tbuckley/cabot-search huggingface dataset:
Utilization of post-lumpectomy radiation therapy in women 70 years of age or older: A report from the National Cancer Data Base.
Authors: Katharine Yao, Tomasz Czechura, Dezheng Huo, David Porter Winchester, Stephen B. Edge, David J. Winchester
Journal: Journal of Clinical Oncology (2012)

1033 Background: The Cancer and Leukemia Group B (CALGB) 9343 trial published in 2004 showed no overall survival benefit from radiation in patients &gt;70 years old with estrogen receptor (ER) positive, pT1 tumors with the use of tamoxifen. We tested the hypothesis that the use of radiotherapy decreased in this group of patients following publication of the trial, utilizing the National Cancer Data Base. Methods: 34,853 breast cancer patients 70 years or older with pT1N0/NX, ER positive tumors who underwent a lumpectomy between 2004 and 2007 were studied. Chi-square tests and logistic regression models were used to determine trends and factors related to the use of radiation. Results: The use of radiation decreased from 70.6% in 2004 to 66.4% in 2005, 66.6% in 2006, and 67.2% in 2007 (p&lt;0.001). The use of standard external beam radiation decreased from 58.8% in 2004 to 45.8% in 2007 while the use of accelerated partial breast radiation using brachytherapy (APBI) increased from 4.5% to 10.0%, IMRT radiation from 3.1% to 5.3%, and 3D conformal radiation from 3.7% to 5.7% (p&lt;0.001). Patients between the ages of 86+ years old were less likely to undergo radiation than patients 70-75 years old (OR=0.12, 95% CI: 0.11-0.13). Asian Pacific Islanders were more likely to undergo radiation than whites (OR=1.39, 95% CI: 1.13-1.70). In community cancer programs, 67% patients received radiation, compared to 69.1% in comprehensive community programs and 65.5% in academic programs (p&lt;0.001). The use of radiation varied by facility location; 73.5% of facilities located in the Midwest radiated these patients as opposed to 62.6% in the South. In patients who had no nodes examined, 37% underwent radiation as opposed to 74% who did have nodes examined (p&lt;0.001). Likewise, 79.4% of patients who received hormone therapy underwent radiation as opposed to 54.6% of patients who did not receive hormonal therapy (p&lt;0.001). Conclusions: The use of radiation therapy decreased only slightly and remained high in women with ER+ stage I breast cancer over the age of 70, despite findings from the CALGB 9343 study. However, there was a large shift in radiation modality over the study period in the older patients.
Change in mammographic density with metformin use: A companion study to NCIC study MA.32.
Authors: Marie E. Wood, Rui Qin, Huong T. Le-Petross, E Shelley Hwang, Jennifer A. Ligibel, Ingrid A. Mayer, James Roger Marshall, Pamela Jean Goodwin
Journal: Journal of Clinical Oncology (2013)

TPS1608 Background: Metformin may have growth inhibitory effects on many cancer types including breast cancer. NCIC MA.32 is a randomized placebo-controlled trial examining the effects of 5 years of metformin in women with breast cancer ( http://clinicaltrials.gov/show/NCT01101438 ). This trial offers us the opportunity to explore the effects of metformin on breast cancer biomarkers to gain an understanding of the potential chemo preventive effects of this drug. The primary aim of this companion to MA.32 (Alliance trial # A211201) is to examine the effects of 1 year of metformin vs placebo on breast density for women with Estrogen Receptor negative (ER-) breast cancer. Secondary aims of this study include: evaluation of breast density following 2 years of metformin use, and correlation of density with fasting insulin, glucose and Homeostasis Model Assessment (HOMA). Exploratory aims include examination of the effects of metformin on second cancer rates. Methods: Eligible women must have been enrolled on MA.32 (North America accrual completed January 23, 2013), have hormone receptor-negative breast cancer, and breast composition on mammography &gt;25% glandular density, have a digital mammogram within 12 months of registration on MA.32 and have an intact, unaffected contralateral breast. Women enrolled on this study must provide menstrual cycle data (if premenopausal) and digital mammograms. All other study related information is gathered through participation in MA.32. Mammographic density will be calculated using Cumulus software (the Boyd method). Our accrual goal is 458 patients (229 per arm) and with an assumption of 20% drop out due to drug intolerance and another 20% due to ineligibility. Therefore, with a sample size of 274 (137 per arm) we will have at least 85% power to detect a 4% difference between study arms, i.e., 5% change from baseline to one year of treatment for metformin vs. 1% for placebo, using the two-sided two-sample t-test at a significance level of 5%. This study was activated in the United States on 8/22/2012 and 15 patients have been accrued to date. This study is sponsored by the NCI and the Alliance for clinical trials. Clinical trial information: NCT01666171.
What is the significance of CCR5 status in HIV-associated non-Nodgkin lymphoma (NHL)?
Authors: John Zaia, Karl Gaal, Joycelynne Palmer, Shirley Li, Jennifer Simpson, Stephen J. Forman, Amrita Y. Krishnan
Journal: Journal of Clinical Oncology (2012)

