tbuckley/cabot-search huggingface dataset:
Racial/ethnic differences in job loss for women with breast cancer
Authors: M. S. Mujahid, N. K. Janz, A. S. Hamilton, S. J. Katz
Journal: Journal of Clinical Oncology (2008)

6513 Background: Breast cancer diagnosis and treatment may have adverse consequences on employment. However, potential racial/ethnic variation in work outcomes after breast cancer diagnosis and treatment has received inadequate attention. Methods: 2,030 women with non-metastatic breast cancer diagnosed between 8/05–5/06 and reported to the Los Angeles County, Surveillance Epidemiologic and End Results (SEER) registry, were identified and asked to complete a survey after initial treatment (mean time from diagnosis = 9.2 months). Latina and African American (AA) women were over-sampled (n=1,338, eligible response rate 71.2%). Results: 747 women (57.0%) worked for pay at time of diagnosis (54%, 61%, and 60% of Latinas, AA, and Whites, respectively). Of these women, 16.7% lost their job during the treatment period. Latina women were much more likely to lose their job than other women (27.4% vs 9.7% and 7.2% for AA and Whites, respectively, p<.001). Receipt of chemotherapy (59.7% of the sample) coupled with an unsupportive work environment was particularly devastating to Latinas: 56% lost their job vs 19% and 8% of AA and white women. No racial/ethnic differences were found for women who received chemotherapy but had a fully supportive working environment. Women who lost their job were much more likely to cut down on family purchases of household items (54% vs. 30%, p<.001); not make payments on credit cards or other bills (17% vs. 9%, p<.001); and were more worried about getting a job in the future (73% vs. 49%, p<.001). Conclusions: Job loss can have serious consequences for women being treated for breast cancer. Clinicians and staff need to be aware of aspects of the treatment course and work place environment that place women at highest risk for job loss, especially for ethnic minorities. % of Job Loss by Race, Treatment, and Work Support Chemo-yes Chemo-no Latina AA White Latina AA White Work support * None 56 19 8 15 17 10 One 27 17 10 10 6 3 Two 4 2 2 3 4 5 Total 37 11 6 14 9 7 * no work support, only one type of support (paid leave/flexible schedule), both types of support No significant financial relationships to disclose.
Robert Archibald Buchanan
Authors: Linda Mackenzie
Journal: BMJ (2017)

Born in a nursing home in Riccarton, Robert Archibald Buchanan arrived on the Isle of Arran in the sidecar of his father’s motorbike when he was 10 days old. His ambition in life was to become a doctor, and although his early education was disrupted by the war, he was proud to qualify from Glasgow University. He then spent six months …
Phase II study of mFOLFOX6 with bevacizumab (Bev) in metastatic gastric and esophageal (GE) adenocarcinoma.
Authors: J. Li, J. S. Kortmansky, M. Saif, N. A. Fischbach, L. Ravage-Mass, K. Elligers, C. Hahn, M. K. Cohenuram, J. Lacy
Journal: Journal of Clinical Oncology (2010)

