bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histologic subtypes of ductal intraepithelial neoplasia (DIN) of the breast: Characteristic associations and biology
Authors: Schwartz J. D. , Christy C. , Grube B. , Rishi M. , Tavassoli F. , Bossuyt V. , Harris L. , DiGiovanna M. P. , Lannin D. R. 
Published: August 2020

633 Background: Most invasive breast cancers are associated with more than one histologic subtype of DIN. The clinical and biologic significance of these DIN subtypes is under-appreciated. Methods: We reviewed 853 cases of DIN diagnosed at our University based Breast Center between 2003 and 2008, 568 (67%) of which were associated with an invasive cancer. Cases of pure invasive cancer without DIN were excluded. Results: A single histologic subtype was present in 41% of the cases, two subtypes in 43%, and three in 16%. The most common DIN subtypes present were solid (52%) and cribriform (50%), while the comedo (18%), micropapillary (11%), papillary (9%) and flat (6%) subtypes were less common. Comedo and solid DIN were frequently found together (Odds ratio [OR]) for coexpression 1.94, p< .001) as were micropapillary and papillary subtypes (OR 2.58, p< .005). Comedo DIN was much less likely to be found with papillary (OR .24, p< .005), flat (OR .34, p< .05), cribriform (OR .42, p< .001) or micropapillary (OR .48, p< .05) subtypes. We also examined multiple biological parameters and their association with the different DIN subtypes as shown in the table below. Solid and comedo subtypes tend to be hormone receptor negative, Her2 positive and high grade while the cribriform subtype tends to be hormone receptor positive, Her2 negative and low grade. Papillary and comedo DIN are most likely to be larger lesions. Papillary DIN is least likely to be associated with an invasive cancer. Conclusions: The histologic architecture provides clues to the underlying molecular changes and biological behavior of DIN. This study will begin to help us understand the molecular basis for the different histologic subtypes of DIN, their different clinical behaviors and tendencies to progress to invasive cancer. [Table: see text] No significant financial relationships to disclose.
Role of progesterone receptor status (PR) as predictive factor of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients (pts)
Authors: Perez Garcia J. M. , Saura C. , Muñoz E. , Sanchez-Olle G. , Gomez P. , Peg V. , Sabadell D. , Cortes J. , Baselga J. , Bellet M. 
Published: August 2020

637 Background: While estrogen receptor (ER) negativity has been consistently associated to higher pCR rates after NACT in BC, few data regarding the association of PR with pCR has been reported. PR positivity has been related to taxol resistance in in vitro chemosensitivity assays. Our aim was to investigate the putative role of PR in the prediction of pCR in a cohort of BC pts receiving NACT. Methods: Medical reports of all pts receiving NACT and breast surgery between 2004 and 2006 in our institution were reviewed. Baseline clinical and histological features, along with type of preoperative therapy were examined as variables for association with pCR (no invasive tumor in breast and axilla) using univariate and multivariate analyses. Results: 128 pts were included. 73.4% received anthracycline and taxanes (A&Tx) based CT and 9.4% also received trastuzumab (T). PR+ (≥ 10%) was significantly associated with low histological grade (HG), low Ki67 (<10%), HER-2- (Herceptest 0,1,or 2 with FISH-) and ER+ (≥10%). Overall pCR rate was 18.8%. No PR+ patient achieved pCR. In univariate analysis, high HG, ER-, PR-, HER-2-, high Ki67, T therapy, and number of CT cycles were significantly associated with pCR. In multivariate analysis only HER-2 and PR status were statistically significant. Similarly, PR and HER-2 status were independently related to pCR in the subgroup of pts receiving A&Tx (N = 94, 20.2%pCR). In the HER-2- subgroup (n = 89, 9%pCR) only ER independently predicted pCR, while in the HER-2+ subgroup (n = 33, 42.4%pCR, 57.1%pCR with T), both PR- and T therapy were the only predictive factors for pCR in the univariate and multivariate analyses. When the 24 HER-2+ pts treated with A&Tx (23 taxol/1 taxotere) ± T were separately analyzed, only PR retained statistical significance in the multivariate model. Conclusions: In our cohort of BC pts treated with NACT, PR status independently predicts pCR in the whole population as well as in the A&Tx-treated and in the HER-2+ subgroups. In the HER-2+ pts receiving A&Tx ± T PR negativity was the only factor associated with pCR. PR status merits further investigation as a predictive factor for pCR to NACT, in particular in HER-2+ population. No significant financial relationships to disclose.
Routine preventive care and cancer surveillance in long-term survivors (LTS) of colorectal cancer: Results from NSABP Protocol LTS-01
Authors: Kunitake H. , Zheng P. , Yothers G. , Land S. , Fehrenbacher L. , Giguere J. K. , Wickerham D. L. , Ganz P. A. , Ko C. Y. 
Published: August 2020

