Commencement Of Chemotherapy Research Articles

Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial

Introduction: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC). Methods: A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m² and cisplatin 25 mg/m² on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy. Results: Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1–8). The median OS was 13.6 months (95% CI: 5.4–21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3–25.2) and the median PFS was 9 months (95% CI: 3.2–13.1). The response rate was 25% (95% CI: 3.8–46.2%), and the disease control rate was 75% (95% CI: 53.8–96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7–42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2). Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.

P-P58 The role of PET-CT in the management of pancreatic cancer. A Northern Ireland experience

BackgroundDiagnosis and staging has proven to be difficult in 10-20% of patients with pancreatic cancer. The PET-PANC study found that PET-CT significantly influenced the staging and management of pancreatic cancer and therefore the NICE guidelines now advise PET-CT in all patients who have localised potentially resectable disease. This study aimed to investigate the impact of PET-CT on the management of pancreatic cancer patients in a single tertiary referral centre.MethodsThere were 288 patients with pancreatic cancer discussed at the Northern Ireland Regional Hepatobiliary MDM from January 2020 to March 2021. Of these patients, 176 were deemed to have inoperable disease based on initial CT, 5 had borderline resectable disease, 1 had holding chemotherapy due to COVID restrictions and 57 were excluded from surgical resection for a variety of reasons. These included the patient being unfit for surgery, the patient declining operative intervention and an alternative treatment offered as result of COVID-19 pandemic. Therefore, there were 49 patients with pancreatic adenocarcinoma which the MDT concluded should be considered for surgical resection.ResultsA total of 27 patients who were due to undergo a curative resection had a pre-operative PET-CT scan (55.1%). This demonstrated metastatic disease in 9 cases (33.3%). Four patients who did not have a preoperative PET-CT were found to have metastatic disease at operation (9.7%). This equated to a total metastatic incidence of 26.5% in those who had been initially deemed resectable based on CT scan alone. The time interval from MDM decision to surgery averaged 25.4 days in those who did not have a PET/CT compared to 40.43 days in those who did. This was an average delay of 15.07 days until treatment.ConclusionsThis study demonstrates the important role the PET-CT has in the management of patients with pancreatic cancer. A significant number of patients avoided an unnecessary operation which would have delayed the commencement of chemotherapy. However, there are limitations to PET-CT, demonstrated in the patient with an inconclusive result, who was found to have liver metastases at surgery. The introduction of PET-CT in the staging process does undoubtedly cause delays to surgical resection and a more streamlined pathway needs to be developed to limit the delay to curative treatment.

Hepatitis B Virus Screening Before Cancer Chemotherapy in Taiwan: A Nationwide Population-Based Study.

Background: Reactivation of the hepatitis B virus (HBV) during cancer chemotherapy is a severe and sometimes fatal complication. In 2009, the National Health Insurance (NHI) in Taiwan recommended and reimbursed screening for HBV infection and prophylactic antiviral therapy before cancer chemotherapy. In this study, we determined the HBV screening rate in patients with cancer undergoing chemotherapy in Taiwan.Methods: We retrospectively collected data from the National Health Insurance Research Database on patients who received systemic chemotherapy for solid or hematologic cancers from January 2000 through December 2012. We defined HBV screening based on testing for serum HBsAg within 2 years of the first chemotherapy commencement. We calculated overall and annual HBV screening rates in all patients and subgroups of age, gender, cancer type, hospital level, physician's department, and implementation of NHI reimbursement for HBV screening before cancer chemotherapy.Results: We enrolled 379,639 patients. The overall HBV screening rate was 45.9%. The screening rates were higher in males, those with hematological cancer, those at non-medical centers and medical departments. The HBV screening rates before (2000–2008) and after the implementation of NHI reimbursement (2009–2012) were 38.1 and 57.5%, respectively (p < 0.0001). The most common practice pattern of HBV screening was only HBsAg (64.6%) followed by HBsAg/HBsAb (22.1%), and HBsAg/HBcAb/HBsAb (0.7%) (p < 0.0001). The annual HBV screening rate increased from 31.5 to 66.3% (p < 0.0001). The screening rates of solid and hematological cancers significantly increased by year; however, the trend was greater in solid cancer than in hematological cancer (35.9 and 26.2%, p < 0.0001).Conclusions: The HBV screening rate before cancer chemotherapy was fair but increased over time. These figures improved after implementing a government-based strategy; however, a mandatory hospital-based strategy might improve awareness of HBV screening and starting prophylactic antiviral therapy before cancer chemotherapy.