TPS203 Background: 5-FU in combination with oxaliplatin is active in GE adenocarcinoma, with response rates (RR) of 38-55%, time to progression (TTP) of 4.9 to 7.1 mos, and median survival of 8 to 11.4 mos. Bev has demonstrated promising activity in metastatic GE adenocarcinoma when used in combination with cisplatin-based regimens. We have treated 19 pts with metastatic GE adenocarcinoma at our institution with FOLFOX/Bev and reviewed our experience with respect to efficacy and toxicity. Characteristics: gastroesophageal junction (GEJ)/gastric 11/8; median age 58 years (33- 76); M/F 17/2; median ECOG PS 1 (0-2); lymph node metastases (mets) only 3; visceral mets 16 (liver 10, lung 4, peritoneum 4, other 3); primary tumor unresected 14; prior chemotherapy 9. The median number of cycles administered was 13 (6-24). Overall RR was 73.7% (2 CR and 12 PR). mTTP was 29 wks, mOS was 12 mos. One pt is alive and disease free at 38 mos. We observed no episodes of ATE, GI bleeding or perforation; there was one episode of grade 4 hypertension (updated from initial report at 2008 GI ASCO abstract 74). Based on this retrospective experience, we are conducting a phase II trial to investigate the efficacy of Bev in combination with modified FOLFOX6 in pts with metastatic GE adenocarcinoma. Methods: Pts with measurable metastatic GE adenocarcinoma received mFOLFOX6/Bev as follows: leucovorin 400 mg/m2, 5-FU 400 mg/m2 bolus and 2,400 mg/m2 46 hr continuous infusion, oxaliplatin 85 mg/m2, Bev 10 mg/kg q 2 wks. Prior chemotherapy for metastatic disease was not permitted. (Neo)adjuvant chemotherapy was allowed (interval ≥ 12 mos). Response was evaluated by CT q 8 wks. Toxicity was assessed q 2 wks per CTCAE v3. Target accrual is 35 pts. Primary objective is TTP. The study is designed to detect an increase in TTP by 70% from 5 to 8.5 mos with addition of Bev to mFOLFOX6. Secondary objectives are safety, RR, OS and correlation of outcome with early response on PET scan. We have accrued 11 pts: median age 65 yrs (54-79); M/F 7/4; mECOG PS 1; GEJ/gastric 8/3; lymph node only mets 2; visceral mets 9 (liver 6, lung 2, peritoneum 1); adjuvant chemotherapy 1. Further accrual and evaluation for efficacy and toxicity are ongoing. This study is supported by Genentech. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, sanofi-aventis Bayer, Bristol-Myers Squibb, Genentech, Novartis, Roche, sanofi-aventis Enzon, ImClone Systems, Merck, PhytoCeutica, Roche, Taiho Pharmaceuticals
Everolimus for patients with metastatic renal cell carcinoma (mRCC) refractory to anti-VEGF therapy: Preliminary results of a pooled analysis of noninterventional studies.
Authors: Laurence Albiges, Lothar Bergmann, Jean-Christophe Eymard, Manuela Schmidinger, Aristotelis Bamias, Meryem Ktiouet, Gregor Fischer, Despoina Xanthaki, Gernot Guderian
Journal: Journal of Clinical Oncology (2013)

392 Background: In RECORD-1, the oral mTOR inhibitoreverolimus significantly improved PFS compared with placebo in patients with mRCC refractory to 1 or 2 prior VEGFr-TKIs. Here, we provide prospective data from European countries on everolimus use in patients with mRCC after failure of anti-VEGF therapy. Methods: To evaluate the safety and efficacy of everolimus in routine clinical practice, data were pooled from 4 prospective, noninterventional studies conducted in Germany, France, Greece, and Austria. Results: Data from the first 6 months of treatment are available for 534 patients. At baseline, median time since diagnosis of first metastasis from RCC was 1.8 years, and 91% of patients were of favorable or intermediate MSKCC risk prognosis. Predominantly clear cell mRCC was evident in 90% of patients, and most patients had prior nephrectomy (89%). Best overall response by investigator assessment was partial response in 13%, stable disease in 56%, and progressive disease in 32%. Overall, 77% of patients experienced ≥1 adverse event (AE) and 22% experienced ≥1 serious AE. AEs occurring in &gt;5% of patients included stomatitis (25%), anemia (13%), asthenia (9%), fatigue (8%), pneumonitis (8%), rash (8%), diarrhea (7%), decreased appetite (7%), hypertriglyceridemia (6%), dyspnea (6%), nausea (6%), and peripheral edema (5%). Serious AEs occurring in &gt;2% of patients included stomatitis (3.4%), general health deterioration (2.2%), anemia (2.1%), dyspnea (2.1%), and pneumonitis (2.1%). Median everolimus duration was 4.8 months. Treatment was discontinued due to disease progression in 50% of patients and AEs in 24% of patients. A similar proportion of patients had Karnofsky performance status ≥70 at baseline (86%) and at end of analysis (80%). Updated data will be available in February 2012. Conclusions: Preliminary results of this pooled analysis of 4 European studies substantiate the safety of everolimus reported in the pivotal RECORD-1 trial and provide evidence for the effectiveness of everolimus in routine use. The results support the use of everolimus as a standard of care for VEGF-refractory patients with mRCC.
Acute and late side effects after intraoperative electron radiotherapy during breast conserving surgery of breast cancer.
Authors: Christiane Matuschek, Edwin Boelke, Wolfgang Janni, Karin Zwiefel, Ioannis Simiantonakis, Freddy-Joel Njanang, Wilfried Budach, Marina Alessandro
Journal: Journal of Clinical Oncology (2013)

