tbuckley/cabot-search huggingface dataset:
Chemotherapy-induced amenorrhea is increased in patients treated with adjuvant doxorubicin and cyclophosphamide (AC) followed by a taxane (T)
Authors: R. Kramer, Y. L. Tham, K. Sexton, L. Friedman, H. Weiss
Journal: Journal of Clinical Oncology (2005)

651 Background: 25% of invasive breast cancers occur in premenopausal women. Adjuvant chemotherapy may induce amenorrhea, resulting in infertility, influencing hormonal therapy options, and potentially increasing risks of late toxicity. Methods: We retrospectively surveyed women who were premenopausal and < age 50 at initiation of chemotherapy to determine if giving T after AC (AC → T) altered rates of chemotherapy induced amenorrhea (CIA). Women who received either AC x 4 or AC x 4 followed by 3 months of T (either paclitaxel or docetaxel) with or without adjuvant tamoxifen were recruited from a dedicated breast clinic and the Young Survival Coalition. CIA was defined as cessation of menses within one year of starting chemotherapy and lasting ≥ 6 months. Results: 195 eligible patients completed the survey. 160 were ≤ 40. 35 were > 40 but < 50. 77 patients received AC, 118 received AC → T. In patients ≤ 40, the rate of CIA was greater for those who received AC → T (61%) as compared to AC (44%), p=0.04 (OR 1.97, 95% CI 1.01 to 3.84). Many of these young women subsequently resumed menstruating (33% receiving AC, 43% receiving AC → T). Women > 40 had a high likelihood of experiencing CIA with both AC (81%) and AC → T (84%), p=0.35 (95% CI 0.20 to 8.31) and for 82% this was permanent. Results of multivariate logistic regression analysis show that the odds of developing CIA was nearly 5 fold higher for women > 40 than for those ≤ 40 (p=0.002). Those receiving AC → T had an odds ratio of CIA of 1.9 compared to those receiving AC (p=0.05). Tamoxifen did not influence CIA in either group of patients. Conclusion: The addition of T to AC increases the risk of CIA in patients ≤ 40. Women ≤ 40 who experience CIA have a substantial chance of resuming menstruation even after 6 months of amenorrhea and this should be carefully considered when planning hormonal therapy and contraception in this age group. No significant financial relationships to disclose.
Analysis of time-dependent patterns of treatment effect and failure to explain the predictive role of deficient mismatch repair (dMMR) in stage II and III colon cancer (CC).
Authors: G. P. Kim, S. Marsoni, G. Monges, C. J. Allegra, S. N. Thibodeau, S. R. Hamilton, B. Kabat, G. A. Yothers, S. Gallinger, D. J. Sargent
Journal: Journal of Clinical Oncology (2010)

