Long-term trend of quality-adjusted time without symptoms or toxicities (Q-TWiST) of nivolumab+ipilimumab (N+I) versus sunitinib (SUN) for the first-line treatment of advanced renal cell carcinoma (aRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6568-6568
Author(s):  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Jessica May ◽  
Youngmin Kwon ◽  
Nifasha Rusibamayila ◽  
...  
Keyword(s):  
Good Health ◽  
Group Differences ◽  
Parametric Bootstrapping ◽  
Clinical Benefits ◽  
Grade 3 ◽  
Relative Gains ◽  
Clinical Trial Information ◽  
Over Time

6568 Background: After a minimum follow-up of 48 months (mos), the CheckMate 214 trial (phase 3, NCT02231749) continued to demonstrate a significant overall (OS) and progression-free (PFS) survival benefit for N+I vs. SUN in aRCC patients (pts) with intermediate (I) or poor (P) International Metastatic RCC Database Consortium (IMDC) risk factors (median OS: 48.1 vs. 26.6 mos, HR: 0.65, 95% confidence interval [95% CI]: 0.54, 0.78; 48-mos PFS: 32.7% vs. 12.3%, HR: 0.74, 95% CI: 0.62, 0.88) (Albiges et al. ESMO Open 2020). To further understand the clinical benefits and risks of N+I vs. SUN, we evaluated the Q-TWiST over time using up to 57 mos of follow-up in CheckMate 214. Methods: OS was partitioned into 3 states: time with any grade 3 or 4 adverse events (TOX), time without symptoms of disease or toxicity (TWiST), and time after progression (REL). The Q-TWiST is a metric that combines the quantity and quality (i.e., “utility”) of time spent in each of the 3 states TWiST, TOX, and REL. Prior research (Revicki et al, Qual Life Res, 2006) has established that relative gains in Q-TWiST (i.e., Q-TWiST gain divided by OS in SUN) of ≥ 10% and ≥ 15% can be considered as “clinically important” and “clearly clinically important”, respectively. Non-parametric bootstrapping was used to generate 95% CIs. To observe changes in quality-adjusted survival gains over time, absolute and relative Q-TWiST were calculated up to 57 mos at intervals of 12-mos. Results: With 57-mos follow-up, compared to SUN pts, N+I pts (N = 847) had significantly longer time in TWiST state (+7.1 mos [95% CI: 4.2, 10.4]). The between-group differences in TOX state (0.3 mos [95% CI: -0.2, 0.8]) and REL state (-1.2 mos [95% CI: -4.1, 1.5]) were not statistically significant. The Q-TWiST gain in the N+I vs. SUN arms was 6.6 mos (95% CI: 4.1, 9.4), resulting in a 21.2% relative gain. Q-TWiST gains progressively increased over the follow-up period and exceeded the “clinically important” threshold around 27 mos (Table). These gains were driven by steady increases in TWiST gains from 0.4 mos (after 12 mos) to 7.1 mos (after 57 mos). Conclusions: In CheckMate 214, N+I resulted in a statistically significant and “clearly clinically important (≥ 15%)” longer quality-adjusted survival vs. SUN, which increased over the longer follow-up time. Q-TWiST gains were primarily driven by time in “good” health (i.e., TWiST), which largely resulted from the long-term PFS benefits seen for N+I vs. SUN. Clinical trial information: NCT02231749. [Table: see text]

Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9500-9500 ◽  
Author(s):  
Suresh S. Ramalingam ◽  
Tudor Eliade Ciuleanu ◽  
Adam Pluzanski ◽  
Jong-Seok Lee ◽  
Michael Schenker ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Stage Iv ◽  
Primary Analysis ◽  
Response Status ◽  
Treatment Naïve ◽  
Report Data ◽  
Grade 3 ◽  
Clinical Trial Information