1101 Background: Intraoperative boost irradiation as part of breast-conserving therapy is a perfect method to adequately capture the high risk tumor relapse area. The most homogeneous dose distribution is achieved with electrons. Intraoperative electron radiotherapy (IOERT) as a boost for breast cancer releases a high single dose of radiation to the breast tissue; therefore acute toxicity is of particular attention. To date there is only inadequate information available on breast cancer patients treated with IORT using electrons applied as a boost. We therefore analyzed the acute toxicity and late side effects after radiotherapy with 10 Gy as a boost with a minimum follow-up of 3 months. Methods: A total of 385 patients treated with IOERT (10 Gy with 5, 7 and 9 MeV electrons) with a dedicated robotic linac (NOVAC 7, New Radiant Technology, Aprilia, Italy) to the tumor bed during breast-conserving surgery as a boost followed by whole-breast radiotherapy (WBRT,50- 50.4 Gy; 1.8-2 Gy per fraction) were included in this study. All patients underwent a retrospective follow-up regarding acute and late side effects. Toxicities were documented using the common toxicity criteria (CTC 4.0 of the European Organization for Research and Treatment of Cancer) and normal tissues subjective, objective, management and analytic scales (LENT-SOMA). Results: The IOERT was well tolerated and the cosmetic results were good. As a side effect there were five patients with seroma. Two patients developed a secondary wound healing. Two patients developed chronic pain in the irradiated breast. Ten patients developed a grade 2 fibrosis. The remaining patients did not develop any grade 3 or 4 side effects. The observed toxicity rates were not influenced by age, tubus size, electron energy or systemic therapy. 80 patients had a follow up longer than 5 years. Three of them developed distant metastasis and one patient died. Conclusions: After IOERT of the breast using electrons we did not find any unexpected acute and late toxicity rates.
A phase I study of temsirolimus in combination with gemcitabine in previously untreated metastatic pancreatic cancer.
Authors: Jason Edward Faris, Lawrence Scott Blaszkowsky, Thomas Adam Abrams, Peter C. Enzinger, Aram F. Hezel, Brian M. Wolpin, David P. Ryan, Eunice Lee Kwak
Journal: Journal of Clinical Oncology (2012)

