tbuckley/cabot-search huggingface dataset:
Systemic inflammatory response in predicting survival in patients with operable colorectal cancer.
Authors: K. A. Kwon, S. Oh, S. Kim, S. Lee, J. Han, H. Choi, K. Park, M. Roh, H. Kim, H. Kwon
Journal: Journal of Clinical Oncology (2011)

456 Background: Several inflammatory response materials could be biomarkers for prediction of prognosis of cancer patients; elevated C-reactive protein (CRP), increased white cell, neutrophil, platelet, and decreased albumin. The Glasgow Prognostic Score (GPS) combines circulating CRP and albumin level, the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) has been introduced for prognostic scoring system in colorectal cancer (CRC). Thus, in this study, we attempted to identify an more adequate prognostic model related with systemic inflammatory response for CRC. Methods: Between Mar 2005 and Dec 2008, 200 patients who underwent curative resection for colorectal cancer were enrolled in this study. Systemic inflammatory parameters (CRP, albumin, neutrophil, lymphocyte, and platelet count) were checked for making 3 scoring systems. Based on clinical survival data, we then compared PFS and OS with GPS, NLR, and PLR. Results: Male to female were 123:77. Median age of the patients was 64 years (range, 26-83 years). Median follow-up duration was 27.2 months (range 7.8-52.7 months). 36 patients were observed disease progression or death. 19 patients were passed away during follow-up duration. 3 year PFS and OS were 72% and 86%, respectively. Numbers of GPS 0,1, and 2 patients were 154 (77%), 44 (22%), and 2 (1%), respectively. Survival analysis according to GPS, PFS and OS could not be able to show the prognostic significance (P=0.313 and P=263). Cut-off value of NLR and PLR were determined 3 and 180 by ROC curve. Both of NLR and PLR were observed as a good prognostic biomarker of PFS and OS (P=0.009 and P&lt;0.001 in PFS, P=0.006 and P=0.001 in OS). Conclusions: Although GPS, NLR, and PLR were introduced as prognostic scoring systems for operable CRC, PLR which is constructed of platelet/lymphocyte count may represent a useful prognostic index for the prediction of PFS and OS in operable CRC. No significant financial relationships to disclose.
Priapism in SCD: Clinical and Genetic Correlations.
Authors: Allison E. Ashley-Koch, Laura M. De Castro, Felicia Lennon-Graham, Jude Jonassaint, Terry L. Jackson, Jennifer Price, Jason Galloway, Susan Jones, Eldrida Randall, Charles Packman, Charles Knupp, James R. Eckman, Rupa Redding-Lallinger, Eugene P. Orringer, Jeffery M. Vance, Marilyn J. Telen
Journal: Blood (2005)
Quality of life among breast cancer survivors treated with breast-conserving therapy in Hawaii.
Authors: Francisco A. Conde, Andrea R. Wilburn
Journal: Journal of Clinical Oncology (2013)

154 Background: Aim of this study was to compare quality of life (QOL), treatment-related side effects, and needs of recent and long-term breast cancer survivors following breast-conserving therapy. Methods: Surveys were sent to 750 women with Tis, T1 – T4 breast tumors without lymph node involvement who received lumpectomy followed by radiotherapy at a large, tertiary care facility in Hawai‘i from January 2001 to December 2010. To assure adequate representation across years, 75 women were randomly selected from each year. Surveys included demographic items, City of Hope Quality of Life – Breast Cancer Instrument, and Breast Cancer Prevention Trial Symptom Scales. Completed surveys were received from 265 (35.3%) women, and findings were analyzed for long-term survivors (diagnosed from 2001-2003, n=76), mid-range survivors (diagnosed from 2004-2007, n=95), and recent survivors (diagnosed from 2008-2010, n=94). Results: Overall, respondents reported high QOL. Similarly to recent breast cancer survivors, long-term survivors reported slight to moderate side effects, including hot flashes, vaginal problems, musculoskeletal pain, and cognitive dysfunction. After controlling for age, ethnicity, and cancer stage, there was no significant differences in QOL physical, psychological, and social well-being subscale scores across time periods. Long-term survivors were more likely than shorter-term survivors to want information regarding nutrition (p&lt;.01), physical activity (p=.018), and ways to restore strength, mobility, and cognition (p&lt;.01). Conclusions: Breast cancer survivors treated with breast conserving therapy report relatively good QOL between 2 and 12 years post-treatment, although they continued to experience physiological issues (which could be exacerbated by age), and anxieties about their cancer. Healthcare professionals should continually assess for ongoing cancer-related side effects even years after completing treatment. Funding: This research was supported by ‘Imi Hale Native Hawaian Cancer Network (U54 CA153459).
