tbuckley/cabot-search huggingface dataset:
Surgical and oncologic outcomes in patients with breast cancer undergoing tattooing prior to neoadjuvant chemotherapy.
Authors: D. R. Lannin, B. J. Grube, B. K. Killelea, N. Horowitz, L. Harris
Journal: Journal of Clinical Oncology (2011)

100 Background: Neoadjuvant chemotherapy for breast cancer increases the breast preservation rate, but also increases the rate of local recurrence, probably because there is no standard technique to determine the amount of breast tissue to be removed. In 2007 we described a technique where the surgeon maps the extent of a breast tumor, plans a surgical incision, and tattoos the breast prior to the patient receiving neoadjuvant chemotherapy. After the chemotherapy, digital photographs are retrieved that allow the surgeon to precisely reconstruct where the margins of the original tumor were in the breast, and to proceed with a planned operation to remove the entire tumor bed but minimal surrounding breast tissue. The purpose of this study is to describe a series of patients treated with this technique and to evaluate the surgical and oncologic outcomes obtained. Methods: Data were collected from a prospective breast cancer database and from chart review on all patients treated with this technique at a single institution. Most patients receiving neoadjuvant chemotherapy underwent the tattooing, unless they knew beforehand that they were going to undergo a mastectomy. Results: Between June 2005 and January 2011, 87 patients underwent breast tattooing followed by chemotherapy. Of patients who have completed subsequent definitive therapy, the initial surgery was mastectomy in 31 and lumpectomy in 53. Most patients’ tumors became nonpalpable following the therapy, and the pathologic complete and partial response rates were 22% and 64% respectively. Of patients who underwent an initial lumpectomy, 5/53 (9%) had positive margins and underwent further surgery (2 mastectomy and 3 wider lumpectomy). With a median follow-up of 36 months, only 1 patient has had an in-breast local recurrence. Conclusions: These early results clearly show a lower rate of re-excision and a lower rate of local recurrence than commonly reported in the literature for breast preservation following neoadjuvant chemotherapy. The technique warrants wider application and further study.
Detecting hereditary nonpolyposis colorectal cancer syndrome (HNPCC) in patients with colorectal cancer (CRC): Optimal strategies at lower costs.
Authors: Daniel Erik Abbott, Scott B. Cantor, Miguel A. Rodriguez-Bigas, George J. Chang, Patrick M Lynch, Barry W. Feig, John Michael Skibber, Y. Nancy You
Journal: Journal of Clinical Oncology (2012)

396 Background: The optimal strategy to detect HNPCC in CRC pts remains controversial, and may include testing tumors for microsatellite (MSI) status and/or pts for mutations in DNA mismatch repair (MMR) genes. Costs of 6 testing strategies were compared against their risks of missing pt managed as HNPCC. Methods: 185 consecutive CRCs were prospectively tested by both immunohistochemistry (IHC, for protein expressions of MLH1, MSH2, MSH6, PMS2) and PCR-based MSI. Secondary tests included MLH1 promoter methylation, BRAF mutation, and germline mutation, as appropriate. A decision tree compared the strategy of performing both IHC and MSI in all (Strategy 1) to five alternatives (Strategies 2-6, Table ). Costs were obtained from commercial list prices, Medicare reimbursement, and literature; probabilities were calculated from pt data. Incremental cost-effectiveness ratios (ICERs) were reported for each additional pt managed as HNPCC Results: 20 (10.8%) pts were identified as being managed as HNPCC. Performing IHC and MSI in all (Strategy 1) or IHC first in all followed by MSI when IHC was normal (Strategy 4) detected all 20 cases. When compared to performing IHC only (Strategy 2), Strategy 4 demonstrated an ICER of $31,821 per additional case detected, while other strategies were more costly and/or less effective (Table). Between the two strategies that detected all cases of HNPCC, Strategy 4 was less costly ($1,049 vs $1,098 per patient, Table). Conclusions: When combined with appropriate secondary and confirmatory testing, performing IHC and MSI in all or IHC in all followed by MSI when IHC were normal, both showed a zero miss rate, while the latter was slightly more cost-effective. [Table: see text]
Stereotactic body radiation therapy following transarterial chemoembolization for Child-Pugh A and B hepatocellular carcinoma.
Authors: Craig Joseph Baden, Benjamin Hinton, Rojymon Jacob
Journal: Journal of Clinical Oncology (2014)

