tbuckley/cabot-search huggingface dataset:
Pas de deux
Authors: Ian Wicks
Journal: JAMA (2017)

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Second primary tumors in head and neck squamous cell carcinoma patients: A cross-sectional study.
Authors: Luciana Garcia Landeiro, Damila Trufelli, Leandro Luongo Matos, Daniel de Iracema Gomes Cubero, Jossi Ledo Kanda, Auro Del Giglio, Gilberto Castro
Journal: Journal of Clinical Oncology (2012)

5588 Background: Head and neck squamous cell carcinoma (HNSCC) patients (pts) are at elevated risk of developing a second primary tumor (SPT). Here we aimed to study the frequency of SPTs and those characteristics related to an increased probability of SPT occurrence. Methods: It is a cross-sectional study in pts diagnosed with SCC primary located in oral cavity, oropharynx, hypopharynx or larynx, treated in two Brazilian institutions, with an index tumor diagnosed from Jan/2000 to Jan/2009. All pts were followed according the current recommendations, including clinical visits, imaging and endoscopic procedures. A SPT was defined following the Warren and Gates criteria (Am J Cancer 51:1358,1932), and they were classified as synchronous or metachronous if detected less or more than six months after the diagnosis of the index tumor, respectively. Results: 38 out of 318 HNSCC pts (12%) were diagnosed with 41 SPTs in their follow-up, being 12 synchronous (29%) and 29 metachronous (71%), all classified as SCC. Regarding the index tumor, it was primary located in oral cavity (114 pts, 36%), oropharynx (87 pts, 27%), larynx (83 pts, 26%) and hypopharynx (34 pts, 11%), and staged as I-II (30%) or III-IV (67%). The SPTs were located more frequently in oral cavity (27%), lungs (27%), oropharynx (15%) and esophagus (12%) and staged as I-II (44%) or III-IV (42%). Among the 29 metachronous SPTs, 12 (41%) were diagnosed in the first two years of follow-up, 11 (38%) between two and five years, and 6 (21%) after five years. Considering all the studied HNSCC pts and index tumor characteristics, including primary site, persistence of tabacco and alcohol habits, and treatment, none was identified as related to an increased probability of developing a SPT. In the median follow-up of 40 mo., the median overall survival was not reached in all 318 HNSCC pts. No difference in overall survival was observed between those pts diagnosed or not with a SPT (HR 0.35, p=0.555). Conclusions: We found a 12% incidence of SPTs in these HNSCC pts. At diagnosis, SPTs were located more frequently in oral cavity and lungs, in advanced stages, and may occur even after five years after the index tumor. More efficient primary and secondary preventive strategies of SPTs must be developed.
Hand-foot syndrome (HFS) and asthenia/fatigue (A/F) as biomarkers of sunitinib efficacy in Chinese patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Shukui Qin, Jie Jin, Jun Guo, Jin-Wan Wang, Fang-Jian Zhou, Yi-Ran Huang, Xiu-Bao Ren, Ding-Wei Ye, Sharon Pan, Peter Sajben, Qiao Wang
Journal: Journal of Clinical Oncology (2013)

