Higher Rate Of Grade Research Articles

Efficacy of the ketogenic diet on ACTH- or corticosteroid-resistant infantile spasm: a multicentre prospective control study.

To determine the efficacy of ketogenic diet (KD) therapy on adrenocorticotropic hormone- (ACTH) or corticosteroid-resistant infantile spasm (IS), and identify relevant associated factors. A prospective controlled study was undertaken at 10 tertiary children's medical centres in mainland China. Participants were non-randomly assigned to KD therapy or control (adjustment of antiepileptic drugs). The primary outcome was the reduction in spasms and remission of hypsarrhythmia at the 16th week, divided into Grade I (spasm-free for at least one week with hypsarrhythmia remission), Grade II (≥50% spasm reduction and/or hypsarrhythmia remission) and Grade III (<50% spasm reduction with hypsarrhythmia). In total, 227 patients were recruited and assigned to the KD (135 patients) and control (92 patients) groups. The efficacy in the KD group was superior to that in the control group (Grade I: 13.4% vs. 10.9%; Grade II: 40.7% vs. 20.7%, p=0.025). Patients with a ketogenic ratio <3:1 had a higher rate of Grade I than those with ketogenic ratio ≥3:1 (66.7% vs. 33.3%, p=0.037). No significant correlation was found between the efficacy of KD and level of serum ketosis, aetiology of IS, or age. The efficacy of KD therapy was superior to adjustment of oral antiepileptic drugs in children with ACTH- or corticosteroid-resistant infantile spasms.

High-dose regimens of hypomethylating agents promote transfusion independence in IPSS lower-risk myelodysplastic syndromes: a meta-analysis of prospective studies.

The hypomethylating agents (HMAs) azacytidine (AZA) and decitabine (DAC) are usually administered after the failure of erythropoietin-stimulating agents for lower-risk myelodysplastic syndromes (LR-MDS). However, it is unclear whether one of these HMAs has superior efficacy and safety. This was investigated in the present study by means of a meta-analysis of prospective studies published between January 1990 and July 2020 in PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov databases; 19 studies with 1076 patients were included in the final analysis. The transfusion independence (TI) rate (66.7% [95% confidence interval: 41.7%–87.4%]) was higher with AZA 75 mg/m2/day for 7 days than with other regimens (all p<0.025). The proportion of patients with intermediate-1 risk influenced overall survival (p<0.05). There were no differences in treatment response, survival, and adverse event rates between patients treated with AZA (75 mg/m2/day for 5 days) and DAC (20 mg/m2/day for 3 days), although the latter group had a higher rate of grade 3/4 anemia (15.8% vs 0.0%; p<0.0001) and lower rate of diarrhea/constipation (6.9% vs 25.0%; p=0.002). Thus, both HMAs at high doses achieved reasonable response and TI rates with acceptable side effects, but did not prolong the overall survival in LR-MDS patients.

The Clinical Significance of Donor Lung Weight at Procurement and during Ex Vivo Lung Perfusion

<h3>Purpose</h3> Elevated donor lung weight can result from excess extravascular lung water and adversely affect transplant suitability and post-transplant outcomes. We sought to define the impact of lung weight on 1) donor lung suitability and 2) post-transplant graft dysfunction in lungs transplanted with and without ex vivo lung perfusion (EVLP). <h3>Methods</h3> From Feb 2016 to Aug 2020, 365 human lung donors were reviewed. Of 365, 239 were transplanted without EVLP, 74 treated with acellular EVLP (50 went on to transplant), and 52 declined for transplant without EVLP. Lung weights were measured at two time points: at 0 hr (LW0; after lung explant or start of EVLP), and after EVLP was completed (LWend). LW0 data were divided into 4 quartiles (Category 1=0-25%, Category 2=25-50%, Category 3=50-75%, and Category 4=75-100%) within 3 height groups (< 160, 160-180, and ≥ 180 cm) [Figure]. LWend data were also divided into the same 4 quartiles as LW0 data. <h3>Results</h3> For LW0 Category 4, EVLP was utilized more frequently (45 vs. 17%, p < 0.05). Higher rates of Grade 3 PGD at 72 hrs (18 vs. 9%, p = 0.44), longer times to extubation, and longer ICU/hospital days (p < 0.05, each) were observed vs. LW0 Categories 1-3. For lungs treated with EVLP, LW0 Category 4 lungs were associated with a significantly lower transplant suitability rate (57 vs. 75%, p = 0.02) and higher incidence of PGD grade 3 at 72 hrs vs. LW0 Categories 1-3 (26 vs. 3%, p < 0.05). LWend Category 4 lungs were also associated with lower transplant suitability after EVLP (55 vs. 90%, p < 0.01), and an increased incidence of PGD grade 3 at 72 hrs (21 vs. 0%, p < 0.01), compared to LWend Categories 1-3. <h3>Conclusion</h3> Donor lungs in the highest quartile of lung weight are associated with increased need for EVLP, but lower transplant suitability rates after EVLP when compared to lungs with lower weight. Donor lungs in the highest quartile are also associated with higher Grade 3 PGD rates and longer ICU/hospital stay. These findings should be taken into account when high weight donor lungs are considered for clinical use.

