Delivery Of Systemic Treatment Research Articles

Prognostic impact of the number and total tumor burden of secondary cerebral lesions in patients with resected brain metastases of non-small cell lung cancers.

Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.

Current state assessment of the organization and delivery of systemic treatment in Ontario.

20 Background: In 2019, Ontario Health (Cancer Care Ontario) published 54 standards to ensure high quality and safe delivery of systemic treatment (ST) in Ontario, along with 16 recommendations for take-home cancer drugs (THCD). The standards/recommendations focused on 7 domains for the delivery of ST delivery and 8 domains for THCD. These domains varied between the two documents but also overlapped on issues including prescribing, patient care, patient education and training and education for providers. The standards for ST delivery were also prioritized according to Very High, High or Medium priority with regards to implementation expectations. The objective of this project was to obtain a baseline assessment of alignment with the standards/recommendations for all ST sites within Ontario. Methods: A validated electronic survey that linked to all standards/recommendations was distributed to 75 ST sites in August 2019. Sites had 8 weeks to complete the survey with their multi-disciplinary teams. Data was analyzed centrally using quantitative analysis methods by region as well as by site level. Results: The response rate was 100%. Overall, alignment in all domains was higher for intravenous cancer drug (IVCD) delivery as compared to THCD delivery. Important areas of gaps include CPOE/PPO use (75% for both IVCD and THCD); appropriate drug labels (90% for IVCD versus 52% for THCD); prescribing/dispensing independent double checks (IDC) (95% for IVCD versus 38% for THCD); pump independent double check (83% of sites); continuous ST with central line (86% of sites); standardized tool for THCD education (40%); and oncology training/education (96% of RNs versus 20% of pharmacists). Conclusions: The main gaps that were identified through the current state assessment were related to THCD, as opposed to IVCD. To ensure alignment with the standards/recommendations, these gaps should continue to be an area of focus for quality improvement. The survey was instrumental in informing provincial, regional, and local strategies to address these gaps and to ensure high quality, safe practices are embedded in ST delivery as outlined in the published best practice documents.

Abstract PD10-10: Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy

Abstract Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity (dRDI &amp;lt; 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion. Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI &amp;lt; 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI. Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide [TC] (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI &amp;lt;85%). HR+/HER2- and TNBC had similar RDI (p = 0.74). In bivariate analysis, older age &amp;gt; 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS &amp;lt; 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age &amp;gt;70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS &amp;lt; 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p &amp;lt; 0.001). Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged &amp;gt; 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS &amp;lt; 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population. Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-10.

Reviewing systemic treatment regimens to reduce unintentional errors.

51 Background: Use of systemic treatment computerized prescriber order entry (ST CPOE) and pre-printed orders (PPO) are proven error reduction measures. Such systems are not failsafe, as regimen development depends on cognitive input at critical points and is susceptible to human error. No known guidance currently exists in oncology to ensure regimens are of high quality and built as intended. The purpose of this initiative was to improve the quality of oncology regimens in Ontario. Methods: A review of 35 centres, representing 75 treatment centres in a hub-and-spoke model, was conducted for all active regimens (PPO and CPOE) to ensure they were built as intended, with respect to drugs and doses. Centres completed an exploratory survey to report any unintentional discrepancies and existing maintenance review processes. The survey collected centre demographics and contained descriptive questions to document details of the regimen review and maintenance processes. Results: The review yielded an 86% response rate (12 regional and 18 community cancer centres). Upwards of 700 regimens were reviewed by a multidisciplinary team at each participating centre. Unintentional discrepancies were reported by 7 of the 30 (23%) centres (range of 2 – 141 per centre); types and examples are presented in the Table. Only 2 of 30 centres (7%) had an established regimen maintenance process. Conclusions: The review identified unintentional discrepancies and, due to the potential for patient harm, corrective action has been taken. There is a need for guidance and adoption of a standardized approach in order to sustain a high-quality regimen build and review process across the province. Consensus-based recommendations for ST CPOE and PPO regimen development and maintenance have been developed. Identified discrepancies have been amended and maintenance review processes are now implemented to improve the quality and safety of systemic treatment delivery. [Table: see text]

Assessing the quality of chemotherapy in an episode-based funding model in Ontario.

1 Background: On April 1, 2014, the delivery of systemic treatment in Ontario transitioned to an episode-based funding model, which provides bundled payments for a full course of therapy delivered with adjuvant/curative intent and a monthly bundled payment for palliative intent. Disease Site Teams have defined treatment options and “best practice” for each funded adjuvant/curative regimen. Methods: The utilization of treatment according to disease and intent was analyzed for 35 systemic treatment facilities in Ontario, comparing actual practice (AP) with “best practice” (BP) (dose/schedule/cycle number), for common adjuvant/curative regimens. Variation in the choice of chemotherapy regimen was also reviewed. Results: Cases were included if they started a new course of adjuvant/curative therapy after January 1, 2014, and completed their treatment before July 31, 2015 (17,341 cases). For all disease sites and facilities, AP was equal to BP in 34.6% of cases, AP &lt; BP in 57.5%, and AP &gt; BP in 7.8% (Table). There was significant variation by disease site and facility. As a specific example, 1,368 courses of adjuvant mFOLFOX were completed for colorectal cancer: AP = BP (12 cycles) in 34% (range 7-70%), AP &lt; BP in 66% (range 30-93%), and AP &gt; BP in 1% (range 0-4%). Variation in choice of adjuvant regimen for breast cancer was also observed. Provincially, 21.5% of patients received non-anthracycline containing therapy, but the range in the 20 largest volume centers was 0% to 39.8%. Conclusions: With the administration of potentially curative therapy, it might be assumed that BP would be administered in the majority of cases. However, initial results demonstrate significant variation in practice in an episode based funding model. There is a need to understand the reasons for this variation and to identify potential opportunities to drive efficiency and to increase standardization by engaging clinical experts and practitioners. [Table: see text]

