tbuckley/cabot-search huggingface dataset:
Bevacizumab plus irinotecan therapy in relapsed, heavily pre-treated malignant glioma: A case series
Authors: D. M. Friedland, S. A. Ali, A. Ahmad, M. Rahman, G. Bejjani, M. Braffet
Journal: Journal of Clinical Oncology (2007)

12500 Background: Endothelial proliferation has been recognized as a marker of high grade or aggressive glioma in several grading classifications and it has been demonstrated that the degree of microvascularity as assessed by the endothelial cell/capillary density correlates well with the biologic aggressiveness of these tumors. These features suggest that high grade gliomas are a suitable target for angiogenesis inhibiting therapies. Bevacizumab (B) is a humanized IgG1 monoclonal antibody to VEGF that has been shown to have activity in malignant gliomas when combined with irinotecan (CPT-11), a topoisomerase 1 inhibitor. Methods: We report a case series of 10 patients with recurrent, heavily pre-treated malignant glioma who were treated with the combination of B and CPT-11. Nine patients had WHO grade 4 tumors while one had a grade 3 lesion. All patients had failed standard therapy with primary resection followed by adjuvant chemotherapy and radiation. Most had also failed additional resection, chemotherapy and radiation after their initial relapse. The mean number of failed therapies in addition to adjuvant therapy prior to starting B and CPT-11 was 3 (range 1–6) and the median ECOG performance status was 2 (range 1–3). Nine patients were started on B at a dose of 5 mg/kg every 2 weeks and were given CPT-11 at a dose of 125 mg/m 2 every week for 3 weeks with 1 week off. The tenth patient received B at a dose of 10 mg/kg but with CPT-11 at 125 mg/m 2 every 2 weeks. Results: This regimen was well tolerated with no CNS hemorrhages or &gt;grade 1 bleeding. One patient had treatment held for repair of an anal fissure but then had it restarted. One patient had a DVT while on therapy. The objective response rate was 80% (8 PR and 2 SD).The median progression- free interval on treatment is 25 weeks with 5 patients still having a response at the time of this report. In patients with progressive disease, the median time to progression is 25 weeks. The median overall survival has not been reached, and exceeds 6 months. There has been one death due to disease progression. Conclusion: The combination of B and CPT-11 is safe and has excellent activity even in this relapsed, heavily pre-treated population of patients with high grade malignant glioma, most of whom would not be candidates for clinical trials. No significant financial relationships to disclose.
Tumor-derived mesenchymal stem cells in human gliomas: Isolation and biological properties
Authors: F. F. Lang, J. Gumin, T. Amano, N. Hata, A. B. Heimberger, F. Marini, M. Andreeff, K. D. Aldape, E. Sulman, H. Colman
Journal: Journal of Clinical Oncology (2008)

2001 Background: Evidence suggests that gliomas are maintained by cancer stem cells (CSCs), whose biology is influenced by the microenvironment. However, the stroma of gliomas is poorly defined and the potential that stem cells, distinct from CSCs, are recruited into gliomas has been largely unexplored. We have shown that exogenous bone marrow-derived human mesenchymal stem cells (BM-hMSCs) localize to gliomas after intravascular delivery (Nakamizo et al. Cancer Res 65:330, 2005). This raises the possibility that endogenous hMSCs may be recruited into gliomas. Thus, we hypothesized that hMSC-like cells can be isolated from human gliomas and that hMSCs alter the biology of gliomas. Methods and Results: Surgical specimens from 60 patients with gliomas (31 grade IV, 21 grade III, 8 grade II) were cultured according to the same protocols used for culturing BM-hMSCs. In 49 cases (82%) we isolated cells (called Tumor-Derived hMSCs, TD-hMSCs) that met the criteria of BM-hMSCs, including adherent growth as spindle cells in culture, appropriate surface markers (i.e. CD34-, CD45-, CD105+, CD73+, CD90+), and tri-differentiation into adipocytes, osteocytes, and chondrocytes. TD-hMSCs were CD133- and thus were distinct from glioma CSCs (CD133+). Injection of 10^6 cells into the brains of SCID mice from 31 specimens resulted in tumor formation in only 1 (3%), indicating that TD-hMSCs were not tumorigenic. However, several analyses showed that TD-hMSCs contribute to the biology of gliomas: 1) TD-MSCs were more commonly isolated from high grade tumors (96% of specimens) compared with low grade gliomas (29% of specimens), suggesting that TD-hMSCs are involved in progression from low to high grade gliomas. 2) hMSCs increase the proliferation of U87 glioma cells in both in vitro and in vivo mixing experiments. 3) TD-hMSCs express the mesenchymal proteinsYKL-40 and VEGF. 4) TD-hMSCs express high levels of immunosuppressive factors, e.g. TGF-beta, whereas CD133+ CSCs do not. Conclusions: Cells similar to BM- hMSCs can be isolated from human gliomas. Although not tumorigenic, these TD-hMSCs contribute to the glioma phenotype by increasing proliferation of glioma cells, expressing mesenchymal proteins, and promoting immunosuppression. These recruited TD-hMSCs may represent a new target for therapy. No significant financial relationships to disclose.
Differential Prognostic Implications of Peak Troponin Level in Acute Coronary Syndrome Treated With and Without Revascularization
Authors: Akshay Bagai, Zhen Huang, Yuliya Lokhnygina, Robert A. Harrington, Paul W. Armstrong, John Strony, Edmond Chen, Harvey D. White, Claes Held, Frans Van de Werf, Lars Wallentin, Pierluigi Tricoci, Kenneth W. Mahaffey
Journal: Circulation (2013)

