bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of febrile neutropenia management in cancer patients in Spain
Authors: Mayordomo J. I. , López A. , Viñolas N. , Castellanos J. , Pernas S. , Alonso J. D. , Frau A. , Layola M. , Gasquet J. A. , Sánchez J.
Published: March 2020

6089

Background: Febrile neutropenia (FN), a dose-limiting event for many myelosuppressive chemotherapy (CT) regimens, often causes subsequent CT dose delays (DD) and reductions (DR), lengthens hospital stay and increases monitoring, diagnostic and treatment costs. No studies are known to date on economic costs of FN in common clinical practice in Spain. Methods: This is a multicentre, retrospective, observational chart review of adult patients with breast cancer, lung cancer or non-Hodgkin’s lymphoma (NHL) who suffered from at least one FN episode related to cytotoxic CT from 16 Spanish hospitals. Resource use and subsequent costs including days of hospitalization, number of RBC transfusions, number and type of complementary tests, use of colony-stimulating factors (CSF), antibiotics and other drugs to manage FN were assessed. Potential impact of FN on planned CT dose and/or schedule was also analysed. P-value was obtained by one-way ANOVA using the Bonferroni correction. Results: A total of 194 medical charts including 238 documented FN episodes were reviewed. Women, 59.8%; age > 60 yrs, 49.5%; breast cancer, 43% (83% treated with taxane or anthracycline-based CT); lung cancer, 22% (95.5% treated with platinum-based CT); NHL, 35% (58.2% treated with CHOP-like CT). Hospitalization due to FN lasted a median of 7 days. During the episode, 32.3% of pts needed 1 or more RBC transfusions, 97.9% required a blood test and 87% a blood culture. CSFs were used in 67.6% of pts. All pts were treated with antibiotics and 78.2% with other drugs. 58.4% of FN episodes had an impact on planned CT dose and/or schedule: DR was observed in 34.9% of cases, DD in 28% and CT withdrawal in 14.7%. Conclusions: Main drivers of cost of FN are hospitalization and antibiotic treatment. FN is more costly in NHL pts than breast or lung pts (statistically significant in lung pts). FN episodes have a relevant impact on planned CT dose and/or schedule. In each row statistically significant differences ( p<0.05) were obtained between values with the same letter.

[Table: see text]

[Table: see text]
Metastatic breast cancer: A regional audit of HER2 testing and trastuzumab access
Authors: Scullin P. , Drake A. T. , Coyle V. M. , McAleer J. J.
Published: March 2020

6097

Background: Clinical trials have clearly established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. This is based on median survival gains for patients with HER2 positive tumours treated with trastuzumab plus taxane chemotherapy compared to taxane alone. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in 2004 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: One hundred and fifty six patients commenced chemotherapy, of whom 145(93%) had HER2 testing. In 69(44%) patients the HER2 result was already available at the time of this relapse. In the remaining 76(49%) patients the result became available in a median of 41.5 (range 0–368) days. Of those tested, 48 patients (33%) were HER2 positive (immuno-histochemistry 3+ or fluorescence in situ hybridization positive). Thirty eight of these patients were treated with trastuzumab, either as a single agent or in combination with chemotherapy. There were valid reasons for trastuzumab omission in 7 of 10 patients not given trastuzumab (4 given first line anthracycline-based regimen, 1 had cardiac dysfunction, 1 had extensive lung metastastes and 1 was unfit for treatment). The data were examined for variations in chemotherapy and trastuzumab use across the 4 health boards which comprise the region. The number of patients commencing chemotherapy ranged from 6.9 to 11.4 patients per 100,000 population indicating a significantly different utilisation (p<0.001). Conclusions: In our region 145 of 156 patients who received chemotherapy for MBC were tested for overexpression of the HER2 receptor (93%). Of those patients who were eligible to receive trastuzumab 31 out of 34 (91%) received trastuzumab. There were inequalities in the region regarding chemotherapy for MBC and the time required to obtain a HER2 result averaged 41.5 days. Testing of HER2 status at time of original diagnosis would streamline management of metastatic disease.

No significant financial relationships to disclose.
Delays in diagnosis and initiating treatment for patients with lung cancer
Authors: Vandermeer R. L. , Dimitry S. J. , Arnold A. , Ellis P. M.
Published: March 2020

6102

Background: Many patients with lung cancer report delays in the diagnosis of their disease. This situation may contribute to advanced stage at diagnosis and poor long term survival. This study explores the delays experienced by patients referred to a regional cancer centre with lung cancer. Methods: A prospective cohort of patients referred to a regional cancer centre with newly diagnosed lung cancer were surveyed over a 3 month period. Surgically resected patients were not included as they were treated at another site. Patients were asked when they first experienced symptoms, when they saw their doctor, what tests were done, when they saw a specialist and when they started treatment. A medical record review was employed to validate the data patients provided. Descriptive statistics were used to summarize the different time intervals. Results: 56 of 73 patients consented (RR 77%). However, only 52 patients (30M, 22F) were interviewed as two expired before being interviewed and two could not be contacted. The mean age was 68 yrs. Stage distribution was as follows: IB/IIA 10%, IIIA 20%, IIIB/IV 70%. The initial treatment was as follows: 10% of patients supportive care alone, 19% chemotherapy, 44% radiation and 27% had combined chemoradiation. Patients waited a median of 21 days (IQR 7–51d) before seeing a doctor and a further 22d (IQR 0–38d) to complete any investigations. The median time from presentation to specialist referral was 27d (IQR 12–49d) and a further 63d (IQR 44–102d) to complete investigations. The median wait time to start treatment once patients were seen at the cancer centre was 10d (IRQ 2–28d). The overall time from development of first symptoms to starting treatment was 139d (IQR 100–174d). Conclusions: Lung cancer patients experience substantial delays from development of symptoms to first initiating treatment. There is a need to develop and evaluate rapid assessment clinics for patients with suspected lung cancers.