3518 Background: dMMR is a favorable prognostic marker and a predictive marker for lack of benefit from 5FU-based adjuvant chemotherapy (AT). To better understand the relationship between MMR status, treatment benefit, relapse, and survival, time patterns of recurrence risk (RR) in patients with dMMR and proficient MMR (pMMR) tumors were compared. Methods: 1,562 patients (pts) from randomized phase III trials including 5FU-based AT and surgery alone (S) arms were analyzed. The trials included data previously presented by Sargent (ASCO 2008) and additional data from several NSABP trials. Tumors from stage II (n=757) and III (n=805) pts were assayed for MMR status. Time- dependent patterns of recurrence (TTR), disease free (DFS), and overall survival (OS) were analyzed by MMR status and treatment received. Results: Over the 8-year study period, in pts treated with S alone, dMMR pts maintained a consistent advantage in the endpoints TTR, DFS, OS compared to pMMR pts (see Table). dMMR pts treated with S alone had an approximately two-fold lower RR than pMMR pts in particular during the first 4 years after treatment. dMMR patients recur less overall, without a trend towards later recurrences. 5FU-based AT provided pMMR pts a pronounced RR reduction within the first four years of follow-up that is not observed in dMMR pts, in whom AT was not associated with a reduced RR. Survival is poor (∼ 1 year) following recurrence and is independent of MMR status (p=0.71 S, p=0.99 AT). Conclusions: The favorable prognosis and low RR in dMMR pts is maintained throughout the natural course of the disease. In particular, in dMMR pts, the RR is low, and no benefit from AT is observed at any point. Conversely, pMMR pts have an increased RR during the first four years postsurgery that is significantly reduced with 5FU-based AT. Annualized risk for recurrence MMR status Year 0-2 Years 2-4 Years 4-6 Years 6-8 S AT S AT S AT S AT dMMR 16.8% 15.5% 4.8% 5.2% 3.8% 2.7% 0.0% 2.3% pMMR 25.1% 18.1% 13.1% 8.2% 4.1% 4.6% 1.8% 0.7% No significant financial relationships to disclose.
Maintenance therapy with gefitinib (G)/pemetrexed (P) versus P alone after induction therapy with P/platinum for metastatic lung adenocarcinoma (MLADC) harboring no sensitizing epidermal growth factor receptor mutation (sEGFRm): A phase II multicenter randomized open-label study (GENIUS trial).
Authors: Chun-Ming Tsai, Chun-Liang Lai, Chao-Hua Chiu, Te-Chun Hsia, Chen-Hsin Chen, Gee-Chen Chang, Jin-Yuan Shih, Ching-Liang Ho, Yuh-Min Chen, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2015)

8043 Background: Synergistic EGFR-tyrosine kinase inhibitor (TKI)-chemotherapeutic interaction in lung cancer cells has 3 basics: no platinum, cells not sensitive to EGFR-TKI, and using a synergistic chemo partner, e.g., pemetrexed (Tsai, et al. Lung Cancer 82:305, 2013). Methods: GENIUS (NCT01579630) was a prospective trial comparing maintenance G/P v P in patients (pts) with MLADC harboring no sEGFRm detected by high sensitivity methods following a 4-cycle P/Platinum induction therapy in frontline setting. Pts with no disease progression (PD) were 1:1 randomized to receive P (500mg/m2, 3-week cycle) ± G (250mg, daily) until PD or treatment failure, and stratified by center and response. The primary endpoint was progression free survival (PFS) by both independent radiologist review (IRR) and investigator assessment (IA), secondary endpoints included time to treatment failure (TTF), overall survival, safety and toxicity profile. Results: Between 03/2011 and 11/2013, 55 pts were randomized, G/P 26, P 29. Baseline characteristics were balanced between arms (age 57; female 42%; never smoker 55%; ECOG1 91%; ≥ 2 metastatic sites 38.2%; ALK+ 16%). Median follow-up was 15.9 mo. Median cycle of treatment was G/P 8.5 (range 1-27) and P 4 (2-17). Median PFS was substantially longer for G/P than P, both by IRR (3 deemed as PD at randomization were excluded; n = 25 v 27): 8.4 v 3.8 mo; HR [95% CI] 0.35 [0.18-0.68]; p = 0.0014, and by IA: 8.5 v 2.9 mo; HR 0.34 [0.18-0.64], p = 0.0005. Response with induction therapy, age, and smoker had interactions with treatment for PFS. Median TTF: 7.0 v 2.9 mo; HR 0.43 [0.24-0.79], p = 0.005. There were more treatment-related diarrhea, liver and skin toxicities on G/P v P, but generally mild. 2 G/P pts were off-study due to liver toxicity. Death occurred in 8 G/P and 14 P pts. Conclusions: GENIUS is the first prospective trial to show robust PFS benefit of EGFR-TKI plus chemo in the maintenance phase of 1st line treatment for MLADC with no sEGFRm and proved our concept. This strategy deserves phase III study to confirm. Clinical trial information: NCT01579630.
The Peripheral Nervous System.
Journal: Annals of Internal Medicine (1966)