6500 Background: Little is known about the use of routine preventive care and cancer surveillance in long-term colorectal cancer survivors. NSABP LTS-01 is a study that examines the use of such services in long-term colorectal cancer survivors previously treated in NSABP adjuvant trials. Methods: Long-term colorectal cancer survivors (≥ 5 years) were recruited from five completed NSABP treatment trials (Protocols C-05, C-06, C-07, R-02, R-03) at 65 study sites. A survey battery for long-term survivors of colorectal cancer (LTS-01) was developed. A 1:4 comparison cohort case-matched by age, gender, race, and education was created from the 2005 National Health Interview Survey. Contingency tables and multivariate models were used to compare cohorts and determine predictors of preventive care and cancer surveillance. Results: 649 LTS-01 patients (625 colon, 24 rectal) completed the interview; 57% male, mean age 66.1yr (SD 10.5), median survival 8 yrs. LTS-01 patients were more likely to have a usual source of healthcare than the NHIS cohort (98% vs. 93%, p < 0.0001). The number of ER visits in the previous 12 months was not significantly different between the two groups. LTS-01 patients were more likely to have received a flu shot in the past 12 months (68% vs. 42%, p < 0.0001) and were also more likely to have undergone cancer screening by Pap smear (67% vs. 54%, p < 0.001), mammogram (85% vs. 71%, p < 0.001), and PSA test (84% vs. 75%, p < 0.001). For CRC surveillance, 3% did not have a colonoscopy, 13% had not had a CEA test, and 34% did not have a CT scan in the last 5 years. The best predictor of the receipt of these cancer screening tests was the presence of health insurance (OR 2.6–4.5). No factor was uniformly associated with colorectal cancer surveillance. Conclusions: Long-term survivors of colorectal cancer achieve better routine preventive care including cancer screening than the general population. However in these stage II and stage III cancer patients cancer surveillance is variably performed. No significant financial relationships to disclose.
A study of physician investigator (PI) disclosure of alternatives of care and prognostic information to advanced cancer patients (ACP) enrolling in phase I trials
Authors: Daugherty C. , Kass N. E. , Roter D. , Larson S. , Sugarman J. , Kasza K. , Ratain M. J. , Hlubocky F. J. 
Published: August 2020

6508 Background: ACP in phase I trials have been described as having an inadequate understanding of several elements of informed consent. However, actual PI disclosure of alternatives to trial participation and prognostic information, and subsequent ACP understanding of these elements, have not been described. Methods: Clinical encounters between 131 ACP entering phase I trials and 25 oncologists at three institutions (University of Chicago; Johns Hopkins; and Duke University) were audio-taped. ACP completed follow-up questionnaires one week later to assess understanding of informed consent elements. Audiotapes were analyzed using the Roter Interaction Analysis System (RIAS) and specifically coded for terms associated with trial alternatives and patient prognosis. Results: To date, 85 encounters have been analyzed. Average encounters length: 30.4 min (range: 5.7–77.8 min). For ACP: median age 60y (33–83); 55% female; 88% Ca; 55% <college educ; 52% income <$60,000. The PI was recorded as discussing options other than anticancer treatment in 47% of encounters. The terms “palliative” or “hospice” were used in 1% and 2.3% of encounters respectively. In 29% of encounters the PI described the option of “doing nothing”. The PI used the terms “death” or “terminal” in 5.8% encounters. The PI was never recorded using the term “dying”. Within these encounters, no ACP was recorded as using any of the following terms: “palliative,” “hospice,” “terminal,” “death,” “dying.” Within follow-up interviews, 30% reported no alternatives to trial participation were discussed; 1% reported that palliative care/hospice was discussed. Based on coding of qualitative responses, 53% of ACP said that either their prognosis was excellent or they didn't know their prognosis. An association was found between recorded physician statements regarding general prognosis and ACP subsequently reporting having discussion regarding life expectancy (59% v. 33%, p = 0.04). Conclusions: PI communication and subsequent measured understanding regarding alternatives to trial participation and prognosis remain inadequate in the setting of phase I trial enrollment. [Table: see text]
The impact of the inclusion of clinical data review on overall radiographic response and progression in oncology clinical trials as assessed by blinded independent central review
Authors: Wangler N. , Borradaile K. , Ford R. 
Published: August 2020