Differential Prognostic Implications of Peak Troponin Level in Acute Coronary Syndrome Treated With and Without Revascularization
Predictive factors for the underutilization of adjuvant chemotherapy in colon cancer in Southwestern Sydney
Authors: W. L. Ng, G. Gabriel, E. Moylan
Journal: Journal of Clinical Oncology (2006)

6070 Background: Adjuvant chemotherapy improves survival in stage III and high risk stage II colon cancers and is therefore recommended in current treatment guidelines. Despite this, retrospective studies demonstrate that utilization rates remain suboptimal in Australia and other countries. In this study we aimed to identify predictive factors for adjuvant chemotherapy underutilization in the Southwestern Sydney Area Health Service (SWSAHS). Methods: We examined data collected on all patients with a diagnosis of stage II or III colon and rectosigmoid cancers from SWSAHS colorectal database between 1997 and 2003. Follow-up and survival were calculated until October 2005. SPSS was used for statistical analysis and Kaplan-Meier for survival analysis. Results: 704 patients were identified. The overall adjuvant chemotherapy utilization rate was 48% (68% for stage III and 26% for stage II). Overall 5 year survival was 69% for patients who received adjuvant chemotherapy compared with 39% for those who did not receive chemotherapy (p&lt;0.001). The main predictive factor identified for not receiving chemotherapy in both stages was increasing age. Rates of utilization of adjuvant chemotherapy for stage III colon cancer were 90% (&lt;50 yrs), 81% (50–69 yrs) and 50% (70+ yrs). The trend was similar for stage II patients with corresponding utilization rates of 69%, 37% and 10%, respectively. The difference in chemotherapy utilization by age groups is highly significant (p&lt;0.001). Other factors including sex, health insurance status, site of primary colon cancer and index of relative socioeconomic disadvantage did not show significant difference in chemotherapy usage. We were unable to evaluate the effect of co-morbidity on chemotherapy use from our database. Conclusions: Increasing age is the single most important predictive factor in the underutilization of adjuvant chemotherapy in colon cancer despite evidence that the elderly can accrue the same benefit from adjuvant chemotherapy as their younger counterparts. No significant financial relationships to disclose.
Oblimersen in combination with dacarbazine prolongs prognostic factor-adjusted overall survival
Authors: F. G. Haluska, A. Y. Bedikian, A. C. Pavlick, M. Millward, M. Gore, H. Pehamberger, U. Trefzer, A. Eggermont
Journal: Journal of Clinical Oncology (2006)