Skeletal muscle loss during chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study

PurposeWe showed in a previous study that the PG-SGA score is associated with survival and chemotherapy-related toxicities in metastatic colorectal cancer (mCRC) patients. The objective was to evaluate the association between pretherapeutic sarcopenia and variation in skeletal muscle index (SMI) during treatment with these outcomes in the same population. MethodsThis prospective, multicenter, observational study enrolled non-pretreated mCRC patients. SMI was measured on routine CT scan at day 0 (D0) and day 60 (D60). Nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Results149 patients were included from 7/2013 to 11/2016. Pretherapeutic sarcopenia was not significantly associated with survival or chemotherapy-related toxicities. The decrease in SMI > 14% was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95% CI 1.1−3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.6, 95% CI 1.4−4.8, p = 0.002), independently of hypoalbuminemia and malnutrition defined by PG-SGA. Patients with a SMI decrease > 14% had a higher rate of grade ≥ 2 clinical toxicities (40% vs 22%, OR 3.0, 95% CI 1.2−7.7, p = 0.02), but the difference was not statistically significant in multivariable analysis. ConclusionTo our knowledge, this is the first study to assess prospectively the association of skeletal muscle loss with survival and treatment toxicities in non-pretreated patients with mCRC. Pretherapeutic sarcopenia was not associated with poor outcomes, but the loss of skeletal muscle mass within 60 days from treatment start was highly prognostic, independently of other prognostic and nutritional factors.

Subcutaneous daratumumab in Asian patients with heavily pretreated multiple myeloma: subgroup analyses of the noninferiority, phase 3 COLUMBA study

The phase 3 COLUMBA study demonstrated noninferiority of subcutaneous daratumumab (DARA SC) to intravenous daratumumab (DARA IV) in relapsed or refractory multiple myeloma. We present a subgroup analysis of Asian patients from COLUMBA. Eligible patients had ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were double refractory. Co-primary endpoints were overall response rate (ORR) and maximum trough concentration (Ctrough). Secondary endpoints included rates of infusion-related reactions, progression-free survival, and patient-reported satisfaction with therapy. Sixty-seven Asian patients (DARA SC, n = 30; DARA IV, n = 37) were randomized, including 42 Japanese patients (DARA SC, n = 18; DARA IV, n = 24). Comparable ORRs for DARA SC versus DARA IV were seen in the Asian cohort (66.7% vs 43.2%) and Japanese-only cohort (61.1% vs 54.2%), including patients weighing ≤ 65 kg. Similarity of Ctrough was seen in both Asian and Japanese-only cohorts; the ratio of the geometric mean of the Ctrough concentrations for DARA SC/DARA IV was 143.96% (90% confidence interval (CI), 112.03–185.00%) and 148.02% (90% CI, 113.32–193.34%), respectively. The Asian cohort (both treatment groups) and Japanese-only cohort (DARA SC group) experienced higher rates of grade 3/4 cytopenias compared with the global COLUMBA population, occurring predominantly in patients of low bodyweight; no patients discontinued treatment due to cytopenias. The Cancer Therapy Satisfaction Questionnaire results generally favored DARA SC. In the Asian and Japanese-only cohorts, DARA SC was comparable to DARA IV. The efficacy, pharmacokinetic, safety, and satisfaction results were generally consistent with the global COLUMBA population regardless of patient bodyweight. ClinicalTrials.gov Identifier: NCT03277105

Cumulative operative time and postoperative complication risk in synchronous resections of colorectal liver metastases and primary tumors