e15622 Background: In an open-label phase IV study of sunitinib as 1st-line treatment (Tx) in Chinese pts with mRCC, median progression-free survival (PFS) and overall survival (OS) were 61.7 and 133.4 wk, respectively; objective response rate (ORR) was 31.1% (Ann Oncol 2012;23:851P). We retrospectively investigated correlations between on-Tx HFS or A/F and efficacy endpoints in pts from this trial. Methods: AEs were recorded and graded using NCI CTCAE v3. Median PFS and OS were estimated by Kaplan−Meier method. The log-rank test was used to compare PFS and OS between groups with and without HFS or A/F. Fisher’s exact test was used for ORR. Multivariate and time-dependent covariate analyses were conducted to assess the influence of various prognostic factors on the association between AEs and efficacy and to address potential bias from longer drug exposure, respectively. Landmark analyses were used to compare outcomes in pts with and without HFS or A/F after 6 and 12 wk of Tx. Results: Of 103 pts included in the analyses, 67 (65%) and 54 (52%) had on-Tx HFS and A/F, respectively. Pts with HFS had greater ORR and significantly longer PFS and OS than pts without HFS (Table). Pts with A/F had greater ORR and longer PFS and OS than pts without A/F. By multivariate analysis, HFS was a significant predictor for both PFS and OS, and A/F was a significant predictor for PFS (Table). However, no findings were significant in the time-dependent covariate (Table) or landmark analyses (not shown). Conclusions: The development of HFS or A/F at any time during Tx with sunitinib was significantly associated with better outcome; however, time-dependent covariate and landmark analyses suggest that these AEs may not be reliable predictors of efficacy at early time points. Clinical trial information: NCT00706706. [Table: see text]
CALGB 30704: A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer (NSCLC).
Authors: Rebecca Suk Heist, Xiaofei F. Wang, Lydia Hodgson, Gregory Alan Otterson, Tom Stinchcombe, Everett E. Vokes, Mark A. Socinski
Journal: Journal of Clinical Oncology (2012)

7513 Background: Second line chemotherapy improves survival modestly and new strategies are needed. This trial was designed to evaluate the paradigm of an anti-VEGF strategy with or without standard chemotherapy in previously treated NSCLC. Methods: Patients with Stage IIIB/IV NSCLC, PS 0-1 progressive after first-line chemotherapy were eligible for randomization to P (pemetrexed 500 mg/m2 d1), S (sunitinib 37.5 mg d1-21), or P+S (pemetrexed 500 mg/m2 d1 + sunitinib 37.5 mg d1-21). Pts were stratified by PS (0/1), stage (IIIB/IV), and gender (M/F). Primary objective was 18-week PFS rate; secondary objectives were response, OS, and toxicity. Target accrual was 225. The study was terminated early due to decreasing accrual rates. Results: Between 4/08 and 9/11, 130 pts registered; 128 pts treated (P=41, S=46, P+S=41). Median follow-up 99 weeks. Baseline characteristics in the three arms (P/S/P+S) were well balanced: Male (54%/54%/54%); PS 0 (32%/35%/34%); Stage IV (88%/83%/93%). Histology was predominantly adenocarcinoma (66%/57%/66%); squamous was allowed (10%/15%/15%). Toxicity was higher in the S-containing arms: Grade 3/4/5 hematologic toxicity: P 5/0/0 (12%), S 8/1/0 (21%), P+S 5/9/0 (36%); Grade 3/4/5 non-hematologic toxicity (excluding disease related deaths): P 6/2/0 (20%), S 21/3/1 (58%), P+S 21/3/1 (63%). The 18-week PFS rate in the three arms was: P 51% (38-69), S 36% (24-54), P+S 47% (34-65). There is an overall statistically significant difference in OS between the three arms (2-sided p=0.0179) with HR 0.65 (95%CI: 0.38-1.13) for P/S; HR 0.47 (95%CI: 0.27- 0.82) for P/P+S. Median OS was 10.5 mo (8.3-22.5) for P, 7.0 mo (6.0-13.0) for S, 6.7 (4.1-10.4) mo for P+S. Median PFS was 4.4 mo (1.7-8.8) for P, 3.3 mo (2.7-4.3) for S, 3.7 mo (2.5-4.3) for P+S (p=0.3). Fewer patients in the P+S arm received any subsequent therapy (29%) than either P (54%) or S (57%). Conclusions: Pemetrexed had a superior toxicity profile to either sunitinib or the combination of pemetrexed and sunitinib. OS was significantly better with P alone compared to the two S-containing arms, with P+S performing worst for OS.
Neoadjuvant vascular targeted photodynamic therapy in urothelial cancer: Preclinical data.
Authors: Barak Rosenzweig, Renato B Corradi, Sadna Budhu, Ricardo Alvim, Pedro Guiraldes Recabal, Stephen LaRosa, Alex Somma, Sebastien Monette, Avigdor Joshua Scherz, Kwanghee Kim, Jonathan Coleman
Journal: Journal of Clinical Oncology (2017)