18006 Backgound: In a stratified randomized study comparing dacarbazine (DTIC) and oblimersen (Obl) with DTIC alone in metastatic melanoma, overall survival (OS) was increased in the Obl+DTIC group (P = .077). We report results from a multivariate analysis, including prognostic factors. Methods: The study enrolled 771 patients; 2.2% data were missing. Stratification factors included elevated LDH (&gt;1.1 ULN), performance status (PS) &gt;0, and metastatic site (MET): MET A = liver, MET B = other visceral, MET C = skin, subcutaneous, or lymph nodes only. Each stratification factor was evaluated using monovariate analysis for treatment interaction. Cox model included treatment, any identified factor, gender, or interaction term for OS and progression-free survival (PFS), and a logistic regression for response rate (RR). Results: The stratification factor with the greatest impact on survival was elevated LDH (HR 2.212, P &lt; .0001), followed by PS &gt; 0 (HR 1.497, P &lt; .0001), MET A (HR 1.456, P &lt; .0001), and MET C (HR 0.670, P &lt; .0004). Interaction significance between treatment and LDH, PS, MET A, and MET C were 0.023, NS (0.279), NS (0.419), and NS (0.329), respectively. MET B was used as the reference category for MET A and MET C. Conclusion: As expected, all stratification factors were prognostic, with LDH being the most important factor (HR 2.2). The addition of Obl to DTIC treatment improved outcomes for all efficacy end points. A statistical interaction between Obl treatment and LDH was found for survival. Multivariate analysis was significant in all efficacy end points. Patients with abnormal baseline LDH, already understood to have a poor prognosis, were unlikely to benefit from this therapy and should not be included in future trials of combination oblimersen treatments. [Table: see text] No significant financial relationships to disclose.
A multicenter phase II trial of mFOLFOX6 plus bevacizumab as treatment for liver-only metastases from colorectal cancer unsuitable for upfront resection (TRICC 0808).
Authors: Hiroyuki Uetake, Masamichi Yasuno, Megumi Ishiguro, Shingo Kameoka, Yasuhiro Shimada, Keiichi Takahashi, Toshiaki Watanabe, Kei Muro, Hideo Baba, Junji Yamamoto, Nobuyuki Mizunuma, Hiroshi Tamagawa, Izumi Mochizuki, Yusuke Kinugasa, Yoshihiro Matsubara, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2013)

543 Background: Liver resection is a standard treatment for resectable liver metastases (mets) from colorectal cancer. In patients (pts) with multiple or large liver mets, liver tumors may not be resected completely or recurrence after complete resection are frequently observed. Methods: This prospective single arm phase II trial assessed R0 liver resection rate after mFOLFOX6 + bevacizumab (BV) in pts with liver mets considered unsuitable for upfront resection. Pts with liver-only mets, those were larger than 5cm in diameter or more than 4 in number, were treated with 6 cycles of mFOLFOX6 + BV (without BV in the 6 th cycle). After chemotherapy, resectability of liver mets was assessed by CT or MRI. Secondary endpoints included liver resection rate, conversion rate from unresectable to resectable, safety of liver resection, recurrence rate, and survival. Results: Between May 2009 to October 2011, 46 pts were registered (one was excluded after registration due to ineligibility). Among the 19 pts with resectable mets at entry, 18, except one who refused the continuation of chemotherapy after the first cycle, underwent liver resection after 6 cycles of chemotherapy. In 16 of the 18 pts, R0 resection was performed. Among the 26 pts with unresectable mets at entry, 6 underwent liver resection and 4 had R0 resection. Overall R0 resection rate, liver resection rate and conversion rate were 44.4% (20/45), 53.3% (24/45) and 23.1% (6/26), respectively. The grade 3/4 adverse effects (AEs) by mFOLFOX6 + BV included fatigue (6.5%), stomatitis and nausea (2.2%), neutropenia (16.3%) and increase of serum total bilirubin (2.2%). As to BV related grade 3/4 AEs, hypertension (6.5%) and thromboembolism (2.2%) were observed. After liver resection, grade 3 wound infection, intra-abdominal abscess and delayed wound healing were complicated in two, in one and in one, respectively. Conclusions: In pts considered unsuitable for upfront resection of liver-only mets, mFOLFOX6 + BV was associated with high R0 resection rate, liver resection rate and conversion rate without severe toxicities and surgical complications. Updated results including survival will be presented. Clinical trial information: UMIN000002101.
Skin Diving
Authors: Donald E. Butterfield, Joel D. Mack, Guido Majno
Journal: New England Journal of Medicine (1963)

SKIN diving affects health in a manner somewhat reminiscent of flying: it causes accidents rather than diseases, and the accidents tend to have an all-or-none quality. The doctor is usually consulted for a checkup by a would-be diver who wants to know if he is fit. The doctor may be an ear, nose and throat specialist, and the chances are that he will not be consulted again. Another specialist who may be called upon is the coroner. This does not mean, however, that physicians can afford to ignore the problems of skin diving. They are in a position to understand . . .
18-fluorodeoxyglucose positron emission tomography in initial diagnosis and staging of inflammatory breast tumors
Authors: F. Gutman, J.-L. Alberini, F. Lerebours, E. Gonthier, M. Wartski, M. Al Nakib, E. Brain, J.-L. Floiras, A.-P. Pecking
Journal: Journal of Clinical Oncology (2005)