No significant financial relationships to disclose.
Providing practitioner-specific outcomes is associated with higher patient satisfaction with information about prostate cancer treatment
Authors: Gilbert S. M. , Sanda M. G. , Dunn R. L. , Greenfield T. , Hembroff L. , Klein E. , Saigal C. , Michalski J. , Sandler H. , Litwin M. S. , Wei J. T.
Published: March 2020

6106

Background: After being diagnosed with prostate cancer, patients must assimilate abundant cancer related information. Satisfaction with Information (SWI) is a patient’s cognitive evaluation of information sources used to understand and select therapy. We sought to describe sources of information used by prostate cancer patients and to identify factors associated with SWI. Methods: 1,072 men with newly diagnosed prostate cancer have enrolled in the prospective, multi-center PRostate cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROST-QA) study. Reports of source(s) of information were documented prior to treatment (radical prostatectomy, external radiation, brachytherapy or combination). The validated SWI domain of the Service Satisfaction Scale-Cancer (SSS-Ca) was completed by patients 2 months following treatment. Relationships between socio-economic factors, demographics, cancer severity, and types of information sources and satisfaction (SWI) were evaluated with multivariate regression. Results: Sources of information endorsed by patients varied by race ( Table ), education, and study site. The most helpful sources of information were description of treatment by a physician (32.8%), books and internet (18.3% each), family/friends (16.6%) and pamphlets/brochures (11.4%). In bivariate analysis internet use was negatively associated with SWI (p=0.025). In multivariable models patient age (p=0.005) and information provided by the physician regarding their own outcomes (p=0.01) were independently associated with SWI. Conclusions: Although a variety of informational sources were endorsed by patients, only printed results for physician’s own patients was associated with SWI. Because SWI is a function of both experiences and expectations, providing patients with a treating physician’s results may improve satisfaction by enhancing concordance of expectations and outcomes.

[Table: see text]

[Table: see text]
Potential clinical and economic impact of switching U.S. women to exemestane following 2–3 years of therapy with tamoxifen for early breast cancer
Authors: Thompson D. , Taylor D. C. , Montoya E. L. , Jones S. E. , Weinstein M. C.
Published: March 2020

6109

Background: Switching postmenopausal women with early breast cancer to exemestane after 2–3 years of tamoxifen therapy has been reported to increase disease-free survival. However, the potential impact of this management strategy on the U.S. health-care system is unknown. The objective of this study was to estimate the 10-year clinical and economic consequences that would accrue if all eligible U.S. patients in 2006 were switched from tamoxifen to exemestane. Methods: A Markov model with a 10-year time horizon was used to predict patients’ transitions across various health states based on treatment strategy (continuing tamoxifen versus switching to exemestane), breast cancer status (no recurrence, local or distant recurrence, contralateral breast cancer), and other related health events (osteoporosis, endometrial cancer, death). Disease- and treatment-related events were estimated using data from the Intergroup Exemestane Study (IES); survival and medical-care costs by type of recurrence were estimated using SEER-Medicare data and published literature. The switch-eligible cohort was defined to be consistent with IES selection criteria and its size in 2006 estimated based on SEER-Medicare and market research data. Costs incurred in future years were discounted at 3% annually. Results: We estimate that 71,800 U.S. women would be eligible to switch from tamoxifen to exemestane in 2006. Doing so would be expected to prevent 3,000 cases of recurrence (21,100 vs 24,100) and 2,000 breast cancer deaths (12,800 vs 14,800) over 10 years. The net budgetary impact over 10 years is projected to be $320M ($992M vs $672M), reflecting a $336M increase in costs of adjuvant hormonal therapy ($500M vs $164M), a $32.1M increase in costs of monitoring and treatment of adverse events ($73.7M vs. $41.6M), and a $47.4M reduction in recurrence-related treatment costs ($419M vs $466M). Conclusion: Switching all eligible U.S. breast cancer patients from tamoxifen to exemestane in 2006 would increase medical-care costs by $4,460 per patient but reduce breast cancer recurrences by 12% and breast cancer deaths by 14% over 10 years.

[Table: see text]
Separate DCIS progression pathways derived from breast disease heterogeneity data
Authors: Maskery S. M. , Hu H. , Mural R. , Hooke J. , Shriver C. D. , Liebman M. N.
Published: March 2020

