bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transition from phase II to phase III studies
Authors: Tannock I. , Gulamhusein A. , Berthold D. R. 
Published: March 2020

6514 Background: Phase II trials are performed to detect potential anti-tumor effects of a new treatment and should be used to decide whether to proceed to a phase 3 trial or not. However, many phase 2 trials never lead to a phase 3 trial despite encouraging results. Here we sought to determine how often (i) positive phase 2 trials have led to phase 3 trials, and (ii) how often phase 2 trials were designed to lead to a phase 3 trial. Methods: We reviewed 200 phase 2 trials, presented at ASCO meetings in 1995–1996, and 2006, selecting randomly 20 abstracts with encouraging results for 5 cancer sites (breast, lung, GI, GU, Gyn) in each time period. For those presented in 1995–1996, we searched systematically for subsequent randomized studies where one treatment arm was similar to that in the phase 2 study. For those presented in 2006, a questionnaire was sent to authors asking whether they recommend evaluating the regimen in a phase 3 trial, whether a phase 3 trial is planned and whether resources (budget, patients, drugs) are available to conduct a phase 3 trial. Results: Ten years after presenting phase 2 trials with positive results, only 13 regimens have been evaluated in a phase 3 trial. Of 100 investigators who presented a phase 2 trial in 2006, 42 returned the questionnaire, 36 confirmed that the results met criteria of efficacy and 25 thought the regimen should be evaluated in a phase 3 trial. Only 10 investigators plan to undertake a phase 3 trial, and 8 stated they had resources to do so. Reasons for not planning a phase 3 study included insufficient efficacy (7), insufficient access to patients (5) or financial support (5), lack of interest from colleagues (6), and lack of support from the company (8). Conclusions: Few (∼13%) phase 2 trials with promising activity are followed by phase 3 trials and this is not increasing with time. Reasons include lack of resources such as money, drugs and patients. Many of these limitations are known when planning the phase 2 study, implying that many phase 2 trials are not planned as precursors of phase 3 trials. Resources spent on such trials would be better applied to practice-changing phase 3 trials. No significant financial relationships to disclose.
A regression model for predicting conditional survival for head and neck cancer patients: A SEER analysis
Authors: Wang S. J. , Fuller C. D. , Sittig D. F. , Holland J. M. , Thomas C. R. 
Published: March 2020

6527 Background: Survival probability changes as patients survive longer periods of time after diagnosis, and estimates of prognosis at diagnosis are no longer valid. Conditional survival (CS) accounts for the changing hazard rate over time and is a more accurate estimate of survival probability for these cancer survivors. The specific aim of this project was to build a statistical model and web-based tool to predict conditional survival for an individual head & neck cancer patient based on tumor and patient characteristics. Methods: Using 27,825 patients diagnosed with head & neck cancer between 1988–97 from the Surveillance, Epidemiology, and End Results 17 (SEER) database, we built a multivariate Cox proportional hazards regression prediction model. Patient and tumor characteristics included as covariates were age, sex, race, tumor site, stage, and grade. The primary endpoint was conditional overall survival. The model was validated for discrimination using the concordance index and a calibration plot was constructed. Bootstrapping was used to correct for optimistic bias. We also built a web-browser software tool to allow a user to enter patient information into the model and calculate conditional survival probability. Results: The regression model showed very good calibration and discrimination with a bootstrap-corrected C-index of 0.71. For a 65-yr old white male with a moderately-differentiated tonsil cancer with regional lymph nodes, the model predicted that the 5-yr conditional overall survival would increase from 50% at the time of diagnosis to 63% at 3 years after diagnosis. For a 75-yr old black male with a well-differentiated localized lip cancer, 5-yr conditional survival would improve from 58% at diagnosis to 70% by 3 years from diagnosis. Conclusions: Our regression model can accurately predict conditional survival for head & neck cancer patients based upon specific patient and tumor characteristics. This tool allows the calculation of more specific prognosis predictions for individual cancer patients who have already survived a period of time after diagnosis and treatment. No significant financial relationships to disclose.
Quality of psychosocial care in oncology: A national survey of oncologists
Authors: Pirl W. F. , Muriel A. , Hwang V. , Greer J. , Kornblith A. , Greenberg D. B. , Donelan K. , Temel J. , Schapira L. 
Published: March 2020

