinal obstruction rate after postoperative pelvic 3DCRT was high, no concurrent chemotherapy was applied until 2015. The median follow-up period for patients with 3DCRT and IMRT was 82 months (6–113) and 50 months (5–74), respectively. There was no significant difference in overall survival (OS) (4-year OS: 85% vs 78%, P = 0.744) or disease-free survival (DFS) (4-year DFS: 73% vs 64%, P = 0.696) between the two groups. Eleven (33%) and 13 (33%) patients experienced recurrence after 3DCRT and IMRT, respectively. The patients who had vaginal invasion from the postoperative pathological finding more frequently had loco-regional recurrence than the patients who did not have vaginal invasion (2.3% vs 17%, P = 0.033). Gastrointestinal obstruction was observed in 9 (27%) and 3 (7.5%) patients for 3DCRT and for IMRT, respectively (P = 0.026). Severe gastrointestinal obstruction that required surgery was observed in 6 (19%) patients, all of whom received adjuvant RT by 3DCRT. IMRT could reduce the incidence of late severe gastrointestinal obstruction after postoperative pelvic RT with a non-inferior clinical efficacy compared with 3DCRT.

Dose escalation (81 Gy) with image-guided radiation therapy and volumetric-modulated arc therapy for localized prostate cancer: A retrospective preliminary result.

Objectives:The objective of the study is to report the acute and late toxicity and preliminary results of localized prostate cancer treated with high-dose radiation therapy (RT).Materials and Methods:Between March 2010 and October 2018, a total of 53 patients with clinically localized prostate cancer were treated with definitive RT at our institution. All patients were planned to receive a total dose of 81 Gy with the volumetric-modulated arc therapy technique. Patients were stratified by prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. The definition of biochemical failure was using the 2005 ASTRO Phoenix consensus definition. Median follow-up time was 46.5 months (range: 4.7–81.0 months).Results:The 3-year biochemical failure-free survival rates for low-, intermediate-, and high-risk group patients were 100%, 87.5%, and 84%, respectively. The 3- and 5-year overall survival rates were 83% and 62%, respectively. Three (5.6%) patients developed Grade II acute gastrointestinal (GI) toxicity. Four (7.5%) patients developed Grade II acute genitourinary (GU) toxicity, and none experienced Grade III or higher acute GI or GU symptoms. One (1.8%) patient developed Grade II or higher late GI toxicity. Six (11.3%) patients experienced Grade II late GU toxicity. No Grade III or higher late GI and GU complications have been observed.Conclusions:Data from the current study demonstrated the feasibility of dose escalation with image-guided and volumetric-modulated arc therapy techniques for the treatment of localized prostate cancer. Minimal acute and late toxicities were observed from patients in this study. Long-term prostate-specific antigen controls are comparable to previously published results of high-dose intensity-modulated RT for localized prostate cancer. Based on this favorable outcome, dose escalation (81 Gy) has become the standard treatment for localized prostate cancer at our institution.

Desmoplastic Small Round Cell Tumor: Long-Term Complications After Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT. A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed. Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2). Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.

Salvage High-Dose Rate (HDR) Brachytherapy as a Treatment for Locally Recurrent Prostate Cancer after Primary Radiation Therapy

Salvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer following definitive radiotherapy. We report the tumor control and toxicity outcomes from using high-dose rate (HDR) brachytherapy (BT) alone for local salvage. Between 2013 and 2017, thirty-two patients with biopsy-proven (n = 23) or radiologically-evident (n = 9) locally recurrent prostate cancer were treated with salvage HDR brachytherapy. Dose-fractionation schedules included: 19Gy single fraction (n = 24), 15Gy single fraction (n = 5), 26Gy in two fractions (n = 2) and 31.5Gy in three fractions (n = 1). Three patients received treatment to the whole gland; the remaining 29 received focal therapy mapped according to combined pelvic magnetic resonance (MR) imaging and template biopsy findings (n = 21) or MR imaging alone (n = 8). The median time from completion of primary treatment to salvage HDR BT was 57 months. Seventeen patients received androgen deprivation therapy (ADT) as part of their primary treatment. In all cases, ADT had been discontinued prior to salvage HDR BT and was not re-commenced following the procedure. Biochemical progression-free survival (bPFS) using the Kaplan-Meier method was defined according to the Phoenix standard of nadir prostate-specific antigen (PSA) plus ≥2mg/ml. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Late toxicity was defined as that occurring ≥90 days after completion of salvage brachytherapy. Median follow-up after salvage HDR brachytherapy was 24 months. Median PSA nadir value was 0.8 reached at a median of 5 months from day of implant. The 2-year biochemical progression-free survival rate was 60.0%. The 2-year local relapse rate was 9.3% with 8 out of the 11 recurrences occurring at distant sites. Acute and late GU and GI toxicities are shown in Table 1. Two patients developed late grade 3 urinary toxicity, both urethral strictures requiring surgical correction. No late GI complications of grade 2 or higher were encountered with no reports of rectal fistulae or requirement for defunctioning colostomy.Abstract SU_28_2277; Table 1Number of patients presenting with acute (<90 days) and late (≥90 days) genitourinary and gastrointestinal toxicities following salvage high-dose rate brachytherapyToxicityACUTELATEGenitourinarynnGrade 1/22219Grade 302Grade 400GastrointestinalGrade 1/241Grade 300Grade 400 Open table in a new tab High-dose rate brachytherapy is an effective modality for the salvage treatment of locally recurrent prostate cancer with very good local control rates and an acceptable long-term toxicity profile. The high rate of distant relapse underscores the current challenge of accurate staging of systemic disease and appropriate patient selection in the salvage setting. The use of more sensitive imaging modalities such as PSMA-PET may improve this in the future.

Late Gastrointestinal Complications of Allogeneic Hematopoietic Stem Cell Transplantation in Adults

Gastrointestinal (GI) complications including graft-versus-host disease (GVHD) are a major cause of morbidity and mortality in allogenic stem transplant recipients. Although several studies have previously looked into the acute GI complications, fewer smaller studies have reported late complications. In this large study we focus on the late (100 days post-transplant) GI complications in allogenic stem transplant recipients. In this single-center, retrospective study of all adult allogenic stem cell transplant recipients who had their transplant at Duke University over a 6-year period, 479 patients underwent allogenic stem cell transplant, of whom 392 recipients survived for at least 100 days post-transplant. Late GI symptoms were noted in 71 patients, prompting endoscopic evaluation. The primary endpoint of our study was the diagnosis of GI-GVHD based on endoscopic findings, whereas overall survival and nonrelapse mortality were the secondary endpoints. Of the 71 patients who underwent endoscopy, 45 (63%) had GI-GVHD. Of these 45 patients, 39 (87%) had late acute GVHD, 1 (2%) had chronic GVHD, and 5 patients (11%) had overlap disease. Of the patients who did not have GVHD, the symptoms were mostly related to infectious and inflammatory causes. Less common causes included drug toxicity, food intolerance, disease relapse, and motility issues. In a multivariate analysis the factors most indicative of GI-GVHD were histologic findings of apoptosis on the tissue specimen (odds ratio, 2.35; 95% confidence interval, 1.18 to 4.70; P = .015) and clinical findings of diarrhea (odds ratio, 5.43; 95% confidence interval, 1.25 to 23.54; P = .024). The median survival time from the first endoscopy was 8.5 months. The incidence of nonrelapse mortality at 6 months was 31% in patients with GI-GVHD and 19% in patients without GI-GVHD (P = .42). All patients with GI-GVHD were on steroid therapy, and 31% of them received total parenteral nutrition. In our population close to one-fifth of allogenic transplant recipients experienced late GI complications, warranting endoscopic evaluation. Most of these patients were found to have GI-GVHD that had a high incidence of nonrelapse mortality at 6 months and close to one-third of these patients needed total parenteral nutrition.

