tbuckley/cabot-search huggingface dataset:
Interleukin-2 (IL-2), interferon-α (IFN- α), 5-fluorouracil (5-FU) and vinblastine (VBL) for treatment of metastatic renal cell carcinoma (MRCC). A prospective phase II study
Authors: R. Rubinov, E. Gez, N. Haim, A. Kuten, S. Meritick
Journal: Journal of Clinical Oncology (2004)

4671 Background: Immunochemotherapy is the treatment of choice for patients with MRCC, but the long-term results are poor Methods: January 1966 - May 2000, 62 pts with MRCC treated with an immunochemotherapy combination. Median age 63 (26–80), ECOG performance status: 1 –45 pts (73%) and 2 –17 pts (27%), the histology was clear cell carcinoma in 46 pts, spindle cell sarcomatoid type in 2, mixed type in 8 and unknown in 6. 32 pts diagnosed with localized disease underwent nephrectomy and later developed metastases. 30 pts had metastatic disease at presentation and 23 underwent nephrectomy. Site of disease: lungs in 66%, lymph nodes in 50%, bones in 35% and liver in 8% of pts. Site of metastases/pt was 1 in 24 pts (39%), 2 in 17 (27%) and 3+ in 21 (34%). Treatment: IL-2 10MIU/m2, SC x 3/week, weeks 1–4; IFN- α 6MIU/m2, SC once a week, weeks 1–4 and 10MIU/m2 x 3/week, weeks 5–7; 5-FU 600mg/m2 and VBL 6mg/m2, iv bolus, weeks 5 and 8. Each treatment course was followed by a 2-week interval for tumor response and toxicity evaluation. Results: In a median follow-up of 64 months, 62 pts were evaluated for toxicity and 58 for response. 4 pts were excluded for response due to intolerance of treatment. Response rate to immunochemotherapy: CR 7% (4 pts), PR 24% (14 pts), SD 34.5% (20) and PD 34.5% (20). 7 pts (5 PR and 2 SD) underwent complete resection of residual tumor (retroperitoneum 3, lung 3, and mediastinum 1). Therefore, CR achieved in 11 pts (19%). Median respectively. Common side effects were flu-like symptoms, nausea, headache and depression..survival after treatment for CR, PR, SD, PD and NE pts was: 69, 14, 19, 7 and 8 months, Conclusions: Immunochemotherapy is effective and well tolerated by pts with MRCC. Surgical intervention for resection of residual disease is justified. No significant financial relationships to disclose.
CA 11-19 as a tumor marker for the diagnosis of colorectal cancer.
Authors: Bergein F Overholt, Tommye Jordan, Donald J Wheeler, Herbert A. Fritsche
Journal: Journal of Clinical Oncology (2014)

3555 Background: Colorectal cancer remains the second most frequent cause of cancer deaths in both sexes in the United States. Both fecal and blood tests using tumor related antigens are increasingly being used to monitor treatments and in some cases aid in diagnosing colorectal cancers. However, higher sensitivity and specificity are needed before an acceptable tumor antigen blood test for colon cancer is clinically useful. Methods: Using double monoclonal ELISA analysis, a new colon cancer antigen, CA 11-19, (100 kDa glycoprotein) was measured in 670 colonoscopy confirmed patients including normal, benign GI diseases, polyps and colon cancer in a blinded IRB approved study. Results: Using a cutoff of below 6.4 units/ml as normal, CA 11-19 was positive (>6.4) in 132 of 139 of colorectal cancer cases. 100% of 63 cases of Stage I and II were positive. Sensitivity of CA 11-19 for diagnosis of colorectal cancer was 95%. Negative results were found in 94% of normals (175/187) and 80% of benign GI diseases (161/202). The specificity for the assay was 80.2% for all benign groups combined (426 negative assays for 531 benign patients). Conclusions: Ca 11-19 is a serologic tumor marker for colorectal cancer with a demonstrated sensitivity of 95% and a specificity of 80%. Diagnostically, a positive assay result increases the odds of finding colorectal cancer by a factor of five. The test appears to be highly sensitive for detection of early stage colorectal cancer. Additional prospective studies are needed to validate the use of CA 11-19 as an aid in the diagnosis of colorectal cancer.
Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis
Authors: So Young Park, Sanjeeb Shrestha, Young-Jin Youn, Jun-Kyu Kim, Shin-Yeong Kim, Hyun Jung Kim, So-Hee Park, Won-Gyun Ahn, Shin Kim, Myung Goo Lee, Ki-Suck Jung, Yong Bum Park, Eun-Kyung Mo, Yousang Ko, Suh-Young Lee, Younsuck Koh, Myung Jae Park, Dong-Keun Song, Chang-Won Hong
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined.We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia.Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis.Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism.These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.
Vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX for first-line therapy of patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: A New York Cancer Consortium led phase II randomized study.
Authors: Deirdre Jill Cohen, Paul J. Christos, Hedy Lee Kindler, Daniel Virgil Thomas Catenacci, Tanios B. Bekaii-Saab, Sanaa Tahiri, Yelena Yuriy Janjigian, Michael K. Gibson, Emily Chan, Lakshmi Rajdev, Susan Urba, James Lloyd Wade, Peter Kozuch, Erica Love, Katherine Vandris, Naoko Takebe, Howard S. Hochster, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2013)

