tbuckley/cabot-search huggingface dataset:
The impact of HistoScannin in prostate cancer detection: A sextant-specific analysis of detection and on tumor volume.
Authors: Daniel Porres, David J. K. P. Pfister, Timur H. Kuru, Axel Heidenreich
Journal: Journal of Clinical Oncology (2015)

96 Background: In the search of optimized screening for prostate cancer (PCa), HistoScanning (HS) has been introduced to support detection and assessment of cancer foci. The aim of our study was the evaluation of the impact of HS in the diagnosis of prostate cancer by a comparison with the histopathological results after prostatectomy. Methods: 282 patients between 37 and 75 years with histologically confirmed, organ-confined PCa that were scheduled for radical prostatectomy underwent transrectal ultrasound prior to surgery. HS was evaluated compared to histology that was performed on removed prostates as to: 1) prediction of overall tumor volume and 2) accuracy of HS in detection of PCa lesions bigger than 0.2 or 0.5 ml, respectively, separated for each sextant. Results: HS tends to underestimate volume of cancerous lesions, particularly larger lesions &gt; 8 ml. Using a 0.2 ml detection threshold, specificity and sensitivity of HS was between 29%-68% and 46-78%, depending on the sextant. For a 0.5 ml detection threshold, sextant-specific specificity increased to 59-92% and sensitivity decreased to 16-54%. Stratification according to pre-operational PSA-values did not improve performance characteristics of HS. Separate analysis of data from low grade tumor after d’Amico criteria showed that HS is not able to reliably detect these tumors. Conclusions: Overall, our study does not support a significant contribution of HS to PCa diagnostics.
Use of disseminated tumor cells to predict outcome in patients with stage I-III breast cancer.
Authors: Sarah Marie Gainer, Savitri Krishnamurthy, Anirban Bhattacharyya, Ashutosh Lodhi, Carolyn S. Hall, Isabelle Bedrosian, Henry Mark Kuerer, Anthony Lucci
Journal: Journal of Clinical Oncology (2012)

119 Background: Published studies from Europe have shown the presence of disseminated tumor cells (DTCs) to independently predict outcomes in patients with non-metastatic breast cancer. The purpose of this study was to assess the experience with DTCs at a tertiary cancer center and to see if these cells indeed predict outcomes in patients with stage I-III breast cancer. Methods: Clinical stage I-III breast cancer patients seen at a single tertiary cancer center provided consent to participate in an IRB-approved study involving collection of bone marrow (5 ml x 2 tubes) at the time of surgery for their primary breast cancer. DTCs were assessed by anti-CK antibody cocktail (AE1/AE3, CAM5.2, MNF 116, CK 8 and 18) following cytospin. A positive result was defined as the presence of one or more cells per 5 ml of bone marrow. Statistical analyses used chi-square and Fischer’s exact tests. Results: Three hundred and sixty-six patients were prospectively enrolled. Mean age was 53 years. Median follow-up was 32 months. DTCs were identified in 109 patients (30%). Ten percent of patients with DTCs (11/109) and 3% of patients without DTCs (8/257) died (p = 0.009). Overall survival (OS) in patients with DTCs was 30 months vs. 31 months in those without DTCs. DTCs did not predict relapse free survival (P=NS). On multivariate analysis the presence of DTCs was an independent predictor of worse overall survival (p &lt; 0.0001). No correlation was observed between the presence of DTCs and lymph node metastases and/or other clinicopathologic variables. Conclusions: The presence of DTCs was an independent predictor of worse OS in patients with stage I-III breast cancer. Consideration should be given to the utilization of DTCs as predictors of outcome in clinical practice.
Traditional Japanese oral mucositis medicine hangeshashinto to upregulate antimicrobial peptides in human salivary gland cells.
Authors: Toru Kono, Atsushi Kaneko, Yuji Omiya, Kanako Miyano, Yasuhito Uezono
Journal: Journal of Clinical Oncology (2014)