321 Background: Hepatocellular carcinoma (HCC) incidence continues to increase, but recent improvements in treatment of localized tumors have contributed to modest gains in survival rates. Though transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) are increasingly used in the management of unresectable HCC, outcomes data regarding the combination of these treatments is limited. Here we report institutional outcomes for patients with Child-Pugh A (CPA) and B HCC treated with TACE followed by SBRT. Methods: We completed an institutional retrospective review of all patients treated with combination TACE and SBRT between 2009 and 2013. After compiling dosimetry, toxicity, and outcomes data for each patient we calculated descriptive statistics for the cohort and determined local control (LC), distant liver control (DLC), progression free survival (PFS), and overall survival (OS) utilizing the Kaplan-Meier method. We also compared these disease-related outcomes between CPA and CPB groups with the Mantel-Cox test for equality. Results: Thirty-one patients with HCC, median age 65, were treated with TACE and SBRT and followed for a median 16.6 months (range: 6.2-50.8). Twenty-two patients had CPA disease and 9 CPB at the time of initial treatment. Following TACE and a median interval of 10.5 days (range: 4.4-25.6) patients underwent SBRT, the majority (23) with 45 Gy in 3 fractions. All but 3 patients were treated with respiratory gating, and all had cone-beam CT for image guidance. One and 2 year disease-related outcomes were as follows: LC 92.0 and 82.8%, DLC 81.5 and 61.0%, PFS 73.6 and 61.8%, OS 96.8 and 64.2%. There were no statistically significant differences between CPA or CPB patients with respect to any of these disease-related outcome measures. Median survival times for class A and B patients were 34.2 months (95% CI 12.3-56.1) and 27.2 months (14.9-39.5) respectively. Conclusions: The combination of TACE and SBRT is generally well tolerated, and results in very good local control in both CPA and CPB patients. Distant liver failure remains a major problem in these patients and requires further study.
PET scans in HIV-related Hodgkin lymphoma (HIV-HL): Results of a retrospective study.
Authors: M. Hentrich, M. Berger, C. Hoffmann, J. Siehl, T. Wolf, M. Nickelsen, J. Rockstroh, D. Schuermann, A. Rieke, R. Schmidmaier, H. Knechten, M. Mueller, G. Fätkenheuer, R. Meyer, K. Arastéh, F. A. Mosthaf, C. Wyen
Journal: Journal of Clinical Oncology (2011)

8044 Background: No data are available on using PET-scans in HIV-HL. The goal of the present study is to analyse consecutive patients (pts) with HIV-HL who had at least one PET scan conducted during their course of primary chemotherapy (CT). Methods: In the German prospective multicenter trial pts. with HIV-HL are planned to receive 2x ABVD + 30 Gy involved field (IF) radiation (RT) for early stage (ES) favourable HL (stage I/II without risk factors), 4x BEACOPP baseline or 4x ABVD + 30 Gy IF for ES unfavourable HL, and 6-8 x BEACOPP baseline for advanced stage HL with BEACOPP being replaced by ABVD in pts with far advanced HIV-infection or poor performance status. Since the role of PET-scans is not specifically addressed in this trial FDG-PET is not routinely scheduled. However, as PET-scans are being performed on physician’s choice we retrospectively analyzed results and clinical impact of FDG-PET in this cohort of pts. Results: From 03/04 to 12/10 105 pts (median age 43.9 yrs, 8 females) were included in the trial. 23 pts (22%) had ES favourable HL, 14 (13%) ES unfavourable HL, and 68 (65%) advanced stage HL. 26 of 105 pts had a total of 37 PET/PET-CT scans done at some point during their course of treatment. FDG-PET was conducted as part of the initial staging and for response assessment in 8 and 28 cases, respectively. 1 pt had a PET-scan performed to rule out a late relapse of HL or a second malignancy. A negative FDG-PET had an impact on further management in 15 pts with additional RT being omitted in 9 pts and CT for advanced HL being terminated after 6 or 7 cycles of BEACOPP in 5 pts and 1 pt, respectively. A PET-scan performed after 2 cycles of ABVD (PET2) proved negative (neg) in 3/3 pts with 2 of those not receiving IF-RT. PET4 proved negative in 4 of 5 pts with ES-unfavourable HL with IF-RT not being given in all PET4 neg. pts. All PET2/PET4 neg. pts who did not receive IF-RT (n=6) remain disease-free after a median follow-up of 24 months. RT was also successfully omitted in 3 pts with neg. FDG-PET after 6 or 8 cycles of CT. Conclusions: Given the high negative predictive value of FDG-PET in HIV-negative HL, these preliminary data suggest that in pts with HIV-HL a negative PET-scan conducted after 2, 4 or 6-8 cycles of CT may allow the omission of IF-RT.
Electronic medical records: Assessment of recorded cancer stage in support of quality of care.
Authors: Gregory P. Hess
Journal: Journal of Clinical Oncology (2012)

