tbuckley/cabot-search huggingface dataset:
Cessation of VEGF-targeted therapy in patients with metastatic renal cell carcinoma (mRCC): Feasibility and clinical outcome.
Authors: S. Sadeghi, L. Albiges, L. S. Wood, S. L. Black, T. D. Gilligan, R. Dreicer, J. A. Garcia, B. J. Escudier, B. I. Rini
Journal: Journal of Clinical Oncology (2011)

307 Background: Standard practice in the treatment (tx) of mRCC with VEGF targeted agents is continuous tx until progression of disease (PD) or unacceptable toxicity. Chronic mild to moderate toxicity and risk of long-term toxicity ensue for a subset of pts. It is hypothesized that a subset of pts with an initial response to tx can maintain disease control off all tx for a period of time. Methods: A retrospective study of mRCC pts who initiated VEGF-targeted tx between January 2004 and November 2009 was conducted. Pts had achieved disease control on tx, then were taken off all tx. Pt, disease and tx characteristics were recorded. Progression free survival (PFS) was measured as the time from discontinuation of tx to RECIST PD. Results: A total of 30 pts were identified. All pts had prior nephrectomy and had clear cell histology, and 9 patients had prior immunotherapy. At the time tx was stopped 16 pts were receiving sunitinib, 7 pts were receiving sorafenib (2 in combination with AMG 386), and 7 pts were receiving bevacizumab (6 in combination with temsirolimus, 1 with IFN-alpha). Six pts had achieved CR, 19 PR and 5 SD by RECIST. Using Heng's prognostic risk group criteria, 14 pts had favorable, 14 had intermediate, and 2 had poor risk disease prior to initiation of VEGF-targeted tx. Therapy was held for severe adverse events (5pts; 2 MIs, 3 CVAs), toxicity (16 pts; 4 diarrhea, 3 skin, 3 proteinuria, 2 cardiac, 1 fatigue, 1 stomatitis, 1 pneumonitis, 1 nausea), cost (1 pt; high co-pay), pt choice (6 pts) and interventions (2 pts; 1 angioplasty and 1 kidney stone). Median follow up is 29 months (range 11– 82). Median duration of tx prior to discontinuation was 14.6 months (range 3–79). Thirteen pts (43%) had PD off tx (lymph nodes (6), lungs (8; 3 with new lesions), bones (1), brain (2; 1 with new lesions)) with a median PFS of 10 months (range 3–27). After PD, 4 pts were offered sunitinib, 1 pazopanib, 1 everolimus, 1 local RF tx, and 6 continued expectant management. After a median follow-up to date of 7.5 months (2–28), 17 pts (57%) still did not have RECIST PD. Conclusions: Select mRCC pts with disease control on VEGF-targeted tx can be safely observed off all tx. Further prospective investigation is needed to define the risks and benefits of this approach. [Table: see text]
Fludarabine and Busulfan (FluBuP Regimen) as Myeloablative Conditioning Regimen for Allogeneic PBSCT in 71 Leukemic Patients (A Unicenteric Study).
Authors: Masoud Iravani, Maryam Tavakoli, Ahmad Reza Shamshiri, Mohammad Reza Evazi, Asadollah Mousavi, Babak Bahar, Ardeshir Ghavamzadeh
Journal: Blood (2004)
The prognostic significance of extra-intestinal tumor location for primary nonmetastatic gastrointestinal stromal tumors.
Authors: Mary Lydon Guye, Rebecca A. Nelson, Amanda Kathleen Arrington, Steven L. Chen, Warren Allen Chow, Joseph Kim
Journal: Journal of Clinical Oncology (2012)

