Need For Salvage Therapy Research Articles

Results from METIS (EF-25), an international, multicenter phase III randomized study evaluating the efficacy and safety of tumor treating fields (TTFields) therapy in NSCLC patients with brain metastases.

2008 Background: For non-small cell lung cancer (NSCLC) with brain metastases (BM) stereotactic radiosurgery (SRS) is the current preferred therapy. Due to frequent intracranial failures, there is a high unmet need for salvage therapies. Whole brain radiotherapy (WBRT) reduces intracranial failure but used less frequently due to cognitive consequences. Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell division and have shown improved survival and safety in patients with glioblastoma and metastatic NSCLC. Phase 3 METIS trial [NCT02831959] aimed to evaluate the efficacy and safety of TTFields therapy in NSCLC patients with BM treated with SRS, specifically in terms of lengthening time to intracranial progression without cognitive decline. Methods: Mutation negative (M-) NSCLC patients with 1–10 BM were randomized 1:1 to receive stereotactic radiosurgery (SRS) followed by Tumor Treating Fields (TTFields; 150 kHz) therapy with best supportive care (BSC) or SRS followed by BSC. Patients with Karnofsky Performance Status (KPS) ≥70, newly diagnosed with one inoperable or 2–10 supra-/infratentorial brain metastases suitable for SRS and receiving optimal extracranial disease therapy were included. Exclusions were prior WBRT and single operable or recurrent brain metastases. Primary endpoint was time to first intracranial progression (RANO-BM) based on cumulative risk. Patients were followed every two months until second intracranial progression. Cognition and patient quality of life (QoL) were evaluated. Results: Between July 2016 and September 2022, 298 patients were randomized. Baseline characteristics were balanced: median age was 63.5 (range 37-84) years, 37.6% females, majority of patients had a KPS ≥ 80, median time from initial NSCLC diagnosis was 1.8 months (range: 0.2-55.7), 77% had adenocarcinoma. Median treatment duration of TTFields was 16 weeks, with a median usage time of 67%. Primary endpoint, time to intracranial progression from SRS, was significantly prolonged with SRS followed by TTFields therapy with BSC vs. TTFields plus BSC arm (median of 21.9 vs. 11.3 months); HR=0.67 [0.48-0.93], p=0.02. TTFields-related AEs were mainly dermatological, and Grade ≤2. TTFields therapy also improved deterioration-free survival of global health status, physical functioning, and fatigue according to QoL, and did not negatively impact cognition. Conclusions: METIS study met its primary endpoint, demonstrating that TTFields therapy following SRS in mutation negative NSCLC patients with BM, significantly prolongs time to intracranial progression and could postpone WBRT, without QoL and cognition decline. Clinical trial information: NCT02831959 .

Management of recurrent giant hemangiopericytoma: illustrative cases.

Hemangiopericytoma (HPC) is a rare malignancy accounting for 0.4% of intracranial tumors. HPCs are characterized by local aggressiveness, high rates of recurrence, and a tendency to metastasize to extracranial sites. These features make management of HPCs challenging, often requiring a combination of radical resection and radiation. Given their rarity, optimal treatment algorithms remain undefined. The authors report a series of four patients who underwent resection of intracranial HPC. Mean age at presentation was 49.3 years. Three patients had reoperation for progression of residual tumor, and one patient was surgically retreated for recurrence. One patient received adjuvant radiotherapy following initial resection, and three patients received adjuvant radiotherapy following resection of recurrent or residual disease. There was one death in the series. Average progression-free survival and overall survival following the index procedure were 32.8 and 82 months, respectively. Progression occurred locally in all patients, with metastatic recurrence in one patient. The current gold-standard treatment for intracranial HPC consists of gross-total resection followed by radiation therapy. This approach allows satisfactory local control; however, given the tendency for these tumors to recur either locally or distally within or outside of the central nervous system, there is a need for salvage therapies to improve long-term outcomes for patients.

Difficult-to-treat HIV in Sweden: a cross-sectional study.

Our aim was to examine the prevalence and characteristics of difficult-to-treat HIV in the current Swedish HIV cohort and to compare treatment outcomes between people with difficult and non-difficult-to-treat HIV. In this cross-sectional analysis of the Swedish HIV cohort, we identified all people with HIV currently in active care in 2023 from the national register InfCareHIV. We defined five categories of difficult-to-treat HIV: 1) advanced resistance, 2) four-drug regimen, 3) salvage therapy, 4) virologic failure within the past 12 months, and 5) ≥2 regimen switches following virologic failure since 2008. People classified as having difficult-to-treat HIV were compared with non-difficult for background characteristics as well as treatment outcomes (viral suppression and self-reported physical and psychological health). Nine percent of the Swedish HIV cohort in 2023 (n=8531) met at least one criterion for difficult-to-treat HIV. Most of them had ≥2 regimen switches (6%), and the other categories of difficult-to-treat HIV were rare (1-2% of the entire cohort). Compared with non-difficult, people with difficult-to-treat HIV were older, had an earlier first year of positive HIV test and lower CD4 counts, and were more often female. The viral suppression rate among people with difficult-to-treat HIV was 84% compared with 95% for non-difficult (p= 0.001). People with difficult-to-treat HIV reported worse physical (but not psychological) health, and this remained statistically significant after adjustment for age, sex, and transmission group. Although 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed, and challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.