321 Background: Recurrence and progression following surgical treatment of locally advanced urothelial cancer is high spurring a need to develop effective, well-tolerated neoadjuvant strategies. We examined the efficacy and immunotherapeutic mechanism of neoadjuvant sub-ablative vascular targeted photodynamic therapy (sbVTP) in urothelial cancer. Methods: Following urothelial tumor implantation, mice were randomized to receive neoadjuvant sbVTP (WST-11; TOOKAD Soluble, Steba Biotech, France) or sham treatment 17 days prior to surgical resection. Therapeutic efficacy was evaluated by local and systemic response and survival studies. Immunohistochemistry and flow cytometry were used to elucidate mechanism. Kaplan-Meier, Mann-Whitney and Fischer exact test were used to analyze the data. All statistical tests were two-sided. Results: On the day of surgery, tumor volume was 1222 mm 3 (95% CI 976-1468 mm 3 ) vs. 135 mm 3 (95% CI 66-204 mm 3 , p &lt; 0.0001) and systemic progression was 30% vs. 7% (p&lt;0.05), for control vs. sbVTP treated animals, respectively. Median progression free survival and overall survival were 45 and 55 days respectively for surgery only group and significantly longer (50% not reached, p&lt;0.05) for the sbVTP + surgery group. Local recurrence rates were significantly lower in neoadjuvant treated animals. Neoadjuvant sbVTP was associated with increase in early antigen presenting cells followed by long term memory, effectory and active T-cell increase in spleen, lungs and blood. Conclusions: Neoadjuvant sbVTP treatment demonstrates evidence of therapeutic efficacy through an immune mediated response in this murine urothelial cancer model by delaying local and systemic progression, prolonging progression free and overall survival, and reducing local recurrence. Evaluation of this form of therapy in clinical trials is warranted.
Association Between Ustekinumab Trough Concentrations and Clinical, Biomarker, and Endoscopic Outcomes in Patients With Crohn’s Disease
Authors: Robert Battat, Uri Kopylov, Talat Bessissow, Alain Bitton, Albert Cohen, Anjali Jain, Myriam Martel, Ernest Seidman, Waqqas Afif
Journal: Clinical Gastroenterology and Hepatology (2017)
Abstract 13: Nur77 Translocation from Nucleus to Mitochondria Contributes to the Enhanced Susceptibility to Ischemia-Reperfusion Injury in Diabetic Hearts
Authors: Jingyi Liu, Peilin Liu, Min Jia, Haifeng Zhang, Chao Gao, Wenjun Yan, Yi Liu, Lu Yang, Lu Sun, Ling Tao
Journal: Circulation Research (2012)

