tbuckley/cabot-search huggingface dataset:
Results of a randomized phase III study to compare the overall survival of gefitinib (IRESSA) versus docetaxel in Japanese patients with non-small cell lung cancer who failed one or two chemotherapy regimens
Authors: S. Niho, Y. Ichinose, T. Tamura, N. Yamamoto, M. Tsuboi, K. Nakagawa, T. Shinkai, H. Jiang, Y. Nishiwaki, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

LBA7509 Background: This phase III study (V-15–32) compared gefitinib vs docetaxel on overall survival (OS) in Japanese patients (pts) with pretreated advanced NSCLC. Methods: Pts with advanced or metastatic (Stage IIIb or IV) NSCLC who failed 1 or 2 chemotherapy regimens were randomized to gefitinib (250 mg/day) or docetaxel (60 mg/m 2 every 3 weeks). Non-inferiority of the primary endpoint, OS, was assessed by the confidence interval (CI) of the hazard ratio (HR; gefitinib/docetaxel) derived from an unadjusted Cox proportional hazard model. Results: 489 eligible pts were recruited. Non-inferiority in OS was not achieved (HR 1.12; 95.24% CI 0.89, 1.40) according to predefined criterion (upper CI limit for HR &lt;1.25); however, no significant difference in OS (p=0.330) or PFS (p=0.335) was apparent between treatments. Post study, 36% of gefitinib-treated pts received subsequent docetaxel and 40% received no other therapy apart from gefitinib; 53% of docetaxel-treated pts received subsequent gefitinib and 26% received no other therapy apart from docetaxel. Gefitinib significantly improved ORR (22.5% vs 12.8%; p=0.009), TTF (HR 0.63; 95% CI 0.51, 0.77; p&lt;0.001), and QoL (FACT-L trial outcome index 20.5% vs 8.7%; p=0.002; FACT-L 23.4% vs 13.9%; p=0.023), vs docetaxel. Additional subgroup analyses will be presented. Grade 3/4 AEs occurred in 40.6% (gefitinib) and 81.6% (docetaxel) of pts. Incidence of interstitial lung disease (ILD) was 5.7% (n=14) and 2.9% (n=7), respectively. There were 4 deaths due to AEs in the gefitinib arm (3 possibly treatment-related due to ILD; 1 due to pneumonia that was not considered treatment-related) and none in the docetaxel arm. Conclusions: Whilst non-inferiority in OS between gefitinib and docetaxel was not demonstrated according to predefined criteria, there was no statistically significant difference in survival between the two arms. Secondary endpoints largely unaffected by subsequent therapy provide further evidence of clinical efficacy of gefitinib in these pts. AEs were consistent with those previously observed for both treatments. [Table: see text]
A multicenter, phase II trial of preoperative gemcitabine and nab-paclitaxel for resectable pancreas cancer: The AGITG GAP study.
Authors: Andrew Barbour, Nicholas O'Rourke, Jaswinder S. Samra, Koroush S Haghighi, James Kench, Jenna Mitchell, Nick Pavlakis, Matthew E. Burge, Jonathan Fawcett, Sivikumar Gananadha, Marion Harris, Morteza Aghmesheh, Yu Jo Chua, Warren Lance Joubert, Matthew MK Chan, Manju Dashini Chandrasegaram, Sonia Yip, John Simes, Val Gebski, David Goldstein
Journal: Journal of Clinical Oncology (2015)

