tbuckley/cabot-search huggingface dataset:
Risk-reducing surgery by skin-sparing mastectomy (SSM) and immediate implant-based reconstruction with and without titanized meshes and quality of life.
Authors: Mahdi Rezai, Andre Scherag, Stefanie Kessel, Rainer Kimmig, Peter Kern
Journal: Journal of Clinical Oncology (2012)

48 Background: The impact of risk-reducing surgery with skin sparing mastectomy and immediate reconstruction on quality of life using new textured implants and titanized meshes (Tiloop bra ) has not beed evaluated by standardized quality of life questionnaires (EORTC) with regards to surgery-related morbidity and patients' satisfaction. Methods: This large case cohort trial (n=197) evaluates safety, aesthetic outcome and patient's satisfaction with immediate reconstruction with and without the use of titanized a mesh versus a corial flap after SSM. Results: This large retrospective case cohort trial analysed 197 skin sparing mastectomies (SSM) in 161 patients (45 bilateral cases) and immediate breast reconstruction (IBR). We used a double-plane technique covering the implant by the submuscular pouch in its cranial half and a corial-fat-flap or titanized mesh (Tiloop bra) for covering its lower pole or a de-epithelized corial flap in breasts with macromastia following an inferior-pedicled reduction mammaplasty pattern according to Ribeiro in the modification of Rezai. Conclusions: 163 women, with a median age of 41 years, with a total of 197 SSMs were evaluated. The majority did not experience pain and expressed satisfaction with volume, symmetry, aesthesis and quality of life in general. Partner interaction after breast reconstruction was normal. The use of titanized meshes was perceived as favourable with regards to better fitting of the breast in the bra and clothing and yielded low complication rates. The rating of patients in terms of self-perception after the reconstruction was good. Immediate reconstruction has a significant positive impact and gives the patient a considerable physical and psychological support.The oncological safety of the method is high with 2 recurrences only in this cohort of 163 women (1.2% ) and a follow-up of up to 6 years.
Whole body positron emission tomography (PET) for the detection of residual disease in gestational trophoblastic tumors (GTTs)
Authors: T. Dhillon, C. Palmieri, E. Newlands, J. Franks, M. Seckl
Journal: Journal of Clinical Oncology (2005)

5109 Background: GTTs including invasive mole and choriocarcinoma are usually cured with chemotherapy assessed by a normalisation of the pregnancy hormone hCG. Relapses detected by a rising hCG can be cured by subsequent surgery/chemotherapy. Identification of the active site of recurrence for potential surgical resection can be difficult, particularly when there are mutliple lesions seen on CT/MRI. Whole-body 18fluorodeoxyglucose (18FDG)-PET may provide a solution to this problem and its value is examined here. Methods: The Charing Cross GTT database was screened and 9 patients were identified post- initial chemotherapy with rising or persistently elevated hCG who underwent CT/MRI and whole body 18FDG-PET to identify potential sites of active disease. The subsequent effect of surgery and or chemotherapy was assessed by the fall in hCG levels and the value of 18FDG-PET in management was determined. Results: 3 patients with residual lesions on CT/MRI which were active on PET, subsequently had surgery alone resulting in normalisation of hCG levels. One patient had a normal CT/MRI, but was PET positive in the lungs. The affected lung area was resected and the hCG normalised. Two patients had CT/MRI lesions not positive on PET. Further chemotherapy led to normalisation of hCG and CT/MRI. One patient with a lesion seen on CT and PET had resolution of these changes with chemotherapy. The 8th patient had a persistently raised hCG post-chemotherapy with a normal CT/MRI but was PET positive in the stomach, which resolved with chemotherapy. The 9th patient had a persistently raised serum hCG between 20–30iu/l, despite no lesion on CT/MRI or PET, and has remained well off treatment for 24 months. Conclusion: We report the largest series to date of the use FDG- PET scanning in GTT. PET scanning can be useful for confirming sites of active disease seen as lesions on CT/MRI scans. In two cases PET scanning found sites of disease not seen on conventional imaging. No significant financial relationships to disclose.
A phase Ib, open-label, dose-escalation study of tivozanib and FOLFOX6 in patients (pts) with advanced gastrointestinal (GI) tumors.
Authors: F. Eskens, C. N. Oldenhuis, P. Bhargava, W. Loos, B. Esteves, L. van Doorn, M. M. Cotreau, R. Dhillon, J. A. Gietema, E. De Vries
Journal: Journal of Clinical Oncology (2011)

