tbuckley/cabot-search huggingface dataset:
Sunitinib and altered parathyroid function.
Authors: R. Mazzanti, V. Baldazzi, R. Tassi, A. Lapini, S. Caruso, E. Garofoli, A. Lunghi, M. Carini
Journal: Journal of Clinical Oncology (2011)

e15138 Background: Sunitinib malate is a tyrosine kinase inhibitor, active against tyrosine kinase receptors involved in tumour growth and angiogenesis. As sunitinib it involves many pathways in healthy tissues its use may result in unexpected side effects. Here we report the incidence of newly onset hyperparathyroidism in a cohort of sunitinib receiving patients affected by metastatic renal cell carcinoma (mRCC). Methods: Between July 2008 and November 2010, 25 mRCC patients received a daily 50 mg sunitinib administration according to classic 6-week schedule. In every patient, intact parathyroid hormone (PTH), serum and urinary phosphate and calcium, serum 25-hydroxyvitaminD and 1,25-dihydrovitaminD were measured before the beginning of treatment as well as at the end of each sunitinib ON period prospectively. Results: During sunitinib, 18 patients (72%) developed elevated PTH levels [median PTH at baseline 56.6 pg/mL; 139.5 pg/mL during sunitinib, + 146% median increase]. On average patients presented an elevation of PTH after 2.2 cycles (range 1-6). Patients presenting elevated PTH showed low or undetectable urinary calcium levels, while urinary phosphate remained within laboratory range. Serum phosphate resulted slightly decreased in 5 patients. Vitamin D and serum calcium resulted stable over time. Conclusions: Newly onset hyperparathyroidism may develop in an high percentage of patients undergoing sunitinib. A similar observation was reported among imatinib receiving patients, as a consequence of PDGF receptor α/β inhibition both on osteoclasts and osteoblast. As sunitinib also inhibits PDGF receptors, similar events could be hypothesized. Our observation suggests that abnormalities in bone metabolism may be a feature common to tyrosine kinases that inhibit the PDGF receptor family. A routine monitoring of bone metabolism during sunitinib administration is recommended, to recognise in vivo effects on bone mass of sunitinib especially during longer-term therapy.
The DISTAL-2 phase III randomized trial of single agent weekly docetaxel (wD) <i>vs</i> wD plus gemcitabine (G) or vinorelbine (V) vs wD plus capecitabine (X) as second-line treatment of advanced non-small-cell lung cancer (NSCLC) patients (pts)
Authors: V. Gebbia, R. Morena, L. Frontini, E. Aitini, B. Daniele, T. Gamucci, M. Di Maio, A. Morabito, C. Gallo, C. Gridelli
Journal: Journal of Clinical Oncology (2008)

19057 Background: Doublet chemotherapy is more effective than single-agent as 1st line treatment of advanced NSCLC. The aim of DISTAL-2 was to compare two doublets with wD as 2nd line treatment. Methods: NSCLC pts, aged <75, PS 0–2, who had failed platin-based therapy, were randomly assigned with a 3:1:1 ratio to: arm A, wD (33.3 mg/m2 dd 1, 8, 15 q4w); arm B, wD (30 mg/m2 dd 1, 8, 15) plus G (800 mg/m2 dd 1, 8 q4w) or plus V (20 mg/m2 dd 1, 8 q4w) depending on which of the two had been used in 1st line; arm C, wD (as in arm B) plus × (625 mg/m2 twice daily dd 5–18 q4w [supplied by Roche, Italy]). Primary endpoint was overall survival (OS). Two comparisons were planned: arm B vs A and arm C vs A. Overall, 375 pts had to be randomized. Response was assessed with RECIST, quality of life (QoL) by EORTC questionnaires. Results: 84 pts were randomized (A 47, B 18, C 19) from May’05 to Dec’06 when the trial was prematurely stopped due to slow accrual. After 62 deaths, median OS was 40.0 wks in arm A, 32.6 wks in arm B (p = 0.18 vs A) and 39.7 wks in arm C (p = 0.90 vs A). Response rate was 6.4%, 16.7% and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 wks, for arms A, B and C, respectively. Pts in arm B had significantly more grade 3–4 hematological and non-hematological toxicity compared to arm A, and pts in arm C had significantly more grade 3–4 non-hematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for pts in arm B. Conclusions: Due to early termination, the trial has not the planned statistical power. However, available data do not support the role of the studied doublets as 2nd line in advanced NSCLC No significant financial relationships to disclose.
16-covariate propensity score matching between trimodality (TMT)-eligible esophagogastric cancer (EC) patients who had surgery and those who declined surgery after preoperative chemoradiation.
Authors: Takashi Taketa, Lianchun Xiao, Akihiro Suzuki, Mariela A. Blum, Kazuki Sudo, Jeffrey H. Lee, Brian Weston, Manoop S. Bhutani, Steven H. Lin, Roopma Wadhwa, Stephen Swisher, Wayne Lewis Hofstetter, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2013)