Congenital Dyserythropoietic Anemias: Molecular Diagnosis and Diagnostic Approach in a Cohort of Italian Patients
Authors: Veronica Agrigento, Sclafani Serena, Paolo Rigano, Rita Barone, Giuseppina Calvaruso, Rosario Di Maggio, Massimiliano Sacco, Lorella Pitrolo, Angela Vitrano, Aurelio Maggio, Elena D'Alcamo
Journal: Blood (2015)
Impact of multidisciplinary bladder cancer care for muscle invasive bladder cancer: A propensity score matched analysis of survival outcomes.
Authors: Girish S. Kulkarni, Thomas Hermanns, Kathy Li, Yanliang Wei, Bimal Bhindi, Cynthia Kuk, Srikala S. Sridhar, Theodorus van der Kwast, Peter W. M. Chung, Robert G. Bristow, Padraig Richard Warde, Michael F. Milosevic, Neil Eric Fleshner, Michael A.S. Jewett, Alexandre Zlotta
Journal: Journal of Clinical Oncology (2016)

455 Background: We started in 2008 a Multidisciplinary Bladder Cancer Clinic (MDBCC), where complex bladder cancer patients are assessed concurrently by urologic and radiation oncologists, with support from medical oncologists. Patients have the opportunity to discuss various treatment options including radical cystectomy (RC) or bladder sparing trimodal therapy (TMT; endoscopic resection, radiotherapy and chemotherapy). Although reports have shown comparable outcomes of TMT to cystectomy, no direct comparison to RC has been published and no randomized studies are available. We report our long term outcomes of multidisciplinary care, comparing TMT to surgery using propensity-matched analyses. Methods: Patients seen in our MDBCC receiving TMT for MIBC from 2008 to 2012 were identified and matched, using propensity scores, to patients operated by RC. Matching occurred on age, ECOG status, Charlson comorbidity score, cT stage, cN stage and date of treatment. Overall survival (OS) and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: Between 2008 and 2012, 248 patients were assessed in the MDBCC. Of these, 162 (65%) had MIBC. Nearly half (80) opted for radiotherapy +/- concurrent cisplatin chemotherapy and 49 underwent full bladder preservation with TMT as their primary therapy. We matched 48 TMT patients with 48 RC patients with no imbalances. Median age of the cohort was 67.5 years with 29.2% cT3/cT4. With a median follow up time of 3.62 years, there were 19 (39.6%) deaths (7 from bladder cancer) in the RC group and 15 (31.3%) deaths (6 from bladder cancer) in the TMT group. 5 year DSS was 85.2% and 84.7% with TMT and surgery, respectively (p &gt; 0.05). There was no statistically significant difference in DSS between the two groups (HR for TMT 1.31 (0.40-4.23), p = 0.66) or in OS (HR for TMT 0.77 (0.34-1.75), p = 0.53). Conclusions: Bladder cancer patients benefit from a multidisciplinary approach.. In selected patients with MIBC, chemo-radiation yields survival outcomes similar to matched RC patients. BC patients should be offered the possibility to discuss various treatment options.