549 Background: Tivozanib (AV-951), a highly potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, has shown additive antitumor activity with fluorouracil (5-FU) in preclinical studies. An open-label phase Ib study was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK), and antitumor activity of escalating doses of tivozanib combined with standard-dose FOLFOX6 (i.e., oxaliplatin, leucovorin, and 5-FU) in pts with advanced GI tumors. Methods: Tivozanib was administered orally once daily in 4-week cycles (3 weeks on, 1 week off), with FOLFOX6 administered on days 1 and 15 of each cycle. Pts were allowed to continue tivozanib following discontinuation of FOLFOX6. Results: 22 pts (14 male/8 female; median age of 58 years [range, 40-75]) received 0.5 mg (n = 9), 1.0 mg (n = 3), or 1.5 mg (n = 10) tivozanib plus FOLFOX6. Pts received a median of 8.1 weeks (range, 0.1 - 43.1) of treatment. DLTs were observed in 2 pts receiving 0.5 mg tivozanib (reversible grade 3 diarrhea and grade 3 and 4 transaminase elevations, respectively) and in 2 pts receiving 1.5 mg tivozanib (reversible grade 3 seizures and grade 3 vertigo, respectively). Other grade 3/4 drug-related adverse events (AEs) included neutropenia, fatigue, and hypertension (n = 2 each); and pyrexia, pulmonary embolism, and thrombosis (n = 1 each). There was no indication that drug-related AEs in this study were more frequent or severe than those observed with tivozanib or FOLFOX6 alone. The MTD was 1.5 mg tivozanib with full dose FOLFOX6. The PK profiles of tivozanib, oxaliplatin, and 5-FU will be presented. Several durable partial responses were observed. Additional safety and efficacy data are being obtained in 8 pts currently being treated at the 1.5-mg dose level. Conclusions: The combination of tivozanib and FOLFOX6 is tolerable and safe, with tivozanib given at its recommended dose of 1.5 mg. Observed clinical activity merits further exploration in several GI tumors, and these studies are being planned. [Table: see text]
Prognosis and survival of patients with T1a breast carcinoma: A single center retrospective study
Authors: V. Massard, G. MacGrogan, M. Debled, C. Tunon de Lara, L. Mauriac
Journal: Journal of Clinical Oncology (2008)

11515 Background: Management of patients with breast cancer ≤ 5mm remains controversial. No clear-cut treatment guidelines are currently available for this increasing population. The aim of this study was to better characterize these tumors and to find prognostic factors. Methods: We retrospectively studied 247 patients treated at the Bergonié Institute (France) between 1980 and 2006. All patients with breast tumors measuring > 0,1 cm and ≤ 5mm (pathological size, pt1a) were included in this study. Patients having bilateral or anterior contralateral invasive breast cancer were excluded. Axillary lymph node dissection was done in 139 patients. Survival curves were evaluated by Kaplan-Meier method and univariate analysis by the log-rank test. Results: Median follow-up was 90.9 months. Overall survival was 96% at 5 years and 94% at 10 years. Distant disease free survival was 98% at 5 years and 94% at 10 years. Distant disease free survival was 98% at 5 years and 97% at 10 years for pT1aN0 versus 68% at 5 years and 57% at 10 years for pT1aN+. In univariate analysis, axillary nodal status, mitotic index, lymphovascular invasion and estrogen receptor status (positive or negative) were significant prognostic factors. (p=7.3 ×10–9; p=0.01; p=0.05 and p = 0.05). Conclusions: pT1a breast tumors have an excellent prognosis. Axillary nodal status seems to be the strongest prognostic factor. Randomized studies are needed to better codify the therapeutic sequence in order to spare patients from unnecessary secondary effects and iatrogenic complications. No significant financial relationships to disclose.
Association between cetuximab response and differential immunologic gene expression signatures in colorectal cancer metastases.
Authors: Michael Sangmin Lee, Benjamin Garrett Vincent, Autumn Jackson McRee, Hanna Kelly Sanoff
Journal: Journal of Clinical Oncology (2016)

