Chemotherapy Prescription Research Articles

Adjuvant Chemotherapy De-Escalation with Genomic Assay Protocol in Patients with Early Breast Cancer: A Single-Centre Prospective Cohort Study.

Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation. Prospective cohort study of all consecutive women diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-negative early breast cancer, tested with the 21-gene Recurrence Score (RS) assay from August 2015 to July 2018 at a Portuguese cancer centre. For being tested, patients should meet at least one of the pre-defined inclusion criteria: i) luminal A-like, pT2pN0; ii) luminal A-like, 1 - 3 positive nodes and comorbidities with higher risk of chemotherapy-induced toxicity; iii) pT1-2pN0, progesterone receptor ≤ 20% and/or Ki67 14% - 40%. Adjuvant treatment was de-escalated to isolated endocrine therapy if RS was less than 18. We measured the reduction in chemotherapy prescribing and its clinical impact, the RS association with pathologic features, and the protocol feasibility. We tested 154 women with a median age of 61 years old (range: 25 - 79), 69% postmenopausal. Tumours were mainly pT1 (55%), pN0 (82%), invasive ductal (73%), G2 (86%), luminal B-like (69%) and stage IA (85%). We obtained a RS less than 18 in 60% of women, with an overall adjuvant chemotherapy reduction of 65%. Seven (95% confidence interval: 5 - 10) patients needed to be screened with the 21-gene RS assay to prevent one clinically relevant adverse event during the first six months of adjuvant treatment. Considering the currently used RS cut-off, only 9% of node-negative and 11% of node-positive patients had RS over 25. We found no relevant associations between RS and pathologic features. The protocol was feasible and did not compromise the adequate timing for adjuvant treatment. These criteria allowed the de-escalation of adjuvant systemic treatment in at least six out of ten women.

Association of chemotherapy and comorbidities with overall survival in elderly patients with early breast cancer: a French population-based propensity score-matched analysis.

Additional systemic treatment for early breast cancer in elderly is challenged by increasing comorbidities with age. We aimed to examine the effect of additional chemotherapy on overall survival in patients aged 70years or older and the impact of comorbidities on chemotherapy benefit. This retrospective monocentric cohort study includes data from all patients aged 70years and older who underwent surgery for an early breast cancer from 1997 to 2016. A propensity score analysis allowed adjustment for chemotherapy prescription preferences based on tumour characteristics. Of 15,599 patients who had surgery for an early breast cancer, 1743 (11.2%) over 70years old were included, of whom 269 (15.4%) had received additional chemotherapy. Median follow-up was 5.3years. Multivariate analyses on the propensity-score weighted cohort (n = 1 354) identified improved overall survival in patients with chemotherapy versus without (HR 0.54, 95% CI 0.31-0.92). Chronic obstructive pulmonary disease (HR, 2.16, 95% CI 1.40-3.34) and polypharmacy (HR 1.40, 95%CI 1.07-1.84) were associated with worse overall survival. No statistically significant interactions were identified between these comorbidities and chemotherapy prescription. Additional chemotherapy in elderly with early breast cancer is feasible and associated with overall survival benefit, supporting the importance of chemotherapy considerations in this population, and of avoiding undertreatment based on chronological age considerations alone.