296 Background: The PI3K/mTOR/Akt pathway has been demonstrated to be active in pancreatic cancer, and preclinical data in mouse xenograft models has suggested possible synergy between gemcitabine and temsirolimus, an inhibitor of the mTOR pathway. The objective of this Phase I study was to assess toxicity and tolerability of gemcitabine and temsirolimus combination therapy in patients with newly diagnosed metastatic pancreatic cancer. Methods: The study was conducted with a modified, 3+3 phase I design for dose escalation. Patients in cohort 1 received temsirolimus at a fixed dose of 10mg IV on days 1,8,15, and 22, while gemcitabine was administered at 800mg/m 2 IV on days 1 and 15 of each 28 day cycle. Results: Between November 2007 and September 2008, 9 patients were enrolled in the trial, with a median age of 56. 6/9 patients were male, and all enrolled patients had a performance status of 1. One patient discontinued prior to starting treatment. 5 of the 8 patients receiving at least one infusion of gemcitabine and temsirolimus were removed from the study for toxicities associated with treatment. There were two episodes of Grade 4 neutropenia, and multiple Grade 3 toxicities, including cytopenias (neutropenia, leukopenia, and lymphopenia), elevated liver function tests, hyperglycemia, hypophosphatemia, diarrhea, and allergic reaction. There were no partial or complete responses observed. One patient demonstrated stable disease, receiving 6 cycles; this patient developed grade 3 neutropenia, requiring a dose delay and subsequent 20% dose reductions for temsirolimus and gemcitabine. No patients were enrolled after the first cohort, and no patients remain on study. In the 8 patients who began the study, the median time on study was 22 days, and overall survival was 126 days from study administration (range 88-416 days). Conclusions: This is the first published report of a human study involving gemcitabine and temsirolimus, which was associated with substantial toxicity in patients with advanced, previously untreated pancreatic cancer precluding further exploration of this combination.
Neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) in patients with high-grade upper-tract urothelial carcinoma.
Authors: Jean H. Hoffman-Censits, Edouard John Trabulsi, David Y. T. Chen, Alexander Kutikov, Jianqing Lin, Rosalia Viterbo, Gary R. Hudes, Kelly A. Healy, Scott Hubosky, Yu-Ning Wong, Deborah Kilpatrick, Beth Adair, Charlotte Cione, Elizabeth R. Plimack
Journal: Journal of Clinical Oncology (2014)

326 Background: Improved safety and response rates of AMVAC over standard MVAC in patients (pts) with metastatic bladder cancer support study of neoadjuvant AMVAC for pts with muscle invasive bladder cancer (MIBC) and prenephroureterectomy (NU) for pts with high-grade upper-tract urothelial cancer (UTUC). We performed a phase II study of neoadjuvant AMVAC in MIBC and UTUC, and herein report the results of the UTUC exploratory subgroup. Methods: Pts with UTUC (ureter or renal pelvis) with high-grade UC on biopsy, or positive urine cytology and mass on cross sectional imaging, N0-N1, CrCl &gt;=50, adequate hepatic and marrow function were eligible. Pts received 3 cycles of AMVAC (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, cisplatin 70mg/m2) day 1, pegfilgrastim 6 mg day 2 or 3, every 2 weeks. NU, with lymph node dissection at surgeon discretion, was performed 4-8 weeks after last cycle. Exploratory endpoint was pathologic complete response (pCR) rate. Results: Accrual is complete with 10 evaluable UTUC pts enrolled at 2 institutions (FCCC, TJU) over 46.5 months. Median age 67 (range 49-83). Of 10 pts, 6 completed all 3 cycles of AMVAC. Four pts received &lt; 3 cycles due to grade 3 acute kidney injury (1), pyelonephritis and grade 3 diverticulitis (1), flare of underlying hepatitis (1), grade 3 fatigue (1). Additional related grade 3 adverse events (AE) were anemia (1) and nausea/vomiting (1), no grade 4 or 5 AE. All pts underwent NU within 8 weeks of last chemotherapy, median 5.5 weeks. Median time from day 1 AMVAC to NU was 9 wks. 1/10 pts had a pCR, 4/10 patients were staged &lt;pT1, 2/10 pT2, and 3/10 &gt;pT3 or N+. An additional 21.5 months of enrollment were needed in this expansion cohort to accrue 10 pts with UTUC, compared to 44 MIBC pts in 25 mos. All pts completed study treatment as of July 2013. Conclusions: In this small sample, neoadjuvant AMVAC prior to NU was clinically active with manageable toxicity. With short duration from start of chemotherapy to NU, 3 neoadjuvant AMVAC cycles should be considered for further study for high-grade UTUC prior to NU in the cooperative group setting. Clinical trial information: NCT01031420.
A validated algorithm for sensitive and cost-effective mutation detection in clinical cancer specimens.
Authors: S. Querings, J. Altmüller, S. Ansen, T. Zander, D. Seidel, F. Gabler, J. Wolf, P. Nuernberg, R. K. Thomas
Journal: Journal of Clinical Oncology (2010)