558 Background: Different immune cell infiltrates into colorectal cancer (CRC) tumors are associated with different prognoses. Tumor-associated macrophages contribute to immune evasion and accelerated tumor progression. Conversely, tumor infiltrating lymphocytes at the invasive margin of CRC liver metastases are associated with improved outcomes with chemotherapy. Cetuximab is an IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR) and stimulates antibody-dependent cellular cytotoxicity (ADCC) in vitro. However, it is unclear in humans if response to cetuximab is modulated by the immune response. We hypothesized that different immune patterns detected in gene expression profiles of CRC metastases are associated with different responses to cetuximab. Methods: We retrieved gene expression data from biopsies of metastases from 80 refractory CRC patients treated with cetuximab monotherapy (GEO GSE5851). Samples were dichotomized by cetuximab response as having either disease control (DC) or progressive disease (PD). We performed gene set enrichment analysis (GSEA) with GenePattern 3.9.4 using gene sets of immunologic signatures obtained from the Molecular Signatures Database v5.0. Results: Among the 68 patients with response annotated, 25 had DC and 43 had PD. In the PD cohort, 59/1910 immunologic gene sets had false discovery rate (FDR) &lt; 0.1. Notably, multiple gene sets upregulated in monocyte signatures were associated with PD. Also, gene sets consistent with PD1-ligated T cells compared to control activated T cells (FDR = 0.052) or IL4-treated CD4 T cells compared to controls (FDR = 0.087) were associated with PD. Conclusions: Cetuximab-resistant patients tended to have baseline increased expression of gene signatures reflective of monocytic infiltrates, consistent with also having increased expression of the IL4-treated T-cell signature. Cetuximab resistance was also associated with increased expression of the PD1-ligated T cell signature. These preliminary findings support further evaluation of the effect of differential immune infiltrates in prognosis of metastatic CRC treated with cetuximab.
A multicenter, open-label study to determine the effect of intravenous zoledronic acid (ZOL) on pain and quality of life in patients with bone metastases with or without skeletal-related events (SREs) resulting from breast cancer (BC) and prostate cancer (PC).
Authors: Y. B. Al Farhat, J. Cseh, K. Boer, M. Csepreghy, L. Pajor, L. Thurzo, L. Mangel, O. Esik
Journal: Journal of Clinical Oncology (2011)

e19558 Background: The primary objective was to assess pain course over time measured by a visual analog scale (VAS) for patients who reported pain and who did not have pain upon entry into the trial. The secondary objectives are time in chair, quality of life, and safety of ZOL administered with or without SREs. Methods: 72 patients from 5 Hungarian centre enrolled (12 dropouts), of which 38 patients had BC and 32 patients had PC. ZOL in 4 mg starting dose administered as intravenous infusions over a no less than 15-minute duration, every 3-4 weeks for a maximum of 6 infusions. Dose adjustments occurred according to creatinine clearance. The evaluations criteria used in the study are pain evaluated on VAS, quality of life (Functional Assessment of Cancer Therapy Scale – General (FACT-G) and time in infusion treatment chair. Results: The mean baseline pain score was 36.3 mm, 43,1mm for the BC subgroup and 28,7mm for the PC subgroup. At the end of the study the pain was found to be 16,0 mm and 20,7mm respectively. Analysis results confirm a significant reduction in pain from baseline during the treatment (p<0.0 5). The corresponding p-values for time of infusion at Visit 3 and Visit 5 are 0.699 and 0.273, respectively. A significant reduction in FACT-G total score from baseline is apparent during the treatment (p<0.05), primary cancer diagnosis and presence of SRE do not combine to influence the overall mean total score. During the study period 18 patients experienced adverse events. The rate and number of patients experienced adverse events are similar in both groups defined by primary cancer diagnosis. Conclusions: This study showed that treatment with ZOL appeared to be effective and safe to control pain in BC and PC patients with bone metastasis.
Fcγ-receptor IIa polymorphism and cardiotoxicity in patients with breast cancer treated with adjuvant trastuzumab.
Authors: N. Cresti, D. Jamieson, M. W. Verrill, M. Pinkilgton, A. V. Boddy
Journal: Journal of Clinical Oncology (2011)

