bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stage migration in breast cancer: Better detection or semantics in staging?
Authors: Elson Leah , Bilani Nadeem , Liang Hong , Elimimian Elizabeth Blessing , Saravia Diana , Nahleh Zeina A. 
Published: June 2021

e18800 Background: As oncology treatment has evolved to become more individualized, prognostic rationale has also undergone important changes. In breast cancer, disease staging was historically based upon anatomic features of the primary tumor, in combination with involvement of adjacent/distant tissues. However, as the understanding of molecular/genomic involvement became more advanced, staging definitions were redefined to incorporate receptors, histologic grade, and genetic expression. In this analysis, we use autoregressive integrated moving average (ARIMA) forecasting to understand how AJCC updates to prognostic definitions have contributed to stage migration, and to comment on whether better detection, or definitional changes, may be responsible for the increasing incidence in early stage breast cancer. Methods: In this time series forecast, ARIMA models, per stage (early: stage I/II vs. late: stage III/IV) were constructed based on 2004-2016 historic breast cancer incidence rates, as reported by the NCDB. Multiple models were generated, using differing autoregressive parameters; the most predictive model was chosen using the lowest Bayesian Information Criteria (BIC), and mean absolute percentage error (MAPE) to ensure best fit. Similar methodology has already been published to predict prostate cancer incidence. The best fit models were applied to forecast annual incidence, in the NCDB, in 2017. These data were compared to the real-world data captured in 2017. Statistics were performed using modeling systems in SPSS, version 27. Results: n=1,661,971 cases were included for these models, and 12 years of pre-AJCC updated NCDB breast cancer data were used. Using ARIMA modeling, best fit, stationary averages were identified, with autoregressive and difference terms which contributed to the lowest BIC, and MAPE < 5%, for both models. The best fit models forecasted 2017 incidence, by stage, without AJCC updates to staging criteria, and this data is compared to actual 2017 incidence with current updated AJCC 8th staging criteria (Table). Conclusions: During 2017, the first year of AJCC staging updates, there was an observed decrease in late stage diagnoses, and increase in early stage diagnoses, when compared with incidence rates that were forecasted using the old, anatomic AJCC criteria. Therefore, part of the stage migration noted may be a product of staging semantics, using updated definitions. Confirming appropriate improvement in long-term outcomes, based on new staging would be helpful. It is also important for clinicians and public health officials to bear this in-mind when interpreting epidemiologic data, for allocating resources, as shifts in staging may be a product of guideline changes, and not necessarily screening efficacy or early detection only.[Table: see text]
Propping up the parents: An environmental scan of childcare programs available to cancer patients in North America.
Authors: Preston Katherine , MacDonald Mackenzie , Giuliani Meredith Elana , Melosky Barbara L. , Leung Bonnie , Ingledew Paris-Ann 
Published: June 2021

e18805 Background: Approximately 20% of newly diagnosed cancer patients are between the ages of 20 and 54, and many of these patients are also the primary caregivers of children. Qualitative studies focusing on this demographic indicate that patients who are parents struggle to balance their own care needs with those of their children. Further, a lack of childcare support during cancer treatments can negatively impact compliance and increase existing psychological stress for patients. In the efforts to establish a child-minding program at a major Canadian cancer centre, we carried out an environmental scan to evaluate the current state of childcare support for cancer patients. Methods: Firstly, a literature scan was conducted in order to assess current knowledge about childcare and cancer patients, which included the use of search engines, directed internet searches, a review of oncology conference proceedings and websites of oncology associations. Literature was selected based on pre-determined criteria. Secondly, 12 representatives from major Canadian cancer centres (CCC) completed a questionnaire assessing current childcare strategies at their respective institutions. Finally, a broad scan of the grey literature was conducted by investigating 161 Canadian and American hospitals for on-site childcare services, using lay-accessible searching techniques (hand-searching hospital websites, phone and email correspondences). Results: The literature scan identified seventeen primary articles, which focused largely on exploring the role strain faced by patients who are also parents. A single study explored the instrumental challenges of being a parent with cancer, and formally assessed the childcare needs of these patients. The questionnaire results indicated that only two of the twelve investigated CCCs had established an approach to child-minding for patients. The grey literature scan identified twenty-six on-site, patient-accessible child-minding centres at hospitals in Canada and the US based on pre-determined inclusion criteria. Of these, 76.9% of centres were associated with pediatric hospitals, and 69.2% were located in the United States. Most centres (76.9%) were open for over 30 hours per week, and 88.5% of centres were free of charge to users. Conclusions: These findings generally indicate that a minority of Canadian and American hospitals and cancer centres have formal childcare services in place to support patients who are also parents. As cancer patients are at increased risk for financial toxicity, they may be particularly in need of this kind of instrumental support. This highlights the importance of carrying out a targeted needs assessment in order to fully elucidate the need for patient-accessible childcare services at CCCs.
Impact of COVID-19 on initial treatment of breast and colorectal cancers in one integrated healthcare system.
Authors: Sundaram Jayasree P. , Liang Su-Ying , Colocci Natalia , De Bruin Monique A. 
Published: June 2021