612

Background: Observation of heterogeneity in breast pathology has been a consistent theme but one that has had little detailed analysis and/or interpretation. Typically, this research has been limited due to variation in pathology description by different pathologists. We have utilized a unique breast disease tissue and data repository to infer multiple pathways from breast disease to breast cancer. Methods: Breast pathology diagnoses are drawn from 1029 standardized and highly expanded pathology reports. A single pathologist records the occurrence of any and all pathologies seen in a patient’s breast biopsy. This co-occurrence data is analyzed using a Bayesian network learning algorithm that links data observations in a probabilistic order of events. The resultant Bayesian network is a visualization of how breast disease diagnoses can predict the presence or absence of other diagnoses. For example, a connection between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) visualizes the statement: the presence of DCIS alters the likelihood of the presence of IDC. Results: Separate progression pathways are implicated for DCIS comedo to IDC and DCIS non-comedo to IDC. Multiple breast lesions predict DCIS non-comedo occurrence. One pathway inferred from these predictive lesions is: columnar cell hyperplasia-florid ductal hyperplasia-atypical ductal hyperplasia-DCIS non-comedo-IDC. In contrast, no hyperplasia or atypical lesion can predict DCIS comedo occurrence. That DCIS comedo and DCIS non-comedo have very different progression pathways implies these two pathologies may be two separate diseases. Parallel genomic studies at our institute provide strong evidence that DCIS non-comedo and DCIS comedo are two separate genomic entities. Conclusions: Bayesian network analysis provides a mechanism for the use of heterogeneity in breast disease pathology to predict multiple breast disease progression pathways. Using novel bioinformatic techniques and traditional genomic analysis methods we have gathered compelling evidence that DCIS progression follows two separate pathways.

No significant financial relationships to disclose.
Survival trends for advanced colorectal cancer (CRC): Are improvements only for patients in clinical trials?
Authors: Price T. J. , Roder D. , Pittman K. , Patterson K. , Rieger N. , Hewett P. , Rodda D. , Colbeck M. , Maddern G. , Luke C.
Published: March 2020

6124

Background: Significant improvements in the outcome for patients with advanced CRC have been achieved. We have reviewed the prospective CRC database at our institution from 1992 to 2004 to explore whether the availability of new chemotherapy drugs (irinotecan & oxaliplatin) and surgical advances has impacted on survival in the normal population. Earlier results had suggested a trend to improved survival (1). Methods: In Australia the first of these drugs became available at the end of 1997 thus we have taken this as the time point to compare outcomes pre and post. Disease-specific survivals were analysed from the date of diagnosis for stage D, and from the date of distant recurrence for stages A, B and C, with a date of censoring of live cases at December 31st, 2004. The Kaplan-Meier product-limit estimate was used for univariate analyses and Cox proportional hazards regression for multivariable analyses. Results: The current analysis is of 744 patients; 92–97 n=313, 98–04 n=431. Survival for the respective time periods were 47.6% and 54.9% 12 mths; 28.0% and 34.8% 24 mths; 18.9% and 23.0% 36 mths; 12.6% and 17.2% 48 mths; and 10.4% and 14.9% 60 mths. Cox proportional hazards regression indicated a lower risk of case fatality for 1998–2004 than 1992–1997 cases (p=0.048) after adjusting for age measured in years. The key predictors of case fatality in a multivariate analysis were found to be period (i.e., 1992–97/1998–04), age, and stage of disease at time of initial diagnosis. While an upward trend in survival was recorded for all ages, it was most pronounced for 70–79 year olds (n=272), where the increase in 24 mth survival was from 21.1% for 1992–97 to 36.1% for 1998–2004 (p=0.015). For patients aged 80 years and over (1992–97 n=40 & 1998–2004 n=67) the 24mth survivals were 18.6% (6.7%) and 26.4% (6.9%) respectively (p>0.200). Conclusions: Clinical trials have shown improvements in survival for highly selected patients. This current analysis confirms an improvement in survival over time for advanced CRC and this is seen in unselected patients including the elderly. Preliminary data has suggested that a number of factors have contributed to the trend of improved survival. Final analysis, including updated chemotherapy trends, will be presented at the meeting. (1) Proc ASCO 2004, #3707

No significant financial relationships to disclose.
Drug interactions in ambulatory cancer patients receiving cancer-directed therapy
Authors: Riechelmann R. P. , Wang L. , Tannock I. F. , Krzyzanowska M. K.
Published: March 2020

6129

Background: Cancer patients (pts) are susceptible to drug interactions (DI) because they receive multiple medications. Here we evaluate the epidemiology of potential DI in cancer patients. Methods: Ambulatory, adult pts with solid malignancies who were receiving antineoplastic treatment completed a questionnaire about drugs taken in the previous month. Drug Interactions Facts software was used to screen for potential DI and to classify them in terms of severity (major, moderate and minor, where major is a life-threatening interaction) and level of scientific evidence (1 to 5, with 1 being the highest level). Summary statistics and logistic regression were used to describe the results. Results: Between Sept -Dec 2005, 183 pts completed the questionnaire: median age was 61 (range 26–88), and 114 (62%) were women. Cancer sites included breast 63 (35%), gastrointestinal 45 (25%), and genitourinary 36 (20%). Treatment intent was palliative in 139 (60%). Most pts (76%) were receiving chemotherapy; 111 (66%) had at least one co-morbid condition, and 72 (47%) had abnormal liver and/or renal function. The median number of drugs per pt was 5 (range 0–16). Among the 183 pts, 131 potential DI were identified of which 65 (50%) were due to pharmacokinetic interactions. Sixteen (12%) of all potential DI were major, 94 (72%) were moderate, and 21 (16%) were minor. Fourteen (11%), 54 (41%), 5 (4%), 42 (32%), and 16 (12%) were supported by levels 1,2,3,4,5 of evidence respectively. Most potential DI involved non-chemotherapy agents such as warfarin, antihypertensives, and anti-inflammatory drugs. In multivariate analyses, number of comorbidities (p= .0001), number of drugs (p= .005), and cancer type (p= .03) were significant risk factors for DI. Conclusion: PotentialDI are common in oncology, and usually involve non-chemotherapeutic drugs. Risk factors for potential DI include comorbid illness, number of medications and type of cancer. Oncologists should be aware of such an important issue.

