tbuckley/cabot-search huggingface dataset:
Hepatic artery infusion of 5-fluorouracil, folinic acid plus oxaliplatin for liver metastasis from colorectal cancer. Final analysis of a phase I/II studay
Authors: N. Moosmann, W. Kern, T. Waggershauser, W. Hiddemann, V. Heinemann, A. Schalhorn
Journal: Journal of Clinical Oncology (2005)

3628 Objective: Numerous studies and meta-analyses have shown significantly higher response rates of hepatic artery infusion (HAI) compared to systemic chemotherapy for liver metastasis from colorectal cancer (CRC). The combination of oxaliplatin with 5-FU and folinic acid can be safely administered as HAI. This final analysis of a phase I-/II-study evaluates toxicity and efficacy of this intraarterial regimen. Methods: Patients with histologically documented CRC with exclusive liver metastasis after surgery of the primary tumor were included. Pts received HAI with folinic acid (200mg/m2, 1 hour infusion) followed by 5-FU (600mg/m2, 2 hour infusion) on days 1 to 5, combined with oxaliplatin (62,5mg/m2, 4 hour infusion) on days 2 and 4. As a long term intrahepatic access, a chamber device was implanted into the groin connected to a catheter radiologically placed into the hepatic artery. Supportive treatment consisted of a 5-HT3-receptor antagonist p.o., paracetamol 1000mg p.o. and a H2-antagonist. Furthermore dexamethasone 8mg p.o. was given 30 min prior and 2 hours after application of oxaliplatin. Results: Twenty-four pts were enrolled (66% colon cancer, 34% rectum cancer). Median age was 62 years (range 34–77), ECOG PS≤2. They were either chemonaive (n=14) or had received an adjuvant treatment ≥6 months before start of study (n=10). Median number of HAI cycles was 7 (range 2–26). WHO grade 3/4-toxicities included leucopenia (19%), thrombocytopenia (10%), hyperbilirubinemia (10%), diarrhea (5%), and abdominal pain (10%). The overall response rate was 70,8%. Complete remission was observed in 5 pts (20,8%), PR in 12 pts (50%), 3 pts obtained SD (12,5%), and 4 had PD (16,7%). Median TTP was 8,8 months. Median overall survival reached 25,5 months. Four years after start of treatment, 5 pts (20,8%) were alive. Two pts (8,3%) had obtained partial liver resection, and 2 pts (8,3%) were treated with radiofrequency ablation after remission had been achieved by the intrahepatic chemotherapy. Conclusion: This final analysis indicates that HAI of 5-FU, folinic acid and oxaliplatin is safe and highly effective in patients with exclusive liver metastasis from CRC. No significant financial relationships to disclose.
Chemo-immunotherapy with bendamustine hydrochloride (BH) and alemtuzumab (ALZ) in T-prolmphocytic leukemia (T-PLL): A clinico-in-vitro correlative study.
Authors: H. X. Yong, Y. C. Linn, K. H. Ong, D. C. Tan
Journal: Journal of Clinical Oncology (2011)

e18557 Background: T-PLL is a rare, but chemo-resistant malignancy, associated with a dismal median survival of about 7.5 months.The optimal treatment for T-PLL is still unknown. Preliminary data indicated high induction response rate with the human CD52 antibody, ALZ. The median remission duration of 7 months however, is short. Moreover, use of ALZ is frequently complicated by infectious complications, thereby limiting the prolonged use of ALZ as a single agent. The results with conventional chemotherapy are disappointing. There is an unmet need to define better treatment strategies for T-PLL. Methods: A 55-year-old female with advance T-PLL presenting with leukocytosis, bicytopenia, hepatosplenomegaly and lymphadenopathy was treated with ALZ for 3 cycles with only minor response attained. BH at 90mg/m2 for 2 days was subsequently given and resulted in remarkable response, with normalization of blood counts within a week and reduction in size of tumor masses. As T-PLL cell lines are not commercially available, T-PLL cells (CD4+CD8+) from peripheral blood frozen at diagnosis were enumerated by flow cytometry via staining with AnnexinV and 7AAD after incubation with BH, ALZ and the combination of both agents at various achievable serum concentrations for 2, 6 and 24 hours. Results: ALZ alone did not result in any significant cell death at all concentrations and time-points.Incubation with BH at concentration above 30µg/ml for 24 hours resulted in cell death in a concentration dependent manner. Combination of BH and ALZ resulted in a time and concentration dependent increase in cell death contributed by both apoptosis and necrosis (Table). Conclusions: BH is an active agent in T-PLL and synergizes with ALZ in tumor cell killing. This study provides an important proof of principle for frontline clinical trials exploring this novel chemo-immunotherapy combination in treating T-PLL. Total percentage cell death over control with different concentrations of BH and ALZ at 6 and 24 hours. Agents Total % cell death (mean±SD) 6 hours 24 hours 10 µg/ml BH + 5 µg/ml ALZ 5.2±3.1 8.51±0.5 30 µg/ml BH + 10 µg/ml ALZ 7.3±1.9 28.7±3.6 100 µg/ml BH + 30 µg/ml ALZ 13.4±2.2 57.6±1.1
Overall survival of patients with hepatocellular carcinoma in lieu of transplant: A retrospective study comparing the Milan and San Francisco criterias.
Authors: S. Campos Gomez, A. K. Dip Borunda, F. D. Huitzil Melendez
Journal: Journal of Clinical Oncology (2011)