9500 Background: In the phase 3 CheckMate 227 Part 1 (NCT02477826; minimum follow-up, 29.3 mo), 1L NIVO + IPI significantly improved overall survival (OS) vs chemo in treatment-naive patients (pts) with aNSCLC and tumor PD-L1 expression ≥ 1% (primary analysis) or < 1% (pre-specified descriptive analysis). Here we report data with 3-y minimum follow-up. Methods: Pts with stage IV / recurrent NSCLC and PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W) alone, or chemo. Pts with PD-L1 < 1% (n = 550) were randomized to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Primary endpoint was OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1%. An exploratory analysis of OS in pts by response status (CR/PR, SD, progressive disease [PD]) at 6 mo was conducted. Results: After a median follow-up of 43.1 mo (database lock, 28 Feb 2020), pts with PD-L1 ≥ 1% continued to derive OS benefit from NIVO + IPI vs chemo (HR: 0.79; 95% CI, 0.67–0.93); 3-y OS rates were 33% (NIVO + IPI), 29% (NIVO), and 22% (chemo). At 3 y, 18% of pts with PD-L1 ≥ 1% treated with NIVO + IPI remained progression-free vs 12% with NIVO and 4% with chemo; 38% of confirmed responders remained in response in the NIVO + IPI arm at 3 y vs 32% in the NIVO arm and 4% in the chemo arm. In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 3-y OS rates were 34% (NIVO + IPI), 20% (NIVO + chemo), and 15% (chemo); 13%, 8%, and 2% of pts remained progression-free; and 34%, 15%, and 0% of confirmed responders remained in response, respectively. Pts with PD-L1 ≥ 1% with either CR/PR at 6 mo had longer subsequent OS with NIVO + IPI vs chemo; pts with SD or PD at 6 mo had generally similar subsequent OS between treatments (Table); results in PD-L1 < 1% pts will be presented. Any-grade / grade 3–4 treatment-related AEs were observed in 77% / 33% of all pts treated with NIVO + IPI, and 82% / 36% with chemo. Conclusions: With 3 y minimum follow-up, NIVO + IPI continued to provide durable and long-term OS benefits vs chemo for pts in 1L aNSCLC. Pts with PD-L1 ≥ 1% who achieved CR/PR at 6 mo had marked OS benefit with NIVO + IPI vs chemo. No new safety signals were identified for NIVO + IPI. Clinical trial information: NCT02477826. [Table: see text]

PRINT: Prostate cancer intensive, non-cross reactive therapy for CRP—Early observations of efficacy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 89-89
Author(s):  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao ◽  
Matt D. Galsky ◽  
Richard Lorne Bakst ◽  
Robert Stewart ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Radium 223 ◽  
Psa Response ◽  
Psa Progression ◽  
Therapy Completion ◽  
Grade 3 ◽  
Daily Prednisone ◽  
Clinical Trial Information

89 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay/prevent drug resistance, and minimize toxicity. Methods: Enrolled patients all received 3 consecutive treatment modules, each 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 10/2019, 35 of 40 planned men with mCRPC were enrolled, 25 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 52 weeks, median time to PSA progression after therapy completion is 15.5 weeks (95%CI; 5-26.1+ weeks). PSA response rates show successive improvements with each sequential treatment module (Table). Six (24%) patients continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (64+ weeks, 54+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (14.3%), diarrhea (5.7%), anemia (2.9%), fatigue (2.9%), neutropenia (2.9%), and thrombocytopenia (2.9%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160. [Table: see text]

Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 609-609 ◽  
Author(s):  
Nizar M. Tannir ◽  
David F. McDermott ◽  
Bernard Escudier ◽  
Hans J. Hammers ◽  
Osvaldo Rudy Aren ◽  
...  
Keyword(s):  
Clear Cell ◽  
Complete Response ◽  
Review Committee ◽  
First Line ◽  
Intention To Treat ◽  
Independent Review ◽  
Grade 3 ◽  
Clinical Trial Information ◽  
Over Time

609 Background: N+I demonstrated superior OS and ORR v S in intention-to-treat (ITT) and intermediate/poor-risk (IP) pts with aRCC in CheckMate 214. Here, we report OS, response outcomes per independent radiology review committee (IRRC), and safety with extended min follow-up of 42 mo. Methods: Pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3W×4 and then N 3 mg/kg Q2W, or S 50 mg daily for 4 wk on, 2 wk off. Endpoints were OS, ORR, and PFS per IRRC using RECIST v1.1 in IP (primary), ITT (secondary), and favorable pts (FAV; exploratory). Results: OS remained superior in ITT (HR 0.72) and IP (HR 0.66) pts with N+I v S (Table). ORR per IRRC was higher and more responses were ongoing with N+I v S (68% v 53% [ITT] and 68% v 52% [IP]). More pts achieved complete response (CR) with N+I and these were ongoing in 86% [ITT] and 84% [IP] of pts. The PFS probability with N+I stabilized after 24 mo at ~35% in ITT and IP pts, whereas probabilities declined over time with S. Among FAV pts, while ORR was 29% with N+I v 54% with S, more pts achieved CR (13% v 6%), and more responses were ongoing (69% v 54%) with N+I v S; 94% of CRs in FAV pts were ongoing with N+I. OS benefits were similar in both arms and PFS probabilities are stabilizing with N+I and declining with S in FAV pts. The incidence of any and grade 3–4 treatment-related AEs was consistent with previous reports and no new drug-related deaths occurred in either arm. Response outcomes per investigator will also be reported. Conclusions: Superior OS and ORR with N+I v S was maintained in ITT and IP pts. More pts treated with N+I experienced CR compared with S, responses and CRs were durable, and PFS probabilities stabilized with N+I after extended follow-up. No new safety signals emerged. Clinical trial information: NCT02231749 .[Table: see text]