111 Background: Localized EC patients should receive chemoradiation followed by surgery (TMT). Nevertheless, some patients decline surgery after preoperative chemoradiation. Reports on the outcome of such patients are scant. Methods: Between 2002 and 2011, we identified 622 TMT-eligible EC patients in our databases. Of 622 patients, 425 achieved clinical complete response (negative biopsy and PET in the physiologic range) after preoperative chemoradiation. Of 425, 244 patients underwent surgery but 61 patients declined surgery. We were able to matched 16 covariates between 36 patients who declined surgery and 36 patients who had TMT. Results: Baseline characteristics between the two groups were well-balanced (p=NS). Within this matched cohort, the median overall survival (OS) and relapse-free survival were 57.9 months (95% CI, 27.7-NA), and 18.5 (95% CI, 11.5-30.4) for the declined surgery group and those were 50.8 months (95% CI, 30.7-NA), and 26.5 months (95% CI, 15.5-NA) for the TMT group. OS and RFS for both groups were not different (p=0.28, and 0.45, respectively). However, 11 of 36 patients in the declined surgery group had salvage surgery (median OS was 66.1 months). Conclusions: These provocative results are in a small series but need to be interpreted with caution. Nevertheless, the results reinforce a possibility of esophageal preservation strategy that could encompass biomarkers and sophisticated imaging. Currently, however, trimodality remains the gold standard. Supported by UTMDACC and generous donors.
Overall survival and clinical characteristics in <i>BRCA</i> mutation carriers with stage I/II pancreatic cancer (PC).
Authors: Talia Golan, Tal Sella, Milind M. Javle, Ayelet Borgida, Eileen Mary O'Reilly, David Paul Kelsen, Ron Epelbaum, Hedy Lee Kindler, Matthew H. G. Katz, Steven Gallinger
Journal: Journal of Clinical Oncology (2015)