A phase II study of cabozantinib in metastatic castration-resistant prostate cancer (mCRPC) with visceral metastases (VM) with very small nuclear circulating tumor cell (vsnCTC) association studies.
Authors: Richard Huynh, Jie-Fu Chen, Mourad Tighiouart, Margarit Sievert, Amy Oppenheim, Nancy P. Moldawer, Beatrice Knudsen, Michael Freeman, Neil Bhowmick, Andre Rogatko, Hsian-Rong Tseng, Leland Wk Chung, Kevin Scher, Robert A. Figlin, Edwin M. Posadas
Journal: Journal of Clinical Oncology (2016)

208 Background: Cabozantinib is a multi-targeted tyrosine kinase inhibitor (TKI) that has recognized clinical activity in mCRPC. While phase 3 studies did not show a significant improvement in overall survival (OS), patients with VM had improved OS compared to those with only osseous metastases in subgroup analysis. Our group has also identified a subgroup of CTCs strongly associated with the presence of VM (Chen, Cancer 2015). We hypothesized that cabozantinib would yield clinical benefit and changes in vsnCTC counts would reflect disease behavior. Methods: This study was designed as an open label study of cabozantinib 60 mg daily, for mCRPC patients with visceral disease. The primary endpoint is clinical benefit rate (radiographic stable disease + partial response (PR) by RECIST 1.1) at 12 weeks (CBR12). Serum PSA concentrations were not used as a primary endpoint. CTCs were enumerated by NanoVelcro CTC Assay and characterized using published methods. Results: Thirteen patients have completed at least 8 weeks of treatment. In this group, 38% had pulmonary metastases; 77% had hepatic metastases; CBR12 was 92% at the time of this report. A quarter of the patients experienced a PR. Mean time to radiographic progression for responders was 38 weeks (19-57). Discordant responses were noted between VM and bone scans. Grade 3 or higher toxicities were compatible with prior studies and observed in 50% of patients. In this advanced mCRPC and relatively heavily pre-treated population, treatment discontinuation due to toxicity was 33%. Eleven of 13 patients were assessable for CTC and imaging. Of the 11 patients, 7 had vsnCTCs detected at baseline. All 7 patients reported subjective improvement that was associated with a decrease in vsnCTCs by 6-8 weeks. In patients who had a PR, no vsnCTCs were detected at 6 weeks while on active treatment. An increase in vsnCTCs was seen prior to visceral progression. Conclusions: Cabozantinib is a TKI with activity in mCRPC with visceral metastases. Toxicity is consistent with previous reports and manageable. The NanoVelcro vsnCTC assay may be a predictive marker of response. Clinical trial information: NCT01834651.
Second-line therapy in advanced non-small cell lung cancer: Cytotoxic agents or tyrosine kinase inhibitors? Our experience.