Endoscopic treatment of obstructive jaundice in patients with Klatskin tumor

To improve treatment outcomes in patients with Klatskin tumor and obstructive jaundice by using of endoscopic bilioduodenal stenting. There were 1904 transpapillary interventions between August 2017 and February 2022. Endoscopic bilioduodenal stenting was performed in 250 patients including 25 (10%) ones with Klatskin tumor. Bilioduodenal plastic and self-expanding stents were installed in 19 (76%) and 6 (24%) patients, respectively. In Klatskin tumor type I, 11 patients (44%) underwent bilioduodenal stenting of common hepatic duct with plastic stent; 5 (20%) patients with Klatskin tumor type II received self-expanding stents. In case of tumor type IIIA, 3 (12%) patients underwent stenting of the right lobar duct with plastic stent. Four (16%) patients with Klatskin tumor type III B underwent stenting of the left lobar duct. Two 2 (8%) patients with Klatskin tumor type IV underwent bilateral bilioduodenal stenting with plastic and bifurcation self-expanding stents. Peroral cholangioscopy using the SpyGlass DS system was performed in 4 (16%) patients. No intraoperative complications were identified. One (4%) patient developed gastrointestinal bleeding in 2 postoperative days after retrograde intervention that did not require surgery. Moreover, 1 (4%) patient with distal dislocation of plastic bilioduodenal stent required redo bilioduodenal stenting. Three (12%) patients died from multiple organ failure despite adequate biliary decompression, and 22 (88%) patients were discharged in 8±5 days after retrograde intervention. Bilioduodenal stenting as minimally invasive and physiological method was highly effective for obstructive jaundice in patients with Klatskin tumor. Peroral cholangioscopy using the SpyGlass system provides effective and safe direct visualization of the biliary tract, as well as biopsy for morphological verification and prescription of chemotherapy in patients with intraductal growth of tumor.

Design, implementation, and evaluation of a CPOE system in a cancer care setting: A case study on the gastric cancer patients.

Chemotherapy is a complex, multi-disciplinary, and error-prone process. Information technology is being increasingly used in different health care settings with complex work procedures such as cancer care to enhance the quality and safety of care. In this study, we aimed to develop a computerized physician order entry (CPOE) for chemotherapy prescribing in patients with gastric cancer and to evaluate the impact of CPOE on medication errors and order problems. A multi-disciplinary team consisting of a chemotherapy council group and system design and implementation team was formed for chemotherapy process evaluation, requirement analysis, developing computer-based protocols, and implementation of CPOE. A before and after study was conducted to evaluate the impact of CPOE on the chemotherapy process and medication errors and problem orders. To evaluate the level of end-user satisfaction, an ISO Norm 9241/110 usability questionnaire was chosen for the evaluation. Before the implementation of the CPOE system, 37 medication errors (46.25%) and 53 problem orders (66.25%) were recorded for 80 paper-based chemotherapy prescriptions. After implementation of the CPOE system, 7 (8.7%) medication errors and 6 (7.5%) problem orders were recorded for 80 CPOE prescriptions. The implementation of CPOE reduced the medication error by 37.55% and the problematic order by 58.75%. The results for usability evaluation indicate that the CPOE was within the first class of the ISONORM level rating; this shows that a CPOE is with very high satisfaction and a very high functionality rate. Developing a CPOE system significantly improved safety and quality of the chemotherapy process in cancer care settings by reducing the medication error, deleting unnecessary steps, improving communication and coordination between providers, and use of updated evidence-based medicine in direct chemotherapy orders. However, the CPOE system does not prevent all medication errors and may cause new errors. These errors can be human-related factors or associated with the design and implementation of the systems.

Review of 20 years of Adult Medulloblastoma Treatment at a High-Volume Center – Chemotherapy Prescription Trends and Survival