6561 Background: Little is known about the quantity and quality of psychosocial care being delivered by oncologists in the United States. This study surveyed oncologists about their management of psychosocial distress, using the National Comprehensive Cancer Network (NCCN) guidelines for psychosocial distress as a standard. Availability of mental health services and routine screening for distress were used as measures of quality care. Methods: A random sample of 1,000 oncologists in the United States belonging to ASCO were surveyed with an anonymous e-mail and mail-based questionnaire between 9/05 and 7/06. Initial univariate analyses were used to test differences in frequencies among groups using Chi-square for categorical variables, and t-tests and ANOVA for continuous variables. Variables that were associated with reported routine screening at the .05 significance level in the univariate analyses were entered into a logistic regression model to determine independent predictors of screening. Results: Forty-six percent (448/965) of oncologists responded. Almost two-thirds (63.6%, 285/448) practiced in community settings, 27.2% (122/448) at cancer centers, and 6.9% (31/448) in hospitals. Only half (50.3%, 95% CI 45.7–54.9%; 225/448) reported having any mental health services affiliated with their practice. Availability differed by practice setting, with cancer centers having the most and community having the least (P<.001). Only one-third (32.3%, 144/445) reported being at least somewhat familiar with the NCCN guidelines. Two-thirds (65.0%, 95% CI 60.6–69.4%; 290/446) reported routinely screening for distress, but only 14.3% (64/447) use a screening instrument. Availability of mental health services, knowledge of NCCN guidelines, experience, time, certainty about identifying distress and being female were independent predictors of reported screening. Conclusion: Only 36.4% (95% CI 34.1–38.7%; 162/445) reported both of our measures of quality care, available mental health services and routine screening for distress. While the majority report routinely screening for distress, only a small percentage follow NCCN guidelines by using a screening instrument, and only half report having mental health services available. No significant financial relationships to disclose.
Incidence of minimally invasive colorectal cancer (CRC) surgery in patients treated at NCCN institutions
Authors: Weiser M. , Romanus D. , terVeer A. , Rajput A. , Skibber J. , Earle C. , Shibata S. , Martin E. , Engstrom P. , Schrag D. 
Published: March 2020

6575 Background: In May 2004 the Clinical Outcomes of Surgical Therapy Study Group published the results of the North American randomized trial demonstrating that oncologic outcome is similar for laparoscopic assisted and open surgery for CRC. This and other studies have shown quicker recovery with laparoscopic CRC surgery including earlier resolution of postoperative ileus, less discomfort, and earlier discharge from the hospital. The extent to which surgeons have adopted the minimally invasive surgical (MIS) approach in CRC is unknown. Methods: Using the NCCN Colon/Rectal Cancer Outcomes Project Database, 715 patients were identified who underwent CRC resection in 2005–6. The distribution of lesions included right colon (39%), left colon (31%), and rectum (30%). The incidence of MIS for CRC and clinicopathologic features associated with this approach were analyzed by logistic regression; results are reported as odd ratio (OR) with 95% confidence intervals (CI), and significance defined at p<0.05 level. Results: A total of 167 (23%) patients underwent MIS colorectal surgery (laparoscopy in 98% and robotic in 2%). Conversion to open surgery was noted in 33 cases (20%). Surgery was performed in outside institutions in 21% of cases prior to patients presenting to NCCN institutions for further treatment. The MIS approach was more common in colon than rectal cancer (30% vs.12%, OR 2.96, CI 1.94–4.51, p<0.0001). Within the colon cancer cohort, right sided lesions were more likely to be approached with MIS techniques rather than left sided lesions (32% vs. 25%; OR 1.42, CI 1.96–2.21, p<0.0001). Stage I tumors were also more likely to be managed with the less invasive approach: Stage I-41%; II-20%; III-21%; IV-19% (Stage I vs. IV, OR=3.00, CI 1.74–5.16 p<0.0001). No differences in surgical approach were noted based on age, gender, race, Charlson comorbidity score, insurance type, or location of surgery (NCCN vs outside facility). Conclusion: The majority of CRC surgery for patients presenting to NCCN institutions is performed by open techniques. Right sided and early stage CRCs were more likely treated with MIS, possibly related to the less demanding nature of the procedure. The adoption of MIS is expected to rise as surgeons become trained in MIS techniques for CRC. No significant financial relationships to disclose.
DNR patterns in cancer patients (pts) 16 years after the Patient Self Determination Act (PSDA)
Authors: Helft P. R. , Qi R. , Brown B. P. , Drabiak K. , Morrell E. D. 
Published: March 2020