129 Background: Electronic medical records (EMRs) are being increasingly adopted in part driven by reports of their positive impact on patient’s quality of care. An underlying assumption is that data recorded will be relatively complete. As a field of primary importance, this study assessed the frequency with which cancer stage was recorded within an EMR data field during a historical and recent 12-month period. A random sample of records with missing stage was assessed to identify at a qualitative level reasons that stage may be omitted. Methods: Two datasets were constructed. The first comprised of oncology EMRs from 77 practices covering 476 sites of care across 34 states from 1/1/2000-12/31/2010. The second dataset from 58 practices covering 391 sites of care across 37 states. Inclusion criteria required patients to have a valid visit (i.e., not simply ‘scheduled’) and ≥ 1 diagnosis of a primary, malignant, neoplasm (except brain or spine). All data fields utilized to record stage (stage I, II, etc.) or from which stage could be reliably derived (T, M, N fields) were defined as "recorded." Practices were not required to exist in each dataset. Recorded stage by age, gender, state, and payer type was also assessed. Results: Reasons reported for absent stage within the data field included: consult visit only, written in the progress notes, text present in a scanned report, stage X (insufficient information), continuing treatment initiated elsewhere, and missing entry error. Conclusions: A significant proportion of cancer patients may not have stage recorded in the designated, searchable, data field within an EMR. The frequency of recorded stage is increasing over time. Reasons for unpopulated stage field(s) include use of nonsearchable text entries, scanned reports, and short episodes of care. Further research is needed to validate the observations in this study, determine root causes, and employ appropriate solutions. [Table: see text]
The effect of food on the pharmacokinetics of BMS-275183, a novel oral taxane, in patients with advanced solid malignancies
Authors: M. H. Woo, L. E. Broker, M. J. Pilat, L. Malburg, M. B. Cohen, T. W. Griffin, M. Valdivieso, G. Giaccone, P. M. Lorusso
Journal: Journal of Clinical Oncology (2005)

2053 Background: BMS-275183 is a novel oral taxane with promising activity against NSCLC and other tumor types. The effect of food on absorption of BMS-275183 is not known. In this study, the effect of food on the pharmacokinetics (PK) of BMS-275183 was assessed in patients with advanced solid tumors refractory to standard therapy. The inter-patient PK variability after a fixed dose was also compared to that after a dose based on body surface area. Methods: Thirty-two patients were randomized to receive weekly 200 mg doses of BMS-275183 on each of three occasions: after a fast of 10 hours, 30 minutes after a standard low-fat meal, or 30 minutes after a standard high-fat meal. Patients were subsequently treated at the 200 mg/m2 Phase II dose on a continuous, weekly schedule under fasted conditions. Blood samples for BMS-275183 PK were collected predose and over 72 hours from the start of dosing on Days 1, 8, 15, and 22. BMS-275183 plasma concentrations were measured using a validated LC/MS/MS assay. Determination of food effect was based on bio-equivalence criteria Cmax and AUC. Results: BMS-275183 PK data are summarized for the 24 patients fully evaluable for PK assessment in the following table. Analysis of provisional data showed diminished Cmax and delayed Tmax, but no effect on AUC of BMS-275183 when given with food compared to the fasted state. The inter-patient variability of BMS-275183 AUC after a 200 mg dose was 84% and that after a 200 mg/m2 dose was 66%. BMS-275183 was generally well tolerated. Conclusions: Food affected the Cmax, but not the AUC of BMS-275183 and could moderate Cmax-related toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Using the PAM50 breast cancer intrinsic classifier to assess risk in ER+ breast cancers: A direct comparison to Onco<i>type</i> DX.
Authors: R. R. L. Bastien, M. T. W. Ebbert, K. M. Boucher, C. M. Kelly, B. Wang, T. Iwamoto, S. Krishnamurthy, L. Pusztai, P. S. Bernard
Journal: Journal of Clinical Oncology (2011)