e14539 Background: Liver transplantation (LT) represents the beast treatment for hepatocellular carcinoma (HCC) showing a 70% 5- year survival rate. The Milan Criteria (MC) are often used for patient selection for LT. Expanded criteria for liver transplantation have been proposed for some centers. Our study compares overall survivals among patients who fit Milan Criteria (MC) or San Francisco Criteria (UCSFC) and had not undergone liver transplantation. Methods: All patients diagnosed with HCC at our institution from 2004 to 2009 were evaluated retrospectively. We analyzed age, gender, indication for orthotopic liver transplant (OLT), adjuvant treatments (chemotherapy, radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and liver resection) maximum tumor size and survival. Outcomes were compare for patients who met Milan Criteria ( single tumor < 5 cm, maximum of 3 total tumors with none > 3 cm) or University of California, San Francisco (UCSF) criteria ( single tumor < 6.5 cm , maximum of 3 total tumors with none > 4.5 cm, and cumulative tumor size < 8 cm) and were not under liver transplant. Results: From 2004 to 2009, a total of 194 patients were diagnosed with hepatocellular carcinoma in our institution. 61 patients (31%) had MC, and only 32 were eligible for OLT. 11 patients (5.6%) exceeded MC but fits UCSF criteria for OLT. A 5-year survival was 56% for the MC group versus 33% UCSF group. Hepatitis C virus was the most common etiology of HCC. Conclusions: Survival for patients with tumor beyond UCSF criteria was significantly lower and below 50% at 5 years, this important difference supports the use of expanded criteria to offer OLT as treatment for this group.
Hypermethylated circulating DNA detection using picoliter droplet-based PCR in colorectal cancer.
Authors: Geraldine Perkins, Sonia Garrigou, Fanny Garlan, Corinne Normand, Audrey Didelot, Delphine Le Corre, Claire Mulot, Ralph Niarra, Pascaline Aucouturier, Gilles Chatellier, Sanam Peyvandi, Olivier Bouche, Jean-Francois Emile, Denis Pezet, Frederic Bibeau, Darren R Link, Aziz Zaanan, Iradj Sobhani, Pierre Laurent-Puig, Valerie Taly
Journal: Journal of Clinical Oncology (2016)