Presenter: Allison N Martin MD, MPH | The University of Texas MD Anderson Cancer Center Background: Selection of patients for synchronous resection of colorectal liver metastases (CLM) and primary colorectal cancers (CRC) is complex due to inherent complication rates. We sought to identify perioperative factors associated with postoperative morbidity after synchronous resection. Methods: Using a prospectively maintained quality improvement database, adult patients undergoing synchronous CLM and CRC resection from 1/1/2017-7/1/2020 were included, and 90-day postoperative outcomes were collected. The primary outcome of this study was to estimate effects of clinical covariates on the occurrence of grade 2 or worse (grade ≥2) complications as defined by the Accordion Severity Grading System. Univariate and sequential multivariable logistic regression models were used to estimate the impact of colorectal resection type, Kawaguchi-Gayet complexity grade of hepatectomy and perioperative risk factors on outcomes, including 90-day postoperative complications. Results: A total of 120 patients underwent synchronous CLM and CRC resection during this study period. Most patients (62%) underwent a low-complexity hepatectomy (Kawaguchi-Gayet 1 [KG1]), and the most common CRC resections were right colectomy (n=37, 31%) and proctectomy (n=40, 33%). The most common synchronous resection was a KG1 CLM resection with proctectomy (n=30, 25%). Nearly 40% (n=46) of patients experienced grade ≥2 complications, and 12% (n=14) experienced grade ≥3 complications. Grade ≥2 complication was associated with longer length of stay (median LOS 7.5 vs. 4 days, p506 minutes) had higher rates of grade ≥2 complications (37% vs. 15%, p=0.04) and were associated with a greater than 4-fold increased risk of grade ≥2 morbidity (OR 4.3, 95% CI 1.41-13.1, p=0.01). As an intraoperative surrogate for complexity of hepatectomy, Pringle inflow occlusion time above the median (33 minutes) was not significantly associated with increased risk of grade ≥2 morbidity (p=0.26). In multivariable analysis, increasing operative time was independently associated with grade ≥2 complications, especially for those resections in the highest quartile (OR 7.28, 95% CI 1.73-30.6, p=0.007; Table 1). Conclusion: In patients preoperatively selected for synchronous CLM and CRC resection, prolonged operative time is independently associated with grade ≥2 complications. Surgical teams should consider preoperative initiatives to address factors related to total operative time, including team dynamics, communication, and case selection, to accurately predict and reduce cumulative operative time as a strategy to mitigate complication risk. Operative time may also inform intraoperative decisions after the hepatectomy to continue with or delay the colorectal resection.

Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD.

The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.

Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer.

A proper estimation of the magnitude of the overall survival (OS) benefit from infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab versus doublets + bevacizumab is lacking because all trials that have investigated this regimen had primary end points other than OS. To test OS with higher power and to explore the interaction of treatment effect with main patient and disease characteristics, we performed an individual patient data (IPD) meta-analysis. IPD from 5 eligible trials were collected: CHARTA (ClinicalTrials.gov identifier: NCT01321957), OLIVIA (ClinicalTrials.gov identifier: NCT00778102), STEAM (ClinicalTrials.gov identifier: NCT01765582), TRIBE (ClinicalTrials.gov identifier: NCT00719797), and TRIBE2 (ClinicalTrials.gov identifier: NCT02339116). The primary end point was OS. Secondary end points were progression-free survival (PFS), objective response rate (ORR), R0 resection rate, grade 3/4 adverse events, and subgroup analyses according to clinical and molecular characteristics. A total of 1,697 patients were randomly assigned to FOLFOXIRI + bevacizumab (n = 846) or doublets + bevacizumab (n = 851). Most (78%) had an Eastern Cooperative Oncology Group performance status of 0, and the median age was 61 years. After a median follow-up of 39.9 months, patients assigned to FOLFOXIRI + bevacizumab had significantly longer OS than those assigned to doublets + bevacizumab (median, 28.9 v 24.5 months; hazard ratio [HR], 0.81; 95% CI, 0.72 to 0.91; P < .001), with no significant heterogeneity among trials (P = .39; I2 = 2%). No significant interaction effect between treatment arm and investigated characteristics was demonstrated. Patients assigned to FOLFOXIRI + bevacizumab had longer PFS (median, 12.2 v 9.9 months; HR, 0.74; 95% CI, 0.67 to 0.82; P < .001), higher ORR (64.5% v 53.6%; P < .001), higher R0 resection rate (16.4% v 11.8%; P = .007), and higher rates of grade 3/4 neutropenia (45.8% v 21.5%; P < .001), febrile neutropenia (6.3% v 3.7%; P = .019), and diarrhea (17.8% v 8.4%; P < .001). FOLFOXIRI + bevacizumab significantly and meaningfully improves survival of patients with metastatic colorectal cancer compared with doublets + bevacizumab and provides advantage in PFS, ORR, and R0 resection rate at the price of a moderate increase in toxicity. No increased benefit is observed among patients with BRAF-mutant tumors.

ERCC1, XRCC1, and GSTP1 Polymorphisms and Treatment Outcomes of Advanced Epithelial Ovarian Cancer Patients Treated with Platinum-based Chemotherapy.