Predictors of laboratory spontaneous tumour lysis syndrome in children with high-grade tumours in Uganda.

High-grade malignancy is endemic in sub-Saharan Africa and is prone to the spontaneous tumour lysis syndrome. However, data on spontaneous tumour lysis syndrome remain scanty in our setting. We sought to determine the prevalence and factors associated with laboratory spontaneous tumour lysis syndrome in children in Uganda. We conducted a cross-sectional study among children <18 years old with histologically confirmed high-grade malignancy between October 2013 and April 2014. Laboratory spontaneous tumour lysis syndrome was defined as the presence of ≥2 of each of hyperkalaemia, hypocalcaemia, hyperuricaemia and hyperphosphatemia prior to administration of chemotherapy when alternative diagnoses had been excluded. A p < 0.05 was considered statistically significant. Of 108 children, of median age 7.7 years, where boys outnumbered girls 2:1, high-grade, malignancy included Burkitt's lymphoma, acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, acute myeloid leukaemia and Burkitt's leukaemia, with 14 suffering with laboratory spontaneous tumour lysis syndrome. Hypocalcaemia was its most common electrolyte imbalance; and four children died prior to commencement of chemotherapy. Bulky disease, lactate dehydrogenase levels ≥500 iu/l and serum creatinine levels >1.2 mg/dl were associated with laboratory spontaneous tumour lysis syndrome. However, only bulky disease was significantly predictive of laboratory spontaneous tumour lysis syndrome. Such children would benefit from routine screening.

Childhood leukemia outcomes in a low-resource tertiary care setting

Context Acute leukemia (AL) is the commonest hematological malignancy in childhood. The cause is largely multifactorial and unknown, with exogenous and endogenous factors interacting with genetic susceptibility. Its incidence is on the rise globally including developing countries like Nigeria. Although the prognosis in developed countries has improved, poor outcomes are still the norm in resource-poor areas. Aims This review was undertaken to document the sociodemographic characteristics, management challenges, and outcomes of leukemia in an African tertiary care setting. Settings and design The study was a retrospective review of patients managed for AL over a 30-month period. Patients and methods This is a retrospective review of clinical case notes of children admitted with diagnosis of AL. Results A total of 31 children had morphological diagnosis of AL; half of them had acute lymphoblastic leukemia, a third acute myeloid leukemia, and one-sixth bilineal leukemia, respectively. Most patients were from low socioeconomic status. All patients sought alternative or complimentary care, and source of health care expenditure was out of pocket. The mean duration of symptoms was 12.9±10.3, time to diagnosis in our hospital was 3.7±2.1 days, and duration of hospital stay was 36.7±43.4 days. The mean packed cell volume, white blood cell, and platelet counts were 14.2±5.3, 37.9±30.2×109/l, and 45.4±54.3×109/l, respectively. Only four patients attained remission of the 15 (48.4%) who received chemotherapy. The mortality was 11 (35.5%) cases, with eight cases being owing to hemorrhage from severe thrombocytopenia. Conclusions The study shows delay in time from symptoms to presentation, time to diagnosis, and commencement of chemotherapy with associated poor outcomes. All patients sought alternative and/or complementary interventions before presentation.

Tumour brain: Pretreatment cognitive and affective disorders caused by peripheral cancers.

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood-brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis.

The Effects of Chemotherapy on Circulating Plasma Carotenoids and Fat-Soluble Vitamins in Breast Cancer Patients