e12009 Background: Patients with EGFR-mutant lung cancer experience tumor shrinkage and prolonged survival when treated with EGFR inhibitors. Furthermore, drugs targeting additional mutational activated proto-oncogenes are currently being evaluated clinically. Thus, validated approaches for sensitive and accurate mutation detection in a clinical setting are urgently needed but have, so far, been lacking. Methods: Here, we performed a careful and systematic validation of two sequencing approaches (namely, Sanger sequencing and pyrosequencing) against the gold standard, massively parallel sequencing. Results: Prospective mutational annotation of clinical lung tumor samples as a function of tumor content revealed previously recognized limitations of Sanger sequencing but also indicated that pyrosequencing is a reliable and sensitive approach to mutation detection in the setting of limited tumor content. Importantly, pyrosequencing is highly cost effective and dramatically extends the fraction of tumors that can be analyzed without the need for costly massively parallel sequencing. Furthermore, we identified severe limitations of histopathological estimates of tumor content, thus supporting the application of sensitive mutation detection approaches as apposed to microdissection of cancer specimens. Conclusions: In summary, we have established an analytical algorithm for mutation detection in an everyday clinical setting, taking into account quality and type of tumor specimens, tumor content as well as sensitivity, feasibility and costs of appropriate sequencing assays. Furthermore, we suggest thorough evaluation of all mutation detection approaches against massively parallel sequencing as a prerequisite for any clinical implementation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, Sequenom Boehringer Ingelheim, Infinity, Roche AstraZeneca
Evaluation of the prognostic significance of human mammaglobin expression in pleural effusion from patients with negative thoracoscopy.
Authors: A. Vigani, P. A. Canessa, C. Manta, P. Ferro, M. C. Franceschini, A. Morabito, M. Sivori, V. Fontana, F. Fedeli, M. P. Pistillo, S. Roncella
Journal: Journal of Clinical Oncology (2011)

10534 Background: It has been reported that application of the RT-PCR test for human mammaglobin (hMAM) may provide diagnostic information to evaluate the neoplastic origin of pleural effusion (PE). Our main goal was to assess the value of hMAM RT-PCR as an adjunctive test to thoracoscopic biopsy which represents the conventional gold standard in PE diagnosis. Methods: This study included 288 patients who underwent thoracoscopy. Histological analysis of pleural biopsies showed malignant diseases (MT) in 155/288 (53.8%) patients and non-malignant diseases (NMT) in 133/288 (46.2%) patients. The cells obtained from PE were analyzed by a nested RT-PCR protocol for hMAM mRNA gene detection. We evaluated the association between hMAM expression and MT vs NMT status by the diagnostic odds ratio (DOR). The diagnostic performance parameters of sensitivity (Se), specificity (Sp), accuracy (Ac), predictive positive value (PPV), predictive negative value (PNV) were also analysed. In addition, the relative risk of cancer in negative thoracoscopy patients showing hMAM expression in PE was evaluated by multivariate logistic regression analysis. Results: hMAM transcript was found in 68/288 (23.6%) of the total PE. Among them, 51/155 (Se=32.9%) positive cases were from MT and 17/133 (1-Sp=12.8) were from NMT. Statistical analysis showed significant correlation between hMAM expression and MT (DOR value of 3.04). The diagnostic performance parameters of hMAM detection were as follows: Sp=87.2.%, Ac=58.0%, PPV=75.0% and NPV=52.7%. The 18 month follow up of negative thoracoscopy patients showed that 5/17 (29,4%) of hMAM positive PE had a tumour in contrast to 10/126 (7.9%) of hMAM negative PE with a relative risk of 4.6 for developing malignancy (p=0.023). Conclusions: Our findings suggest a prognostic value of PE hMAM in non-specific pleuritis and may point out a false-negative thoracoscopy.
Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis
Authors: Ferda Cevikbas, Joao M. Braz, Xidao Wang, Carlos Solorzano, Mathias Sulk, Timo Buhl, Martin Steinhoff, Allan I. Basbaum
Journal: Journal of Allergy and Clinical Immunology (2017)
Randomized phase II study comparing dose-escalated weekly paclitaxel (wPTX) versus standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC).
Authors: Daisuke Takahari, Kohei Shitara, Satoshi Yuki, Michio Nakamura, Chihiro Kondo, Takashi Tsuda, Takayuki Kii, Yasushi Tsuji, Setsuo Utsunomiya, Daisuke Ichikawa, Ayumu Hosokawa, Atsushi Ishiguro, Keitaro Matsuo, Isao Oze, Kei Muro
Journal: Journal of Clinical Oncology (2013)