2 Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the GI tract. Tumor size, tumor location, and mitotic index are established factors that risk stratify recurrence and survival. Extra-intestinal GISTs are infrequently observed and our objective was to investigate the outcomes of patients with primary GISTs found outside the GI tract. Methods: The Surveillance Epidemiology and End Results registry was used to identify patients with GIST treated with surgery between 1996 and 2008. Patients were evaluated by standard clinical and pathological indices including: age, primary tumor location (extra−intestinal vs. GI tract), tumor size, tumor grade, and extent of disease. Overall survival differences between primary site groups were assessed by Kaplan-Meier method. Univariate and stepwise multivariate Cox proportional hazards analyses were performed. Results: Of the 2812 patients with surgically treated GIST, 2489 (88.5%) had a primary tumor location in the GI tract and 323 (11.5%) were located in extra-intestinal sites. Comparison of patients by primary tumor location demonstrated more locally advanced cancers with lymph node involvement (40.2% vs. 18.4%; p&lt;.0001) and a higher occurrence of distant metastatic disease (22.3% vs. 16.6%; p&lt;.0001) among the extra-intestinal GISTs. When comparing overall survival, patients with extra-intestinal GISTs had significantly worse 5 year survival (62% vs. 70%, respectively; p=0.002) than patients with primary tumors within the GI tract. Stepwise multivariate analysis showed that non-intestinal site was an independent predictor of poorer survival (HR 1.29, 95% CI [1.05-1.59], p=0.015). Conclusions: Our data indicates that extra-intestinal location for primary non-metastatic GIST is an independent poor prognostic factor, with worse overall survival, compared to GISTs located within the GI tract. Risk stratification for prognosis should account for these rare GIST locations.
Early Elevation of Plasma Periostin Is Associated with Chronic Ventilator-Dependent Bronchopulmonary Dysplasia
Authors: Shawn K. Ahlfeld, Stephanie D. Davis, Katherine J. Kelley, Brenda B. Poindexter
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

absorbed granuloma doses can be assumed to be rather modest, both a subjective and an objective treatment response were achieved.This case is the first description of successful therapeutic targeting of somatostatin receptors in inflammatory diseases.We conclude that PRRT might be a new valuable tool in patients with otherwise treatmentrefractory sarcoidosis.Further evaluation of this treatment option is warranted.
Reproductive health algorithm.
Authors: A. Patel, E. K. Radeke, A. Uy, H. A. Zaren
Journal: Journal of Clinical Oncology (2011)

263 Background: About 692,000 women are newly diagnosed with various cancers yearly in the US, with breast being the most common, and 10% within reproductive age group. When concerned about survival, reproductive health is overlooked. The objective of this study was to incorporate a reproductive health algorithm into oncologic care of reproductive aged women. Methods: This prospective observational study was conducted at John H. Stroger, Jr. Hospital of Cook County. Eleven newly diagnosed patients were recruited. The algorithm was implemented for each participant and they were surveyed quarterly for 2 years. Results: The mean age of participants was 39 and mean living children was 1.9. Of the 11 women, two (18%) were pregnant at the time of recruitment and nine were not. Both pregnant subjects had an obstetric consultation and chose to continue the pregnancies. They delivered without complications. One began chemotherapy in the second trimester, the other began postpartum. After completion of the pregnancies, these women went into the “not pregnant” cohort. Of the now 11 women in the “not pregnant” cohort, one (9%) had not completed childbearing and 10 (91%) had. The one woman interested in childbearing underwent REI consultation and fertility preservation counseling. Of the women who had completed childbearing, 70% had adopted a long term contraceptive method, 10% a short term method and 20% were abstinent. All 11 women had a family planning consultation. Eighteen percent had already undergone permanent sterilization and 27% had an IUD in place at the time of diagnosis. An additional 27% selected an IUD. Seventy-two percent continued or began long term contraception. Eighteen percent remained abstinent throughout study period. Conclusions: Conclusions from this study demonstrate that with the intervention of the algorithm and referral system, 100% of patients had a basic management plan consistent with reproductive health goals. Most selected a form of long term contraception prior to or on study. All sexually active women had a contraceptive plan in place post diagnosis and during treatment of cancer consistent with long term reproductive health goals. A cluster-design, multicenter, randomized controlled trial has been developed to further investigate and validate our findings.
FGFR3 Tyrosine Kinase Inhibitor AB1010 as Treatment of t(4;14) Multiple Myeloma.
Authors: Bertrand Arnulf, David Ghez, Veronique Leblond, Sylvain Choquet, Karim Belhadj, Margaret Macro, Didier Bouscary, Thierry Facon, Philippe Moreau, Arnaud Jaccard, Jean Soulier, Lionel Karlin, Olivier Hermine, Jean-Paul Fermand
Journal: Blood (2007)
Pathologic characteristics of second breast cancers (SBC) among women previously treated for ductal carcinoma in situ (DCIS) with breast conservation.
Authors: N. D. Arvold, R. S. Punglia, M. E. Hughes, W. Jiang, S. B. Edge, S. H. Javid, C. Laronga, J. C. Niland, R. L. Theriault, J. C. Weeks, Y. Wong, S. J. Lee, M. J. Hassett
Journal: Journal of Clinical Oncology (2011)