Abstract Objectives Chemotherapy upregulates inflammatory processes as measured by circulating concentrations of pro-inflammatory cytokines and their signaling lipids. Our objective was to observe if breast cancer chemotherapy influenced the circulating concentrations of provitamin A and non-provitamin A carotenoids and fat-soluble vitamins (FSVs) in free-living patients. Methods Serum samples were collected from patients (n = 34) immediately prior to standard adjuvant and neo-adjuvant chemotherapy for breast cancer, and 4 months following chemotherapy commencement. Patient multivitamin and non-steroidal anti-inflammatory (NSAID) drug use was noted at both visits. Lipophilic extracts of serum were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to quantify α- and β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol and phylloquinone. Linear mixed models were developed to assess the relationship between the main factors (i.e., chemotherapy, multivitamin, and NSAID use), and their interaction effects, on serum carotenoid and fat-soluble vitamin concentrations. Random effects included a fixed intercept for each subject. Results Chemotherapy was significantly associated with reduced serum concentrations of α-carotene (P = 0.053) and retinol (P = 0.042), with a trend observed for reduced β-carotene (P = 0.076) and phylloquinone (P = 0.082). There was no main effect of multivitamin or NSAID use on any analytes investigated. An interaction effect was observed for chemotherapy * multivitamin use, with increased concentrations of serum retinol (P = 0.004) and lycopene (P = 0.004), and a trend observed for zeaxanthin (P = 0.087) for those who took multivitamins. Chemotherapy * NSAID use was also significantly associated with a trend in increased serum lutein (P = 0.061) for those who consumed NSAIDS. Conclusions Our results suggest randomized, controlled trials of multivitamin use and/or provitamin A carotenoid-rich food consumption merit further investigation in patients undergoing chemotherapy treatment. Funding Sources This research was supported by The Ohio State University Stefanie Spielman Breast Cancer Center Kroger Fund, Pelotonia, NIH R01CA189947, NIH Award Number Grant P30 CA016058, OSU, and OSUCCC.

Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients.

Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.

The effectiveness of EVOSKIN®Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial.

This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy. Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks. During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194). The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

Impact of oncology pharmacist services on humanistic outcome in patients with breast cancer.

This study aims to investigate the change in quality adjusted life-years (QALYs) after providing oncology pharmacist services to assess its impact on humanistic outcome. It was a prospective, single-centered study conducted for a period of two years at Bharat cancer Hospital and Nirali memorial radiation center, Surat. Patients were recruited into the control group (CG) and the intervention group (IG). The oncology pharmacist services (OPS) were provided only to the IG. The humanistic outcome was measured by incorporating the EQ-5D-5L instrument to calculate quality-adjusted life-years (QALYs) in both the groups. Patients have been provided with the EQ-5D-5L questionnaire at the pre-determined intervals i.e. before the commencement of chemotherapy and then after every chemotherapy cycle till the completion of treatment. The analysis was carried out using descriptive analysis (frequency distribution for categorical variables and measures of central tendency (median and average) and dispersion (std. deviation) for quantitative variables). A total of 230 patients were screened and from them 105 patients were recruited, out of which 54 patients were in CG and 51 patients in IG. AC regimen followed by weekly paclitaxel was prescribed in majority of the patients (CG: 59.3%; IG: 60.8%) followed by AC-TRA and AC regimen alone. The majority of patients in the CG were facing improper administration of pre-medication (83.3%), lack of knowledge regarding chemo-mixing, counselling in nursing staff (66.7%) and a sub-therapeutic dose of anti-emetics (37%). The baseline QALY at the inception of chemotherapy was 0.040 and 0.014 in CG and IG, respectively. After the completion of the 6 chemotherapy cycle, the QALY was found to be 0.042 and 0.043 in CG and IG, respectively. The study has demonstrated that the improvisation in QALY after provision of oncology pharmacist services reflect the positive impact of oncology pharmacist on humanistic outcomes. The study also provided the opportunity to identify the thrust area where more clinical pharmacy exposure is needed in order to improve patient care.

Oncological Safety, Surgical Outcome, and Patient Satisfaction of Oncoplastic Breast-Conserving Surgery With Contralateral Balancing Reduction Mammoplasty.

Oncoplastic breast-conserving surgery (OBCS) is considered a cornerstone in the management of locally invasive breast cancer. We evaluated patient-reported outcomes of OBCS with contralateral balancing breast reduction mammoplasty and reviewed its oncologic outcomes and complications. This is mixed method study design using retrospective chart review and prospective cohort study. Patient demographics were reviewed. Outcome measures included clinicopathologic characteristics, complications, margin status, local recurrence, tumor histopathologies, duration of follow-up, patient satisfaction, self-esteem, event-related stress, and quality of life. A total of 48 patients were included in this study. Complete excision with negative margins was obtained in 42 (87.5%) patients, positive margins in 6 (12.5%) patients, all who had re-excision with repeat lumpectomy. Thirteen patients developed minor complications, defined as being managed as an outpatient. No patients developed major complications requiring inpatient admission. These complications did not delay commencement of chemotherapy or radiotherapy. Postsurgery BREAST-QTM26 scores demonstrated no statistical difference in satisfaction with breasts, nipples, and sexual well-being. There was high satisfaction with overall outcome with average score of 80.8%. For the Rosenberg self-esteem scale, the results were similar for 3- and 12-month post-operative indicating maintenance of normal self-esteem post-operatively. The Impact of Events Scale showed statistically significant difference at 12-month post-operative (25.1) when compared with preoperative scores indicating that patients had lower event-related stress. There was no significant change in Hospital Anxiety and Depression Scale. Our study has shown that the patient who undergo OBCS have high patient-reported outcomes with acceptable oncologic outcomes and complication rates.

