tbuckley/cabot-search huggingface dataset:
Combining risk-reducing salpingo-oophorectomy with mastectomy and reconstructive surgery in BRCA1 and BRCA2 mutation carrier
Authors: L. Chen, B. Crawford, J. McLennan, E. S. Hwang, R. Foster, C. B. Powell
Journal: Journal of Clinical Oncology (2008)

1532 Background: Women who test positive for a germline BRCA1/2 mutation are offered cancer surveillance or risk reducing surgery. Coordinating risk reducing gynecologic surgery with breast and reconstructive surgery is a strategy to consider. Methods: Review of the Cancer Risk Program registry identified 43 BRCA1/2 mutation carriers undergoing concurrent or sequential surgery for RRSO and bilateral mastectomy by the Gynecologic Oncology, Breast Oncology, and Plastic Surgery services. This study evaluates the surgical outcomes of combining risk reducing gynecologic surgery with breast and reconstructive surgery. Student's t-test and chi-square comparisons were used. Results: Between August 1998 to July 2007, 21 women underwent a concurrent procedure of RRSO and bilateral mastectomy, while 14 had RRSO preceded by mastectomy, and 8 had oophorectomy followed by mastectomy. The mean age of all women was 44.9 (range 33–75). In comparison to those undergoing a concurrent procedure, women who had a subsequent separate risk reducing gynecologic procedure had shorter operative time (139 vs. 453 minutes, p< 0.0001) and median hospital stay (1.5 vs. 5 days, p=0.0002). Seventeen of 21 (81%) women having concurrent surgery had a current or prior diagnosis of breast disease. Nine of 21 (43%) women undergoing concurrent RRSO and mastectomy underwent transverse rectus abdominus myocutaneous flap reconstruction, while 2 had deep inferior epigastric perforator flaps, 1 had latissimus dorsi flaps, 5 had implants, and 4 chose no reconstruction. Complications included 2 patients each with fever and transfusion, one patient with ileus, and one with reoperation for flap perfusion. All patients with complications after concurrent surgery had undergone flap reconstruction, and both transfused patients had received breast cancer chemotherapy. Four of 21 women had hysterectomy in combination with the other concurrent surgeries; the median hospital stay for these women was 6 days, and included one of the transfused patients. Conclusions: A multidisciplinary approach to risk reducing surgery offers coordinated care for BRCA1/2 mutation carriers. Particularly in women undergoing breast cancer surgery and flap reconstruction, adding RRSO seems reasonable. No significant financial relationships to disclose.
RECODE: RCT on effectiveness of integrated COPD management in primary care
Authors: Annemarije Kruis, Melinde Boland, Pim Assendelft, Jacobijn Gussekloo, Apostolos Tsiachristas, Maureen Rutten, Jaap Sont, Niels Chavannes
Journal: European Respiratory Journal (2011)

Background:  There is insufficient evidence of the (cost)effectiveness of primary care COPD disease management programmes.   Aim and objective:  To evaluate the (cost)effectiveness of an ICT-supported, integrated, multidisciplinary disease management program for primary care COPD patients. We expect health care providers to improve inter-collegial communication, personalized treatment planning and better adherence to guidelines. As a result, we expect quality of care and quality of life in patients to improve.   Methods:  The study has a two-group cluster-randomized design in which 40 clusters of primary care teams are being randomized. Required sample size is 1080 COPD patients, in accordance with GOLD. Few exclusion criteria are applied. The intervention consists of a multidisciplinary course (2 days) in which primary care givers (general practitioners, practice nurses, physiotherapists, dieticians) within a particular region are trained as a team. The course will emphasize efficient task delegation within the team, active patient involvement in treatment planning, and designing time-contingent practice plans. Primary outcome is difference in health status as measured by Clinical COPD Questionnaire (CCQ). Programme costs, costs of healthcare utilization and productivity loss will also be calculated. Primary endpoint is at 12 months, while total study duration is two years.   Results:  Until now 496 patients have been included, which preliminary baseline means of FEV1/FVC ratio 56%, FEV1 65% predicted, CCQ score 1.65, MRC score 2 and EQ-5D score 0.71.   Conclusion:  The RECODE study is a cluster randomized trial which will provide insight in the cost-effectiveness of this particular primary care COPD disease management programme.