1042 Background: While the number of women in the U.S. diagnosed with DCIS is increasing and many go on to develop SBC, pathologic characteristics of SBC and the degree of pathologic correlation with index DCIS are not well characterized. Methods: We identified women in the National Comprehensive Cancer Network (NCCN) Outcomes Database diagnosed with DCIS from 1997−2008 and treated with breast conserving surgery (BCS) who subsequently developed SBC (DCIS or invasive; ipsilateral or contralateral) at one of eight NCCN institutions. We describe the pathologic characteristics of SBC and examine the degree of correlation with the index DCIS using Fisher exact and Spearman tests. Results: Among 2,636 women receiving BCS for DCIS with a median follow-up of 55.5 months, 150 women (5.7%) experienced SBC at a median of 33.2 months after index DCIS. Of these 150 women, 105 (70.0%) had received adjuvant radiotherapy (RT) and 50 (33.3%) had received tamoxifen (Tam) for index DCIS. SBC was ipsilateral in 54.7% of cases and invasive in 50.7% of cases. For index DCIS and SBC, 60.6% and 77.5% were estrogen receptor (ER) positive, and 54.0% and 48.2% were high grade, respectively. Among all cases, grade of the index DCIS was highly correlated with grade of the SBC (p = .003), and ER status was also highly correlated between index DCIS and SBC (p = .020). There was no significant correlation for tumor size (p = .873), progesterone receptor status (p = .227), or comedo subtype (p = .074). After stratification, tumor grade remained significantly correlated among early (less than the median follow-up time) but not late SBC, and ER status was not significantly correlated among women who received RT. Tam had no significant impact on any pathologic correlations, but among women who had received Tam and developed SBC, the SBC was more likely to be a contralateral event (p = .015). Conclusions: After BCS for DCIS, SBC are likely to exhibit grade and ER status concordant with the index DCIS. This information could be complementary to estimates of overall recurrence risk for a given patient receiving BCS for DCIS, by helping predict prognostic features of a SBC and potentially influencing management of the index event.
Treatment of ductal carcinoma in situ (DCIS) with lumpectomy and accelerated whole breast radiation therapy with concomitant boost (ARTB).
Authors: M. Chadha, J. Portenoy, S. K. Boolbol, L. Kierstin, K. Baoch-Abaje, L. B. Harrison
Journal: Journal of Clinical Oncology (2011)

93 Background: The efficacy of accelerated radiation therapy (RT) for treating early stage invasive breast cancer has been established (Whelan T et al: NEJM, February 2010). But the role of accelerated schedules in treating patients with DCIS still needs to be defined. We have previously described the feasibility and low toxicity when using ARTB after lumpectomy (Chadha M et al: Int J Radiat Oncol Biol Phys 2007; 69). The objective of this study is to evaluate early outcomes in patients with DCIS treated with lumpectomy and ARTB, and to compare local recurrence rates of ARTB and conventional fraction (fr) RT with sequential boost (CRT). Methods: This study includes patients diagnosed to have primary DCIS treated with lumpectomy and RT. Patients with DCIS who had history of contralateral synchronous or metachronous invasive cancer were excluded. We identified 215 patients from our breast cancer database as having met this selection criteria; 54 patients received ARTB on an IRB approved protocol, and 161 patients matched by prognostic factors constituted the comparative CRT group. ARTB delivered 40.5Gy in 15fr to the breast, and with concomitant boost 45Gy in15fr was delivered to the lumpectomy boost volume. CRT delivered 46.8Gy in 26fr with sequential boost of 14Gy in 7fr. The patients were well matched with no significant difference in the distribution of known prognostic factors including age, nuclear grade, margin status, receptor status, and Body Mass Index between the groups. Results: The overall median follow up was 3.5 years (0.5 years–11.4 years). Actuarial 5-year local relapse-free survival was 95%. The actuarial 3-year local relapse rate was 2% and 0% for CRT and ARTB groups, respectively (p = 0.22). Local recurrence was observed in 9 patients with a median time to failure of 4.3 years (0.5 years to 8.6 years); 4/9 had grade 3 DCIS; 1 patient with grade 3 had close final margin (&lt;1 mm); 5/9 patients received hormone therapy. Conclusions: With the follow up to date, we observed excellent outcomes in patients with DCIS treated by lumpectomy and RT. These preliminary results suggest comparable local control between ARTB and CRT. Additional studies and longer follow-up are needed.
Male breast carcinoma in United States: Survival rate and determinants of prognosis.
Authors: S. Talluri, R. Kakarala, T. Karedan, M. Kakarala
Journal: Journal of Clinical Oncology (2011)

