bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional survival for patients with colon cancer: An analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06
Authors: Wang S. J. , Zamboni B. A. , Wieand H. S. , Yothers G. , Dignam J. J. , Raich P. C. , O’Connell M. J. , Wolmark N. , Thomas C. R. 
Published: March 2020

6005 Background: Survival for cancer patients is usually only reported as survival from time of diagnosis to some time landmark (e.g., 5 yrs). For pts surviving one or more years after diagnosis, however, their survival probability changes, and is more accurately depicted by conditional survival (CS), defined as the probability of surviving for an additional fixed time interval given that the pt has already survived a period of time. The purpose of this study was to determine the 5-yr CS of colon cancer pts in 4 NSABP trials. Methods: We analyzed long-term overall survival data from the 5587 colon cancer pts who were enrolled in fluorouracil (or equivalent) arms of NSABP trials C-03 through C-06. We computed observed 5-yr overall CS for pts who had already survived without disease from 0 to 5 yrs after diagnosis, and stratified the results by age, sex, race, stage, number of positive nodes, number of nodes resected, tumor location, and performance status. Results: The Table below shows the 5-yr overall CS for all pts and for selected subgroups for different survival times since diagnosis. As disease-free survival time since diagnosis increased, 5-yr observed overall CS increased from 76% to 90% at 5 yrs. For pts under age 50, CS increased from 78% to 95% at 5 yrs, but for pts > 70 yrs, CS remained fairly constant (71–82%). For pts with > 10 positive nodes, CS increased from 37% to 81% at 5 yrs, but did not change appreciably for node-negative pts (87–92%). Dukes’ C pts saw an increase in CS from 68% to 88% at 5 yrs, while CS for Dukes’ B pts did not change appreciably. Conclusion: Projected survival probability generally increases with time for colon cancer pts who remain disease-free for a period of time after diagnosis, and conditional survival can provide more informative prognostic information for these pts. An additional effect is that prognostic factors that are important at baseline become less important for conditional survival as the disease-free period increases. [Table: see text] No significant financial relationships to disclose.
A timing and process flow analysis of opening clinical trials within an oncology cooperative group setting: The case of the CALGB
Authors: Dilts D. M. , Sandler A. B. , Baker M. , Cheng S. , McGuire S. , Menon G. , Wu A. , Karas K. , Sawyer D. , Schilsky R. L. 
Published: March 2020

6015 Background: Cooperative oncology groups are major sponsors of Phase III clinical trials, yet the number of steps and times required to setup and open such a trial have yet to be studied. This study assesses these items in the Cancer and Leukemia Group B (CALGB) for all Phase III studies opened in a 3 year period. Methods: Step 1: headquarters and statistical center staff were interviewed to discover the detailed steps required for a study to transit from initial concept submission by a potential study chair to final activation of the study. The formal procedures manuals were also reviewed. All study records and draft protocol documents were inspected to verify and identify additional setup steps. Finally, data was collected through direct contact with study chairs and disease committee chairs. Step 2: timing data for each of the major functions or processes were collected. All times are from initial initiation of the function to the final completion of the task. Times represent calendar time. Step 3: creation of stream-lined process flows, currently underway. Members from the CALGB and the Vanderbilt Center for Management Research in Healthcare (cmrhc.org) will spend 2 days creating a process to significantly reduce the time and the number of steps to opening a trial. Results: A total of 13 Phase III studies were activated during the 3 years study period. 372 processes are required to open a Phase III at CALGB, which include 314 work steps, 43 major decision points. Interesting, most of the decision points (63%) are external to CALGB. There are 23 processing loops that require repeating processes. The process map, which lists all processes, is a chart 243.5” × 41 in 8 pt font (or about the length of a 20 passenger bus). Median calendar days to activate a Phase III study at CALGB is 767 days (min = 488, max = 1,441). The three functions requiring the greatest median days are protocol development (477), forms development (434), and regulatory affairs (350). Conclusion: It can require years to open a Phase III study at a major cooperative oncology group. Using process redesign techniques, we expect to be able to significantly streamline the process. Support provided by the NCI. No significant financial relationships to disclose.
Measuring chemotherapy safety in a community oncology practice: Results of a three-year prospective study
Authors: Jacobson J. O. , Krzyzanowska M. K. , Schwartz J. H. , Maloney B. , Lavino A. , Treacy J. 
Published: March 2020