6582 Background: In 1991, the PSDA required institutions receiving federal funding to inform pts about the right to refuse life prolonging treatments such as CPR. Studies conducted around 1991 suggest that most DNR orders are written by oncologists less than 3 days prior to death in hospitalized pts, raising ethical concerns. 16 years later, are oncology clinicians writing DNR orders earlier in cancer pts’ hospital course compared to non-cancer pts? Methods: We conducted a chart review of 284 of the 296 total adult deaths during 2005 at Indiana University Hospital. Demographic, diagnostic, and attending service info was collected from hospital billing records. Pts’ DNR status, timing of DNR orders, and presence of a written advanced directive (AD) were assessed through chart review. Results: 76 of 284 (26.8%) patients had cancer diagnoses. Of these, 59 had documented DNR orders. There was no difference in presence or absence of DNR orders at the time of death for cancer vs. non-cancer pts (77.6 vs 72.7%, p=0.35). Mean time from writing of the DNR order to death was 3.51 ± 4.61 days for cancer pts compared to 3.26 ±3.81 days for non-cancer pts (p=0.40), however, the majority of DNR orders written by oncologists were written less than 2 days prior to death. We calculated a ratio of the time between DNR order writing and death to the overall length of stay for cancer and non-cancer pts, excluding pts with very short lengths of stay ( = 5 days). In univariate analyses, this ratio trended toward statistical significance (p=0.08). In multivariate analyses, cancer pts had a higher ratio of the time between DNR order and death to LOS (0.30 vs 0.21, p=0.05). Existence of an AD had no significant impact on this ratio. Surgical specialists wrote DNR orders less frequently (64.2 vs 77.3%, p=0.02) and later than non-surgical specialists (mean 21 vs 10 days from admission, p=0.0008). Conclusions: In this study, DNR ordering patterns among hospitalized cancer and non-cancer pts have changed little since the PSDA. Although cancer pts on average had DNR orders written relatively earlier in their terminal hospital stay than non-cancer pts, the timing varied little from pts in prior studies. Although the majority of hospitalized pts in this sample died with DNR orders, these orders were written very late in their hospital stay. No significant financial relationships to disclose.
Impact of timeliness of breast radiotherapy on health outcomes in early breast cancer
Authors: Gold H. T. , Do H. T. 
Published: March 2020