e18542 Background: The chemokine receptor CCR5 is a co-receptor for HIV. Carriers of the delta 32 gene (D32) mutation who lack CCR5 are protected from HIV infection by the R5 variant of the virus. Heterozygotes have slower progression to AIDS. For HIV NHL patients, the effects of the presence of the gene mutation are unclear. Methods: 93samples obtained from the ASCR (AIDS and Cancer Specimen Resource ) tissue bank of patients with HIV NHL were assayed for the presence of the mutation. We then studied if there was an association with the mutation and subtype of diffuse large cell lymphoma (DLBCL) (germinal center GC vs non GC), EBV status, or cell activation markers. Date of NHL diagnosis was from 1989 to 2005. Samples predating 1996 were characterized as pre HAART (highly active antiretroviral therapy) and all others post HAART. Results: There were 87 DLBCL, 3 plasmablastic lymphoma, 2 plasmacytoma and 1 anaplastic large cell T-cell subtype. Of the DLBCL, 48 were GC subtype and 39 were non GC subtype. GC subtype was 8.3 % (4/48) heterozygous for the D32. Non GCB subtype was 10.3 % (4/29) heterozygous. There was no difference in the percent heterozygosity for D32 pre or post HAART (14.8% vs 11.1%). The pre HAART specimens had greater EBV+ (44% vs 29% P=0.16) and more frequent BLIMP(B lymphocyte induced maturation protein) positivity ( 27% vs 17%. P=0.39) ). CCR5 heterozygous mutants were less often BLIMP positive (10% vs 21.4% P=0.68) and more often overexpressed p53 by immunostain (40% vs 23.9% P=0.47) compared to wild type CCR5. There was no correlation between EBV status and the presence of the mutation (36.3% vs 33.3%). Conclusions: CCR5 gene mutation status did not influence the subtype of DLCL. but the differences seen in BLIMP expression may have implications. Additional larger studies are needed to bear out suggested but statistically non-significant trends. BLIMP is a known repressor of p53. The overexpression of p53 and decreased BLIMP seen in CCR5 heterozygotes suggests alternate oncogenic pathways may be operative compared to wild type CCR5 lymphoma patients. Our ongoing clinical trial of HIV NHL pts undergoing transplant is assessing CCR5 status to see if there is a correlation with disease free and overall survival.
Phase II trial of concomitant hyperfractionated-accelerated radiotherapy (HART) with cisplatin (Cis) plus cetuximab (Cet) for locoregionally advanced inoperable squamous cell carcinoma of the head and neck (LA SCCHN): Feasibility and 2-year OS.
Authors: Thomas Kuhnt, Andreas Schreiber, Anett Pirnasch, Matthias Hautmann, Peter Hass, Frank Sieker, Rita Engenhart- Cabilic, Michael Richter, Kathrin Dellas, Juergen Dunst
Journal: Journal of Clinical Oncology (2013)