PRINT: Prostate cancer intensive, non-cross reactive therapy for CRPC—Early observations of efficacy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17575-e17575
Author(s):  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao ◽  
Matt D. Galsky ◽  
Richard Lorne Bakst ◽  
Robert Stewart ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Radium 223 ◽  
Psa Response ◽  
Psa Progression ◽  
Therapy Completion ◽  
Grade 3 ◽  
Daily Prednisone ◽  
Clinical Trial Information

e17575 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients received treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 1/2020, 38 of 40 planned men with mCRPC were enrolled, 28 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 54+ weeks, median time to PSA progression after therapy completion is 14.7+ weeks (95%CI; 5.5-23.9+ weeks). PSA response rates showed successive improvements with each sequential treatment module (Table). Eight patients (21.1%) continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (82+ weeks, 79+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (15.8%), diarrhea (5.3%), anemia (2.6%), fatigue (2.6%), neutropenia (2.6%), and thrombocytopenia (2.6%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160 . [Table: see text]

Long-Term Effect of Ruxolitinib (RUX) in Inadequately Controlled Polycythemia Vera (PV) without Splenomegaly: 5-Year Results from the Phase 3 Response-2 Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 40-41
Author(s):  
Francesco Passamonti ◽  
Francesca Palandri ◽  
Guray Saydam ◽  
Miklos Egyed ◽  
Jeannie Callum ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Final Analysis ◽  
Jak2 V617f ◽  
Advisory Committees ◽  
Associated Symptoms ◽  
Adjusted Rate ◽  
Grade 3 ◽  
Over Time

BACKGROUND RUX, a JAK 1/2 inhibitor, is a second-line treatment for symptom management and control of trilineage expansion in patients (pts) with PV who are resistant or intolerant to hydroxyurea (HU). In the RESPONSE study, RUX showed a superior and durable response in controlling hematocrit (HCT) and improving splenomegaly in PV pts resistant or intolerant to HU. RESPONSE-2 (NCT02038036) is a multicenter, open-label, Phase 3 trial comparing RUX with best available therapy (BAT) in HU-resistant/intolerant PV pts without splenomegaly. The primary analysis at Week (Wk) 28 and follow-ups at Wks 80 and 156 proved superiority of RUX over BAT. Here we present the final study results of the 5-year follow-up (Wk 260). METHODS Pts were randomized (1:1) to RUX 10 mg twice daily or BAT; crossover from BAT to RUX was allowed from Wk 28. The final analysis at Wk 260 evaluated durability of HCT control, complete hematologic response (CHR), and safety. Durability of HCT control was defined as absence of phlebotomy eligibility from Wk 8 to Wk 260 with ≤1 phlebotomy eligibility post-randomization to Wk 8. CHR was defined as HCT control with a white blood cell count &lt;10×109/L, platelet count ≤400×109/L. Safety is reported as exposure-adjusted rates per 100 pt-years. Other evaluated endpoints were changes in pt-reported outcomes (PRO) and JAK2 V617F allele burden over time. RESULTS Pts were randomized to RUX (n=74) or BAT (n=75). A total of 59/74 RUX pts and 61/75 BAT pts completed the treatment duration. Among the 75 BAT pts, 58 pts crossed over to RUX, with 38 of them completing the study, allowing for long-term follow-up of 97 pts treated with RUX. Median (range) exposure was 260.0 (0.1 - 273.1) wks in RUX, 28.4 (6.7 - 83.0) wks in BAT, and 224.7 (2.7 - 236.1) wks in crossover arms. At Wk 260, 21.6% of RUX pts (16/74) achieved durable HCT control. The Kaplan-Meier (KM) -estimated median duration of HCT control was not reached (Fig. A). Durable CHR was achieved in 24.3% of RUX pts (18/74; estimated median duration, 34.0 wks). Crossover pts derived RUX benefit by achieving HCT control with HCT levels decreasing over time (median HCT was 46.2% at the crossover baseline and 38.9% at the end of treatment). JAK2 V617F allele burden reduced over time for pts treated with RUX from baseline with a median decrease of 14.8% in RUX (59 evaluable pts) and 13.5% in crossover arms (42 evaluable pts). RUX showed durable improvement in PV-associated symptoms; about 45% of RUX pts continued to achieve ≥50% reduction in MPN-SAF TSS at Wk 260. RUX pts also continued to experience improvements in all 5 dimensions of the EQ-5D-5L assessment. Total number of phlebotomies was 60 in the RUX arm (at Wk 260) vs 106 for BAT (Wk 80). At Wk 260, RUX- (vs BAT-) treated pts required &gt;0 − ≤2 phlebotomies in 16.2% (vs 38.7%), &gt;2 − ≤4 in 9.5% (vs 21.3%), &gt;4 − ≤6 in 5.4% vs (2.7%), and &gt;6 − ≤8 in none (vs 1.3%). The most common AEs (&gt;5%, exposure-adjusted rate) were anemia, arthralgia, and increased weight in the RUX arm and anemia, and hypertension in pts after crossover. Of note, exposure-adjusted rates of herpes zoster were 3.9 in both RUX (Grade 3/4, 0.9) and crossover pts (no Grade 3/4) and none in the BAT arm. The exposure-adjusted rate of thromboembolic events was higher with BAT than RUX (3.7 vs 1.5). As expected given prior HU exposure, non-melanoma skin cancer was the most common secondary malignancy in RUX (exposure-adjusted rates: randomized, 2.7; crossover, 2.9) and BAT-treated pts (1.9). No RUX pts developed AML, whereas myelofibrosis was reported in 2 pts (exposure-adjusted rate, 0.6%). On-treatment death was reported in 5 pts: 1 each in the RUX arm (metastatic melanoma) and BAT arm (septic shock), and 3 in crossover (1 pt each - cardiac disorder, general health deterioration, and PV progression). The KM-estimated median overall survival was not reached in both RUX (95.8%; 95% CI: 87.4, 98.6) and BAT arms (90.7%; 95% CI: 80.3, 95.7; Fig. B) at ≥260 wks. Transformation-free survival (KM-estimated, 95% CI) in the RUX arm was 94.18% (85.23, 97.78) at ≥260 wks. CONCLUSIONS In line with the RESPONSE study outcomes, final analysis from the 5-yr follow-up of RESPONSE 2 proved superiority of RUX over BAT with a safety profile that remained consistent with previous reports. RUX provided durable HCT control with a decrease in the need for phlebotomies, CHR, improved PV-associated symptoms and PRO scores, with fewer thromboembolic events in PV pts without splenomegaly, who are HU resistant or intolerant. Disclosures Palandri: Novartis: Consultancy, Honoraria. Callum:Canadian Blood Services: Research Funding; Octapharma Canada: Research Funding. Devos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vannucchi:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprint: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zor:Novartis: Current Employment. Gilotti:Novartis: Current Employment. Zhang:Novartis: Current Employment. Griesshammer:Celgene: Honoraria, Speakers Bureau; AOP Orphan: Honoraria, Speakers Bureau; CTI: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapy-refractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4014-4014 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Patrick Alexander Ott ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Clinical Activity ◽  
Heavily Pretreated ◽  
Long Term Follow Up ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

