tbuckley/cabot-search huggingface dataset:
Effect of simultaneous or sequential treatment with Imatinib mesylate on the radiosensitivity of U343MG glioblastoma cells in vitro
Authors: C. Herskind, T. Körschgen, F. Lohr, A. Hochhaus, P. Vajkoczy, F. Wenz
Journal: Journal of Clinical Oncology (2006)

13125 Background: In a current clinical study, the tyrosine kinase (TK) inhibitor, imatinib mesylate, is given alternately with radiotherapy in inoperable glioblastoma patients. Imatinib inhibits phosphorylation of certain protein TKs including activated Bcr-Abl, c-kit, and the PDGF receptor. To study the interaction between imatinib and irradiation, a translational study on glioblastoma cells in vitro was conducted in parallel with the clinical study. The purpose of the present work was to study the effect of simultaneous or sequential treatment of the two agents. Methods: U343MG glioblastoma cells were grown in medium supplemented with 10% foetal bovine serum (FBS) or 5% platelet poor plasma (PPP). The colony formation assay was used to test the cytostatic effect of imatinib alone and clonogenic cell survival after irradiation. The surviving fraction as function of dose was fitted by the linear-quadratic model. Results: Irradiation in dilute culture conditions showed a moderate enhancement of radiation-induced cell inactivation by 3–10 μM imatinib. The sensitising effect was similar when the medium was supplemented with PPP instead of FBS. The inhibitory effect on colony formation was the same whether imatinib was added before or after irradiation. However, the inhibitor was required to be present during colony formation since no significant effect was observed when the inhibitor was present only during irradiation and repair. Pretreatment of mass cultures with imatinib for 2–5 days had no effect on the radiosensitivity in delayed plating experiments where imatinib was absent during colony formation. Conclusions: Imatinib showed a synergistic effect in combination with radiation but did not act as a classical radiosensitiser. We suggest that the interaction of imatinib with radiation may be associated with an inhibitory effect on cell proliferation. [Table: see text]
Bone health in prostate patients: An opportunity for screening and intervention.
Authors: George A. Dawson, Anne Greener, Sarah Weinbrom, Dalila Reyes-Dawson, Maria D. Kelly
Journal: Journal of Clinical Oncology (2014)

9623 Background: Despite known risk factors, men are not routinely screened for bone health. Men with prostate cancer are at an increased risk of bone disease because of treatment with androgen deprivation therapy (ADT). Risk factors include family history, calcium and vitamin D deficiency, certain medications, being thin or small-boned, tobacco use, alcohol abuse. and lack of physical activity. We started a screening and management program to mitigate the effects of ADT on bone health in veterans beginning treatment for prostate cancer. This study evaluates the pre-existing risk factors in pts who had baseline dexa scans before ADT. Methods: We completed a retrospective chart review of 182 veterans diagnosed with prostate cancer and referred to Radiation Oncology for radical treatment from 2009 to 2013. This reports on the 160 pts who had baseline dexa scans. Clinical variables analyzed were demographics, tobacco and alcohol use, vitamin D levels, incidence of AODM (adult onset diabetes mellitus), and calcium or vitamin D use. Descriptive statistics as well as bivariate analysis including Chi Square tests and odds ratios were calculated. Results: The mean age of the study participants was 66.6 yrs (47-82.8 yrs); 52% were African American, 45% White, 3% Hispanic. Baseline dexa scans were abnormal in 63% of pts, showing osteoporosis and /or osteopenia. Vitamin D levels were abnormal in 61%. Abnormal vitamin D levels were found in 26% of pts with normal DEXA scans. Almost 99% pts received calcium and Vitamin D supplements. Twenty percent had a history of alcohol abuse, 56% used tobacco, and 33% had AODM. Ethnicity may be a factor ( p<0.05) but the sample sizes per group were not equivalent. Smokers with an abnormal Vitamin D level were at increased risk of bone disease as comparedto non smokers (p<0.01) . Conclusions: Pre-ADT screening confirms the risk of underlying bone disease in this previously unscreened veteran population. Guidelines for treatment and prevention of bone disease should be implemented in all patients over age of 50. An opportunity exists to identify and treat men at risk when seen for prostate cancer treatment whether they receive ADT or not.
Erratum: Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation (Kidney International 47: (1426-1433))
Authors: S. C. Textor, J. C. Burnett, J. C. Romero, V. J. Canzanello, S. J. Taler, S. J. Wiesner, R. Porayko, M. Krom, G. Gores, E. Hay
Journal: Kidney International (1995)
Sidedness matters: Surrogate biomarkers prognosticate colorectal cancer upon anatomic location.
Authors: Irit Ben-Aharon, Tal Goshen-Lago, Ravit Geva, Alexander Beny, Ygael Dror, Mariana Steiner, Ayala Hubert, Efraim Idelevich, Ofer Purim, Moshe Mishaeli, Katerina Shulman, Sofia Man, Lior Soussan-Gutman, Nicky Liebermann, Baruch Brenner
Journal: Journal of Clinical Oncology (2017)