<h3>Purpose/Objective(s)</h3> Medulloblastomas are WHO grade 4 tumors and represent less than 1% of adult brain malignancies. Standard of care is maximal safe resection follow by craniospinal and primary site radiation – the role for chemotherapy has been unclear. The objective of this study was to review 20-year chemotherapy prescribing trends in adult medulloblastoma patients at a high-volume center, with secondary objectives assessing overall and progression free-survival. We hypothesized that primary chemotherapy (concurrent or adjuvant) would be associated with prolonged survival and that patients treated in the most recent decade would have received chemotherapy more often. <h3>Materials/Methods</h3> A retrospective review was performed of adult medulloblastoma patients at a high-volume center from 1999-01-01–2020-12-31. Eligible patients were 18 years and older with a pathologic diagnosis of medulloblastoma – those with supratentorial primitive neuroectodermal tumors were excluded. Descriptive statistics were used to present population data and Kaplan–Meier estimators for survival analysis. <h3>Results</h3> Forty-nine patients were eligible; median age was 30 and male: female ratio was 2:1. Desmoplastic and classical histologies were the most common. Molecular subgroup was available for 6 patients, with SHH predominating. Of all patients, 47% (23/49 were classified as high risk – most commonly due to large cell/anaplastic histology or large residual. Only 10 (20%) received primary chemotherapy, 70% of which had high risk disease. Of the patients who received primary chemotherapy, 30% went on to receive chemotherapy for recurrence or metastases; of the entire population, this was only 39%. Primary regimens were mainly cisplatin/lomustine/vincristine, while recurrence regimens were often cisplatin/etoposide. The majority who received primary chemotherapy were treated from 2010–2020. Median overall survival was 7.8 years (95% CI 5.7–∞), with 1-, 5-, and 10-year survival 95.8%, 67.5% and 42.2% respectively. Overall survival was marginally better for those who did not receive primary chemotherapy (8.5 years) vs those who did (7.4 years) <i>but this was non-significant</i>. The main chemotherapy toxicity was hematologic and neuropathy - 90% of primary chemotherapy patients experienced toxicity <h3>Conclusion</h3> This study reviewed 20 years of treatment trends for a group of adult medulloblastoma patients at a high-volume center. We found only a small proportion of patients received chemotherapy as their primary treatment with surgery and radiation. Patients who received primary chemotherapy had marginally worse overall survival, but this was non-significant – perhaps due to baseline worse clinical status not captured by the definition of high vs. intermediate risk disease. Despite calls for adjuvant chemotherapy for all adult medulloblastoma patients, there is clinical equipoise and future randomized trials are needed.

Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer

Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan–Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox’s proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33–65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96–3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.

Characterizing and learning from medical malpractice cases against medical oncologists using a national claims database.

318 Background: Malpractice cases may contain valuable information to inform safety improvement efforts in cancer care. No analyses of malpractice cases have been published focusing on medical oncologists as the primary defendant. The recent development of a new safety incident taxonomy for medical oncology enabled us to classify malpractice cases and identify patient safety improvements.1. Methods: We conducted a qualitative analysis of case vignettes naming medical oncologists as the primary defendant. Case vignettes were obtained from CRICO’s Candello database. Of 452 cases against medical oncologists, a random sample of 100 cases was selected. Cases were coded for the type of safety incident, and whether a system solution could plausibly reduce the risk of a future event. Coding was performed by 3 physicians with experience caring for patients with cancer. Two reviewers reviewed each case; discrepancies were resolved by the third reviewer. Results: Ninety-nine cases were included in the final analysis; 1 was determined to be misassigned to medical oncology as the primary defendant when the case vignette was entirely about radiation oncology treatment and side effects. The most frequent cancer types were breast (16%), acute leukemia (9%), aggressive lymphoma (8%), and gynecologic malignancies (7%). The most common safety incidents identified were provider clinical management errors (41%), adverse drug reactions (20%), relational issues among providers, patients, and other healthcare staff (13%), and prescriber ordering errors (6%). 47 case vignettes described safety incidents that might have been prevented by a systems intervention. The most common interventions were “tumor board or expert review of rare or uncertain cases” (19%), “pharmacist review for safe prescribing of chemotherapy” (17%), “cancer navigator for appointment scheduling in high-risk settings” (9%), “closed loop communication with radiology” (6%), and “electronic patient portal access to all test results” (6%). Conclusions: Using a new medical oncology-focused incident coding taxonomy, we were able to classify all 99 malpractice cases. Human factors issues accounted for the majority of claims. We determined that more comprehensive use of existing improvement interventions might substantially reduce the risk of future events. 1 Jacobson, J. et al. Development of a taxonomy for characterizing medical oncology-related patient safety and quality incidents: A novel approach. BMJ Open Quality. [Manuscript in press]. Accepted June 10, 2022. DOI 10.1136/bmjoq-2022-001828.R2.