565 Background: Trastuzumab, a humanized monoclonal antibody targeting HER2, is a mainstay of the treatment of advanced and early stage HER2-positive breast cancer patients. It is generally well tolerated but the occurrence of cardiac dysfunction can be a major concern in a proportion of patients. Although a number of clinical parameters have been associated with trastuzumab-related cardiotoxicity, we hypothesized that germline genetic variations may also play a role. In particular we considered four common, coding, non-synonymous single nucleotide polymorphisms (SNPs) in the HER2 gene (Ile655Val and Ala1170Pro) and the Fc gamma receptor genes (FCGR2A His131Arg and FCGR3A Val158Phe). Methods: We evaluated a population of early HER2-positive breast cancer patients treated with three-weekly trastuzumab after adjuvant chemotherapy. Relevant clinical data included baseline clinical characteristics of patients, occurrence of cardiac-related symptoms during trastuzumab therapy, ejection fraction variations and subsequent medical decisions. Germ-line DNA was extracted from peripheral nucleated blood cells and genotyping of the four SNPs was performed using the TaqMan assay. Results: One hundred one patients were recruited in the study. As expected, cardiac risk (age > 60 and/or pre-existing cardiovascular disease) was associated with a higher likelihood of definitive suspension of trastuzumab for cardiotoxicity (log-rank p = 0.018). The FCGR2A 131His homozygous genotype was also associated with the same end-point (log-rank p = 0.006). When these two parameters were combined, we observed no permanent discontinuation of trastuzumab due to cardiotoxicity in patients who had no cardiac risk and were carriers of the FCGR2A 131Arg allele. Interestingly, two patients who experienced severe congestive heart failure were both FCGR2A 131His homozygous. The other SNPs were not associated with cardiac events. Conclusions: The germline FCGR2A His131Arg SNP might contribute to the development of trastuzumab-related cardiotoxicity. If validated in a different population, this finding may impact on trastuzumab prescribing and monitoring of heart function in patients on treatment.
Annexin II overexpression correlates with a poor prognosis in surgically resected non-small-cell lung cancer
Authors: M. Ichikawa, T. Mio, S. Toyokuni, F. Tanaka, H. Wada, M. Mishima, K. Yanagihara
Journal: Journal of Clinical Oncology (2005)

7249 Background: Annexin II is a calcium-regulated phospholipid binding protein, and a cell surface receptor for plasminogen and tissue plasminogen activator. Overexpression of annexin II has been reported in various carcinomas such as brain, breast, pancreatic and gastric cancer. The expression has been also reported to correlate with poor prognosis of colorectal cancer. However, the expression of annexin II in lung cancer is not clear. Methods: Annexin II expression was evaluated in surgically resected tissues from 114 patients with non-small cell lung cancer, including 69 adenocarcinomas, 36 squamous cell carcinomas, 9 large cell carcinomas. Their post operative staging were stage I: 56, II:22; IIIa 33, IIIb:3. Annexin II expression was evaluated with immunohistochemical method using anti-human annexin II monoclonal antibody. Results: Annexin II expression was observed in 105 cases out of 114 (92%). Mean survival time (MST) of patients whose annexin II expressions were stronger than average was significantly shorter than that of patients with weaker expression (1240 days vs. 1826 days; p=0.0431 by log-rank test). The difference of MST between patients with stronger expression and weaker expression was larger, when tested in adenocarcinoma (1406 days vs.1895 days; p<0.0236), while there was no significant differences in squamous cell carcinoma (1530 days vs. 1530 days: p=0.6199). Conclusions: Annexin II expression was detected in most of lung cancer. In patients with adenocarcinoma, annexin II overexpression predicts shorter survival, thus representing a valuable prognostic factor. No significant financial relationships to disclose.
A Candidate Trans-Acting Modulator of Fetal Hemoglobin Gene Expression in the Arab-Indian Haplotype of Sickle Cell Anemia
Authors: Vinod Vathipadiekal, John Farrell, Zhang Shuai, Heather Edward, Heather Shappell, A.M Al-Rubaish, Fahad Al-Muhanna, Z Naserullah, A Alsuliman, Irene Simkin, Lindsay Farrer, Zhihua Jiang, Hong Yuan Luo, Shengwen Huang, Gustavo Mostoslavsky, George J. Murphy, P.K. Patra, David H.K. Chui, Abdulrahman Alsultan, Amein Al-Ali, Paola Sebastiani, Martin H. Steinberg
Journal: Blood (2015)
Association of perineural invasion with outcomes after neodjuvant chemoradiation for locally advanced rectal adenocarcinoma.
Authors: Priyanka Vinod Chablani, Phuong Nguyen, Charles Andrew Robinson, Xueliang Jeff Pan, Steve Andrew Walston, Evan John Wuthrick, Terence Marques Williams
Journal: Journal of Clinical Oncology (2015)

