tbuckley/cabot-search huggingface dataset:
Rate of complete pathological responses (pCR) to docetaxel/cisplatin/5-fluorouracil (TPF) induction chemotherapy in patients with newly diagnosed, locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: R. I. Haddad, R. Tishler, L. Wirth, C. Norris, L. Goguen, C. Sullivan, L. O’Donnell, Y. Li, M. R. Posner
Journal: Journal of Clinical Oncology (2005)

5511 Background: Sequential chemoradiotherapy using induction chemotherapy (IC) followed by chemoradiotherapy (CRT) is often used in patients with SCCHN. Two recent large phase III studies have shown that adding a taxane to standard PF induction regimen improves outcome and is better tolerated than PF (Hitt et al ASCO 2003, Vermorken et al. ASCO 2004). It is our standard practice to biopsy the primary site after IC before CRT. We report the rate of complete pathological response (pCR) after IC with TPF. Material and Methods: All patients received three cycles of IC with TPF followed by CRT. Chemoradiotherapy consisted of weekly carboplatin/ paclitaxel or docetaxel with standard or concomitant boost XRT. All patients were biopsied after IC, before starting CRT. Neck dissection (ND) was performed 6–12 weeks after CRT for N3 patients and incomplete responders to CRT. Results: Between June 1999 and May 2004, 72 patients underwent biopsy of the primary site after IC. Stage IV: 95%, Oropharynx 75%: Biopsy was negative in 64 patients (89%) and positive in 8 patients (11%). Median follow up is two years. In the positive biopsy group 2/8 (25%) died of disease vs. 3/64 (4%) in the negative biopsy group. Twenty-nine ND were performed: Seven positive (all alive NED) and 22 Negative (21 Alive, NED). The overall 2 and 5- year progression-free survival currently projects at 85% and 85% respectively and the overall 2-year and 5-year survival at 95% and 90% respectively. Importantly, T4 presentation did not predict a positive biopsy at primary site or a positive ND (p =0.6031 and p=0.5557 respectively). N3 presentation (12 patients) did not predict a positive biopsy (p=0.8668), but did correlate with positive ND: 6/12 (p<0.001). Conclusion: TPF induction chemotherapy results in high rate of pCR (89%). This rate is higher than PF, reported in previous studies to be between 25–50%. Chemoradiotherapy is currently an accepted standard of care but IC continues to be investigated. Based on the recent phase III results and the data presented here, we propose that the three-drug combination be used as the new platform when using IC. No significant financial relationships to disclose.
Variability in immune infiltrates and HLA expression in cholangiocarcinoma.
Authors: Francesco Sabbatino, Lucia Milham, Vikram Deshpande, Ioannis T. Konstantinidis, Andrew X. Zhu, Daniela Dias Santos, Nabeel Bardeesy, Theodore S. Hong, Kenneth Tanabe, Soldano Ferrone, Keith Lillemoe, Cristina Ferrone
Journal: Journal of Clinical Oncology (2014)

