Higher Incidence Of Grade Research Articles

Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations.

To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs). Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated. In the genotype-toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P=0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P=0.047). A higher incidence of grade 3-4 leucopaenia was found in groups with UGT1A1*1/*28 (P=0.023) and UGT1A1*28/*28 (P=0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P=0.027) or any UGT1A1*6 variants (P=0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes. The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.

Comparing Physician-reported Toxicity in Men with Localized Prostate Cancer Undergoing External Beam, Brachytherapy, or Combination Radiation Therapy

The purpose of this study is to compare physician-reported gastrointestinal (GI), genitourinary (GU) and sexual toxicity outcomes of men with localized prostate cancer undergoing dose-escalated external beam radiation therapy (EBRT), high-dose-rate (HDR) brachytherapy or low-dose-rate (LDR) brachytherapy monotherapy (HDRm or LDRm), EBRT with HDR BT boost (HDRb), and EBRT with LDR BT boost (LDRb). We performed a retrospective cohort study of a prospectively collected database of patients with localized prostate adenocarcinoma treated with EBRT, HDRm, LDRm, HDRb, or LDRb between 2004-2019 at our institution. Hormone therapy was delivered per physician discretion. Physician-reported GI, GU, and sexual toxicity were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at time points of 3 months, 6 months, 12 months, 18 months, and 24+ months. Stratified Fisher exact tests and generalized linear mixed effects models were used to assess for differences in the physician-graded toxicity rate between radiation treatment modalities. 555 men with prostate cancer met selection criteria. 277 (49.9%) received EBRT, 76 (13.7%) received LDRm, 30 (5.4%) received LDRb, 130 (23.4%) received HDRm, and 42 (7.6%) received HDRb. Median follow-up was 33 months (interquartile range [IQR]: 15-59). 130 (23%) had low risk, 280 (50%) had intermediate risk, and 145 (26%) had high risk disease. After 24 months, Grade 3+ GI toxicity with LDRb (15%) was higher than those in the EBRT group (1.2%), and it was higher than those in the HDRb cohort (0%; p = 0.01). No other pairwise comparisons were significant. The risk of Grade 2+ GU toxicity was higher with LDRm over HDRm at months 3, 21, and 24 (p = 0.03; p = 0.02; p = 0.03). HDRm patients had higher incidence of Grade 2+ sexual toxicity than EBRT patients in the first 3 months (p = 0.02). Compared to patients receiving EBRT, patients receiving HDRb, HDRm, or LDRm had higher sexual toxicity by month 15 (p = 0.002; p < 0.001; p = 0.004). By month 21, patients receiving HDRm remained more likely than those receiving EBRT to have sexual toxicity (p = 0.01). There were no significant differences in the sexual toxicity rates between groups after 24 months. In men treated with radiation therapy for localized prostate cancer, there are differences in physician-reported toxicity across radiation treatment modalities. Our study suggests lower rates of chronic GI toxicity in patients treated with HDRb as compared to LDRb and EBRT, lower rates of acute and chronic GU toxicities in patients treated with HDRm as compared to LDRm, and similar long-term sexual toxicity among the groups. The differences in the physician-graded toxicity profiles between radiation treatment modalities can be used in shared decision-making when selecting the best radiation therapy option for each patient.

Use of Potentially Inappropriate Medications in Older Allogeneic Hematopoietic Cell Transplantation Recipients