Evaluating the Fragility of Long-Term Outcomes for Neoadjuvant versus Adjuvant Chemotherapy Prescription in Early Breast Cancer: Pooled Data from 10 Randomised Clinical Trials.

IntroductionRandomised clinical trials (RCTs) report similar outcomes following neoadjuvant (NAC) and adjuvant chemotherapy (AC) in breast cancer. “Fragility Indices” (FI) test significance reversal reported in RCTs.AimTo evaluate the FI of findings from RCTs assessing outcomes of NAC and AC.MethodsA systematic review was performed as per PRISMA guidelines. RCTs of interest were identified and data pooled. Fisher’s exact test was used to calculate FI for reversal of statistical significance for dichotomous outcomes. “Fragility Quotient” (FQ) was calculated by division of the calculated FI by the sample size.ResultsTen RCTs including 4928 patients. Mean follow-up was 8.2 years. For breast conservation surgery (BCS), the FI was 500 and FQ was 0.10781. For local recurrence (LR), the FI was 42 and FQ was 0.00852. FI and FQ varied for LR at 0–4 years (FI: 9), 5–9 years (FI: 2), 10–14 years (FI: 4), and 15+ years (FI: 3). Regarding distant recurrence (DR), the FI was 13 and FQ was 0.00264. FI and FQ trended downwards over time: 0–4 years (FI: 56), 5–9 years (FI: 18), 10–14 years (FI: 4), and 15+ years (FI: 4). For breast-cancer-specific mortality (BCSM), the overall FI was 51 and FQ was 0.01035. FI and FQ varied for BCSM at 0–4 years (FI: 5), 5–9 years (FI: 19), 10–14 years (FI: 8), and 15+ years (FI: 5). For overall survival (OS), the FI was 17 and FQ was 0.00345. FI and FQ were calculated with respect to OS at 0–4 years (FI: 19), 5–9 years (FI: 17), 10–14 years (FI: 19), and 15+ years (FI: 1).ConclusionFIs comparing survival following NAC and AC were of moderate-to-high fragility, indicating weak statistical significance. BCS eligibility following NAC was of low fragility, ratifying the oncological and surgical safety of NAC versus AC.Level of EvidenceSystematic Review of Level I Randomised Control Trials.

Review of 20 years of adult medulloblastoma treatment: Chemotherapy prescription trends and survival.

The historic standard of care for adult medulloblastoma has been considered surgery and radiation, while chemotherapy is increasingly being prescribed. This study reviewed 20-year chemotherapy trends at a high-volume center, as well as overall and progression free-survival. Adults with medulloblastoma treated at an academic center from January 1, 1999 to -December 31, 2020 were reviewed. Patient baseline data were summarized and Kaplan-Meier estimators were used for survival. Forty-nine patients were included; median age was 30 years and male: female ratio was 2:1. Desmoplastic and classical histologies were most common. Of all patients, 23 (47%) were high risk and 7 (14%) metastatic at diagnosis. Only 10 (20%) received initial chemotherapy, of which 70% were high risk and 30% metastatic, with most treated from 2010 to 2020. Forty percent of initial chemotherapy patients received salvage chemotherapy for recurrence or metastases (of all patients, 49% required salvage). Initial chemotherapy regimens were mainly cisplatin/lomustine/vincristine, and at recurrence cisplatin/etoposide. Median overall survival was 8.6 years (95% CI 7.5-∞), with 1-, 5-, and 10-year survival at 95.8%, 72%, and 46.7%. Median overall survival for those who did not receive initial chemotherapy was 12.4 years and 7.4 years for those who did (P-value .2). Twenty years of adult medulloblastoma treatment was reviewed. Initial chemotherapy patients, most of whom were high risk, trended towards worse survival, but this was nonsignificant. The ideal timing and choice of chemotherapy for adult medulloblastoma is unknown-challenges of administering chemotherapy following photon craniospinal irradiation may have prevented it from becoming routine.