230 Background: Cholangiocarcinoma continues to have a dismal prognosis. The lack of effective therapy prompted us to determine whether patients develop an immune response against their own tumors. The aim of this study is to evaluate the CD8 infiltrate and expression of HLA class I antigen processing machinery (APM) components in cholangiocarcinoma. The HLA class I antigen processing machinery (APM) components play a crucial role in expression of HLA class I tumor antigen derived peptide complexes. These complexes mediate the recognition of tumor cells by cognate T cells. Defects in the expression of HLA class I APM components by tumor cells suggests that the infiltrating lymphocytes impose selective pressure on tumor cells. This selective pressure would facilitate the outgrowth of tumors by escaping T cell recognition. Methods: Retrospective review of clinicopathologic factors was performed for 18 peripheral cholangiocarcinomas. Formalin fixed, paraffin embedded tumors were evaluated for the content of lymphocyte infiltrates and for the expression of HLA class I APM components. Results: Eighteen patients underwent a partial hepatectomy for peripheral cholangiocarcinoma of whom 10 were female. Median age was 63yo. The majority of patients had node negative tumors (10/12). All tumors had lymphocytic infiltration. Median number of lymphocytes in the fibrous septae between tumor lobules was 42 CD8 T cells per 10 high power field, but only 4 CD8 T cells within tumor lobules. HLA class I APM components was defective and not detected in three tumors, all of which were poorly differentiated. HLA expression was down regulated in 9 tumors. HLA expression was in normal range in the remaining 6 tumors. Median overall survival has not been reached. Conclusions: Lymphocytic infiltrates were seen in all resected cholangiocarcinoma specimens. The loss of HLA class I APM component expression in cholangiocarcinoma suggests that infiltrating lymphocytes reflect a patient’s immune response to his/her tumor. This information provides a sound rationale to consider immunotherapy in the treatment of cholangiocarcinoma, specifically with antibodies to check point molecules which enhance patients’ immune response against his own tumors.
Patterns of intensity of end-of-life care for adolescents and young adults with cancer: A population-based study.
Authors: Emily E. Johnston, Elysia Marie Alvarez, Olga Saynina, Lee Sanders, Smita Bhatia, Lisa J Chamberlain
Journal: Journal of Clinical Oncology (2016)

132 Background: Cancer is the leading cause of non-accidental death amongst adolescents and young adults (AYA), aged 15-39, in the U.S. It is critical to understand end of life (EOL) care of AYA cancer decedents, including use of medically intense interventions like intubation. Although desired by some, most patients prefer a natural death. We sought to determine rates of medically intense interventions at end of life for AYA cancer decedents and associated factors. Methods: Using the California Office of Statewide Health Planning and Development private administrative database linked to death certificates, we performed a retrospective population based analysis of patients aged 15-39 with cancer who died between 2000-2010. We used previously defined administrative codes indicative of intense EOL care: intubation, CPR, hospital re-admission, and ICU admission in the last 30 days of life, and location of death. The frequencies of each intense item were calculated and multivariate logistic regression was used to determine clinical (including treatment at specialty center vs non) and socio-demographic factors associated with each item and receipt of ≥ 2 items. Results: The 8,978 AYA cancer decedents were 46% non-Hispanic white, 29% Hispanic, 10% non-Hispanic black, 11% Asian; 21% had hematologic malignancies, 70% had solid tumors, and 9% had secondary neoplasms; 58% were hospitalized only at non-specialty centers in the last 6 months of life. 62% received ≥ 1 medically intense EOL care intervention, and 32% received &gt; 2. Factors associated with &gt; 2 intense EOL care interventions were: non-Hispanic black (OR 1.38, 95% CI 1.16-1.65), Hispanics (1.19, 1.06-1.35), Asians (1.30, 1.10-1.52); those sometimes (2.19, 1.87-2.56) or never (1.44, 1.26-1.65) seen at specialty centers; hematologic malignancies (1.77, 1.57-2.00 ref grp: solid tumors) whereas secondary malignancies were not associated with &gt; 2 intense markers (0.68, 0.56-0.83). Conclusions: Nearly two-thirds of the AYA cancer decedents received medically intense EOL interventions and disparities exist in receipt of such care. Further research needs to determine if the disparities are due to healthcare system, patient preference, or other factors.
ATDC as a novel oncogene in bladder cancer.
Authors: Phillip Lee Palmbos, Lidong Wang, Huibin Yang, Taylor Detzler, Gina Ney, Yair Lotan, J E Wilkerson, Priya Kunju, Mats Ljungman, Monica Liebert, Diane M. Simeone
Journal: Journal of Clinical Oncology (2012)

269 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: The dominant phenotype in these mice was the development of both papillary and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. Analysis of a human bladder cancer tissue microarray (311 samples) showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, whereas normal bladder had no expression. 22% (5/23) of papillary tumors also expressed elevated levels of ATDC. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which was determined to be due to ATDC abrogation of p53 function by cytoplasmic sequestration and ATDC-mediated methylation of the PTEN promoter. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.
Effect of everolimus plus octreotide LAR treatment on chromogranin A and 5-hydroxyindoleacetic acid levels in patients with advanced neuroendocrine tumors: Phase III RADIANT-2 study results.
Authors: E. Baudin, E. M. Wolin, D. E. Castellano, G. Kaltsas, J. Lebrec, Z. Tsuchihashi, J. Klimovsky, S. Saletan, J. C. Yao, D. Gross
Journal: Journal of Clinical Oncology (2011)