6077 Background: To report the mature data of a prospective phase II-trial to investigate the feasibility, efficacy and safety of combination therapy with Cis, Cet and HART in LA SCCHN. Methods: Patients (pts) with stage III or IV, M0 SCCHN were enrolled and treated with an initial dose of Cet (400 mg/m 2 ), followed by weekly dose of 250 mg/m² before HART, which started with a prescribed dosage of 2.0 Gy per day for three weeks followed by 1.4 Gy twice daily to a total dosage of 70.6 Gy to the gross tumor volume. Cis 40 mg/m² was administered weekly for 6 weeks. Results: From February 2007 through November 2010, 74 pts were enrolled, 68 pts with a median age of 56 years (range 37 to 69 years) were evaluable. 50% had oropharyngeal SCC. Of these, 65 pts (96%) received &gt; 90% RT dosage, 50 pts (74%) &gt; 90% Cet dosage and 56 pts (82%) &gt; 4 cycles Cis 40 mg/m². 3D-CRT was used in 72% and 28 patients are currently still being followed up. The most common grade &gt;3 toxicities were mucositis (59%) and dysphagia (52%). Cet-related grade &gt;2- toxicities included dermatitis (15%) within the radiotherapy portals. Nine (14%) pts were missing for response evaluation (e.g. withdrawal of consent). Complete remission rate [(p)CR] was observed in 23/68 (34%) including with 16 pts (24%) who reached a CR of the primary tumor but a selective lymph node dissection was performed 6-8 weeks after end of radiation treatment for residual neck disease. Furthermore, partial remission (PR) was achieved in 29/68 (43%), so an overall response (OR) of 52/68 (77%) was reached. No change/stable disease occurred in 3/68 pts (4%), progressive disease (PD) occurred in 1 pt (1%) and 3 pts (4%) have died due to disease progression. The 2-year overall survival and disease-free survival were 64.2% and 45.3%, respectively. Conclusions: Combination therapy of LA SCCHN consisting of HART-Cis-Cet is an highly active regimen. The addition of Cet to weekly Cis and daily RT was well tolerated and resulted in encouraging local disease control and survival rates. Clinical trial information: 2005-000355-15.
Proton beam therapy (PBT) and concurrent chemotherapy using cisplatin (CDDP) and vinorelbine (VNR) for locally advanced non-small cell lung cancer (NSCLC).
Authors: Seiji Niho, Atsushi Motegi, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Hironobu Ohmatsu, Masamichi Toshima, Satoko Arahira, Masakatsu Onozawa, Koichi Goto, Tetsuo Akimoto
Journal: Journal of Clinical Oncology (2015)

e18525 Background: PBT with concurrent chemotherapy for the treatment of patients (pts) with locally advanced NSCLC was introduced at our hospital in Dec 2011. We retrospectively evaluated the treatment compliance, toxicity, and efficacy of PBT with concurrent chemotherapy using CDDP plus VNR in pts with locally advanced NSCLC. Methods: The medical records of NSCLC pts who received PBT with concurrent chemotherapy with 80mg/m2 of CDDP (d1) and 20mg/m2 of VNR (d1, 8), q4w, at the National Cancer Center Hospital East between Dec 2011 and Aug 2014 were reviewed. Results: Thirty-three pts received PBT and concurrent chemotherapy with CDDP plus VNR. The patient characteristics were as follows: median age 65 years (44-74 years); 23 pts were male; 20 pts had adenocarcinoma, 11 had squamous cell carcinoma, and 2 had NSCLC-NOS; 6 pts had stage II disease, 8 pts had stage IIIA disease, 16 had stage IIIB disease, and 3 developed local recurrence after surgery. The reasons for the selection of PBT included the pts’ request (n = 21), and lack of suitability of the patient for radical photon radiotherapy due to excessive V20 or dose to the spinal cord (n = 12). The median lung V20 in the PBT was 23% (range: 10-32). All pts received the planned PBT dose (60 Gy [n = 16] or 66 Gy [n = 17]). PBT was suspended in 9 pts because of the development of febrile neutropenia (n = 5), esophagitis (n = 3), or fever (n = 1). Three pts (9%) developed grade 3 esophagitis. The grade 2 toxicities included esophagitis (n = 14), dermatitis (n = 10), and pneumonitis (n = 2). There were no cases of grade 3 pneumonitis. The response rate was 58% (95% CI, 39-45). Disease progression was observed in 17 pts. In-field recurrence was observed in 6 pts, distant metastasis was observed in 12 pts, and both types of recurrence were observed in 1 patient. The median progression-free survival was 10.6 months (95% CI, 6.1-15.2). The OS data are immature. Conclusions: PBT and concurrent chemotherapy with CDDP plus VNR are feasible, although the potential complications, such as radiation esophagitis and dermatitis, seem to be rather severe as compared with the severity of these complications encountered during standard chemoradiotherapy using photons.
Resectable central nervous system (CNS) metastases from colorectal cancer (CRC): Patient characteristics, outcome, and molecular correlations between primary tumor and metastases.
Authors: Elisa Bellini, Mario Airoldi, Paola Francia di Celle, Sara Mariani, Roberta Ruda, Riccardo Soffietti
Journal: Journal of Clinical Oncology (2013)