The use of potentially inappropriate medications (PIMs) using Beers criteria and its impact on older allogeneic hematopoietic cell transplantation (HCT) recipients is not known. Here the use of any PIMs and their therapeutic classes in reduced-intensity conditioning allogeneic HCT recipients were compared between older (≥65 years; n=114)and younger (40 to 64 years; n=240) patients during their initial HCT admission, defined as the number of days that a patient received 1 or more PIMs between day -14 and day +28. Poisson regression was used to determine rate ratios (RRs) in the 2 groups. In the ≥65 years group, we evaluated the impact of PIMs on Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 toxicities within 100 days and on overall mortality within 1 year post-HCT. The rate of any PIM use was similar in the older and younger groups (RR, .98; 95% confidence interval [CI], .90 to 1.06; P=.65). In terms of PIM classes, the older group had a 48% higher rate of gastrointestinal (GI) medication use (RR, 1.48; 95% CI, 1.32 to 1.65; P < .01) and a 25% higher rate of genitourinary (GU) medication use (RR, 1.25; 95% CI, 1.02 to 1.53; P=.03). Compared with males, females had a 19% higher rate of central nervous system (CNS) medication use (RR, 1.19; 95% CI, 1.03 to 1.37; P=.02) and a 30% higher rate of benzodiazepine use (RR, 1.30; 95% CI. 1.09 to 1.54; P < .01). A high-risk HCT-CI was associated with a higher rate of use of any PIMs (RR, 1.13; 95% CI, 1.01 to 1.26; P=.02), CNS medications (RR, 1.26; 95% CI, 1.04 to 1.53; P=.02) and GU medications (RR, 1.46; 95% CI, 1.09 to 1.94; P=.01). Compared with matched sibling donor HCT recipients, umbilical cord blood transplantation recipients had higher rates of GI medication use (RR, 1.32; 95% CI, 1.14 to 1.53; P < .01) and anticholinergic medication use (RR, 1.30; 95% CI, 1.06 to 1.61; P=.01). In the ≥65 years group, increasing duration of narcotic use was associated with a 1.3-fold (95% CI, 1.0 to 1.7; P=.05) higher risk of overall mortality and a 1.6-fold (95% CI, 1.02 to 2.69) greater odds of CTCAE grade 3-4 toxicities (P=.04). Our data show that older recipients (≥65 years) were as likely as their younger counterparts to receive PIMs. Among older recipients, the use of PIMs, particularly narcotics, was associated with higher mortality and higher incidence of grade 3-4 toxicities.Identifying and reducing the use of PIMs in older HCT recipients may help decrease the burden of adverse events and associated health care costs.

Oncolytic virus combined with traditional treatment versus traditional treatment alone in patients with cancer: a meta-analysis.

Oncolytic virus therapy has shown benefits for multiple cancers, while limitations remain for traditional treatment. However, few studies have concentrated on comparing whether oncolytic virus combined with traditional treatment is better than traditional treatment alone in patients with cancer. We conducted a meta-analysis of the curative effect and safety of oncolytic virus combination therapy. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases comprehensively for articles comparing oncolytic virus combined with traditional treatment to traditional treatment alone in patients with cancer. A meta-analysis and trial sequential analysis were performed. A total of 12 studies involving 1494 patients (combination therapy group, 820 patients; traditional treatment group, 674 patients) were included in the study. Compared with traditional treatment alone, combination therapy was significantly associated with high objective response rate [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82, p = 0.04]. There were no significant differences for other outcomes such as 1- and 2-year survival rate, and 4- and 12-month progression-free survival rate. Combination therapy was significantly associated with high incidence of grade ≥ 3 adverse effects (OR 1.47, 95% CI 1.06-2.05, p = 0.02) and high incidence of grade ≥ 3 neutropenia (OR 1.65, 95% CI 1.13-2.43, p = 0.01). There were no significant differences for other grade ≥ 3 adverse effects, e.g., gastrointestinal adverse effects, influenza-like illness, fatigue, anemia, and thrombocytopenia. Despite partially increased toxicity, the combination therapy improves the effectiveness of cancer treatment. However, high-quality, large-scale studies are needed to evaluate its effectiveness and safety.

DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality

AbstractCytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.

P-334 Perioperative chemotherapy in the treatment of resectable and locally advanced gastric and junctional esophagogastric adenocarcinoma: Experience of a Portuguese central hospital