Objective:The first line regimen for treating epithelial ovarian cancer (EOC) is platinum-based chemotherapy. Various factors impact its effectiveness including polymorphisms of enzymes in platinum-related metabolism processes. Methods:We conducted the study to investigate the association between polymorphisms of ERCC1, XRCC1 and GSTP1, which responsible for platinum’s metabolisms in Thai epithelial ovarian cancer patients. Results:Fifty-two patients with advanced epithelial ovarian cancer were enrolled into this study. Genotyping analysis of ERCC1 (C->A, rs3212986), XRCC1 (A->G, rs25487) and GSTP (A->G, rs1695) were performed which variant allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. Patients with homozygous variant type (A/A) of ERCC1 C8092A had higher rate of platinum-resistance (75% vs 16.7%, p =0.046). In addition, the significant association of GSTP1 polymorphism and grade 2 anemia was found. Patients with A/G genotype of GSTP1 had higher rate of grade 2 anemia (81.8% vs 46.3%, p =0.036). Conclusions:Genetic polymorphisms of ERCC1, and GSTP1 might be useful biomarkers for prediction of clinical benefit and toxicities of platinum-based chemotherapy in Thai epithelial ovarian cancer patients.

Simultaneous Versus Staged Resection of Colorectal Cancer Liver Metastasis: A Retrospective Single-Center Study

BackgroundFor patients with colorectal cancer and synchronous liver metastasis, either a simultaneous, or a two-staged resection of the primary tumor and the liver metastases is possible. There are currently no guidelines preferring one approach to the other. Material and methodsConsecutive patients who underwent hepatic resection at our university hospital from 2007-2016 were included. Clinical, histopathologic, serologic, and survival data were analyzed. The primary end point was tumor-specific survival for patients with simultaneous versus staged resections. ResultsOf all 140 patients, 68 underwent simultaneous resection and 72 underwent staged resection. The characteristics of both groups were comparable. Patients with simultaneous resections had a shorter duration of cumulative operation time (299 versus 460 min; P = 0.003) and a shorter cumulative length of hospital stay (23 versus 43 d; P = 0.002). Perioperative mortality (P = 0.257) did not differ significantly; however, patients with simultaneous resections had higher rates of grade 2 complications according to Clavien-Dindo (P < 0.001). Tumor-specific 1-y survival was 85 ± 5% for simultaneous and 83 ± 5% for staged resection (P = 0.631). On multivariable analysis, pT4 (P = 0.038), pN3 (P = 0.003), and G3/4 (P = 0.041) of the primary tumor and postoperative complications (Clavien-Dindo 3/4/5, P = 0.003) were poor prognostic factors regarding tumor-specific survival. ConclusionsThis is one of the largest and most thoroughly documented retrospective single-center studies of consecutive patients with synchronous hepatic metastases. Simultaneous resection of colorectal cancer together with hepatic metastases is a safe procedure in selected patients and does not have a significant influence on long-term survival.

What Awaits on the Other Side: Post-Lung Transplant Morbidity and Mortality After Pre-Transplant Hospitalization.

BackgroundMorbidity and mortality rates after lung transplantation remain high compared to other solid organ transplants. In the lung allocation score era, patients given the highest priority on the waitlist are those with the greatest severity of illness, who often require preoperative hospitalization.Material/MethodsTo determine the association of pre-transplant hospitalization with post-transplant outcomes, we retrospectively evaluated 448 lung transplant recipients at our center between January 2010 and July 2017 (114 hospitalized; 334 outpatient).ResultsSurvival was similar between the groups (hazard ratio 0.93 [95% CI 0.61 to 1.42], p=0.738). However, hospitalized patients had longer hospital and intensive care unit length of stay compared to outpatients – 25 vs. 18 days, (p<0.001) and 9.5 vs. 6 days, (p<0.001), respectively. Hospitalized patients had higher rates of Grade 3 primary graft dysfunction – 29.8% vs. 9.6%, p<0.001 – and remained mechanically ventilated longer – 6 vs. 3 days, p<0.001. A greater percentage of hospitalized patients needed a tracheostomy and a re-operation within 30 days – 39.5% vs. 15.3% (p<0.001) and 22.8% vs. 12.0% (p=0.005) – respectively. After discharge, 28% of hospitalized patients required acute rehabilitation compared with 12% of outpatients (p=0.001).ConclusionsWhile pre-transplant hospitalization is not associated with mortality, it is associated with significant morbidity after transplant.

Robotic sphincter saving rectal cancer surgery: A learning curve analysis.