287 Background: BRCA1/2 mutation carriers with PC may have distinct biologic outcomes. We recently described favorable overall survival (OS) in patients with early-stage resected PC. However the prognostic impact of germline (GL) BRCA1/2 mutations in surgically-resected PC cases has not been yet compared with institution-matched controls. Methods: A multi-center, case-control retrospective analysis was performed of patients with surgically-resected, BRCA1/2 mutated PC from years 2001-2012. Non-hereditary PC controls were defined as BRCA negative or absence of a personal and first degree familial history of breast, ovarian or PC. Cases were matched by: age at diagnosis (+/- 5 years), treatment (neoadjuvant vs. adjuvant) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 and Fisher's exact test and median DFS/OS using Kaplan-Meier method and log-rank testing. Results: 20 patients with GL BRCA1/2 mutation PC were identified and matched (1:2) with 40 non-hereditary controls. Cases were comparable to controls in all tumor and treatment (neoadjuvant vs. adjuvant) related variables except lymphovascular involvement (30.6% vs 64.7%, p= 0.014). However, BRCA cases frequently received neoadjuvant (8/10 vs 6/14)/adjuvant (7/15 vs 3/34) platinum-based treatment. Clinical characteristics of GL BRCA1/2PC cases: BRCA1=3, BRCA2=17. Mean age was 56.7 years (41-78, SD 10.0), 65% (n=13) were female, 55% (n=11) were Jewish, 55% (n=11) had a family history and 95% (n=19) were stage II at resection. We demonstrated no difference in median OS (23.8 vs 25.9 months, p=0.397) and in DFS (13.6 vs 12.6 months, p=0.404) in BRCA1/2 mutation carriers vs controls. BRCA1/2mutation carriers did not experience improved DFS or OS with platinum-based chemotherapy. Conclusions: In this retrospective analysis, the prognosis of surgically-resectable BRCA associated PC is no different than that of sporadic PC from the same institution. The role of DNA damaging agents in this setting is still inconclusive.
Clinical Response to Oral Low-Dose Cyclosporin in Myelodysplastic Syndrome: Study of 31 Cases from India.
Authors: Rajat Kumar, Manoranjan Mahapatra, Lakshmi S. Pillai, Ashish Dixit, Pravas P. Mishra, Dharma R. Choudhary, Hara P. Pati, Atul Kotwal, Renu Saxena, V. P. Choudhry
Journal: Blood (2005)
The trajectory of physical functioning during breast cancer treatment of older women.
Authors: C. Owusu, M. D. Schluchter, S. M. Koroukian, N. A. Berger
Journal: Journal of Clinical Oncology (2011)

9129 Background: We sought to characterize the trajectory of physical functioning during the first 12 months following initial breast cancer diagnosis in older women with stage I-III breast cancer. Methods: Between April 2008 and March 2010 a cohort of women ≥65 years with incident stage I-III breast cancer, were enrolled into a prospective cohort study following primary surgery or prior to neoadjuvant chemotherapy. Participants completed a comprehensive geriatric assessment at study entry, six and 12 months. The primary end-points was mean change in the total Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) scores from baseline to six and 12 months, respectively. A decrease in ADL/IADL scores denoted functional decline. Results: Of sixty-one women enrolled, 48 completed baseline and 12th month CGA, four withdrew from the study, five were lost to follow-up and four have pending 12th month assessment as of 12/31/2010. This report includes the 48 evaluable women. The median age was 73 years, (inter-quartile range 68.5-80 years), 90% had stage I-II disease, 35% had node positive disease, 85% had hormone-receptor positive disease and 35% received adjuvant chemotherapy and/or trastuzumab. The mean change in ADL/IADL scores at six and 12 months was -0.58 [(sd=1.39), p= 0.008] and -0.85 [(sd=2.37), p= 0.02], respectively. The proportion of women who had a decrease, an increase or no change in ADL/IADL scores at six and 12 months from baseline were 24%, 5% and 71%, and 29%, 10% and 61%, respectively. Women with lower than high school education (46% vs. 14%, p=0.03), Karnofsky Performance Status scores ≤80% (67% vs. 17%, p=0.002), any IADL dependency (63% vs. 13%, p=0.0003), Timed-Up-and-Go Test time >14 seconds, (67% vs. 22%, p=0.05) and tumor size ≥ 2cm, (50% vs. 13%, p=0.01) at baseline were more likely to develop functional decline at 12 months. Conclusions: One out of every four older woman with breast cancer developed functional decline within six months of treatment increasing to almost one out of every three older woman by 12 months. Studies to identify biologic, molecular and clinical determinants of functional decline in older women with breast cancer in the adjuvant setting are warranted to inform remediation.
A 19-gene prognostic GEP signature to determine metastatic risk associated with thymomas.
Authors: Yesim Gokmen-Polar, Chirayu Pankaj Goswami, Robert W. Cook, Kristen M. Oelschlager, Derek Maetzold, Ioan Tudor Vladislav, Kristen L. Shirar, Kenneth Kesler, Patrick J. Loehrer, Sunil S. Badve
Journal: Journal of Clinical Oncology (2012)