Does age predict perceptions of recovery and long-term chest and upper body morbidity after postmastectomy breast reconstruction?
Authors: Donald Brooks Johnson, Brittany Lapin, Chihsiung Wang, Katharine Yao, Mark Sisco
Journal: Journal of Clinical Oncology (2014)

23 Background: Despite evidence that postmastectomy breast reconstruction (PMBR) yields important quality of life benefits, older women (≥ 65 years) rarely receive it. While the perception is that PMBR may result in greater physical morbidity in older women, the additive effects of age and PMBR on physical morbidity have not been studied. This study sought to assess long-term chest and upper body morbidity in older women who receive PMBR. Methods: Women with AJCC stage 0 to III breast cancer who underwent a mastectomy ± PMBR in 2006 to 2011 were surveyed; physical well-being was assessed using the BREAST-Q. Patients were grouped into (3) cohorts: younger (&lt; 65 years) women who underwent PMBR, older women who underwent PMBR, and older women who underwent mastectomy alone. The groups were propensity matched (1:1) to control for differences. Data were analyzed using chi-square and t-tests. Results: 74 younger PMBR, 60 older PMBR, and 88 older unreconstructed mastectomy patients returned surveys (75.3% response rate). The median time from mastectomy to survey was 4.2 years. Younger women were more likely to undergo bilateral mastectomy than older women (54.3% vs. 28.4%, p &lt; 0.001). 63.5% of women underwent implant-only reconstruction and 36.5% underwent autologous reconstruction; there were no significant differences in reconstruction type between age groups. Neither bilateral surgery nor reconstruction type affected BREAST-Q physical well-being scores. Among older women, PMBR was associated with lower mean physical well-being scores than mastectomy alone (79.4 vs. 87.4, p = 0.017, Cohen’s d = 0.56). However, there was no difference in physical well-being scores between older and younger PMBR patients (79.4 vs. 78.5, p = 0.614). Older PMBR patients perceived recovery from surgery as difficult more often than older unreconstructed patients (46% vs. 33%, p = 0.013), but less often than younger PMBR patients (46% vs. 61%, p = 0.036). Conclusions: Older women who undergo PMBR have more long-term chest and upper body morbidity than those who do not have PMBR. However, their morbidity from PMBR and perception of recovery from surgery is comparable to that of younger women. Older women should be counseled that while PMBR is associated with more long-term chest and upper body morbidity, this outcome is independent of age.
Abstract 18548: Validation of a New Imaging Parameter, Ultrasonic Intensity of Blood Speckles, Measured by Intravascular Ultrasound for Assessment of Coronary Stenosis Severity Comparing with Fractional Flow Reserve
Authors: Jun Tanno, Shinataro Nakano, Nobuyuki komiyama
Journal: Circulation (2012)

Background : Little is known regarding intravascular ultrasound (IVUS) criteria to determine functional severity of coronary stenosis. Ultrasonic intensity of blood speckles (IBS) increases as blood flow decreases below coronary stenosis in clinical observation of gray-scale IVUS. The present study was conducted to determine IVUS parameters indicating functional significance of intermediate coronary stenotic lesions. Methods and Results : Thirty consecutive patients with angiographically single intermediate stenotic lesion in left anterior descending coronary artery were enrolled in this study. They were evaluated by means of IVUS and intracoronary pressure measurements. In IVUS analysis conventional gray-scale images were recorded and averaged integrated backscatter (IB) values of blood speckles were measured in cross-sectional vessel lumens at left main trunk (proximal) and 5 mm distal of targeted lesion (distal) using Terumo radiofrequency IVUS (RF-IVUS) system. IBS was defined as difference of IB values between the proximal and the distal sites (distal IB - proximal IB). Fractional flow reserve (FFR) was measured at maximal hyperemia induced by intravenous adenosine infusion. FFR &lt; 0.80 at maximum hyperemia was seen in 19 (63%) of total 30 lesions. IBS had significantly negative correlation with FFR (r = - 0.57, p = 0.001). The optimal cutoff value of IBS for FFR &lt; 0.80 was 10.0 which was obtained from receiver operating characteristic curve (area under curve 0.88; p = 0.001) (Figure). Sensitivity and specificity at the cutoff were 85 % and 70 %, respectively. Also, IBS wasan independent determinant of FFR (H.R. 1.23; 95% confidence interval [CI], 0.008 to 0.031; p = 0.008) in multivariate analysis. Conclusion : IBS, a brand-new IVUS parameter, obtained by RF-IVUS analysis showed a significant correlation to FFR values and can be a predictor for functional significance of epicardial coronary stenosis.