10527 Background: Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are important biomarkers of tumor burden and carcinoid syndrome in patients with neuroendocrine tumors (NET). The goals of this analysis were to characterize serum CgA and 24-h urinary 5-HIAA level changes from baseline in response to treatment with everolimus, oral inhibitor of mTOR, + octreotide LAR vs placebo + octreotide LAR (P+O) in patients with advanced NET in the phase III RADIANT-2 trial. Methods: Patients (n=429) received everolimus 10 mg/d + octreotide LAR 30 mg IM q 28 days (E+O; n=216) or P+O (n=213). Serum samples were collected and analyzed for CgA and urine samples for 5-HIAA at baseline and, if elevated (>ULN), were repeated on day 1 of each subsequent cycle. CgA and 5-HIAA response, defined as normalization or ≥50% reduction, was described by treatment arm, and changes from baseline over time were analyzed using a mixed-effects model including least squares estimates of treatment effect. Results: Patients with elevated baseline values had biomarkers assessed for a median number of 10 cycles in both the E+O and the P+O arms. Patients on E+O had a higher incidence of CgA and 5-HIAA response (45.7% [75/164] and 60.7% [85/140]) than patients on P+O (28.8% [42/146] and 46.8% [66/141]). Patients in the E+O group vs those in the P+O group showed greater reductions of both serum CgA (P=0.0041) and urinary 5-HIAA (P<0.0001) over time. During the first cycle, the ratio in fold change from baseline for the E+O group vs the P+O group was 0.754/0.891=0.85 (95% CI, 0.70-1.02) and 0.749/0.891=0.84 (95% CI, 0.71-1.00) for CgA and 5-HIAA, respectively. A positive treatment effect with E+O was maintained over the subsquent treatment cycles. Conclusions: E+O resulted in early, sustained decreases in both serum CgA and urinary 5-HIAA vs P+O. In addition to the improvement in progression-free survival (PFS) seen in RADIANT-2, these results demonstrate that E+O provides a significant reduction in both biomarkers used to evaluate patients with carcinoid syndrome. Future studies should examine the correlation between serum CgA and urinary 5-HIAA response and PFS.
Synergistic Anti-Myeloma Activity of a Proteasome Inhibitor Marizomib and IMiD® Immunomodulatory Drug Pomalidomide
Authors: Deepika Sharma Das, Durgadevi Ravillah, Arghya Ray, Yan Song, Paul G. Richardson, Mohit Trikha, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2014)
The association between diabetes mellitus and HCC: Noise or real? A meta-analysis of epidemiologic evidence.
Authors: S. Janarthanan, I. C. Ditah, N. Tageja, A. Kutait
Journal: Journal of Clinical Oncology (2011)

184 Background: Diabetes mellitus (DM) has been linked to an increase in the incidence of hepatocellular carcinoma (HCC). However, these studies have yielded controversial findings. This study evaluates the association between DM and risk of HCC in a meta-analysis. Methods: Two investigators independently conducted a search of studies on the association between DM and HCC from January 1970 through August 2010 on Medline. Identified articles were manually reviewed for additional references. Only full articles that provided risk estimates for the association were selected. The most adjusted risk estimates were abstracted and synthesized using the random-effects model. A stratified analysis by study design and study region has also been done. All studies were evaluated for publication bias before analysis. Results: A total of 35 studies, 20 case-control and 15cohort studies, were eligible for analysis. The overall summary risk ratio for HCC in DM was 1.60 (95% CI 1.49, 1.70; p&lt;0.001). Among the case-control and cohort studies, the pooled risk estimate was 1.33 (95% CI 1.21, 1.46; p&lt;0.001) and 2.24 (2.05, 2.44; p&lt;0.001) respectively. By geographic location, the association remained significant among the European (15) and U.S. (10) based studies with risk ratios of 2.7 (95% CI 2.37, 3.05; p&lt;0.001) and 1.58 (95% CI 1.45, 1.7) respectively. However, among the Japanese (10) based studies there was a nonsignificant 3% reduction in the risk of HCC (RR 0.97; 95% CI 0.71, 1.24; p&gt;0.05). There was no evidence of publication bias among the studies included. Conclusions: The evidence in support of DM as an independent risk factor for HCC remains unclear. Though not significant, the finding among the Japanese based populations raises concerns over the potential role of environmental and/or genetic factors in the observed association. Further studies with great attention to potential confounders are warranted to definitively define the association between DM and HCC. No significant financial relationships to disclose.
Temozolomide in the management of progressive metastatic renal cell cancer (RCC) following immunotherapy
Authors: E. Özgür, C. H. Ohlmann, U. H. Engelmann, G. Haupt, A. Heidenreich
Journal: Journal of Clinical Oncology (2005)