68 Background: Therapeutic decisions for patients with thymomas are made on tumor stage as histologic classification is of limited prognostic value. A molecular prognostic tool may better predict the likelihood of metastasis in thymomas and enable better management of patients. Methods: Reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for 23 genes (19 test and 4 reference genes) was performed on archival paraffin-embedded primary thymomas (n=36). The gene expression levels were used to compute gene expression profile (GEP) signature and classify tumors into low or high risk. The GEP was validated in an independent test set (n=75) of patients. Results: We developed and validated a 19-gene prognostic GEP signature for predicting metastatic behavior in thymomas. Using radial basis machine (RBM) modeling in the training set, both 5-year and 10-year MFS rates were 85% and 22% for predicted low risk and high risk of metastasis (p&lt;0.0005, log-rank), respectively. For the validation set, 5-year MFS rates were 93% and 35% for predicted low and high risk patients (p&lt;0.0018 log-rank), respectively. The 5-year MFS rates for Masaoka stage in the validation set were 53% and 41% for stage I/II and stage III/IV(p&lt;0.0433 log-rank), respectively. In a multivariate Cox model, the GEP was the only independent predictor of metastasis free survival compared to age at diagnosis and stage (p=0.048). Conclusions: Using archival tissues, we identified and validated a 19-gene signature that predicts likelihood of metastases of thymomas more accurately than traditional staging. The signature provides insights for both patient stratification and targeted therapy.
Evolution and prognosis of adult patients with non-Hodgkin lymphoma
Authors: L. A. Casanova, C. Flores, C. Samanez, J. León
Journal: Journal of Clinical Oncology (2008)

19527 Background: Non-Hodgkin Lymphoma (NHL) is a malignant neoplasm of lymphoid system with marked differences in presentation and prognosis. The objective was to determine the clinical behavior and prognostic factors of the patients with NHL. Methods: 2834 clinical records of patients with LNH diagnosed at INEN between 1990 and 1999 were reviewed. We described the clinical-pathological characteristics, treatment and response. The complete response (CR) and recurrence rate were compared by Chi-square or exact Fisher test. The survival curves were estimated by Kaplan-Meier and comparisons by Logrank or Breslow test. The prognostic factors for CR were identified by logistic regression and for survival by Cox model. Results: The median age was 55 years (range: 14–96), most of them between 45 and 74 years, and 50% were male. The clinical characteristics were: zubrod ≥2 (28%), primary node disease (64%), B-symptoms (36%), clinical stage III-IV (52%), anemia (51%), leukocytosis (20%), increased DHL and β2M in 48% and 36% respectively. 90% had aggressive lymphoma and 53% intermediate-high and high risk IPI. 2221 (78%) patient received treatment: chemotherapy alone (CT) 67%, radiotherapy alone (RT) 8% and CT+RT 20%; CHOP was the most frequent CT scheme (84%). 64% had CR and 21% PR; 191/723 (26%) had recurrence. The median follow-up was 15 months. The 5-year DFS (disease-free-survival) and OS (overall survival) were 58% and 48%. The prognostic factors for CR were age > 60 (p=0.027, RR: 0.71), male sex (p=0.001, RR: 1.6), zubrod ≥2 (p<0.001, RR: 1.8), stage III-IV (p<0.001, RR: 2.0) and increased DHL (p<0.001, RR: 1.9). CS III-IV (p<0.001, RR: 2.0) and increased DHL (p<0.001, RR: 1.7) for DFS. Zubrod ≥ 2 (p<0.001, RR: 2.2), B symptoms (p=0.030, RR: 1.3), CS III-IV (p<0.001, RR: 2.0), leukocytosis (p<0.001, RR: 1.7) and increased DHL (p<0.001, RR: 1.8) for OS. Conclusions: The presentation of NHL was similar to other series, although with higher frequency of anemia, advanced disease, aggressive lymphoma that conditioned the prognosis. CR, DFS and OS, were similar to other series. Clinical stage and increased DHL are prognostic factors to take into consideration in the follow-up, since they are related to the tumor volume. In our serie, leukocytosis was also an important prognostic factor for OS. No significant financial relationships to disclose.
Aprepitant is active in biologic therapies induced severe pruritus: Proof of concept study.
Authors: D. Santini, B. Vincenzi, F. Guida, A. M. Frezza, O. Venditti, M. Silletta, G. Tonini
Journal: Journal of Clinical Oncology (2011)