387 Background: Pancreatic cancer (PC) outcomes remain poor, recent series show approximately 37% of patients achieve R0 resection (all margins ≥ 1mm) for resectable disease. Recent data in metastatic disease shows that nab-paclitaxel (nab-PC) and gemcitabine (GEM) chemotherapy (CX) is an active regimen. We aimed to determine the feasibility and R0 resection rate with peri-operative nab-PC and GEM for resectable PC. Methods: A multicentre, single arm, phase 2 trial. Patients with operable PC received 2 cycles of neo-adjuvant GEM 1000mg/m 2 and nab-PC 125mg/m 2 CX on days 1, 8 and 15 of a 28 day cycle followed by surgical resection and then 4 cycles of post-operative CX. The primary endpoint was R0 resection with the aim to assess if a rate of 85% could be achieved. Secondary endpoints included feasibility, toxicity, pathological response (College of American Pathologists Cancer Reporting Protocol for Exocrine Pancreatic Cancer, 2009), recurrence and survival. Results: Forty-one patients were enrolled from 2012-14. Median age was 65 (range 43-79), 41% male, 49% stage I and 51% stage II. Twenty nine (71%) patients underwent resection with evaluable cancer: 1 did not have proven cancer on central pathology review; 5 did not go to surgery (2 disease progression, 2 refused surgery, 1 due to cholangitis); and in 6 patients surgery was abandoned (unresectable disease). No deaths were surgery-related. Median tumor size was 27.5mm (IQR = 25-35). Pre-operative GEM and nab-PC produced an R0 rate of 52% (15/29) (95% CI 34-69%). 15/29 (52%) of resected tumors showed grade 0-2 tumor regression grade. Twenty-nine patients (71%) experienced &gt;1 grade 3/4 toxicities (total 52 events) during pre-operative CX, neutropenia (46%) being most frequent with 8% febrile neutropenia. 39/41 (95%) patients received 2 cycles of pre-operative CX. Conclusions: Peri-operative GEM and nab-PC CX is feasible and well tolerated. The pre-operative regimen was associated with an R0 resection rate comparable or higher than surgical series without pre-operative therapy, although the primary endpoint of 85% could not be met. The value of this regimen will also depend on longer term outcomes related to recurrence and survival. Clinical trial information: 12611000848909.
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) following treatment for ovarian cancer
Authors: B. Gupta, S. N. Sait, A. W. Block, L. A. Ford, K. B. Moysich, M. R. Baer
Journal: Journal of Clinical Oncology (2007)

17506 Background: Therapy-related AML (t-AML) has been reported in ovarian cancer patients treated with chemotherapy and has been associated with the use of platinum. However, little is known about these patients’ clinical characteristics, cytogenetic changes, clinical course or treatment outcome. Methods: Roswell Park Cancer Institute patients with diagnoses of AML or MDS by French-American- British (FAB) Group or World Health Organization criteria following a diagnosis of ovarian cancer were retrospectively reviewed. Results: Ten patients were identified between 1990 and 2006. All 10 had received platinum chemotherapy, and 8 (80%) had also received taxanes, 4 (40%) cyclophosphamide and 3 (30%) adriamycin. The median age at ovarian cancer diagnosis was 56 (range, 49–78) years, and the median age at AML/MDS diagnosis was 62 (range, 56–81) years. The median interval from diagnosis of ovarian cancer to AML/MDS was 5.5 (range, 3–11) years, while the median survival time of 395 ovarian cancer patients treated at RPCI between 1982 and 1998 was 4.1 years (range, 1 month to 23 years). Eight patients had AML and 2 had MDS. AML FAB types were M2 in 3, M0 and M4 in 2 each, and M6 in 1. Among 9 patients with cytogenetic data available, 6 had complex karyotypes, all of which included monosomy 5 or del(5q), and three had single clonal abnormalities, all involving chromosome 7. Of 7 AML patients who received induction chemotherapy, only 3 achieved complete remissions, and remissions were brief (3, 4.5 and 5 months). Median overall survival for all ten patients after diagnosis of AML or MDS was 4 months (range, 0.5 months to 9.5 months). Conclusions: Patients with t-AML/t-MDS following therapy for ovarian cancer have unfavorable cytogenetic abnormalities, including complex karyotypes and involvement of chromosomes 5 and 7, which are typical findings following alkylating agent therapy, and these patients have a very poor prognosis. No significant financial relationships to disclose.
Monocytes Are Associated with Impaired T-Cell Immunity and Residual Interim-PET/CT Avidity After 4 Cycles of CHOP-R In Patients with High-Risk DLBCL,
Authors: Maher K Gandhi, Mark S. Hertzberg, Erica Han, John F. Seymour, Rodney Hicks, Devinder S Gill, Colm Keane, Pauline Crooks, Kristen Radford, Frank Vari
Journal: Blood (2011)
Chemotherapy-induced amenorrhea: Influence on disease-free survival and overall survival in receptor positive premenopausal early breast cancer patients
Authors: M. Vanhuyse, C. Fournier, M.-E. Bonneterre, J. Bonneterre
Journal: Journal of Clinical Oncology (2005)