2084 Background: Aim of this study is to describe clinical characteristics and outcome of CRC patients with CNS metastases undergone to surgical resection, and report preliminary data on the comparison between molecular aspects of primary tumor and metastasis. Methods: Thirty-two pts (17 males, 15 females) with a median age of 65 yrs (range 38-80 yrs) with brain metastases from colon (23 pts, 72%) or rectum (9 pts; 28% ) adenocarcinoma (G1 in 3 pts, 9%; G2 in 12 pts, 37%; G3 in 17 pts, 53%) underwent total surgical resection. Primary tumor TNM was: T2 in 1 pt (3%), T3 in 22 pts (69%) and T4 in 9 pts (28 %); no patient had N0 status , 10 pts had N1 lesions (31%) and 22 pts had N2 (69%) lesions; 25 pts were M0 (78%) while 7 (22%) were M1. Results: One patient had neurological symptoms as first manifestation of CRC; the other cases had metachronous metastases in the SNC after a median of 35.5 months (range 4-96). The CNS location was cerebellum in 15 pts (47 %), frontal lobe in 9 pts (28 %), spinal cord in 5 pts (16% ), parietal lobe in 2 pts (6%) and occipital lobe in 1 pt (3%). Perioperative mortality was 3%. Ten pts (31%) received post-operative whole-brain radiotherapy. Six patient (19%) had local recurrence. Primary cancers harbored a K-RAS mutation in 13 cases (41%) and a BRAF mutation in 1 case (3%). Preliminary data in 20 pts indicate a 100% mutation concordance between primary tumor and CNS metastases. Conclusions: Resectable CNS metastases from CRC adenocarcinoma were seen after a median of 3 yrs originating from T3-4 N1-2 M0-1 lesions. The preferential locations in the CNS were cerebellum and frontal lobe, being spinal metastases relatively frequent. The total resection was feasible with a good long-term local control ; the whole-brain irradiation given to one third of cases could have contributed to local control. Almost all pts died of extranervous metastases. There was a concordance of KRAS and BRAF mutation in primary and CNS lesions.
Clinical characteristics at diagnosis of patients who survive more than 5 years after diagnosis of metastatic colorectal cancer (mCRC).
Authors: Manuel Cruz Abrahao, Joao Paulo Velloso Medrado Santos, Thayse Pavan, Paulo M. Hoff, Artur Katz, Jorge Sabbaga, Fernanda Azevedo, Daniela Freitas, Daniel F. Saragiotto, Frederico Costa
Journal: Journal of Clinical Oncology (2013)

e14590 Background: Metastatic disease is a prevalent condition that will develop in close to 40% of patients diagnosed with colorectal cancer. Most patients with mCRC will eventually die due to tumor related causes. Advances in surgical intervention and systemic therapies have significantly increased the life expectancy of such patients. Only, a minority of patients with mCRC will survive more than 5 years. The clinical characteristics at initial presentation have not been reported in the era of novel therapies. Methods: All medical charts from patients with colorectal cancer consulted at HSL from 1998 to 2012 were reviewed. Patients with synchronous or metachronous mCRC were selected and only patients who survived more than 5 years from the date of confirmed diagnosis of metastasis were included in the analysis. Results: 1,406 patients with colorectal cancer were reviewed and 793 patients (56,4%) were confirmed with mCRC. 57 of them survived more than 5 years (4%). The clinical characteristics at diagnosis are presented in the Table. 93% of the patients are alive with a median follow-up of 88 months. 91% of them remained ECOG 0/1. The reported objective response to systemic therapy was 97% in first line, 79% in second line, and 66% in third line. All patients with liver only metastasis underwent surgery and 36% are disease-free with median follow-up of 107 months. Conclusions: Patients with mCRC who survived more than 5 years represent a distinctive group not identified by clinical characteristics at the initial presentation. They are highly sensitive to systemic therapy and this seems to be a good marker for patients who will have long survival. Our next step will be to attempt to identify molecular markers for those patients. [Table: see text]
Cyclophosphamide/fludarabine-based nonmyeloablative matched related/unrelated allotransplant for myelodysplasia.
Authors: Muhammad Rizwan-ul-Haq Khawaja, Larry Dean Cripe, Jennifer E. Schwartz, Patrick Kiel, Christopher A. Fausel, Hamid Sayar, Michael J. Robertson, Rafat Abonour, Kenneth Cornetta, Sherif Farag, Robert P Nelson
Journal: Journal of Clinical Oncology (2014)