Authors: N. Caristi, T. Franchina, C. Proto, G. Chiofalo, G. Toscano, A. Scimone, M. Zanghì, R. Berenato, R. Briguglio, N. Denaro, L. Noto, V. Adamo
Journal: Journal of Clinical Oncology (2011)

e18063 Background: Despite a number of effective first-line regimens, virtually all patients (pts) with advanced NSCLC will relapse. A second line therapy with docetaxel or pemetrexed, according to tumour histotype, represents the standard treatment for pts with a good performance status (PS). The introduction of tyrosine kinase inhibitors (TKIs) for pre-treated NSCLC pts have added a valid option in this setting. Methods: We have analyzed outcome data of 85 NSCLC pts (table), who received after a platinum-based chemotherapy, a second-line therapy with docetaxel, pemetrexed, erlotinib or gefitinib (expanded access program), in order to assess and compare their efficacy and tolerability in this setting. Results: As regards chemotherapy, pemetrexed was superior to docetaxel in all measures (RR 45% vs 5 %, TTP 5.5 vs 4.5 months, median survival 13.8 vs 9.9 months), but only RR was statistically significant (p=0.003). Gefitinib obtained a better TTP and OS than erlotinib, although the differences were not statistically significant (7.9 vs 7.6 months; 15.4 vs 13.3 months respectively). But, RR was more relevant for erlotinib (29.2% vs 15% (p=0.2), even if an increased number of disease stabilization was recorded for gefitinib (65% vs 29.1%). Significant differences were observed in RR between pemetrexed and gefitinib (p=0.03) and erlotinib and docetaxel (p=0.03). All toxicities recorded were manageable. Conclusions: In our study, TKIs, above all gefitinib, seem to be a favourable choice for second line treatment, obtaining good response rates, with important stabilizations of disease and a relevant median survival, not strictly related to the histotype. Neverthless, for non squamous pts pemetrexed remains an important therapeutic choice. Patients characteristics. Docetaxel (21 pts) Pemetrexed (20 pts) Erlotinib (24 pts) Gefitinib (20 pts) Male/female 18/3 15/5 14/10 15/5 Median age 64.2 (50-78) 61.4 (46-79) 63.1 (42-80) 70.8 (54-81) PS0/PS1/PS2 9/10/2 10/9/1 9/11/4 7/9/4 Squamous Adenocarcinoma Others 12 1 8 1 16 3 11 12 1 9 7 4 Stage (IIIB/IV) 11/10 5/15 2/22 5/15 Third line therapy 11 10 8 8
Linear immunoglobulin A dermatosis mimicking toxic epidermal necrolysis: a case report of etanercept treatment
Authors: M. Prieto-Barrios, V. Velasco-Tamariz, F. Tous-Romero, S. Burillo-Martinez, C. Zarco-Olivo, J.L. Rodriguez-Peralto, P.L. Ortiz-Romero
Journal: British Journal of Dermatology (2017)

A 65-year-old pluripathological woman attended our hospital with a cutaneous eruption of sudden appearance after vancomycin treatment. She presented targetoid lesions affecting approximately 25-30% of her body surface, large erosions with mucosal lesions and positive Nikolsky sign. Under the initial clinical suspicion of toxic epidermal necrolysis (TEN), and considering the recent literature of successful use of etanercept in these cases, she was treated with a single dose of this antitumour necrosis factor (anti-TNF) agent. Subsequently, the exanthema progression stopped and resolution of the lesions happened in a few days. Later on, histopathology revealed a subepidermal blister with dense neutrophilic infiltrate and linear deposits of immunoglobulin A (IgA) on the dermoepidermal junction, allowing us to establish the diagnosis of drug-induced linear IgA dermatosis mimicking TEN. Linear IgA dermatosis can have severe clinical manifestations, even mimicking TEN, and can have high mortality, especially in drug-induced cases. We have not found any other report of linear IgA dermatosis treated with etanercept in the English literature. Anti-TNF medications could represent useful therapeutic alternatives in this dermatosis.
Masitinib in nonresectable pancreatic cancer: Results of a phase III randomized placebo-controlled trial.