6511 Background: The United States Food and Drug Administration (USFDA) advocates blinded independent central review (BICR) of radiographic exams for oncology registration studies when the primary study endpoint is based on tumor measurements, such as progression-free survival, time to progression or objective response rate. However, a proportion of subjects progress clinically prior to radiographic evidence of disease progression and in certain indications, measurement of cutaneous lesions may be incorporated into response criteria calculations. Methods: BICR data from 4,183 subjects in the following indications: lymphoma, melanoma, breast cancer, and colorectal cancer, was blinded, pooled, and reviewed to determine the impact of clinical review on best response and date of progression following BICR of radiographic images. Results: Inclusion of clinical data and/or clinical photography impacted 27% (47/171) of lymphoma subjects, affecting the assessment of the best response (13%), best response date (16%) and/or the date of progression (19%); 12% (13/107) of melanoma subjects, affecting the assessment of the best response (6%), best response date (5%), and/or the date of progression (8%); 10% (308/2,947) of breast cancer subjects, affecting the assessment of the best response (4%), best response date (4%), and/or the date of progression (9%); 3% (32/958) of colorectal cancer subjects, affecting the assessment of the best response (2%), best response date (2%), and/or the date of progression (2%). Conclusions: When using BICR to determine endpoints in oncology clinical trials, inclusion of a clinical review may be relevant in 27% of subjects for lymphoma, 12% for melanoma, 10% for breast cancer, and 3% for colorectal cancer. [Table: see text]
Factors associated with chemotherapy receipt and intensity for stage IV colorectal cancer (CRC): A multihealth system, population-based study
Authors: Zafar Y. , Grambow S. C. , Abbott D. H. , Malin J. L. , Zullig L. L. , Kolimaga J. T. , Provenzale D. T. 
Published: August 2020

6519 Background: Little is known about chemotherapy practice patterns for patients with stage IV CRC. Methods: Cancer Outcomes Research & Surveillance Consortium (CanCORS) is a prospective cohort study including patients with incident CRC sampled from a set of defined populations and health systems. Eligible patients for this analysis (n = 742) had stage IV CRC and abstracted medical record data, including stage, chemotherapy, comorbidity (measured by the Adult Comorbidity Evaluation 27 index), and sociodemographic data. Logistic regression models were used to evaluate factors associated with chemotherapy receipt and intensity. Results: A majority of patients were male (62%) and white (62%). 27% were ≥75 years old, and 14% had severe comorbidity. 34% had private insurance, 32% had public insurance (including Medicare/Medicaid), 18% were Veterans Affairs patients, 4% had no insurance, and 13% were missing insurance information. Overall, 77% received chemotherapy, and 57% received >1 line of therapy. Patients were less likely to receive chemotherapy if they were older (65–74 vs. <55 years = adjusted odds ratio [OR] 0.14, 95%CI 0.06–0.33, p < 0.001; ≥75 vs. <55 years = OR 0.04, 95%CI 0.02–0.64, p < 0.001), or had severe comorbidity (OR 0.38; 95%CI 0.23–0.64; p < 0.001). When treated, patients ≥75 years were more likely to receive capecitabine vs. 5-fluorouracil (5-FU) (p < 0.001), less likely to receive >1 line of therapy (p < 0.001), and less likely to receive oxaliplatin or irinotecan combination therapy vs. a single-agent fluorouracil (p < 0.001). Although only 4% were uninsured, lack of insurance did not appear to be a factor in receipt of chemotherapy. Patients with public vs. private insurance were more likely to receive chemotherapy (OR 2.58; 95%CI 1.49–4.47; p < 0.001) but were less likely to receive combination therapy versus a single-agent 5-FU (p = 0.02). Conclusions: The elderly are less likely to receive standard therapy. While patients with public insurance are more likely to receive chemotherapy, they are less likely to receive recommended first-line combination regimens. Future research should investigate how insurance coverage and demographics influence physician and patient preferences for advanced CRC treatment. No significant financial relationships to disclose.
Accuracy and comprehensiveness of pathology reportage after lung cancer resection
Authors: Farooq A. , Osarogiagbon R. U. , Allen J. W. , O'Brien T. F. , Spencer D. , Berry A. 
Published: August 2020