523 Background: Recent evidence indicate that the anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided. The Oncotype DX, a 12-gene colon cancer assay, is a clinically validated predictor of recurrence risk in stage II colorectal cancer (CRC) patients. Previous studies had indicated that CDX2-negative colorectal tumors are often associated with several adverse prognostic variables. Recently, it has been shown that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors were associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors. We aimed to evaluate whether these validated two prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC. Methods: We retrospectively analyzed a cohort of patients with T3 mismatch repair proficient (MMR-P) stage II CRC for whom 12-gene assay was performed (between 1/2011-2/2016). Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. Recurrence score (RS) and CDX2 expression were correlated with primary tumor location. Results: The analysis included 1087 patients with MMR-P stage II CRC (median age 69 years (range 29-93)). Tumor distribution across the colon was as follows: 46% (n = 500) were right-sided (cecum, ascending colon, transverse colon) and 54% (n = 587) were left-sided (splenic flexure, descending colon, sigmoid colon and rectum). Recurrence score was higher in right-sided tumors compared with left-sided tumors (p = 0.01). The RS gradually decreased across the colon (cecum - highest score, sigmoid-lowest score, p = 0.04). Right-sided tumors exhibited more CDX2-negative tumors compared with left-sided tumors (p = 0.07). Conclusions: Our study indicate that right-sided colorectal tumors may display worse prognosis compared with left-sided tumors in MMR-P stage II CRC. Primary tumor location may serve as a prognostic factor that should be accounted for recurrence risk assessment and consideration of adjuvant treatment.
Lack of effect of pegfilgrastim on anemia in breast cancer patients treated with dose-dense chemotherapy
Authors: M. Manzoni, K. Bencardino, B. Rovati, S. Mariucci, F. Cappuzzo, S. Chatzileontiadou, D. Grasso, S. Delfanti, M. Danova
Journal: Journal of Clinical Oncology (2007)

11071 Background: A greater risk of anemia has been evidenced among breast cancer (BC) pts receiving dose-dense CT. A recent report showed that filgrastim may play a role in worsening anemia in BC pts receiving intensified Epirubicin (E) + Cyclophosphamide (CTX), by inducing stem cells to differentiate into more committed hematopoietic progenitors (Papaldo P. JCO, 2006). No data are available about the impact of pegfilgrastim-induced leucocytosis on Hb levels without prophylactic erythropoietic support. Methods: We have focused on this point in 36 BC pts. 14 N+ pts received 4 cycles of E 90 mg/sqm + CTX 600 mg/sqm every 14 days in adjuvant setting. 22 pts with locally advanced disease received 4 cycles of E 75 mg/sqm + Docetaxel 80 mg/sqm every 14 days as primary CT. All pts received prophylactic pegfilgrastim 6 mg s.c, after CT. Three groups were defined on the basis of WBC: A = &lt;10 x 10 3 /mL; B = between 10 and 20 x 10 3 /mL and C = &gt; 20 x 10 3 /mL. WBC and Hb levels at the beginning of treatment were normal in all pts and were subsequently determined on day 1 of each treatment cycle. Results: All pts received the planned CT dose intensity. Only 3 pts developed G2 anemia and were excluded from the analysis, because of receiving darbepoietin alpha support. Among the 14 pts treated in adjuvant setting, 5 dropped in group A, 6 in group B and 3 in group C. The mean Hb decrease from the baseline to the last CT course was - 1.5 g/dL; -1.4, -1.8 and -1.4 in group A, B and C, respectively. In the primary setting, 4 pts dropped in group A, 12 in group B and 4 in group C. The mean Hb decrease was -1.5 g/dL; -1.3, -1.4 and -1.8 in group A, B and C respectively. No statistically significant correlation was found between the Hb levels and the degree of leukocytosis. Conclusions: Pegfilgrastim does not worsen anemia in BC pts treated with dose- dense CT, even when its use is related to some degree of leucocytosis. No significant financial relationships to disclose.
Prognostic significance of serum vascular endothelial growth factor per platelet count in gastric cancer patients
Authors: H. Seo, H. Sung, I. Choi, S. Oh, J. Seo, S. Shin, Y. Kim, K. Park, J. Kim
Journal: Journal of Clinical Oncology (2009)