Authors: Gael Deplanque, Martin Demarchi, Mohamed Hebbar, Patrick J. Flynn, Bohuslav Melichar, James Atkins, Philippe Ruszniewski, Eric Raymond, Olivier Hermine, Pascal Hammel
Journal: Journal of Clinical Oncology (2013)

158 Background: Masitinib is a selective c-Kit inhibitor that efficiently inhibits mast cell function. Increased mast cell activity in the tumor microenvironment has been linked to poor prognosis in pancreatic cancer (PC) patients. Methods: In a randomized (1:1 ratio), double-blind, international phase III trial, chemo-naïve PC patients (n=348) received either masitinib (9 mg/kg/day) in combination with gemcitabine (1000 mg/m 2 /wk) (M+G) or placebo plus gemcitabine (P+G). Primary endpoint was overall survival (OS). An ancillary pharmacogenomic study, based on RNA extracted from whole blood prior to treatment, was conducted in a subset of patients. Results: In the overall population median OS was not significantly improved in the M+G arm as compared with the P+G arm (median OS: 7.7 vs. 7.0 months, respectively; p=0.74, HR=0.90 [0.71; 1.14]). However, M+G treatment led to a significant survival advantage in two subpopulations. First, in patients with ‘pain’ at baseline (defined as a VAS score &gt;20 mm on a 100 mm scale) (44% of patients with pain intensity data available) median OS was significantly increased from 5.4 months in the P+G arm to 8.1 months in the M+G arm (p=0.010; HR:0.61 [0.42; 0.88]); OS rates at 12 and 18 months were respectively, 32.2% and 18.2% in the M+G arm vs. 17.8% and 7.8% in the P+G arm. Second, in patients with a specific deleterious genomic biomarker (GBM) consisting of a limited number of genes (66% of patients with genetic data available), median OS was significantly increased in the M+G arm as compared with the P+G arm (11.0 vs. 5.0 months, respectively) (p=0.000038; HR=0.29 [0.17; 0.51]); OS rates at 12 and 18 months were respectively, 41.4% and 18.5% in the M+G arm vs. 11.1% and 4.2% in the P+G arm. In patients without pain (defined as VAS &lt;5 mm and no need for opioid analgesics), median OS was 15.4 months in the P+G arm. In patients without the deleterious GBM, median OS in the P+G arm was 14.3 months. In these two patient populations M+G treatment was contraindicated. The general safety profile of the M+G combination regimen was acceptable. Conclusions: Masitinib in combination with gemcitabine provides a significant survival advantage over gemcitabine monotherapy in PC patients with ‘pain’ and patients with a specific GBM. Clinical trial information: NCT00789633.
The effects of sequential chemotherapy on locally advanced breast cancer (LABC) in African-Americans
Authors: S. M. Ferguson, C. Rodriguez-Burford, D. C. Chhieng, W. E. Grizzle
Journal: Journal of Clinical Oncology (2005)

901 Background: It is unknown whether the sequence of chemotherapy alters pathologic complete response (pCR) in breast cancer. We report the outcome of 23 women, 16 were African-American (AA) with LABC breast cancer presenting to a county hospital from January 2000-July 2003 treated initially with docetaxel followed by doxorubicin. Correlation with ER/PR, Ki-67, Her2neu and menopausal status is reported. Methods: Twenty-three women (16 AA) with LABC received primary chemotherapy treatment (PCT) utilizing docetaxel (38mg/m2) q 8 days for 8 cycles followed by doxorubicin (75mg/m2) q 21 days for 3 cycles. All patients underwent surgical resection of the tumor and lymph node dissection. Immunohistochemistry was performed on formalin-fixed, paraffin embedded tissue using antibodies against ER/PR, Her2neu and Ki-67. Results: 22/23 patients (95.65%) responded to PCT with pCR or pPR. 15/16 (93.75%) of AA were responders. Of these AA responding 57% were ER negative, 50% PR negative, 60% Ki-67 positive, 13% Her2neu positive, and 53% were premenopausal. 10/15 (66.6%) of responding AA have not relapsed. Disease free survival (DFS) is 20months and Overall Survival (OS) is 22.5 months in the AA responders. Conclusion: Altering the sequence of PCT in AA women with LABC may afford increased pathologic response rates(pRR). Reasons for this response are not clear though ER/PR negative, Ki-67 positive tumors were seen more frequently in AA women and may have different biologic characteristics. Whether improved pRR leads to improved DFS/OS in these women remains to be see. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Aventis via Jefferson Clinic, PC
A model to optimize treatment case-to-machine assignment in radiation oncology.