Spatial features of dose–surface maps from deformably-registered plans correlate with late gastrointestinal complications

This study investigates the associations between spatial distribution of dose to the rectal surface and observed gastrointestinal toxicities after deformably registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for 118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction were 3D-summed. Rectum dose–surface maps (DSMs) were obtained by virtually unfolding the rectum surface slice-by-slice. Associations with late peak gastrointestinal toxicities were investigated using voxel-wise DSM analysis as well as parameterised spatial patterns. The latter were obtained by thresholding DSMs from 1–80 Gy (increment = 1) and extracting inferior–superior extent, left–right extent, area, perimeter, compactness, circularity and ellipse fit parameters. Logistic regressions and Mann–Whitney U-tests were used to correlate features with toxicities. Rectal bleeding, stool frequency, diarrhoea and urgency/tenesmus were associated with greater lateral and/or longitudinal spread of the high doses near the anterior rectal surface. Rectal bleeding and stool frequency were also influenced by greater low-intermediate doses to the most inferior 20% of the rectum and greater low-intermediate-high doses to 40–80% of the rectum length respectively. Greater low-intermediate doses to the superior 20% and inferior 20% of the rectum length were associated with anorectal pain and urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and proctitis were also related to greater low doses to the posterior side of the rectum. Spatial features for the intermediate-high dose regions such as area, perimeter, compactness, circularity, ellipse eccentricity and confinement to ellipse fits were strongly associated with toxicities other than anorectal pain. Consequently, toxicity is related to the shape of isodoses as well as dose coverage. The findings indicate spatial constraints on doses to certain sections of the rectum may be important for reducing toxicities and optimising dose.

PD72-10 ASSESSING THE RISK OF EARLY AND LATE TOXICITY OF POST-PROSTATECTOMY RADIATION THERAPY: A LONG-TERM MULTI-INSTITUTIONAL ANALYSIS

PD72-10 ASSESSING THE RISK OF EARLY AND LATE TOXICITY OF POST-PROSTATECTOMY RADIATION THERAPY: A LONG-TERM MULTI-INSTITUTIONAL ANALYSIS

PD36-12 COMPARING COMPLICATIONS AND SURVIVAL OF PRIMARY CYSTECTOMY VS. SALAVAGE CYSTECTOMY AFTER TRIMODAL THERAPY

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2017PD36-12 COMPARING COMPLICATIONS AND SURVIVAL OF PRIMARY CYSTECTOMY VS. SALAVAGE CYSTECTOMY AFTER TRIMODAL THERAPY Matthew Mossanen, Ross E. Krasnow, Alberto C. Pieretti, Adam S. Feldman, Jason A. Efstathiou, Michael L. Blute, Niall M. Heney, and Matthew F. Wszolek Matthew MossanenMatthew Mossanen More articles by this author , Ross E. KrasnowRoss E. Krasnow More articles by this author , Alberto C. PierettiAlberto C. Pieretti More articles by this author , Adam S. FeldmanAdam S. Feldman More articles by this author , Jason A. EfstathiouJason A. Efstathiou More articles by this author , Michael L. BluteMichael L. Blute More articles by this author , Niall M. HeneyNiall M. Heney More articles by this author , and Matthew F. WszolekMatthew F. Wszolek More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1561AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with advanced bladder cancer may receive radical cystectomy (RC) or Trimodal therapy (TMT) as treatment. After TMT, failure to respond to induction therapy or recurrence may be followed by salvage RC. We compare the timing and nature of complications, and overall survival between these two procedures at our institution. METHODS We retrospectively identified patients from our contemporary cohort spanning from 2002 to 2013 that underwent primary RC and 22 patients that underwent TMT followed by salvage RC for disease progression. Patients were limited to those with a diagnosis of bladder cancer without radiographic evidence of lymph node or distant metastasis. Early (≤90 day) complication rates were compared using Fisher′s exact test. Overall survival and late (>90 day) complications were compared using Kaplan Meier curves, and the log-rank test. RESULTS From 2003 to 2013 we identified 239 patients who underwent primary RC and 22 patients who underwent salvage RC. The median age of the cohort was 68, 76% were male and the median follow-up was 5 years. The groups had similar baseline characteristics, except that those that underwent salvage RC had higher rates of tobacco use (95% vs 68%, p=0.006), and were less likely have a neobladder (4.6% vs 8.8%, p=0.03). 43 patients (17%) that underwent primary cystectomy received neoadjuvant chemotherapy. There were no significant differences between salvage RC and primary RC in terms of overall survival (log-rank P=0.8) or disease specific survival (P=0.7). The overall early complication rate was 77% after salvage RC compared to 57% after primary RC (p=0.07). Early infectious complications were significantly higher after salvage (36% vs 11%, p=0.002). The 1-, 3-, and 5-yr overall late complications rate after salvage RC was 8.3%, 36%, and 68% compared to 5.8%, 14%, and 16% after primary RC (log-rank p=0.033, Figure 1), respectively. After salvage, there was an increased rate of late infectious (23% vs 7.5, p=0.03) and late gastrointestinal (27% vs 4.0%, p=<0.001) complications. CONCLUSIONS The overall survival, disease specific survival, and overall early complication rates are comparable between primary cystectomy and salvage cystectomy after TMT. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e673 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Matthew Mossanen More articles by this author Ross E. Krasnow More articles by this author Alberto C. Pieretti More articles by this author Adam S. Feldman More articles by this author Jason A. Efstathiou More articles by this author Michael L. Blute More articles by this author Niall M. Heney More articles by this author Matthew F. Wszolek More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications.

BackgroundDerivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment.MethodsOne hundred and eighteen patients received EBRT in 23 fractions of 2 Gy and HDR (TG43 algorithm) in 3 fractions of 6.5 Gy. Results for the Late Effects of Normal Tissues — Subjective, Objective, Management and Analytic toxicity assessments were available with a median follow-up of 72 months. The HDR CT was deformably-registered to the EBRT CT. Doses were corrected for dose fractionation. Rectum dose-volume histogram (DVH) parameters were calculated in two ways. (1) Distribution-adding: parameters were calculated after the EBRT dose distribution was 3D-summed with the registered HDR dose distribution. (2) Parameter-adding: the EBRT DVH parameters were added to HDR DVH parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate parameters with late peak toxicity (dichotomised at grade 1 or 2).ResultsThe 48–80, 40–63 and 49–55 Gy dose regions from distribution-adding were significantly correlated with rectal bleeding, urgency/tenesmus and stool frequency respectively. Additionally, urgency/tenesmus and anorectal pain were associated with the 25–26 Gy and 44–48 Gy dose regions from distribution-adding respectively. Parameter-adding also indicated the low-mid dose region was significantly correlated with stool frequency and proctitis.ConclusionsThis study confirms significant dose-histogram effects for gastrointestinal toxicities after including deformable registration to combine phases of EBRT/HDR prostate cancer treatment. The findings from distribution-adding were in most cases consistent with those from parameter-adding. The mid-high dose range and near maximum doses were important for rectal bleeding. The distribution-adding mid-high dose range was also important for stool frequency and urgency/tenesmus. We encourage additional studies in a variety of institutions using a variety of dose accumulation methods with appropriate inter-fraction motion management.Trial registrationNCT NCT00193856. Retrospectively registered 12 September 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-016-0719-2) contains supplementary material, which is available to authorized users.

Prediction of toxicities of prostate cancer radiotherapy.

We treated acohort of 116 patients with prostate cancer with three-dimensional conformal hypofractionated radiotherapy to atotal dose of 52.8 Gy in 16 fractions (3.3 Gy per fraction). The correlation between acute and late gastrointestinal (GI) and genitourinary (GU) toxicity and dose-volume parameters was analysed. Comparison of observed incidence of toxicity and normal tissue complication probability calculated from dose-volume histograms (DVH) of all patients using radiobiological Lyman-Kutcher-Burman model was performed. The results of our study suggest that acute gastrointestinal toxicity ≥ grade 2 (G2) is the significant predictor of late toxicity ≥ G2 (p=0.006). Observed incidence of acute and late GI toxicities ≥ G2 was 9.7% and 11.5%, respectively. NTCPs of acute and late GI complications ≥ G2 were 11.3% and 2.5%. Observed incidence of late GU toxicity ≥ G2 was 14.2%, NTCP was 0.8%. Comparison of calculated probability of acute GI toxicity ≥ G2 and observed incidence indicates that parameters of radiobiological models are set appropriately. Comparison of observed incidence of late GI and GU complications ≥ G2 and calculated NTCPs shows the need of refinement of LKB model parameters for acute and late GI and GU complications ≥ G2. prostate cancer, radiotherapy, acute and late toxicity, radiobiological modeling.