6019 Background: Chemotherapy administration is associated with a risk for severe toxicity and mortality. Limited data are available to assess these risks outside of clinical trials or administrative databases. We sought to determine the risk of chemotherapy administration in a community-based oncology practice, to identify potential risk factors, and to look for trends over time. Methods: The North Shore Medical Center Cancer Center (NSCC) is a community-based cancer facility in Peabody, MA. In 1/03, we began a prospective study to identify and categorize all adult patients admitted to hospital with severe chemotherapy toxicity and to compare them to all chemotherapy recipients. Consecutive cases admitted to hospital from NSCC were reviewed in a monthly multidisciplinary peer review meeting. Admissions deemed to be treatment-related were entered into a toxicity database. Results: Between 1/1/03 and 11/30/05, 2206 courses of chemotherapy were administered to 1574 patients resulting in 12,380 treatment-months of therapy. 162 patients required 174 hospital admissions, for an annualized risk of treatment-related hospitalization (TRH) of 16.6% and a mean length of stay of 7.0 days. Mean age of cases was similar for those admitted for toxicity compared to all chemotherapy patients (65.3 versus 64.6 yrs.). GI toxicity and infection (principally fever and neutropenia) accounted for 77% of TRH. Between 2003 and 2005, the risk of a TRH declined for colorectal cancer cases while it increased for breast cancer and lung cancer cases. There were 14 treatment-related deaths (TRD) for an annualized risk of 1.1%. TRD’s were infectious in 9, GI in 4 and cardiac in 1. Median age was 67, similar to the entire cohort. TRD occurred early (median 28 days from the inception of chemotherapy, range 1–120 days). Significant comorbidity was identifiable in 12 of 14 cases. 10 of 14 cases were being treated palliatively. Conclusions: These prospectively collected data confirm that chemotherapy administration in a community-based practice can be associated with a low risk of severe toxicity and a very low risk of mortality. TRH and TRD could become standard measures of quality care for cancer facilities. No significant financial relationships to disclose.
Trastuzumab for all? A decision analysis examining tradeoffs between efficacy and cardiac toxicity of adjuvant therapy in HER2 positive breast cancer
Authors: Gupta A. K. , Mekan S. F. , Eckman M. H. 
Published: March 2020

6022 Background: Early results from three randomized trials showed that adjuvant trastuzumab (T) results in significant reduction in recurrence rates in high risk HER2 positive breast cancer patients (pts). However, the long term survival benefits and the balance of risk and benefit of adjuvant T in pts with lower risk of cancer recurrence and a higher risk of cardiac toxicity (elderly and pre-existing heart disease) remain undetermined. Methods: We evaluated these tradeoffs through a Markov state transition decision analytic model to simulate the survival benefits in a variety of subpopulations of HER2 positive cancer pts. Efficacy and cardiac toxicity of T were based on B-31 and N9831 trials. Outcomes were expressed in quality adjusted life years (QALYs) and 10 year survival rates. We explored a number of prototypic scenarios that varied in age, risk of cancer recurrence, and cardiac toxicity rates. Our base case focused on a 50 year-old, 2 cm, node positive, ER/PR negative pt with a 6% cumulative risk of cardiac toxicity. Results: Survival rates and the cardiac death rates for the base case and a hypothetical elderly pt with low risk of cancer recurrence are illustrated in the table . One-way sensitivity analyses on the base case, across a wide range of values for age (50–80); hazard ratio for T efficacy (0.48 to 0.95); annual cancer recurrence risk (0.5–5%) and cardiac toxicity (4–60%) demonstrated that adjuvant T was the more effective strategy. Conclusions: The addition of T in HER2 positive cancer is more effective than standard chemotherapy alone in most cases, including elderly pts with node negative disease and those with increased risk of cardiac toxicity. However, the incremental benefit decreases with advancing age, higher risk of cardiac toxicity and in pts with lower risk of recurrence. This model is a useful clinical tool to quantify risks and benefits of adjuvant T and in predicting long term survival in different subpopulations of HER2 positive breast cancer pts. [Table: see text] No significant financial relationships to disclose.
Socioeconomic and demographic factors associated with use of sentinel node biopsy and adjuvant biologic response modifiers in melanoma
Authors: Lange J. R. , Chang D. , Palis B. E. , Balch C. M. 
Published: March 2020