149: Review of 20 Years of Adult Medulloblastoma Treatment at a High-Volume Centre - Chemotherapy Prescription Trends and Survival

149: Review of 20 Years of Adult Medulloblastoma Treatment at a High-Volume Centre - Chemotherapy Prescription Trends and Survival

The use of healthcare datasets to investigate the impact of dose intensity in the adolescent and young adult cancer population.

Objectives To investigate whether the dose intensity of chemotherapy received by Adolescent and Young Adult (AYA) cancer patients impacts on their survival. To assess and compare the utility of existing healthcare data available at a regional, national and international level to answer this question. ApproachA regional dataset has been created through linkage of the Yorkshire Specialist Register of Cancer in Children and Young People to electronic chemotherapy prescribing data from Leeds Teaching Hospitals NHS Trust, providing a detailed dataset. The national dataset comprises of data from the National Cancer Registry and Analysis Service (NCRAS) linked to the Systemic Anti-Cancer Therapy (SACT) dataset which collects chemotherapy prescribing data from all hospitals in England. This dataset provides bigger patient numbers but data at a pseudonymised level. The international dataset comprises of anonymised data from clinical trials. ResultsThe data has being linked, cleaned and validated. Survival analysis is being carried out using a causal inference framework. ConclusionThis study will describe the value of existing healthcare care sets in the AYA cancer population. Identification of areas in which the datasets are lacking will help inform data controllers regarding ways in which data collection can be optimised for this important patient group.

Using failure mode and Effects Analysis to increase patient safety in cancer chemotherapy.

Medication errors may occur during chemotherapy and can have fatal consequences. Healthcare Failure Mode and Effects Analysis (FMEA) is a method used to detect potential risks and prevent them. Aim of this study was to evaluate the medication process of intravenous tumor therapy in order to guarantee a high standard of patient safety. The main part of the study was performed at the University Hospital of Bonn, Germany. After assembling a multidisciplinary team, the individual steps of prescription, compounding, transport, and administration of chemotherapy were mapped in a flow diagram. The possible failures were identified and analyzed by calculating the risk priority numbers (RPNs). Finally, corrective actions were developed and after hypothetical implementation re-analyzed to measure their effects on the process. Subsequently, a shortened FMEA based on the catalogue failure modes developed in Bonn was carried out at the University Hospital of Cologne in order to evaluate its transferability to another hospital. A total of 52 potential failure modes was identified in Bonn. Relating to the RPNs the most critically steps in the process were associated with the prescription, namely, incorrect information about individual parameters of the patient; non-standardized chemotherapy protocols; and problems related to supportive therapy. A significant risk reduction for most of the failure modes was assessed by implementing suitable corrective actions. The shortened FMEA in Cologne led to a different ranking of failure modes. The implementation of this analysis has not only identified various safety gaps, but also shows how patient safety during chemotherapy can be enhanced. Moreover, it has sensitized the practitioners to failure modes potentially occurring in their work routine.

Abstract 1939: Multimodal prediction of metastatic relapse using federated deep learning outperforms state-of-the-art methods in soft-tissue sarcoma