4011 Background: The HH pathway is overexpressed in gastroesophageal (GE) tumors. Pre-clinically, HH inhibitors have demonstrated a reduction in GE tumor growth, cell motility and invasiveness. V, an oral small-molecule antagonist of the Hh pathway, has previously been safely combined with FOLFOX chemotherapy. Methods: Pts with untreated metastatic or locally advanced gastric or GEJ adenocarcinoma were randomized 1:1, stratified by institution and disease status (with or w/o distant mets) to FOLFOX (ox 85 mg/m 2 , LV 200 mg/m 2 , 5-FU bolus 400 mg/m 2 , 5-FU infusion 2400 mg/ m 2 over 48 hrs) q14d plus V or placebo (P) (150mg PO daily). Cycle defined as 2 weeks and no crossover allowed at progression. FFPET and blood were collected for biomarker analyses. Response assessed every 8 weeks (RECIST 1.1). Primary endpoint was progression-free survival (PFS), secondary objectives were overall survival (OS), response rate (RR), and toxicity. Results: 124 pts enrolled at 20 sites between 10/09-2/12. 123 pts eligible for analysis (V/P 60/63). Pt characteristics (V/P): median age 58/62; ECOG PS 0: 24 (40%) / 30 (48%); male 39 (65%) / 52 (83%); GEJ 37 (62%) / 39 (61%); diffuse or mixed histology 19 (32%) / 10 (16%), recurrent disease 10(17%) / 16 (25%). Median number of FOLFOX cycles 10/11. Most common Grade ≥3 toxicities: (% pts V/P) neutropenia 50/32 (p=0.07), neuropathy 19/13 (p=0.49), fatigue 15/10 (p=0.50), thrombosis 14/11 (p=0.92), anemia 10/10 (p=0.99), hemorrhage-GI 8/11 (p=0.77), hypokalemia 10/5 (p=0.76), nausea 8/8 (p=0.99). Death on or within 30 days of treatment 6.7%/15.6% (p=0.20). Median PFS in intent to treat population 7.3/8.0 mo (95% CI 4.6-10.1/5.1-11.0; p=0.64) and median OS 11.5/14.9 mo (95% CI 9.6-13.4/11.3-18.4; p=0.23). Overall RR (%) 35/35 (p=0.99). Conclusions: Addition of V to FOLFOX did not improve PFS in an unselected advanced GE carcinoma population. Blood and tissue biomarker analyses are ongoing to determine if there is a subset of patients who may derive benefit from V. Supported by: N01-CM-62204, -62201, -62207, -62206, -62209, -62208 and 2UL1 TR000457-06. Clinical trial information: NCT00982592.
A prospective, randomized study of low molecular weight as supplemental therapy in metastatic colorectal cancer patients treated with FOLFIRI regimen and target agents.
Authors: Hsiang-Lin Tsai, Chi-Jung Tai, Ching-Wen Huang, Jaw-Yuan Wang
Journal: Journal of Clinical Oncology (2017)