The effect of opposed versus unopposed hormone replacement therapy (HRT) on the risk of colorectal cancer (CRC).
Authors: K. Lin, W. Y. Cheung, J. Y. Lai, E. L. Giovannucci
Journal: Journal of Clinical Oncology (2010)

3619 Background: Separate studies suggest that estrogen alone (E) versus estrogen plus progesterone (EP) may have different effects on CRC risk, but data are conflicting. Prior meta-analyses did not address the role of opposed versus unopposed HRT specifically. We conducted a meta-analysis to summarize the relative risks (RR) of CRC due to E versus EP. Methods: From a total of 2,317 articles identified from PubMed and EMBASE, 5 randomized controlled trials (RCTs) and 13 observational studies were eligible for analyses. We considered these variables: study year/size/design/population, duration and recency of HRT use, method of exposure assessment, and outcome definition and ascertainment. RR were synthesized by random-effects models. Results: E was associated with a marginally significant decreased risk of CRC (RR 0.88, 95% CI 0.78-1.00). Adding progesterone significantly strengthened this association (RR 0.74, 0.67-0.82, p value for the difference between E and EP = 0.01). We found significant heterogeneity for E, but not for EP studies. Several factors were predictive of lower RR in the E arm and can potentially explain the heterogeneity, including current use, case-control design, and HRT exposure assessed by self-report (see Table). Recency was less important for the association between EP and CRC risk. Conclusions: There is consistent evidence supporting the association between EP and CRC risk reduction. While literature for the effect of E on CRC risk is inconclusive, our analyses suggest only current use of E is associated with a decreased CRC risk. HRT Variable Subgroups No. Pooled estimates Heterogeneity p values Meta-regression p values HRT E 12 0.88 (0.78-1.00) 0.003 0.01 EP 16 0.74 (0.67-0.82) 0.58 E Design RCT 1 1.08 (0.75-1.55) N/A <0.01 Cohort 4 0.99 (0.81-1.2) 0.14 <0.01 Case-control 6 0.76 (0.62-0.92) 0.01 Ref Recency Current user 3 0.73 (0.54-0.98) 0.03 <0.01 Former user 3 0.93 (0.62-1.41) 0.04 HRT assessed by self-report Yes 6 0.78 (0.63-0.97) 0.001 0.03 No 6 0.96 (0.84-1.09) 0.22 EP Design RCT 4 0.73 (0.57-0.94) 0.49 0.78 Cohort 5 0.76 (0.64-0.9) 0.33 0.85 Case-control 6 0.74 (0.63-0.87) 0.75 Ref Recency Current user 3 0.77 (0.57-1.04) 0.38 0.47 Former user 3 0.64 (0.46-0.89) 0.99 No significant financial relationships to disclose.