Abstract Soft Tissue sarcomas (STS) are a group of heterogeneous and complex diseases. Being able to predict the appearance of metastases is key to inform clinical decisions, especially the prescription of perioperative chemotherapy. While multiple methods including multivariable nomograms have been developed to tackle this issue, we leveraged artificial intelligence (AI) to extract information from raw images with Deep-Learning. In this study, we developed SarcNet: a multimodal deep-learning algorithm based on histological slides and clinical variables to predict metastatic relapse in patients affected with limbs and trunk wall STS. Two independent series were investigated simultaneously: Centre Léon Bérard, n=221 and Institut Bergonié, n=390. This study was able to gather a sufficient number of patients in this rare disease by training all the algorithms in a multicentric fashion using Federated Learning (FL). It is one of the first real-world applications of FL in Healthcare which allows to keep patients’ data behind hospital firewalls. The SarcNet algorithm achieved unprecedented performance. By leveraging an AI-driven analysis of digitized whole slide images in addition to clinical variables, our multimodal model achieved a 0.80 AUC to predict 5-year MFS (metastatic free survival) compared to 0.77 for Sarculator (current state-of-the-art nomogram). It also greatly outperformed current standard of care practices like FNCLCC grading that reached an AUC of 0.70. Interpretability investigations of the SarcNet model highlighted histological patterns that drive the prediction of metastatic relapse such as atypia, tumoral cellularity and mitosis. This model could lead to more informed clinical decisions by identifying high-risk patients that could benefit from perioperative chemotherapy. Finally, deeper investigations of the model and the highlighted biomarkers could lead to a better understanding of metastatic relapse in STS Performance of models to predict 5y MFS (AUC evaluated in 5 repeated 5-fold cross validation) Methods Whole cohort (n=611) IB (n=390) CLB (n=221) SarcNet 0.800, 95% CI [0.786-0.814] 0.770, 95% CI [0.750-0.791] 0.842, 95% CI [0.824-0.859] Sarculator 0.767, 95% CI [0.752-0.783] 0.736, 95% CI [0.718-0.755] 0.808, 95% CI [0.785-0.831] FNCLCC (French Federation of Centers for the Fight against Cancer) grading 0.699, 95% CI [0.684-0.714] 0.723, 95% CI [0.708-0.738] 0.637, 95% CI [0.612-0.663] Citation Format: Charles Maussion, Jean-Michel Coindre, Jean-Yves Blay, Kathryn Schutte, Axel Camara, François Le Loarer, Raul Perret, Myriam Jean-Denis, Alexandra Meurgey, Françoise Ducimetiere, Antoine Giraud, Jean-Baptiste Courrèges, Clément Gautier, Etienne Bendjebbar, Jean Du Terrail, Antoine Italiano, Marie Karanian. Multimodal prediction of metastatic relapse using federated deep learning outperforms state-of-the-art methods in soft-tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1939.

P-115 Bevacizumab in metastatic colorectal carcinoma: A retrospective review of real-world efficacy