Gastric cancer is the 5th most prevalent cancer in Portugal and the 3rd most deadly worldwide. Currently, perioperative chemotherapy is the standard of care for resectable and locally advanced gastric and junctional esophagogastric (JEG) adenocarcinoma. During several years, the MAGIC study catapulted ECF/ECX/CF regimens into the spotlight. Since publishing the FLOT4-AIO trial results in 2017 - associated with higher R0 resection and pathological response ≤T1 rates, as well as extended overall survival in 15months - the FLOT regimen has become the preferred perioperative option in most national and international clinical centers. The aim of this study was to compare in the real-life setting the FLOT vs ECF/ECX/CF perioperative regimens used in the treatment of resectable and locally advance gastric adenocarcinoma, in terms of safety and efficacy. We conducted a retrospective and observational study, which included patients diagnosed with resectable and locally advanced gastric and JEG adenocarcinoma treated with perioperative chemotherapy regimens between 01/01/2016 and 31/06/2019, namely FLOT (Group A) and ECF/ECX/CF (Group B). Toxicity assessment was made according to CTCAE V.5.0. The study included 64 patients [A:58%(n=37); B:42%(n=27)]. Most patients were male [A:57%(n=21); B:82%(n=22)], median age was 64 years old [A:63 years[39-78]; B:70 years[53-79]] and had cT3/T4 [A:70%(n=26); B:85%(n=23);p=0,164] and cN+ [A:67%(n=25); B:93%(n=25);p=0,017] disease at diagnosis. The median follow-up time was 10 months [2-22] and 21 months [0-37] for groups A and B, respectively. The preoperative regimen was completed by 81% of patients in both groups. Most patients underwent curative surgery [A:84%(n=31); B:81%(n=22);p=0,533]. Most patients initiated postoperative cycles [A:54%(n=20); B:63%(n=17)] but only 43% (n=16) of the patients in group A and 63%(n=17) of group B completed the perioperative treatment. Treatment readjustments was performed in 70% of patients in the group A and 96% of the group B, including delays [A: 40%(n=15); B: 44%(n=12);p=0,755], suspension [A: 27%(n=10); B: 96%(n=26);p< 0,01] and dose reduction [A: 27%(n=10); B: 41%(n=11);p=0,249]. Except for one patient in group A who had R1, all the other patients in the two groups had R0 resection. Compete pathological response (ypT0N0) was reported in 13% of the patients in group A and 9% of group B (p=0,511). Overall survival (OS) was 19 (IC95% 17-21) and 26 months (IC95% 21-32) (p=0,368) and Disease-Free Survival (DFS) was 20 (IC95%:18-22) and 31 months (IC95%:27-36) (p=0,098) in groups A and B, respectively. During the perioperative treatment, the majority of patients experienced grade 3-4 toxicity at some point in treatment [A:57%(n=21); B:70%(n=19);p=0,267], most common being neutropenia [A:35%(n=13); B:63%(n=17);p=0,028]. Two patients died of infectious complications in group A. According to our study, there was no significant difference between the two groups regarding complete pathological response (ypT0N0). The higher incidence of grade 3-4 toxicity especially neutropenia and treatment suspension seemed to occur in the ECX/ECF/CF group. The short follow-up time and small sample size can justify the OS and DFS results.

A new aortoiliac calcification scoring system to predict grade C anastomotic leak following rectal cancer surgery.

Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3cm, 2: > 3cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral).AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066-6.686, p = 0.036). Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.

Safety of weight-based dosing of nivolumab with or without ipilimumab by body mass index (BMI) stratified by sex across 14 CheckMate clinical trials.

e15114 Background: Associations between obesity and cancer risk, prognosis, and therapeutic outcomes have been extensively researched. However, the impact of BMI on safety in patients receiving immunotherapy has not been well described. Methods: A descriptive, retrospective analysis examined associations between BMI (kg/m2) (underweight/normal, BMI &lt; 25; overweight, 25 ≤ BMI &lt; 30; obese, BMI ≥ 30) and incidence of any-grade and grade 3/4 immune-mediated adverse events (imAEs) in patients receiving ≥ 1 dose of nivolumab 3 mg/kg as monotherapy (NIVO3; n = 2746). Data were pooled from CheckMate clinical trials across 8 tumor types. Data from nivolumab in combination with ipilimumab cohorts (n = 1026) and safety analyses by specific imAEs and tumor types will be presented. Results: Select NIVO3 monotherapy cohort patient demographics were: 68.5% male, median age of 61 years, median 10 doses received, and median BMI of 25.3 kg/m2. Results showed a trend towards higher incidence of any-grade, but not grade 3/4, imAEs in obese vs overweight and obese vs underweight/normal BMI patients (Table). BMI associations with imAE incidence were consistent with the overall trend across pre-defined subsets, including smoking status, age, and ECOG performance status. Both male and female patients had an increased incidence of any-grade imAEs with obesity; however, obese female patients had a higher incidence of grade 3/4 imAEs vs underweight/normal BMI (Table). Conclusions: This was a novel analysis of BMI and safety in 2746 patients across 8 tumor types in CheckMate clinical trials who were treated with nivolumab monotherapy. While obese patients showed a trend towards higher incidence of any-grade imAEs than those with overweight and underweight/normal BMI, incidence of grade 3/4 imAEs was consistent across BMI categories. Clinical trial information: CheckMate 017,026,057,025,039,205,040,066,067,141,275,142,016,214 (NCT numbers do not fit in field) . [Table: see text]

Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: BIBABRAX study.