P1218 Non-invasive point-of-care stool sample for detection of Cytomegalovirus infection in patients with Active or Refractory Ulcerative Colitis using multiplex polymerase chain reaction (mPCR): a pilot feasibility study

Abstract Background Cytomegalovirus (CMV) infection is associated with more flare-ups and deteriorates the prognosis of active inflammatory bowel disease (IBD). Patients with refractory IBD should be tested for CMV colitis, especially if they are not responding to immunosuppressive therapy. The prevalence of CMV co-infection ranges from 10% to 30% in steroid-refractory acute colitis. Concurrent CMV-colitis is associated with an increased risk of worse therapeutic outcomes, resistance to corticosteroids, and need for salvage therapy. One of the two gold standards of diagnosis of CMV colitis in IBD patients with active disease requires the analysis of tissue biopsies using PCR. The aim of our pilot study was to evaluate the diagnostic accuracy of non-invasive point-of-care faecal samples using mPCR for detecting CMV in patients with ulcerative colitis compared to standard practice biopsies PCR. Methods We performed a prospective, observational, feasibility study including 62 consecutive patients with active ulcerative colitis (UC) requiring intravenous steroids or steroid-refractory UC in the Department of Gastroenterology of University Hospital „Tsaritsa Yoanna – ISUL", from April 2022 to October 2023. In all UC patients, colonic tissue biopsies were performed and analyzed by qualitative CMV PCR. Faecal sample mPCR CMV was performed on the positive patient cohort to compare the feasibility of (ME) Panel IVD using FilmArray mPCR (Biofire, bioMerieux, France). All the tested patients had undergone immunosuppressive therapy and initial stool specimen cultures were obtained to exclude infection with C. difficile and other pathogen flora. Results Out of 62 active UC patients with colonic tissue samples qualitative CMV PCR, n=5 (8%) were positive. Of these n=5 UC patients, n=4 (80%) were positive from the Fecal sample mPCR CMV, resulting in a compatibility of 80% for diagnosing CMV in these patients by the two DNA extraction methods. Calculated Sensitivity and diagnostic accuracy was 80% (95% CI) for the mPCR CMV. The patient cohort predominantly comprised males (75%) with a median age of 45 years (range: 30–72 years). Three patients (75%) out of this cohort group were treated with peroral antiviral agent Valganciclovir, one (25%) of them went into clinical and endoscopic remission after the treatment and two patients (50%) received colectomy. The median time performing the Faecal sample mPCR CMV was approx. 1 hour. Conclusion This novel faecal mPCR point-of-care test is a promising, fast and easy non-invasive tool for detection CMV in active or refractory UC patients, comparable with the colonic tissue CMV-DNA PCR.

Curability of Light Chain (AL) Amyloidosis with Conventional Dose Regimens

Novel immunotherapies in AL amyloidosis (AL) are associated with improved outcomes while the use of ASCT in selected patients can offer long term remissions. Since the plasma cell clones are usually small or modest, sustained hematologic remissions are not uncommon in AL amyloidosis; however, the “curability” of the disease remains to be demonstrated: even in patients (pts) who achieve deep and sustained hematologic responses, irreversible organ damage can lead to inferior survival. To identify clinical and disease characteristics that are associated with potential “functional cure” (“cure”) of the disease we analyzed a cohort of patients with AL treated without ASCT and with a follow up of at least 5 years. We defined“ ”cure“ as survival of at least 5 years without hematologic disease progression (PD) and without need for any salvage therapy. The analysis included consecutive pts with AL, treated in the Department of Clinical Therapeutics, Athens Greece, diagnosed until 6/2018; pts who survived < 6 months were excluded to adjust for early mortality associated with severe cardiac involvement. The final cohort included 210 pts and we focused on pts who: had not had hematologic PD, had not received any salvage therapy, were still alive or had died from causes not related to AL. These pts were defined as “functionally cured” while the rest as “non-cured”. Among the “cured” we identified a group of pts that despite hematologic response they progressed to end-stage renal disease. We considered that this was “predetermined” due to the advanced organ damage already at diagnosis. Lastly, we compared the outcome of “cured” pts with the outcome of “non-cured” pts who were on CR/VGPR and had ≥1-year or ≥5-year OS. The rate of “curability” was 17% (N=35). “Cured” pts had more often renal (84% vs 61%, p=0.045) and less frequent cardiac involvement (53% vs 62%, p=0.049), lower BM infiltration (8% vs 15%, p<0.001) and lower baseline dFLC (p=0.031) but higher levels of baseline proteinuria (p=0.031). The characteristics as well as the differences between “cured” and “non-cured” pts, are shown in Table 1. Most “cured” pts received bortezomib-based therapies (27 pts, 77%), oral melphalan was given in 4 pts (11%), while in 15 pts (42%) treatment also included lenalidomide and in 7 (20%) daratumumab (with or without bortezomib). Regarding hematologic response, 33 (94%) “cured” pts had achieved ≥ VGPR (CR: 22, VGPR: 11) vs 46% for “non-cured” (p<0.001), 18 pts (51%) had ≥ VGPR with low dFLC response criteria (dFLC <10mg/L) vs 20% (p<0.001); 6 pts (17%) had only low dFLC VGPR and 4 (11%) were not evaluable for response due to low dFLC levels. At 1- and 3-months from start of therapy, 24 (68%) and 27 pts (77%) “cured” pts had achieved ≥VGPR. MRD evaluation was available in 19 “cured” pts, and 11 (31%) were MRD negative (vs 3 (2%) for “non-cured” pts, p<0.001). Cardiac response was observed in 9 pts (25%) and renal response in 18 “cured” pts (51%). Among “cured” pts there was a group of 7 pts (20%) with end-stage renal disease; 1 (2.8%) was already on dialysis at the time of diagnosis, while 6 (17%) initiated dialysis during disease course, despite deep hematologic responses (3 CR, 3 VGPR); 3 pts were renal stage 2 and 3 were renal stage 3. Median time to dialysis was 27 months. Baseline clinical and disease characteristics were comparable among pts with and without end-stage renal disease. The median follow-up of the whole cohort was 88 months, and among “cured” pts, 3 (8.5%) died from causes unrelated to AL amyloidosis. The 7- year OS rate for “cured” pts was 100% and for “non-cured” was 41%, respectively. In 1- and 5-year landmark survival analysis, “cured” pts had significantly superior outcome compared to “non-cured” pts with CR/VGPR, with median OS not reached vs 66 months (p<0.001) and not reached vs 98 months (p=0.014), respectively (Fig 1). In conclusion, a subgroup of pts with AL, not treated with ASCT, can have long-term survival (≥ 5 years) without need for additional or salvage therapy. Such patients could be considered as functionally “cured”. High rates of rapid and deep hematologic responses, relatively high rates of MRD negativity and relatively low tumor and free light chain burden characterize this subset, further emphasizing the need for early diagnosis and active therapy to maximize clonal responses. Thus, “curability” in AL amyloidosis is feasible, especially in the era of novel therapies.