Therapeutic effects of anti-CEA (CEACAM5) and anti-NCA90 (CEACAM6) antibody monovalent fragments <b><i>in vitro</i></b> and <b><i>in vivo</i></b>
Authors: R. Blumenthal, M. Rodriguez, C. Damoci, L. Osorio, H. J. Hansen, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2004)

2555 Background: CEA and NCA-90 are overexpressed in many cancers. We have evaluated the effect of several antibody fragments (Fabs) on in vitro tumor cell growth and in vivo survival and chemosensitivity. Methods: HT-29, LS174T, Moser (human colonic tumor lines), MCA38 and MCA38cea (murine colonic tumor lines), BT-20 (human breast tumor line) were grown in culture. MN-14 and MN-6 anti-CEA Fabs and MN-3 and MN-15 Fabs that crossreact with NCA-90 were evaluated. In vitro growth inhibition was determined with the MTT assay; in vivo therapy was done with the GW-39 human colonic intrapulmonary micrometastatic model. In one study, cells were pre-incubated with Ab Fab prior to implantation and then mice were dosed once at 24h post implantation with the Fab. In the second study, mice were treated after cell inoculation with Ab Fab alone (10 μg x 5d), CPT-11 (Camptosar) alone (160 μg x 5d) or both Ab Fab and drug. Results: None of the Fabs had a significant effect on growth of the parental MCA38 cell line, which is CEA- and NCA-90-negative. In contrast, growth of MCA38cea cells (CEA+/NCA-90-) was inhibited by 33.3% and 16.8% by MN-3 and MN-15 Fab, respectively. MN-6 and MN-14 anti-CEA Fabs caused an 8.0% and 14.0% growth inhibition (GI), respectively. MN-3 Fab was also the most effective agent tested against LS174T, Moser, and BT-20 cells, resulting in 18.2%, 26.0% and 15.0% GI, respectively. In the HT-29 line, GI was greatest for MN-6>MN-3=MN-15>MN-14 Fabs, with no effect by an irrelevant Fab. In vivo studies showed that pretreatment of GW-39 cells with MN-3 or MN-15 Fab increased survival (P<0.025 and P<0.01, respectively), while MN-14 and MN-6 did not. If cells were not pretreated with Fab, but instead were dosed after cell implantation with either 10 or 100 μg/d of the Fab, no survival advantage was observed. However, dosing with either MN-15 Fab or MN-3 Fab increased the efficacy of CPT-11 therapy in vivo (P<0.001 and P<0.05 vs. CPT-11 alone, respectively). Conclusions: Antibody Fabs targeting both CEA and NCA-90 are more effective in vitro at inducing growth inhibition and more effective in vivo at increasing the sensitivity of cells to the cytotoxic effects of CPT-11. No significant financial relationships to disclose.
Phase I/IIa trial of autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma.
Authors: Y. Muragaki, T. Maruyama, H. Iseki, K. Tsuboi, A. Matsumura, T. Yamamoto, M. Matsutani, K. Karasawa, Y. Nakazato, T. Ohno
Journal: Journal of Clinical Oncology (2010)

2069 Background: Autologous formalin-fixed tumor vaccine (AFTV) has been shown to have a potential role in effective adjuvant therapy for hepatocellular carcinoma and recurrent malignant glioma. We tried to determine the efficacy and safety of AFTV concomitant with radiation for newly diagnosed GBM patients from two institutions. Methods: Patients with supratentorial GBM who underwent debulking surgery were eligible. The AFTV was injected intradermally 3 times, with 7 days between injections, starting when the cumulative radiation dose reached 32-36 Gy. Results: A total of 24 patients were treated. Two patients were excluded by the radiation protocol or by the patient's consent. Although grade 1 dermal toxicity was observed at the injected sites in all patients, no grade 2 or higher hematologic or other toxicity was observed. The trial met the prospectively-defined primary endpoints, with 21.4 months median survival time (range 6.1 to 42 months), 40.0% 2-year survival, and 7.6 months median progression-free survival time (PFS, range 2.2 to 25.6 months). The PFS of the patients with greater delayed type hypersensitivity (DTH) reaction (13.9 months) was statistically longer (p < 0.01) than that of the patients with weaker DTH reaction (4.3 months). Conclusions: The AFTV immunotherapy concomitant with radiation is a safe treatment for patients with newly diagnosed GBM and seems to have a positive effect on the PFS. Additional testing of AFTV in combination regimens is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell-Medicine, Inc. Cell-Medicine, Inc.