Improving the safe delivery of systemic treatment by assessing concordance with labeling guidelines.

257 Background: Improper labeling of medication may lead to errors. In 2009, Cancer Care Ontario published Key Components of Chemotherapy Labeling, with recommendations for the necessary components and formatting of intravenous chemotherapy labels. A jurisdiction-wide evaluation for concordance occurred in 2011. Results were shared, improvement efforts were supported through a provincial quality network, and a re-evaluation was conducted in the fall of 2013. Methods: Three defined chemotherapy labels were evaluated at baseline and after improvement strategies were implemented at each of Ontario’s 77 hospitals providing systemic treatment. Labels were reviewed centrally and awarded points for concordance for each of 15 guideline-specified criteria. Results: The provincial average overall score for concordance increased from 59% to 80% (p&lt;0.001). Improvement was seen for 12 of the 15 criteria evaluated and for 64 of the 77 facilities. The greatest increase in overall score by a facility was 53.4%. The greatest overall improvement in score for an individual component was 67% (TALLman lettering). The scores of 2 components were unchanged, as 100% concordance was achieved on both the baseline and re-evaluation. Conclusions: Improvement in concordance to chemotherapy labeling guidelines was observed following the implementation of a measurement strategy and improvement plans. This approach is one component of a larger strategy to promote a culture of safety in chemotherapy delivery in Ontario. [Table: see text]

Enabling quality improvement in systemic cancer treatment through a collaborative approach.

88 Background: The Regional Systemic Treatment Program at Cancer Care Ontario (CCO) aims to ensure the highest quality of systemic treatment is available to Ontarians, as close to home as possible. CCO initiated a provincial collaborative with the aim of improving the safe delivery of parenteral chemotherapy from orders through preparation, to administration, for patients, and providers. Methods: From April 2011 to March 2012, interdisciplinary hospital teams across Ontario followed multiple Plan, Do, Study, Act cycles to perform QI projects focusing on safe delivery of systemic treatment. Over this period, three in-person sessions educating participants on improvement methodology were held. Monthly teleconferences and an electronic discussion forum encouraged a culture of knowledge sharing and collaboration. Results: 113 participants from 26 teams participated in a total of 81 improvement initiatives. 96% of participants surveyed indicated that the collaborative provided a valuable opportunity to network with peers, share ideas, and discuss lessons learned. During the collaborative, teams reported their progress on a scale of 1-5. At May 2011, teams averaged a self-assessment score of 1, indicating no progress had been made. By February 2012, this increased to an average score of 4, indicating significant progress and achievement of at least one improvement objective/goal. CCO has leveraged the foundations built by the collaborative to develop a Regional Quality and Safety Network. This network provides a regular forum for health care providers and administrators to share knowledge and collaborate on strategies for improving quality and safety in the delivery of systemic treatment. Conclusions: The collaborative demonstrated that the use of a formal quality improvement model is a successful mechanism for regional engagement; that provides the foundation necessary for building a provincial network with common goals and understanding regarding quality improvement. By educating participants, supporting local efforts and enabling knowledge transfer and exchange, the collaborative showed that shared ideas and even small changes can lead to large-scale improvements for patients and providers.

A Framework for the Organization and Delivery of Systemic Treatment

Increasing systemic treatment and shortages of oncology professionals in Canada require innovative approaches to the safe and effective delivery of intravenous (IV) cancer treatment. We conducted a systematic review of the clinical and scientific literature, and an environmental scan of models in Canada, the United Kingdom, Australia, and New Zealand. We then developed a framework for the organization and delivery of IV systemic treatment. The systematic review covered the medline, embase, cinahl, and HealthStar databases. The environmental scan retrieved published and unpublished sources, coupled with a free key word search using the Google search engine. The Systemic Treatment Working Group reviewed the evidence and developed a draft framework using evidence-based analysis, existing recommendations from various jurisdictions, and expert opinion based on experience and consensus. The draft was assessed by Ontario stakeholders and reviewed and approved by Cancer Care Ontario. The poor quantity and quality of the evidence necessitated a consensus-derived model. That model comprises four levels of care determined by a regional systemic treatment program and three integrated structures (integrated cancer programs, affiliate institutions, and satellite institutions), each with a defined scope of practice and a specific organizational framework. New models of care are urgently required beyond large centres, particularly in geographically remote or rural areas. Despite limited applicable evidence, the development and successful implementation of this framework is intended to create sustainable, accessible, quality care and to measurably improve patient outcomes.