691 Background: Inflammatory breast cancer (IBC) is a subset of locally advanced breast cancer with poorer prognosis. Most of the time neoadjuvant chemotherapy is required. We prospectively evaluated the usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) scans in patients with inflammatory breast tumors in the diagnosis and staging. Methods: A total of 27 women (mean age 65±18 y) presenting with inflammatory breast tumors (PEV2 (n=17) or PEV3 (n=10) according to UICC classification) were included. Infiltrating ductal carcinoma was found in 22/27 patients, apocrine carcinoma in 1/27 patients and benign mastitis in 4/27 patients. FDG-PET/CT was performed before biopsy. The routine workup consisting of physical examination, bone scintigraphy, abdominal ultrasound and serum tumor markers was used for correlation. The intensity of FDG uptake was quantified using the Standard Uptake Value (SUVmax). Results: Sensitivity and positive predictive value of FDG-PET/CT for detecting IBC were 100% (23/23) and 88% (23/26). FDG-PET was false positive in 3/4 mastitis (SUVmax = 12.7±8.3). A diffuse increased FDG uptake was observed in all IBC (SUVmax=9.3±5.9) and associated with an overlying skin enhancement in 78% (18/23). In 12/23 (52%) patients, PET showed additional lesions compared to the clinical examination located in the lymph node areas (10/23) and/or distant organ (6/23). FDG-PET/CT showed additional ipsilateral axillary lymph nodes in 4/23, infra- or supraclavicular lymph nodes in continuity with the axillary lymph nodes in 5/23, and internal mammary lymph nodes in 1/23. Distant lesions located in the mediastin (2), bone (1) and liver (1) were confirmed by other imaging modalities. Among the 23 IBC, 8 patients were upstaged by PET (35%), 2 from stage IIIB to IIIC, and 6 to stage IV. Conclusions: FDG-PET/CT provides additional information on lymph node involvement or distant lesions related to metastases in patients with IBC. Moreover it can frequently upstage patients. Unfortunately its ability to differentiate breast cancer and mastitis is limited. No significant financial relationships to disclose.
cDNA micro array profiling indicates selection of therapy resistant breast cancer cell clones in vivo
Authors: U. Vogt, N. Tidow, B. Brandt, B. Dominik, D. Kemming, C. M. Schlotter
Journal: Journal of Clinical Oncology (2005)

847 Background: cDNA micro array profiling performed on clinical tissue specimens can potentially provide significant information regarding human cancer biology. Drug resistance in breast cancer is a major obstacle to successful chemotherapy. In this study we used cDNA micro array technology, RT-PCR methods and the ex vivo chemo sensitivity testing of the tumor cells to examine gene expression profiles of patients breast tumors before and after systemic chemotherapy. Methods: Expression Array System (ABI) is based on highly sensitive, chemiluminescent technology for gene expression detection. The 60mer oligonucleotides enable tighter binding to the target, which leads to the detection of more genes with greater selectivity and specificity. The system includes an internal control probe for every gene spotted on the array which can be used for normalisation on the array and between arrays. The system-setup followed a gene-centric approach supplying 28.000 highly annotated genes on a single micro array. Age 35 female patient was first presented to us with a 25mm carcinoma of the left breast during pregnancy. After wide excision and caesarean delivery therapy resulted in combined radio chemotherapy (TAC) and axillary dissection. Despite of this regimen progression could not be stop neither by further chemotherapy (Xeloda), antibody treatment (Herceptin) and tyrosine kinase inhibitors nor operation. Tumor cells were found as well in the contra lateral axillary region twice, liver, right ovary, appendix and the pancreatic region. The patient died 18 months after the first operation. Results: Expression analysis before/after each treatment decision showed higher expression levels of drug resistance genes, salvage pathway genes and erb B-family gene. Therefore, ex vivo chemo sensitivity testing showed no sensitivity against multiple drug regimes. Proliferation index in each tissue was high (S-Phase > 10%). Conclusions: cDNA expression levels may figure out important genes which are related to adjuvant chemo responsiveness and resistance. Further studies with primary systemic chemotherapy and cDNA micro array technology are needed to predict individual responsiveness to specific targeted therapies. No significant financial relationships to disclose.
Effect of bevacizumab on rate of oxaliplatin-induced thrombocytopenia and splenomegaly.
Authors: Kanwal Pratap Singh Raghav, Karime Kalil, Renata Ferrarotto, Binsah George, Cathy Eng, Chris R. Garrett, Evelyn Loyer, Paulo Hoff, Chusilp Charnsangavej, Scott Kopetz, Michael J. Overman
Journal: Journal of Clinical Oncology (2012)