U radu su sustavno opisane: funkcijske vrste živcanih vlakana, funkcijski nizovi jezgara kranijalnih živaca u moždanom deblu, nervus oculomotorius, nervus trochlearis, nervus trigeminus, nervus abducens, nervus facialis, nervus, nervus glossopharingeus, nervus vagus, nervus accessorius, nervus hypoglossus, plexus cervicalis, plexus brachialis, nervi thoracici, plexus lumbosacralis, plexus coccygeus, pars sympatica autonomnog sustava, pars parasympatica autonomnog sustava, te topografska anatomija autonomnog sustava. Na kraju poglavlja opisani su klinicki slucajevi vezani uz sadržaj poglavlja.
Abstract P184: Smoking, Menthol Cigarettes and All Cause, Cancer and Cardiovascular Mortality: Evidence from the National Health and Nutrition Examination Survey (NHANES)
Authors: Miranda R Jones, Ana Navas-Acien
Journal: Circulation (2013)

Introduction: Cigarette flavorings, with the exception of menthol, have been banned under the Family Smoking Prevention and Tobacco Control Act. The U.S. Food and Drug Administration has the authority to regulate tobacco product constituents, including the use of menthol, if the scientific evidence indicates harm; however few studies have evaluated the health effects of menthol as compared to nonmenthol cigarette use. Objective: To investigate the prospective associations of cigarette smoking and menthol cigarette use with all cause, cancer and cardiovascular mortality in U.S. adults. Methods: We studied 10,158 adults 20 years of age and older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999-2004 and were followed for an average of 4.7 years. Results: Fifty-five percent of participants were never smokers compared to 23%, 17% and 5% of former, current nonmenthol and current menthol cigarette smokers, respectively. The multivariable adjusted hazard ratios (95% confidence intervals [CI]) for former, current nonmenthol cigarette smokers and current menthol cigarette smokers compared to never smokers were 1.21 (0.93, 1.56), 2.46 (1.57, 3.83) and 2.10 (1.21, 3.66), respectively, for all-cause mortality, 0.86 (0.58, 1.27), 2.10 (1.05, 4.21) and 3.53 (1.55, 8.02) for cardiovascular mortality, 1.32 (0.73, 2.38), 4.04 (1.96, 8.35) and 5.50 (1.90, 15.88) for heart disease mortality and 1.94 (1.23, 3.05), 3.88 (2.21, 6.80) and 2.08 (1.01, 4.28) for cancer mortality. Compared to current nonmenthol cigarette smokers, adjusted hazard ratios (95% CI) for current menthol cigarette smokers were 0.87 (0.54, 1.42) for all-cause mortality, 1.66 (0.75, 3.68) for cardiovascular mortality, 1.39 (0.52, 3.67) for heart disease mortality and 0.57 (0.28, 1.18) for cancer mortality. Conclusions: In a representative sample of U.S. adults, menthol cigarette smoking was associated with increased all-cause, cardiovascular and cancer mortality with no differences compared to nonmenthol cigarettes, except maybe an increased risk for cardiovascular disease.
Pathogenesis of Desmoplasia. I. Immunofluorescence Identification and Localization of Some Structural Proteins of Line 1 and Line 10 Guinea Pig Tumors and of Healing Wounds 1,2<xref ref-type="fn" rid="FN2">2</xref>
Authors: H F Dvorak, D M Form, E J Manseau, B D Smith
Journal: JNCI Journal of the National Cancer Institute (1984)