Longer operation time is one of the major obstacles in front of the proposed benefits of robotic rectal surgery. We intended to evaluate the learning process for robotic surgery in sphincter saving rectal cancer surgery. The learning curve was evaluated using the cumulative sum (CUSUM) method. The variable evaluated for learning curve calculation was the operative time. The learning curve was divided into two phases: initial 52 operations comprised phase 1 and the following 44 operations represented phase 2. Interphase comparisons showed that phase 2 patients had shorter operation times (323.3 ± 102.8 vs. 379.9 ± 108.7 min, p = 0.011), less blood loss (37.2 ± 51.0 vs. 87.7 ± 124.8 mL, p = 0.009), longer distal resection margins (4.5 ± 4.3 vs. 2.5 ± 1.7 cm, p = 0.008), and higher rates of grade 3 mesorectal completeness (p = 0.001). In this study, we saw that the cut-off level in the learning curve of a laparoscopically experienced surgeon could be beyond the numbers reported in the literature.

Salvage radiotherapy after chemotherapy for unresectable locally advanced non-small cell lung cancer in real world.

e21052 Background: For patients with unresectable stage III disease, combined modality therapy (chemoradiation) is superior to radiation alone, and concurrent chemoradiotherapy (CCRT) is superior to sequential chemoradiotherapy (SCRT). The current standard of care for unresectable stage III disease is CCRT. Consequently, CCRT is commonly given to patients with minimal or no comorbidities, a good general condition, and who are relatively young. SCRT may be a valuable alternative for patients who are not eligible for CCRT. However, the role of salvage radiotherapy (SRT) after chemotherapy for patients with unresectable stage III disease without CCRT or SCRT is currently unknown. Methods: Patients with unresectable stage III disease receiving chemoradiotherapy were enrolled. All patients were treated with CCRT, SCRT or SRT. Overall survival (OS) was estimated by Kaplan-Meier curves. Results: From May 2014 to September 2018, 216 patients were enrolled, including 65 (30.1%) who received CCRT, 80 (37.0%) who received SCRT, and 71 (32.9%) who received SRT. No significant difference in gender, age, performance status, TNM stage, or EGFR gene status among the three groups. The median OS for the entire cohort was 22.1 (range: 18.4–25.8) months. The median OS in CCRT, SCRT, and SRT group were 29.7, 21.3, and 19.1 months, respectively (P = 0.011). The difference was statistically significant between CCRT group and SCRT or SRT group but was not between SCRT and SRT group. The 1-year survival rate in CCRT, SCRT, and SRT group were 89.2%, 75.0%, and 75.2%, respectively. However, the 3-year survival rate in CCRT, SCRT, and SRT group were 42.7%, 32.7%, and 9.6%, respectively. However, CCRT also has a higher rate of Grade 3 or 4 acute esophagitis and pneumonitis . Conclusions: The current study demonstrated compared with CCRT and SCRT, SRT had reduced patient survival survival time significantly.

Leukocytes with bound platelets as a predictive biomarker for immune-related adverse events (irAEs) in advanced non-small cell lung cancer (NSCLC) patients (pts) receiving anti-PD-(L)1 agents.

e15047 Background: Anti-PD-(L)1 blocking agents can induce irAEs, compromising treatment continuation and patient safety. Since complexes of leukocyte-platelet have been shown to play a role in inflammation by reducing cytokine production, we hypothesize that the percentage of these complexes could be used as a predictor of irAEs in pts receiving anti-PD-(L)1 agents. Methods: From May 2015 to January 2019, 87 advanced NSCLC pts treated with anti-PD-(L)1 agents at our institution were prospectively included. Percentages of circulating CD4+T lymphocytes and monocytes with bound platelets (CD4+PLT+ and CD14+PLT+, respectively) were obtained by flow cytometry and compared between NSCLC pts and healthy donors (HD, n = 26). The association of leukocyte-platelet complexes with the presence of irAEs was analyzed. According to CD4+PLT+ and CD14+PLT+ levels, NSCLC pts were grouped as CD4+PLT+ high (n = 29), CD4+PLT+ low (n = 58) and as CD14+PLT+ high (n = 36) and CD14+PLT+ low (n = 51). Frequencies and grade of irAEs were compared between groups using Chi-square test. Results: NSCLC pts showed significant higher percentages of circulating CD4+PLT+ and CD14+PLT+ than HD (9.41±0.54% vs. 6.01±0.45% and 57.44±2.42 vs. 35.43±2.22, respectively; p&lt; 0.001). No significant differences in CD4+PLT+ and CD14+PLT+ were found according to the presence of irAEs. CD4+PLT+ high group presented a higher rate of dermatological irAEs while CD4+PLT+ low group showed higher rate of non-dermatological irAEs (dermatological: 44.85% vs. 8.6%; non-dermatological: 10.3% vs. 39.7%, respectively; p&lt; 0.001). Lower percentage of grade ≥2 irAEs was observed in the CD4+PLT+ high group than in the CD4+PLT+ low group (17.3% vs. 41.4%; p&lt; 0.05). No significant differences in the type of irAEs were observed between CD14+ PLT+ high and low groups. Pts with CD4+PLT+ high and CD14+PLT+ low levels showed the lowest rate of irAEs, presenting only grade ≤1 irAEs (53.8% dermatological, 7.7% dermatological + non-dermatological, 38.5% no-irAEs). In contrast, pts with CD4+PLT+ low and CD14+PLT+ high levels presented higher rate of grade ≥3 irAEs (50% grade 0-1, 20% grade 2, 30% grade ≥3; p&lt; 0.05) and predominantly developed non-dermatological irAEs (45% non-dermatological, 30% dermatological + non-dermatological, 25% no-irAEs; p&lt; 0.01). Conclusions: Combining CD4+ PLT+ and CD14+ PLT+ levels may be used as predictive of development and severity of irAEs in advanced NSCLC pts receiving anti-PD-(L)1 agents.