850 Purpose: To evaluate the influence of early chemotherapy-induced amenorrhea (CT-IA) on disease free survival (DFS) and overall survival (OS), we studied data from premenopausal patients (pts) with receptor positive early breast cancer treated with adjuvant chemotherapy without any hormone therapy. Patients and Methods: Retrospectively, we reviewed data from 130 premenopausal pts with localized hormone-sensitive cancer. These pts were treated between 1985 and 1995. They all underwent a loco-regional treatment and adjuvant chemotherapy. Early CT-IA was defined as an amenorrhea arising during the first year following the beginning of the chemotherapy. Univariate predictors of early CIA were examined. DFS and OS analyses were performed with Kaplan Meier method and Cox models. Results: Median follow-up was 9 years. Mean age was 42.9 ± 5 years. Ninety two percent of pts had histologically proven positive axillary nodes. One third of the pts had received an anthracycline containing chemotherapy. Early CT-IA occurred during or after adjuvant chemotherapy in 57% of pts. It was definitive in 91% of pts. In both the univariate and the multivariate analyses, age was the only CT-IA predictor in our study. Women who experienced early CT-IA tended to have a better disease-free survival, but the difference was not significant, probably due to the small number of pts. OS was not different. Conclusion: Early CT-IA increases the cytotoxic effect of chemotherapy in hormone sensitive breast cancer pts. The importance of this effect on DFS and possibly on OS could be shown with studies including a higher number of pts. No significant financial relationships to disclose.
Impact of the <sup>18</sup>F- PET/CT scan in the management of patients with high-risk or intermediate-risk prostate cancer at initial diagnosis or at recurrence.
Authors: Gilles Pasticier, Marine Chicart, Marine Gross-Goupil, Laurence Donon, Gregoire Robert, Jean-Marie Ferriere, Philippe Ballanger, Jean-Christophe Bernhard, Francois Cornelis, Yann Lebras, Nicolas Grenier, Alain Ravaud, Thibaut Haaser, Philippe Fernandez, Henri De Clermont-Gallerande
Journal: Journal of Clinical Oncology (2015)