6591 Background: The objective of this study is to understand the impact of timely radiotherapy on disease-free survival (DFS) in early breast cancer patients ages 65 and above. Methods: The study population is women diagnosed from 1991–1999 in the linked SEER-Medicare database who underwent breast-conserving surgery and radiotherapy within 6 months of diagnosis. Median followup varies from 4 years for ductal carcinoma in situ (DCIS)(n=1,185) to 5 years for Stage 1 disease (n=7,481), and ranges from 0–11 years. Descriptive and proportional hazards analysis of this longitudinal cohort were conducted. Covariates include age, race, poverty, marital status, comorbidity, rurality, radiation completion and delay, elapsed time since diagnosis, comedo necrosis histology (DCIS only), and chemotherapy receipt (Stage 1 only). Subjects were censored at end of followup (including enrolling in Medicare managed care from Medicare fee-for-service) or death. Treatment delay is defined as radiotherapy beginning 8+ weeks post-surgery without chemotherapy or 4+ weeks after chemotherapy ends; other definitions also were explored. Radiotherapy is considered complete if the patient received greater than 16/22 of expected treatments, based on scientific literature. Results: DFS is negatively associated with radiation delay (OR=1.24, p=0.003 for Stage 1; OR=1.40, p=0.054 for DCIS) and Klabunde's inpatient comorbidity index (OR=1.32, p=0.004 for Stage 1; OR=1.66, p=0.065 for DCIS). Additional analyses suggest that a longer delay of 12+ weeks post-surgery (16+ weeks post-chemotherapy) further reduces DFS (OR=4.66, p<0.0001 for Stage 1; OR=12.4, p<0.0001 for DCIS). Non-white women with Stage 1 disease are more likely to delay radiotherapy (p<0.0001), but are not more likely to have worse outcomes (p>0.3). Conclusions: Delayed initiation of radiation therapy is associated with decreased DFS following radiotherapy for early breast cancer and DCIS. Non-white race is associated with delay, but not reduced DFS. Programs targeting referring physicians and patients should be developed to promote timely receipt of radiotherapy by early breast cancer patients, thereby reducing the risk of adverse health outcomes. No significant financial relationships to disclose.
Economic value of zoledronic acid compared with placebo in the treatment of skeletal metastases in patients with solid tumors: The case of the United Kingdom (UK)
Authors: Marfatia A. A. , Botteman M. F. , Foley I. , Brandman J. , Langer C. J. 
Published: March 2020

6603 Background: Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in patients with solid tumors (i.e., renal cell carcinoma, thyroid, head and neck, small cell lung, or others cancers, excluding breast, prostate and non small cell lung [NSCLC] cancers) and bone metastases. This analysis assessed, from the perspective of the UK National Health Service, the economic impact of ZA in this patient population. Methods: A literature-based decision-analytic model was developed to compare the direct costs and quality adjusted life years (QALY) of patients with bone metastases secondary to solid tumors receiving ZA or placebo. Survival, SRE incidence, and number of infusions administered were obtained from a clinical trial comparing patients randomized to 4 mg ZA or placebo for up to 21 months. Drug acquisition and administration costs and SRE costs were estimated using published sources and national fee schedules (e.g., NHS reference costs, British National Formulary). The impact of SREs on quality of life was estimated using the literature. Consistent with previous economic analyses of bisphosphonates in cancers (e.g., Hillner et al, 2000), patients were assumed to experience quality of life improvements lasting 1 month for each SRE avoided. Results: The average remaining life expectancy was conservatively assumed equal in both groups and was 9.54 months (median, 6.61 months). Patients receiving placebo were projected to experience 2.64 SREs on average v. 1.64 SREs among ZA patients. QALYs were estimated at 0.3917 per patient (pp) and 0.3728 pp in the ZA and placebo groups, respectively. ZA drug- related costs were estimated at £1,386 pp, based on an average of 5.52 infusions pp. The use of ZA was associated with a reduction of £1,830 pp in SRE costs. Overall, ZA saved costs and increased QALYs v. no therapy, by £445 pp and 0.0189 QALYs pp, respectively. In sensitivity analyses, ZA cost £25,000 or less per QALY under a wide range of assumptions. Conclusions: The use of ZA leads to fewer SREs, better estimated quality of life, and lower costs relative to placebo in UK patients with bone metastases secondary to solid tumors other than breast, prostate or NSCLC cancer. ZA appears therefore highly cost effective in this population. No significant financial relationships to disclose.
Economic value of zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer: The case of the United Kingdom (UK)
Authors: Botteman M. F. , Foley I. , Marfatia A. A. , Brandman J. , Langer C. J. 
Published: March 2020