6523 Background: Decisions about prognosis, adjuvant chemo/radiation therapy and clinical trial eligibility require careful examination of the surgical resection specimen. In January 2004, the College of American Pathologists (CAP) and the American College of Surgeons Committee on Cancer mandated reportage of specific items after resection of lung cancer. The extent of compliance is unknown. Methods: We examined final pathology reports for all lung cancer resections in the Memphis Metropolitan Area from January 2004 to December 2007. End-points were the percentage of reports with each CAP item and the 6 most vital determinants of post-operative management and accuracy of TNM staging. Chi-square test was used for year to year comparisons. Results: Table 1 shows frequency of reportage of CAP items. Of those with reported pT stage, it was accurate in 242 of 263 (92.02%) identified as T1; 193 of 208 (92.79%) T2; 21 of 24 (87.5%) T3; 11 of 11 (100%) T4. The most common T-staging error, understaging of satellite nodules (T4), occurred in 12 of 21 (57%) mis-staged as T1, 11 of 15 (73%) T2, 3 of 3 (100%) T3. Overall, 62.6% of reports accurately identified pT-stage. Of those with reported pN-stage, 351 of 352 (99.7%) accurately identified N0; 69 of 81 (85.2%) accurately identified N1, 12 of 81 (14.81%) N1 designations were actually N2; 27 of 27 (100%) N2 designations were accurate; 31 of 34 (91.2%) identified as Nx (no lymph nodes in the specimen) were accurate, 3 (8.8%) were truly N0. Overall, 64.08% of reports accurately identified pN-stage. 4 of 503 identified as pMx (0.8%) had pM1. There was no change in proportion of incomplete and/or inaccurate pathology reports over the 4 years of analysis. Conclusions: Pathology evaluation of lung cancer resection specimens is frequently incomplete or inaccurate, potentially impairing clinical decision-making. Satellite nodules are often understaged. Simple corrective interventions such as enforcement of mandatory institutional utilization of the CAP checklist and AJCC staging manual need to be investigated. [Table: see text] [Table: see text]
Patient and health system disparities in timeliness of treatment for individuals with colorectal cancer (CRC)
Authors: Halpern M. T. , Holden D. J. 
Published: August 2020

6540 Background: Timely initiation of treatment following cancer diagnosis can improve morbidity, quality of life, and survival. We used SEER-Medicare data for individuals diagnosed with CRC to explore disparities in the timeliness of initial cancer therapy. Methods: Medicare patients diagnosed with CRC in 2000–2001 while living in SEER regions were identified. Only patients who received cancer treatment (surgery, radiation therapy, or chemotherapy), were diagnosed at age 66 or later, and were enrolled in Medicare at least one year post-diagnosis were included. Multivariate logistic regression analysis was used to evaluate the impact of patient sociodemographic, clinical, community, and health system factors on receipt of timely care, defined as treatment initiation within the 95th percentile of waiting time for all CRC patient (two months). Results: Black and Hispanic CRC patients were significantly more likely to experience delays in treatment than were White patients. Males and patients from areas with more non-English speakers were also more likely to experience delays. Among earlier stage patients who received surgery, those treated at physician offices (10.2%) were significantly more likely to experience delays than were those treated at hospitals (as inpatients or outpatients). Among patients with distant stage disease, those initially treated as hospital inpatients were significantly less likely to experience delays than were those treated as hospital outpatients or in physician offices. For these patients, initial treatment with chemotherapy or radiation therapy was associated with significantly greater likelihood of delays compared to patients initially receiving surgery. Conclusions: Controlling for other factors, significant disparities in timeliness of care were observed for racial/ethnic minority patients, males, and those from non-English speaking areas. Treatment site and modality also affected timeliness of care. While more research is needed, programs should target these at-risk populations for education and follow-up after diagnosis. No significant financial relationships to disclose.
Risk factors for severe cancer chemotherapy toxicity in the outpatient setting: Results of a nested case control study using a novel patient cohort
Authors: Jacobson J. O. , Brozovic S. , Stahl J. E. , Papi M. , Stankiewicz R. 
Published: August 2020

