Negative Prognostic Factor For Overall Survival Research Articles

OR12-5 | LBSAT57 Long-term Follow-Up of Pheochromocytoma/Paraganglioma (PPGL) after first diagnosis: a retrospective single-center study of 173 patients

Abstract Background Pheochromocytoma (Pheo)/Paraganglioma (PGL), together PPGL, are rare but life-threatening tumors, with tumor relapse (TR) rates after initial surgery of 16.5%, and genetic mutations in about 30-40% of patients. Long-term follow-up (FU) and genetic testing in all patients are recommended. Questions remain, however, as to the most suitable duration of FU, the prognostic value of genetic diagnoses and of clinical, biochemical or radiological findings during FU, of the incidence of TR after recommended 10 years FU of low-risk sporadic Pheos, or of TR on morbidity and mortality. Objective, patients, and methods: We retrospectively determined the overall survival (OAS), progression-free survival (PFS) and tumor-recurrence (TR) in 173 patients with PPGL initially operated and followed-up at a single tertiary referral center from 1988 to 2020 by Kaplan-Meier Estimates, and assessed age, sex, hormonal activity, tumor size, and metastatic spread at first diagnosis, pathohistological PASS score, mutation-positive PPGLs (MP-PPGL), TR, and comorbidities (associated with increased cardiovascular risk) as to independent prognostic markers thereof by multivariate Cox-regression. Certificats of the Austrian death registry were also obtained. Results In 8 (5%) PPGLs there was no FU in the charts, but death certified occurring 65±28 (mean±SD, median 2.7) months after first diagnosis. Mean (±SD) age of the remaining 165 (43.9% female) patients (94.5 Pheos, 3.0% multiple PGLs, 2.5% head-and-neck PGLs) was 49(±16) years, mean (range) FU 90(3-537) months. 93 (54%) patients underwent genetic testing, 37 (40%, 21% of entire cohort) had MP-PPGL (mean±SD age 33.8±13.2 yrs, OAS 391 months). 5 of these 37 (13.5%), and 7 of 57 (12%) mutation-negative (MN-PPGL, mean±SD age 53.3±14.8 years, p<0.01 vs. MP-PPGL, OAS 190 months) died during FU (p=0.03). Male sex, higher age, presence of comorbidities, and primary metastatic disease were independent negative prognostic factors for OAS by univariate, but only age and metastatic disease remained significant by multivariate analysis. As to PFS, higher age and no hormonal activity were negatively associated by univariate, but not by multivariate analysis, as were all other tested parameters. Conclusions The cohort of our study is the third-largest original report on long-term FU and prognostic markers in PPGL. While others (Ayola-Ramirez et al, JECM 2011) in 371 patients found tumor size and sympathetic PGL independently associated with OAS, we did not. Patients may have harbored more aggressive tumors in that study, as higher primary metastatic spread (25% of Pheos, 60% of sympathetic PGL) was identified. We identified only age and metastatic disease as independent predictors of OAS, in line with data from Korea (Kim J H, et al., Endocrinol Metab. [Seoul]) in 1048 patients (9% with primary metastatis) and with a metaanalysis comprising 703 PPGLs (Crona J, Endocr Relat Cancer, 2019). Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.

Utilization Rate and Prognostic Impact of Brachytherapy for Bridging to Transplant in Intrahepatic Cholangiocarcinoma