4615 Background: FOLFIRINOX and nab-paclitaxel plus gemcitabine (nab-P+G) are the standard of care in the first-line treatment of mPC patients (pt) with good performance status. However, no standards of care exist for elderly ( &gt; 70 years) pt as they are usually excluded in clinical trials. This study aimed to evaluate whether the clinical benefit of nab-P+G could be extended to elderly pt with mPC. Methods: This was an open-label, single-arm, multicenter, phase II trial, to assess the efficacy and safety of Nab-P+G in elderly pt (≥ 70 years) with ECOG PS 0–1 and untreated unresectable locally advanced or metastatic PC. Pt received four-week cycles of intravenous (i.v.) nab-paclitaxel 125 mg/m2, followed by i.v. gemcitabine 1,000 mg/m2, on days 1, 8 and 15, until disease progression. Efficacy was evaluated according RECIST v 1.1 criteria and safety according NCI-CTCAE v 4.0 criteria. Results: Eighty pt were enrolled in the study. Median age was 74.6 years (range 70-87.9), 57.5% were men, 71% had ECOG PS 1 and 86% metastatic disease. 16.3% of patients had a history of prior tumor surgical resection, 12.5% received chemotherapy and 3.8% radiotherapy. Primary tumor was located in head (32.5%), tail (25.0%) and body (22.5%). Nab-P and G was reduced in 49% and 41% of pt respectively. 15 pt definitely interrupt study treatment due to toxicity: neurotoxicity (7), asthenia (5), neutropenia (1), leukocytosis (1) and hepatotoxicity (1). Time until definite deterioration (reduction ≥10 points as compared to baseline in EORTC-QLQ C30) was 1.6 months and deterioration-free rate at 3 months was 54.3%. Overall response rate was 13.8%, clinical benefit rate 67.5%, median PFS 7.2 months and median OS 9.2 months. The most common treatment-related adverse events were asthenia (60.0%), diarrhea (40.0%), neutropenia (33.8%), hair loss (28.8%), thrombocytopenia (26.3%), and nausea (23.8%). Only asthenia and neutropenia presented a relatively high incidence of grade 3 and 4 toxicities (21.3%). At least 1 SAE was reported in 55% of pt. Conclusions: BIBABRAX study confirms the clinical benefit of nab-P+G in an elderly population with mPC, in terms of survival, clinical response and tolerance, therefore it could be considered a treatment option for elderly patients. However, it was unable to demonstrate the preplanned benefit on the quality of life. Further research is needed on treatment strategies that could reduce deterioration of the quality of life in these pt. Clinical trial information: NCT02391662 .

Neoadjuvant chemotherapy regimens for triple-negative breast cancer: Insights from network meta-analysis.

e12635 Background: The best regimen for neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin improves the rate of pathological complete response (pCR) in TNBC). Therefore, we performed a network meta-analysis to define the overall most effective neoadjuvant systemic therapy for TNBC. Methods: We searched MEDLINE, Cochrane Library, and EMBASE from inception to December 2019 for studies comparing the efficacy of different neoadjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens in the selected studies using the random-effects model. We focused on anthracycline (A), bevacizumab (B), everolimus (E), and platinum salts (Pl) because these are the medications commonly added to taxane based regimens. All studies contained a taxane regimen. We analyzed the rate of pCR (ypT0/is, N0) and the incidence of grade 3-4 neutropenia, thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared eight different classes of regimens. We found that regimens containing Pl were significantly superior to Pl non-containing regimens for the rate of pCR. (risk ratio (RR) for pCR [95% confidence interval (CI)]: 1.66 [1.19-2.31], 1.37 [1.14-1.64], and 1.36 [1.14-1.62] for no medications of special interest vs Pl, A vs A+Pl, and A+B vs A+B+Pl, respectively). Regimens containing B were associated with a significantly better rate of pCR. (RR for pCR [95% CI]: 1.24 [1.06-1.46] and 1.23 [1.01-1.51] for A vs A+B and A+Pl vs A+B+Pl, respectively) In contrast, adding A into the regimen did not improve the rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of grade 3-4 neutropenia and thrombocytopenia. Regimens containing B showed a higher incidence of grade 3-4 nausea/vomiting, and diarrhea. Conclusions: For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding A to the neoadjuvant chemotherapy regimen for TNBC is not apparent.