e18806 Background: There has been a significant decline in office visits and cancer screening interventions such as mammograms and colonoscopies during the COVID-19 pandemic. The aim of this study is to analyze treatment patterns and to identify if there was also a delay in time to treatment for breast and colorectal cancers diagnosed during the pandemic. Methods: We utilized a dataset linking the institutional tumor registry and electronic health records from a large ambulatory group practice in Northern California. We analyzed data from 1,047 patients with newly diagnosed breast and colorectal cancers between 1/2019 and 8/2020 who received care at Sutter Health-Palo Alto Medical Foundation until 12/2020. We performed a T-test to examine whether patterns of treatment status (surgery vs chemotherapy vs neither) and time-to-treatment are different in pre-COVID vs pandemic eras. Results: The proportion of patients who did not receive surgery or chemotherapy during the pandemic was significantly higher, compared to the pre-COVID era (34.5% vs. 13.0%, p < 0.01). Among the breast and colorectal cancer patients who received care, the time to initial treatment did not significantly vary in the pre-COVID (median 34 days, mean 36.8 days) era as compared to during the pandemic (median 30 days, mean 32.2 days) (p = 0.15). There was no difference when accounting for surgery (p = 0.15) vs chemotherapy (p = 0.52) as the initial treatment modality. A statistically significant difference was seen amongst the 888 breast cancer cases identified during the study period, but the mean time to treatment during the pandemic (31 days) was actually shorter than the mean time to treatment identified prior to the pandemic (38 days). This difference in breast cancer time to treatment was mainly driven by a statistically shorter time to surgery (p = 0.04) in the pandemic era with no statistically significant difference in time to chemotherapy following a breast cancer diagnosis in the pandemic era as compared to the pre-COVID era (p = 0.99). Conclusions: There was a significant difference in the number of patients who did not receive surgery or chemotherapy during the pandemic for newly diagnosed breast and colorectal cancers. However, amongst those patients who did receive treatment, there were no significant delays observed in time to initial treatment, regardless of treatment modality.[Table: see text]
U.S. budget impactanalysis of body surface area (BSA)dosing for a rituximab biosimilar vsflat-fixed-dosing for subcutaneous rituximab in non-Hodgkin lymphoma (NHL)and chronic lymphocytic leukemia (CLL).
Authors: Thompson Stephen , Trautman Holly , McBride Ali , Choudhry Azhar , James Elizabeth 
Published: June 2021

e18822 Background: The first rituximab biosimilar approved in the US, rituximab-abbs, is a CD20-directed monoclonal antibody that is expected to significantly reduce drug acquisition costs. This economic analysis evaluated budgetary impact of BSA-based rituximab-abbs (IV-R-BIOSIM) vs flat-fixed rituximab/hyaluronidase human subcutaneous injection (SC-R) dosing in NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL]) and CLL. The objective was to project incremental cost differences per patient between IV-R-BIOSIM and SC-R from a US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated 1-year costs for IV-R-BIOSIM and SC-R. The model assumed equal efficacy and safety between products. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Costs for the first infused rituximab (IV-R) dose were excluded for appropriate comparison. IV-R-BIOSIM doses used BSAs of 1.6 m2, 1.8 m2, infusion duration was 3 hours. Annual dose counts of IV-R-BIOSIM or SC-R were: 9 untreated FL with maintenance; 7 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 5 CLL. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was 2020 Medicare Part B 20% cost-share for office visits and drugs. A scenario analysis was also performed to estimate FL maintenance costs for 2-year dosing. Results: Estimated 1-year savings with IV-R-BIOSIM for 1.8 m2 BSA dosing were $1,067–$6,893 with variability between indications (Table). For 1.6 m2 BSA dosing, estimated 1-year savings with IV-R-BIOSIM were $3,819–$10,856. Estimated 2-year savings with IV-R-BIOSIM for FL maintenance dosing were $9,191 for 1.8 m2 BSA dosing and $14,475 for 1.6 m2 BSA dosing. Savings of up to $1,900 were seen for higher-than-average BSA dosing, regardless of regimen. Conclusions: These findings demonstrate the potential economic benefits of replacing a proportion of SC-R use with BSA-based IV-R-BIOSIM from a US payer perspective, especially when lower BSA dosing is used. Savings are driven by drug costs and may increase with IV-R-BIOSIM as patient BSA decreases due to static costs with SC-R doses. These data also suggest that drug wastage may occur with SC-R in lower BSA patients.[Table: see text]
Cost-effectiveness of subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf for the treatment of high-risk HER2+ early breast cancer.
Authors: Sussell Jesse , Roth Joshua A. , Hansen Svenn , Meyer Craig S. , Fung Anita M. 
Published: June 2021