6027 Background: Cancer management may be influenced by factors other than disease characteristics. Little is known about the association of demographic and socioeconomic factors with melanoma care. Methods: The National Cancer Data Base, a hospital-based registry, was queried on reported use of adjuvant biologic response modifiers (BRM) for patients with resected regional metastases and the use of sentinel node biopsy (SNBx) for patients with clinical stage I and II melanoma in patients ages 1–69 between 1994 and 2003. Independent variables were age, sex, race, severity of disease, income, insurance type, U. S. Census region and type of treating facility. Analysis was performed by forward stepwise logistic regression. Results: Between 1994 and 2003, 37.8% of 10,790 patients with resected node-positive melanoma received BRM. Between 1998 and 2002, 61,251 patients with clinical stage I and II melanoma had a SNBx in 13.2%, 46.2%, 55.9%, and 41.7% of those with T1, T2, T3, and T4 tumors, respectively. In multivariate analysis, geographic variance in use of BRM and SNBx was striking ( Table ). Insurance type (commercial vs. others) and facility type (teaching/research vs. others) were also significantly associated with these modalities. Use of BRM was also associated with age, number of positive nodes and earlier treatment year, but not with sex, income or race. Use of SNBx was also associated with T stage, later treatment year, age and income, but not with sex or race. Conclusions: BRM and SNBx use varied significantly with geographic region, insurance type, and type of treating facility; this may have implications for provider education and public policy. [Table: see text] No significant financial relationships to disclose.
Randomized clinical trials in oncology stopped early for benefit (RCTSEB)
Authors: Segota E. , Soares H. P. , Djulbegovic B. , Kumar A. , Bassler D. , Guyatt G. H. 
Published: March 2020

6039 Background: Randomized clinical trials (RCT) that stop earlier than planned because of apparent benefit often receive great attention. However, how often these early results get confirmed by other subsequent meta-analysis/randomized studies, and how often results get included in clinical guidelines is not known. We conducted systematic review of oncologic RCTSEB to further determine if the results from RCTSEB are confirmed by the subsequent studies and/or included in guidelines. Methods: RCT of any intervention reported as having stopped early because of the results favoring the intervention were previously identified (JAMA.2005;294:2203).Trials with interventions in prevention and treatment of solid and hematologic malignancies were included for this review. Citation search was conducted by two reviewers to identify meta-analysis (MA), systematic reviews (SR) and RCTs that used similar trial design as the RCTSEB. National Comprehensive Cancer Guidelines were reviewed to identify the impact of the results on recommendations on clinical practice. Results: 33 trials were identified, and 5 were excluded because they did not fit the inclusion criteria. MA/SR were available for the assessment of interventions reported in 15/28 RCTSEB. Results of subsequent MA confirmed 12/15 findings, while 3 trials were contradicted. Of the remaining 13 trials, for 7 there was at least one subsequent RCT identified. 6/7 were confirmed as beneficial in the subsequent RCTs and 1 was contradicted. For 6/28 RCTSEB we did not find any subsequent MA/SR/RCTS. We also looked at the inclusion of interventions from RCTSEB in the clinical guidelines. 18/28 interventions from RCTSEB were mentioned in the formulation of clinical guidelines.16/18 were recommended as true positive recommendations. The other 2 interventions which were addressed in the guidelines were either not confirmed (n = 1) or incorrectly recommended (n = 1). Conclusions: In this set of oncology of RCTSEBs the findings were subsequently confirmed in 64% (18/28) cases. Guidelines developers used 2/28 (7%) of RCTSEB for which reliable confirmatory data were available. However, caution should be applied in the interpretation of our results because the same RCTSEB was also included in confirmatory MAs which possibly could have introduced bias. No significant financial relationships to disclose.
The cost burden of trastuzumab and bevacizumab monoclonal antibody therapy in solid tumors: Can we afford it?
Authors: Drucker A. , Virik K. , Skedgel C. , Rayson D. , Sellon M. , Younis T. 
Published: March 2020