Final results of a phase III randomized trial of comparison of three paclitaxel-based regimens concurrent with radiotherapy for patients with local advanced esophageal squamous cell carcinoma.

4564 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC). Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) 20 were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. Median follow-up of patients who survived was 36.3 months (IQR 27.9–45.2). The 3-yr OS was 58.2% in TF group and 59.5% in both TP and TC group. (TF vs. TP, HR 0.935, 95% CI 0.627-1.417; TF vs. TC, HR 0.881, 95% CI 0.578-1.342; P = 0.839). No significant differences were found in 3-yr PFS between TF, TP and TC groups [48.3% vs. 45.5%(TP) or 48.3% (TC). P = 0.820]. TP group had a significant higher incidence of acute Grade 3/4 neutropenia [60.7% vs. 16.8%(TF) or 32.7%(TC)], thrombocytopenia [13.1% vs. 2.8%(TF) or 4.7%(TC)], anemia [5.6% vs. 1.9%(TF) or 3.7% (TC)], fatigue [10.3% vs. 1.9%(TF) or 0.9%(TC)] and vomiting [5.6% vs. 0%(TF) or 0.9%(TC))]than other two groups ( P&lt; 0.05). TF group had a significant higher incidence of Grade 3/4/5 esophagitis [11.2% vs. 0.9%(TP) or 4.7%(TC))]and pneumonitis [4.6% vs. 0%(TP) or 1.9% (TC)]than other two groups ( P&lt; 0.05). Conclusions: No statistical differences were found in OS and PFS among TF, TP and TC groups. TC might be an option used in CCR in ESCC patients with mild of side effects compared with other two groups, although it did not significantly prolong OS. Clinical trial information: NCT02459457 .

Hypersensitivity to platinum salts according to BRCA status in ovarian cancer: Retrospective analysis of clinical outcomes.

6053 Background: Hypersensitivity reactions (HSRs) to platinum salts are an important issue in the treatment of ovarian cancer (OC) patients (pts). Few data suggest that, along with number of previous cycles, germline BRCA mutations could be a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum salts in a large group of OC pts with known BRCA status and correlated them with drug exposure time. Methods: Between March 2003 and September 2019, 432 pts with a diagnosis of OC and a known BRCA status, were recorded in our 5 Institutions and retrospectively analyzed. The following data were collected: histology, BRCA status, type of surgery and first line therapy, number of total lines and cycles received, line and cycle of HSR onset, symptoms, history of other allergies and if desensitization was attempted. We graded the severity of HSRs according to CTCAE v5.0. We calculated the total duration of exposure to platinum salts, summing up the duration of all platinum lines received by the pts. Results: Four hundred nine of 432 (94.7%) pts were treated with at least one platinum-based line of therapy and were eligible for the analysis. Among them, 314 pts were BRCA wild type (BRCAwt) (76.8%) and 95 were BRCA mutated (BRCAmut) (23.2%). There was no statistical difference in number of prior lines of therapy [median 1 (2-6) for BRCA wt and 2 (1-6) for BRCAmut pts (p = 0.194)] and duration of exposure to platinum [median 126 (42 – 893) and 197 (42 – 896) days for BRCAwt and BRCAmut pts, respectively (p = 0.145)]. Incidence of any grade HSRs was 29 / 314 (9.2%) among BRCAwt pts vs. 17/ 95 (17.9%) among BRCAmut pts (Odds ratio [OR] 0.47, 95% CI 0.24 – 0.89, p= 0.019). All recorded HSRs to platinum salts were related to carboplatin. We observed a numerically higher incidence of Grade 3-4 HSRs in BRCAmut pts (5.1% in BRCAwt vs. 10.5% in BRCAmut cohort, OR 0.46, 95% CI 0.20 – 1.04, p = 0.057). The risk to develop HSRs increases with duration of exposure to platinum, particularly in BRCAmut pts. The cumulative incidence of any grade HSRs was 20.6% vs. 23.3% after 12 months and 38.4% vs. 59.7% after 18 months in BRCAwt and BRCAmut pts, respectively (Hazard Ratio [HR] 1.72, 95% CI 0.94 – 3.12, p = 0.073). The cumulative incidence of severe HSRs was 10.9% vs. 15.7% after 12 months and 26.5% vs. 41.0% after 18 months in BRCAwt and BRCAmut pts, respectively (HR 1.88, 95% CI 0.85 – 4.16, p = 0.11). Conclusions: In BRCAmut OC pts, there is a significantly higher incidence of HSRs to carboplatin, that seems not justified by longer drug exposure only.