6545 Background: Risk factors for severe cancer chemotherapy-related toxicity (resulting in hospitalization and/or death) in the adult outpatient setting are largely unknown. Between 2003–2006, we identified all chemotherapy patients from a single hospital-affiliated outpatient cancer center who required admission to the hospital, and using a structured process that included monthly peer review meetings, we determined which admissions were due to chemotherapy toxicity. Among 2,082 patients who received chemotherapy, 185 required at least one admission. In this study we describe the development of a prediction model for severe chemotherapy-related toxicity. Methods: We undertook a nested case control study by randomly selecting 98 patients admitted to the hospital within 30 days of their last chemotherapy administration and 173 controls. We selected 33 clinical and demographic variables that we hypothesized might predict severe toxicity, and used standard descriptive, univariate and regression methods to characterize the data and develop a prediction model. Results: We were able to identify the following variables that predicted for severe chemotherapy toxicity: increasing age; increasing Charlson Comorbidity index (CCI); treatment with a prior chemotherapy regimen; prior admission for chemotherapy toxicity; decreasing hemoglobin and absolute neutrophil count (ANC) and increasing creatinine, and albumin. Independent variables that did not predict for increased risk for severe toxicity included the following: performance status; chemotherapy intent (curative, adjuvant or palliative); full dose versus reduced dose for cycle I; cisplatin-based chemotherapy; median income (by postal codes). Using logistic regression we created a parsimonious model (ROC AUC of 0.69) that included four clinical independent variables: CCI; prior chemotherapy regimen; ANC; and albumin. Conclusions: This analysis may permit the development of a predictive model which will include CCI, prior chemotherapy regimen, ANC, and albumin to help identify patients prior to the initiation of chemotherapy who are risk for severe toxicity. No significant financial relationships to disclose.
Clinical trial metrics: Protocol performance and resource utilization from 14 cancer centers
Authors: Durivage H. J. , Bridges K. D. 
Published: August 2020

6557 Background: Observations at the authors’ institutions and by Dilts et al (JCO 2008, abstr 6534) indicate a high percentage of industry (IND)- and cooperative group (CG)-sponsored therapeutic clinical trials (TCTs) with minimal enrollment. We observed most of the enrollment from a small proportion of the TCTs. To determine if this data was representative of other cancer centers (CCs) we examined accrual to IND- and CG-sponsored adult TCTs from 14 CCs. Methods: Accrual data to IND- and CG-sponsored TCTs was obtained from 14 U.S. CCs. Data for the 3-year period from 2005 through 2007 was analyzed. Pediatric TCTs were excluded. Results: Of 2,685 TCTs, 1455 (54.2%) did not accrue any patients (pts). Only 713 (26.6%) TCTs enrolled > 2 pts and these TCTs provided 88.8% of the total enrollment. Resource utilization: We estimate > 230,000 hours (median: 3,773 hours per CC per year) were devoted to study start up and regulatory maintenance for the 1,455 TCTs that did not accrue any pts (Guidance Document for Implementing Effective Cancer Clinical Trials, www.c-changetogether.org/pubs/default.asp). Conclusions: Approximately 90% of the accrual to IND and CG TCTs is from 26% of these TCTs. Significant resources are used on TCTs that do not contribute significantly to overall accrual. Effective rules governing selection of IND and CG TCTs for activation are needed. Effective rules will enable centers to re-direct valuable resources to useful activities without adverse effect on overall enrollment. [Table: see text] No significant financial relationships to disclose.