Long-Term Evaluation of Ifosfamide-Related Nephrotoxicity in Children

2009 ◽  
Vol 27 (32) ◽  
pp. 5350-5355 ◽  
Author(s):  
Odile Oberlin ◽  
Oumaya Fawaz ◽  
Annie Rey ◽  
Patrick Niaudet ◽  
Vita Ridola ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Renal Toxicity ◽  
Moderate Dose ◽  
Median Dose ◽  
Glomerular Function ◽  
Term Evaluation ◽  
Grade 3 ◽  
Length Of Interval

PurposeIfosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors.Patients and MethodsOf the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system.ResultsThe median dose of ifosfamide was 54 g/m2(range, 18 to 117 g/m2). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR.ConclusionRenal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.

Long-term evaluation of ifosfamide-related nephrotoxicity in children: The French experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9551-9551
Author(s):  
O. Fawaz ◽  
A. Rey ◽  
P. Niaudet ◽  
D. Orbach ◽  
C. Bergeron ◽  
...  
Keyword(s):  
Renal Toxicity ◽  
Univariate Analysis ◽  
Multivariate Analyse ◽  
French Experience ◽  
Term Evaluation ◽  
Tubular Toxicity ◽  
Grade 3 ◽  
Median Interval

9551 Background: Ifosfamide-induced nephrotoxicity is a significant issue in patients treated for tumours during childhood. This study aimed at documenting incidence of late renal toxicity of ifosfamide and its risk factors. Methods: 183 patients have been investigated. 100 were male. Median age at treatment was 9.3 years (0.4–18 years). Median dose of ifosfamide was 54 g/m2 (18–77 g/m2). No patients received cisplatin and/or carboplatinum. Diagnoses included rhabdomyosarcoma (77), other soft tissue sarcoma (39), Ewing (39), and osteosarcoma (28). Investigations were performed at a median interval of 10.3 years (5–20.7) after the end of the treatment, at a median age of 21.6 years (7.1–44.2). No patient had electrolyte or vitamine supplementation. Glomerular and tubular functions were graded according to the Skinner's system. Results: After 5 year minimal follow-up 55% had normal tubular and 79% had normal glomerular functions. Natraemia, kalaemia, serum HCO3 and calcaemia were normal in all patients. Hypomagnesaemia was observed in 4, hypophosphaetemia in 8 %. The tubular threshold for phosphate was reduced in 44% of the patients (grade 2 or 3 in 15%, grade 3 in 1 pt). Significant glycosuria (> 0.5 g/24h) was detected in 5 % of the patients but it was clearly abnormal only in 5 patients. 34% of the patients had beta2 microglobulinuria, however, proteinuria was observed in only 12%. Cumulative dose of ifosfamide, older age at treatment and follow-up since treatment were predictor for tubulopathy in univariate and multivariate analyse. The glomerular filtration rate was normal in 79% of the patients. 21% had a grade 1 toxicity and 1 patient a grade 2. Univariate analysis did not find any prognostic factor for glomerular toxicity apart from the association with tubular toxicity. Conclusions: Since ifosfamide-induced renal toxicity can be severe, long term evaluation is important and this risk should be balanced carefully against efficacy. No significant financial relationships to disclose.

scholarly journals Postoperative or Salvage Proton Radiotherapy for Prostate Cancer After Radical Prostatectomy

2021 ◽  
Author(s):  
Shivam M. Kharod ◽  
Catherine E. Mercado ◽  
Christopher G. Morris ◽  
Curtis M. Bryant ◽  
Nancy P. Mendenhall ◽  
...  
Keyword(s):  
Proton Therapy ◽  
Median Dose ◽  
Scattered Proton ◽  
Prostate Bed ◽  
Genitourinary Toxicity ◽  
Patient Reported ◽  
Grade 3