No significant financial relationships to disclose.
Prophylactic oophorectomy in premenopausal women with non-metastatic colon cancer: A decision analysis
Authors: Mourton S. M. , Hollenberg J. P. , Abu-Rustum N. R. , Chi D. S. , Wong W. D. , Temple L. K.
Published: March 2020

6130

Background: There is data to suggest that prophylactic oophorectomy (PO) in premenopausal women with colon cancer may improve survival. However, the potential for improved survival must be balanced against the trade-off of premature menopause and its affect on quality of life (QOL). The objective of this study was to determine the value of PO in premenopausal women undergoing surgical excision of colon cancer. Methods: We constructed a decision-analytic model comparing PO versus no PO for premenopausal women undergoing resection of stage I-III colon cancer. The model included detection of ovarian micrometastases (OMM), adjuvant chemotherapy, development of metachronous ovarian metastases, subsequent risk of ovarian cancer and QOL. Probabilities and utilities were estimated from published data. Life expectancy (LE) and quality adjusted LE (QALE) were calculated using the Declining Exponential Approximation of Life Expectancy. Results: With a baseline OMM incidence of 8%, a 5 yr survival of OMM removed (19%) vs OMM left in situ (11%), there was a gain in LE of 2.8 months with PO. With QOL adjustments for menopause (utility 0.77) and colon cancer (utility 0.37–0.85 ), QALE was 1.7 months less with PO. One-way sensitivity analysis (SA) demonstrated that the utility of menopause had the greatest effect on QALE differences, with a threshold value of 0.86 at which QALE was greater with PO. With increasing OMM incidence and 5-year survival with removed OMM, QALE became greater in the PO cohort. All 1, 2, and 3 way SAs demonstrated that the model was robust through the probable range of variables. Conclusions: Our model demonstrated the significant effect of menopause QOL on overall QALE. Although PO may lead to a small gain in LE, the trade-off of premature menopause must be considered when counseling patients.

No significant financial relationships to disclose.
Temporal trends in oncology product approvals in the United States, 1986–2005
Authors: Ross D. B. , Weiss K. D. , Keegan P. , Justice R. , Pazdur R.
Published: March 2020

6131

Background: No systematic examination of temporal trends in oncology approvals in the United States (US) has been conducted. Methods: Internal databases at the US Food and Drug Administration (FDA) were queried to determine the number of first-time approvals for New Molecular Entities (NMEs) (both traditional drugs and therapeutic biologics) for oncology indications between the years 1986 and 2005, inclusive; 1986 was the first year for which database records were available for both drugs and biologics. Correlation analysis was used to analyze the data for time-dependent changes in approvals and approval rates. Results: During the period examined, 70 NMEs received first-time approval for an oncology indication ( Table ); 52 (74%) were drugs and 18 were biologics. The median annual number of approvals was 3 (range, 1 to 7); the maximum number of approvals during the period examined occurred in 2004. Statistical analysis showed a weak positive correlation between the number of oncology approvals and time, and between the proportion of applications approved as a percentage of all oncology product applications and time. Conclusions: Available data suggest that the number and rate of oncology product approvals has remained stable in the US over the last two decades.

[Table: see text]

No significant financial relationships to disclose.
Hyperglycemia treatment is associated with longer length of hospital stay in colorectal cancer surgery patients
Authors: Geraci J. M. , Busaidy N. , Wang J. , Lam T. P. , Skibber J. M. , Freeman J. H. , Goodwin J. S.
Published: March 2020

6133

Background: Diabetes mellitus (DM) is associated with longer hospital stays in some medical and surgical inpatient populations. Aggressive control of blood sugar may prevent complications and decrease hospital length of stay (LOS). Methods: We conducted a retrospective study of 519 patients at UT MD Anderson Cancer Center (UTMDACC) who had major surgery for colon or rectal cancer in calendar years 2000–2003. Patient data extracted from the UTMDACC Institutional Database included demographics, admission and discharge dates and diagnoses, surgical procedures, and diabetes medication use during the hospitalization. Known DM was defined as present if the patient had a diabetes diagnosis prior to or at admission; hyperglycemia treatment was defined as receipt of a medication for diabetes (insulin or oral medication) during the index hospitalization. Chi-square and t tests were performed to assess associations between patient characteristics and long LOS, and multiple logistic regression was used to identify independent predictors of hospital LOS at or greater than the 75th percentile for the study population (long LOS). Results: The mean age of the study population was 60.4 years (median 61, range 18–91). Known DM was present in 10.4% of cases; the same percentage received hyperglycemia treatment during their hospital stay, although not all were known diabetics. Mean LOS was 8.9 days; median 7 days and the 75th percentile 9 days. 50% of patients treated for hyperglycemia had long LOS (27 of 54 cases, p< 0.0005). In a logistic regression model controlling for patient demographic and clinical characteristics and the occurrence of post-operative complications, hyperglycemia treatment was an independent predictor of long LOS (odds ratio 4.1, 95% confidence interval 1.6, 10.3). Conclusions: Hyperglycemia treatment is associated with longer LOS in patients undergoing surgery for colon or rectal cancer at UTMDACC. Further studies should determine whether patients at risk for long LOS can be identified prospectively such that they might benefit from an intervention to reduce their LOS.