622 Background: Circulating tumor DNA (ctDNA) is thoroughly investigated as a surrogate biomarker of tumor follow-up, in different cancer types, such as colorectal cancer (CRC). Droplet-based digital PCR (ddPCR) is a highly sensitive and also quantitative method for detection of very low amount of ctDNA. Since many different genes can be mutated within a specific tumor type and also wide mutation spectrum can occur within a specific gene, procedures for ctDNA monitoring can be time consuming and need to be improved for a routinely use. To overcome these drawbacks, we characterized the methylation status of 3 genes frequently hypermethylated in CRC to identify universal markers for tumor follow-up. Methods: The characterization of the methylated status of the WIF, NPY and PENK genes in the tumor DNA was performed in 56 CRC of different stages and 45 corresponding plasma samples using droplet-based dPCR, after DNA bisulfite conversion. A two-panels assay (with albumin as a reference) was developed. Methylation level of these 3 genes in tumor tissues was compared to corresponding normal tissues (n = 22) and plasma samples (MetctDNA). To validate, plasma samples of additional 91 patients were analyzed for the presence of ctDNA both by the characterization of KRAS, BRAF, TP53 and PIK3CA mutations (MutctDNA) and of MetctDNA, at various stages of their follow-up, and 9 of them had MetctDNA assessment during treatment follow-up. Results: All tumor samples were positive for WIF1 and/or NPY markers. Hypermethylation of these two genes was significantly higher in tumor tissue compared to normal, independently of the tumor stage (p &lt; 0.0001). MetctDNA could be detected in 75% of metastatic CRC patients and 24% of localized CRC patients (stage 1 to 3). MetctDNA and MutctDNA fractions were strongly correlated (R 2 &gt; 0.9, p &lt; 0.0001). During follow-up, MetctDNA levels changes allowed monitoring of tumor evolution in different stages CRC patients. Conclusions: These results indicate that determination of MetctDNA by droplet-based dPCR can reach same efficiency than MutctDNA for ctDNA assessment, using only 2 markers, and thus could be considered as a universal surrogate marker of tumor follow-up in CRC patients.
Comprehensive kinase profiling to classify clear cell (cc)-renal cell carcinoma (RCC).
Authors: Amitkumar N. Mehta, Christopher Douglas Willey, Joshua Anderson, Karim Youssry Welaya, Dongquan Chen, Pooja Ghatalia, Ankit Madan, Sunil Sudarshan, Gurudatta Naik, William E. Grizzle, Toni K. Choueiri, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

409 Background: Comprehensive high throughput functional kinase activity in localized cc-RCC tumors may assist in devising a classification system and help identify potential therapeutic targets. Methods: Patients (pts) with localized tumors undergoing surgery with minimum follow-up of 18 months underwent kinomics of fresh frozen cc-RCC tumors and matched normal renal tissue using the PamStation12 high-content phospho-peptide substrate microarray system (PamGene). The protein tyrosine kinome (PTK) and serine/threonine kinome (STK) PamChips were used to measure global kinase activity. Advanced network modeling of altered phospho-peptides was performed using MetaCore while upstream kinase prediction scoring was based off of phosphonet (phosphonet.ca). Both unsupervised analyses and supervised analyses of kinomics were done guided by tumor recurrence. Kinomics of tumor and matched normal tissue were compared. Results: Of 41 evaluable pts, the median age was 61 and pathologic stage was 1, 2, 3 and 4 in 19, 1, 20 and 1 pts, respectively. Unsupervised clustering analyses of tumor kinomics showed 3 groups: A (N=12), B (N=16), C (N=13). Potential driver kinases implicated were PFTK1, PKG1 and SRC in groups A, B, and C, respectively. Network modeling of these groups identified many Process Mappings including, but not limited to Inflammation pathways (A), translation initiation (B) and immune response and cell adhesion pathways(C). 5 of 9 pts who progressed were classified as Group C, 1 progressor was in Group B, and 3 were in Group A. Supervised analysis showed decreased CDK1, RSK1-4, ERK1-2, PKG2 and AKT2 kinase activity in those who progressed compared to others. 12 tumors showed increased PIM1 and MAPKAPK3, and decreased JNK2 and CDK1 compared to adjacent normal tissue. Conclusions: Comprehensive kinomics of localized cc-RCC was used to classify tumors based on unsupervised clustering, which appeared to confer differential long-term outcomes while supervised analysis also identified potential pathways related to recurrence. Kinases amplified in renal tumors compared to adjacent normal renal tissue were also identified. Significant heterogeneity of kinases was found with no single dominant kinase across all analyses.
Thalidomide and dexamethasone in newly diagnosed multiple myeloma: Long-term results in patients not undergoing upfront autologous stem cell transplantation
Authors: S. V. Rajkumar, D. Dingli, G. Nowakowski, M. Gertz, M. Q. Lacy, A. Dispenzieri, S. Hayman, S. R. Zeldenrust, R. Fonseca, J. A. Lust, P. R. Greipp, R. A. Kyle, T. E. Witzig
Journal: Journal of Clinical Oncology (2005)