32 Background: Male breast cancer (MBC) is rare and accounts for less than 1% of all cancers in men. It causes significant morbidity and mortality due to late diagnosis. The primary objective of our study is to update information about the receptor status, pathology, survival rates, and prognostic factors for MBC. Our secondary objective is to determine racial differences in survival of MBC and compare tumor characteristics with female breast cancer (FBC) patients. Methods: We analyzed a retrospective cohort of breast cancer patients included in National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) from 1990 to 2007. Differences between patient and disease characteristics at the time of diagnosis among MBC and FBC patients were compared using chi-square test. Overall survival was estimated using Kaplan-Meier method. Cox proportional hazards regression model was used to determine the independent variables that affect survival. Results: We included 2,475 men and 393,259 women with breast cancer in our analysis. Median age at diagnosis was higher in men compared to women (67 vs 61years). Men had more frequent lymph node involvement (32% vs. 22%), ER positivity (66% vs. 57%) and PR positivity (57% vs. 49%) breast cancer than women (P&lt;0.001). Overall median survival in MBC was 9 years, 5-year survival was 63% and 10-year survival was 43%. Increased age, larger tumor size, higher grade, lymph node involvement, ER and PR negative status were significantly associated with decreased survival in univariate analysis (P &lt;0.05). In multivariate analysis, age &gt; 65 years at the time of diagnosis, larger tumor size, positive lymph node status, ER negative status and poorly differentiated grade were associated with decreased survival (P &lt;0.02). However PR status was not a significant predictor of survival. The median survival in African American males was lower as compared to Caucasians (7.08 vs. 9.2 yrs.) (P=0.02). Conclusions: Male breast cancer differs from female breast cancer in important biological characteristics with a higher age at diagnosis and frequent lymph node involvement. Age greater than 65 years, tumor size, grade, lymph node involvement and ER status of the tumor are independent predictors of survival in MBC.
Long-term outcome of DCIS patients: p53 as a biomarker of ipsilateral recurrence.
Authors: T. J. Hieken, V. Krishnamurthy, M. Farolan, J. M. Velasco
Journal: Journal of Clinical Oncology (2011)

39 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous and potentially curable disease with a long natural history. DCIS represents 21% of breast cancers diagnosed in 2010. The risk of dying after a diagnosis of DCIS is low, emphasizing the importance of treatment-related morbidity, yet the risk of recurrence remains substantial. Optimum individualized therapy remains elusive. We previously identified p53 overexpression as a biomarker for ipsilateral tumor recurrence (IBTR). The purpose of the current study was to investigate its prognostic validity in an expanded patient cohort with long-term follow-up. Methods: We studied 186 consecutive pure DCIS patients from our Breast Cancer Registry and identified 142 cases with sufficient histopathologic material to perform evaluable immunostaining for p53. Median follow-up was 11 years. Statistical analysis was performed with SAS software. Results: Median patient age was 66 (range 35-91) years and 47/153 (31%) presented with palpable disease. Median tumor size was 10 (range 2-165) mm. Predominant histologic subtype included 34 (24%) comedo, 43 (30%) solid, 50 (35%) cribiform and 15 (11%) micropapillary/papillary cases. Necrosis was present in 74/142 (52%) of tumors. Overexpression of p53 was identified in 33/142 (23%) and was associated with necrosis, but not with any other patient, tumor or treatment variables. Fifteen patients (11%) were diagnosed with an IBTR at a median of 56 (range 11-154) months after their initial diagnosis; 3 recurrences were DCIS, while 12 were invasive cancer. p53 overexpression, present in 10/15 (68%) of cases with recurrence versus 23/127 (18%) of non-recurrent tumors, p &lt; 0.001, and no adjuvant tamoxifen, p = 0.003, were associated with IBTR. No other patient, tumor or treatment factors studied were predictive of IBTR. The type of IBTR did not correlate with the p53 status of the index tumor. Conclusions: These data suggest that p53 may be a biomarker for elevated risk of IBTR after a diagnosis of DCIS and support the value of adjuvant tamoxifen for DCIS patients. Further investigation to validate these findings and to identify clinically useful individualized risk stratification for DCIS patients is warranted.
Parametric effect size estimates from sipuleucel-T randomized trials.
Authors: Brent A. Blumenstein
Journal: Journal of Clinical Oncology (2012)