Diabetes is associated with increased prevalence of ischemic heart disease which accounts for the high incidence of death in the diabetic population. In response to various pro-apoptotic treatments, Nur77, a nuclear orphan receptor, translocates from the nucleus to mitochondria where it induces cytochrome c release and apoptosis in cancer cells. However, the role of Nur77 in diabetic myocardial ischemia/reperfusion (MI/R) injury remains elusive. Ten-week-old male C57BL/6J mice (WT) and ob/ob mice (OB) were subjected to 30 min of ischemia and 3 or 24 hrs of reperfusion. Compared with WT, the OB hearts exhibited more severe MI/R injury as evidenced by more ROS production, increased infarct size, caspase-3 activity, TUNEL staining and decreased cardiac function (n=8, all P &lt;0.05). There was no significantly difference in total Nur77 expression levels between sham and MI/R group in WT mice. However, MI/R caused significant Nur77 mitochondria translocation as evidenced by decreased nuclear and increased cytosolic/mitochondrial Nur77 levels (all P &lt;0.01). Comparing to WT, total Nur77 expression levels were significantly reduced in OB heart before MI/R ( P &lt;0.01 vs. WT). However, MI/R caused more significant Nur77 mitochondrial translocation in OB mice, reaching a level that was not different from that seen in WT after MI/R ( P &gt;0.01 vs. WT). Intramyocardial small-interfering RNA (Nur77-siRNA) injection specifically knocked-down the myocardial Nur77, increased ejection fraction and reduced infarct size/apoptosis after MI/R in both WT and OB mice (all P &lt;0.05). However, more significant cardioprotection of Nur77 knockdown was observed in OB mice than that seen in WT. Collectively, we demonstrated firstly that the increased translocation of Nur77 from nucleus to mitochondria partly contributes to the enhanced susceptibility to MI/R in diabetic hearts. Interventions blocking this subcellular redistribution of Nur77 may be a potential therapy for the treatment of diabetic heart injury. Key Words: Nur77 • Mitochondria Translocation • Myocardial ischemia/reperfusion • Diabetes
Antitumour activity of pemetrexed (Pem) and irinotecan (Iri) in second-line metastatic colorectal cancer (MCRC) patients: A multicenter phase II study
Authors: C. Louvet, T. Andre, E. Gamelin, M. Hebbar, M. Mabro, M. Bennamoun, A. De Gramont
Journal: Journal of Clinical Oncology (2007)

4103 Introduction: 5FU + Iri (i.e. FOLFIRI) is a validated second line treatment after 5FU + Oxaliplatin (i.e. FOLFOX) induction in MCRC, with a response rate ranged from 10 to 15%. Pem is a multi-antifolate with wide range of target inhibition as compared to 5FU suggesting that Pem + Iri could have a better efficacy as compared to FOLFIRI. We then studied the antitumour activity and the safety of Pem + Iri combination in patients treated with FOLFOX for MCRC. Methods: Forty-six patients with measurable second line MCRC and no brain metastases were included in this trial. Pem 400 mg/m 2 over 10min on d1 with folic acid and vitamin B12 supplementation followed by Iri 180 mg/m 2 (90min) on the same day were given q2w for 12 cycles. Results: 44/46 patients (95%) received at least one cycle of the combination with median age: 63 yrs, baseline ECOG performance status = 2: 100%. Metastatic sites were: liver: 70%, lung: 41%, lymph node: 7% and peritoneum: 5%. The median number of administered cycles was 4.5. Seven out of 44 patients (16%) received at least 12 cycles of study therapy. The objective response rate (intent-to-treat, RECIST criteria, assessed by investigators) was 14% (95% CI [5.2; 27.4]), 41% had stable disease. Grade 3/4 toxicities were: neutropenia: 19%, anemia: 9%, elevated AST/ALT 10%, diarrhea: 16%, vomiting: 7%, nausea: 5% and fatigue: 20% which was the most limiting toxicity for this combination. Conclusion: The combination of Pem + Iri is active in second line MCRC. However, response rate seems to be in the same range as compared to historical data for FOLFIRI. Patients are still in the follow-up period. Data of PFS and OS will be presented at the meeting. No significant financial relationships to disclose.
Phase II trial of radiotherapy (RT) with concurrent cisplatin (C) plus panitumumab (pmAb) for patients (pts) with high-risk, resected head and neck cancer (HNC).
Authors: Robert L. Ferris, Nicole Cherie Schmitt, Dwight Earl Heron, Jonas Talmadge Johnson, Seungwon Kim, Umamaheswar Duvvuri, David Andrew Clump, Jennifer Grandis, Julie E. Bauman, William E. Gooding, Athanassios Argiris
Journal: Journal of Clinical Oncology (2014)