e18846 Background: Standard therapy for high-risk HER2+ early breast cancer (EBC) begins with neoadjuvant dual targeted therapy with pertuzumab (P) + trastuzumab (T) + chemotherapy (CTX). After surgery, patients who achieve pathological complete response (pCR) should complete one year of dual targeted therapy, while patients with residual disease should receive ado-trastuzumab emtansine (T-DM1). Recently, a subcutaneously administered formulation of P, T, and hyaluronidase-zzxf (Phesgo) was approved for use in the U.S. This study assesses the value of this new formulation in EBC patients vs. a strategy in which patients initiate standard therapy, but discontinue P following ascertainment of pCR. Methods: We developed a six-state Markov model to assess EBC costs and quality-adjusted life years (QALYs) from a healthcare sector perspective over a lifetime time horizon. Two strategies were modeled: 1) Neoadjuvant therapy with subcutaneous P, T, and hyaluronidase-zzxf + CTX with adjuvant continuation if pCR is achieved, and T-DM1 if not (“intervention”), and 2) neoadjuvant therapy with infused P, T + CTX with adjuvant infused T if pCR is achieved, and T-DM1 if not (“comparator”). Event-free and invasive-disease free survival were derived from the PEONY and KATHERINE/APHINITY trials, respectively. Utility values, drug prices, and procedure costs were derived from KATHERINE EQ-5D data, Wholesale Acquisition Costs, and claims analyses, respectively. We assessed comparator costs using both biosimilar and branded T pricing. The primary outcome was the incremental cost-effectiveness ratio (ICER). Outcomes were discounted at 3%/year and costs are presented in 2020 U.S. dollars. Uncertainty in outcomes was assessed through Monte Carlo simulation (1,000 replicates). Results: The table shows key results. The intervention resulted in a gain of 0.092 QALYs. With biosimilar T pricing in the comparator (base case), the intervention increased costs by $7,575 (ICER = $81,793). With branded T pricing in the comparator (scenario analysis), the intervention increased costs by $982 (ICER = $10,602). In probabilistic analyses, the intervention was favored in 52% and 81% of simulations at a willingness-to-pay of $100,000/QALY with biosimilar and branded T pricing, respectively. Conclusions: This study provides additional evidence to support adjuvant continuation of P+T among patients achieving pCR. Neoadjuvant P, T, and hyaluronidase-zzxf + CTX (with adjuvant continuation of dual targeted therapy) is expected to be cost-effective ( < $100,000/QALY) vs. neoadjuvant P and T + CTX (with adjuvant T continuation) for patients with high-risk HER2+ EBC irrespective of whether the comparator uses biosimilar or branded T.[Table: see text]
Cost-effectiveness of adjuvant chemotherapy for stage III colon cancer in the South African public healthcare setting.
Authors: Pumpalova Yoanna S , Rogers Alexandra M. , Tan Sarah Xinhui , Herbst Candice-Lee , Ruff Paul , Neugut Alfred I. , Hur Chin 
Published: June 2021

e18849 Background: Colon cancer incidence and mortality rates are increasing in low- and middle-income countries, such as South Africa (SA). Adjuvant chemotherapy after curative resection for stage III colon cancer prolongs overall survival, but it is unclear which regimen is most cost-effective in resource-constrained settings, such as the SA public healthcare system. Methods: A decision-analytic Markov model was developed to compare lifetime costs and health outcomes for 60-year-old stage III colon cancer patients treated with six adjuvant chemotherapy regimens in a public hospital in SA: fluorouracil, leucovorin, and oxaliplatin (FOLFOX) for 3 and 6 months, capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, capecitabine for 6 months, and fluorouracil/leucovorin (5-FU/LV; Mayo regimen) for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Costs from a SA societal perspective and utility estimates were obtained from literature and local expert opinion. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life year (DALY) averted, with a willingness-to-pay (WTP) threshold of one times the 2020 GDP per capita of SA (I$13,006.57; ZAR89,225). Results: Our model found CAPOX for 3 months to be the most cost-effective strategy, at a lifetime cost below the local WTP threshold (I$5,380.82; ZAR36,912.44) and 5.74 DALYs averted, compared to no chemotherapy. FOLFOX for 6 months was also on the efficiency frontier, with a higher total cost (I$22,747.47; ZAR156,047.64) and 0.18 additional DALYs averted (ICER = I$99,021.35/DALY averted). All other strategies were absolutely dominated. One-way sensitivity analyses found that FOLFOX for 6 months is optimal when the administration cost (i.e.: port and pump) falls to 20% of the base case price. Conclusions: In the SA public healthcare system, CAPOX for 3 months is the most cost-effective adjuvant treatment for stage III colon cancer. FOLFOX for 6 months, with a greater effectiveness, may be cost-effective if the administration cost decreases significantly. The optimal strategy in other settings may vary according to the local WTP threshold.[Table: see text]
MRD assessment using NGS in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation: Meta-analysis.
Authors: Mosalem Osama , Abdelsamia Mahmoud , Abdelhakim Haitham 
Published: June 2021