6617 Objectives: Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in lung cancer patients with bone metastases and may improve survival among those patients with high levels of bone metabolism. This analysis assessed, from the UK National Health Service's perspective, the economic impact of ZA therapy in patients with bone metastases secondary to lung cancer. Methods: A literature-based decision analytic model was developed to compare the direct costs and quality adjusted life years (QALY) experienced by lung cancer patients with bone metastases receiving placebo or ZA. Survival, SRE incidence, and number of infusions administered were obtained from a randomized clinical trial comparing 4 mg ZA with placebo. Drug acquisition and administration costs and SRE costs were estimated using published sources and national fee schedules (i.e., NHS reference costs, British National Formulary, Personal Social Services Research Unit reference costs). The impact of SREs on quality of life was estimated using the literature. Consistent with previous economic analyses of bisphosphonates in cancers (e.g., Hillner et al, 2000), patients avoiding SREs were assumed to experience quality of life improvements for 1 month. Results: The average remaining life expectancy was conservatively assumed equal in both groups and was 8.50 months (median, 5.89 months). During those months, patients receiving placebo were projected to experience 2.07 SREs on average compared to 1.32 SREs among ZA patients. QALYs were estimated at 0.3523 per patient (pp) and 0.3350 pp in the ZA and placebo groups, respectively. ZA drug-related costs were estimated at £1,473 pp, based on 5.87 infusions pp and a cost of £251.01 per infusion. The use of ZA was associated with a reduction of £1,562 pp in SRE costs. Overall, ZA saved costs and increased QALYs compared to no therapy, by £89 pp and 0.0173 QALYs pp, respectively. In sensitivity analyses, ZA cost £25,000 or less per QALY under a wide range of assumptions. Conclusions: The use of ZA leads to fewer SREs, better estimated quality of life, and lower costs relative to placebo in UK lung cancer patients with bone metastases. The use of ZA in this population therefore appears highly cost effective. No significant financial relationships to disclose.
Palliative chemotherapy and cancer-related fatigue in advanced NSCLC patients
Authors: Cleeland C. S. , Shi Q. , Lu C. , Johenson V. , Mendoza T. , Palos L. , Mobley G. , Wang X. 
Published: March 2020

6622 Background: Cancer-related fatigue is one the most severe and prevalent symptoms in patients with advanced-stage non- small cell lung cancer (NSCLC). Whether palliative chemotherapy causes additional fatigue, beyond that which is caused by the disease itself, is unknown. Methods: Study subjects were 88 patients with advanced NSCLC who were treated with platinum-based chemotherapy at The University of Texas M. D. Anderson Cancer Center. Fatigue severity and other symptoms were measured weekly using the 0–10 rating scales of the M. D. Anderson Symptom Inventory (MDASI). Using mixed-effect modeling, we assessed fatigue severity over time of receiving chemotherapy. Results: Over the time of this longitudinal symptom assessment study, fatigue severity was overwhelmingly higher than all other symptoms. We observed no significant impact on fatigue severity by age, sex, or race/ethnicity variation; however, there was a significant difference in fatigue severity using longitudinal analysis between patients who discontinued chemotherapy within 0–6 week vs beyond 12 weeks (P<.05), and within 6–12 weeks vs beyond 12 weeks (P<0.01). By each cycle of chemotherapy, the fatigue pattern showed a consistent trend of reduced severity at day 0–3, a fatigue peak on day 5–6 (P<.05), then unchanged during days 7–21. Fatigue was most severe during the first cycle. Discussion: Cancer-related fatigue was the most severe symptom in the study sample, especially for patients only able to receive 2–4 cycles of chemotherapy. However, patients who received over 4 cycles of chemotherapy had a stable level of fatigue, which indicates that continued chemotherapy does not increase fatigue. Additional analysis demonstrated that fatigue was at it's lowest immediately following chemotherapy, possibly related to the use of steroids in conjunction with chemotherapy administration. No significant financial relationships to disclose.