Avatrombopag in Immune Thrombocytopenia (ITP). Real-Life Experience of Its Use in Hospitals within the Community of Madrid, Spain (AVAMAD STUDY)

Introduction Thrombopoietin receptor agonists (TPO-RAs) are recommended as second-line treatment for immune thrombocytopenia (ITP) according to the Spanish ITP group (GEPTI) guidelines. Avatrombopag (AVA) is an oral TPO-RA, recently launched in Spain, for which we have little data available beyond the pivotal trial. The main objectives of our study were to evaluate the efficacy and safety of AVA in patients with ITP. Methods In this observational, retrospective, multicenter study in 10 hospitals in the Community of Madrid, we have analyzed adult patients with ITP treated with AVA from July 2022-May 2023. Demographic characteristics, response, rescue therapy, adverse effects and treatment discontinuation were analyzed. The definition of ITP and response were those described by Provan et al. The study protocol was designed and applied in accordance with the principles of the Declaration of Helsinki. Statistical analysis was performed using IBM SPSS Statistics v28.0. Fisher and Mann-Whitney tests were used for bivariate analysis and Kaplan-Meier curves for response time. Results A total of 66 patients were included. The median age was 52 years old (IQR 34-71). Table 1 describes the general characteristics. There was a median of 2 (IQR1-3) previous lines of treatment before starting AVA. The reasons for its initiation were: refractoriness to previous treatment and/or corticodependence in 39% (25/66), loss of response in 34% (22/66), switch due to patient preference in 14% (9/66) and switch due to adverse effects with previous treatment in 5% (3/66). In 8% (5/66) there was more than one reason for change. The previous line of treatment is described in Table 1. The median platelet count at baseline was 36x10 9/L(IQR 13-61). With a median follow-up of 16 weeks (IQR 8-28), 86% of the pateints (57/66) were responders. 73% had complete response. 24% percent (16/66) required salvage therapy. In the bivariate analysis, 100% of those aged ≥65 years presented response vs. 75% in <65 years (p=0.003). A complete response was achieved in 88.6% of women versus 54.8% of men (p=0.002). Patients with complete response received fewer lines of treatment (1 [IQR 1-3] vs 3.5 [IQR 2-6]); p< 0.001). Complete response was achieved in 60.5% of patients who received previous treatment with eltrombopag (p=0.01), in 47.8% of those with romiplostim (p<0.001), in 40% with rituximab (p=0.02), in 33.3% with splenectomy (p=.0.01) and in 22.2% with fostamatinib (p=0.00).The median time from initiation of AVA to response was 2,1 weeks [IQR 2-4] (Figure 1). Twelve patients (18%) discontinued AVA due to: lack of response (n=6), adverse effects (n=3), one patient prior to scheduled surgery, and In these patients AVA was restarted with dose adjustment. Adverse effects are described in Table 1. Conclusions The results of the use of AVA in real-life demonstrated a high response rate, more favorable in the initial lines of treatment. In addition, it reduces the need for salvage therapy and has a low adverse effect profile. A larger number of patients and a longer follow-up are needed to verify these results and to answer some questions such as whether it is possible to discontinue AVA treatment after response and the percentage of patients with sustained response following AVA discontinuation.

Long-Term Outcomes of NRG/RTOG 0126, a Randomized Trial of High Dose (79.2 Gy) vs. Standard Dose (70.2 Gy) Radiation Therapy (RT) for Men with Localized Prostate Cancer

NRG/RTOG 0126, a phase III trial for men with localized prostate cancer testing whether dose escalation to 79.2 Gy with 3DCRT/IMRT improved overall survival (OS). Long-term results of this trial are presented. Patients with clinical stage T1b-T2b and either Gleason Score (GS) 2-6 and 10 ≤ PSA < 20 or GS 7 and PSA < 15 were eligible and randomized to receive 79.2 Gy or 70.2 Gy. No previous or concurrent androgen withdrawal therapy was administered. Treatment was delivered with 3DCRT/IMRT to a dose of 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions to the PTV encompassing the prostate and seminal vesicles. Image guidance was not required. ASTRO and Phoenix definitions were used for biochemical failure (ABF and PBF, respectively). OS was estimated by the Kaplan-Meier method and arms compared with the log-rank test. ABF, PBF, local progression (LP), distant metastases (DM) and time to late GI/GU toxicities were estimated by the cumulative incidence method and arms compared with Gray's test. One thousand five hundred thirty-two men were randomized, 763 to 79.2 Gy and 769 to 70.2 Gy. 1499 were eligible, 748 and 751 in the 79.2 Gy and 70.2 Gy arms respectively. Median age was 71, 70% had PSA < 10 ng/ml, 84% with GS 7, 57% had T1 disease, and 66% treated with 3D-CRT. Outcomes are shown in the TABLE: . With a median follow up of 12 years, there was no significant difference in OS. There was a statistically significant decrease in the cumulative incidence of ABF, PBF, DM, LP, and salvage therapies in the 79.2 Gy arm. There were significantly higher rates of grade 2+ GI and GU toxicity in the 79.2 Gy arm. There were no statistically significant differences in the rates of grade 3+ GU or GI toxicity between either arm. Long term follow up confirms no improvement in OS with dose escalation in this study population. However, there are significant improvements in ABF, PBF, DM, LP, and need for salvage therapy. Despite the use of more salvage therapy in the low dose arm, dose escalated RT resulted in lower rates of DM, a clinically relevant endpoint. Patients receiving dose escalation do experience a higher rate of grade 2+ GU and GI toxicity but no worse grade 3+ toxicities.

Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09–09): a randomised, open-label, multicentre, phase 3 trial

Acute myeloid leukaemia with mutated NPM1 is associated with high CD33 expression and intermediate-risk cytogenetics. The aim of this study was to evaluate intensive chemotherapy with or without the anti-CD33 antibody-drug conjugate gemtuzumab ozogamicin in participants with newly diagnosed, NPM1-mutated acute myeloid leukaemia. This open-label, phase 3 trial was conducted at 56 hospitals in Germany and Austria. Eligible participants were 18 years or older and had newly diagnosed NPM1-mutated acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly assigned, using age as a stratification factor (18-60 years vs >60 years), 1:1 to the two treatment groups using allocation concealment; there was no masking of participants and investigators to treatment groups. Participants received two cycles of induction therapy (idarubicin, cytarabine, and etoposide) plus all-trans retinoic acid (ATRA) followed by three consolidation cycles of high-dose cytarabine (or an intermediate dose for those older than 60 years) and ATRA, without or with gemtuzumab ozogamicin (3 mg/m2 administered intravenously on day 1 of induction cycles 1 and 2, and consolidation cycle 1). The primary endpoints were short-term event-free survival and overall survival in the intention-to-treat population (overall survival was added as a co-primary endpoint after amendment four of the protocol on Oct 13, 2013). The secondary endpoints were event-free survival with long-term follow-up, rates of complete remission, complete remission with partial haematological recovery (CRh), and complete remission with incomplete haematological recovery (CRi), cumulative incidences of relapse and death, and number of days in hospital. This trial is registered with ClinicalTrials.gov (NCT00893399) and has been completed. Between May 12, 2010, and Sept 1, 2017, 600 participants were enrolled, of which 588 (315 women and 273 men) were randomly assigned (296 to the standard group and 292 to the gemtuzumab ozogamicin group). No difference was found in short-term event-free survival (short-term event-free survival at 6-month follow-up, 53% [95% CI 47-59] in the standard group and 58% [53-64] in the gemtuzumab ozogamicin group; hazard ratio [HR] 0·83; 95% CI 0·65-1·04; p=0·10) and overall survival between treatment groups (2-year overall survival, 69% [63-74] in the standard group and 73% [68-78] in the gemtuzumab ozogamicin group; 0·90; 0·70-1·16; p=0·43). There was no difference in complete remission or CRi rates (n=267 [90%] in the standard group vs n=251 [86%] in the gemtuzumab ozogamicin group; odds ratio [OR] 0·67; 95% CI 0·40-1·11; p=0·15) and complete remission or CRh rates (n=214 [72%] vs n=195 [67%]; OR 0·77; 0·54-1·10; p=0·18), whereas the complete remission rate was lower with gemtuzumab ozogamicin (n=172 [58%] vs n=136 [47%]; OR 0·63; 0·45-0·80; p=0·0068). Cumulative incidence of relapse was significantly reduced by gemtuzumab ozogamicin (2-year cumulative incidence of relapse, 37% [95% CI 31-43] in the standard group and 25% [20-30] in the gemtuzumab ozogamicin group; cause-specific HR 0·65; 0·49-0·86; p=0·0028), and there was no difference in the cumulative incidence of death (2-year cumulative incidence of death 6% [4-10] in the standard group and 7% [5-11] in the gemtuzumab ozogamicin group; HR 1·03; 0·59-1·81; p=0·91). There were no differences in the number of days in hospital across all cycles between treatment groups. The most common treatment-related grade 3-4 adverse events were febrile neutropenia (n=135 [47%] in the gemtuzumab ozogamicin group vs n=122 [41%] in the standard group), thrombocytopenia (n=261 [90%] vs n=265 [90%]), pneumonia (n=71 [25%] vs n=64 [22%]), sepsis (n=85 [29%] vs n=73 [25%]). Treatment-related deaths were documented in 25 participants (4%; n=8 [3%] in the standard group and n=17 [6%] in the gemtuzumab ozogamicin group), mostly due to sepsis and infections. The primary endpoints of the trial of event-free survival and overall survival were not met. However, an anti-leukaemic efficacy of gemtuzumab ozogamicin in participants with NPM1-mutated acute myeloid leukaemia is shown by a significantly lower cumulative incidence of relapse rate, suggesting that the addition of gemtuzumab ozogamicin might reduce the need for salvage therapy in these participants. The results from this study provide further evidence that gemtuzumab ozogamicin should be added in the standard of care treatment in adults with NPM1-mutated acute myeloid leukaemia. Pfizer and Amgen.

Proton Radiotherapy for Vestibular Schwannomas in Patients with NF2-Related Schwannomatosis: A Case Series.