Authors: Nicholas Carl Kukshtel, Robert Mersereau, Sarah Kadish, Spyros Potiris, Todd Vivenzio, Neil E. Martin
Journal: Journal of Clinical Oncology (2014)

231 Background: The department of Radiation Oncology at the Dana-Farber/Brigham and Women’s Cancer Center operates seven linear accelerators treating approximately 200 patients per day. These machines are regularly shut-down for upgrades, requiring the redistribution of patients to available machines. Previous machine downtimes have caused disruptions to patient care and required extended operating hours to accommodate displaced patient volume. For the next machine downtime, we sought to create a model to optimize the reassignment of patients to available machines, maximizing treatment type-machine compatibility while minimizing overtime, costs, and patient care impact. Methods: This collaboration between Radiation Oncology and the Process Improvement team retooled the Assignment Problem Method, an Industrial Engineering technique used to assign tasks, in order to solve for case allocation to radiation machines. A spreadsheet model was developed to optimize the allocation of treatment cases for each machine, without violating working hours or treatment type-machine constraints. Input data included case duration, radiation technique, daily demand, and machine compatibility for each treatment type. In addition to finding an optimal case allocation, department administrators created “what-if” scenarios to identify how demand fluctuations would shift cases across machines. Proposed solutions were validated by comparing the model’s output to feasible treatment volumes identified by department administrators. Results: The model revealed that under idealized conditions, the current daily patient volume can be accommodated with two fewer machines and 1.5 fewer operating hours each day. The time it took department administrators to prepare for the next downtime was reduced from several weeks of manual planning, to a few days using the model. Conclusions: Simple industrial engineering tools can help solve complex problems. Developing optimization models can eliminate complex calculations, allowing end-users to refine and implement a suitable solution without fear of mathematical error. A robust model can provide end users the ability to assess the impact of future changes in capacity or demand.
Phase II study of bortezomib in advanced or metastatic urothelial cancer. A trial of the Princess Margaret Hospital [PMH] Phase II Consortium
Authors: S. S. Sridhar, W. Stadler, L. Le, D. Hedley, G. Pond, J. Wright, E. Vokes, S. Thomas, M. Moore
Journal: Journal of Clinical Oncology (2005)

4677 Background: The ubiquitin-proteasome proteolytic pathway regulates the metabolism of several key proteins (p53, p21, p27, NF-kappaB) involved in cell cycle, apoptosis, metastasis and angiogenesis. PS341 (Bortezomib;Velcade) is a dipeptidyl boronic acid derivative that is a potent and highly specific inhibitor of the proteasome, which shows preclinical evidence of antitumor activity. Methods: Patients had advanced or metastatic transitional cell cancer of the bladder, renal pelvis, or ureter treated with 1 or more prior lines of therapy for metastatic disease. The primary endpoint was response rate. Bortezomib was administered at a dose of 1.3mg/m2/day IV on days 1, 4, 8, and 11 of a 21 day cycle. Tumor response was assessed by RECIST criteria every 3 cycles. Tumor biopsies in suitable consenting patients were planned at baseline and within 24 hours of treatment on day 8 or 11 to assess pre and post-treatment levels of NF-kappaB and HIF1 alpha. In order to minimize the number of patients treated if the regimen was not active, a two stage phase II design will be used based upon P0 = 0.05, P1= 0.20, α = 0.10 and β =0.10. In stage I 20 evaluable patients are planned with continuation if at least 2 patients have an objective tumour response. Results: In total 18 pts (3F:15M), median age 70 (49–81) were entered on study and received a total of 34 cycles (range 1–3) of treatment. 1:11:2:1 had received 0:1:2:3 prior therapies for advanced disease. 11 pts are evaluable for response and all had progressive disease (PD); 7 are inevaluable (1 did not receive drug; 2 never completed 1 cycle due to toxicity; 4 too early). Most common adverse events, of any grade were fatigue (76% cycles), anemia (76%), lymphopenia (62%), and hyperglycemia (47%). Conclusions: At present, single agent PS341 has not shown activity in advanced transitional cell cancer of the kidneys, ureters or bladder. Accrual continues to complete stage 1 of the study. No significant financial relationships to disclose.