<h3>Purpose/Objective(s)</h3> Intrahepatic cholangiocarcinoma (ICCA) patients who are dispositioned to liver transplant (LTX) can be bridged in the interim with any combination of systemic therapy and liver directed therapies such as radiotherapy (RT). The purpose of this study is to assess the utilization rate and prognostic impact of brachytherapy (BT) in a large national database. <h3>Materials/Methods</h3> The National Cancer Database (NCDB) was queried (2004-2017) for patients with ICCA who underwent LTX. Pearson chi-square testing was used to compare categorical frequencies between patients who received external beam RT without BT (EBRT alone) and patients who received BT. Propensity score matching (PSM) was performed to create a 1:1 matched cohort of patients who received EBRT alone v. BT. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which demographic and clinical factors were prognostic for OS. <h3>Results</h3> A total of 352 patients with median age 56 (IQR 49-62) were included in this study. A total of 212 (61%) received chemotherapy while 134 (39%) did not. A total of 216 (61%) received no RT, 92 (26%) received EBRT alone, and 44 (13%) received BT. RT began a median of 57 days (IQR 39- 89) after diagnosis. LTX occurred a median of 126 days (IQR 61- 202) after RT began. EBRT doses ranged from palliative doses of 20 Gy to definitive doses of 60 Gy (median 45 Gy, IQR 45- 45). BT doses were not available in >90% of cases. Surgical margins were negative in 298 (90%) patients, microscopically positive in 16 (5%) patients, & macroscopically positive in 18 (5%) patients. Within 30 days of LTX, 10 (5%) patients who received no RT died compared to 1 (1%) patient who received EBRT alone & 1 (3%) patient who received BT (p= 0.26). Compared to EBRT alone, patients who received BT were more likely diagnosed in 2012 or later (p= 0.02) and more likely grade 1 (p= 0.04). After PSM, there were no differences in demographic or clinical factors between patients who received EBRT alone v. BT. After PSM, the 4-year OS was 25% for EBRT alone & 62% for BT (p= 0.01). After PSM, on UVA BT (HR 0.36, p=0.02; 95% CI 0.16- 0.84) & insured status (HR 0.19, p=0.03; 95% CI 0.04- 0.86) were positive prognostic factors for OS while grade 3 disease (HR 4.0, p=0.04; 95% CI 1.07- 14.89) & positive surgical margin (HR 2.55, p=0.04; 95% CI 1.05- 6.18) were negative prognostic factors for OS. On MVA, over 50% of cases were dropped due to cumulative missing data and no factors remained prognostic. <h3>Conclusion</h3> The utilization rate of BT has increased as a bridging therapy for ICCA patients dispositioned to LTX. This study demonstrated a positive prognostic impact of BT relative to EBRT alone on UVA. This finding did not persist on MVA due to cumulative missing data from the various prognostic factors. A future prospective clinical trial should evaluate this.

1040P Nivolumab or atezolizumab in the second-line treatment of advanced non-small-cell lung cancer? Prognostic index based on real-world data

The efficacy of nivolumab and atezolizumab in NSCLC was documented in prospective trials. We aimed to confirm the benefits and indicate prognostic factors in daily practice. This study was a retrospective analysis of patients (pts) treated in the daily practice in Poland. The median of progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The log-rank test was used for comparisons. Cox regression analysis was used for multivariate analyses. SASS v.27.0 software was used. A total of 260 pts (ECOG 0-1) were qualified to nivolumab (134 pts) or atezolizumab (126 pts). 18% of pts ended the treatment before radiological assessment. At landmark time-points of 12 and 24 months 31 % and 9 % pts remained alive. Median PFS and OS were 3 (95% CI 2.57-3.42) and 10 months (95%CI 8.03-11.96) for overall population. For atezo and nivo mPFS were 3 vs 3 months (p=0.175), mOS - 8 vs 14 months (p<0,018). In a univariate analysis for all pts, sum of measurable lesions (SML) >100.5 mm (p<0.001), liver mets (p=0.024), bone mets (p<0.001), short response for chemo (<4 mths) (p<0.001), BMI <25.6 (p=0.039), platelets (PLT) >281.5 G/l (p <0.007), a neutrophil-to-lymphocyte ratio >3.68 (p = 0.0001), platelet-to-lymphocyte ratio >182.9 (p<0.001) and LIPI 2 score (p=0.028) had a negative impact on OS. Other factors were less relevant. In a multivariate analysis SML >100.5mm (p=0.007; HR=1.003, 95% CI 1.001- 1.005), PLT>281,5 G/l (p<0.001; HR=1.003, 95%CI 1.001-1.003) and bone mets (p<0.004; HR=1.58, 95% CI 1.04-2.38) were independent negative prognostic factors for OS. Drug type was not shown to affect OS. Based on analyses, a prognostic index was constructed with formula: PI = 0.002 x (Platelets) + 0.003 x (Bones) - 0.725 x (SML). After estimating regression coefficients for individual variables, points were assigned to them to obtain three prognostic groups. Median OS differed significantly-16 (95%CI 13.3-18.7), 7 (95% CI 4.83-9.17) and 4 months (95%CI 2.88-5.13), respectively. Nivolumab and atezolizumab produced similar clinical benefit, but the treatment outcomes were worse than in clinical trials. Prognostic indices may help to indicate subgroups likely to benefit.