(1) Background: This study aimed to evaluate the efficacy and treatment-related toxicity of proton radiotherapy (PRT) for vestibular schwannoma (VS) in patients with neurofibromatosis type 2-related schwannomatosis (NF2). (2) Methods: Consecutive NF2 patients treated with PRT for VS between 2004 and 2016 were retrospectively evaluated, focusing on tumor volume, facial and trigeminal nerve function, hearing, tinnitus, vestibular symptoms, and the need for salvage therapy after PRT. (3) Results: Eight patients were included (median age 36 years, 50% female). Median follow-up was 71 months. Five (63%) patients received fractionated PRT and three (38%) received PRT radiosurgery for VS. Six patients (75%) received prior VS surgery; three also received bevacizumab. Six patients (75%) did not require salvage therapy after PRT. Two patients (25%) with residual hearing lost it after PRT, and six had already lost ipsilateral hearing prior to PRT. Tumor and treatment-related morbidity could be evaluated in six patients. Following PRT, conditions that occurred or worsened were: facial paresis in five (83%), trigeminal hypoesthesia in two (33%), tinnitus in two (33%), and vestibular symptoms in four patients (67%). (4) Conclusion: After PRT for VS, the majority of the NF2 patients in the cohort did not require additional therapy. Tumor and/or treatment-related cranial nerve deficits were common. This is at least partly explained by the use of PRT as a salvage treatment after surgery or bevacizumab, in the majority of cases. There remains the further opportunity to elucidate the efficacy and toxicity of proton radiotherapy as a primary treatment.

The influences of timing of urgent endoscopy in patients with acute variceal bleeding: a cohort study

Therehas always beena debateontheoptimal timingofendoscopy in patients with acute variceal bleeding(AVB). This study aimed to examine the relation between the timing of endoscopy and the short-term outcomes of patients with AVB. Patients with AVB who underwent endoscopy within 24h after admission at our tertiary care center from 2014 to 2022 were evaluated retrospectively. The primary outcomes were the 6-week mortality and re-bleeding. The secondary outcomes included the total number of blood units transfused, the length of hospital stay, and the need for salvage therapy. WeusedCox proportional hazards model to analyze the predictors of 6-week mortality in all patientsaswellasin those who were at high risk of further bleeding or death. A total of 312 patients were enrolled. Among them, 170 patients (54.49%) underwent urgent endoscopy (< 6h), and 142 patients (45.51%) underwent early endoscopy (6-24h). There were no significant differences between the urgent-endoscopy group and the early-endoscopy group, regarding the 6-week mortality (16.47% vs. 10.56%; P value = 0.132) and 6-week re-bleeding rate (11.2% vs. 16.2%; P value = 0.196). In multivariate analysis, time to endoscopy was independent of 6-week mortality (P value = 0.170), but the time between the beginning of bleeding and endoscopy (within 12h) was significantly associated with low 6-week mortality (OR: 0.16; 95% CI: 0.06-0.46; P value = 0.001). Time to endoscopy was still not associated with 6-week mortality in patients at high risk for further bleeding or death (Glasgow-Blatchford score ≥ 12, n = 138, P value = 0.902). Endoscopy performed within 6h of admission, rather than within 6 to 24h, did not improve six-week clinical outcomes in patients in stable condition with AVB and even those who were at high risk of further bleeding and death.

Antibiotic prophylaxis in cirrhosis patients with upper gastrointestinal bleeding: An updated systematic review and meta‐analysis

AbstractObjectiveEmerging evidence suggest that antibiotic prophylaxis may be omitted in early cirrhosis patients with upper gastrointestinal bleeding (UGIB), which question the benefits of antibiotic prophylaxis on rebleeding, mortality related to ongoing bleeding, and the need for salvage therapy. As the management of UGIB has improved over time since the last review a decade ago, we performed an updated meta‐analysis to review the benefits of antibiotic prophylaxis in cirrhosis patients with UGIB.MethodSix electronic databases including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, Cochrane library, and ClinicalTrial.gov were systematically searched up to December 1, 2021. The primary outcome was 6 weeks mortality. Secondary outcomes include the risk of infection, rebleeding at 7 days and 6 weeks, mortality related to ongoing bleeding, need for salvage therapy, and infection‐related mortality.ResultEighteen studies (12 randomized controlled trials [RCT], 6 non‐RCT) from 3180 subjects were identified among 2129 citations. Antibiotic prophylaxis reduces mortality at 6 weeks, risk of infection, and infection‐related mortality (pooled relative risk: 0.72, 0.39, and 0.41, respectively). Although antibiotics reduce the risk of rebleeding and the amount of blood transfusion, they did not reduce the risk of mortality from ongoing bleeding nor the need for salvage therapy. Antibiotic prophylaxis may shorten the length of stay in the intensive care unit.ConclusionAntibiotic prophylaxis reduces rebleeding, 6‐week mortality, and infection‐related mortality. Due to the low risk of infection and death, dedicated studies are warranted to evaluate the benefit of antibiotic prophylaxis in early cirrhosis with UGIB.

Serum Cytomegalovirus Polymerase Chain Reaction Test Is a Valuable Negative Predictor of Infection in Acute Severe Ulcerative Colitis.

Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC. This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists. Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p < 0.0001). ROC analysis showed that a CMV PCR level of 259IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p < 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates. Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC.

