Severe toxicity is experienced by a substantial minority of patients receiving fluoropyrimidine-based chemotherapy, with approximately 20% of these severe toxicities attributable to polymorphisms in the DPYD gene. The DPYD codes for the enzyme dihydropyrimidine dehydrogenase (DPD) important in the metabolism of fluoropyrimidine-based chemotherapy. We questioned whether prospective DPYD mutation analysis in all patients commencing such therapy would prove more cost-effective than reactive testing of patients experiencing severe toxicity.All patients experiencing severe toxicity from fluoropyrimidine-based chemotherapy for colorectal cancer in an Irish private hospital over a 3-year period were tested for 4 DPYD polymorphisms previously associated with toxicity. The costs associated with an index admission for toxicity in DPD-deficient patients were examined. A cost analysis was undertaken comparing the anticipated cost of implementing screening for DPYD mutations versus current usual care. One-way sensitivity analysis was conducted on known input variables. An alternative scenario analysis from the perspective of the Irish health-care payer (responsible for public hospitals) was also performed.Of 134 patients commencing first-line fluoropyrimidine chemotherapy over 3 years, 30 (23%) patients developed grade 3/4 toxicity. Of these, 17% revealed heterozygote DPYD mutations. The cost of hospitalization for the DPYD-mutated patients was €232 061, while prospectively testing all 134 patients would have cost €23 718. Prospective testing would result in cost savings across all scenarios.The cost of hospital admission for severe chemotherapy-related toxicity is significantly higher than the cost of prospective DPYD testing of each patient commencing fluoropyrimidine chemotherapy.
Background: Endothelial function testing using a 5-minute arm-cuff occlusion have always focused on hemodynamic measures from the occluded arm. No publication is found in PubMed (as of May 2019) on...
BACKGROUND: Data of febrile neutropenia (FN) from rural cancer centers is sparse. We did a audit of outcome of patients with FN in the period of March 2013-August 2013. The aim was to help us to develop rational antibiotic usage policies. MATERIALS AND METHODS: Retrospective analysis of all consecutive patients presenting with FN. Data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. SPSS (Statistical Product and Service Solutions) 16 was used for analysis. RESULTS: 67 patients had FN and there were 91 episodes. The median day of presentation with FN after start of chemotherapy was 10 days. The nadir absolute neutrophil count was 161.5 and nadir platelet count 1,00,000. The median multinational association for supportive care in cancer (MASCC) Score was 24. In accordance with MASCC there were 27 high risk FN and 64 low risk FN episodes. On multivariate analysis using logistic regression MASCC score strata was the only significant variable that predicted failure to 1st line antibiotics (P = 0.03) and mortality (P = 0.01). Nine patients (9.9%) had positive isolates on blood cultures. The blood culture isolates were predominantly Gram negative (66.7%). CONCLUSION: The importance of developing local guidelines for rational antibiotic usage is highlighted.
e18194 Background: TLS is a potentially fatal oncologic emergency featuring a sudden breakdown of tumor cells, with the release of intracellular metabolites. It can lead to renal failure, arrhythmias and death. International expert consensus panels have published risk classification models which enable patients to be assigned to TLS risk groups and managed with appropriate prophylaxis. We developed a web-based application (Lysassist) based on these guidelines to assist with TLS risk assessment. We assessed the accuracy of TLS risk assignment and the appropriateness of prophylaxis among patients starting therapy for advanced malignancies before and after implementation of this tool at our institution. Methods: 30 patients were assessed in each treatment period before (June-Dec 2014) and after (June-Dec 2015) implementing Lysassist (10 advanced solid tumors, 10 lymphomas and 10 other hematologic malignancies). We recorded the cancer type, bulk of disease, chemotherapy received and pre-treatment laboratory parameters. Based on these results and according to international guidelines patients were assigned into low (LR), intermediate (IR) or high risk (HR) groups. The medical records were reviewed to see if TLS risk had been correctly identified, and whether it was managed appropriately for their risk group. Results: Patients in the pre- and post-Lysassist periods were LR in 60% and 63% respectively, IR in 20% and 14% and HR in 20% and 3%. Correct prophylaxis was assigned in 27% in the initial period and 53% post intervention (χ2 P = 0.035). Prophylaxis was below the recommended level for risk group in 50% and 20% (χ2 P = 0.015), and above the recommended level in 23% and 27% respectively (ns). Among IR and HR patients, inadequate prophylaxis was used in 100% prior to the introduction of Lysassist, and 55% afterwards (χ2 P = 0.008). Conclusions: Implementation of a user-friendly web based tool to assess TLS risk and assign prophylaxis increases the likelihood of patients receiving prophylaxis appropriate to their risk group. In particular the likelihood of inadequate prophylaxis is reduced. We plan to make this tool available for free download to assist with patient management.