746 Background: Fucoidan is recently studied for its anti-cancer and anti-inflammatory effects. It also has been used as food supplements in Asia for many years. This study is the first prospective, randomized trial to compare the clinical outcomes and adverse events in metastatic colorectal cancer (mCRC) patients, who are treated with FOLFIRI regimen and target agents as the first line setting with or without low molecular weight Fucoidan (LMF). Additionally, the study also aimed to evaluate the inhibitory effect of LMF in EGFR-KRAS-BRAF-ERK signaling pathway. Methods: A total of 54 patients with mCRC were randomly divided into a study group (28 cases, 4g BID oral low molecular weight Fucoidan powder) and a control group (26 cases, 4g BID oral placebo powder). The supplements were given for 6 months during the therapeutic period. The primary endpoint was the disease-control rate (DCR), and the secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects between the two groups. MTT cell viability assay and western blotting analysis were used to evaluate synergic effect of LMF plus 5-FU or Cetuximab on Caco-2, SW620 and HCT-15. Results: 54 mCRC patients were enrolled, including 28 patients in the study group and 26 patients in the control group. The DCR was 92.8% vs. 69.2% in study and control group respectively ( P = 0.026) in median follow up time of 11.5 months. The PFS was 15.93 ± 1.20 vs. 10.80 ± 1.06 months ( P = 0.075), ORR was 60.7% vs. 46.2% ( P = 0.284) and OS was 18.04 ± 0.91 vs. 12.96 ± 0.83 months ( P= 0.092). There were no statistical differences in adverse effects between two groups. In vitrostudy, LMF plus 5-FU or Cetuximab showed synergic cytotoxic effect (maximal 24% increase) through the inhibition of the expression of p-EGFR, p-ERK and p-Akt. Conclusions: The preliminary results show that LMF as supplemental therapy in mCRC patients may improve DCR. In vitro, Fucoidan showed the synergic cytotoxic effect with 5-FU or Cetuximab. The possible mechanism may involve the inhibition effect of Fucoidan in phosphorylation of EGFR-KRAS-BRAF-ERK signaling pathway.
HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells
Authors: D Germini, T Tsfasman, M Klibi, R El-Amine, A Pichugin, O V Iarovaia, C Bilhou-Nabera, F Subra, Y Bou Saada, A Sukhanova, D Boutboul, M Raphaël, J Wiels, S V Razin, S Bury-Moné, E Oksenhendler, M Lipinski, Y S Vassetzky
Journal: Leukemia (2017)
Evaluation of p75 expression and patterns of recurrence in patients with malignant gliomas treated with bevacizumab.
Authors: Gloria Roldan Urgoiti, Sam Lawn, James Scott, Jacob C. Easaw, Rajappa Kenchappa, Jennie Webster Taylor, Nina Paleologos, David Schiff, Jennifer Chan, Peter A. J. Forsyth
Journal: Journal of Clinical Oncology (2015)

e13006 Background: There is no standard treatment for patients with recurrent malignant gliomas (MGs) and after antiangiogenic therapy, 15% recur in a distant location suggesting the development of VEGF independent invasive mechanisms. We hypothesized that p75NTR expression could be associated to the pattern of recurrence/progression in patients with MGs treated with bevacizumab. Methods: Adult patients with MGs (gliomas Grade III and Glioblastoma) treated with bevacizumab who had given written consent were identified. Clinical data were extracted from the charts. Pathology was centrally reviewed by a neuropathologist (JC) who also evaluated p75NTR by immunohistochemistry using a scoring system (intensity index, prevalence index - % of positive cells- and a combination index - the product of the two). Brain MRIs underwent central neuroradiology review (JS). All researchers were blinded to others’ results. Results: Thirty patients were included; 83% were male; 87% had glioblastoma and 84% received bevacizumab as second line therapy. Recurrences were 42% local (n = 10), 21% diffuse (n = 5) and 12% distal (n = 3). Six patients (25%) had radiologic stability despite clinical deterioration. There was no association between p75 expression and pattern of progression. In univariate analysis, progression free survival (PFS) was associated with KPS [HR 0.94 (CI 95% 0.89 – 0.990; p = 0.046], prevalence index for p75 [HR 1.8 (CI 95% 1.17-1.34); p = 0.007], and combined score for p75 expression [HR 1.18 (CI 95% 1.03-1.34); p = 0.012]. Patients with > 50% p75 positive cells had shorter PFS [HR 3.3 (CI 95% 1.12-8.89); p = 0.018]. Tumors with any p75 positive cell had worse PFS than p75 negative tumors [HR 3.64 (CI 95% 1.18-11.22); p = 0.024]. Conclusions: The expression of p75 was associated with PFS in recurrent MGs. We were not able to find an association between the pattern of recurrence/progression and the expression of p75 in patients with MGs after treatment with Bevacizumab.
Long-term results of ultrasound (US)-guided fine needle aspiration cytology (FNAC) in conjunction with sentinel node biopsy (SNB) to support step-wise approach in melanoma.
Authors: Alexander Christopher Jonathan Van Akkooi, Petra Siegel, Alfred Schoengen, Joachim Roewert-Huber, Alexander M. Eggermont, Christiane A. Voit
Journal: Journal of Clinical Oncology (2015)