Abstract Purpose Postprostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality of life with proton therapy. Method and Materials The first 102 patients who were enrolled on an outcome tracking protocol between 2006 and 2017 and treated with double-scattered proton therapy after prostatectomy were retrospectively reviewed. Eleven (11%) received adjuvant radiation, while 91 (89%) received salvage radiation. Seventy-four received double-scattered proton therapy to the prostate bed only. Twenty-eight received a double-scattered proton therapy prostate-bed boost after prostate-bed and pelvic-node treatment. Eleven adjuvant patients received a median dose of 66.6 GyRBE (range, 66.0-70.2). Ninety-one salvage patients received a median dose of 70.2 GyRBE (range, 66.0-78.0). Forty-five patients received androgen deprivation therapy for a median 9 months (range, 1-30). Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0 criteria, and patient-reported quality-of-life data were reviewed. Results The median follow-up was 5.5 years (range, 0.8-11.4 years). Five-year biochemical relapse-free and distant metastases-free survival rates were 72% and 91% for adjuvant patients, 57% and 97% for salvage patients, and 57% and 97% overall. Acute and late grade 3 or higher genitourinary toxicity rates were 1% and 7%. No patients had grade 3 or higher gastrointestinal toxicity. Acute and late grade 2 gastrointestinal toxicities were 5% and 2%. The mean values and SDs of the International Prostate Symptom Score, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 7.5 (SD = 5.9), 10.2 (SD = 8.3), 92.8 (SD = 11.1), and 91.2 (SD = 6.4), respectively, at baseline, and 12.1 (SD = 9.1), 10.1 (SD = 6.7), 87.3 (SD = 18), and 86.7 (SD = 13.8) at the 5-year follow-up. Conclusion High-dose postprostatectomy proton therapy provides effective long-term biochemical control and freedom from metastasis, with low acute and long-term gastrointestinal and genitourinary toxicity.

scholarly journals 439 Conservative Versus Surgical Management of Complicated Diverticulitis - A Retrospective Study of Long-Term Outcomes

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
E Durity ◽  
G Elliott ◽  
T Gana
Keyword(s):  
Complicated Diverticulitis ◽  
Complication Rates ◽  
Long Term Outcomes ◽  
Female Ratio ◽  
Stoma Reversal ◽  
Group A ◽  
Grade 3 ◽  
Group B

Abstract Introduction Management of complicated diverticulitis has shifted towards a conservative approach over time. This study evaluates the feasibility and long-term outcomes of conservative management. Method We retrospectively evaluated a consecutive series of patients managed with perforated colonic diverticulitis from 2013-2017. Results Seventy-three (73) patients were included with a male to female ratio of 1:2. Thirty-one (31) underwent Hartmann’s procedure (Group A) and 42 patients were managed with antibiotics +/- radiological drainage (Group B). Mean follow-up was 64.9 months (range 3-7 years). CT Grade 3 and 4 disease was observed in 64.5% and 40.4% of Group A and Group B patients, respectively. During follow-up, 9 (21.4%) Group B patients required Hartmann’s. Group A had longer median length of stay compared to Group B (25.1 vs 9.2 days). Post-operative complications occurred in 80.6% with 40% being Clavien-Dindo grade III or higher in group A. Stoma reversal was performed in 8 patients (25.8%). Conclusions In carefully selected cases, complicated diverticulitis including CT grade 3 and 4 disease, can be managed conservatively with acceptable recurrence rates (16.7% at 30 days, 4.8% at 90 days, 19.0% at 5 years). Surgical intervention on the other hand, carries high post-operative complication rates and low stoma reversal rates.

scholarly journals Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuhei Miyasaka ◽  
Hidemasa Kawamura ◽  
Hiro Sato ◽  
Nobuteru Kubo ◽  
Tatsuji Mizukami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Therapeutic Benefit ◽  
Carbon Ion Radiotherapy ◽  
Safety And Efficacy ◽  
Carbon Ion ◽  
Grade 3 ◽  
Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

scholarly journals A 16-year prospective cohort study to evaluate effects of long-term fluctuations in obesity indices of prediabetics on the incidence of future diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shahla Safari ◽  
Maryam Abdoli ◽  
Masoud Amini ◽  
Ashraf Aminorroaya ◽  
Awat Feizi
Keyword(s):  
High Risk ◽  
Transition Probabilities ◽  
Clinical Settings ◽  
High Tendency ◽  
Mean Values ◽  
Latent Markov Model ◽  
Term Evaluation ◽  
Obesity Indices