P596: CLINICAL IMPACT OF TP53 DISRUPTION IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED WITH A BCR INHIBITOR. A CAMPUS CLL EXPERIENCE

Background: In chronic lymphocytic leukemia (CLL), the presence of TP53 aberration (mutations and/or deletion) predicts an increased risk of relapse and death after chemo-immunotherapy (CIT). Although TP53 deletion and mutations mostly co-occur and are considered equal prognosticators, the clinical impact of isolated or concomitant mutations and deletions remains unclear in the context of targeted agents. Aims: To investigate the clinical relevance of isolated or concomitant TP53 aberrations in a large cohort of CLL patients treated with BCR inhibitors. Methods: In the framework of an institutional Italian multicenter working group on CLL (Campus CLL), a retrospective analysis of 229 CLL patients (51 treatment naïve, and 178 relapsed/refractory) treated with ibrutinib was carried out. All patients referred to a single institution for del17p analyses by FISH (167-kb 17p13 orange probe, MetaSystems) and TP53 mutations by NGS, both analyses carried out on CD19-purified (>85% pure) CLL samples within 6 months prior the start of ibrutinib treatment. The median follow-up from ibrutinib treatment was 36.3 months (95% CI 29.5-41.5 months). Overall survival (OS) and progression free survival (PFS) were computed from the start of ibrutinib treatment. Results: In the CLL cohort, 76 patients with del17p showed a trend for inferior OS respect to wt cases (P=0.0662, Fig.1A), while a significant correlation was found with PFS (P=0.0162). With regard to TP53 mutations, 296 TP53 mutations were found in 126 patients (range of mutations/patients 1-11). As with CIT, TP53-mutated patients, irrespective of VAF (Fig.1B), experienced a significantly worse OS and PFS than wt cases also by univariate analyses (P=0.0160, and P=0.0378, respectively). The combination of del17p with TP53 mutation data identified 95 cases with no TP53 aberrations, 8 cases del17p only, 58 cases TP53-mutated only, and 68 cases bearing both del17p deletion and TP53 mutation (Fig.1CD). Only patients with concomitant TP53 mutations and del17p experienced significantly shorter OS and PFS compared to TP53wt cases (P=0.0122, and P=0.0076, respectively; Fig.1CD). Conversely, patients presenting a single aberration showed no significant differences compared to wt patients (Fig.1CD). The simultaneous presence of TP53 mutations and del17p remained an independent predictor factor both for OS and PFS by multivariate analysis, together with the previous therapy lines (0-1 vs. >1), and anemia. The evolution of TP53-mutated clones was assessed by longitudinal NGS analysis of sequential PB samples collected from 38 patients (16 relapsed, and 22 on treatment) corresponding to 127 TP53 mutations. Among relapsed cases, 7 showed a prominent expansion of the TP53-mutated clone, 8 remained stable, and the remaining case displayed an evident decrease (Fig.1E). In non-relapsed patients, 3 cases presented an increase of TP53 mutations, 13 remained stable, and 6 showed a reduction (Fig.1F), with no significant difference compared to relapsed cases (P=0.0623, c2 test). BTK and PLCG2 mutations were found in 9/16 (56%) relapsed cases and in 3/22 (14%) patients still on ibrutinib (P=0.0492, c2 test). Of note, only 3/7 relapsed cases that presented a positive selection for TP53 mutations showed the presence of BTK mutations at the time of relapse. Image:Summary/Conclusion: This retrospective study indicates that only the concomitant presence of TP53 mutations and deletion is an independent negative prognostic factor for OS and PFS in patients with CLL on ibrutinib treatment; the simultaneous investigation of del17p and TP53 mutations may lead to a more precise risk assessment.

Outcomes in patients with acute lymphoblastic leukemia who underwent second allogeneic hematopoietic cell transplantation for relapse after first transplantation.

Outcomes in patients with acute lymphoblastic leukemia (ALL) who experience relapse after allogeneic hematopoietic cell transplantation (HCT) are unsatisfactory. This study aimed to evaluate the outcomes of patients with ALL who underwent second HCT (HCT2) for relapse after first HCT. It was a single-center retrospective study including adult patients with ALL who underwent HCT2 between 1991 and 2020. The cohort was stratified according to the transplant year, and included 39 patients with a median age of 29years. A more recent transplant year was associated with achievement of complete remission (CR) and use of reduced-intensity conditioning (RIC), compared with an earlier transplant year. The overall survival (OS) rate and 2-year cumulative incidence of non-relapse mortality (recent vs. earlier) were 55% vs. 8% (P < 0.001) and 26% vs. 75% (P < 0.001), respectively. In multivariate analysis, non-CR (vs. CR; HR 3.6, 95% CI 1.2-11.3, P = 0.025) and myeloablative conditioning (vs. RIC; HR 3.5, 95% CI 1.3-9.4, P = 0.011) were negative prognostic factors for OS. Outcomes of the recent cohort from real-world data are promising, and achieving CR and using the RIC regimen at HCT2 may be an important therapeutic strategy.