The structural proteins of the scirrhous line 1 and the medullary line 10 bile duct carcinomas, both syngeneic in strain 2 Sewall-Wright inbred guinea pigs, were studied. Tumor structural proteins were compared with those of healing wounds. A provisional stromal matrix of cross-linked fibrin and fibronectin was initially deposited in both tumors and wounds and was subsequently replaced by granulation tissue containing collagen types I and III. The amounts of stromal fibrin-fibronectin and collagen were characteristic of each tumor: Line 1 contained significantly greater amounts than line 10. These differences were augmented when line 1 tumor rejection was prevented with cyclosporine, permitting time for stromal maturation. In tumors and wounds laminin and collagen type IV were found only in basement membranes. The findings suggest that 1) tumor desmoplasia is analogous to wound healing, 2) both processes involve replacement of an antecedent fibrin-fibronectin provisional matrix, 3) the extent of fibrin-fibronectin is characteristic of each tumor, and 4) tumor desmoplasia correlates with the amount of fibrin-fibronectin matrix deposited.
Need for Supportive Counselling – the Professionals’ versus the Patients’ Perspective
Authors: W Söllner, M Zingg-Schir, G Rumpold, G Mairinger, P Fritsch
Journal: Psychotherapy and Psychosomatics (1998)

&lt;b&gt;Background: &lt;/b&gt;The aim of the study was to identify melanoma patients who suffered significant distress and were judged to be in need of supportive counselling, on the one hand, and, on the other, to investigate patient interest in such support. &lt;b&gt;Methods:&lt;/b&gt; Out of 236 melanoma patients, who constitute a representative sample of melanoma patients in Western Austria, 215 patients participated in the study and were assessed with regard to psychosocial distress, coping strategies, social networks and interest in receiving psychosocial support. Multiple logistic regression analyses were performed with regard to patient interest in receiving psychosocial support either from the attending oncologist or from a mental health professional. &lt;b&gt;Results: &lt;/b&gt;65 patients (30.2%) experienced moderate and 30 patients (14.0%) severe distress, which was predominantly caused by tumour-related fears, tension and disturbance of emotional well-being. 83% of the severely distressed patients wanted psychosocial support from their oncologists, whereas only half of them were interested in additional support from a psychotherapist. In particular, patients who showed fear of tumour progression and felt that they were insufficiently informed about their disease preferred to consult their dermatologist for psychosocial support. On the other hand, patients with poor prognosis, receiving only low levels of support from their social network, and exhibiting a depressive coping style, showed interest in getting supplementary support from a psychotherapist. &lt;b&gt;Conclusions: &lt;/b&gt;These findings underline the importance of educating oncologists with a view both to improve their communication skills and to help them identify patients making poor adjustment to illness in order to offer them appropriate emotional support.
Integration of specialist palliative care services into a multidisciplinary adolescent and young adult (AYA) oncology team.
Authors: Rachel Elizabeth Hughes, Kate Thompson
Journal: Journal of Clinical Oncology (2014)

64 Background: Palliative care is recommended alongside standard oncological care for patients with advanced cancer or high symptom burden (Smith TJ, Temin S, et al. American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. Journal of Clinical Oncology. 2012;30(8)880-7.). AYA oncology patients are distinguished by several age-specific developmental and biopsychosocial factors, resulting in a unique impact profile (Wein S, Pery S, Zer A. Role of palliative care in adolescent and young adult oncology. J Clin Oncol. 2010;28:4819-4824). Methods: To examine the benefits of multidisciplinary AYA care, a palliative care fellow was incorporated into an existing AYA oncology team in Australia, for a 12 month period. This role facilitated assessment/management of symptoms, general health issues, treatment toxicity, end of life care and bereavement support. Results: Between 2012 and 2013, of 83 new patients were referred to the AYA oncology service, 27 (32.5%) were referred the palliative care fellow. Notably, 37% of patients referred were receiving curative intent treatment. 10 patients (37%) were referred at diagnosis for symptom management. Pain was the most frequent reason for referral (n=17 63%). A total of 7 patients (26%) were referred for advanced disease/terminal care. Conclusions: Evaluation demonstrates that onsite availability of palliative care services is acceptable, facilitates early referral and has encouraged collaborative, AYA multidisciplinary care. A significant additional finding has been recognition of the demand for symptom management of patients early in their cancer experience. Further development and evaluation of AYA specific palliative care is warranted.
Aroyl-Pyrrolyl-Hydroxy-Amides (APHAs), a Novel Family of Synthetic Histone Deacetylases Inhibitors, Are Potent Inducers of Human g-Globin Gene Expression.
Authors: Antonello Mai, Silvio Massa, Antonella Di Noia, Katija Jelicic, Elena Alfani, Cristina Di Rico, Angela Di Baldassarre, Anna Rita Migliaccio, Giovanni Migliaccio
Journal: Blood (2004)
Predicting renal functional outcomes after surgery for renal cortical tumors: A multifactorial retrospective analysis
Authors: R. Korets, L. Barlow, M. Laudano, M. Benson, J. McKiernan
Journal: Journal of Clinical Oncology (2009)