[Table: see text]
Prognostic significance of quality of life index in breast cancer
Authors: Gupta D. , Grutsch J. F. , Granick J. , Neelam R. , Vashi P. G. , Daehler M. , Wodek T. , Lis C. G.
Published: March 2020

6135

Background: Quality of Life (QoL) is a multidimensional construct. There is extensive data showing that QoL tools measuring the activities of daily life provide prognostic information in cancer. However, similar information on QoL tools measuring patient satisfaction with their life is sparse. The Ferrans and Powers Quality of Life Index (QLI) is one such instrument. The goal of this study was to evaluate the statistical strength of association between QLI and survival in breast cancer patients undergoing care in a non-clinical trial setting. Methods: We examined a case series of 251 breast cancer patients treated at Cancer Treatment Centers of America between 04/01 and 11/04. QLI defines QoL in terms of satisfaction with the aspects of life that are important to the patient. QLI measures overall QoL and QoL in four major subscales: health and physical, social and economic, psychological and spiritual, and family. All scores range from 0 to 30 with higher scores indicating better QoL. Study patients were dichotomized into 2 groups based on median scores for all QoL subscales. Kaplan Meier method was used to calculate survival. Log-Rank test was used to study the equality of survival distributions. Results: Of 251 patients, 74 were newly diagnosed and 177 had prior treatment history. The median age was 48 years (range 25 - 74 years). 45 patients had stage I disease, 105 stage II, 38 stage III, and 32 stage IV. The table describes the median survival for all QLI subscales. Health and physical functioning subscale and QLI subtotal subscale were significantly associated with survival. Conclusions: This study shows that baseline levels of patient satisfaction with their QoL provide useful prognostic information in breast cancer. While these findings need to be evaluated further to ascertain which subscales of QoL have a role in predicting patients’ prognosis, they have important implications for patient stratification in clinical trials and may aid decision-making in clinical practice.

[Table: see text]

No significant financial relationships to disclose.
Elevated preoperative serum level of tumor markers CEA and CA 15–3 in breast cancer patients
Authors: Park B. , Kim H. , Oh J. , Kim S. , Kim K. , Sohn J.
Published: March 2020

621

Background: Serological tumor markers: Cancer Antigen 15–3 (CA 15–3), Carcinoembryonic Antigen (CEA), have been investigated as useful markers for monitoring of response to treatment and for predicting outcome in breast cancer patients. Methods: A total of 820 breast cancer patients, treated over the period April 1999 through December 2003, had preoperative CA15–3 and CEA concentrations measured. The stage of the primary tumor ranged from 0 to IV. The median age of the patients was 47years (range 20–88 years old). The concentration of markers was investigated with regard to clinico-pathological parameters and patients outcome by both univariate and multivariate analysis. We determined the range of normality by the mean + 2 standard deviations of the markers distribution in populations of healthy females, who took an annual health screening program. Survival curves for disease free survival and death from disease were estimated by the method of Kaplan-Meier method and differences between groups in survival were tested using the log-rank test. All statistical analyses were carried out using SPSS statistics software (ver 10.5). Results: Among 820 patients, elevated preoperative level of CA15–3 and CEA was identified in 100 (12.2%) and 83 (10.1%) patients, respectively. Tumor size (>5cm), lymph node metastases (≥4), advanced stage (stage III and IV) were associated with significantly higher level of both preoperative CA15–3 and CEA. Elevated preoperative values of CA15–3 and CEA were associated with poor disease free survival (DFS, p=0.0019, p=0.0001, respectively) and distant relapse-free survival (DRFS, p=0.011, p=0.0034), but the level was marginal for overall survival (OS, p=0.0848, p=0.0895). By Cox’s multivariate analysis, younger age (<35 years), larger tumor size(>2cm), axillary node metastases, negative ER expression, elevated preoperative values of CA15–3 and CEA were independent prognostic factors for DFS and DRFS. Conclusions: High level of preoperative CA 15–3 and CEA might reflect a tumor burden, and is associated with advanced disease condition and disease-free survival. Measuring preoperative levels of CA 15–3 and CEA might be helpful for predicting the outcome and for planning the adjuvant therapy in breast cancer patients.

No significant financial relationships to disclose.
Analysis of the pathological response to primary chemotherapy in patients with locally advanced breast cancer (LABC) grouped according to ER, PR and HER2 status
Authors: Fernandez-Morales L. A. , Dalmau E. , Martinez S. , Arcusa A. , Pericay C. , Lain J. M. , Font J. , Tortajada L. , Saigi E. , Segui-Palmer M. A.
Published: March 2020