3544 Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI) leading to portal hypertension. This results in splenic sequestration of platelets and thrombocytopenia. Evidence suggests that bevacizumab may protect against HSI, although the clinical impact of this has not been well examined. The purpose of our study was to evaluate rate of thrombocytopenia and splenomegaly as clinical end-points indicative of bevacizumab mediated modulation of oxaliplatin-induced hepatic toxicity. Methods: We performed a retrospective review of metastatic colorectal cancer patients treated at M D Anderson Cancer Center from 1/2003 to 1/2010 with ≥ 3 months of frontline fluoropyrimidine and oxaliplatin (FOLFOX) with or without bevacizumab. Patients with prior liver disease, liver surgery or absence of spleen were excluded. Splenic volumes pre, during and post FOLFOX therapy were determined with CT scans and correlated with platelet counts and treatment. Results: A total of 184 patients [Bev cohort: FOLFOX/Bev (n =138); Non-Bev cohort: FOLFOX alone (n = 46)] were identified. Baseline characteristics (age, gender, spleen size and platelet counts) were similar in both groups. Median number of oxaliplatin cycles for each cohort was 9.00 (p = 0.9). The median total oxaliplatin dose did not differ between the two cohorts (p = 0.9). Development of splenomegaly (volume increase ≥ 30%) was more common in the Non-Bev cohort (48% vs. 32%; p = 0.013). The median time to develop splenomegaly was significantly longer in the Bev cohort (7.6 vs. 5.5 months; p = 0.023). Splenomegaly correlated with a higher rate of thrombocytopenia (defined as platelets &lt; 150K) at 3 months (40% vs. 16%, p = 0.0005) and beyond (during 3 to 6 months of treatment, p &lt; 0.0001). Correspondingly, bevacizumab therapy was associated with lower rates of thrombocytopenia at 3 months (24% in Bev cohort vs. 43% in Non-Bev cohort, p = 0.006) and beyond (p = 0.003). Conclusions: In our cohort, addition of bevacizumab to oxaliplatin chemotherapy reduces the occurrence of splenic enlargement, which correlates with a decreased rate of thrombocytopenia. Further studies to understand the potential hepato-protective mechanism of anti-VEGF therapy are needed.
Trade-offs between survival and breast preservation for three initial treatments of ductal carcinoma-in-situ of the breast.
Authors: B E Hillner, C E Desch, R W Carlson, T J Smith, L Esserman, H D Bear
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the trade-offs between survival and breast preservation of currently accepted approaches for ductal carcinoma-in-situ (DCIS) of the breast. PATIENTS AND METHODS Decision analysis was performed using the Markov model of hypothetical cohorts of 55-year-old white women with nonpalpable mammographic abnormalities found to be DCIS. Strategies were breast-conserving surgery (BCS), BCS with 50-Gy radiation (RT) or initial mastectomy. Recurrence rates were derived from the published literature. Main outcomes were overall, breast cancer-free, and event-free survival plus years of both breasts preserved. RESULTS Using the conditions defined in this model, the actuarial survival rates at 10 and 20 years were 91.7% and 74.1% for the initial mastectomy strategy, 91.0% and 72.1% for BCS plus RT, and 89.6% and 68.2% for BCS alone. At 20 years, the initial mastectomy strategy also had a greater breast cancer-free survival rate of 74.5%, compared with 63.3% for BCS plus RT, or 46.8% for BCS alone. However, BCS alone had the highest survival rate with both breasts preserved (64.2%) compared with BCS plus RT (56.0%) or initial mastectomy (0%). Of the breast-conserving strategies at 20 years, the breast event-free survival rate (no invasive cancer or DCIS) was greater for BCS plus RT (47.2%) compared with BCS alone (28.4%). Using just survival as the primary end point, mastectomy is the optimal strategy by a small margin. However, if quality-adjusted survival is at issue, mastectomy is the choice only if the yearly reduction in quality of life due to mastectomy is less than 1%. CONCLUSION BCS with or without radiation compared with mastectomy as initial management of DCIS of the breast trades a slight decrease in survival rates for the value of breast preservation. This model should aid clinicians in matching treatments to their patients' preferences.