e19002 Background: The presence of measurable residual disease (MRD) preceding hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) is increasingly recognized as a risk factor for leukemic relapse and decreased survival. Over many years, attempts have been looking at developing tools to detect MRD; this includes multiparametric flow cytometry, quantitative polymerase chain reaction, and most recently, next-generation sequencing (NGS). NGS offers higher sensitivity and detection rate of disease-related gene mutations, thereby potentially improving disease outcomes. Our study sought to review the scientific literature that included NGS‐detected molecular MRD in patients with AML who underwent bone marrow transplantation. Methods: We performed a systematic search using PubMed, Google Scholar, EMBASE, and SCOPUS up until October 2020. Inclusion criteria included articles that reported the association between pre-HSCT MRD detected by NGS and post HSCT outcome in patients with AML. We extracted hazard ratios for the cumulative incidence of relapse (CIR), overall survival (OS) and leukemia free survival (LFS). A random-effect model was utilized to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Results: Six studies met our inclusion criteria. Our meta-analysis showed that the detection of pre-transplant MRD by NGS was associated with increased risk of cumulative incidence of relapse (hazard ratio=2.5, CI= 1.6-3.9, with p-value <0.001) and decreased overall survival (hazard ratio=1.6, CI= 1.6-2.3, p-value 0.005). LFS was significantly higher in those who had negative MRD detection by NGS before transplantation (HR=1.9, CI= 1.3-2.8 with p-value 0.001). These results were independent of the cytogenetic risk of conditioning intensity. There was heterogeneity between our studies (I2 = 53%, 52%, and 59% for CIR, OS, and LFS, respectively). Conclusions: The application of NGS to detect MRD is a strong predictor of outcome in patients with AML who are undergoing hematopoietic stem cell transplantation. NGS-detected MRD positive status prior to HSCT is indicative of a higher risk of relapse and decreased overall survival in this meta-analysis. Despite the limitations in our study, it demonstrates the value of MRD detection by NGS in HSCT recipients.
Treatment outcomes of cohesin complex-mutant myelodysplastic syndrome and acute myeloid leukemia.
Authors: Sadagopan Narayanan , Simin Karl , Shi Qiming , Cerny Jan , Gerber Jonathan Michael , Patel Shyam Ajay 
Published: June 2021

e19007 Background: Mutations in the genes STAG1, STAG2, SMC1A, SMC3, and RAD21 which are part of the cohesin complex are recurrent in myelodysplastic syndrome and acute myeloid leukemia. The cohesin complex is involved in sister chromatid attachment during cell division and in DNA loop formation bringing enhancers and genes together. Prognosis and treatment efficacy for this subgroup has not been well studied in MDS or AML. We evaluated the treatment outcomes of a subgroup with cohesin mutations from a database of MDS and AML patients at the University of Massachusetts. Methods: We performed a retrospective analysis of adult patients with a new diagnosis of AML and/or MDS from 2015-2019 in the University of Massachusetts Leukemia Registry. Fisher’s exact test was used to compare initial response to treatment via induction chemotherapy or hypomethylating agents. Kaplan-Meier curves for overall survival were compared using the log-rank test. We considered < 5% blasts by morphology to be complete remission (regardless of hematologic recovery). Four patients who did not undergo treatment were excluded from treatment and survival analysis. Results: A total of 19 patients had mutations in a cohesin complex gene with one patient having mutations in both STAG2 and SMC1A. The cohesin complex mutation frequency was 9.95% (19 out of 191 patients) with STAG2 representing 70% of the mutations. First-line induction chemotherapy resulted in an improved rate of complete remission 83.3% compared to hypomethylating agents 0% (p = 0.002). For AML patients alone, there was improvement in complete response rate for induction chemotherapy vs. hypomethylating agents (p = 0.048). There was no overall survival benefit for induction chemotherapy compared to hypomethylating agents (44.4% vs 41.7% probability of survival at 2 years) with p = 0.87. Excluding the MDS patients, there was still no difference in overall survival with p = 0.63. Conclusions: In this retrospective analysis of cohesin complex-mutant MDS and AML, induction chemotherapy resulted in significantly improved complete remission rates compared to hypomethylating agents. There was no overall survival benefit. We also found one patient with simultaneous mutations in two cohesin genes while cohesin mutations were previously reported to be mutually exclusive. Further work looking at additional samples may be able to show induction chemotherapy is the treatment of choice for cohesin mutant AML.[Table: see text]