4014 Background: In the phase 3 ONO-12 study, 3rd- or later-line nivolumab (N) monotherapy prolonged OS vs placebo in Asian pts with adv G/GEJ cancer (median OS, 5.3 vs 4.1 mo; HR, 0.63; P < 0.0001; ASCO-GI 2017, Kang YK et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). The phase 1/2 CheckMate 032 study showed favorable clinical activity of N ± ipilimumab (I) in Western pts with adv CTx-R G/E/GEJ cancer (NCT01928394). We report updated long-term follow-up data of G/E/GEJ pts in CheckMate 032. Methods: Pts received N 3 mg/kg Q2W (N3), N 1 mg/kg + I 3 mg/kg Q3W (N1+I3), or N 3 mg/kg + I 1 mg/kg Q3W (N3+I1). Primary endpoint was ORR. Secondary endpoints included DOR, OS, PFS, and safety. Efficacy in pts by PD-L1 status was assessed. Results: 160 heavily pretreated pts (79% had ≥ 2 prior Tx) were enrolled (N3, n = 59; N1+I3, n = 49; N3+I1, n = 52); 24% had PD-L1+ (≥ 1%) tumors. ORR was 12% in N3, 24% in N1+I3, and 8% in N3+I1. In pts with PD-L1 ≥ 1%, ORR was 19% (3/16) in N3, 40% (4/10) in N1+I3, and 23% (3/13) in N3+I1; in pts with PD-L1 < 1%, ORR was 12% (3/26), 22% (7/32), and 0% (0/30), respectively. Median DOR was 7.1 mo in N3, 7.9 mo in N1+I3, and NA in N3+I1. OS in all pts and in pts with PD-L1 ≥ 1% is in the Table. Grade 3–4 treatment-related AEs reported in ≥ 10% of pts in any treatment arm were diarrhea (N3, 2%; N1+I3, 14%; N3+I1, 2%), ALT increased (N3, 3%; N1+I3, 14%; N3+I1, 4%), and AST increased (N3, 5%; N1+I3, 10%; N3+I1, 2%). Conclusions: N ± I led to durable responses and long-term OS in heavily pretreated Western pts with adv G/E/GEJ cancer, which is consistent with the clinical activity observed in Asian pts in the ONO-12 study. Safety was consistent with prior reports. These data support ongoing investigation of N ± I in pts with adv G/E/GEJ cancer. Clinical trial information: NCT01928394. [Table: see text]

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 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 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.

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