Long-term oncologic outcomes in esthesioneuroblastoma: An institutional experience of 143 patients.

Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival. We performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were reported. Among 143 included patients, the 5-year OS was 82.3% and the 5-year PFS was 51.6%; 5-year OS and PFS have improved in the modern era (2005-present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p<0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p<0.05). Positive margin status had a negative effect on PFS (p<0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p<0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p<0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p<0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p<0.05). Patients with low Hyams grade and mKadish stage have favorable 5-year OS, PFS, and DMFS.

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis

目的探讨增强剂量免疫化疗联合自体外周血造血干细胞移植（ASCT）治疗初治、年轻、高危侵袭性B细胞淋巴瘤患者的疗效及预后因素。方法回顾性分析2011年1月至2018年12月在中国医学科学院血液病医院应用增强剂量免疫化疗联合ASCT治疗的63例初治、年轻、高危侵袭性B细胞淋巴瘤患者的临床和生存资料。结果63例患者的中位年龄为40（14～63）岁。诱导治疗方案包括R-DA-EP(D)OCH（52例）和R-HyperCVAD/R-MA（11例）。16例（25.4％）患者中期疗效评估为部分缓解，其中10例移植后获得完全缓解。中位随访50（8～112）个月，3年无进展生存（PFS）率和总生存（OS）率分别为（83.9±4.7）％和（90.4±3.7）％。单因素分析显示年龄调整的国际预后指数评分≥2分是影响OS的预后不良因素（P＝0.039），骨髓受累（BMI）是影响OS（P<0.001）和PFS（P＝0.001）的预后不良因素。多因素分析显示BMI是OS（P＝0.016）和PFS（P＝0.001）的唯一独立预后不良因素。结论一线应用增强剂量免疫化疗联合ASCT治疗年轻、高危侵袭性B细胞淋巴瘤可获得良好的长期疗效，BMI为不良预后因素。

Survival after cytoreductive surgery for peritoneal metastases in colorectal cancer patients: Does a history of resected liver metastases worsen the prognosis?

BackgroundNowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown. AimThe aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR). MethodsAnalysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020. ResultsAll patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found. ConclusionsLR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.

Polish Multi-Institutional Study of Children with Ependymoma-Clinical Practice Outcomes in the Light of Prospective Trials.

We performed a multi-institutional analysis of 74 children with ependymoma to evaluate to what extent the clinical outcome of prospective trials could be reproduced in routine practice. The evaluation of factors that correlated with outcome was performed with a log rank test and a Cox proportional-hazard model. Survival was estimated with the Kaplan–Meier method. The majority of patients had brain tumours (89%). All had surgery as primary treatment, with adjuvant radiotherapy (RTH) and chemotherapy (CTH) applied in 78% and 57%, respectively. Median follow-up was 80 months and 18 patients died. Five- and 10-year overall survival (OS) was 83% and 73%. Progression was observed in 32 patients, with local recurrence in 28 cases. The presence of metastases was a negative prognostic factor for OS. Five- and 10-year progression-free survival (PFS) was 55% and 40%, respectively. The best outcome in patients with non-disseminated brain tumours was observed when surgery was followed by RTH (+/−CTH afterwards; p = 0.0001). Children under 3 years old who received RTH in primary therapy had better PFS (p = 0.010). The best outcome of children with ependymoma is observed in patients who received radical surgery followed by RTH, and irradiation should not be omitted in younger patients. The role of CTH remains debatable.

The Survival Benefit for Optimal Glycemic Control in Advanced Non-Small Cell Lung Cancer Patients With Preexisting Diabetes Mellitus.