e22031 Background: Recent studies have shown that VEGF expression not in tissues but in serum sample is correlated with tumor vascularity, and high serum VEGF levels could predict poor prognosis in cancer patients. However there are limited data regarding the clinical and prognostic significance of serum VEGF levels per platelet count in advanced gastric cancer. In this study, we conducted a study to evaluate the prognostic implication of serum VEGF per platelet count in patients with advanced gastric cancer. Methods: 111 patients with histologically confirmed gastric cancer, 10 patients with early gastric cancer were included and control serum samples were acquired from 10 healthy volunteers. The levels of VEGF were measured using human VEGF quantitative enzyme-linked immunosorbent assay (ELISA). Survival curves were calculated using the Kaplan-Meier method and survival comparisons were made by the log rank test in metastatic gastric cancer. The Cox proportional hazards regression model was utilized for multivariate analyses after univariate analysis defined relevant prognostic variables. Results: A trend toward a significant positive correlation between serum VEGF and platelet counts was observed in patients of AGC (r = 0.477, P = 0.000) and there was a significant correlation between serum VEGF levels and differentiation of tumor (p = 0.014), stage (p = 0.036). The overall survival (log rank, p =0.0432) and the progression free survival (median 4.5 vs. 8.9 months; log rank, p =0.0116) were significantly shorter in patients with high VEGF per platelet count (≥1.626 pg/10 6 ). In the multivarivate analysis, performance status (P=0.025), the presence of peritoneal carcinomatosis (P=0.006), serum VEGF per platelet (P=0.005) were found to be significantly associated with poor progression free survival. Conclusions: This study demonstrated that serum VEGF per platelet count are correlated with poor overall survival and progression free survival in patients with advanced gastric cancer. Therefore measurement of serum VEGF per platelet might be useful markers for predicting disease progression and prognosis of advanced gastric cancer. No significant financial relationships to disclose.
Factors associated with survival in non-small cell lung cancer (NSCLC) patients with a solitary metastasis.
Authors: Ravi Parikh, Angel Cronin, David E. Kozono, Geoffrey R. Oxnard, Raymond H. Mak, David Michael Jackman, Peter C. Lo, Elizabeth H. Baldini, Bruce E. Johnson, Aileen B. Chen
Journal: Journal of Clinical Oncology (2013)

