tbuckley/cabot-search huggingface dataset:
Incidence and benefits of surgical therapy for third primary lung cancers.
Authors: Dong-Seok Daniel Lee, Emanuela Taioli, Andrew Kaufman, Andrea S Wolf, Faiz Y. Bhora, Suresh Ramanathan, Raja Michael Flores
Journal: Journal of Clinical Oncology (2015)

e18512 Background: Continued surveillance of lung cancer patients after curative surgery allows for the diagnosis of new disease. However, there is a relative paucity of data in regards to the development of third primary lung cancers. The goals of this study were to examine the incidence of third primary cancers and the results of surgical therapy. Methods: Surgically resected Stage 1 second primary lung cancers with complete data were identified in The Survival Epidemiology and End Results (SEER) database between 2004 and 2010. Among these 238 cases, those which developed a third primary lung cancer 6 or more months after the diagnosis of the second primary were analyzed. Statistical methods were performed using Kaplan-Meier and multivariate analysis. A p value < 0.05 was considered statistically considered significant. Results: Twenty-four patients (10.1%) experienced a third primary lung cancer; sixteen cases (66.7%) were diagnosed in stage I. Twelve patients (50% of cases) underwent cancer surgery. Nine patients (37.5%) were treated with beam radiation – alone (8 cases, 89%) or in combination with surgery (1 case, 11%). Surgery was performed more frequently in early stages (75% of surgical cases were stage I versus 58% of non-surgical cases). There was no difference in age between patients who underwent any treatment and those who did not. Length of follow-up in third primary cancers was 18 months if surgically treated and 8 months if not surgically treated (p < 0.02). At multivariate analysis, the only independent predictor of improved survival was treatment (Hazard ratio (HR) 0.21, 95% CI: 0.07-0.66; p=0.007). Both surgery (HR=0.02; 95% CI: 0.002-0.29) and radiation (HR= 0.04; 95% CI: 0.002-0.54) significantly improved survival. Conclusions: The overall incidence of third primary lung cancers after a second primary is 10.1%. Surveillance and intervention at early stage results in improved survival. Treatment Total Overall Dead Percent No Surgery 12 5 42 Surgery 11 3 27
Prognostic significance of autophagy-related proteins expression in resected pancreatic cancer.
Authors: Hye Sung Won, Yoon-Ho Ko, Young-Seok Cho, Eun Kyoung Jeon, Myung Ah Lee
Journal: Journal of Clinical Oncology (2012)

e14634 Background: Autophagy is a critical intracellular pathway for removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins on clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: The expression of five autophagy-related proteins in the PDCA tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results: Of the 73 patients, autophagy-related proteins expression frequencies were 49.3% (36/73) for ATG5, 63.9% (46/72) for Ambra 1, 47.9% (35/73) for Beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was statistically significant in all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (p = 0.059). Multivariate analysis revealed that Beclin 1 overexpression or increases in alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio 5.365, p=0.001 and hazard ratio 5.270, p=0.022, respectively). Conclusions: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDCA. The awareness and inhibition of autophagy offer a potential therapeutic target for PDCA.
Assessment of early tumor response to induction chemotherapy (IC) in locally advanced squamous-cell carcinoma of head and neck (LASCCHN) with 18FDG PET-CT: A prospective trial.
Authors: Ulisses Ribaldo Nicolau, Eduardo Nobrega Pereira Lima, Marclesson S. Alves, Thiago Bueno Oliveira, Victor Hugo Fonseca Jesus, Tadeu Ferreira Paiva, Loureno Cezana, Virgilio Sousa Silva, Paula Nicole Pinto, Gislaine Machado Porto, Antonio Cassio Assis Pellizzon, Genival Barbosa Carvalho, Luiz Paulo Kowalski
Journal: Journal of Clinical Oncology (2013)