BackgroundDiabetes mellitus (DM) is a frequent comorbidity in patients with cancer. This study aimed to evaluate the prognosis of advanced non-small cell lung cancer (NSCLC) patients with DM and to assess whether an optimal glycemic control improves overall survival (OS).MethodsA total of 1279 advanced NSCLC patients including 300 (23.5%) with preexisting DM were retrospectively reviewed. The continuous relationship between glycated hemoglobin A1C (HbA1c) level and OS was analyzed by restricted cubic spline (RCS) function. Optimal HbA1c cut-off point was determined using X-tile analysis. Survival was analyzed with the Kaplan–Meier method and compared among groups stratified by diabetes status and HbA1c. Multivariable Cox proportional hazards regression analysis was employed to identify prognostic factors for OS after adjusting for baseline characteristics.ResultsDM and non-DM patients had similar OS (median (95% CI): 22.85 (20.05-26.73) vs. 22.22 (20.35-24.76) months, P=0.950). The multivariate Cox regression analyses showed that DM status was not a prognostic factor for OS (HR: 0.952, 95% CI: 0.808-1.122, P=0.559). However, there existed a non-linear but generally positive relationship between the elevated HbA1c level and increased risk of overall mortality. HbA1c > 6.6% was a negative prognostic factor for OS (HR: 1.593, 95% CI: 1.113-2.280, P=0.011). The median OS (95% CI) for nondiabetic patients, DM patients with HbA1c ≤6.6% and those with HbA1c > 6.6% was 22.22 (20.01-24.43), 25.28 (21.79-28.77) and 15.45 (7.57-23.33) months, respectively. Well-controlled DM patients had a comparable crude OS (HR (95% CI): 0.90 (0.76-1.08), P=0.273] compared to nondiabetic patients while patients with HbA1c>6.6% had a worse crude OS than patients without DM (HR (95% CI): 1.70 (1.24-2.34), P=0.001]. The survival benefit of good HbA1c control was prominent in all subgroups.ConclusionImpaired glycemic level negatively affects survival for patients with advanced NSCLC while proper glycemic control with HbA1c ≤6.6% improves the OS.

Baseline Serum Ferritin Differentially Predicts W24 Transfusion Independence Response for Momelotinib and Ruxolitinib in Patients with Myelofibrosis

Baseline Serum Ferritin Differentially Predicts W24 Transfusion Independence Response for Momelotinib and Ruxolitinib in Patients with Myelofibrosis

Treatment of 120 adult osteosarcoma patients with metachronous and synchronous metastases: A retrospective series of the French Sarcoma Group.

Treatment options for metastatic osteosarcomas are scarce. Following failure of standard first line therapy, patients who relapse present a challenging treatment dilemma, and have a poor prognosis. Surgical removal of all metastases is essential. A retrospective analysis of patients with metastatic osteosarcomas was conducted in 15 French Sarcoma Group centers. From January 2009 to December 2018, we identified 120 adult patients; 36 with synchronous and 84 with metachronous metastases with 74 males and 46 females. Mean age was 30 years (18-53). Metastatic sites were lung, bone and other in 91, 11 and 24 patients, respectively. Mean time to first metachronous metastases was 22 months (4-97). All patients except 13 (10.8%) with metachronous metastases received a first line systemic treatment for relapse, and 39 patients (32.5%) were included in a clinical trial. Eighty-one patients (67.5%) had local treatment of distant metastases. Median progression free survival (PFS) and overall survival (OS) were 5.5 (95% CI 4.6-6.4) and 20.5months (95% CI 13.2-27.7) respectively for the overall group. In multivariate analysis, more than five metastases, time to first metastases <24 months, were statistically significant negative prognostic factors for OS and PFS (P= .002, ≤.001 and P= .006, ≤.001, respectively). Surgery of metastases was associated with better prognosis on OS and PFS (P= .001 and .037, respectively). The presence of bone metastases was a negative prognostic factor on OS but not on PFS (P= .021). In reference sarcoma centers, relapsed osteosarcoma patients with more than one metastasis commonly receive more than one line of systemic therapy, and are included in clinical trial if available.

MP24-10 NEWLY-DIAGNOSED LOW-VOLUME METASTATIC PROSTATE CANCER; IS THERE A PLACE FOR CYTOREDUCTIVE RADICAL PROSTATECTOMY?