MP15-04 SAFETY AND FEASIBILITY OF SALVAGE RADICAL PROSTATECTOMY FOLLOWING PRIMARY IRE TREATMENT FOR RECURRENT LOCALIZED PROSTATE CANCER: AN INTERNATIONAL AND MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP15-04 SAFETY AND FEASIBILITY OF SALVAGE RADICAL PROSTATECTOMY FOLLOWING PRIMARY IRE TREATMENT FOR RECURRENT LOCALIZED PROSTATE CANCER: AN INTERNATIONAL AND MULTICENTER ANALYSIS Luigi A.M.J.G. van Riel, Alexander Blazevski, Ertunc Kabaktepe, Bart Geboers, Daan Reesink, Pascal Stijns, Philip D. Stricker, Juan Casanova, Jose Luis Dominguez-Escrig, Theo M. de Reijke, Matthijs J. Scheltema, and Jorg R. Oddens Luigi A.M.J.G. van RielLuigi A.M.J.G. van Riel More articles by this author , Alexander BlazevskiAlexander Blazevski More articles by this author , Ertunc KabaktepeErtunc Kabaktepe More articles by this author , Bart GeboersBart Geboers More articles by this author , Daan ReesinkDaan Reesink More articles by this author , Pascal StijnsPascal Stijns More articles by this author , Philip D. StrickerPhilip D. Stricker More articles by this author , Juan CasanovaJuan Casanova More articles by this author , Jose Luis Dominguez-EscrigJose Luis Dominguez-Escrig More articles by this author , Theo M. de ReijkeTheo M. de Reijke More articles by this author , Matthijs J. ScheltemaMatthijs J. Scheltema More articles by this author , and Jorg R. OddensJorg R. Oddens More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002544.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Irreversible electroporation (IRE) is among the available ablative techniques in carefully selected prostate cancer (PCa) patients. Yet, there is a risk of recurrence leading to the need for salvage therapy. It is unknown whether initial IRE treatment jeopardizes functional and oncological outcomes following salvage radical prostatectomy (sRP) for recurrent localized PCa. The aim of this study is to evaluate safety, feasibility, functional and short-term oncological outcomes of sRP for recurrent localized PCa after initial primary IRE treatment. METHODS: An international, multicenter and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localized PCa after initial primary IRE treatment. Data were reported on functional outcomes (urinary continence and erectile function), quality of life and oncological outcomes (time interval between IRE and sRP, pathology, overall survival) and safety (surgical complications) and feasibility of sRP (as reported by surgeons). RESULTS: In four participating centers a total of 39 patients with a median (IQR) age of 64 (7.0) years were identified that underwent sRP following initial IRE treatment. Median (IQR) time to recurrence after IRE was 14.3 (29.8) months. sRP was feasible without dissection difficulties and serious adverse events. Location of recurrence was observed in-field the initial IRE ablation zone in 23 patients (59%), see Figure 1. Significant positive surgical margin (PSM) rate was 15.4%. A persistent detectable PSA was found in one case post-sRP (2.6%), caused by metastatic disease. One patient (2.6%) had a biochemical recurrence 6 months following sRP. These two cases, together with a PSM case, required additional therapy following sRP. Overall survival was 100% with a median (IQR) follow-up duration of 6.9 (12.2) months. At last follow-up urinary continence and erectile function were preserved in 26 patients (76.5%) and 14 patients (41.2%), respectively, while quality of life remained stable. CONCLUSIONS: sRP is safe and feasible for PCa patients with recurrent localized disease following initial IRE treatment. Functional outcomes following sRP seem comparable to primary RP. Source of Funding: Cure for Cancer foundation © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e242 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luigi A.M.J.G. van Riel More articles by this author Alexander Blazevski More articles by this author Ertunc Kabaktepe More articles by this author Bart Geboers More articles by this author Daan Reesink More articles by this author Pascal Stijns More articles by this author Philip D. Stricker More articles by this author Juan Casanova More articles by this author Jose Luis Dominguez-Escrig More articles by this author Theo M. de Reijke More articles by this author Matthijs J. Scheltema More articles by this author Jorg R. Oddens More articles by this author Expand All Advertisement PDF DownloadLoading ...

Predictors of Recurrence After Sub-total or Near-total Resection of Vestibular Schwannoma: Importance of Tumor Volume and Ventral Extension.

To evaluate the predictors of remnant tumor regrowth and need for salvage therapy after less than gross total resection (GTR) of vestibular schwannoma (VS). Retrospective chart review. Tertiary neurotologic referral center. Patients who underwent VS resection between 2008 and 2019 either with GTR, near total resection (NTR), and subtotal resection (STR). Microsurgical resection, salvage radiosurgery. Regrowth free interval, salvage free interval, tumor doubling rate. Three hundred eighty five cases (GTR = 236, NTR = 77, and STR = 71) from 2008 to 2019 were included. STR cohort had much larger and complex tumors with significant differences in tumor volume, ventral extension and brainstem compression (p < 0.001). On single predictor analysis, tumor volume, ventral extension, brainstem compression as well as STR strategy was associated with significant increased risk of regrowth and need for salvage therapy. Multivariate analysis revealed STR strategy as significant predictor of regrowth (hazard ratio 3.79, p < 0.0005). Absolute remnant volume and extent of resection (EOR) did not predict regrowth. A small proportion of cases (NTR = 4%, STR = 15%) eventually needed salvage radiosurgery with excellent ultimate local tumor control with no known recurrence to date. Conservative surgical strategy employing NTR or STR can be employed safely in large and complex VS. While there is increased risk of regrowth in the STR cohort, excellent local control can be achieved with appropriate use of salvage radiosurgery. No disceret radiologic or operative predictors of regrowth were identified.

Clinical outcomes of benign brain tumors treated with single fraction LINAC-based stereotactic radiosurgery: Experience of a single institute.