6044 Background: Monoclonal antibodies (MAb), such as trastuzumab (TZ) and bevacizumab (BZ), have become an important yet expensive component of cancer treatment. The potential cost impact on health care budgets needs to be assessed in the context of its potential utilization. An estimate of the additional costs incurred by adopting TZ and BZ therapy in breast (BRC), lung (LUC) and colorectal (CRC) cancers was undertaken. Methods: The MAb costs per patient were estimated based on treatment indications, length of treatment, standard doses / schedules and local pharmacy data. Supportive medications, diagnostics and health resources utilization only required for the MAb therapy were also examined. This analysis was performed in Canadian dollars ($), and assumes complete drug delivery and uncomplicated cycles. Drug costs were based on average 2005 wholesale prices in Canada. The analysis took a direct payer perspective. We subsequently estimated the cost of MAb therapy per patient relative to the total costs of conventional cancer management without MAb therapy. Budget impact estimates on Canada’s health care system were then derived according to constructed schema, which accounts for absolute numbers of target patients and systemic therapy utilization. Results: The average costs of TZ per treated patient were $47,278 and $26,648 for adjuvant and metastatic BRC, respectively. For BZ, these were $47,250 and $38,500 for metastatic LUC and CRC, respectively. Other costs associated with MAb therapy were in the range of 3–6%. The predicted TZ drug costs in metastatic breast cancer were within 10% of the actual costs derived from pharmacy data. The potential life-time absolute costs to Canada’s health care system were approximately $118 million for TZ, and $262 million for BZ. This corresponds to an average of approximately 21% increase in the health care expenditure for BRC, LUC, and CRC. Conclusions: MAb therapy, such as TZ and BZ, may add a significant cost burden to Canada’s publicly funded health care system. The developed schema in this analysis may be of potential use to health care providers and policy makers in assessing the impact of MAb therapy on health care budgets. No significant financial relationships to disclose.
Patient survival and health care utilization in Medicare beneficiaries diagnosed with cancer of unknown primary
Authors: Tong K. B. , Murtagh K. N. , Hubert H. , Santry B. , Layton A. J. , Anderson G. G. 
Published: March 2020

6064 Background: For patients presenting with cancer of unknown primary (CUP), identifying the site of origin can improve survival and treatment outcomes. We analyzed outcomes in patients who present with an initial diagnosis of malignant neoplasm without specification of site (ICD-9 199.0 and 199.1). Methods: Based on a 5% Medicare beneficiary sample from 2002 through 2004, we conducted a retrospective claims data analysis identifying patients who were cancer free in 2002 and who subsequently had a claim with a CUP diagnosis (ICD-9 199.0 or 199.1) in 2003. We evaluated survival and Medicare charges by procedure and diagnosis code for four consecutive quarters following CUP diagnosis. We assigned patients to one of two groups. The “differential” group consisted of CUP patients having a subsequent claim with a differential diagnosis code (ICD-9 140–229, excluding 199.0 and 199.1). The “unknown” group consisted of CUP patients with no later change in diagnosis. We applied chi-square and t-tests to examine differences in survival, resource utilization, and Medicare charges between groups. We developed Cox survival and linear regression models for multivariate analyses. Results: Of the 388 patients, 277 (71%) did not have a claim with a differential diagnosis during the follow-up period. Both groups were similar in race (80% white) gender (60% female) and age (range 70–79). The one-year mortality of the unknown group was 32.9% compared to 19.8% in the differential group (p=0.01). First quarter charges were higher for the unknown group: $2,549 vs. $1,683 (p < 0.001). Total allowed charges were higher for the differential group over the one-year follow up period: $7,493 vs. $5,540 (p < 0.05), even when adjusted for survival. Conclusions: Following a diagnosis of CUP, patients who obtain a differential diagnosis live longer and incur higher charges over time as a result of ongoing management and intervention. Improved diagnostic tests may affect patient survival and how Medicare resources are applied. No significant financial relationships to disclose.
Agreement between physicians and patients about what constitutes shared decision making
Authors: Charles C. A. , Ellis P. M. , Dimitry S. J. , O’Brien M. A. , Whelan T. J. 
Published: March 2020