7042 Background: Hematopoietic cell allotransplant (HCT) with reduced intensity conditioning (RIC) offers curative treatment for myelodysplasia (MDS) in patients that are traditionally excluded from myeloablative (MAT) HCT due to age or comorbidities. Concerns regarding disease control with this approach are based on retrospective data pooled from multiple institutions using different RIC regimens. Cyclophosphamide/fludaraine (Cy/Flu) is a minimal intensity RIC regimen which has not been independently compared to MAT. Methods: This retrospective study was conducted to compare disease control and survival outcomes of MAT versus Cy/Flu-based nonmyeloablative allotransplant (NMAT), performed at a single institution during 2000-2013. Results: Seventy-four patients underwent MAT (n=27) or NMAT (n=47) from a related (n=36) or unrelated (n=38) donor. Patients who received NMAT were older (mean, 57 vs. 44 years; p<0.001), were more likely to have ECOG performance status (PS) greater than zero (17% vs. 0%; p=0.024), to receive mobilized peripheral blood grafts (100% vs. 81%; p=0.005) and cyclosporine-based GVHD prophylaxis (68% vs. 31%; p=0.002) rather than tacrolimus/sirolimus-based prophylaxis. Distribution of related or unrelated donors and IPSS categories were similar in NMAT and MAT groups. Median follow-up was approximately 49 months. Median progression free survival (PFS) was 429 days after NMAT compared to 349 days after MAT (p=0.585); median overall survival (OS) was 488 days and 608 days (p=0.517), respectively. Eighty percent of patients achieved remission following NMAT compared to 71% following MAT (p=0.416). Twenty percent of patients after NMAT experienced progression versus 33% after MAT (p=0.248). After adjusting for age, IPSS categories, PS, donor source, graft source and GVHD prophylaxis, no statistically significant difference in PFS [HR 0.74 (95% CI 0.25-2.17)] or OS [HR 0.73 (95% CI 0.25-2.17)] was found between NMAT and MAT. Conclusions: Cy/Flu based NMAT may provide similar disease control and survival in MDS compared to MAT.
A randomized, multicenter, double-blind phase III study of palbociclib (PD-0332991), an oral CDK 4/6 inhibitor, plus letrozole versus placebo plus letrozole for the treatment of postmenopausal women with ER(+), HER2(–) breast cancer who have not received any prior systemic anticancer treatment for advanced disease.
Authors: Richard S. Finn, Veronique Dieras, Karen A. Gelmon, Nadia Harbeck, Stephen E. Jones, Maria Koehler, Miguel Martin, Hope S. Rugo, Seock-Ah Im, Masakazu Toi, Eric Roland Gauthier, Xin Huang, Sophia Randolph, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2013)

TPS652 Background: Palbociclib (PD-0332991) is an orally bioavailable selective inhibitor of CDK4/6 that prevents DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase. In a randomized phase II trial comparing palbociclib (PD-0332991) plus letrozole (P + L) to letrozole (L) in postmenopausal women with ER(+), HER2(–) advanced breast cancer (ABC) who had not received any prior systemic anticancer therapy for their advanced disease, P + L demonstrated significantly longer progression-free survival (PFS) vs L (26.1 vs 7.5 mo; HR = 0.37, P &lt; .001) and was generally well tolerated, with uncomplicated neutropenia as the most frequent adverse event (Finn et al SABCS 2012). Methods: Based on phase II data, a global, randomized, double-blind, phase III clinical trial was designed to demonstrate that P + L provides superior clinical benefit compared with L + placebo in postmenopausal women with ER(+), HER2(–) ABC who have not received any prior systemic therapy for their advanced disease. The study aims to assess whether P + L improves median PFS over L at HR of at least 0.7. Approximately 450 eligible patients with locoregionally recurrent or metastatic, pathologically confirmed ABC who are candidates to receive L as first-line treatment for their advanced disease will be randomized 2:1 to receive either P (125 mg QD 3 wk on, 1 wk off) + L (2.5 mg QD) or L (2.5 mg QD) + placebo. Patients who received anastrozole or letrozole as part of their (neo)adjuvant regimen are eligible if their disease progressed more than 12 months from completion of adjuvant therapy. Tumor tissue is required for participation. Secondary endpoints include overall survival, objective response, duration of response, clinical benefit, safety and tolerability, and patient-reported outcomes of health-related quality of life and disease- or treatment-related symptoms. Clinical trial information: NCT01740427.
The intensive care medicine research agenda in nutrition and metabolism
Authors: Yaseen M. Arabi, Michael P. Casaer, Marianne Chapman, Daren K. Heyland, Carole Ichai, Paul E. Marik, Robert G. Martindale, Stephen A. McClave, Jean-Charles Preiser, Jean Reignier, Todd W. Rice, Greet Van den Berghe, Arthur R. H. van Zanten, Peter J. M. Weijs
Journal: Intensive Care Medicine (2017)