503 Background: Multianalyte gene expression assays have proven valuable in the management of breast cancer, however, the methodologies and indications for these assays can differ. In ER+ breast cancer, there continues to be debate about the most important components of these tests for determining risk of relapse. The PAM50 test has genes relevant to ER+ and ER− disease, while the Oncotype Dx recurrence score (RS) was tailored specifically for ER+ breast cancer. The components of the PAM50 that are most relevant to the RS are assessed. Methods: A total of 151 ER+ breast cancers, that were sent to Genomic Health Inc for Oncotype Dx testing from the University of Texas M. D. Anderson Cancer Center at the time of diagnosis (2004-2008), were re-analyzed at ARUP Laboratories Inc using the PAM50 Breast Cancer Intrinsic Classifier. Formalin-fixed, paraffin-embedded tissue blocks containing invasive breast carcinoma were selected after H&E review by a pathologist. RNA was extracted from full face scrolls and directed punches using the High Pure RNA Paraffin Kit (Roche). Multivariate analysis was used to identify components of the PAM50 test that contribute independently to the Oncotype Dx risk score (RS). Linear models were fit to the data. Bootstrap methods were used to correct for bias in the predictions. Results: After quality control, there were 119 invasive breast cancers that were successfully assayed on both clinical platforms. The subtype distribution consisted of 76 Luminal A (64%), 27 Luminal B (23%), 4 HER2-enriched (3%), 1 Basal-like (0.8%), and 11 Normal-like (9.2%). None of the Luminal A subtype samples had a high RS and 90% (9/10) of high RS samples were Luminal B. There was a negative correlation between the RS and PAM50 Luminal A centroid (r=−0.44; p<0.0001). The best linear prediction of the RS using PAM50 included subtype – Luminal A vs Luminal B (p=0.044), Luminal Score (p=0.003), Proliferation Score (p=2.34e-05), and PGR Score (p=0.0014). Conclusions: The PAM50 Breast Cancer Intrinsic Classifier and Oncotype Dx use different gene sets and algorithms, however, there is a very large and significant overlap in the ability of these clinical tests to determine risk in ER+ breast cancers.
Acute Differentiated Dendritic Cell Leukemia: A New Form of Pediatric Acute Myeloid Leukemia (AML) with MLL Translocations.
Authors: Luca Lo Nigro, Laura Sainati, Anna Leszl, Elena Mirabile, Monica Spinelli, Caterina Consarino, Andrea Di Cataldo, Saverio Magro, Carolyn Ann Felix, Giuseppe Basso
Journal: Blood (2005)
The Cancer Institute of New Jersey (CINJ) Network: A model for quality cancer care and research in the community.
Authors: M. Gabel
Journal: Journal of Clinical Oncology (2010)

e16547 Background: CINJ, an NCI-designated Comprehensive Cancer Center, provides educational programs and research through the CINJ Network of 16 hospitals and primary care practices, with the potential to reach over 15,000 cancer patients and 800,000 primary care patients throughout New Jersey. Methods: In 2004, the CINJ Oncology Group (CINJOG) was created to offer research education, work assistance and oversight to implement and conduct clinical research in community practices. CINJ Network educational programs and services were simultaneously enhanced. In 2007, CINJ began to design culturally sensitive multilingual educational programs and materials and to train Network health professionals in evidence-based cancer outreach programs. In 2008, The Commission on Cancer's National Cancer Data Base (NCDB) created a custom CINJ Network dataset to design and assess annual quality and research initiatives. Performance on several outcome measures was assessed in 2009. Results: In 2009, the education programs led to 161 community nurses attending symposia and almost 100 obtaining online CNE credit. Over 80 patient educational materials were developed and translated into 12 languages. The clinical trial menu grew from 15 to 88 trials, 20% of which are investigator-initiated studies. Accrual YTD 2009 is 192; community physicians accrued 148 and 46% of enrollments are onto investigator-initiated trials. Comparison accrual in 2005 was 83. There is concordance between Network population demographics and minority accrual into clinical trials. The Network population is comprised of 10.4% African American (AA), 4.6% Hispanic and 5.5% Asian patients. In 2006 (midpoint of the program) 23% of patients accrued were minorities (16.2% AA, 7.2% Hispanic, and 3.4% Asian). Conclusions: The CINJ Network is a successful model for promoting cancer knowledge and research throughout community physician practices. Clinical research success is dependent upon linking research resources with custom audience-specific education and training initiatives. Future work will focus on disparities, multi-institutional quality improvements and further increase the depth and breadth of clinical research participation. No significant financial relationships to disclose.
A phase III study of xilonix in refractory colorectal cancer patients with weight loss.
Authors: George A. Fisher
Journal: Journal of Clinical Oncology (2015)