64 Background: wPTX is one of the standard second-line chemotherapies for AGC. Meanwhile, retrospective analysis of neutropenia during wPTX showed better overall survival (OS) among patients with neutropenia compared to patients without neutropenia. Therefore, we conducted randomized phase II trial comparing dose-escalated wPTX with dose adjustments determined by degree of neutropenia versus standard-dose wPTX for patients with previously treated AGC. Methods: Patients with AGC that progressed during 1 or more previous chemotherapy regimens were randomized to a standard dose of weekly paclitaxel (80 mg/m 2 , standard dose arm) or an escalated dose of weekly paclitaxel (80 mg/m 2 on day 1, 100 mg/m 2 on day 8, and 120 mg/m 2 on day 15 unless severe toxicity nor neutropenia&lt;1500 is observed, escalated dose arm). The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and safety Results: From September 2010 to November 2011, a total of 90 patients were randomised. Number of previous line of chemotherapy was 1 in 55% and 2 or more in other 45%. Among the 44 patients of dose escalated arm, the dose of wPTX was escalated to 100 mg/m 2 in 41 patients (93.2%) and then to 120 mg/m 2 in 29 patients (65.9%). Median PFS was significantly longer in dose escalated arm than standard dose (4.3 months. vs. 2.5 months, HR, 0.61; 95% CI, 0.39-0.95; p=0.03). ORR was 30.3% with dose escalation and 17.1% with standard dose (p=0.2). DCR was significantly higher with dose escalation (78.8% vs. 48.6%, p=0.009). Frequency of neutropenia (grade 1-4) was significantly higher with dose escalation (88.7% vs. 60.0%, p=0.002), but no significant difference was observed in grade 3/4 (40.9% vs.31.1%, p=0.34). Grade 3 peripheral sensory neuropathy was relatively common in dose escalated arm (13.6% vs. 6.7%, p=0.27). Conclusions: Dose escalated wPTX was associated with significantly longer PFS and higher DCR in patients with previously treated AGC in comparison with standard dose. The result of OS will be presented at the meeting Clinical trial information: UMIN000004055.
Abnormality in a fetus on ultrasound
Authors: Yong-Hai Zhou, Ming-Hua Zheng
Journal: BMJ (2017)

A pregnant 18 year old woman had an antenatal examination at 30 weeks’ gestation. She was healthy and had no history of smoking, drug abuse, or positive family history of chromosomal disease or encephalodysplasia. She had experienced mild flu-like symptoms during the first month of pregnancy but had not taken any medication, and the symptoms had disappeared after three days. During the antenatal appointment she had an ultrasound scan (fig 1⇓). What does the ultrasound image show?



Fig 1 …