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-10 NEWLY-DIAGNOSED LOW-VOLUME METASTATIC PROSTATE CANCER; IS THERE A PLACE FOR CYTOREDUCTIVE RADICAL PROSTATECTOMY? Elise De Bleser, Nicolaas Lumen, Sarah Buelens, Wesley Verla, Wietse Claeys, Valérie Fonteyne, Sofie Verbeke, Geert Villeirs, Kathia De Man, Sylvie Rottey, Charles Van Praet, Karel Decaestecker, and Piet Ost Elise De BleserElise De Bleser More articles by this author , Nicolaas LumenNicolaas Lumen More articles by this author , Sarah BuelensSarah Buelens More articles by this author , Wesley VerlaWesley Verla More articles by this author , Wietse ClaeysWietse Claeys More articles by this author , Valérie FonteyneValérie Fonteyne More articles by this author , Sofie VerbekeSofie Verbeke More articles by this author , Geert VilleirsGeert Villeirs More articles by this author , Kathia De ManKathia De Man More articles by this author , Sylvie RotteySylvie Rottey More articles by this author , Charles Van PraetCharles Van Praet More articles by this author , Karel DecaesteckerKarel Decaestecker More articles by this author , and Piet OstPiet Ost More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiotherapy to the prostate (RTp) has recently been shown to prolong survival in patients with low-volume newly-diagnosed metastatic prostate cancer (ndmPC). Therefore it was suggested to be a possible standard of care treatment strategy in these patients. In contrast, to date, there is no data available whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp for these patients. The objective was to evaluate the efficacy and safety of cRP in low-volume ndmPC. METHODS: Eligible patients had low-volume ndmPC and were included in this prospective, multicentric study. Patients were included from 2014 until the end of 2020. In total, 109 patients entered the study and were offered cRP, RTp or no local therapy (NLT) (48, 26, 35, respectively). Treatment allocation was dependent on patient's preference. Median follow-up was 32 months (IQR: 16-49). The aim was to compare the outcome of cRP to RTp and NLT. Kaplan-Meier statistics were used to assess overall survival (OS), cancer-specific survival (CSS) and local-event free survival (LEFS). Uni- and multivariate Cox regression analysis was used to identify prognostic factors influencing OS. RESULTS: 3y-OS was 87%, 100% and 69% and 3y-CSS was 87%, 100% and 75% for cRP, RTp and NLT, respectively. OS was better for cRP and RTp compared to NLT (p=0.007 and p=0.04, respectively). However, no difference in OS was observed between cRP and RTp (0.9) (Figure 1). The 3y-LEFS was 86%, 70% and 55% for cRP, RT and NLT, respectively. Following cRP, LEFS was better compared to RTp (p=0.02) and NLT (p=0.004). No significant difference was seen between RTp and NLT (p=0.5). Negative prognostic factors for OS were advanced tumor stage, Eastern Cooperative Oncology Group ≥2 and NLT.Important selection bias was present as a consequence of treatment allocation being dependent on patient’s preference. CONCLUSIONS: OS and CSS of cRP was similar to RTp and was better compared to NLT and is an effective treatment strategy to prevent local events. Source of Funding: Kom Op Tegen Kanker (Stand Up to Cancer), Belgium © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e415-e416 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elise De Bleser More articles by this author Nicolaas Lumen More articles by this author Sarah Buelens More articles by this author Wesley Verla More articles by this author Wietse Claeys More articles by this author Valérie Fonteyne More articles by this author Sofie Verbeke More articles by this author Geert Villeirs More articles by this author Kathia De Man More articles by this author Sylvie Rottey More articles by this author Charles Van Praet More articles by this author Karel Decaestecker More articles by this author Piet Ost More articles by this author Expand All Advertisement Loading ...

Polyposis and Oncologic Outcomes in Young-onset Sporadic Colorectal Cancer.

AimThe present study aimed to investigate the effect of the presence of polyposis in sporadic early-onset colorectal cancer (EOCRC) on clinicopathological and oncological outcomes.MethodsThe retrospective study included patients with sporadic colorectal cancer aged 16 to 50 years who underwent curative resection at the general surgery clinics in two healthcare centers between 2013 and 2019. Patients were divided into two groups: polyposis and nonpolyposis. Clinicopathological characteristics and oncological outcomes were compared between the two groups.ResultsA total of 127 patients were included, of whom 60.6% were men. There were 25 (19.68%) patients in the polyposis group and 102 (80.31%) patients in the nonpolyposis group. Seventy-one (69.6%) of the nonpolyposis group and 23 (92.0%) of the polyposis group had adenocarcinoma histological types. The total number of patients with mucinous tumor and signet ring cell carcinoma in the nonpolyposis and polyposis groups was 31 (30.4%) and 2 (8.0%), respectively (p = 0.042). Five-year overall survival (OS) was 60 and 72% in the nonpolyposis and polyposis groups, respectively, and no significant difference was found (p = 0.332). In univariate analysis, American Joint Committee on Cancer (AJCC) tumor stage (pT) ≥3–4, lymph node positivity, presence of mucinous tumor and signet ring cell carcinoma, lymphovascular invasion, and advanced tumor-lymph nodesmetastasis (TNM) stage (III–IV) were found to be significant negative prognostic factors for OS, whereas none of these parameters were found to be prognostic factors in multivariate analysis. The presence of polyposis was not a significant factor on both univariate and multivariate analyses.ConclusionAlthough the sporadic EOCRC cases developing on the basis of polyposis can have slightly better oncological outcomes, these outcomes are mostly similar to those of cases with nonpolyposis.How to cite this articleAday U, Kafadar MT, Oğuz A, et al. Polyposis and Oncologic Outcomes in Young-onset Sporadic Colorectal Cancer. Euroasian J Hepato-Gastroenterol 2021;11(1):6–10.