87 Background: It is reported that a Fcholine Positron Emission Tomography (PET/CT) scan can change the management of the patients with prostate cancer up to 20% of the cases. The aim of this study was to evaluate the impact of 18 FCholine PET/CT when its indication was taken by a multi-disciplinary staff in case of initial diagnosis or in case of recurrence. Methods: This retrospective study involved 84 patients between May 2013 and July 2014. After a selective approach 86 18 F-PET/CT were performed consecutively: 37 (43%) for the initial staging and 49 (57%) in biochemical failure. The acquisition protocol included a pelvic dynamic scan after injection of 4 MBq/kg of 18FCholine followed by a whole-body scan. Mean age, PSA level and Gleason score were respectively in relapse and initial staging: 71 years (59-82), 4.9 (0.12-32.8), 7 (6-9) and 63 years (48-76), 16 (2.42-55) and 8 (6-10). Results: In initial diagnosis, prostate cancer was identified in all the patients on PET/CT. Local disease was seen in 23/37 scans (62.2%); loco-regional node involvement in 8 (21.6%) and metastatic disease in 6 (16.2%). PET/CT confirmed the therapeutic decision in 48.6% of cases and led to a therapeutic modification in 43.2% of cases,avoiding radical prostatectomy and lymphadenectomy in 25% of cases or modifying the extend of radiotherapy (25%) . In biochemical recurrence, PET/CT showed relapse in the prostatic area in 14 patients (28.6%); abnormal pelvic lymph nodes in 10 cases (20.4%) and distant metastases in 18 patients (36.7%). It failed to identify the cause of relapse in 7 cases (14.3%). PET/CT confirmed the therapeutic approach in 24.5% and led to a therapeutic change in 61.2% of cases The diagnostic performance of the FCholine PET/CT scan on nodes, according to the pathological results were: sensitivity 80 %, specificity 84.6%, positive predictive value 66.7% and negative predictive value 91.7 % Conclusions: A rigorous selection of the patients before the realization of a FCholine PET/CT scan in the management of a prostate cancer can increase the diagnostic performance and provide a better impact. In this study the treatment modification affected 54.8% of the patients.
Flt-4 and its ligand VEGF-C in metastatic malignant melanoma: Relationships to clinicopathological parameters response and survival
Authors: R. Mouawad, E. Comperat, F. Cajfinger, F. Capron, D. Khayat
Journal: Journal of Clinical Oncology (2008)

9074 Background: Melanoma metastasizes by either direct invasion of surrounding tissue or spreading through the lymphatic or vascular system. Despite their clinical relevance, the mechanisms that guide the way of spreading and localization of metastases in different tissues are not well known. Recent studies have shown that Flt-4, a VEGF receptor, is activated by its ligand, VEGF-C. The resultant signaling pathway promotes angiogenesis and/or lymphangiogenesis. The aim of this study is to assess a possible involvement of the VEGF-C/Flt-4 axis, in lymphoangioginesis and tumor progression in metastatic malignant melanoma patients (MMM). Methods: Using ELISA assays, Flt-4 and VEGFC were measured in sera of 90 patients with MMM in comparison to 40 healthy controls. Flat-4&VEGF-C expressions on melanoma tumor were evaluated by immunohistochemical study. Survivals (DFS and OS) were analyzed using the Kaplan-Meier method. Results: Pretreatment median levels of sFlt-4 and sVEGF-C were significantly higher in MMM patients as compared to healthy ones (p=0.005, p<0.00001). A high expression of Flt-4 and VEGF-C in melanoma tumor was observed. None of the studied markers correlated with gender, age or LDH levels. An inverse correlation between Flt-4 expression & its soluble form was noted (r=-0.33 p=0.040). A positive correlation between sVEGF-C & sFlat-4 was observed (r’=0.430, p=0.0014). Furthermore, high expression & levels of sVEGF-C, sFlat-4 correlated to high tumor burden (p=0.02, p=0.045). Only sVEGFC/sFlat-4 ratio showed a relationship with lymph node metastasis. Pretreatment sFlat-4 level was significantly different (p=0.0125) between R (n=45) & NR patients (n=35) but not sVEGF-C level. After treatment, no change in the median sFlat-4 level was observed. By contrast, sVEGF-C increased specifically in NR patients with high tumor burden. Only elevated level of sFlat-4 concentration exert a significantly unfavorable impact on disease free survival (Χ2= 3,855, p=0.045). Conclusions: Our results suggest that, in MMM patients, the VEGF-C/Flt-4 axis enhances cancer cell invasiveness, contributes to the promotion of cancer cell metastasis and may prospectively identify high-risk patients with a worse prognosis. No significant financial relationships to disclose.
Prostate brachytherapy in men greater than or equal to 75 years of age
Authors: K. E. Wallner, G. S. Merrick, R. W. Galbreath, W. M. Butler, S. G. Brammer, Z. A. Allen, E. Adamovich
Journal: Journal of Clinical Oncology (2008)