Prediction of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer.

BackgroundGastrointestinal (GI) toxicity is a common effect following radiation therapy (RT) for prostate cancer. Purpose of the present work is to compare two Normal Tissue Complication Probability (NTCP) modelling approaches for prediction of late radio-induced GI toxicity after prostate external beam radiotherapy.MethodsThe study includes 84 prostate cancer patients evaluated for late rectal toxicity after 3D conformal radiotherapy. Median age was 72 years (range 53-85). All patients received a total dose of 76 Gy to the prostate gland with daily fractions of 2 Gy. The acute and late radio-induced GI complications were classified according to the RTOG/EORTC scoring system. Rectum dose-volume histograms were extracted for Lyman-Kutcher-Burman (LKB) NTCP model fitting using Maximum Likelihood Estimation. The bootstrap method was employed to test the fit robustness. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive power of the LKB and to compare it with a multivariate logistic NTCP model previously determined.ResultsAt a median follow-up of 36 months, 42% (35/84) of patients experienced grade 1-2 (G1-2) acute GI events while 25% (21/84) of patients developed G1-2 late GI events. The best-estimate of fitting parameters for LKB NTCP model for mild\\moderate GI toxicity resulted to be: D50 = 87.3 Gy, m = 0.37 and n = 0.10. Bootstrap result showed that the parameter fit was robust. The AUC values for the LKB and for the multivariate logistic models were 0.60 and 0.75, respectively.ConclusionsWe derived the parameters of the LKB model for mild\\moderate GI toxicity prediction and we compared its performance with that of a data-driven multivariate model. Compared to LKB, the multivariate model confirmed a higher predictive power as showed by the AUC values.

Clinical outcome and bowel function after surgical treatment in Hirschsprung's disease.

Background:Bowel function has been reported to be adversely affected following surgery in cases of Hirschsprung. We retrospectively studied both the clinical outcome and bowel function status following surgery in patients diagnosed with Hirschprung's disease (HD). 161 cases, who underwent pull-through operations for HD in Sheikh Pediatric Tertiary Centre, Mashhad, Iran. The specified time bracket spanned between 2006 and 2011.Materials and Methods:Data was extracted from Health Information System with the aim of investigating patients for both short and long-term gastrointestinal (GI) complications after surgery bases in addition to the concurrence of any associated anomalies. Three main procedures were analysed in this respect (Swenson, Duhamel and Soave).Results:In a study of 96 (59%) boys and 65 (40.3%) girls, mortality rate was reported to be 15.5% (15 males and 10 females). A considerable majority of almost three fourths were detected with both early and late GI complications after surgery. The latter mainly included constipation (30.8%), incontinence (19.8%), enterocolitis (8%), diarrhea (11%) in a declining order of incidence. Down syndrome and others HD-associated anomalies were detected in 3.7% and 24.3% of cases respectively.Conclusions:Constipation and foecal incontinence were the most prevalent postoperative complications, which were reported almost as frequent in other studies. Yet, Enterocolitis, was reported slightly less in prevalence. Also mortality rates were considerably higher, compared to developed nations.

Ulcerating Ileocolitis in Severe Amatoxin Poisoning.

Amatoxin poisoning is still associated with a great potential for complications and a high mortality. While the occurrence of acute gastroenteritis within the first 24 hours after amatoxin ingestion is well described, only very few descriptions of late gastrointestinal complications of amatoxin poisoning exist worldwide. We present the case of a 57-year-old female patient with severe amatoxin poisoning causing fulminant but reversible hepatic failure that on day 8 after mushroom ingestion developed severe abdominal pain and watery diarrhea. Ulcerating ileocolitis was identified by computed tomography identifying a thickening of the bowel wall of the entire ileum and biopsies taken from the ileum and large bowel revealing distinct ileitis and proximally accentuated colitis. The absence of discernible alternative etiologies such as infectious agents makes a causal relationship between the ulcerating ileocolitis and the amatoxin poisoning likely. Diarrhea and varying abdominal pain persisted over several weeks and clinical follow-up after six months showed a completely symptom-free patient. The case presented highlights the importance to consider the possibility of rare complications of Amanita intoxication in order to be able to respond to them early and adequately.