Differential Effect of t(11;14) Abnormality on Survival and Depth of Response in African American (AA) and Non-AA (NAA) Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) in the Connect® MM Registry

Differential Effect of t(11;14) Abnormality on Survival and Depth of Response in African American (AA) and Non-AA (NAA) Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) in the Connect® MM Registry

Early Weight Loss as a Prognostic Factor in Patients with Advanced Gastric Cancer: Analyses from REGARD, RAINBOW, and RAINFALL Phase III Studies.

BackgroundWeight loss is common in advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA); however, the prognostic implications of weight loss during the first cycle (C1) of chemotherapy remain poorly characterized. In this study, we investigated the impact of early weight loss during systemic treatment as a potential prognostic factor for overall survival (OS) in patients with advanced G/GEA.Materials and MethodsWe performed a post hoc analysis of three phase III studies of ramucirumab. Patients were categorized into two groups: weight loss of ≥3% and <3% based on weight change during C1 (3–4 weeks) of treatment. OS by weight groups was assessed for each study and as a pooled meta‐analysis. The effect of C1 weight change on patient survival was evaluated using univariate and multivariate Cox models.ResultsA total of 1,464 patients with weight data at the end of C1 were analyzed: REGARD (n = 311), RAINBOW (n = 591), and RAINFALL (n = 562). For all three studies, there were fewer patients in the weight loss ≥3% than <3% group. OS was numerically shorter for patients with weight loss of ≥3% than for patients with weight loss of <3% during C1 irrespective of treatment arm. Similar treatment independent effects of early weight loss on OS were observed in the meta‐analysis. Overall, early weight loss ≥3% was associated with shorter survival in patients receiving active drug as well as placebo/best supportive care.ConclusionThis large post hoc analysis demonstrated that weight loss of ≥3% during C1 was a negative prognostic factor for OS in patients with advanced G/GEA.Implications for PracticeThis comprehensive analysis examining early weight loss during systemic treatment as a predictor of survival outcomes in patients with advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA) includes a large sample size, reliable on‐treatment data reported in well‐conducted phase III clinical trials, and global representation of cancer patients with advanced G/GEA. Understanding the impact of on‐treatment weight loss is clinically relevant and may represent an opportunity for targeted interventions.

Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study.

BackgroundProgrammed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM).MethodsFormalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome.ResultsHigh (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS.ConclusionsIn this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.

Prediction of clinical outcomes through assessment of sarcopenia and adipopenia using computed tomography in adult patients with acute myeloid leukemia.

Sarcopenia and adipopenia have prognostic significance in cancer. Analysis of a single abdominal computed tomography (CT) section at the third lumbar vertebra has been widely adopted for this purpose. The approach using a single section at the first lumbar vertebra level (L1) may extend clinical viability. We evaluated the prognostic value of sarcopenia and adipopenia assessed using a CT section at L1 in acute myeloid leukemia (AML). Data from 96 patients with available imaging were retrospectively reviewed. Patients with sarcopenia (37.5%) had significantly worse overall survival (OS) (median 17.8months vs. not reached, p = 0.038) and treatment-related mortality (TRM) (22.2% vs. 3.0%, p = 0.0019) than those without. Subcutaneous adipopenia (51.0%) was significantly associated with inferior OS (median 17.9months vs. not reached, p = 0.0011), progression-free survival (PFS) (median 6.2months vs. not reached, p = 0.004), and TRM (16.3% vs. 4%, p = 0.024). Visceral adipopenia (30.2%) was associated with poor OS (12.7 vs. 31.7months, p = 0.0055) and PFS (3.7 vs. 31.7months, p = 0.003). Multivariable analyses found sarcopenia, subcutaneous adipopenia and visceral adipopenia were significant negative prognostic factors for OS. Sarcopenia and adipopenia assessed using a single CT section at the L1 level are useful in predicting the prognosis of AML.

High serum C-reactive protein levels predict survival in patients with treated advanced lung adenocarcinoma.