6065 Background: Involving patients in making decisions about their own care is increasingly desirable for patients with serious illness. Shared decision making is one such model, the attributes of which have been well defined (Charles et al., Soc Sci Med,1997,1999). However, it is unclear whether physicians and patients agree on what constitutes a SDM interaction. Methods: Semi-structured interviews were undertaken with 21 medical and radiation oncologists and 14 cancer patients attending a regional cancer centre. Participants were asked what they thought it meant for the patient and physician to share in DM. Responses were compared to the theoretical constructs of SDM defined by Charles et al: information exchange (flow, direction, type, amount), deliberation, and who makes the decision. Two analysts independently reviewed the interviews for patient and physician definitions of SDM and compared these with the Charles et al. model of SDM using explicit classification decision rules. There were few discrepancies between analysts and agreement was reached in all cases. Results: 71% of physicians and 29% of patients described a two-way flow and direction of information exchange as necessary for SDM. Only 24% of physicians and 21% of patients described the exchange of both medical and personal information. All participants indicated that more than the minimum legally required amount of information was needed. 67% of physicians and 36% of patients described both patient and physician involvement in deliberation about treatment as a component of SDM. 48% of physicians and 21% of patients identified both patients and physicians are involved in deciding what treatment to implement in a shared approach. Overall, none of the participant definitions identified all the components of the SDM model. Physicians in their definitions, identified more components than did patients. Conclusions: Physicians appear to have a stronger understanding of the elements involved in SDM. These differences may lead to different expectations about patient involvement in DM. Physicians have a responsibility for ensuring that patients are invited to contribute to all components of SDM in the oncology consultation. No significant financial relationships to disclose.
Structure of a physician assistant (PA)-managed survivorship practice within a multidisciplinary breast clinic
Authors: Moore B. A. , Northfelt D. W. 
Published: March 2020

6087 Background: In the last two decades, success in breast cancer screening and treatment has resulted in evolution of a growing patient population with unique medical needs. The American Cancer Society currently estimates a 98% relative five-year survival rate for patients with localized breast cancer, 88% for all stages combined. Caring for survivors represents both opportunity and challenge for the medical community. The integrated team approach in a multidisciplinary breast center is the ideal model to incorporate PAs in providing comprehensive long-term surveillance and support in this setting. Methods: The core mission of a PA-managed survivorship practice is outlined as follows: Maximize health and quality of life in breast cancer survivors, recognizing physical, psychological and spiritual factors; Provide early detection of disease recurrence and/or new breast cancer occurrence in women with a breast cancer history; Aggressively manage and overcome problems resulting from breast cancer treatment; Aid women in understanding and overcoming risks, including genetic risks, for developing breast cancer. Evidenced-based algorithms defining standards of care create the foundation for clinical decision making and establish precedent for continuity of care. The scope of care is enhanced by opportunities to incorporate research and genetic counseling. Results: Of 205 patients seen between 9/1 and 12/31/2005, 48% were younger than 70, 55% were Stage I, 82% were less than 5 years post-treatment, 63% were on hormone therapy. Conclusions: With continued trends in breast cancer survival, specialized long-term surveillance and support is essential to providing quality, comprehensive care that addresses the unique medical needs of these patients. A PA-managed breast cancer survivorship practice within a multidisciplinary breast clinic not only provides forum for such endeavors, but also fosters opportunity for life-long partnership focusing on quality of life, health and well-being. [Table: see text] No significant financial relationships to disclose.