517 Background: The cause of chemotherapy-induced oral mucositis (COM) is thought to be direct injury and indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapy-induced neutropenia. We previously found that gargling with hangeshashinto (HST), a traditional Japanese medicine, was effective for treatment of COM. Focusing on the pain and inflammation of COM, we reported at ASCO-GI 2013 and DDW 2013 that HST exhibited ameliorating effects in a hamster model of COM and multi-targeted effects on prostaglandin E2 (PGE2) production, followed by identification of active ingredients by PGE2 culture systems and LC-MS/MS. Our aim in this study was to address whether HST affects protective oral constituents. Methods: Human oral keratinocytes (HOK) and human salivary gland (HSG) cells were used for cell culture assays. Expression levels of mRNAs for antimicrobial peptides, extracellular matrixes, keratinocyte growth factor, amylase, COX-1/COX-2, and cNOS/iNOS in cells with or without HST (10–300 μg/mL) treatment were measured by RT-PCR. Results: HST increased gene expressions of some antimicrobial peptides (defensin β1, adrenomedullin, cathelicidin antimicrobial peptide), and amylase 1A in HSG cells. Further, HST dramatically inhibited COX-2 and iNOS mRNAs in IL-1β treated HOK cells, while it exerted no or little effect on expressions of any protective oral constituents in non-treated HOK cells. A random test to identify the ingredients that increase defensin β1 revealed that isoquinoline alkaloids like berberine were active. Conclusions: HST is expected to maintain oral homeostasis through two paths: increased production of antimicrobial peptides and decreased oral damage induced by excessive prostanoids and nitric oxide. HST thus functions as a multitarget agent, indicating that it may be beneficial in COM treatment.
Molecular Subtyping and Risk Stratification for the Classification of Myeloma
Authors: Caleb K. Stein, Faith E Davies, Christoph Heuck, Niels Weinhold, Shweta S. Chavan, Brian A Walker, Sharmilan Thanendrarajan, Joshua Epstein, Shmuel Yaccoby, Maurizio Zangari, Frits van Rhee, Martin F Kaiser, Graham H Jackson, Pieter Sonneveld, Hartmut Goldschmidt, Peter Leif Bergsagel, Bart Barlogie, Gareth J Morgan
Journal: Blood (2015)
Effect of regorafenib and TAS-102 in metastatic colorectal cancer (mCRC) patients on survival in salvage line with different toxicity profile.
Authors: Naotoshi Sugimoto, Tetsuhiro Yoshinami, Sachiko Yamamoto, Toshinari Yagi, Fumio Imamura
Journal: Journal of Clinical Oncology (2016)

763 Background: In the CORRECT study, regorafenib has survival benefits in patients with metastatic colorectal cancer (mCRC) in salvage line. In the J-003 and RECOURSE study, TAS-102 has also survival benefit in them, too. But no randomized study is existed about the comparison between regorafenib and TAS-102. So we retrospectively compared the efficacy and toxicity of regorafenib and TAS-102 in patients with mCRC for salvage line in our hospital. Methods: The selection criteria were pathologically proven mCRC; 20 years or older; had a previous treatment history of two or more regimens of standard chemotherapy; no prior regorafenib and TAS-102 therapy; performance status 0-1; able to oral intake; and adequate organ functions. The patients in regorafenib group, regorafenib 160mg/body was given orally once daily for 21days followed by a 7-day rest. In TAS-102 group, TAS-102 35mg/m2 was given orally twice daily 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period. Results: The analysis covered 51 patients over the period from October 2009 to June 2015.The median age was 67 years (range 33-79); 29 males and 22 females; PS 0/1 score 19/32; 23 patients were treated regorafenib and 28 patients were treated TAS-102.Progression-free survival and overall survival were 2.6 and 10.6 months with regorafenib and 3.2 and 9.7 months with TAS-102 (no significant difference). The rate of grade 3-4 toxicity were hypertension (35%), hand-foot syndrome(35%), AST/ALT increased(12%) in regorafenib group, and leucopenia (15%), neutropenia (35%), anemia(10%) in TAS-102 group. There was no treatment death in both groups. Conclusions: Both regorafenib and TAS-102 give mCRC patients survival benefit in salvage line with different toxicity profile.
The relationship of breast density, BMI, and menopausal status in mammography and MRI.
Authors: Jennifer Chun, Ana Paula Refinetti, Ana Klautau Leite, Freya Ruth Schnabel, Tsivia Hochman, Linda Moy
Journal: Journal of Clinical Oncology (2012)