9078 Background: Increasing evidences prove the involvement of keratinocytes NK1 receptors in the pathogenesis of pruritus: this prospective study aims to evaluate the role of aprepitant, a NK1 receptor antagonist, in the treatment of severe pruritus induced by biological therapies. Methods: 22 patients (11 Male/11 Female), 61 years as mean age, affected by lung cancer (10), colorectal cancer (9) or other tumors (3), who developed severe pruritus (VAS ≥7) during treatment with erlotinib (10), cetuximab (10), sunitinib (1) and imatinib (1) were enrolled. After the onset of severe pruritus aprepitant was administered (125 mg day 1; 80 mg day 3; 80 mg day 5). Pruritus intensity was evaluated by VAS score before and after aprepitant administration (day 7 and every other following week until day 90 or the recurrence moment). Results: Initial pruritus intensity was 9 in 6 patients, 8 in 12 and 7 in 4 (median 8). After 1 week of aprepitant therapy the reported pruritus intensity was 0 in 10 patients, 1 in 4, 2 in 4, 3 in 2, 4 in 1 and 6 in 1 (median 1). The median decrease was 88%. Moreover, 91% of patients responded to aprepitant (decrease > 50%), 2 did not. Median duration of one cycle effect was 25 days (7-90 days). Conclusions: This study assessed aprepitant activity in the management of biological therapies induced severe pruritus. Randomized studies are necessary to compare aprepitant activity with those of standard therapies.
What are physician and patient factors important for proper follow-up of high-grade Pap smear abnormalities?
Authors: L. F. Paszat, R. Kupets
Journal: Journal of Clinical Oncology (2010)

6103 Background: In order for expedited care to be provided to women with severe abnormalities on Pap smear, the physician should provide prompt triage of care and the patient should comply with follow-up care provided. This population-based study characterizes available physician and patient factors involved in the follow-up of abnormal Pap smear results. Methods: Women with a first time high grade diagnosis on Pap smear between 2000-2005 were identified utilizing a centralized cervical screening database. Databases containing information on healthcare delivery and physician practice characteristics in a setting of universal health care were linked utilizing patient and physician unique identifiers. Follow-up is defined as referral to colposcopy or any other procedure (Leep, Laser, etc) which can be associated with management of a severe cervical dysplasia. multivariate analysis followed by logistic regression was performed addressing follow-up as the dependant factor. Results: The study population contained 43,792 women with a first time high grade cervical abnormality. The loss to follow-up rate was 26%. Physician factors significantly associated with follow-up included practice duration of less than 5 years OR 1.28 CI (1.09-1.5);a nongynecologic practice was associated with lower follow-up, OR 0.69 CI (0.65-0.73). Patient factors associated with lower follow-up included older age 0.97 CI (0.97-0.98 and a lower comorbidity score 0.58 CI (0.48-0.7); a lower socioeconomic status was associated with a higher rate of follow-up OR 1.17 CI (1.1-1.2). Conclusions: While patient and physician factors impact appropriate follow-up for women with abnormal Pap smears, none of those captured have a high level of influence other than a gynecologic practice. In order to improve upon the high loss to follow-up rate, more information is needed on the practice settings of physicians and the screening program components and policies. No significant financial relationships to disclose.
Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation Using the Donors with the HLA-B*5801-TNFα -308A Haplotype Produced Higher Frequency of Untoward Effects in Acute Lymphocytic Leukemia Patients
Authors: Liyun Yang, Yan Chen, Sainan Zhu, Dingfang Bu, Lixiang Wang, Xiaojie Jiao, Xuechun Lu, Hongxing Liu, Ping Zhu
Journal: Blood (2012)
Tears of colonoscopy
Authors: Michael McFarlane, Ben Disney, Jayne Eaden
Journal: Gut (2017)

A 72-year-old woman was referred to the gastroenterology outpatient clinic reporting an 18-month history of loose and watery stools up to 10 times per day with nocturnal episodes. She also presented with urgency, occasional faecal incontinence, excessive bloating and flatulence. She had lost 14 kg in weight over the same period. There was no blood or mucus in her stools.