e19121 Background: Although palliative chemotherapy is the standard of care for metastatic NSCLC, somepatients with oligometastatic disease may benefit from aggressive local therapy. We investigated factors associated with greater survival among patients diagnosed with a solitary metastatic lesion. Methods: We identified patients diagnosed with stage IV NSCLC who presented with a solitary metastatic lesion based on PET and MRI and who were prospectively consented and enrolled in our institutional database from 2002-2011. Univariable and multivariable Cox proportional hazards models were used to analyze factors associated with overall survival among this cohort. Results: We identified 110 patients (10.7% of stage IV patients) meeting our inclusion criteria. Median age at diagnosis was 61 years, 50% of patients were female, 66% had adenocarcinoma histology, and 35% had N0-1 disease. Median survival from diagnosis was 18.7 months, with a median followup of 31.5 months. On univariable analysis, greater overall survival was associated with ECOG performance status 0-1 vs 2+ (median 21.5 months vs 12.6 months, HR 0.32, p&lt;0.01); weight loss &lt;2 vs &gt;2 kg (22.4 vs 13.8, HR 0.56, p=0.03); and N stage 0-1 vs 2-3 (32.0 vs 17.6, HR 0.52, p=0.02). Adenocarcinoma vs non-adenocarcinoma histology (22.9 vs 13.8, HR 0.65, p=0.07) was borderline significant. Age, gender, race, current smoking, size of primary tumor, and metastatic organ were not significantly associated with survival. On multivariable analysis, adenocarcinoma histology (HR= 0.58, p=0.06); N stage 0-1 (HR= 0.43, p=0.01); and weight loss &lt;2 kg (HR 0.53, p=0.03) were associated with greater overall survival. Conclusions: Select patient and tumor characteristics may predict for improved survival among patients with oligometastatic NSCLC. Future studies will evaluate the impact of aggressive local therapy in these patients.
Investigation of a novel irreversible pan-HER inhibitor combined with chemotherapy in bladder cancer models.
Authors: Petros Grivas, Kathleen C. Day, Stephanie Daignault, Nazia Shakir, Alyssa Paul, Priya Kunju, David C. Smith, Maha Hussain, Mark L. Day
Journal: Journal of Clinical Oncology (2013)

4545 Background: Human Epidermal Receptors (HER) play an important role in bladder cancer (BCa) progression and may mediate chemotherapy resistance. Dacomitinib (Dac) is a novel, potent, irreversible pan-HER inhibitor with activity in several solid tumors, currently in phase III trials in NSCLC. We showed that Dac has single agent anti-tumor activity in human BCa models in vitro and in vivo, inducing apoptosis and G1 arrest. We hypothesized that Dac has additive effects with Gemcitabine (G) and Cisplatin (C) in BCa xenografts. Methods: UM-UC-6 (UC6) or UM-UC-9 (UC9) xenografts were established in age-matched NOD/SCID mice. A week after injection, mice had small tumors, were randomized and treated with i. G 50mg/kg + C 2mg/kg via 3 weekly intra-peritoneal injections (IPI) + daily p.o. buffer for 3 weeks; ii. Dac 6mg/kg p.o. daily for 3 weeks + 3 weekly IPI (saline); iii. GC (same dose/schedule) + Dac starting 1 day after GC (based on cell cycle effect and kinetics); iv. no treatment (control). Mice were monitored daily, weighed weekly, sacrificed at 4 weeks and tumors were weighed. 3 tumors/group were stained for EGFR, HER2, Ki67, E-cadherin, ALDH, p-EGFR, p-ERK, p-Akt. 3rd GC dose in UC6 model was given at 50% due to weight loss; all GC doses were given at 50% in UC9 model. Mann-Whitney test with multiple comparison adjustments was used for analysis. Results: Dac- and GC+Dac-treated mice had no significant weight loss. UC6 tumor weights were significantly lower in Dac and GC+Dac vs control (p&lt;0.0001) or GC (p&lt;0.0001), corresponding to decreased p-ERK %cell expression and staining intensity. GC and control had similar tumor weights (p=0.19). 5 Dac and 3 GC+Dac UC6-injected mice had no tumor at 4 weeks. UC9 tumor weights were significantly lower in Dac (p=0.002, 6x reduction) or GC (p=0.0006; 7x reduction) vs control. GC+Dac had significantly lower tumor weights vs GC (p=0.005), Dac (p=0.06) or control (p&lt;0.0001; 17x reduction). Conclusions: Dac had dramatic singe-agent activity in UC6 xenograft that was GC-resistant. Dac+GC was superior to GC in UC9 xenograft, supporting clinical evaluation. Further investigation of Dac anti-tumor activity and predictive biomarker discovery in additional bladder cancer models is pursued.
Demonstration of an expedited breast care (EBC) clinic
Authors: A. Lopez, C. C. Venker, A. Howerter, G. P. Barker, A. Bhattacharyya, K. M. Scott, M. R. Descour, L. C. Richter, E. A. Krupinski, R. S. Weinstein
Journal: Journal of Clinical Oncology (2006)