Baseline results of lung cancer screening program for family lung cancer risk with low-dose spiral CT in Taiwan.
Authors: C. Wang, Y. Tsai, Y. Cheung, H. Ko, Y. Ni, P. Feng, Y. Chen, P. Yang, G. Chang
Journal: Journal of Clinical Oncology (2010)

7098 Background: The family history is considered as a risk factor for lung cancer in nonsmokers. The value of surveillance for lung cancer with a family risk has not been established. We conduct the study to evaluate the feasibility of lung cancer screening by low- dose spiral CT (LDCT) in lung cancer families. Methods: The nonrandomized study enrolled family members of lung cancer patients. The criteria limited to family members (1) first-degree relatives had lung cancer (simplex family); two or more relatives with lung cancer (multiplex family), and (2) age older than 55 years. They receive annual CT for three years. The modified Early Lung Cancer Action Project protocol was used for investigation. The incidence of noncalcified nodules and prevalence of lung cancer are primary objects in baseline screening. Results: 1,125 participants from 559 families of lung cancer were recruited between August 2007 and November 2009. 810 patients were from 418 simplex families and 315 came from 141 multiplex families. The mean age of participants was 60.74 (±8.99 SD). 515 (45.8%) patients were male. 71.5% of participants are never smokers. Noncalcified nodules (NCN) were detected in 481 (42.8%) patients. The positive test, defined as NCN > 5 mm was 24.9% (280/1,125). The positive screen rates were not different between simplex and multiplex families (24.8% vs. 25.1% , p=0.927).Biopsies were performed in 35 patients. 19 had lung cancer (13 adenocarcinomas, five bronchoalveolar carcinomas [BAC] and one atypical carcinoid tumor) and 16 showed benign lesions. The stages of non-small cell lung cancer included 11 (IA), one (IB), two (IIA), one (IIIA), and four patients (IV), respectively. The mean size of cancer was 18.9 mm (ranged 9 ∼34 mm). The CT morphologies of lung cancer include eight nonsolid pattern (four adenocarcinomas and fours BACs), five part-solid pattern, and six solid nodules. The 11 of 19 lung cancer patients were female (57.9%). Among the 19 cancer patients, 12 patients (12/315; 3.8%) were from multiplex family and the others (7/810; 0.9%) occurred in simplex family (p =0.001). 78.9% (15/19) patients were never smokers. Conclusions: Our study provides evidence of lung cancer prevalence based on family risk. No significant financial relationships to disclose.