685 Background: Xilonix, an anti-interleukin-1α true human monoclonal antibody is being assessed as cancer therapy to improve overall survival (OS) in advanced colorectal cancer (CRC) patients. Methods: An open label multicenter randomized comparator controlled study to evaluate efficacy and safety of Xilonix in CRC complicated with cachexia. Eligible patients had metastatic CRC, failed oxaliplatin or irinotecan based chemotherapy, and lost ≥5% total body weight in the previous 6 months (m). Patients were 1:1 randomized to Xilonix (3.75 mg/kg intravenously every two weeks) or megestrol acetate (MA, oral 800 mg daily) until progression. Primary endpoint was OS. Secondary endpoints included assessment of patient well-being using the EORTC QLQ-C30 questionnaire. Platelets support tumor growth and metastasis and platelet counts increase during cancer progression. IL-1α on platelets may be a target of Xilonix and thus platelet count was a key pharmacodynamic measure. Results: 40 patients were enrolled between March 2013 and July 2014, at which time the study was halted to revise inclusion criteria to reduce screen failures. An eligibility violation excluded 1 Xilonix patient from analysis (Xilonix n=19, MA n=20). MA treatment arm had a 39% shorter median OS (2.0 versus 2.8 months) and a trend in increased risk of death (hazard ratio 2.17, p=0.17). Physical and role function worsened in patients receiving megesterol (median change of -13.3 (p=0.02), -16.7 (p=0.02) respectively), whereas in Xilonix treated patients these functions did not decline during therapy (median change 0, p=0.88 and 0, p=0.69, respectively). Xilonix patients had treatment-related reduction in platelets compared to the MA group (median -60,000/mm3, vs 10,000/mm3, p=0.03). No infusion reactions, no discontinuations due to adverse events (AEs) and no related SAEs were reported for Xilonix. Conclusions: The trend in OS for Xilonix patients was encouraging and consistent with improved function and intended pharmacodynamic activity. An amended Phase III protocol has been developed to simplify enrollment for an ongoing study of Xilonix in an advanced CRC population. (NCT01767857) Clinical trial information: NCT01767857.
A phosphoramidate ProTide (NUC-1031) and acquired and intrinsic resistance to gemcitabine.
Authors: C. McGuigan, N. A. Habib, H. S. Wasan, H. Gabra, L. R. Jiao, M. Slusarczyk, J. A. Chabot, M. W. Saif
Journal: Journal of Clinical Oncology (2011)

e13540 Background: Resistance to gemcitabine is a major problem in the treatment of cancer. The key resistance mechanisms associated with gemcitabine are: lack of nucleoside transporters; lack of kinases for phosphorylation; and/or, rapid metabolism by deaminases. Resistance results in complete response rates of less than 10% in pancreatic cancer. The addition of a phosphoramidate ProTide moiety to gemcitabine enables: passive entry into the cell, by-passing the reliance on transporters; reduced reliance on kinases for phosphorylation; and, less susceptibility to deamination. Methods: The ProTide (NUC-1031) was compared to the parent molecule (gemcitabine) in two pancreatic tumor xenograft models: Mia-Pa-Ca-2 (n=40), which is partially responsive to gemcitabine; and BxPC-3 (n=40), which is resistant. Two dose regimens for each tumor type were used, with NUC-1031 administered IP at doses of 0.076 or 0.19 mMol/kg when tumors had reached 150 - 200mm3. The objective was to determine the ability of a novel agent (NUC-1031) to overcome gemcitabine resistance by measuring tumor growth in partially responsive and resistant pancreatic cell lines. Results: The anti-tumor effect of NUC-1031 was greater and longer lasting than that of gemcitabine and control in both cell lines. NUC-1031 inhibition of tumor growth was significantly different from control in Mia-Pa-Ca-2 on days 4, 11, 14, 18, 21 and 25, and in BxPC-3 cells on days 25, 29, 33 and 37. In Mia-Pa-Ca-2 the tumor volume decreased immediately after first dosing and held at low levels until the end of the experiment. NUC-1031 was well tolerated and animals lost <2% body weight on treatment and this was regained rapidly after cessation of treatment. Conclusions: NUC-1031 showed statistically significant reduction in pancreatic tumor volume compared with gemcitabine and control. A phase I/II study of NUC-1031 in resistant/refractory pancreatic cancer is scheduled.