36 Background: Mammographic breast density (BD) is associated with a 4- to 6-fold increased risk for developing breast cancer. A previous study has shown that background parenchymal enhancement (BPE) as measured on MRI can be correlated with breast cancer risk. Being overweight or obese is also an established risk factor for breast cancer. The purpose of this study was to evaluate the relationship between BD, BPE, FGT (assessment of fibroglandular tissue with contiguous MR images), and BMI in pre- and post-menopausal women. Methods: The Breast Cancer Database at NYU Langone Medical Center was queried and a total of 187 women had completed both screening mammograms and MRIs. Variables of interest included BD, BPE, FGT, BMI, and menopausal status. BD was defined by ACR classifications 1-4. FGT was assessed on a similar scale 1-4. BPE was categorized as minimal, mild, moderate, or marked. BMI (kg/m 2 ) was grouped as underweight (≤18), normal (19-24), overweight (25-29), and obese (≥30). Statistical analyses were performed using Spearman Correlation Coefficients and Cochran Mantel Haenszel tests. Results: The median age in our cohort was 51 years (range 22-87 years). The majority were Caucasian (71%) with early stage breast cancers (75%). There was no correlation between BD and BPE (r=0.132) and a weak correlation between BPE and FGT (r=0.312). However, there was a strong positive correlation between BD and FGT (r=0.733). After adjusting for menopausal status, these correlations remained the same. When we stratified by BMI, we found the strongest positive association between BD and FGT among women with BMI≥25 (r=0.715). Conclusions: In our cohort of newly diagnosed breast cancer patients, BD and BPE were not correlated, even after adjusting for menopausal status. This implies that BD and BPE may represent different characteristics of breast tissue and may have different implications. We found a strong correlation between FGT and BD. This association was strongest in women who were overweight and obese. FGT is a more objective and quantitative measurement of breast density and may be more useful in quantitative breast cancer risk assessment.Further studies are necessary to determine if BPE and FGT are independent risk factors for breast cancer.
Presentation of contralateral axillary involvement from breast cancer.
Authors: Vanessa Leilani Prowler, John Kiluk, Marie Catherine Lee, Nazanin Khakpour, Christine Laronga, Charles E. Cox
Journal: Journal of Clinical Oncology (2012)

49 Background: Metastatic breast cancer to the contralateral axilla is defined as stage IV disease. We postulate that metastatic disease to the contralateral axilla is secondary to extension of aggressive, local regional disease rather than distant metastatic disease and may have a better outcome. Methods: An IRB-approved retrospective review of breast cancer cases presenting to a single institution between January 2005 and December 2011 was performed to identify cases with contralateral axillary disease. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented metastasis to the contralateral axilla without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Results: Thirteen pts were identified that fulfilled eligibility criteria. The average age was 53 years (range 26.3-72.2) with 12/13 (92%) pts presenting with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at presentation or local recurrence. Contralateral metastatic disease occurred synchronously with the initial primary tumor (3pts, 23%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor in (3pts, 23%), and metachronously with a local recurrence in (2pts, 15%). Resection of involved contralateral nodes was performed in 10/13 (77%) pts; 5/13 (38%) patients received contralateral axillary radiation; all 13 (100%) received systemic therapy. 9/13 pts (69%) developed distant metastatic disease with a mean follow up of 2.6 years (range 0.3-6.8 years). 3/13 pts (23%) have no evidence of disease at a mean follow up of 4.7 years (range 1.5-6.8). Conclusions: Contralateral axillary spread of breast cancer carries a poor prognosis but may have different prognostic implications than metastatic disease. Contralateral axillary metastatic disease may occur through dermal lymphatic spread and requires multidisciplinary management. Further study is warranted on the prognosis and management of these challenging and rare cases.
Intraoperative radiotherapy (IORT) in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for locally advanced and borderline resectable adenocarcinoma of the pancreas (PDAC).
Authors: Florence K. Keane, Jennifer Yon-Li Wo, Cristina Ferrone, Jeffrey W. Clark, Lawrence Scott Blaszkowsky, Jill N. Allen, Eunice Lee Kwak, David P. Ryan, Keith D Lillemoe, Carlos Fernandez-del Castillo, Theodore S. Hong
Journal: Journal of Clinical Oncology (2016)