9067 Background: Ultrasound (US) guided Fine Needle Aspiration Cytology (FNAC) is a common diagnostic tool in the work-up of other cancers, i.e. breast and thyroid. The results in melanoma (mel) were poor (sensitivity 20-40%). Introduction of the Berlin Morphology criteria has recently shown potential improvements up to 65 – 80% in selected patients (pts). Methods: Between 2001 and 2010 over 1000 stage I/II consecutive mel pts prospectively underwent US-FNAC prior to Sentinel Node (SN). All pts underwent lymphoscintigraphy prior to US-FNAC. The Berlin US morphology criteria: Peripheral perfusion (PP), loss of central echoes (LCE) and balloon shaped (BS) were registered and FNAC was performed if any factor was present. SN tumor burden was measured according to the Rotterdam criteria. All pts underwent SN or lymph node dissection in case of positive FNAC. Results: Mean/median Breslow thickness was 2.58/1.57 mm. Mean/median follow-up was 69/63 months (IQR 42 - 98). SN positivity rate was 21%. US-FNAC Sensitivity was 71% (US only) and 51% (US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). PP, LCE and BS had sensitivity of 69%, 24% and 24% respectively. Sensitivity of US-FNAC increased with increasing SN tumor burden. PP was an early sign of metastasis (58% in < 0.1 mm metastases). Threshold size of a metastasis for FNAC was 0.3 mm. Survival analyses for different end-points (Melanoma Specific, Disease-Free, Distant-Metastasis-Free) demonstrated that pts with pos FNAC and/or BS/LCE had poor survival. Pts with PP and with neg FNAC had a slightly worse survival (HR 1.61 (P = 0.025), 1.45 (P = 0.034) and 1.72 (P = 0.007) compared to completely neg pts (regardless of SN result). Conclusions: The long-term results support the step-wise approach to melanoma patients. In case of positive FNAC and/or clearly malignant US (BS and/or LCE) patients have larger amounts of SN tumor burden and poor survival, they can be spared a SNB. In case of PP and negative FNAC, patients should proceed to undergo a SNB to detect microscopic occult disease. Completely US-FNAC negative patients might only require follow-up and no SN staging.
Safety and biological activity of the FLT3 inhibitor lestaurtinib in infant MLL-rearranged (MLL-r) ALL: Children's Oncology Group protocol AALL0631.
Authors: Di Sun, Allison Kaeding, Daniel Magoon, Tamekia Jones, Meenakshi Devidas, Andrew J Carroll, Nyla A. Heerema, Mignon L. Loh, Elizabeth A. Raetz, Naomi Joan Winick, William L. Carroll, ZoAnn Eckert Dreyer, Stephen Hunger, Joanne M. Hilden, Patrick Andrew Brown
Journal: Journal of Clinical Oncology (2012)

9548 Background: MLL-r infant ALL overexpresses activated FLT3. Lestaurtinib potentiates chemotherapy(chemo)-induced cytotoxicity in MLL-r ALL. AALL0631 therapy is stratified based on age and MLL status: high risk (HR) &lt;90 days, MLL-r; intermediate risk (IR) ≥ 90 days, MLL-r; standard risk any age, not MLL-r. IR and HR patients (pts) get intensive chemo and are eligible for lestaurtinib. A safety/activity (S/A) phase to determine a safe and biologically active dose of lestaurtinib is followed by an efficacy phase randomizing MLL-r patients to chemo +/- lestaurtinib. The S/A phase proceeds independently for IR &amp; HR pts, as optimal lestaurtinib dosing may differ between neonates and older infants. We previously reported successful completion of the S/A phase for IR pts; here, we report results of the S/A phase for HR pts. Methods: Lestaurtinib-related dose limiting toxicities (DLTs) were defined as grade ≥ 3 non-heme toxicities excluding those expected with chemo alone (e.g., F&amp;N/infection); a dose of lestaurtinib was “safe” if 0 or 1 DLTs were seen in 5 evaluable pts. FLT3 inhibition was assessed using a plasma inhibitory activity (PIA) assay that measures % inhibition of phospho-FLT3 at 5 trough time points relative to pre-treatment baseline. A dose of lestaurtinib was “biologically active” if PIA was &gt; 90% for the majority (≥3 of 5) of troughs in at least 3 of 5 pts. Results: 11 eligible HR pts received lestaurtinib, 6 at dose level 1 (DL1, 3.5 mg/kg/day) and 5 at DL2 (4.25 mg/kg/day). There were no DLTs in 5 evaluable pts at DL1. The inevaluable pt discontinued lestaurtinib due to parental refusal, not toxicity. There was 1 DLT in 5 evaluable pts at DL2. The DLT was grade 4 intestinal perforation secondary to severe typhlitis during neutropenia following reinduction, possibly related to lestaurtinib. The pt was taken off protocol and chemo and died of progressive disease. By PIA assay, 2 of 5 pts treated at DL1, and 4 of 5 at DL2 demonstrated FLT3 inhibitory biologic activity. Conclusions: DL2 is safe and biologically active in HR pts. The efficacy phase of AALL0631 is expanding such that HR pts will join IR pts in being randomized (1:1) post-induction to chemo +/- lestaurtinib at DL2.
Adjuvant nodal radiotherapy for node positive head and neck melanoma: A single institution experience
Authors: M. R. Huber, S. N. Markovic
Journal: Journal of Clinical Oncology (2004)