16069 Background: The management of prostate cancer in elderly men remains controversial. In this study, we evaluated cause- specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in prostate cancer patients ≥ 75 years of age undergoing brachytherapy with or without supplemental therapies. Methods: Between April 1995 and August 2004, 145 consecutive patients ≥ 75 years of age underwent permanent prostate brachytherapy. Median follow-up was 5.8 years. bPFS was defined by a PSA ≤ 0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on survival. Results: Nine-year CSS, bPFS and OS for the entire cohort were 99.3%, 97.1% and 64.5%, respectively. None of the evaluated parameters predicted for CSS, while bPFS was most closely to percent positive biopsies. Overall survival and non-cancer deaths were best predicted by tobacco status. Androgen deprivation therapy did not influence survival. Thirty-seven patients have died with 83.8% of the deaths due to cardiovascular disease (22 patients) or second malignancies (9 patients). To date, only 1 patient (0.7%) has died of metastatic prostate cancer. Conclusions: Following brachytherapy, high rates of cause-specific and biochemical progression-free survival are noted in elderly prostate cancer patients. Overall, approximately 65% of patients are alive at 9 years with survival most closely related to tobacco status. Androgen deprivation therapy did not influence survival. We believe our results support an aggressive locoregional approach in appropriately selected elderly patients. No significant financial relationships to disclose.
Expression of hypoxia-inducible factor-1 alpha is associated with an unfavorable prognosis in non-small cell lung cancer
Authors: Y. Fujita, Y. Nishigaki, M. Aoki, M. Sato, Y. Yamamoto, A. Takeda, Y. Yamazaki, H. Aoki, A. Nagase, S. Fujiuchi
Journal: Journal of Clinical Oncology (2004)

7147
A retropective analysis of colorectal cancer in adolescents and young adults: A report from the Surgical Committee of the Children's Oncology Group
Authors: M. P. La Quaglia, M. Morris, J. Shia, K. Idrees, S. Rosenberg, N. Ishill, R. C. Shamberger, J. J. Doski, G. Heller, P. B. Paty
Journal: Journal of Clinical Oncology (2007)

9568 Background: The genetic origin, clinical features, and prognosis of early onset colorectal carcinomas (CRC diagnosed ≤ 30 years of age) are poorly understood. To evaluate these parameters, we performed a multi-institutional review. Methods: This is a retrospective review accomplished through a survey of Children's Oncology Group Institutions. 167 patients (median age=21yrs., range 10–30 yrs.) with adequate material were reviewed. Immunostaining for mismatch repair (MMR) proteins (MSH2, MLH1, MSH6, PMS1) was performed for 119 cases with sufficient archival tumor. Survival estimates were computed using Kaplan Meier methodology and associations assessed using a log-rank test or Cox proportional hazards. Results: The overall stage of disease at presentation: 9% stage I, 16% stage II, 34% stage III, 38% stage IV, and 4% unknown. Site of origin in the colon included: 17% right, 8% transverse, 14% left, 15% sigmoid, 37% rectosigmoid or rectum, and 9% unknown. 37% of cancers were poorly differentiated and 23% had signet ring cell features. A family history of CRC was reported in 46 (40%) of 114 patients for whom data were available. HNPCC criteria (Amsterdam II) were met in only 10 of these cases. MMR protein expression was deficient in 20 of 119 evaluable cases (17%) and was correlated to HNPCC status (P&lt;0.0001) but not to other clinical features. R0 resection was accomplished in 115 patients. Of 159 patients with follow-up data the median survival was 44 mos. (95% CI: 31–65mos.). The 1, 3, and 5-year overall survival were 81%, 54%, and 42% respectively. Variables associated with overall survival in univariate analysis included: age (p=0.02), family history of CRC (P=0.03), HNPCC status (P=0.03), stage (P&lt;0.0001), grade (P=0.0003), and R0 status (P&lt;0.0001). Conclusions: CRC in this age group is associated with clinical features distinct from adult CRC, including advanced stage, high grade pathology, and poor survival. The majority of cases occur sporadically, and less than 25% can be associated with HNPCC either by clinical criteria or by MMR immunostaining. Future studies should pursue more detailed molecular characterization, improved detection strategies, and better treatment to improve outcome for these aggressive cancers. No significant financial relationships to disclose.
Are there sex biases in rape counseling?
Authors: E Bassuk, R Apsler
Journal: American Journal of Psychiatry (1983)