626

Background: The determination of ER and PR has a considerable importance when evaluating the prognosis and the response to treatment in breast cancer (BC). Assessment of HER2 status is also a standard for the management of BC. Hormone receptors (HR), HER2, and increasingly, genomic profiles distinguish at least four major classes of BC: HER2+; HER2-HR+, which can be divided into two classes, favorable and unfavorable; and basal-like that express neither HER2 nor HR. In the clinical practice is possible to divided BC according to ER, PR and HER2: ER-PR-HER2+, ER-PR-HER2-, ER+PR+HER2-, ER+RP+HER2+; and less frequently ER+PR-HER2-, ER+PR-HER2+, ER-PR+HER2+ and ER-PR+HER2-. In the neoadjuvant setting the pathological complete response (pCR) to primary chemotherapy (PC) is associated to negativity for ER and PR receptors, and in patients (pts) with HER2 + BC, the addition of trastuzumab to PC increasing the rate of pCR. The aims of this study were to determine the pCR of PC with anthracyclines (A) and taxanes (T) in pts with LABC grouped according to ER, PR and HER2 status. Methods: Pts with LABC treated with PC including A and T were grouped according to ER, PR and HER2 status, and the pCR rate were analyzed using the chi-squared test and correlations with a p value of ≤0,05 were considered statistically significant. Results: A total of 103 pts were treated. There were 14.6% of ER-PR-HER2+ BC, 23.3% ER-PR-HER2-, 35.0%ER+PR+HER2-, 8.7% ER+PR+HER2+, 11.7% ER+PR-HER2-, 2.9% ER+PR-HER2+, 1.9% ER-PR+HER2+, and 1.9% ER-PR+HER2-. For the analysis of pCR only 100 pts were included. There were18 pts who achieved a pCR. Of these pts, 9/18 (50.0%) were RE-RP-HER2-, 5/18 (27.8%) ER-PR-HER2+, 3/18 (16.7%) ER+PR+HER2+, and 1/18 (5.6%) ER+PR+HER2- (p≤0.01). The table 1 show the pCR rate for each subgroup of BC. Conclusions: In patients with LABC to group BC according to ER, PR and HER2 status can help to predict pCR to PC.

[Table: see text]

No significant financial relationships to disclose.
Early switch with aromatase inhibitors as adjuvant hormonal therapy for postmenopausal breast cancer: Pooled-analysis of 8,794 patients
Authors: Ciccarese M. , Bria E. , Giannarelli D. , Cuppone F. , Nuzzo C. , Nistico’ C. , Terzoli E. , Cognetti F. , Carlini P.
Published: March 2020

635

Background: The magnitude of the survival benefit of aromatase inhibitors (AIs) after 2–3 years of tamoxifen as adjuvant hormonal therapy for early breast cancer is still unclear. We performed a pooled-analysis of phase III trials, to look how much advantages adjuvant the “early switch” strategy add over standard tamoxifen for 5 years. Methods: All phase III trials were considered eligible. A pooled analysis was accomplished, and event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. Significant differences in primary outcome (EFS and RFS, event- and relapse-free survival), and secondary outcomes (OS, overall survival, deaths in absence of progression, other cancers and toxicities), were explored. Magnitude outcome measures were: absolute benefits (AB) and number of patients needed to treat (NNT). Heterogeneity test was applied as well. Results: Four trials designed to look if AIs after 2–3 yrs of TAM improve EFS (8794 patients) were gathered. Conclusions: Considered all the available phase III trials, the early switch strategy improves survival over standard tamoxifen for 5 years, with a different toxicity profile. The lack of significant heterogeneity in the analysis underscores the homogenous effect across all trials.

[Table: see text]

No significant financial relationships to disclose.
Internet based double-blind cross-over clinical trial to test efficacy of high dose isoflavone soy in controlling breast cancer survivor hot flashes
Authors: Dooley W. C. , Hendricks C. , Gusev Y. , Shockney L.
Published: March 2020

636

Background: Severe hot flashes are common after completion of allopathic breast cancer treatment. Hot flashes are rare in the Orient where high isoflavone soy diets are common. Methods: We enrolled breast cancer survivors experiencing hot flashes after the completion of surgery, radiation and chemotherapy into a 16 week double blind cross-over casein placebo controlled trial of a 160 mg isoflavone soy dietary supplement. Hot flash frequency, severity, and time of day, exercise time and patient journaling was recorded by an internet diary placed on a HIPPA compliant server with password access. Results: Of 168 patients enrolled, 117 actually participated in taking supplementation and completing internet diaries giving adequate data for analysis. Of this group 13 patients dropped out of study for failure to finish all dietary supplements throughout the study period. The hot flash data during the last 4 weeks on each supplement was compared to determine benefit. There was no statistical difference in hot flash frequency, intensity or duration between either supplement independent of exercise level. Interestingly, 82% of patients reported a decrease in hot flashes in the first 4 weeks of study independent of which supplement they were randomized to receive. The journal entries report during this “induction” period that the majority of patients had identified emotional or dietary or other triggers for their hot flashes. The avoidance of the triggers seemed to substantially reduce their reported menopausal symptoms. Conclusions: High dose soy isoflavone dietary supplementation is ineffective in reducing breast cancer survivor hot flashes. Journaling may have a benefit in allowing survivors to find their individual triggers for the most severe hot flashes. Internet patient data entry provides a unique and highly compliant tool for obtaining direct patient reporting in survivorship clinical trials.