Her symptoms began after she underwent an emergency appendicectomy for suspected appendicitis. The histology revealed a carcinoid tumour, but with clear resection margins and a subsequent CT scan showed no …
Arterial elasticity in testicular cancer survivors.
Authors: Anne Hudson Blaes, Daniel A. Mulrooney, Rachel Isaksson Vogel, Bruce A. Peterson, Douglas Yee, Joseph Philip Neglia, Daniel Duprez
Journal: Journal of Clinical Oncology (2014)

9604 Background: Testicular cancer survivors are known to have an increased risk of cardiovascular (CV) disease. We aimed to explore the impact of platinum based chemotherapy on endothelial function. Methods: Survivors < 30 years at diagnosis who received platinum chemotherapy 2002-2012 and 17 similarly-aged healthy male controls were identified. A history of CV disease was excluded. Subjects underwent pulse wave analysis using the HDI/PulseWave CR-2000 Cardiovascular Profiling System and Pulse contour analysis using the Endo-PAT2000 system. Biomarkers were obtained to evaluate lipids and inflammatory markers. Comparisons were made using T-tests and Wilcoxon Rank-Sum tests. Results: 13 survivors (median age 30.2 years, body mass index [BMI] 27.3) and 17 health controls (median age 27.1 years, BMI 24.8) enrolled. Median time from chemotherapy was 4.7 (range 0.8-14) years. Four cases (30.8%) and no controls smoked. There was no difference in lipid profiles between cases and controls.* Median systolic blood pressure (SBP) was elevated (124.5 mmHg cases, 113.4 mmHg controls, p=0.010). Despite the young age of participants, cases had reduced small artery elasticity (9.0 vs 10.4 ml/mmHg x 10, p=0.086). Smoking appears to exacerbate SBP, lipids and artery elasticity. Conclusions: In this pilot study, testicular cancer survivors early after the completion of cancer therapy have elevations in SBP and reduced small artery elasticity, suggesting premature CV risk. Further follow up is warranted. Measure Normals All cases Smoker cases Non-smoker cases Controls p-value* SBP (mmHg) <140 124.5 (10.9) 128.0 (13.7) 122.1 (9.8) 113.4 (10.9) 0.010 Diastolic blood pressure (mmHg) <90 77.7 (9.9) 83.8 (9.3) 74.7 (9.1) 73.4 (5.8) 0.182 Cholesterol (mg/dl) <200 178.2 (45.4) 184.5 (64.8) 176.8 (38.4) 168.4 (39.6) 0.544 Triglycerides (mg/dl) <150 152.6 (124.5) 246 (193.5) 106.0 (49.1) 119.7 (90.7) 0.431 HDL (mg/dl) >45 43.0 (15.6) 33.5 (8.2) 48.6 (49.1) 47.4 (9.4) 0.377 LDL (mg/dl) <130 106.4 (43.7) 109.0 (51.7) 106.6 (44.0) 97.1 (27.8) 0.524 Large artery elasticity (ml/mmHg x 10) 19.9 (6.6) 16.7 (2.1) 21.3 (7.5) 18.6 (3.0) 0.679 Small artery elasticity (ml/mmHg x 10) 9.0 (2.5) 8.0 (1.5) 9.5 (2.7) 10.4 (2.3) 0.086 * Wilcoxon Rank Sum test, comparing all cases and controls.
Effect of Linagliptin on Arterial 18 F-Fluorodeoxyglucose Positron Emission Tomography Uptake
Authors: Stefanie A. de Boer, Hiddo J.L. Heerspink, Joop D. Lefrandt, Marieke C. Hovinga–de Boer, Arie M. van Roon, Luis E. Juárez Orozco, Andor W.J.M. Glaudemans, Pieter W. Kamphuisen, Riemer H.J.A. Slart, Douwe J. Mulder
Journal: Journal of the American College of Cardiology (2017)