AbstractThis study aimed to evaluate the patterns of changes in obesity indices over time in prediabetic subjects and to classify these subjects as either having a low, moderate, and high risk for developing diabetes in the future. This study was conducted among 1228 prediabetics. The patterns of changes in obesity indices based on three measurements including first, mean values during the follow-up period, and last visit from these indices were evaluated by using the latent Markov model (LMM). The mean (standard deviation) age of subjects was 44.0 (6.8) years and 73.6% of them were female. LMM identified three latent states of subjects in terms of change in all anthropometric indices: a low, moderate, and high tendency to progress diabetes with the state sizes (29%, 45%, and 26%), respectively. LMM showed that the probability of transitioning from a low to a moderate tendency to progress diabetes was higher than the other transition probabilities. Based on a long-term evaluation of patterns of changes in obesity indices, our results reemphasized the values of all five obesity indices in clinical settings for identifying high-risk prediabetic subjects for developing diabetes in future and the need for more effective obesity prevention strategies.

scholarly journals Slowly resorbable biosynthetic mesh: 2-year results in VHWG grade 3 hernia repair

Hernia ◽  
2021 ◽  
Author(s):  
M. M. J. Van Rooijen ◽  
T. Tollens ◽  
L. N. Jørgensen ◽  
T. S. de Vries Reilingh ◽  
G. Piessen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hernia Repair ◽  
Hernia Recurrence ◽  
Recurrence Rates ◽  
Elective Repair ◽  
Significant Difference ◽  
Grade 3

Abstract Introduction Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months. Methods A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm2, scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months. Results Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery. Conclusion After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations. Trial registration Registered on clinicaltrials.gov (NCT02720042), March 25, 2016.

Long-Term Evaluation of the Roux-Elmslie-Trillat Procedure for Patellar Instability

2005 ◽  
Vol 33 (8) ◽  
pp. 1220-1223 ◽  
Author(s):  
Joseph R. Carney ◽  
Timothy S. Mologne ◽  
Michael Muldoon ◽  
Jay S. Cox
Keyword(s):  
Confidence Interval ◽  
Case Series ◽  
Level Of Evidence ◽  
Long Term Effect ◽  
Functional Scores ◽  
Study Population ◽  
Term Evaluation ◽  
Subluxation Of The Patella

Background Few published articles exist reporting the long-term evaluation of the Roux-Elmslie-Trillat procedure. Purpose To assess the long-term effect of the Roux-Elmslie-Trillat procedure in preventing recurrent subluxation and dislocation of the patella. Study Design Case series; Level of evidence, 4. Methods Eighteen patients who underwent the Roux-Elmslie-Trillat procedure for dislocation or subluxation of the patella were identified from a group previously evaluated at a mean follow-up of 3 years. The prevalence of recurrent subluxation or dislocation at a mean follow-up of 26 years was compared with the prevalence reported at the mean follow-up of 3 years. Although not the focus of this study, Cox functional scores were obtained from the smaller group and compared with the results at the 3-year follow-up. Results Seven percent (95% confidence interval, 0.00-0.32) of the patients had recurrent subluxation at 26 years compared with 7% (95% confidence interval, 0.03-0.13) of the study population reported at 3 years (P = 1.00). Fifty-four percent (95% confidence interval, 0.27-0.79) rated their affected knee as good or excellent at 26 years compared with 73% (95% confidence interval, 0.64-0.81) of the larger study population reported at 3 years (P = .14). Conclusion The prevalence of recurrent subluxation and dislocation in patients with patellofemoral malalignment who underwent the Roux-Elmslie-Trillat procedure for dislocation or subluxation of the patella is similar at 3 and 26 years after the procedure. The long-term functional status of the affected knee in patients who underwent the Roux-Elmslie-Trillat procedure declined.