Metastasis free survival in older men with nonmetastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: An FDA-pooled analysis.

12038 Background: The FDA has approved three androgen receptor (AR) inhibitors for nonmetastatic castration-resistant prostate cancer (nmCRPC) based on improvements in metastasis-free survival (MFS). MFS is an earlier endpoint, defined as the time from randomization to either imaging-detectable distant disease or death. This pooled analysis examines MFS, time to initiation of cytotoxic chemotherapy (TTCyto), and safety outcomes in men over 80 treated with AR inhibitors. Methods: Data was pooled from three randomized controlled studies (n=4117) of AR inhibitors for nmCRPC. The treatment effect of AR inhibitors on MFS and TTCyto across age groups was evaluated using Kaplan-Meier estimates and a Cox proportional hazards regression model. Hazard Ratios for MFS and TTCyto were adjusted for baseline ECOG, total Gleason score, PSA doubling time, and prior bone-targeting therapy. Results: For patients age 80 years or older (n=675) who were treated with AR inhibitors, the hazard ratio was 0.38 (95% CI 0.29, 0.49) with an estimated median MFS of 40 months (95% CI 36, 41) versus 22 months (95% CI 18, 29) for those treated with placebo (n=348). For patients &lt;80 (n=2019) treated with AR inhibitors, the HR was 0.31 (95% CI 0.27, 0.36) with an estimated median MFS of 41 months (95% CI 36, NR) versus 16 months (95% CI 15, 18) for those treated with placebo (n=1075). Patients over 80 also derived similar improvements in time to initiation of cytotoxic chemotherapy (HR 0.43 95% CI 0.23, 0.82), compared to their younger counterparts (HR 0.41 95% CI 0.33, 0.50). See Table for selected safety outcomes. Conclusions: In an exploratory subgroup analysis, older men (≥80) with nmCRPC derived similar benefit in MFS and time to initiation of cytotoxic chemotherapy with AR inhibitors compared with younger patients. Men age 80 and above experienced higher rates of Grade 3-4 adverse events, serious adverse events, falls, and fractures. This trend towards increased toxicity was observed regardless of treatment arm. Analysis of patient reported outcomes is ongoing. [Table: see text]

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM=79, MA-PB=183, RIC-BM=192, RIC-PB=192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P=.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P=.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P=.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT.Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.

Clinical Outcomes of Dose-escalated Radiotherapy for Localised Prostate Cancer: A Single-institution Experience.

To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p<0.01). Dose escalation to >74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage.

Treatment after breast cancer recurrence: Conserving surgery or adenomastectomy?