4600 Background: Temozolomide (TMZ) is an oral alkylating agent that produces methyl adducts at the 0.6 position of guanine. TMZ has shown in vitro activity against renal cell cancer cell lines. We report the phase-II results of a prospective study evaluating the efficacy of TMZ in the management of patients with metastatic renal cell cancer who progressed after immunochemotherapy. Methods: From January 2001 to September 2004, 45 patients (11 females, 34 males) were enrolled in the study. Patients were eligible if CT scans 6 to 8 weeks following the last cycle of immunotherapy demonstrated an at least 25% increase in tumor volume. Mean age at time of study entry was 66.2 (46 to 79) years, 40 (89%) patients had undergone radical nephrectomy, 14 (31%) had undergone resection of solitary visceral and/or lymph node metastases. All patients had received at least 2 cycles (mean 2.7) immunochemotherapy according to the Hannover protocol before systemic progression developed. Treatment consisted of 6 cycles of TMZ at 200mg/m2 on days 1–5 of a 4-weeks regime. Restaging with computed tomography was performed after 3 and 6 cycles. Results: After a mean follow-up 25 (2 - 45) months, 8 (18%) patients demonstrated a partial response, 19 (42%) exhibited a stable disease resulting in a total response rate of 60%. 18 (40%) developed progressive disease during therapy. The mean time to progression in responding patients was 7.2 months, mean survival time is 11.9 months. Side effects were moderate with WHO grade II nausea and emesis in 24%, fatigue in 25% and headache in 20% of the patients; no WHO grade III/IV side effects were observed. Conclusions: These early results are encouraging and demonstrate that TMZ appears to be a valuable therapeutic alternative in immunorefractory metastatic renal cell cancer with minimal side effects and a total response rate of 60%. Further studies are initiated to explore the clinical utility of TMZ in the primary management of metastatic RCC. No significant financial relationships to disclose.
Toxicity and efficacy of salvage paclitaxel chemotherapy in Royal Marsden (RM) oesophagogastric adenocarcinoma (OGA) patients (pts).
Authors: NOELIA TARAZONA, Elizabeth Catherine Smyth, Clare Peckitt, Ian Chau, David J. Watkins, Sheela Rao, Naureen Starling, David Cunningham
Journal: Journal of Clinical Oncology (2015)