3627 Background: DPD is an enzyme encoded by the DPYD gene involved in the metabolism of the chemotherapy drug 5-fluorouracil (5FU) and the oral 5FU prodrug capecitabine. Patients (pts) with DPYD mutations are at risk of severe toxicities from standard dose 5FU, although they may safely receive lower dose therapy with careful monitoring and dose escalation. Methods: In this retrospective study we identified all pts starting 5FU-based chemotherapy for colorectal cancer (CRC) at our institution between Jan 1 2010 and Dec 31 2012. During this time DPD testing was usually performed in a reactive manner, typically for pts experiencing severe toxicities. We reviewed the charts of pts who tested positive for DPYD mutations and assessed the financial implications of their hospitalizations with toxicity. These costs were compared to the costs which would have incurred if all pts starting such therapy had been proactively tested. Results: A total of 134 pts started first-line 5FU-based chemotherapy for CRC over the study period, 66 in the adjuvant setting and 68 for metastatic disease. 31 pts had DPYD mutation testing performed. 6 tests (19% of those tested, 4.5% of the total population) revealed heterozygote DPYD mutations. 5 pts had already experienced severe treatment-related toxicity resulting in cessation of therapy, while one was tested prospectively and received chemotherapy with dose reduction ab initio. The total cost related to hospitalization with toxicity for these 5 pts was €155,083. At €177 per test, the cost to prospectively test all pts starting first-line 5FU-based therapy over the time period would have been €23,718 representing a saving of €131,365 through avoiding these admissions alone. 4 pts who tested positive for DPYD mutations were receiving adjuvant therapy and none restarted therapy following severe toxicity early in their therapy. 2 pts subsequently relapsed with metastatic disease. Conclusions: Prospective testing for DPYD mutations in pts with CRC starting 5FU-based therapy for the first time represents a considerable cost-saving opportunity, in addition to potentially avoiding prolonged hospitalization and morbidity for a sizeable minority of pts.
The efficacies of several antimalarial drugs in the treatment of uncomplicated Plasmodium falciparum malaria were compared, during an open, randomized trial, in New Halfa, eastern Sudan. The 96 patients who completed the 28 days of follow-up were treated with chloroquine (N = 26), sulfadoxine-pyrimethamine (N = 38) or quinine (N = 32). No treatment failures were observed among the patients given sulfadoxine-pyrimethamine. Only 23.1% of the patients given chloroquine showed adequate clinical response, however, the rest showing early (15.4%) or, more frequently, late (61.5%) treatment failure. In terms of parasitological failure, 54.1% of the patients given chloroquine showed early RI resistance, 7.7% showed late RI, and 15.1% showed RIII. Most (90.6%) of the patients treated with quinine had adequate treatment responses, the rest having late treatment failures (and late RI). The frequency of treatment failure was significantly higher, however, among the patients given chloroquine than in the quinine-treatment arm. The present results and those of earlier investigations indicate that the problem of chloroquine resistance is worsening in eastern Sudan, and that the use of chloroquine as the first-line drug for the treatment of uncomplicated malaria in this area is now compromised. The response to quinine may also be faltering.