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study.

BACKGROUNDFOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer.AIMTo investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODSAnalyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI (n = 165) or FOLFIRINOX (n = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2) and 5-fluorouracil (3200 mg/m2 as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared.RESULTSMedian overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; P = 0.219) and progression-free survival (hazard ratio = 1.27; P = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group vs 47.8% in the FOLFIRINOX group (P = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort vs 19.5% in the FOLFIRINOX cohort (P = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens.CONCLUSIONFOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Posttransplantation cyclophosphamide improves transplantation outcomes in patients with AML/MDS who are treated with checkpoint inhibitors.

There have been concerns regarding increased peritransplantation complications, especially severe acute graft-versus-host disease (aGVHD), in patients with prior use of checkpoint inhibitors (CPI) before hematopoietic stem cell transplantation (HSCT). The authors performed a retrospective study of 43 patients with acute myeloid leukemia and/or myelodysplastic syndromes who were treated with an antiprogrammed cell death protein 1 (PD-1) (32 patients) or anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (9 patients) blockade or both (2 patients) prior to HSCT with the primary outcome of aGVHD by day 100 after HSCT. Outcome analyses were stratified by GVHD prophylaxis as use of post-HSCT cyclophosphamide (PTCy) (22 patients) or not (non-PTCy) (21 patients). The PTCy group demonstrated a trend toward lower grade 3 to 4 aGVHD when compared with the non-PTCy group (5% vs 22%), although the rates of grade 2 to 4 aGVHD were comparable (49% vs 56%). The interval between CPI and HSCT did not appear to impact the incidence of aGVHD. However, a higher incidence of grade 3 to 4 aGVHD was observed in patients who received >4 treatments of CPI prior to HSCT if they were not given PTCy as GVHD prophylaxis (43% vs 12%). Matched control analyses using patients with no prior use of CPI confirmed the increase in grade 3 to 4 aGVHD with those agents. However, that increased risk was limited to patients who did not receive PTCy and was not observed in patients who received PTCy as GVHD prophylaxis. Despite persistent improvement in GVHD with the use of PTCy, disease control was not compromised and progression-free survival at 1year was found to be superior for patients treated with PTCy compared with those not receiving PTCy among patients with prior use of CPI (55% vs 22%). The results of the current study indicated that HSCT with prior use of CPI appears feasible in patients with acute myeloid leukemia and/or myelodysplastic syndromes and the use of PTCy as GVHD prophylaxis improves outcomes.

The efficacy and toxicity of induction chemotherapy plus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A meta-analysis of randomized controlled trials.

A systemic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy, toxicity and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) for locoregionally advanced nasopharyngeal carcinoma (NPC). Research searching was performed in Web of Science, PubMed, The Cochrane Library, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database for Chinese Technical Periodicals and Wanfang Database. RCTs including patients diagnosed with locoregionally advanced NPC without metastasis and randomly treated with IC plus CCRT and CCRT alone were included. Survival and outcome data were extracted and meta-analysis was performed using the Revman 5.3.0 software. Ten RCTs (2280 patients) were selected and used for pooled meta-analysis. In comparison with CCRT, IC plus CCRT treatment significantly improved the overall survival (OS; HR = 0.70, 95%CI 0.56-0.87, P = .002), progression-free survival (PFS; HR = 0.75, 95%CI 0.65-0.87, P < .0001), distant metastasis failure-free survival (DMFS; HR = 0.71, 95%CI 0.58-0.85, P = .0003) and loco-regional failure-free survival (LFES; HR = 0.72, 95%CI 0.59-0.88, P = .002) of patients with locoregionally advanced NPC. Patients treated with IC and CCRT had higher incidence of grade 3-4 leucopenia and thrombocytopenia than patients treated with CCRT alone (P < .0001). No significant difference in other grade 3-4 adverse events and radiation toxicity was observed between the two groups. IC combined with CCRT improved the survival of patients with locoregionally advanced NPC. Combined IC and CCRT therapy was an efficacy treatment regimen for locoregionally advanced NPC.