188 Background: Paclitaxel is a standard global salvage therapy for pts with advanced refractory OGA. Western pts may differ from Asian pts with respect to chemotherapy metabolism and cancer behaviour, and the benefits associated with paclitaxel in this setting have not been assessed outside of Asia. We examined the efficacy and toxicity associated with salvage paclitaxel for advanced OGA at RM over a 3 year period. Methods: This was a retrospective observational study. We identified all pts with OGA treated with salvage weekly paclitaxel from 01/06/2011 to 21/02/2014 from the electronic pt record at RM. The following data was collected: demographics, metastatic sites, resection status, response/duration of response to prior chemotherapy, ECOG PS, haemoglobin, albumin, alkaline phosphatase (ALP), neutrophil/lymphocyte ratio, CEA, CA19.9, RM prognostic score, CT response and date of progression, death or last follow up. Toxicity was collected as per NCI Common Toxicity Criteria (v4.0). Overall and progression free survival (OS/PFS) were estimated using the Kaplan-Meier method. Multivariate Cox regression analysis examined the association between clinical and laboratory variables with survival. Results: 57 pts were identified. Pts were 74% male; median age 64y; 66% PS 0-1; 91% 2nd line. Median number cycles 3 (range 1-8). Median follow up 13.6m. Response rate was 18.4% in evaluable pts. OS and PFS were 5.8m (95% CI: 4.8 – 6.8m) and 2.6m (95% CI: 1.9 – 3.2m). 2y and 3y survival from start of 1st line treatment were 26% and 13%. In multivariate analyses PS ≥2 [HR 2.28, p = 0.018], and ALP ≥100 U/L, [HR=2.01, p= 0.033] were independent negative prognostic factors for OS. ≥ Grade 3 nausea, diarrhea and neuropathy were uncommon (&lt;2% each), rate of ≥ grade 3 fatigue was 11%. Grade 3-4 neutropenia, leucopenia and thrombocytopenia occurred in 12%, 11% and 2% pts. Conclusions: Advanced OGA pts treated at RM with salvage paclitaxel have an OS equivalent to pts in clinical trials with less hematological toxicity than seen in Asian patients. This may be due to regional pharmacogenetic profiles. As a significant proportion of pts now survive 2-3y with limited toxicity, therapeutic nihilism is unwarranted.
Cancer patients’ and physicians’ preferences for decision making regarding pharmacogenomic testing (PGT).
Authors: Sinead Cuffe, Henrique Hon, Xin Qiu, Sohaib Masroor, Bradley De Souza, Graham McFarlane, Chung-Kwun Amy Wong, Kimberly Tobros, Abul Kalam Azad, Ekta Hasani, Natalie Rozanec, Natasha B. Leighl, Nelson A. Atehortua, Shabbir M. H. Alibhai, Wei Xu, Amalia M. Issa, Geoffrey Liu
Journal: Journal of Clinical Oncology (2012)

13 Background: Pharmacogenomics is increasingly utilized in oncology; however, there is little knowledge concerning cancer patients’ or oncologists’ attitudes toward PGT decision-making in clinical practice. Methods: A broad cross-section of cancer patients were interviewed regarding their attitudes toward PGT using hypothetical time, efficacy and toxicity trade-off and willingness-to-pay scenarios (N=278) and/or quantitative choice-based conjoint analysis surveys (N=264); 64 cancer specialists/physicians in training were surveyed similarly. Results: Of patients participating in the trade-off scenario phase of study, &gt;94% accepted chemotherapy, and of these, &gt;98% wanted PGT that identifies a subset of patients either benefiting from chemotheraphy or who were at risk of severe toxicity. Patients were willing to pay between CAD $1,000-$1,900 for PGT and accept wait times for results of 2-3 weeks. Similar findings were observed in the conjoint phase of the study, with preferences for PGT starting to decline when the out-of-pocket costs reached CAD $500-$1,500, wait time for results exceeded 14 days, and when the prevalence of the genetic variant fell below 25%. Adjuvant patients’ acceptance of PGT was most influenced by cost (decision weight [DW]=41%) and prevalence of the genetic variant associated with lack of benefit from chemo (DW=26%). Metastatic patients were most influenced by cost (DW=49%) and wait times (DW=31%). More patients reported difficulty understanding conjoint surveys (14%) than trade-off scenarios (7%; p=0.01). 81% of patients wanted to be involved in decision-making regarding PGT; while 30% of physicians felt it should be a physician-only decision (p=0.006). However, 21% of patients and 5% of physicians admitted to not understanding PGT, while just 14% of physicians rated themselves as very knowledgeable regarding PGT. Conclusions: Cancer patients overwhelmingly accept and want to be involved in decision-making regarding PGT, to a greater extent than what physicians prefer. However, communication of PGT information was a potential barrier, as a considerable minority lacked the necessary knowledge to facilitate informed decision-making. Improved patient and physician education is necessary.