6090 Background: Treatment intensification for human papillomavirus (HPV)-negative HNC is an active area of investigation. Targeting the epidermal growth-factor receptor pathway using the monoclonal antibody pmAb with C chemoradiation was investigated in high-risk resected, primarily HPV- HNC patients. Methods: Eligible were pts with ECOG performance status 0-1 with pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, or hypopharynx, without gross residual tumor and with high-risk factors (margins <1mm, extracapsular spread (ECS), perineural/angiolymphatic invasion, or 2 or more positive lymph nodes). Postoperative treatment started within 7 weeks of surgery, consisting of standard RT (60-66 Gy, once daily fractions in 6-7 weeks) concurrent with weekly pmAb 2.5 mg/kg IV and weekly C 30 mg/m2IV. Carboplatin (AUC 1.5 weekly) substitution was allowed for certain C-associated toxicities. The primary endpoint was progression-free survival (PFS). Results: Of 46 pts accrued, 2 did not receive pmAb, leaving 44 for analysis. Median age was 58 (range 23-81); 16% were female. Primary sites included: oral cavity (73%), larynx (20%), hypopharynx (5%), oropharynx (2%); 86% were stage IVA. Indications for adjuvant therapy included ECS (n=23), perineural invasion (n=22), and/or positive margins (n=3). The median follow-up for 32 pts without recurrence was 27 months (range 3-67). The 2-year PFS was 73% (95% CI, 61-88%) and the 2-year overall survival (OS) was 76% (95 % CI, 64-91%). 12 pts developed recurrence; 8 of them died. An additional 5 pts died from other causes. Grade 3/4 toxicities included mucositis (41%), hyponatremia (25%), leukopenia (25%), dysphagia (18%), neutropenia (21%), nausea/vomiting (14%), anorexia (11%), rash (9%), and neutropenic fever (9%). Prophylactic gastrostomy tubes were placed in 43% of patients; 18% required tube placement during or after therapy. Conclusions: Preliminary analysis of adjuvant treatment intensification by adding pmAb to C chemoradiation suggests promising clinical outcome for high-risk, predominantly HPV- HNC pts. Clinical trial information: NCT00798655.
Hydration Sensing: A Wearable Hydration Sensor with Conformal Nanowire Electrodes (Adv. Healthcare Mater. 6/2017)
Authors: Shanshan Yao, Amanda Myers, Abhishek Malhotra, Feiyan Lin, Alper Bozkurt, John F. Muth, Yong Zhu
Journal: Advanced Healthcare Materials (2017)

A wearable skin hydration sensor is developed by Y. Zhu, J. F. Muth, and co-workers in article number 1601159. The sensor is made of silver nanowires inlaid in a silicone substrate, which renders the sensor flexible and stretchable. Integrated systems with multimodal sensing capability (e.g., hydration, strain/motion and electrophysiological sensing) are demonstrated in two form factors — wristband and chest patch. Image design by Shanshan Yao.
End-of-life experience of patients with rare cancers and their caregivers.
Authors: Elizabeth Trice Loggers, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2013)