Proton Pump Inhibitors Associated with Higher Incidence of Mucositis in Patients Receiving Methotrexate for Graft Vs Host Disease Prophylaxis

<h3>Introduction</h3> Graft-versus-host disease (GVHD) is a major complicating factor in determining morbidity and mortality following allogeneic stem cell transplant. To prevent GVHD, our institution administers calcineurin inhibitors and low doses of methotrexate (MTX) (5-15 mg/m²) on days +1, +3, +6, +11 for GVHD prophylaxis. Proton pump inhibitors (PPIs) are used for the treatment of gastroesophageal reflux disease, pyrosis, and/or peptic ulcer disease. PPIs have been shown to inhibit the ATP-binding cassette drug transporter Breast Cancer Resistance Protein's (BCRP/ABCG2) ability to excrete methotrexate into the urine in a concentration-dependent manner. Delayed excretion of methotrexate can lead to adverse events such as renal impairment, increased severity of mucositis, and increased infection rates. <h3>Objectives</h3> The purpose of this retrospective, single center study is to assess the clinical outcomes of patients receiving MTX and PPIs compared to MTX and no PPI for GVHD prophylaxis. <h3>Methods</h3> A single-site retrospective analysis of patients 18 years of age or older who underwent allogeneic stem cell transplantation from 2013 to 2018. Only patients that received methotrexate for GVHD prophylaxis were included. Cases were identified from clinical databases and were divided into two cohorts, those on PPIs, and those not on PPIs (no-PPI). The primary endpoint was grade of mucositis in each cohort. Secondary endpoints were total parenteral nutrition (TPN) use, need for patient controlled analgesia (PCA), time to engraftment of absolute neutrophil count (ANC) and hospital length of stay (LOS). <h3>Results</h3> 284 cases were identified, 119 (42%) patients were on a PPI at the time of MTX administration. The median age of patients on PPI was younger than those not on PPI (60 vs 54 p <0.0001). There were no differences in sex, BSA, conditioning regimen intent, dose of MTX, degree of match, or stem cell source. Patients on PPI had a higher incidence of grade 1-4 mucositis compared to no-PPI (Table 1) and a higher percentage of grade 3-4 mucositis (Figure 1). Patients on PPIs had a higher incidence of TPN use and need for PCA. Use of PPI did not increase the time to ANC engraftment or LOS. <h3>Conclusions</h3> The concurrent use of PPIs and MTX was associated with a higher incidence and severity of mucositis with increased need for PCA, and TPN. This study was limited by retrospective review. Grading of mucositis was based on clinician assessment and documentation. This study raises the question if PPIs should be discontinued or patients transitioned to a histamine blocker prior to MTX administration to improve severity of mucositis and reduce costs associated with TPN/PCA use.

INDICADOR DE FLEBITE E CUIDADOS DE ENFERMAGEM EM CRIANÇAS E ADOLESCENTES COM CATETER CENTRAL DE INSERÇÃO PERIFÉRICA

The aim of this study was to analyze the prevalence of phlebitis in children and adolescents who used a peripheral venous catheter and a peripherally inserted central catheter (PICC), using the Maddox scale. This is an exploratory-descriptive, retrospective and documentary study, with quantitative clarifications. Ethical-legal precepts were contemplated. A general mean incidence of phlebitis of 0.20% was evidenced. There was a higher incidence of grade 3+ phlebitis in 16 (50%) in children using PICC. Given the above, it is suggested that health teams should institute indicators of adverse events in phlebitis, aiming at prevention and early detection for better care quality. Despite the 48 conducts used by Nursing in the research scenario, it is necessary to establish protocols based on scientific evidence. That is: Apply cold compresses alternating with warm compresses; swabs with chamomile infusion.

Low performance of operational indicators for leprosy control in the state of Bahia: spatiotemporal patterns, 2001-2014.