393 Background: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic PDAC have prompted incorporation of these regimens into neoadjuvant treatment of PDAC. While some patients are still found to be unresectable after neoadjuvant treatment, others are able to undergo resection. Our aims are to evaluate outcomes and toxicities associated with use of IORT in this setting. Methods: We retrospectively analyzed records of 85 patients with locally advanced/ borderline resectable PDAC who received neoadjuvant treatment with chemotherapy and/or chemoradiotherapy followed by surgical exploration in an IORT-equipped operating suite between 2010-2015. Descriptive statistics were used to compare surgical outcomes. Survival analysis was used to calculate overall survival (OS). Results: Of 85 patients, 49 (57.6%) underwent resection after neoadjuvant treatment, 27 (31.8%) were unresectable, and 9 (10.6%) were found to have distant metastases. 24 of 49 patients who underwent resection received IORT for close/positive margins on intraoperative frozen section. There was no significant difference in operative times, postoperative complications, or operative morbidity in patients who underwent resection and IORT vs those who underwent resection alone. Median OS was 31.1 months in patients who underwent resection alone and 35.1 months in patients who underwent resection and IORT. Despite the increased incidence of close/ positive margins in patients who underwent resection and IORT, the rates of local recurrence were similar to those who underwent resection alone. 26 of 27 patients with unresectable disease upon exploration received IORT. Median OS was 20.5 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative time or morbidity. Conclusions: IORT is not associated with increased toxicity when used in conjunction with resection or surgical exploration after neoadjuvant therapy. IORT resulted in median OS of 35 months for patients with close or positive margins and of 20.5 months for patients with unresectable disease.
Effects of body mass index (BMI) on plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment.
Authors: G. Lunardi, L. Del Mastro, C. Bighin, G. Bisagni, P. Driol, O. Garrone, S. Giraudi, P. Marroni, P. Piccioli, R. Ponzone, M. Porpiglia, M. Venturini
Journal: Journal of Clinical Oncology (2011)

515 Background: BMI is associated with an increased risk of BC in postmenopausal women. Moreover, BC overweight women have poorer prognosis compared to women with normal weight. Data from ATAC (the anastrozole, tamoxifen alone or in combination study) trial reported that obesity reduce the efficacy of the aromatase inhibitor (AI) anastrozole in early BC. One possible explanation is that higher estrogens levels resulting from high BMI may lead to lower efficacy of the AI treatment. No clear data are available about the effects of BMI on estrogen circulating levels during AI treatment, and if the increase of AI dosage may result in more complete estrogen suppression in overweight women. Methods: We evaluated the correlation between BMI and plasma concentration of ES in postmenopausal women with early BC during adjuvant treatment with L (2.5 mg/die). Patients were participating in two prospective Italian clinical trials (GIM4 and GIM5) evaluating L treatments after adjuvant tamoxifen. Plasma samples were obtainedafter at least six weeks of L therapy. After a non-chromatographic cleaning procedure of samples, plasma ES levels were evaluated by RIA. Ln values for plasma ES were used for statistics. Geometricmeans and 95% confidence interval (CI) were used as summary measures. Results: ES plasma concentration and BMI were evaluated in 370 women. Median treatment duration was 49wks (range 6-201wks). Median age of patients was 60 yrs (range 34-84 yrs). Table shows data regarding ES concentrations and BMI of patients. Conclusions: Circulating ES levels during L (2.5 mg/die) treatment were super imposable in all BMI groups. Our data indicate that whether BMI influences AI efficacy, this is not due to an insufficient suppression of aromatase activity in women with higher BMI. Increasing the dose of AI to further reduce ES levels in high BMI patients is a questionable way to increase AI efficacy. BMI, kg/m2 No. of pts % ES geom mean (pg/mL) 95% CI <23.0 85 23 21.7 21.2-22.5 23.0-24.9 65 18 20.2 19.6-20.9 25.0-27.9 111 30 24.2 23.8-24.6 28.0-29.9 43 12 22.5 21.5-23.6 >30.0 66 17 19.8 19.2-20.4
Primed-GCSF BMT After Reduced Intensity Conditioning (RIC) In Association with Rituximab for Patients (pts) with Refractory CD20+ Aggressive Lymphomas..
Authors: Rodolfo Calixto, Fabiana Ostronoff, Mauricio Ostronoff, Alexandre Sucupira, Djenane Manso, ANA Patricia Souto Maior, Rodrigo Florencio, Monique Martins, Luis Fabio Botelho, Mariana Coutinho
Journal: Blood (2010)
A phase I trial of concurrent cetuximab (CET), cisplatin (CDDP), and radiation therapy (RT) women with locally advanced cervical cancer (CXCA): A GOG study.
Authors: K. N. Moore, M. Sill, D. S. Miller, P. Disilvestro, K. De Geest, P. G. Rose, H. R. Cardenes, R. S. Mannel, J. H. Farley, R. J. Schilder, P. M. Fracasso
Journal: Journal of Clinical Oncology (2011)