Introduction: Different factors are related with the increased risk of local recurrence, such as tumor grade, surgical margins and age. The recurrence of a tumor shows the aggressiveness of the disease and can be related with progression and worse prognosis. Radical mastectomy is the standard treatment for patients who present local recurrence after conserving surgery (CS); however, different studies have shown oncological safety using a new conserving surgery as an alternative to treat recurrence in selected patients. In the past few years, due to an increasing concern of mastologists with oncological safety, besides the aesthetic result, adenomastectomy (nipple-sparing mastectomy, NSM) became a good therapeutic choice for patients with breast cancer. Several authors have demonstrated similar recurrence and survival rates when compared to NSM techniques and total mastectomy. This study aims at assessing the local recurrence rates and the distance of NSM versus CS for the treatment of breast cancer recurrence. Methods: We assessed data from patients with breast cancer recurrence after conserving surgery who were treated with NSM, 24 patients, or new CS, 22 patients. All surgeries to treat the recurrence were carried out between 2001 and 2017. Results: The mean age of patients submitted to NSM was 52.7 years, and 61.3 years in the CS group. Patients submitted to a new conserving surgery presented 81.8% of tumors smaller than 2 cm; 81.3% grade 1 and 2 tumors; and 43.9% of luminal A tumors. In comparison to these characteristics, the patients who underwent NSM demonstrated lower rates (66.7%) of tumors smaller than 2 cm, higher rates of grade 2 (63.2%) and 3 (36.8%) tumors, and only 26.4% presented luminal A tumors, being the highest percentage (52.6%) of luminal B tumors. After a mean follow-up period of 140 months, the local recurrences were similar for both groups: 20.9% in NSM, and 22.7% in CS. Only 1 (4.2%) patient submitted to NSM presented metastasis, and in the CS group, no patient presented metastasis. Conclusions: By assessing the characteristics of patients submitted to NSM or CS for the treatment of breast cancer recurrence after previous CS, we observed younger patients and more aggressive tumors in the group that underwent NSM. Despite these characteristics, the local recurrence rates were similar in both surgeries. The presented local recurrence rates are high, and show the difficulty to treat the recurrence of previous tumors. No patient in the CS group presented with metastasis, and only one was shown in the group of patients submitted to NSM. These results suggest that NSM can be a surgical option to treat breast cancer recurrence when CS is not possible; however, further studies need to be carried out to elucidate these findings.

The Impact of Age on the Outcome of Primary Treatment for Classical Hodgkin's Lymphoma: 70 Years of Age Is a Clinical Relevant Cutpoint and the Most Important Predictor of Overall Survival

Introduction: Classical Hodgkin lymphoma (cHL) typically affects younger patients but 15-35% are &amp;gt;60 years. The age used to define an elderly population has varied but age 60 is frequently used. A clinically relevant definition of older age could be based on the use of alternate treatments due to different efficacy and/or toxicity. Treatment outcomes may also be influenced by tumor biology and patient comorbidity that vary with age. We evaluated the effect of age on treatment outcomes in cHL. Methods: All cHL patients treated at our centre between Jan 1999 and Dec 2015 were retrospectively analyzed. Clinical data were obtained from prospectively collected Lymphoma database and additional data was manually retrieved. Treatment for localized disease was combined modality (2-4 cycles of ABVD and potentially 6 cycles for bulk disease &amp;gt; 10 cm; radiation doses 20-35 Gy) with advanced disease typically receiving chemotherapy alone (ABVD 6-8 cycles). Older patients received individualized treatment. We used the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), (Sorror Blood 2005) as the elements can be abstracted retrospectively. Results: 607 patients were identified; 14% were &amp;gt;60 years and 6% were age &amp;gt;70. Baseline characteristics are outlined in table 1. Patients &amp;gt;70 presented more frequently with high-risk HCT-CI and worse ECOG PS. Patients &amp;gt; 60 presented more frequently with advanced stage (61-70 age group: 40%; &amp;gt;70 years: 46%). 65% of the patients age &amp;gt;70 presented with an IPS of &amp;gt;3. Chemotherapy alone approaches were used more commonly in older patients (age 61-70: 40%; age 70+: 51%) than in those &amp;lt;60 years (25%). Within the whole cohort 12 patients received non-anthracycline based treatment (&amp;lt;60: n=4; 61-70: n=1; and &amp;gt;70: n=7).For patients &amp;lt;60 and &amp;gt;70 this decision was made due to prior comorbidities that precluded the use of standard treatment, and for the patient in the 61-70 was because of acute toxicity with ABVD-based chemotherapy. Treatment was discontinued in 33% of the patients &amp;gt; 70 (77% due to toxicity), 21% in the 61-70 years group (30% toxicity) and 6% in patients &amp;lt;60 (29% toxicity). Patients &amp;gt; 70 had higher rates of grade 3-5 febrile neutropenia (28% versus 15% [age 61-70] and 7% [age &amp;lt;60]). Bleomycin toxicity was more common in older patients (age &amp;gt;70: grade 3-4 events 12% of the patients with discontinuation in 66%; age 61-70: 13% with discontinuation rate of 20%) compared to a 1% rate of grade 3-5 events in age &amp;lt;60. There was a grade 5 episode of febrile neutropenia in &amp;gt;70 group and 1 death related to bleomycin in age &amp;lt;60. With a median follow up of 8.6 years, the 10-year OS and PFS were 80.5% and 71.2%, respectively. By age-group, the 10-year OS was 88% (&amp;lt;60 years), 57% (61-70 years) and 15% (age &amp;gt;70 years); (p&amp;lt;0.001) (Figure 1a-b). In multivariable analysis for OS, age 61-70 (HR 2.44, p=0.002) and age &amp;gt;70 (HR 5.72, p=0.001), non-anthracycline based chemotherapy (HR 3.69, p&amp;lt;0.001), high-risk HCT-CI (HR 3.03, p=0.001) and ECOG 2-4 (HR 1.8, p=0.017), were significant. Age &amp;gt;70, type of chemotherapy, high-risk HCT-CI, and advanced stage were significant for PFS in the multivariable analysis (Table 2a-b). Death due to disease or toxicity at 10 years was 13.6% (age &amp;lt;60: 9.7%, 61-70 years: 23.2%; and for age &amp;gt; 70: 50.7%; [p=&amp;lt;0.001]) (Figure 2a-b). Multivariable analysis for cause-specific survival identified age &amp;gt;70 years (HR 4.04, p=&amp;lt;0.001), extranodal disease (HR 2.57, p=0.001) and ECOG 2-4 (HR 2.10, p=0.010) as significant predictors(Table 3). Conclusions: Age &amp;gt;70 years is a clinically relevant age cutoff as it has additional prognostic significance and greater rates of treatment discontinuation and toxicity compared to age 60. The HCT-CI is a useful predictor of outcome in cHL and should be validated prospectively. In multivariable analysis, age, type of treatment, comorbidity and ECOG performance status are independent predictors of OS. Further studies are ongoing to validate these findings and assess biologic differences in older versus younger cHL patients. Disclosures Tsang: Nordic Nanovector: Research Funding. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Kuruvilla:Janssen: Research Funding; Roche: Honoraria; Novartis: Honoraria; Merck: Honoraria; Gilead: Honoraria; Seattle Genetics: Consultancy; Roche: Consultancy; Merck: Consultancy; Karyopharm: Consultancy; Celgene: Honoraria; BMS: Honoraria; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Astra Zeneca: Honoraria; Janssen: Honoraria; Roche: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria.