To characterize spatiotemporal patterns of operational indicators for leprosy control in the state of Bahia from 2001 to 2014. This is a population-based ecological study, with spatial distribution and autocorrelation of operational indicators for leprosy control. From 2001 to 2007, 42.7% (n=178) of the municipalities presented a cure rate lower than 75%, increasing to 61.4% (n =291) from 2009 to 2014. Between 2001 and 2007, 32.5% (n=54) of the municipalities reported more than 10% of the total number of relapses in the state, increasing to 36.9% (n=75) between 2008 and 2014. From 2001 to 2014, 38% (n=159) of the municipalities presented an assessment index of disability grading at the time of diagnosis within the regular performance parameter. Between 2009 and 2014, the number of municipalities with a high incidence of grade 2 disability (G2D) at the time of diagnosis increased, reaching 55.3% (n=230) of the municipalities. Most municipalities in the state of Bahia showed poor performance in the implementation of planned actions for leprosy control, with little change or relative worsening in the patterns of operational indicators throughout the historical series. The operational context in Bahia indicates significant institutional vulnerability, leading to the need for expansion and qualification of the surveillance and health care network in the different regions and conditions analyzed in the public health system (Sistema Único de Saúde - SUS).

Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer

BackgroundA previous phase I/II C-TASK FORCE study of trifluridine/tipiracil plus bevacizumab for patients with heavily pretreated metastatic colorectal cancer (mCRC) showed promising activity with an acceptable toxicity profile. This retrospective study aimed to investigate the safety and efficacy of trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC in clinical settings.MethodsRecords of patients with mCRC refractory to standard therapies who initiated trifluridine/tipiracil plus bevacizumab from January 2016 to March 2018 or trifluridine/tipiracil monotherapy from June 2014 to December 2015 were retrospectively reviewed at our institution.ResultsTotally, 60 patients received trifluridine/tipiracil plus bevacizumab and 66 received trifluridine/tipiracil monotherapy. All patients had previously received standard chemotherapy. Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 2.3–5.1] in the trifluridine/tipiracil plus bevacizumab group and 2.2 months (95% CI, 1.8–2.6) in the trifluridine/tipiracil monotherapy group [hazards ratio (HR) 0.69; 95% CI 0.48–0.99]. PFS rate at 16 weeks was 46.6% for the trifluridine/tipiracil plus bevacizumab group and 33.9% for the trifluridine/tipiracil monotherapy group. Although a relatively higher incidence of grade ≥ 3 neutropenia was observed in the trifluridine/tipiracil plus bevacizumab group than that in the other group (50.0% vs. 40.9%, p = 0.371), the incidence of febrile neutropenia was not high (3.3% vs. 7.8%, p = 0.444).ConclusionsIn real-world settings, trifluridine/tipiracil plus bevacizumab prolonged PFS and helped achieve higher 16-week PFS rate compared with trifluridine/tipiracil monotherapy in patients with heavily pretreated mCRC with manageable toxicities.Trial registrationRetrospectively registered.

Risk factors of grade \u2265 2 radiation pneumonitis after gemcitabine induction chemotherapy for patients with non-small cell lung cancer

ObjectivesTo observe the risk factors affecting the occurrence of RP after gemcitabine-based induction chemotherapy.MethodsBetween January 2010 and December 2017, patients with NSCLC received gemcitabine or docetaxel chemotherapy, followed by radiotherapy at Zhejiang cancer hospital were enrolled in this study. Patients were treated with gemcitabine or docetaxel induction chemotherapy, followed by radiotherapy or concurrent chemoradiotherapy. Acute radiation pneumonitis was scored post chemoradiotherapy.ResultsOne hundred and eighty-four patients with NSCLC were included in the gemcitabine group and 144 in the docetaxel group. The gemcitabine group experienced a higher incidence of grade ≥ 2 RP, compared with docetaxel group (25.5% Vs. 13.2%, P = 0.005). The optimal cutoff values of lung V5, V20, V30 and MLD were set at 44% (AUC [area under the curve] = 0.593), 24% (AUC = 0.607), 14.2% (AUC = 0.622) and 1226 cGy (AUC = 0.626). On multivariate analysis, only lung V30 was identified as a predictor for grade ≥ 2 RP (P = 0.03). The grade ≥ 2 RP rate was only 9.4% for the low-risk group (Lung V5 ≤ 44%, V20 ≤ 24%, V30 ≤ 14.2%, and MLD ≤ 1226 cGy) in patients received gemcitabine induction chemotherapy.ConclusionsGemcitabine chemotherapy before thoracic radiotherapy in NSCLC patients was related to a higher incidence of grade ≥ 2 RP, compared with docetaxel chemotherapy. The Lung dose-volume variable V30 was the best predictor of grade ≥ 2 RP.