[Table: see text]
Is tamoxifen prevention in younger women underutilized? Analysis of competing causes of mortality
Authors: Ragaz J. , Spinelli J. J. , Coldman A. , Mihalcioiu C.
Published: March 2020

647

Background: Our past work on Tamoxifen impacting overall mortality outcome among survivors of the 1st breast cancer (JCO, 1998, 16:2018–24) introduced methodology permitting analyses of competing cause mortality, adjustable as new data emerge. This analysis estimates Tamoxifen impact on four conditions among BrCa survivors known to be affected by Tamoxifen, i.e. contralateral breast cancer; uterine cancer, cardiovascular (CVS) mortality, and thromboembolism (TE). Updated RR rates of Tamoxifen impacting the four conditions were obtained from recent literature (Lancet, 2005, 365:1687–1717; JNCI,2005, 97:1652–62; 97:1609–10). Methods: The effect of Tamoxifen was calculated by applying Relative Risk Rates (RR) to the respective underlying Canadian age-specific mortality figures, separately for each condition. The final mortality impact was the “net mortality”, defined as differences of deaths, from each condition, between 1,000 Tamoxifen users vs 1,000 non-users (Dif N/1,000), expressed for ages <50 and >50. (i.e sum of avoidances [-] vs hazards[+]) Results: see Table below. Conclusion: Our results show a favorable Tamoxifen impact on overall mortality, particularly evident for women age <50, in whom the breast cancer mortality reduction significantly outweighs the hazards. These data are applicable to Tamoxifen prevention in population-women who are at high risk for BrCa. Their outcome profiles affected by Tamoxifen mirror those of the survivors of the 1st BrCa. While for women >50, other chemoprevention alternatives exist (i.e. trials of Aromatase Inhibitors), for younger women no chemoprevention trials are presently in existence. Our data indicate that in those, routine use of Tamoxifen may save substantial numbers of lives.

[Table: see text]

No significant financial relationships to disclose.
Dendritic cell (DC) reconstitution is associated with less opportunistic infections (OI) after allogeneic hematopoetic stem-cell transplantation (HSCT)
Authors: Dunbar E. M. , Levine J. B. , Schold J. D. , Samantha G. S. , Meier-Kriesche H. , Marchand E. , Mahmood S. S. , Reddy V. S.
Published: March 2020

6539

Background: Dendritic cells are key antigen presenting cells which coordinate immune responses against infections. We investigated the correlation between DC reconstitution after HSCT and the onset of OI. Methods: We prospectively studied immune reconstitution of DC in 124 patients with predominantly high-risk hematopoetic malignancies. Peripheral blood underwent flow cytometry analysis for DC, defined as lineage negative, HLA-DR+, CD11c+ and CD123+. Cluster analysis demonstrated patients at engraftment with high DC (>6.92/mm3) (n =68), low DC (n=56), and at 60 days with high DC (>3.95/mm3) (n=48), and low DC (n=43). Primary study endpoint was onset of OI, defined as viral and invasive fungal (proven and probable) OI within 6 months of HSCT. A cox proportional hazard multivariate model was adjusted for important covariates, including age, transplant conditioning (myeloablative vs. non-myeloablative), graft source (peripheral blood vs. bone marrow), donor-type (HLA-matched related vs. unrelated), and ANC. Results: Patients with low DC at engraftment had significantly increased onset of acute grade II-IV GVHD by Kaplan-Meier analysis (p=0.004). Patients with onset of GVHD prior to day 60 were less likely to have high DC (32% with GVHD, 72% without GVHD) (p=0.001). Furthermore, low DC at 60 days was adversely associated with: time to viral OI (p=0.04), time to composite of viral OI and death (p=0.02), time to viral or fungal OI (p=0.009), and time to composite of viral or fungal OI and death (p=0.02). In the Cox model, low DC at 60 days, was associated with a 3.7 relative risk (RR) (1.2, 11.8) for onset of OI. Patients with onset of OI prior to day 60 were significantly less likely to have high DC (41% with OI, 61% without OI) (p=0.05). Conclusions: This study emphasizes the clinical importance of measuring DC after transplant. Patients with low DC reconstitution are at an increased risk of OI and death. Measuring DC, and further understanding of the likely complex factors involved in DC reconstitution, may provide rationale towards future therapeutic immune interventions.

No significant financial relationships to disclose.
Sequential imatinib and chemotherapy yield reverse-transcriptase polymerase chain reaction (RT-PCR)-negative peripheral stem cell collections in Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL)—Preliminary results of CALGB 10001
Authors: Wetzler M. , Stock W. , Owzar K. , Sher D. A. , Hoke E. E. , Linker C. A. , Bloomfield C. D. , Larson R. A.
Published: March 2020

6549

Background: Ph+ ALL has a short complete remission duration and survival. Allogeneic stem cell transplantation (SCT) is recommended. We hypothesized that imatinib plus sequential chemotherapy will result in greater leukemia cell cytoreduction than previously achieved with chemotherapy alone, allowing collection of large numbers of normal hematopoietic stem cells uncontaminated by residual t(9;22) lymphoblasts and thus reduce the likelihood of relapse after autologous SCT for patients without donors. Methods: Treatment consisted of a 4–5 drug induction regimen followed by imatinib 400 mg BID for 4 weeks, CNS prophylaxis with high-dose methotrexate, another month of imatinib, and ideally allogeneic SCT following fractionated total body irradiation (FTBI) and etoposide. Those without donors received high-dose cytarabine, etoposide, and G-CSF for stem cell mobilization, leukapheresis, and autologous SCT after FTBI, etoposide and cyclophosphamide. Imatinib maintenance continues until RT-PCR negative for 12 months. Patients had to be < 60 years old. Results: 18 patients have enrolled to date; so far 3 underwent allogeneic SCT and 5 completed peripheral stem cell collections of whom 4 have undergone autologous SCT. Median stem cell yield was 55.74×106/kg (range, 34.8–94.4). Peripheral stem cells were assayed from 3 patients for RT-PCR with a sensitivity of 1:105-106. All 3 samples were negative for BCR-ABL. Of the 3 patients who underwent allogeneic SCT, 1 failed to engraft and died, 1 died due to respiratory failure on day 70, and 1 relapsed on day 113. Of the 4 patients who underwent autologous SCT, all achieved neutrophil engraftment (> 0.5×109/L) between days 8–10 and platelet engraftment (> 50×109/L) between days 7–17. Two patients relapsed (simultaneous CNS and marrow) on days 164 and 309, and 2 patients are alive in continuous remission on days +297 and +359 following autologous SCT. Conclusions: Sequential imatinib and chemotherapy can achieve RT-PCR negativity in Ph+ ALL, allowing autologous SCT. Ongoing accrual will evaluate the efficacy of this approach in adults with Ph+ ALL.