AML-030: The Diagnostic Yield and Safety of Skin Biopsies in Patients with Acute Myeloid Leukemia During Intensive Chemotherapy - A Retrospective Cohort Study

Context Skin eruptions are common in acute myeloid leukemia (AML). However, data on the safety and diagnostic yield of skin biopsies in affected patients are scarce. Objective To evaluate the yield and safety of skin biopsies obtained from adult patients with AML during hospitalization for intensive chemotherapy. Methods The database of a tertiary university-affiliated medical center was retrospectively searched for patients with AML who underwent biopsies for skin eruptions during hospitalization in 2007-2018. Clinical, laboratory, and outcome data were collected. Results Of 216 consecutive patients diagnosed with AML, we identified 35 patients who underwent 37 skin biopsies: 22% at presentation and the remainder after chemotherapy commencement. Histopathological diagnoses were drug eruption (24.3%), infection (11%), leukemia cutis (16.2%), Sweet syndrome (5.5%), and a reactive process (8%); in 35% of biopsies, findings were inconclusive. Tissue cultures, performed in 16 patients, were positive in 4 (25%). Only in 8% of cases did the biopsy results lead to a change in management. One patient had bleeding and fever as a result of the biopsy. Conclusions Our study suggests that skin biopsies are relatively safe to perform in patients with AML undergoing intensive chemotherapy, although their diagnostic yield is limited.

Assessing changes in microstructural integrity of white matter tracts in children with leukaemia following exposure to chemotherapy.

Intrathecal and intravenous chemotherapy, specifically methotrexate, might contribute to neural microstructural damage. To assess, by diffusion tensor imaging, microstructural integrity of white matter in paediatric patients with acute lymphoblastic leukaemia (ALL) following intrathecal and intravenous chemotherapy. Eleven children diagnosed with de novo ALL underwent MRI scans of the brain with diffusion tensor imaging (DTI) prior to commencement of chemotherapy and at 12months after diagnosis, using a 3-tesla (T) MRI scanner. We investigated the changes in DTI parameters in white matter tracts before and after chemotherapy using tract-based spatial statistics overlaid on the International Consortium of Brain Mapping DTI-81 atlas. All of the children underwent formal neurodevelopmental assessment at the two study time points. Whole-brain DTI analysis showed significant changes between the two time points, affecting several white matter tracts. The tracts demonstrated longitudinal changes of decreasing mean and radial diffusivity. The neurodevelopment of the children was near compatible for age at the end of ALL treatment. The quantification of white matter tracts changes in children undergoing chemotherapy showed improving longitudinal values in DTI metrics (stable fractional anisotropy, decreasing mean and radial diffusivity), which are incompatible with deterioration of microstructural integrity in these children.

Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy

BackgroundAlteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.MethodologyWe conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients’ microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.ResultsPrior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.ConclusionOur findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

Endoscopic stenting in colorectal cancer.

Acute malignant large bowel obstruction presents as one of the few emergencies of colorectal cancer (CRC). Management of this condition can either be by (I) upfront surgery or (II) the use of self-expanding metallic stent (SEMS) as a bridge to elective surgery. For patients with metastasis, the use of SEMS is reported to enable earlier commencement of chemotherapy. Although the use of SEMS in patients with acute malignant large bowel obstruction looks promising, it is plagued by its own set of complications and divided opinion over its long-term outcomes. Conflicting data are present, and definitive indication requires further evaluation and debate. This article will describe the typical presentation of patients with acute malignant large bowel obstruction. An introduction to the SEMS insertion procedural steps will be undertaken. Following which the article aims to review the safety profile of SEMS and the short- and long-term outcomes of SEMS in both the curative and palliative setting.