Accelerator-based stereotactic radiosurgery (SRS) is a noninvasive and effective treatment modality widely used for benign brain tumors. This study aims to report 20-year treatment outcomes in our institute. From May 2001 to December 2020, 127 patients treated with LINAC-based single-fraction SRS for their benign brain lesions were included. A neurosurgeon and two radiation oncologists retrospectively reviewed all data. Computed tomography (CT) simulation was performed after head-frame fixation under local anesthesia. All planning CT images were co-registered and fused with gadolinium-enhanced magnetic resonance imaging taken within 3 months for lesions targeting and critical organs delineation. The marginal dose was prescribed at 60%-90% isodose lines, respectively, to cover ≥95% planning target volume. Outcome evaluations included clinical tumor control rate (TCR), defined as the need for salvage therapy, and radiological response, defined as no enlargement of >2 cm in the maximal diameter. Overall survival (OS) and adverse reaction (defined according to CTCAE 5.0) were also analyzed. The present study included 76 female and 51 male patients for analysis. The median age was 59 years (range, 20-88 years). Their diagnoses were vestibular schwannoma (VS, n = 54), nonvestibular cranial nerve schwannoma (n = 6), meningioma (n = 50), and pituitary adenoma (n = 17). Totally 136 lesions were treated in a single fraction, predominantly skull base tumors, accounting for 69.1%. Median and mean follow-up duration was 49 and 61 months (range, 1-214 months), Overall TCR was 92.9%. The 5-year disease-specific TCR for VS, nonvestibular schwannoma, meningioma, and pituitary adenoma were 97.4%, 91.7%, 93.8%, and 83.3%. Salvage therapy was indicated for eight patients at 4-110 months after SRS. Among symptomatic patients, post-SRS symptom(s) was improved, stable, and worse in 68.2%, 24.3%, and 3.6%, respectively. Radiological response rate for 111 evaluable patients was 94.6% (shrinkage, 28.8%; stable, 65.8%). OS was 96.1% without treatment-related mortality. One patient with post-SRS cranial nerve injury (0.8%, involving the trigeminal nerve, grade 2 toxicities). No grade 3-4 acute or late toxicity was found. Our results suggested that LINAC-based SRS effectively controls tumor growth and tumor-related neurological symptoms for patients with benign brain tumors. SRS is less aggressive, associated with low neurological morbidity and no mortality. Continuous follow-up is indicated to conclude longer outcomes.

High-Intensity Focused Ultrasound (HIFU) Focal Therapy for Localized Prostate Cancer with MRI-US Fusion Platform.

Objective The study aimed at investigating the outcome of prostate HIFU focal therapy using the MRI-US fusion platform for treatment localization and delivery. Methods It is a prospectively designed case series of HIFU focal therapy for localized prostate cancer. The inclusion criteria include clinical tumor stage ≤T2, visible index lesion on multiparametric MRI less than 20 mm in diameter, absence of Gleason 5 pattern on prostate biopsy, and PSA ≤ 20 ng/ml. HIFU focal therapy was performed in the conventional manner in the beginning 50% of the series, whereas the subsequent cases were performed with MRI-US fusion platform. The primary outcome was treatment failure rate which is defined by the need of salvage therapy. Secondary outcomes included tumor recurrence in follow-up biopsy, PSA change, perioperative complications, and postoperative functional outcomes. Results Twenty patients underwent HIFU focal ablation. HIFU on an MRI-US fusion platform had a trend of a longer total operative time than the conventional counterpart (124.2 min vs. 107.1 min, p=0.066). There was no difference in the mean ablation volume to lesion volume ratio between the two. The mean PSA percentage change from baseline to 6-month is more significant in the conventional group (63.3% vs. 44.6%, p=0.035). No suspicious lesion was seen at 6-month mpMRI in all 20 patients. Two patients, one from each group, eventually underwent radical treatment because of the presence of clinically significant prostate cancer in the form of out-of-field recurrences during follow-up biopsy. No significant difference was observed before and after HIFU concerning uroflowmetry, SF-12 score, and EPIC-26 score. It was observed that energy used per volume was positively correlated with PSA density of the patient (r = 0.6364, p=0.014). Conclusion In conclusion, HIFU with conventional or MRI-US fusion platform provided similar oncological and functional outcomes.

Early Assessment With Gastrointestinal Ultrasound in Patients Hospitalised for a Flare of Ulcerative Colitis and Predicting the Need for Salvage Therapy: A Pilot Study

Approximately 30% of patients hospitalised with severe ulcerative colitis do not respond to corticosteroids, but the decision to introduce salvage therapy is delayed to at least the third day of treatment, according to the widely applied Oxford criteria to assess response. This pilot study aimed to determine if gastrointestinal ultrasound performed on admission can predict steroid-refractory disease. In 10 consecutive patients with severe ulcerative colitis, gastrointestinal ultrasound was performed within 24 h of admission. Six patients failed corticosteroids and required infliximab salvage therapy. Colonic bowel wall thickness was a median of 4.6 mm (range 4.2–5.6 mm) in those responding to steroids compared with 6.2 mm (6–7.9 mm) in those requiring salvage therapy (p = 0.009). Any colonic segment with a bowel wall thickness of >6 mm was associated with the need for salvage therapy (p = 0.033). Gastrointestinal ultrasound may provide an early indication of poor corticosteroid response and enable a timelier introduction of salvage therapy in patients with severe ulcerative colitis.