9540 Background: Cancers are defined as rare if fewer than 35,000 cases are diagnosed per year. Rare cancers represented 23% of incident cancer cases and 33% of cancer deaths in 2008. However, little is known about the end-of-life (EOL) experience of patients with rare cancers or their caregivers. Methods: From September 2002 to August 2008, 618 advanced cancer patients (195 with rare and 423 with common stage IV cancers following failure of first line chemotherapy) and their caregivers participated in a U.S. multi-site, prospective, interview-based cohort study (Coping with Cancer). Patients were interviewed about EOL preferences, planning, and care at study entry. Interviews with caregivers at baseline assessed caregiver mental and physical health, while post-mortem surveys assessed EOL patient care. Descriptive statistics (t-test, chi-square) were used to characterize the study sample; logistic regression tested the association between cancer type and care received, controlling for confounders. Results: Rare cancer participants were more likely to be younger (57.7 vs 60.7 years, p=.01), Hispanic (19% vs 9%, p=.002) and have fewer co-morbidities (Charlson comorbidity index, mean 5.9 vs 6.5, p=.004), than their common-cancer counterparts. Rare cancers patients were four times more likely to be receiving both radiation and chemotherapy at study entry than common cancer patients (10.3% versus 3.3%, OR 4.31, p=0.003), but equally as likely to acknowledge their illness was terminal, have EOL discussions, and participate in advance care planning as common cancer patients. Caregivers of patients with rare cancers were more likely than common cancer caregivers to report declining health during the prior year of care-giving (22.1% versus 15.7%, p=0.05) and marginally more likely to prefer the patient choose treatment focusing on extending life rather than pain relief (22.3% vs 16.5%, p=0.08). Conclusions: Patients with advanced-stage, rare cancers may be treated more aggressively following failure of first line chemotherapy than individuals with common cancers. Future research should investigate patterns and quality of care for terminally ill patients with rare cancers and caregiver burden.
A phase I study of indoximod in combination with docetaxel in metastatic solid tumors.
Authors: Erica Jackson, Elizabeth Claire Dees, John S. Kauh, R Donald Harvey, Anthony Neuger, Richard Lush, Scott J. Antonia, Susan E. Minton, Roohi Ismail-Khan, Hyo S. Han, Nicholas N. Vahanian, William Jay Ramsey, Charles J. Link, Howard Streicher, Daniel Sullivan, Hatem Hussein Soliman
Journal: Journal of Clinical Oncology (2013)

3026 Background: The indoleamine-2, 3-dioxygenase (IDO) pathway catabolizes tryptophan to create a state of immunosuppression. Indoximod (1-methyl-(D)-tryptophan, D-1MT) is an IDO pathway modulator. Preclinical studies in MMTV-neu mouse models have shown indoximod combined with chemotherapy was more effective in causing tumor regression than either agent alone. Based on this data, a phase IB trial was designed to study the safety of the combination of docetaxel (Doc) and indoximod. The primary goal of this trial was to determine the MTD for the combination of Doc and oral indoximod. Secondary endpoints were PK data and efficacy for indoximod/Doc. Methods: This phase IB study consisted of 5 dose levels (DL). Doc was dosed IV q 3 wks at 60 mg/m 2 in DL 1-4 and 75 mg/m 2 at DL 5. Indoximod was dosed at 300, 600, 1,000, 2,000, and 1,200 mg PO BID continuously in DL 1-5 respectively. MTD was determined using a 3+3 design. The DLT rule was 1 st cycle ≥G3 non-heme AEs or ≥G4 heme AEs despite supportive care or that delay therapy &gt;14d. The PK of indoximod and Doc was analyzed using a HPLC assay. PK was measured on C1D1 and 8. Standard eligibility/exclusion criteria applied along with exclusion of patients previously treated with ipilumimab. Treatment was continued until disease progression, intolerance, or unacceptable side effects. Results: Total # of patients treated at DL1-5 were 7, 6, 6, 2, and 6 respectively, with 22 total patients evaluable for response. DLTs included: G3 dehydration (at 300 mg), G5 neutropenic colitis (at 600 mg), G3 hypotension (at 2,000 mg) and G3 mucositis (at 2,000 mg). DL 5 was well tolerated and is the recommended phase II dose. The most frequent adverse events were fatigue (58.6%), anemia (51.7%), hyperglycemia (48.3%), infection (44.8%), and nausea (41.4%). There were 4 PRs (2 breast, 1 NSCLC, 1 thymic), 9 SD, and 9 PD. There were no drug-drug interactions, and PK was similar to Doc and indoximod single-agent studies. Conclusions: The Doc+ indoximod combination was well tolerated with no increase in expected toxicities or unexpected PK interactions. It was active in a pretreated population of patients with metastatic solid tumors. The RP2D is 75 mg/m 2 of Doc with 1,200 mg of indoximod BID for the current phase II metastatic breast cancer trial. NCT01191216 Clinical trial information: NCT01191216.