e16005 Background: Nephrectomy (Nx) is the standard of care for localized renal tumors. The risk of developing chronic renal insufficiency (CRI) increases after renal surgery. This study examines the functional outcomes for radical and partial Nx stratified by pre- and perioperative variables using estimated GFR. Methods: Using the Columbia Urologic Oncology Database, a retrospective analysis of patients treated with partial or radical Nx for renal cancer from 1988 to 2008 was conducted. Postoperative chronic renal function was measured using GFR as estimated by the MDRD study equation. Three primary outcomes were measured: 1) presence of new onset postoperative CRI (defined as GFR lower than 60 mL/min per 1.73 m 2 ), 2) percent change in postoperative GFR from preoperative value, and 3) change in CRI stage postoperatively. Regression models were used to determine the effect of surgical procedure (radical vs partial Nx), approach, and multiple preoperative characteristics on functional outcomes. Results: 174 patients met the criteria for analysis after radical Nx and 102 after partial Nx for a total of 276 patients. 209 patients had preoperative GFR &gt; 60, 67 had preoperative GFR &lt; 60, and 6 had preoperative GFR &lt; 30. After a minimum of 3 months postoperatively, 108/209 (52%) and 2/209 (1%) patients developed new-onset GFR &lt;60 and &lt;30, respectively. On multivariate analysis controlling for age, sex, race, diabetes and hypertension, preoperative CKD stage (p&lt;0.001) and procedure (p&lt;0.001) were both independent predictors of GFR progression to &lt;60; similarly, preoperative CKD stage (p&lt;0.001) and procedure (p&lt;0.01) were independent predictors of percent change in postoperative GFR. Patient with worsened preoperative CRI stage were less likely to have further progression of CRI postoperatively (p&lt;0.001) independent of the surgical procedure. Surgical approach was not an independent predictor of any renal functional outcomes measured. Conclusions: Patients undergoing renal surgery have a high rate of new-onset postoperative renal failure. After controlling for preoperative risk factors, patients undergoing radical Nx are at higher risk for decline in renal function. Surgical approach, however, was not a significant predictor for the development of CRI. No significant financial relationships to disclose.
Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration
Authors: Frank G. Holz, Pravin U. Dugel, Georges Weissgerber, Robin Hamilton, Rufino Silva, Francesco Bandello, Michael Larsen, Andreas Weichselberger, Andreas Wenzel, Anne Schmidt, Dominik Escher, Laura Sararols, Eric Souied
Journal: Ophthalmology (2016)