[Table: see text]
Pretreatment pulmonary function tests predict risk of mortality following fractionated total body irradiation without lung dose reduction prior to stem cell transplant
Authors: Mansueti J. R. , Singh A. K. , Karimpour S. E. , Guion P. , Ning H. , Savani B. , Wu C. , Altemus R. , Barrett J.
Published: March 2020

6550

Background: Peripheral blood stem cell transplantation (PBSCT) is a key component in the treatment of various malignancies. Preparatory regimens for PBSCT often include total body irradiation (TBI). Pulmonary toxicity is often prominent, and is felt to be related to total lung dose and dose rate. The Radiation Oncology Branch of the National Institute of Health initially administered TBI without lung shielding, however shielding was added in 2002. Pulmonary function testing (PFT) was undertaken both before and after stem cell transplant and TBI for all patients. The PFT results were analysed to test the hypothesis that TBI patients with pre-treatment combined ventilation/diffusion capacity deficits, defined as both FEV1 and DLCO below 100% predicted, would benefit most from reduction of lung dose. Methods: From 1997–2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. The first 85 patients were treated without lung dose reduction to 13.6 Gray (Gy). Thereafter, total body dose was decreased to 12 Gy (1.5 Gy BID for 4 days). Initially, lung dose was limited to 9 Gy by use of lung shielding. Later lung dose was reduced to 6 Gy. All patients received PFTs prior to treatment, 90 days after treatment, and annually. Results: Median F/U was 44 months (range 12–90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO) less than 100% predicted. Of these 61, 27 had lung dose reduction and 34 did not. One-year survival was 71% versus 50% with and without lung dose reduction respectively (log rank test p=0.042). Eighty-five patients had FEV1 and/or DLCO greater than or equal to 100% predicted; 34 were treated with lung dose reduction and 51 without. In both groups, 1 year survival was 70%. Conclusions: Among patients treated without lung dose reduction, survival was significantly worse among those with pretreatment combined ventilation/diffusion capacity deficits. Among those with combined ventilation/diffusion capacity deficits, lung dose reduction significantly improved survival.

No significant financial relationships to disclose.
Tipifarnib in combination with idarubicin and cytarabine in patients with newly diagnosed acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS)
Authors: Ravandi-Kashani F. , Kantarjian H. , Garcia-Manero G. , O’Brien S. , Verstovsek S. , Estrov Z. , Faderl S. , Giles F. , Wright J. , Cortes J.
Published: March 2020

6557

Background: Tipifarnib (Zarnestra [Z]) is a non-peptidomimetic farnesyl transferase inhibitor (FTI) with clinical activity in AML and MDS. In vitro studies have demonstrated synergy when combining tipifarnib with chemotherapeutic agents. Methods: We have conducted a study where pts (aged 15 to 60 years) with previously untreated AML or high-risk MDS (blasts >10%) were treated with Idarubicin 12 mg/m2/d on days 1–3, cytarabine 1.5 g/m2 IV over 24 hours daily on days 1–4 and Z; the first cohort (7 pts) received Z 200mg orally twice daily (BID), and all others 300 mg BID for 21 days. Pts achieving CR received consolidation (5 courses) with Idarubicin 8 mg/m2/d on days 1–2, cytarabine 0.75 g/m2/d on days 1–3, and Z 300 mg BID for 14 days every 4–6 weeks. Maintenance was with Z 300 mg BID for 21 days every 4–6 wk for 6 months. Results: We have treated 33 pts; median age 51 yrs (17–59 yrs). Twenty two pts (67%) have achieved CR, 3 (9%) CRp, and 2 (6%) PR. There were no induction deaths. Response (CR/CRp) by cytogenetics was: 13/15 (86%) for diploid, 5/6 (83%) with −5/−7, 1/2 (50%) with t(8;21), and 6/10 (60%) with other abnormalities. Response by Flt3 was 19/22 (86%) for unmutated Flt3, 3/5 (60%) for mutated Flt3. CR by age (excluding t(8;21)) was 13/16 (81%) if ≤ 50yrs, 4/6 (67%) if >50yrs and diploid, and 5/8 (63%) if >50yrs and other cytogenetics. With a median follow-up of 45 weeks, 5 pts have relapsed after 13 to 39 weeks and 1 died (in CR) after 18 wks. The most common grade 3 adverse events include reversible diarrhea in 7 (21%) and hyperbilirubinemia in 6 (18%). Twenty (61%) and 8 (53%) pts have required dose reductions during induction and consolidation courses, respectively. Conclusions: Z combined with Idarubicin and cytarabine induces a high rate of CR in AML/high risk MDS, with increased incidence of diarrhea and hyperbilirubinemia. Role of Z in prolongation of CR duration requires further follow-up.

[Table: see text]