Long-term hematologic toxicity of 177Lu-octreotate-capecitabine-temozolomide therapy of GEPNET

2021 ◽  
Author(s):  
Murali Kesavan ◽  
Piyush Grover ◽  
Wei-Sen Lam ◽  
Phillip G Claringbold ◽  
J. Harvey Turner
Keyword(s):  
Cumulative Incidence ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Baseline Risk ◽  
Hematologic Toxicity ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Prospective Phase ◽  
Grade 3

Thirty-seven patients with advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) were treated on a prospective phase II single-center study with 4 cycles of 7.8 GBq 177Lu-octreotate combined with capecitabine and temozolomide chemotherapy (CAPTEM). Each 8-week cycle combined radiopeptide therapy with 14 days of capecitabine (1500 mg/m2) and 5 days of temozolomide (200 mg/m2). The incidence of grade ≥3 hematologic toxicity was analysed. We found that at a median follow-up of 7-years (range 1-10), 6 (16%) patients developed persistent hematologic toxicity (PHT, defined as sustained grade ≥3 hematologic toxicity beyond 36-months follow up) and 3 (8%) developed MDS/AL with a median time-to-event of 46 and 34-months respectively. Estimated cumulative incidence of MDS/AL was 11% (95% CI: 3.45 to 24.01). Development of PHT was the only significant risk factor for secondary (RR, 16; 95% CI: 2.53 to 99.55; p<0.001). The median PFS was 48 months (95% CI: 40.80-55.20) and median OS was 86 months (95% CI: 56.90-115.13). 21 deaths were recorded, including 13 (62%) due to progressive disease and all 3 (14%) patients with MDS/AL. We conclude that 177Lu-octreotate CAPTEM therapy for GEPNETs is associated with a risk of long-term hematologic toxicity. The rising cumulative incidence of MDS/AL >10% mandates for the long-term monitoring of treated patients. However, time to onset is unpredictable and incidence does not correlate with conventional baseline risk factors. Novel methods are required for stratification of prospective patients based on genetic risk.

scholarly journals Long-term outcomes of pediatric arteriovenous malformations: the 30-year Pittsburgh experience

2020 ◽  
Vol 26 (3) ◽  
pp. 275-282
Author(s):  
Michael M. McDowell ◽  
Nitin Agarwal ◽  
Gordon Mao ◽  
Stephen Johnson ◽  
Hideyuki Kano ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Arteriovenous Malformations ◽  
Multimodality Treatment ◽  
Treatment Choice ◽  
University Of Pittsburgh ◽  
Poor Outcome ◽  
Poor Outcomes ◽  
The University

OBJECTIVEThe study of pediatric arteriovenous malformations (pAVMs) is complicated by the rarity of the entity. Treatment choice has often been affected by the availability of different modalities and the experience of the providers present. The University of Pittsburgh experience of multimodality treatment of pAVMs is presented.METHODSThe authors conducted a retrospective cohort study examining 212 patients with pAVM presenting to the University of Pittsburgh between 1988 and 2018, during which patients had access to surgical, endovascular, and radiosurgical options. Univariate analysis was performed comparing good and poor outcomes. A poor outcome was defined as a modified Rankin Scale (mRS) score of ≥ 3. Multivariate analysis via logistic regression was performed on appropriate variables with a p value of ≤ 0.2. Seventy-five percent of the cohort had at least 3 years of follow-up.RESULTSFive patients (2.4%) did not receive any intervention, 131 (61.8%) had GKRS alone, 14 (6.6%) had craniotomies alone, and 2 (0.9%) had embolization alone. Twenty-two (10.4%) had embolization and Gamma Knife radiosurgery (GKRS); 20 (9.4%) had craniotomies and GKRS; 8 (3.8%) had embolization and craniotomies; and 10 (4.7%) had embolization, craniotomies, and GKRS. Thirty-one patients (14.6%) were found to have poor outcome on follow-up. The multivariate analysis performed in patients with poor outcomes was notable for associations with no treatment (OR 18.9, p = 0.02), hemorrhage requiring craniotomy for decompression alone (OR 6, p = 0.03), preoperative mRS score (OR 2.1, p = 0.004), and Spetzler-Martin score (OR 1.8, p = 0.0005). The mean follow-up was 79.7 ± 62.1 months. The confirmed radiographic obliteration rate was 79.4% and there were 5 recurrences found on average 9.5 years after treatment.CONCLUSIONSHigh rates of long-term functional independence (mRS score of ≤ 2) can be achieved with comprehensive multimodality treatment of pAVMs. At this center there was no difference in outcome based on treatment choice when accounting for factors such as Spetzler-Martin grade and presenting morbidity. Recurrences are rare but frequently occur years after treatment, emphasizing the need for long-term screening after obliteration.

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