5032 Background: EGFR over-expression is correlated with poor prognosis and decreased survival in CXCA. This study aimed to assess the safety of concurrent chemo-radiation with CET in the treatment of women with CXCA. Methods: Women with untreated advanced CXCA received escalating doses of weekly CDDP (Dose Level 1and 2 were 30 and 40 mg/m2, respectively) and weekly CET (loading dose of 400mg/m2 followed by 250 mg/m2) x 6 concurrent with 45 Gy pelvic RT with brachy therapy. Women with lymph node + disease received an additional 45 Gy to the para-aortic LN (EFRT). The escalation phase evaluated the regimens in a standard 3+3 design. The feasibility phase evaluated the regimens in a 20 patient 2-stage group sequential design. The primary endpoint was dose-limiting toxicities with 20% and 40% considered safe and unsafe, respectively. Results: In the women receiving only pelvic RT, 10 were treated during the dose escalation and 21 in the feasibility phase. In the dose escalation, CDDP 30 mg/m2 resulted in a DLT (febrile neutropenia, FN) and at 40mg/m2 of CDDP led to 2 DLTs (Grade 3 acneiform rash refractory to management and 1 delay of RT >8 weeks). In the feasibility phase with CDDP 30 mg/m2, there are no DLTs in 16 patients, 1 is non-evaluable, and 4 are ongoing. (90% CI 0.0 – 36.1% or less). Of the 24 women with a CET-associated rash, 4 were Grade 3. One woman had a CET hypersensitivity reaction (HSR). Median RT completion was 50 days (42-70). In women receiving EFRT, 9 were treated at the first dose level with one DLT (Grade 3 mucositis) and 24 in the feasibility phase with 8 DLTs and 2 were non-evaluable (90% CI 22.5 – 100%). DLTs included 1 woman each with Grade 3 nausea/vomiting (N/V) and Grade 3 FN, Grade 4 N/V, Grade 3 abdominal pain, Grade 4 thromboembolism, Grade 4 thrombocytopenia, and two with Grade 3 mucositis. In the 22 women with CET-associated rash only 1 had Grade 3. Two women had a CET HSR. Median RT completion was 56 days (36-74). Conclusions: For women receiving only pelvic RT for CXCA, the combination of CET, CDDP in addition to pelvic RT is feasible. For women receiving EFRT, there is a high incidence of gastrointestinal and metabolic toxicity that challenges the feasibility of this regimen.
Association of MRI and locoregional recurrence (LRR) rates in ductal carcinoma in situ (DCIS) patients treated with or without radiation therapy (RT).
Authors: Melissa Louise Pilewskie, Cristina Olcese, Anne Eaton, Sujata Patil, Elizabeth Ann Morris, Monica Morrow, Kimberly J. Van Zee
Journal: Journal of Clinical Oncology (2013)

57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 months there were 184 IBTRs; 5-year LRR rates were 8.5% (MRI) and 7.2% (no MRI) (p = 0.52), and 8-year rates were 14.6% and 10.2%, respectively. MRI was not associated with lower LRR rates after adjustment for age, menopausal status, family history, presentation, adjuvant therapy, margin status, number of excisions, and year of surgery in both the entire cohort and in the subgroup who did not receive RT. Select factors from multivariate analysis for patients with all covariates available are shown in the Table. Conclusions: We observed no association between perioperative MRI and LRR rates for patients with DCIS, even when RT was not given. The benefit of perioperative MRI for DCIS remains uncertain. [Table: see text]