e24088 Background: Up to one third of cancers in high-income populations can be attributed to lifestyle factors (nutrition & physical activity). Data on dietary beliefs in Irish patients with cancer are lacking. This study aims to evaluate how patients with cancer conceptualize the effect of diet on their disease and treatment & determine if attitudes vary according to age, gender, education, disease type, treatment type & treatment intent. Methods: This is a questionnaire-based study, carried out in an Irish oncology unit over a 3-week period in April 2021. Patients with an active cancer diagnosis attending the oncology day ward were invited to participate. We adapted a previously used questionnaire following expert review. A combination of yes/no and Likert scale responses were used: Have you changed your diet since you received your diagnosis? (Yes/no). To what degree do you think that...(Likert): Diet may contribute to the condition that you are being treated for?. Your diet after diagnosis helps your sense of health and wellness?. Diet can help relieve side effects of treatment?. Diet helps in preventing cancer recurrence?. Demographic and treatment data were recorded from patient charts. Responses were compared across demographic variables including gender, age, highest education level, primary cancer location/type and treatment intent using Chi-squared/Fishers exact test. A P-value of < 0.05 was considered significant. Results: 130 patients were invited to take part & 113 responded (response rate 87%). 80% reported changing their diet since diagnosis, with no significant difference according to demographic variables. Most (68%) patients expressed a belief that diet played some role in their cancer development although only 15% believed that diet contributed ‘a lot’. Most patients (83%) believed that diet after a cancer diagnosis has an impact on their sense of health and well-being, and 32% expressed a strong belief in this regard (Likert scale 4, ‘a lot’). 75% believed that diet has some impact on managing treatment side effects. 81% believed that diet has some impact on cancer recurrence, and 30% believed it has a major impact (Likert scale 4). On multivariate analysis we found stronger beliefs in the impact of diet on cancer development (p = 0.049) and recurrence risk (p = 0.05) among men than women, and stronger belief in the impact of diet on recurrence risk among patients receiving treatment with curative versus palliative intent (p = 0.045). Conclusions: Most patients reported changing their diet following their cancer diagnosis, and most patients felt that diet had some impact on all of the areas studied including cancer development, health and well-being, managing side effects and cancer recurrence. Men expressed stronger beliefs than women in the impact of diet on cancer development and recurrence risk, and patients being treated with curative intent also expressed stronger beliefs in the impact of diet on cancer recurrence.
e13018 Background: Approx 20% of patients receiving FP chemotherapy experience grade 3-5 toxicity. Known deleterious DPYD mutations account for 20% of these toxicities. We set out to examine whether polymorphisms/mutations in additional candidate genes involved in FP metabolism might account for severe toxicity in DPYD wild type (WT) individuals Methods: All patients receiving FP chemotherapy in our centre are prospectively screened for 4 common DPYD polymorphisms. Colorectal cancer patients treated between 2012-2015 were eligible if they had previously tested DPYD WT. Patients were identified using an institutional database and medical record review. DPYD WT patients who experienced grade 3/4 toxicity were defined as the case population and those without severe toxicity were categorised as the control population. Following informed consent, buccal swabs were taken to obtain DNA samples in order to genotype candidate genes (TPMT, TYMS and MTHFR). Statistical analysis was carried out on the data set returned. Results: 49 patients were recruited, 24 cases and 25 controls. Repeat testing confirmed DPYD WT status in all patients in concordance with previous genotyping. Polymorphisms in other candidate genes were found in both cases and controls. TPMT *1/*3A or *3C polymorphism was present in 6/24 cases and not found in controls (χ2 p = 0.007). Compound heterozygote status (polymorphisms in both the 5’ promoter and 3’ untranslated regions) of the TYMS gene were present in 21/24 cases and 12/25 controls (χ2 p = 0.003). Conclusions: In patients who are DPYD WT, TPMT *1/*3A or *3C may predict severe toxicity. TYMS compound heterozygote status is also associated with severe toxicity. This remained predictive when patients with concurrent TPMT mutations were excluded. These findings should be replicated in larger data sets, ideally in a prospective trial
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