75 Background: Median survival differences are frequently used as measures of effect size because they are easily understood. Other effect size estimates can more fully represent the whole of survival distributions, however, and are less subject to local variations. The sipuleucel-T D9901 (Small, JCO 2006) and IMPACT (Kantoff, NEJM 2010) trials provide 4.5 and 4.1 month estimated median survival differences, respectively, and hazard ratio estimates of 0.586 and 0.752 (not stratified or adjusted). These estimates are based on non-parametric (median) or semi-parametric (hazard ratio) methods. Parametric statistical models are used to illustrate alternative effect size estimates. Methods: Parametric models used are based on the Weibull distribution and a modification of the Weibull distribution allowing for delay of effect. Delay of effect is often conjectured as being responsible for delayed separation of Kaplan-Meier estimates in immunotherapy evaluations (Hoos, JNCI 2010), and both trials exhibit some degree of delayed separation. Parametric models specify the general shape of the hazard functions. Results: The following table repeats estimates given above and shows parametric modeling results. For D9901 the median difference estimate from the Weibull model suggest a much larger effect, and the median difference and the hazard ratio estimates using the delayed effect Weibull model are both indicative of more effect. For IMPACT the median difference and hazard ratio estimates from the Weibull model indicate more effect, but not as dramatic as for D9901. The delayed effect modified Weibull model for IMPACT does not support the conjecture of delayed effect. Conclusions: Statistical modeling illustrates alternative methods of obtaining effect size estimates. For the sipuleucel-T trials there is a suggestion of more effect than obtained from non-parametric or semi-parametric methods. [Table: see text]
PEG-Intron for Myeloproliferative Diseases: An Update of Ongoing Phase II Study.
Authors: Srdan Verstovsek, Kristie Lawhorn, Francis Giles, Jorge Cortes, Deborah Thomas, Guillermo Garcia-Manero, Alessandra Ferrajoli, Stefan Faderl, Miloslav Beran, Moshe Talpaz, Hagop Kantarjian
Journal: Blood (2004)
Prognostic significance of Ki-67 in node-negative (pN0), triple-negative (TN) breast cancer (BC).
Authors: E. Munzone, E. Botteri, A. Sciandivasci, G. Curigliano, F. Nole, N. Rotmensz, M. Colleoni, G. Viale, A. Esposito, A. Luini, M. G. Mastropasqua, A. Goldhirsch
Journal: Journal of Clinical Oncology (2011)

1056 Background: TNBCs occur more frequently in younger women, tend to relapse and metastasize early and have a poor prognosis. They are associated with a range of adverse features including high Ki-67 values. The aim of this analysis was to investigate if Ki-67 could help to identify different prognostic subgroups within the primary pN0 TNBCs. Methods: Patients (pts) with pN0 BC and with ER negative (0%), PgR negative (0%), HER2 scores of 0 and/or FISH not amplified were identified through the institutional clinical database. All pts underwent surgery at the European Institute of Oncology, Milan, Italy, between January 1997 and December 2005 and did not receive neoadjuvant treatment. The association between Ki-67 and other tumour characteristics was evaluated with the Kruskal-Wallis test. The relationship between Ki-67 and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were applied to the Cox model to analyze Ki-67 as a continuous variable. Results: We identified 496 consecutive pN0 M0 TNBC pts with a median age of 52 years; 443 pts underwent quadrantectomy (89%), and 425 pts (86%) received adjuvant chemotherapy, mainly classical CMF (n=315/425 pts, 74%). The median Ki-67 was 48% (range 4-95). The median follow up was 6 years (range 0.5 −13). Total deaths and deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67 was significantly higher in ductal TNBC when compared to other histological types (p<0.01). Moreover, Ki-67 increased with decreasing age (p<0.01), increasing tumour size (p<0.01) and grade (p<0.01). When analyzing Ki-67 as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67 up to about 35% and remained flat thereafter (adjusted effect of Ki-67 P=0.049; adjusted non-linear effect P=0.021). Accordingly, when dividing pts into lower (≤35%)and higher (>35%) Ki-67 subgroups, the 5−year cumulative incidence of breast related deaths were 2.3% and 9.0%, respectively, with an adjusted HR>35 vs ≤35of 2.5 (95% CI 1.0 – 6.0, p=0.046). Conclusions: Within the group of pts with pN0 TNBC, Ki-67 value was associated with different prognoses. Ki-67 value might be useful in the design of trials of risk-adapted adjuvant therapies.
Connective Tissue Growth Factor (CTGF) Is an Indicator of Bone Involvement in Multiple Myeloma.
Authors: Shoso Munemasa, Akira Sakai, Yoshiaki Kuroda, Yoshiko Okikawa, Yuta Katayama, Hideki Asaoku, Tadahiko Kubo, Noelynn Oliver, Akiro Kimura
Journal: Blood (2006)