We present to you a retrospective review of our institutional use of Bevacizumab in colorectal cancer with respect to chemotherapeutic regimen, efficacy and morbidity relating to its use over a 5-year period in the Maltese islands. We also evaluated whether these outcomes were influenced by patient demographics or tumor characteristics including molecular markers e.g., RAS and BRAF where available. Patients with a diagnosis of metastatic colorectal cancer were identified through our cancer registry and chemotherapy prescribing databases. Patient demographics and tumor characteristics (grade, stage, tumor sidedness) including molecular profiling (K-RAS, BRAF V600E, MSI) were collected. Treatment modality including chemotherapeutic combination and previous lines of therapy as well as radiotherapy, surgery or intervention ablation techniques were documented. Morbidity including hospital admissions during bevacizumab therapy including severity of treatment was documented. Our standard of reference for this audit was the ESMO clinical practice guidelines for the management of metastatic colorectal carcinoma (mCRC). The primary endpoint studied was progression free survival (PFS). Individual variables collected were analyzed for their significance using Cox Regression Analysis via SPSS based software. 54 patients were included in our study over a 5-year period (2015-2020). Folfox was preferred as a first line chemotherapy regimen whilst Folfiri was favored as a second line option. Bevacizumab was used in the first line setting in 29% of the patients and 2nd line agent in in 36% of the patients. 14 patients still received bevacizumab despite showing disease progression with mPFS 48.5 weeks while 38 patients discontinued bevacizumab despite progression with an mPFS of 27.5 weeks. 24 patients had a KRAS mutant tumor whilst 18 patients were KRAS wild type. The mPFS for KRAS mutant tumor was 27 weeks when treated with bevacizumab in combination with Folfox (n=8, mPFS=39 weeks) or Folfiri (n=10, mPFS 26 weeks). For those patients with a K-RAS wild type tumor, the mPFS was 35 weeks (Folfox-Bev n=2, mPFS=69 weeks; Folfiri-Bev n=8, mPFS= 43 weeks). The only variables achieving statistical significance were the contribution of age and use of fluoropyrimidine based cytotoxic therapy. The first parameter noted that an age cut off below or equal to 60 years of age in contrast to patients above 60 years of age had variable outcomes. The second criterion related to the use of fluoropyrimidines in combination with bevacizumab in contrast to those patients treated with a non-fluoropyrimidine regimen such as single agent irinotecan or lonsurf. Only 7% of patients experienced severe toxicity needing hospitalization. In our research, we confirm that it is the addition of a fluoropyrimidine-containing regimen to bevacizumab that is statistically significant, especially in the patient cohort under the age of 60 years. This is in line with current data that confirms that bevacizumab in combination with any fluoropyrimidine-based chemotherapy is more effective than any fluoropyrimidine-based chemotherapy alone. We also presume that the younger patient is likely to have better performance status, less co-morbidities and improved tolerability to chemotherapy, possibly explaining the improved outcomes in PFS.

Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment (SCOT) Trial Findings in colorectal cancer at a National Level

AimsThe Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland. Materials and methodsA retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility. ResultsIn total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14–24) prior to June 2017 to 12 weeks (interquartile range 12–21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends. DiscussionA significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.

Chemoviz: an Interactive Web-based Tool for Time-series Analysis of Systemic Anti-cancer Therapy: Application to Analysis of Dose Modifications of CDK4/6 Inhibitors in Clinical Practice

Purpose: Chemotherapy prescribing systems are not routinely interrogated at unit level for clinical outcome data despite the ready availability of analysis and visualisation tools which could enable useful information to be derived. As an example, the CDK4-6 inhibitors palbociclib and abemaciclib are now used routinely in clinical practice for metastatic oestrogen receptor-positive breast cancer. Myelosuppression is often observed in clinical practice, leading to dose modification and patients not receiving as many cycles as quoted in the literature (12 cycles for palbociclib, 19 for abemacilib). Patients on palbociclib are routinely monitored with full blood counts every cycle, despite manufacturer advice to reduce this to 3-monthly after cycle 6.

Heterogeneity of posttraumatic stress, depression, and fear of cancer recurrence in breast cancer survivors: a latent class analysis.

Breast cancer survivors may demonstrate elevated psychological distress, which can also hinder adherence to survivorship care plans. Our goal was to study heterogeneity of behavioral health and functioning in breast cancer survivors, and identify both risk and protective factors to improve targets for wellness interventions. Breast cancer survivors (n = 187) consented to complete self-reported psychological measures and to access their medical records. Latent class analysis (LCA) was used to classify heterogeneous subpopulations based on levels of depression, post-traumatic stress, fear of cancer recurrence, cancer-related pain, and fatigue. Multinomial logistic regression and auxiliary analysis in a 3-step modeling conditional approach was used to identify characteristics of the group based on demographics, treatment history and characteristics, and current medication prescriptions. Three subpopulations of breast cancer survivors were identified from the LCA: a modal Resilient group (48.2%, n = 90), a Moderate Symptoms group (34%, n = 65), and an Elevated Symptoms group (n = 17%, n = 32) with clinically-relevant impairment. Results from the logistic regression indicated that individuals in the Elevated Symptoms group were less likely to have a family history of breast cancer; they were more likely to be closer to time of diagnosis and younger, have received chemotherapy and psychotropic prescriptions, and have higher BMI. Survivors in the Elevated Symptoms group were also less likely to be prescribed estrogen inhibitors than the Moderate Symptoms group. This study identified subgroups of breast cancer survivors based on behavioral, psychological, and treatment-related characteristics, with implications for targeted monitoring and survivorship care plans. Results showed the majority of cancer survivors were resilient, with minimal psychological distress. Results also suggest the importance of paying special attention to younger patients getting chemotherapy, especially those without a family history of breast cancer.