16023 Background: Women report waiting for a breast biopsy result as a time of psychological distress. Waiting also delays entry into definitive oncology care, and patients in underserved communities may be lost to follow up. In this proof-of-concept demonstration, an Expedited Breast Care (EBC) clinic was developed to give patients the opportunity to receive same-day biopsy results. Methods: Patients requiring core breast biopsy at a community hospital were approached sequentially to participate. Following surgical biopsy, tissue underwent ultra-rapid fixation and processing. After paraffin sections were prepared and stained, the glass histopathology slides were imaged with a virtual slide scanner. Digital images were stored on a server and viewed on the Internet by a telepathologist at a tertiary care center. Light microscopy review was concurrently performed as the gold standard. After telepathology review and light microscopy confirmation, patients presented to the telemedicine suite to receive biopsy results. A teleoncologist at the tertiary care center presented all pathology results to the patient, whether benign or malignant. Time and patient satisfaction data were collected. Results: Nine patients have participated. Within 2 hours from the time the tissue arrived at the laboratory, digital images were available to the telepathologist. The teleoncologist presented results to patients within 3–5 hours after the biopsy procedure. Patients reported satisfaction with the same-day service, and stated they would seek EBC again in the event of a future breast biopsy. Many patients expressed relief at receiving results so promptly and felt they had avoided the stress of waiting longer for results. The elapsed time from mammogram to definitive oncology care was shorter for EBC patients compared to a control group of patients at a clinic not offering EBC, although the results did not reach statistical significance (Mann-Whitney U: Z = −1.804, p = 0.0713). Conclusions: These data indicate EBC can be successfully accomplished. Current studies to assess EBC’s role in facilitating prompt entry into definitive oncology care are underway. By incorporating rapid tissue processing with telepathology and teleoncology, EBC can improve access to breast care in underserved areas. [Table: see text]
Immune evaluation study of sipuleucel-T (Sip-T) in African-American and European-American men with castration-resistant prostate cancer.
Authors: Archana Thakur, Lawrence G. Lum, Clara Hwang, Channing Judith Paller, Dana Schalk, Vidya Kondadasula, Lance K. Heilbrun, Elisabeth I. Heath
Journal: Journal of Clinical Oncology (2017)

206 Background: Sipuleucel-T (Sip-T) is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients and targets the prostate antigen, prostatic acid phosphatase (PAP). In Phase 3 trials of Sip-T, there was a suggestion that AA men treated with Sip-T had enhanced OS benefit compared to the general population. This study was designed to evaluate the peripheral immune parameters in African American (AA) and European American (EA) prostate cancer patients receiving Sip-T treatment. Methods: Peripheral blood mononuclear cell and serum samples were evaluated for T- and B cell responses in 10 AA and 20 EA men with mCRPC. Antigen-specific T cell response was measured by IFN-γ Elispots, antigen-specific IgG and IgM responses to PA2024, PAP, PSMA, and PSA by ELISA, cytokine and chemokine levels by luminex and immune cell phenotyping by flow cytometry in the PBMC at baseline, 6-, and 10-week time points after completion of Sip-T treatment. Results: IFN-γ EliSpots were ≥ 2-fold higher when stimulated with PA2024 and PAP antigens in AA compared to EA patients post treatment. Humoral immune responses (IgM) to PA2024 and PAP was ≥ 100-fold higher at 6 and 10 weeks after completion of the 3 rd infusion in both groups, however, there were no appreciable differences in antibody levels between AA and EA patients. Interestingly, there were ≥ 2-fold higher IgM titers for non-targeted PSA and PSMA at 6 and 10 weeks post treatment compared to baseline levels in both groups suggesting epitope spreading. Humoral responses (IgM) to PAP, PSA and PSMA at baseline were higher in AA patients compared to EA patients. The Th 1 and Th 2 cytokine and chemokine profiles showed no difference between AA and EA men except for inflammatory chemokine IL-8 which gradually decreased at 6 and 10 weeks from the baseline in AA patients compared to the transient decreases in EA patients. Conclusions: Our preliminary results are suggestive of slightly increased IFN-γ EliSpot responses in AA patients compared to EA patients. Both, AA and EA showed potent IgM antibody response to PA2024 and PAP antigens post treatment compared to the baseline levels. Clinical trial information: NCT01727154.