The Yield and Safety of Skin Biopsies in Acute Myeloid Leukemia Patients during Intensive Chemotherapy Treatment

Introduction: Skin eruptions in acute myeloid leukemia (AML) patients are not uncommon. Skin biopsy is a minimal invasive procedure, yet potential complications, such as infection and bleeding, might be expected in these patients due to immunosuppression and thrombocytopenia. Data are scarce regarding the prevalence, etiology and characteristics of skin eruptions among AML patients during intensive therapies. Even less is known regarding the safety and diagnostic yield of skin biopsies in this setting. We sought to evaluate the diagnostic yield and safety of skin biopsies obtained from adult AML patients during hospitalization for intensive chemotherapy. Methods: This is a single-center retrospective cohort study of adult AML patients who underwent skin biopsies for histopathology and tissue culture during induction and consolidation treatment for AML at our hemato-oncology unit between 1.1.2007-1.9.2018. Data collection included demographic details, AML characteristics, chemotherapy regimens, clinical description of rush and associated symptoms (mainly fever, pruritus) and laboratory tests. We recorded whether biopsy results had an impact on patients' care. This study was approved by the Institutional Review Board. Results: 37 skin biopsies from AML patients were identified in our cohort during the study period. Patient demographics and rash characteristics are presented in Table 1. 22% of the skin biopsies were performed at AML presentation prior to chemotherapy, and the remainder after chemotherapy commencement, i.e. after starting either induction or post-induction (consolidation or salvage) treatment (70% and 8%, respectively). Most skin eruptions were grade 1 (53%) or 2 (26%) in severity. Only 21% were grade 3 and 4 rashes. The most common body parts involved were the limbs (51%) and trunk (33%). At the time of skin biopsy 43% of patients had associated fever and 11% had bacteremia. Most patients (62%) had grade 4 neutropenia and 38% and 19% of patients had grade 3 and 4 thrombocytopenia, respectively. Elevated prothrombin time was evident in 66% of patients, whereas 5.5% of patients had an elevated partial thromboplastin time at the time of biopsy. Rash etiology according to skin biopsies histopathological findings consistent with drug eruptions (24.3%), infections (11%), leukemia cutis (16.2%), Sweet syndrome (5.5%) or a reactive process (8%). 35% of biopsies results were inconclusive. In 16 cases (43%) tissue cultures were performed and of those, 4 cultures were positive. However, only in 1 patient the positive culture result has led to a change of antimicrobial coverage. A proactive approach following biopsy results was conducted in 2 additional patients, when a suspected drug leading to the eruption was discontinued (n=1), and systemic steroids were prescribed instead of acyclovir (n=1). Hence, skin biopsy results changed patients' management only in 8% of cases (n=3). Skin biopsies were generally safe and only 1 patient suffered from a complication directly attributed to the biopsy - i.e. she became febrile and suffered from a local hemorrhagic bulla formation, necessitating administration of vancomycin. Conclusions: We suggest that skin biopsies from AML patients hospitalized for intensive chemotherapy treatment are relatively safe. Nevertheless, their diagnostic yield is limited and does not alter the management of most patients. Increased physician discretion should be exercised prior to performing a skin biopsy in this patient population, to avoid unnecessary usage of medical resources and invasive procedures. Further studies are needed to establish the role of skin biopsies in these patients. Disclosures Wolach: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker.

Anti-Leukemic Activity of Single Agent Venetoclax in Newly Diagnosed Acute Myeloid Leukemia: A Sub-Set Analysis of the Caveat Study

Anti-Leukemic Activity of Single Agent Venetoclax in Newly Diagnosed Acute Myeloid Leukemia: A Sub-Set Analysis of the Caveat Study

430P - Emetic risk of carboplatin plus pemetrexed is higher than that of carboplatin plus paclitaxel in patients with lung cancer: A propensity score-matched analysis