A Population-Based Study of Treatment and Survival in Older Glioma Patients

BackgroundPopulation-based analyses of patterns of care and survival of older patients diagnosed with grade II-III oligodendroglioma (OLI) or astrocytoma (AST) can aid clinicians in their understanding and care of these patients.MethodsWe identified patients diagnosed between 2006 and 2015 with primary glioma diagnoses (OLI or AST) who were older than 65 years using the latest release of the Surveillance, Epidemiology, and End Results-Medicare–linked database. Medicare claims were used to identify cancer treatments (surgery, chemotherapy, and radiation therapy) from 2006 to 2016. Kaplan-Meier methodology was used to describe overall survival (OS). Cox proportional hazards regression was used to associate variables of interest, including treatments in a time-dependent manner, with OS. Hazard ratios (HRs) and 95% confidence intervals (CIs) from multivariable, cause-specific competing risk models identified associations with treatments. All statistical tests were 2-sided.ResultsWe identified 1291 patients comprising 158 with OLI, 1043 with AST, and 90 with mixed histologies. Median OS was 6.5 (95% CI = 6.1 to 7.3) months for the overall cohort, 22.6 (95% CI = 13.9 to 33.1) months for OLI, and 5.8 (95% CI = 5.3 to 6.4) months for AST. Patients who received surgery and patients who received both chemotherapy and radiation therapy in combination experienced better OS (HR = 0.87, 95% CI = 0.79 to 0.96, and HR = 0.58, 95% CI = 0.35 to 0.96, respectively). Over the time frame studied, there was a 4.0% increase per year in prescription of chemotherapy (P = .03) and a 2.0% improvement in OS for each calendar year (P = .003).ConclusionsWe provide population-based evidence that patients older than 65 years with grade II-III glioma have experienced increased chemotherapy use as well as improvement in survival over time.

Status of Inquiries to Prescribing Doctors about Cancer Chemotherapy Prescriptions by Pharmacists at an Insurance Pharmacy

Status of Inquiries to Prescribing Doctors about Cancer Chemotherapy Prescriptions by Pharmacists at an Insurance Pharmacy

A Clinical Decision Support System for Increasing Compliance with Protocols in Chemotherapy of Children with Acute Lymphoblastic Leukemia

Objective:In this survey, a protocol-based Chemotherapy Prescription Decision Support System (CPDSS) was designed and evaluated to reduce medication errors in the chemotherapy process of children with ALL.Methods:The CPDSS algorithm was extracted by the software development team based on the protocol used by doctors to treat children with ALL. The ASP.Net MVC and SQL Server 2016 programming languages were used to develop the system. A 3-step evaluation (technical, retrospective, and user satisfaction) was performed on CPDSS designed at 2 children’s hospitals in Tehran. The data were analyzed using descriptive statistics. At the technical evaluation step, users provided recommendations included in the system.Results:In the retrospective CPDSS evaluation step, 1281 prescribed doses of the drugs related to 30 patients were entered into the system. CPDSS detected 735 cases of protocol deviations and 57 (95%, CI = 1.25-2.55) errors in prescribed chemotherapy for children with ALL. In the user satisfaction evaluation, the users approved two dimensions of the user interface and functionality of the system.Conclusions:With the provision of alerts, the CPDSS can help increase compliance with chemotherapy protocols and decrease the chemotherapy prescribing errors that can improve patient safety.