6632 Background: We have previously reported response rates using Thal/Dex as initial therapy in a phase II clinical trial conducted at Mayo Clinic (JCO 20:4319–4323, 2002). Although the regimen was developed as a pre-transplant induction regimen, many patients did not undergo upfront autologous stem cell transplantation (ASCT). The time to progression of patients treated with Thal/Dex as initial therapy without upfront ASCT is not known. In this study we present data on the time to progression of patients with newly diagnosed MM treated with Thal/Dex who did not undergo upfront ASCT. Patients and Methods: We identified 24 patients with newly diagnosed MM who were treated with Thal/Dex but did not undergo ASCT. Patients were treated with thalidomide at a dose of 200mg/day orally and dexamethasone 40mg daily on days 1–4, 9–12, 17 - 20 on odd months. During even months, the dexamethasone dose was 40mg daily for 4 days. Cycles were repeated monthly. Results: Of the 24 patients, 14 were male and 10 female. The median age was 65.5 years (36 - 78). Based on the International Staging System (ISS), 11 (46%) patients had Stage I disease, 7 (29%) were in Stage II and 6 (25%) had Stage III disease. Patients were treated for a median of 5 months (range 1- 42 months) and the median duration of follow-up was 21 months (1 - 52). Two (8%) patients achieved a complete response (CR), 11 (46%) had a partial response (PR) (overall CR+PR =57%), and 7 (29%) patients had stable disease. One patient did not respond to the combination and 3 patients died while on therapy. The disease progressed in 6 patients while on treatment. Nine patients did not complete therapy due to various reasons other than progressive disease. In 3 patients, therapy was stopped due to adverse effects, 3 patients died while on therapy, 2 patients refused further treatment and in 1 patient, therapy was stopped because of another medical condition. The median overall survival (OS) and progression-free survival were 30 months and 19 months, respectively. The median time to progression was 21 months. Conclusion: In patients who do not undergo stem cell transplantation for MM, the median time to progression with upfront Thal/Dex is 21 months. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene
Early breast cancer in elderly women: The value of Comprehensive Geriatric Assessment (CGA)
Authors: G. Albrand, C. Terret, H. Mignotte, S. Gaujard, J. P. Droz, P. Courpron
Journal: Journal of Clinical Oncology (2005)

8172 Background: Increased age-related prevalence of co-morbidity and functional impairment promote the risk of treatment intolerance and mortality in elderly cancer patients (pts). Clinical studies in these pts have shown the negative impact of coexistent disease on prognosis and disability, but few have underlined the relevance of thorough co-morbidity assessment. The Cumulative Illness Rating Scale-Geriatric (CIRS-G) provides a comprehensive co-morbidity assessment, including the measure of their severity. Methods: Women >70 years with early operable breast cancer were asked to undergo CGA at treatment start. CGA was conducted in the GEMU, according to the American Geriatric Society (AGS) guidelines, by a core team directed by a geriatrician. Assessment included information from various sources (pts, caregivers, general practitioners), and usual screening tools (ADL, IADL, POMA, GDS, MMSE, MNA), complete physical examination, standard lab. tests and X-ray. Co-morbidity was classified using the CIRS-G. Results: Of 76 pts (mean age: 77 +/- 4.7 years), 17% were at risk of cognitive deterioration, 30% of depression, 33% nutritional risk, 28% risk of fall. Most (66%) were fully independent in ADL, 46% in IADL. Median CIRS-G total score was 10. When tested, CIRS-G grade ≥2 co-morbidity was distributed as follows: 62% vascular disease, 31% psychiatric disease, 25% musculoskeletal or tegument disorders, 27% heart disease, and 18% sensory, 16% respiratory, 13% genitourinary, or 12% haematopoietic disorders. Results agree with reports from other geriatric teams using CGA. Conversely, when CGA process was used as a screening tool, median CIRS-G scores were lower. Extermann et al reported a median CIRS-G score of 5 in older breast cancer pts (Extermann, Crit Rev Oncol Hematol 2004). Conclusions: Older pts with early breast cancer have a high prevalence of co-morbidity and disability. CGA, done according to AGS guidelines, improves the quality of health status evaluation in the elderly. This work was supported by grant: PHRC n°98.064 of the Ministry of Health. No significant financial relationships to disclose.
Metastatic colorectal cancer (mCRC) with primary in situ: An Australian registry.
Authors: Shu Fen Wong, Kathryn M Field, Suzanne Kosmider, Jeanne Tie, Hui-Li Wong, Ben Tran, Mark Tacey, Jeremy David Shapiro, Joseph J McKendrick, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