R-CHOP Vs. R-CHOP+X for Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Introduction: Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has remained the standard of care as first line treatment for diffuse large B-cell lymphoma (DLBCL) for almost two decades. Treatment outcomes are still suboptimal, as approximately 40% of patients have refractory disease or relapse. Prospective studies recently examined whether the addition of various drugs to R-CHOP (termed R-CHOP+ X) could improve outcomes. The aim of this study was to compare the efficacy and safety of R-CHOP vs. R-CHOP +X as first line treatment for DLBCL. Methods: Systematic review and meta-analysis of randomized controlled trials including patients with DLBCL, comparing first line treatment with R-CHOP vs. R-CHOP+X (i.e. R-CHOP with the addition of another single drug). The Cochrane Library, MEDLINE, conference proceedings and references were searched until June 2019. Two reviewers appraised the quality of trials and extracted data. Primary outcome was overall survival (OS). Secondary outcomes included overall response rate (ORR), complete response (CR) rate, disease control and safety. Results: Our search yielded seven trials conducted between the years 2010 and 2019, including 2939 patients (three abstracts, and four published in peer review journals). Median age of patients ranged between 50 to 67 years. The added drug was bortezomib and lenalidomide - each drug in two trials; gemcitabine, bevacizumab and ibrutinib - each drug in one trial. Three trials included all DLBCL patients regardless of cell of origin, whereas four trials included only patients with non-GCB DLBCL. Characteristics of trials included in the meta-analysis are described in Table 1. Regarding OS, the point of estimate favored improved OS with R-CHOP+X as compared to R-CHOP, yet without statistical significance, HR 0.87, [95% confidence interval (CI) 0.73-1.04, I2=0, 1984 patients, 5 trials]. The ORR and CR rates were similar in the two arms (RR 0.97 [95% CI 0.93-1.02, I2=65%, 2824 patients, 7 trials], and RR 0.99 [95% CI 0.93-1.05, I2=37%, 2826 patients, 7 trials], respectively). However, there was a trend towards improved disease control in the RCHOP+X arm, HR 0.89 [95% CI 0.78-1.01, I2=36]. Regarding safety, three trials (N=1200) reported serious adverse events. There was a significant increase in adverse events in the R-CHOP+X group, RR 1.42 [95% CI 1.24-1.64. I2=55%]. In addition, there was more hematologic toxicity in the R-CHOP+X arm, as reflected by higher rates of grade III/IV thrombocytopenia, anemia and neutropenia. Conclusions: The addition of an extra drug to the conventional first line R-CHOP regimen in patients with DLBCL resulted in a trend towards improved disease control compared to standard R-CHOP. However, there was no significant change in response rates or OS, and R-CHOP+ X was associated with an increased risk for serious and grade III/IV hematological adverse events. R-CHOP still remains the "gold standard" of treatment for DLBCL. Further analyses could perhaps reveal subgroups that would benefit from the addition of an additional drug to this regimen. Disclosures Gurion: Roche: Consultancy.