7537 Background: Despite adequate surgical treatment, head and neck melanoma frequently recurs. It is generally thought of as a chemotherapy and radiotherapy resistant malignancy. The goal of this study is to see if adjuvant post-operative radiotherapy improves outcome for lymph node positive head and neck melanoma. Methods: A single institution retrospective review. Results: All cases (n=86) of lymph node positive head and neck melanoma at Mayo Clinic Rochester were reviewed from 1985–2000. Though formal statistical conclusions could not be drawn, the irradiated and observed groups appeared similar with regards to most baseline characteristics. However, the irradiated group had more limited surgeries, fewer nodes removed but more involved, and more extracapsular extension. Most irradiated patients received a twice-weekly hypo-fractionated regimen. Neck recurrence was 25.0% vs 42.9% favoring the irradiated group, despite higher risk of recurrence. Rates of distant metastases (69.2% vs 52.9%) and overall failure (84.6% vs 67.1%) were higher in the irradiated group, confirming their higher-risk disease. Conclusions: Post-operative radiation appears to reduce the risk of cervical lymph node recurrence in node positive head and neck melanoma. No trial to date has compared radiation to observation in a randomized, controlled fashion. Our group is planning a Phase III trial to address this question. No significant financial relationships to disclose.
A phase II randomized trial of cisplatin/paclitaxel plus lonidamine versus cisplatin/ifosfamide plus lonidamine in the treatment of ovarian cancer
Authors: V. Lorusso, R. Calabrese, A. Latorre, M. Guida, A. Misino, M. Spada, A. Paradiso, M. De Lena
Journal: Journal of Clinical Oncology (2004)

9678 Background:Lonidamine (LND) has been shown to revert the resistance to cisplatin and to potentiate cisplatin activity in experimental models as well as in clinical studies. Methods: The aim of this phase II randomized study was to evaluate the feasibility of a combination of cisplatin, ifosfamide and LND in the treatment of advanced ovarian cancer. Thirty-one patients (pts) with advanced ovarian cancer, were treated with paclitaxel at a dose of 135 mg/m2 intravenously (i.v.) on day 1 (3 h infusion) and cisplatin at a dose of 75 mg/m2iv on day 2 plus LND orally (450 mg/day for 4 consecutive days starting one day before chemotherapy), every 3 weeks for 6 cycles (A), or with LND and cisplatin at the same dosage and schedule combined with Ifosfamide at dosage of 2500 mg/m2 on day 1 (B). Results: Complete (CR) plus partial response (PR) was observed in 13/16 (81%) pts treated with A and in 5/15 pts ( 33%) treated with B. At a median follow up of 18 months, 8 pts (50%) treated with A did not progress compared to only 2 out of 15 (13%) of B. Grade 3–4 neutropenia was observed in 25% and 46% of pts of A and B, respectively. All A patients finished therapy, whereas 4 of 15 pts (26%) treated with B abandoned the therapy after first (3 pts) or second (1 pt) cycle (one pt because of grade 4 renal toxicity, 2 pts because of haematological toxicity and one pt refused to continue). Alopecia was observed in 90% of patients irrespective of the regimen administered. Nausea and vomiting (Grade 3) were observed in 50% and 53% of patients treated with A and B respectively. Conclusions: These preliminary data suggest that the regimen containing ifosfamide seems more toxic and less effective than the paclitaxel containing one. A parallel biologic study on embedded specimens investigating VEGFR, CD34, tyrosine kinase receptors (EGFR HER2–neu), proliferative markers as MIB1, p-53, bcl-2 and of mitochondrial activity on fresh surgical specimen, may give an explanation of this difference in response rate. The study continues in order to achieve the initially planned sample size of 50 pts per arm. Partially supported by MIUR grant # CU03.00439.ST97 No significant financial relationships to disclose.