498 Background: The role of primary tumor resection in patients presenting with mCRC remains controversial. While recent data suggest resection of the primary tumor is unnecessary with modern systemic therapies, other series indicate that non-operative intervention may be associated with inferior survival outcomes. We aimed to evaluate the Australian approach to primary tumor resection in patients with mCRC and to explore its impact on survival outcomes. Methods: This study was conducted using a clinician-designed mCRC registry involving 15 participating Australian sites. Patients were excluded if planned for curative resection of metastatic disease or had incomplete data. Cox logistic regression analyses were used to identify and quantify associations between overall survival (OS) and patient/clinical variables. Results: We identified 533 mCRC patients with median follow up 12.5 mo. 41% (n=220) had their primary in-situ. Rates of primary tumor resection were higher in older patients (&gt;70 yrs old) (64.5% vs 52.7%; p=0.006), colon versus rectal primaries (64.6% vs 42.7%; p&lt;0.001) and those without liver metastases (70.7% vs 52.9%; p&lt;0.001). Median OS was significantly better in patients undergoing primary tumor resection compared to the non-resected population (28.3 mo vs 15.9 mo; Hazard Ratio (HR): 0.52; log-rank p&lt;0.001). Univariate analyses indicate that older age (HR: 1.69; p&lt;0.001), poor performance status (HR: 4.44; p&lt;0.001) and peritoneal involvement (HR: 1.94; p&lt;0.001) were associated with poorer survival outcomes while chemotherapy administration (HR: 0.33; p&lt;0.001) predicted improved survival. Multivariate analyses, when adjusted for known prognostic factors, confirms that primary tumor resection remains an independent predictor of better survival (HR: 0.50; p&lt;0.001). Conclusions: The 41% of primary cancers in-situ is higher than previous mCRC studies and suggests a tendency for non-operative intervention in Australia. Given the survival outcomes demonstrated in this study, a review of Australian clinical practice is required. Future studies will examine the survival differences in patients with de novo versus relapsed metastatic disease, motivation for resection and other confounding variables.
Evaluating a preference-tailored decision tool for increasing colorectal cancer screening.
Authors: Sarah T. Hawley, Bruce Ling, Angela Fagerlin, Sally W. Vernon, Sandeep Vijan
Journal: Journal of Clinical Oncology (2012)

10 Background: Incorporating patient preferences into CRC screening decisions has been identified as one method for improving informed decision making and increasing screening adherence, yet the impact of tailoring screening recommendations to patients’ preferences on these outcomes has not been evaluated. Methods: We compared the effect of a web-based preference-tailored decision tool (intervention) to a standard information decision tool (control) through an RCT at two VA sites. Eligible subjects were age 50-77, due for CRC screening, with a scheduled primary care visit. Participants arrived 45 minutes early to complete consent and were randomized online. Telephone surveys were conducted 3-5 days post-enrollment and CRC screening adherence was collected from medical charts 6 months later. We evaluated the effect of the tool on adherence and compared stated test preferences to test recevived through Chi-square tests and regression. Results: 468 subjects were enrolled from two VAs. CRC screening adherence 6-months post-enrollment was 38.6% and was not significantly different between groups (37.4% intervention, 39.7% control). Most were adherent with fecal occult blood test (FOBT) (22.4%), followed by colonoscopy (COL) (16.7%). The most commonly recommended test by physicians was COL (59.2% of tests recommended), though veterans most commonly stated a preference for FOBT (60.1%). The features of tests most important to veterans were nature of the test (32.8%), effectiveness (27.1%), and risk of complications (17%). Participants significantly more often adhered to the test that they stated they preferred after the intervention than with a non-preferred test (30.4% adhered to preferred test vs. 7.6% adhered to non-preferred test, P&lt;0.001). Conclusions: CRC screening adherence in this population of veterans was low and the preference-tailored intervention did not significantly improve adherence relative to standard information. Veterans preferred a non-invasive test (FOBT) despite higher rates of recommendation for COL by their physicians. Improving concordance between physician recommendations and patients’ preference may be one method for improving CRC screening adherence in this population.
Activation-Induced Release of the TNF-Family Member BAFF By NK Cells Facilitates Resistance of Chronic Lymphoid Leukemia Cells to Direct and Rituximab-Induced NK Lysis
Authors: Julia S Wild, Stefanie Raab, Benjamin J Schmiedel, Andreas Maurer, Pascal Schneider, Lothar Kanz, Helmut R Salih
Journal: Blood (2014)