BackgroundThe prognosis of non-small cell lung cancer (NSCLC) varies greatly depending on whether or not it can receive molecular-targeted drug treatment including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We investigated the clinical utility of C-reactive protein (CRP) levels measured at the time of diagnosis in EGFR-mutant and wild-type NSCLC patients who had undergone first-line therapy.MethodsSerum CRP levels were analyzed in 213 patients, of whom 89 patients had advanced EGFR-mutated NSCLC who underwent first-line EGFR-TKI treatment. We used Cox proportional hazards models to study the relationship between CRP and overall survival (OS). CRP cutoff values were obtained from the receiver operating characteristic curve.ResultsMean serum CRP level in treated NSCLC patients were not significantly different in patients with or without EGFR mutations. The optimal CRP cutoff values were 8.1 mg/L for EGFR-mutated NSCLC and 16.7 mg/L for EGFR-wild NSCLC. Based on multivariate analysis, high CRP level (EGFR-mutated, HR: 2.479, 95% CI: 1.331–4.619, P=0.004; EGFR-wild, HR: 3.625, 95% CI: 2.149–6.116, P<0.001) was a significant and independent negative prognostic factor for OS in patients with or without EGFR mutations.ConclusionsHigh CRP levels predicted a lack of response to treatment in patients with advanced lung adenocarcinoma with or without EGFR mutations. Thus, the CRP level is a good and easy to use prognostic factor and objective indicator for clinical practice.

Abstract PS13-49: Effectiveness of platinum-based chemotherapy for hormone receptor-positive HER2-negative metastatic breast cancer

Abstract Background: Platinum-based chemotherapy (CT) regimens have activity in triple-negative breast cancer (TNBC), with overall response rates around 50%. The evidence for activity of these regimens for hormone receptor (HR)-positive breast cancer is scarce. We aimed to evaluate the effectiveness of platinum-based CT for HR-positive HER2-negative metastatic breast cancer. Methods: We evaluated, retrospectively, electronic medical records of patients with HR-positive HER2-negative metastatic breast cancer who have received, at least, 1 dose of platinum-based CT in the metastatic setting from Jan/2015 to May/2020 in a single cancer center. Data on clinical and demographic features, treatment, and outcomes were collected. The primary study endpoint was the clinical benefit rate at 3 months. Secondary endpoints were overall response rate, progression-free survival (PFS), overall survival (OS), and prognostic factors. Results: 244 patients were included. All patients were female, with a median age of 51.5 years, 59% were premenopause, 32.8% were metastatic at diagnosis, and 63.5% had ECOG-PS 0-1 by the time of platinum-based CT initiation. Although tests for hereditary breast and ovarian cancer were not available, 41% of patients met criteria for hereditary cancer testing. Most patients had invasive ductal carcinoma (90.2%), estrogen receptor &amp;gt;10% positive (92.2%), and progesterone receptor &amp;gt;10% positive (69.7%). Main sites of metastatic disease were bone (76.2%), lymph nodes (59.4%), lung (52.9%), and liver (62.7%). The majority of patients had received previous palliative systemic therapy before platinum-based CT; 36.5% had not received previous palliative endocrine therapy (ET), and 30.7% had not received previous palliative chemotherapy. The preferred platinum-based CT regimen was cisplatin plus gemcitabine (68.8%), and a small proportion received single-agent platinum-based CT (14.3%). Forty-three patients (17.7%) started platinum-based CT during hospitalization. Grade 3-4 treatment-related toxicities occurred in 40.9% of the patients. The clinical benefit rate at 3 months was 41.2% in the overall population, 46.7% when platinum-based CT was used as first-line CT, and 38.6% when used as subsequent CT line. Overall response rate was 26.7% in first-line platinum-based CT and 18.1% in subsequent CT line. Median PFS and OS were 3.2 months (95% CI 2.8 - 3.8) and 8.6 months (95% CI 6.8 - 9.9), respectively. One-year OS rate was 37.1% (95% CI 30.5 - 43.7%). Factors associated with worse OS were ECOG-PS 3-4 (HR 1.85, 95% CI 1.21-2.82, P=0.004), presence of liver metastases (HR 1.61, 95% CI 1.16-2.23, P=0.004), and platinum-based CT initiation during hospitalization (HR 1.74, 95% CI 1.18-2.56, P=0.005). Conclusion: Despite some activity of platinum-based CT for HR-positive HER2-negative metastatic breast cancer, especially as first-line CT, response rates were lower than historically observed in TNBC. Platinum-based CT was associated with poor PFS and OS outcomes. Negative prognostic factors for OS were ECOG-PS 3-4, presence of liver metastases, and initiation of the platinum-based CT during hospitalization. Citation Format: Lucas Fernando Uratani, Francesco Sansone Bermejo, Pedro HenriqueShimiti Hashizume, Renata Colombo Bonadio, Laura Testa. Effectiveness of platinum-based chemotherapy for hormone receptor-positive HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-49.