To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD).Six-month, phase 1/2, prospective, multicenter, double-masked, randomized, ascending single-dose, active-controlled, parallel-group study.A total of 194 treatment-naive patients, aged ≥50 years, with primary subfoveal choroidal neovascularization secondary to AMD.Patients received a single intravitreal injection of RTH258 0.5 mg (n = 11), 3.0 mg (n = 31), 4.5 mg (n = 47), or 6.0 mg (n = 44), or ranibizumab 0.5 mg (n = 61).The primary efficacy end point was the change from baseline to month 1 in central subfield thickness (CSFT) measured by spectral-domain optical coherence tomography. The secondary efficacy end point was the duration of treatment effect measured as time from the initial injection to receipt of post-baseline therapy (PBT) guided by protocol-defined criteria. Adverse events (AEs) were recorded throughout the study.RTH258 demonstrated noninferiority compared with ranibizumab in mean change in CSFT from baseline to month 1 for the 4.5- and 6.0-mg dose groups (margin: 40 μm, 1-sided alpha 0.05). The difference in CSFT change at month 1 comparison with ranibizumab was 22.86 μm (90% confidence interval [CI], -9.28 to 54.99) and 19.40 μm (95% CI, -9.00 to 47.80) for RTH258 4.5 and 6 mg, respectively. The median time to PBT after baseline therapy was 60 and 75 days for patients in the RTH258 4.5- and 6.0-mg groups, respectively, compared with 45 days for ranibizumab. Changes in best-corrected visual acuity with RTH258 were comparable to those observed with ranibizumab. The most frequent AEs reported for the RTH258 groups were conjunctival hemorrhage, eye pain, and conjunctival hyperemia; the majority of these events were mild in intensity.This first-in-human study of RTH258 demonstrated noninferiority in the change in CSFT at 1 month for the 4.5- and 6.0-mg doses compared with ranibizumab and an increase of 30 days in the median time to PBT for the 6.0-mg dose. There were no unexpected safety concerns, and the results support the continued development of RTH258 for the treatment of neovascular AMD.
Derivation of Schwann cell precursors from neural crest cells resident in bone marrow for cell therapy to improve peripheral nerve regeneration
Authors: Haiyan Shi, Yanpei Gong, Liang Qiang, Xiaoli Li, Shibo Zhang, Jiawen Gao, Kai Li, Ximeng Ji, Ling Tian, Xiaosong Gu, Fei Ding
Journal: Biomaterials (2016)
Oxaliplatin rechallenge in patients with metastatic colorectal cancer prior treatment with oxaliplatin.
Authors: Jeong-Eun Kim, Yong Sang Hong, Kyu-Pyo Kim, Seong Joon Park, Jae-Lyun Lee, Tae Won Kim
Journal: Journal of Clinical Oncology (2015)

785 Background: With limited number of available cytotoxic agents for the treatment of metastatic colorectal cancer (mCRC) patients (pts), rechallenge of chemotherapy can be considered for continuum of treatment. We investigated the efficacy and feasibility of oxaliplatin rechallenge in mCRC pts who have been already exposed to prior oxaliplatin-based chemotherapy. Methods: mCRC pts, who were re-treated with oxaliplatin-based chemotherapy as second or later line treatment in the presence of evaluable disease, were retrospectively accrued. Only those who remained disease-free or progression-free at least 6 months after the last dose of prior oxaliplatin were included. Results: Between January 2009 and May 2014, 110 pts were retreated with oxaliplatin-based regimen; 42 (38.2%) patients received prior oxaliplatin as adjuvant chemotherapy and 68 (61.8%) as palliative chemotherapy. Median disease-free or progression-free duration after prior oxaliplatin was 15.4 months (range, 12.9-17.6 months). All of them received oxaliplatin rechallenge in combination with fluoropyrimidines. The overall response rate to the oxaliplatin rechallenge was 30.9% (34/110), and the disease-control rate was 68.2% (75/110) with 1 complete response, 33 partial responses, and 41 stable diseases. Median progression-free survival and overall survival with rechallenge of oxaliplatin-based therapy were 5.9 months (95% CI, 4.6-7.2 months) and 19.7 months (95% CI, 11.9-27.5 months), respectively. Grade 2 or 3 neuropathy was observed in 16 patients. Any grade hypersensitivity reaction was observed in 10 patients within 4 cycle of treatment. Among them, 6 patients stopped treatment due to grade 3 or 4 hypersensitivity reaction. Conclusions: Rechallenge of oxaliplatin-based therapy could be a treatment option in patients who achieved at least 6 months of disease-free or progression-free survival with prior oxaliplatin-based chemotherapy, especially in those who have lack of further treatment option with good performance status. However, neurotoxicity and hypersensitivity reaction should be cautiously monitored in this setting.