To test the common assumption that only women should treat rape victims, the authors examined the effect of therapists' gender on their counseling of 41 rape victims. The men and women counselors did not differ significantly in their descriptions of their affective responses to the patients or in their treatment recommendations. The women therapists rated victims as having more functional impairment on the Global Assessment Scale, possibly suggesting that they were more sensitive to the victims' distress. The total group of therapists viewed the rape victims more positively than they viewed other female emergency room patients, probably reflecting "undesirable" characteristics of persons who use this setting.
Developmental therapeutics
Authors: D Olmos, S Marsoni, J Tabernero, C Gomez-Roca, J Verweij, E Voest, P Scho ¨ffski, N Penel, J Schellens, S Kaye, G Falchook, J Infante, L Fecher, M Gordon, N Vogelzang, D Demarini, Y Xu, V Peddareddigari, N Le, W Messersmith, J Bendell, A Wagner, S Dolly, J Morgan, D Papadatos-Pastos, J Ware, K Mazina, J Lauchle, H Burris, J De Bono, R Tibes, G Shapiro, T Iyengar, G Demetri, G Weiss, J Fridlyand, G Levy, P Lorusso
Journal: Annals of Oncology (2010)
Toric Intraocular Lenses in the Correction of Astigmatism During Cataract Surgery
Authors: Line Kessel, Jens Andresen, Britta Tendal, Ditte Erngaard, Per Flesner, Jesper Hjortdal
Journal: Ophthalmology (2015)

We performed a systematic review and meta-analysis to evaluate the benefit and harms associated with implantation of toric intraocular lenses (IOLs) during cataract surgery. Outcomes were postoperative uncorrected distance visual acuity (UCDVA) and distance spectacle independence. Harms were evaluated as surgical complications and residual astigmatism.Postoperative astigmatism is an important cause of suboptimal UCDVA and need for distance spectacles. Toric IOLs may correct for preexisting corneal astigmatism at the time of surgery.We performed a systematic literature search in the Embase, PubMed, and CENTRAL databases within the Cochrane Library. We included randomized clinical trials (RCTs) if they compared toric with non-toric IOL implantation (± relaxing incision) in patients with regular corneal astigmatism and age-related cataracts. We assessed the risk of bias using the Cochrane Risk of Bias tool. We assessed the quality of evidence across studies using the GRADE profiler software (available at: www.gradeworkinggroup.org).We included 13 RCTs with 707 eyes randomized to toric IOLs and 706 eyes randomized to non-toric IOLs; 225 eyes had a relaxing incision. We found high-quality evidence that UCDVA was better in the toric IOL group (logarithm of the minimum angle of resolution [logMAR] mean difference, -0.07; 95% confidence interval [CI], -0.10 to -0.04) and provided greater spectacle independence (risk ratio [RR], 0.51; 95% CI, 0.36-0.71) and moderate quality evidence that toric IOL implantation was not associated with an increased risk of complications (RR, 1.73; 95% CI, 0.60-5.04). Residual astigmatism was lower in the toric IOL group than in the non-toric IOL plus relaxing incision group (mean difference, 0.37 diopter [D]; 95% CI, -0.55 to -0.19).We found that toric IOLs provided better UCDVA, greater spectacle independence, and lower amounts of residual astigmatism than non-toric IOLs even when relaxing incisions were used.