BackgroundThe emetogenic classification of antineoplastic agents has provided a framework for defining antiemetic treatment recommendations in international guidelines. The most widely used classification schema identified four emetic risk levels. However, information on the emetogenicity of each chemotherapeutic regimen is insufficient. We previously reported that the emetic risk of pemetrexed was higher than that of taxans. Risk factors for chemotherapy-induced nausea and vomiting (CINV) were also assessed in patients with lung cancer receiving carboplatin plus pemetrexed (CBDCA+PTX) or carboplatin plus paclitaxel (CBDCA+PEM), and the CINV incidence was compared between these two regimens. MethodsData were pooled from two prospective studies, and propensity score matching was used to compare the CINV incidence between CBDCA+PTX and CBDCA+PEM groups. Risk factors for CINV were identified using logistic regression models. The pattern of CINV occurrence was evaluated by 7-day patient diary for recording CINV after the commencement of chemotherapy. ResultsAmong 240 evaluable patients, the CINV incidence was higher in the CBDCA+PEM group than in the CBDCA+PTX group at the delayed phase (nausea: 51.1% vs. 36.2%, P = 0.040; vomiting: 23.4% vs. 14.9%, P = 0.138). The pattern of delayed CINV occurrence peaked on days 5 and 4 for CBDCA+PEM and CBDCA+PTX regimens, respectively. Logistic regression analysis identified younger age, female sex, no alcohol consumption, two antiemetics, and CBDCA+PEM regimen as independent risk factors associated with delayed nausea, and female sex and two antiemetics for delayed vomiting. ConclusionsThe emetic risk of CDBCA+PEM regimen was higher than that of CBDCA+PTX regimen. More aggressive antiemetic prophylaxis such as quadruple therapy, including olanzapine, may be considered in patients receiving CDBCA+PEM regimen. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Incidence of vincristine induced neurotoxicity in children with acute lymphoblastic leukemia and its correlation with nutritional deficiencies

Injection vincristine is an important component of therapy for acute lymphoblastic leukemia (ALL). An important adverse effect of vincristine is neurotoxicity. The incidence of this adverse effect is well studied. The present was undertaken to determine the incidence of vincristine-induced neurotoxicity in children with ALL after the induction of remission phase of chemotherapy and to ascertain its correlation with undernutrition, vitamin B12, folate and iron deficiency. Thirty children (1–18 years) with ALL were enrolled at the commencement of chemotherapy. The electrophysiological evaluation was done at baseline and repeated after four doses of vincristine (1.5 mg/m2/dose). Clinical evaluation was done regularly. Anthropometry and serum B12, folate and ferritin levels were assessed at baseline. Twelve children over a 4-week period of observation had peripheral neuropathy clinically. The autonomic system was most commonly involved followed by motor and sensory system respectively. On electrophysiological testing, half of the patients had evidence of neuropathy. Micronutrient deficiencies were present in a significant number of patients—63.3% had a B12 deficiency, 20% were deficient in folate and 43.3% in iron. The incidence of vincristine-induced neuropathy in patients with/without these micro-nutrient deficiencies was not statistically significantly different. Vincristine-induced neuropathy is common in Indian children with ALL. The present study did not find any correlation between the occurrences of vincristine-induced neuropathy and nutritional deficiencies. Larger studies are warranted to evaluate the contribution of micronutrient deficiencies to the development of peripheral neuropathy in childhood ALL.

Advanced Intrahepatic Cholangiocarcinoma: Post Hoc Analysis of the ABC-01, -02, and -03 Clinical Trials.

The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with first-line cisplatin-gemcitabine chemotherapy (current standard of care). Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistical tests were two-sided. Of 534 patients recruited into the ABC-01, -02, and -03 studies, 109 (20.4%) had iCCA. Most patients (n = 86, 78.9%) had metastatic disease at the time of recruitment; 52 patients (47.7%) had liver-only disease. Following random assignment, 66 (60.6%) iCCA patients received cisplatin and gemcitabine. The median progression-free and overall survival (OS) were 8.4 months (95% confidence interval [CI] = 5.9 to 8.9 months) and 15.4 months (95% CI = 11.1 to 17.9 months), respectively. Of these 66 patients, 34 patients (51.5%) had liver-only disease. Following chemotherapy, 30 (45.5%) and 21 (31.8%) were progression-free at 3 and 6 months from chemotherapy commencement, respectively. The median OS for patients with liver-only iCCA at diagnosis and after 3 and 6 months of chemotherapy was 16.7 months (95% CI = 8.7 to 20.2 months), 17.9 months (95% CI = 11.7 to 20.9 months), and 18.9 months (95% CI = 16.7 to 25.9 months), respectively. Multivariable analysis confirmed that iCCA had a longer OS compared with other non-iCCA biliary tract cancers (hazard ratio = 0.58, 95% CI = 0.35 to 0.95, P value = .03); liver-only iCCA patients also showed longer OS even though findings did not reach statistical significance (hazard ratio = 0.65, 95% CI = 0.36 to 1.19, P value = .16). Patients diagnosed with advanced iCCA have a better OS compared with other biliary tract cancers; a similar trend was identified for patients diagnosed with liver-only iCCA. These findings are to be considered for future clinical trial design.