Cardiac safety of docetaxel/cyclophosphamide/trastuzumab (DCH) as adjuvant therapy for HER-2 (+) early stage breast cancer
Authors: A. Mato, M. Cappa, K. Fox, G. Policarpo, J. Cohen, H. Wall, S. Rossi, D. Mintzer
Journal: Journal of Clinical Oncology (2009)

e11577 Background: The addition of trastuzumab to adjuvant chemotherapy is standard for Her2(+) breast cancer. In our practice, adjuvant docetaxel/cyclophosphamide (DC) + 1 yr of trastuzumab is offered to pts with low-risk Her2(+) disease. Although the HERA trial allowed the use of a variety of chemotherapy regimens to combine with trastuzumab, it predates the acceptance of DC as an adjuvant care-standard and therefore the safety profile of DCH has not been reported. Methods: We conducted a two-center, retrospective cohort study including all pts treated with adjuvant DCH between 12/06 and 3/08 to assess its safety profile. Using the CTCAE criteria, records were screened for toxicity from DCH initiation to the present. The primary outcome was cardiac toxicity defined as clinical CHF or a confirmed significant LVEF decline (≥ 16% decrease in EF from baseline or EF &lt; 50% + ≥ 10% decrease from baseline). Results: 27 pts, mean age 54, were identified with a median follow-up of 23.4 months (range 12.2- 42.0 months). The mean tumor size was 1.4 cm (0.5–4.3 cm) with 84% hormone receptor(+), 96% node(-) and 100% Her2(+) by FISH or IHC. 52% of pts received DCH concurrently and 48% received trastuzumab following DC. Baseline mean EF was 65% (53–86%). EF assessments were performed every 3 months/pt. 7.4% and 11.1% of pts had a prior history of anthracycline exposure or cardiac disease respectively. 11.1% of pts experienced a significant LVEF decline occurring on ≥ 2 sequential EF measurements. The trastuzumab discontinuation rate was 3.7% (1 pt). No pt developed clinical CHF. 88% of pts have now completed trastuzumab therapy. 33% of pts received pegfilgrastim with chemotherapy. 25% of pts experienced grade III-IV neutropenia. Grade III-IV anemia and thrombocytopenia were not observed. Trastuzumab-related infusion reactions were observed in 1 pt and did not warrant drug discontinuation. At this time all pts are alive and no patient has experienced disease recurrence. Conclusions: The DCH regimen, given in sequence or concomitantly, appears to be a safe and effective adjuvant treatment for women with Her2(+) disease. Along with docetaxel/carboplatin/trastuzumab, DCH represents another acceptable non-anthracycline containing regimen for low-risk, Her2(+) pts. No significant financial relationships to disclose.
Thymidylate synthase gene polymorphosms and lung cancer susceptibility
Authors: A. N. Lima, A. Araujo, A. Coelho, V. Seabra, R. Medeiros
Journal: Journal of Clinical Oncology (2008)

22168 Background: Lung cancer is the most common type of cancer in Europe and non-small cell lung cancer (NSCLC) accounts for 75%-85% of all histological. The thymidylate synthase (TS) enzyme plays a key role in de novo DNA synthesis, essential for DNA replication and repair, thus it is important in cell proliferation and it is a target for several chemotherapy agents. The TS gene is highly polymorphic in Humans. Three polymorphisms of major relevance in the expression of TS levels were described, namely, on the 5’UTR, a variable number tandem repeat sequence with 28bp (where the most frequent have two and/or three repeats - 2R and/or 3R alleles, respectively) and a single nucleotide polymorphism (SNP) G>C in the 2nd sequence of the 3R allele; in the 3’UTR a deletion/insertion (del/ins) of 6bp. The main goal of this work was to study the influence of TS polymorphisms in the susceptibility to develop NSCLC using a case-control study. Methods: DNA was extracted from peripheral blood leukocytes of 213 patients from the North region of Portugal, admitted in Portuguese Oncology Institute of Oporto, diagnosed with NSCLC. TS genotypes were detected by PCR-RFLP techniques. The control group consisted of 510 individuals with no known oncological disease. Results: According to the results individuals carrying the 3R allele faces a higher risk for developing NSCLC when compared to homozygous 2R (OR=1.57; 95% CI [1.03–2.39]; P=0.034). However, concerning SNP G>C and del/ins polymorphisms, no statistically significant differences were found. Following the hypothesis that the G to C substitution can modulate the effect of TS 3R variant, we analyzed the association between the influence of the del/ins polymorphism and 3RC and 3RG genotype and, when combined analysis for the three polymorphisms were carried out, no statistically significant differences were found for the SNP G>C genotype distribution, where homozygous 3R/3R individuals that carry the ins allele showed no different probability risk to develop NSCLC when carrying the 3G allele, relatively to homozygous 3C/3C. Conclusions: Since the presence of 3R allele appears to be associated with an increased risk for develop NSCLC the pre-establishment of an individual molecular profile could help to predict differential susceptibility to develop this neoplasia. No significant financial relationships to disclose.