750 Background: Perineural invasion (PNI) as a prognostic indicator has not been well studied in patients with rectal adenocarcinoma treated with neoadjuvant chemoradiation (nCRT). In this study, we investigated the incidence and prognostic significance of PNI in patients with stages II-III locally advanced rectal cancer treated with nCRT. Methods: We performed a retrospective study of 110 consecutive patients treated with nCRT for locally advanced rectal adenocarcinoma at a single institution from 2004 to 2011. 88 of these patients had residual tumor in the resected specimen after nCRT. We evaluated the association of PNI with clinical outcomes, including disease-free survival (DFS), distant-metastasis-free survival (DMFS), and overall survival (OS), using log-rank and Cox proportional hazard modeling. Results: Of the 88 patients with residual tumor at surgery, 14 patients (16%) had PNI and 74 patients (84%) did not. Baseline distribution of selected variables in the PNI+ and PNI- groups are shown in Table 1. Median follow-up was 27 months (range 0.9 to 84 months). The median DFS was 13.5 months for PNI+ patients and 39.8 months for PNI- patients (p&lt;0.0001). The median DMFS was 13.5 months for PNI+ patients and median not reached (&gt; 40 months) for PNI- patients (p&lt;0.0001). We did not detect a significant association between the presence of PNI and worse OS, perhaps due to a high rate of censored patients in the OS analysis. In a multivariate model including pT stage, pN stage, tumor location, tumor size, type of surgery, and radial margin status, PNI remained a significant predictor of DFS (HR 16.8, 95% CI, 3.7–75.5, p&lt;0.0002) and DMFS (HR 18.9, 95% CI, 4.4–81.9, p&lt;0.0001). Conclusions: For patients with locally advanced rectal cancer treated with nCRT prior to surgical resection, PNI found at the time of surgery is significantly associated with worse DFS and DMFS. [Table: see text]
The status of intensive care medicine research and a future agenda for very old patients in the ICU
Authors: H. Flaatten, D. W. de Lange, A. Artigas, D. Bin, R. Moreno, S. Christensen, G. M. Joynt, Sean M. Bagshaw, C. L. Sprung, D. Benoit, M. Soares, B. Guidet
Journal: Intensive Care Medicine (2017)
Effect of FSH supplementation on the GnRH antagonist suppressed growth of PC-3 cell xenografts in nude mice.
Authors: Olayiwola Oduwole, Phil Rawson, Nafis Rahman, Wolfgang Koechling, Ilpo Huhtaniemi
Journal: Journal of Clinical Oncology (2016)

e630 Background: One of the fundamental differences between GnRH agonist and antagonist treatment is the permanent suppression of FSH by antagonist, while a rebound in FSH secretion has been documented upon agonist treatments. To assess the potential beneficial effects of permanent FSH suppression in the hormone ablation treatment of prostate cancer we studied the effect of the GnRH antagonist degarelix in the absence and presence of FSH supplementation on the growth of PC-3 human prostate cancer cell xenografts in nude mice. Methods: Intact (n = 20) and gonadectomized (n = 20) nude male mice were inoculated with 2 x 10 6 PC-3 cells. Half of each group received degarelix treatment at 10 mg/kg body weight s.c. In a second experiment (n = 10/group), degarelix treatment was supplemented with recombinant human FSH at10 IU/kg/day using i.p. ALZET osmotic minipumps. Tumor growth in both experiments was monitored for 4 weeks by external inspection and caliper measurement, after which the mice were sacrificed. Results: The first experiment demonstrated that degarelix treatment significantly reduced tumor growth by 33% and 35%, respectively, in intact and gonadectomized mice as compared to non-treated controls (p&lt;0.0001 for each). In the second experiment, FSH reversed the inhibitory effect of degarelix in intact mice. Conclusions: These results demonstrated that the suppression of PC-3 xenograft growth by GnRH antagonist treatment was completely inhibited by concomitant FSH treatment. The findings prove experimentally the principle that combined FSH and LH suppression by GnRH antagonist could offer an advantage over the isolated LH suppression by GnRH agonist upon prostate cancer treatment. [Table: see text]