Mo1274 MID TO LONG TERM EFFICACY OF ENDOSCOPIC THERAPY IN NEOPLASTIC BARETT’S ESOPHAGUS: A SYSTEMATIC REVIEW AND META ANALYSIS

Although endoscopic therapy is recommended in patients with neoplastic BE, there are limited data on long term follow up. Electronic literature search was performed in Pubmed, Embase, Google Scholar and Cochrane for eligible studies meeting following criteria: 1) BE patients with high grade dysplasia (HGD) and/or early cancer who underwent any form of therapy including ablation+/- endoscopic mucosal resection; 2) defined efficacy end-point: complete eradication of intestinal metaplasia (CEIM) defined as confirmation of absence of IM on biopsies post therapy; 3) follow up for treatment endpoints clearly defined as starting after study completion; 4) follow up > 2 years; 5) post treatment surveillance protocol clearly reported. Case series, review articles, editorials, abstracts and studies not meeting these were excluded. Primary outcome was long term efficacy (CEIM) at end of follow up. Secondary outcomes were: pooled rates of CEIM at completion of initial therapy and any recurrence (IM, HGD, cancer) at end of follow up period. Pooled rates with 95% CI and forest plots were created with assessment of heterogeneity (I2) using statistical software R. Meta-regression was performed to examine for co-variates if significant heterogeneity found. Using the focused inclusion criteria, a total of 12 studies with 1958 patients who completed follow up were eligible for analysis; 82.7 % males, average age 62.6 (+/- 4.8) years. Pooled CEIM at study completion was 87.8% (95% CI 82.2%-93.4%) whereas durable remission of CEIM was 72.6% (95% CI 61.7%-83.6%) at an average follow up of 3.5 years (Figure 1). Pooled difference between CEIM at therapy completion and at end of follow up was 14.1% (95% CI 5%-23.2%). Long term follow up (>5 years) information was only available from 2 studies including 112 patients: CEIM 48.2%. At 3.5 years of follow up, pooled recurrence rates for IM and HGD/cancer were 5.77 (95% CI 3.6 to 8) percent and 1.42 (95% CI 0.06-2.3) percent per person years, respectively. Meta-regression did not show a significant effect of BE length on mid term efficacy (p=0.9) whereas duration of follow up did impact the results (p<0.05). There was significant heterogeneity found (I2=96%) in primary outcome; lack of information on salvage therapy from majority of studies precluded further analysis of heterogeneity. There was no significant evidence of publication bias. Endoscopic therapy can provide mid term durable remission of BE in approximately 75% of the treated patients. True long term follow up data are not available currently and such studies are needed to determine the true efficacy, recurrence patterns, stratified surveillance and the need for salvage therapy in neoplastic BE patients.Proportion of patients with CEIM over 2-3 year follow up, 3-5 year follow up and more than 5 year follow upView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Delayed PET/CT scanning in locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving definitive chemoradiation: Outcomes and management of “incidental” findings.

e18558 Background: Comparative PET/CT scanning 3-4 months after chemoradiation is often used to determine the need for salvage therapy, but approaches to managing incidental findings prior to, and incomplete response after, therapy vary. Methods: PET/CT scans before and 3-4 months after completion of definitive combined modality therapy for locally-advanced head and neck cancer (AJCC7 stage III-IVB) from 2008-14 were evaluated for FDG-avid masses and abnormal metabolic activity outside of the expected area of involvement, response to treatment and subsequent management. Results: Of 78 eligible patients, 72 had follow-up scans. Scans prior to therapy demonstrated abnormal FDG uptake in non-enlarged cervical lymph nodes in 17 (22%) and were upstaged. Pre-treatment scans revealed FDG-avid uptake outside of expected involvement in 23 patients (9 lung [ &lt; 1.5 cm or ground glass], 4 GI, 3 bone [without CT correlate], 3 lymph nodes, 1 prostate, 1 thyroid, 3 other; 3 had multiple sites). Lung (2), bone (1) and thyroid (1) lesions were biopsied prior to therapy; on post treatment scans 20/23 demonstrated resolution while 2 had lung resections for new primaries (1 died). After therapy, 43/72 (60%) patients had a complete response (CR) without other abnormal uptake; 10/72 (14%) obtained a CR in treated areas, but developed metastases; 19/72 (26%) had persistent uptake, of whom 10 (14%) were shown to have persistent disease; 11 biopsies, 7 further PET/CT, 18 other imaging, 3 LN dissections (1 malignant) and two other salvage surgeries were performed. CR patients had a 3-year overall survival (OS) of 94%; OS was similar regardless of pre-treatment uptake. Conclusions: Minor FDG uptake outside of the head and neck on initial scanning is frequent and most of these will resolve. Persistent uptake is common 3-4 months after therapy but only half of these are persistent cancer. Patients with a normal PET/CT scan after therapy have excellent survival.

Optimal endoscopy timing in patients with acute variceal bleeding: A systematic review and meta-analysis

Although current guidelines recommend performing endoscopy within 12 hours for acute variceal bleeding (AVB), the optimal timing remains controversial. This study aimed to assess the effect of endoscopy timing on the mortality and rebleeding rates in AVB through a systematic review and meta-analysis of all eligible studies. PubMed, Cochrane Library, and Embase were searched for relevant publications up to January 2019. Overall mortality, rebleeding rate, and other clinical outcomes were determined. For the non-randomized studies, the risk of bias assessment tool was used to assess the methodological quality of the included publications. The Mantel-Haenszel random-effects model of the RevMan software (Cochrane) and the inverse variance method were used to analyse binary end points and continuous outcomes, respectively. This meta-analysis included five studies with 854 and 453 participants who underwent urgent (≤12 hours) and non-urgent endoscopies (>12 hours), respectively. All the included studies were retrospective in nature, because of obvious ethical issues. No significant differences in the severity indexes were found between the urgent and non-urgent groups. Three studies showed 6-week mortality and the others in-hospital mortality as main outcomes. No significant difference in overall mortality rate was found between the groups (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.36–1.45, p = 0.36). The rebleeding rate was similar between the two groups (OR: 1.21, 95% CI: 0.76–1.93, p = 0.41). Other outcomes such as successful haemostasis, need for salvage therapy, length of hospital stay, and number of blood transfusions were also similar between the groups. We demonstrated that endoscopy timing does not affect the mortality or rebleeding rate of patients with AVB. Therefore, an appropriate timing of endoscopy would be more important than an urgent endoscopy depending on each patient’s condition.