6017 Background: Response to IC with triplet regimens adding taxanes to cisplatin and 5-fluorouracil (TPF), followed by chemoradiotherapy (CRT) for LASCCHN, is usually evaluated after 2 cycles of IC, based on bidimensional WHO or modified WHO criteria. Concerns regarding toxicity profile of TPF suggest a potential benefit of an early response evaluation approach that could select patients who would be spared from a toxic regimen and promptly started on an alternative treatment. The aim of this study is to assess the ability of evaluating early response after the first IC cycle based on a 40% decrease in standard-uptake value (SUV) measured by 18 FDG PET-CT on the 14 th day. Methods: Patients with LASCCHN who underwent IC with TPF were prospectively evaluated. Staging procedure included locoregional and chest imaging, endoscopic examination and FDG PET-CT. At day 14 of first cycle, a second FDG PET-CT was performed and treating physicians were blinded for these findings. All cases were conducted according to the usual post-cycle 2 WHO or modified WHO criteria evaluation. Written informed consent was obtained from all recruited patients. Results: Between February 2010 and October 2012, 40 stage III/IV LASCCHN patients (34 oropharyngeal, 3 hypopharyngeal and 3 laryngeal) were recruited. With a median follow up of 11.4 months the actuarial 2 years overall (OS) and disease free survival (DFS) of all patients were 81.4% and 69.2%, respectively. Responders (any decrease of SUV) at day 14 PET CT had a better OS (90 vs. 27% - p&lt;0,001) and DFS (76 vs. 0% - p&lt;0,001) as compared to non-responders. Decrease of at least 40% in the SUV of primary tumor predicted a better DFS (100 vs. 51% - p=0,007). Conclusions: These results suggest a potential role of early response evaluation with 18 FDG PET-CT in patients with LASCCHN undergoing IC. A SUV decrease of at least 40% predicts better DFS. An increase in the SUV predicts a poor prognosis.
Survival following Y90 radioembolization for neuroendocrine tumor liver metastases: A retrospective, single-center analysis.
Authors: Jason Gruener, F. Scott Nowakowski, Reza Fardanesh, Vinit Amin, Edward Kim, Aaron M. Fischman, Rahul S. Patel, Robert Lookstein, Richard R. P. Warner
Journal: Journal of Clinical Oncology (2014)

e15166 Background: Y90 radioembolization has become an increasingly common palliative measure for patients with unresectable metastatic neuroendocrine tumors (NETs) in the liver. The amount by which the procedure extends survival and the prognostic variables impacting survival following the procedure remain uncertain, as most previous studies have investigated relatively smaller numbers of NET patients. Methods: This retrospective study included all patients with metastatic hepatic NETs who underwent their initial Y90 radioembolization at a single institution between 2004 and 2012 and did not have previous or subsequent chemoembolization (n=111). 24 of the 111 patients received <80% of the intended Y90 dose due to flow stasis. There were 76 carcinoid tumors, 25 pancreatic NETs (pNETs), and 10 unclassified NETs. Complete pathology records were available for 94 patients—43 grade I, 40 grade II, and 11 grade III (WHO criteria 2010). The Kaplan-Meier method was utilized to track overall survival from the time of the initial procedure. To examine the impact of potential predictive variables, the univariate log-rank and multivariate Wald tests were used. Results: The aggregate median survival was 45 months from the date of the procedure. Survival varied by tumor type (log-rank p=.0279, Wald p=.0554)—median was 56 mo. in the carcinoid group versus 31 mo. in the pNET group and 28 mo. in the unclassified NET group. Survival also varied by pathological grade (log-rank p<.0001, Wald p<.0001)—the grade I, grade II, and grade III NET groups had median survivals of 71 mo., 56 mo., and 13 mo. respectively. The median survival in patients that received <80% of the intended Y90 dose was 56 mo. versus 39 mo. in those who received ≥80% (log-rank p=.0606, Wald p=.0045). Conclusions: Achieving a median post-procedure survival duration of 45 months, Y90 radioembolization is an effective treatment option for patients with hepatic NET metastases. Patients with carcinoid tumors and other low-grade tumors have the best prognosis. In this study, patients who received <80% of the intended dose paradoxically had better survival outcomes than those receiving ≥80% of the intended dose.
Physical activity intervention for patients with advanced pancreatic cancer.
Authors: Crystal Shereen Denlinger, Michael J. Hall, Steven J. Cohen, Igor A. Astsaturov, Efrat Dotan, Paul F. Engstrom, Brian L. Egleston, Carolyn Y Fang
Journal: Journal of Clinical Oncology (2017)

217 Background: Physical activity (PA) interventions – including low-intensity, home-based walking programs – can lead to improvements in quality of life (QOL) and symptoms among patients with cancer. Despite the evident benefits, no PA interventions have been evaluated in patients with pancreatic cancer, perhaps due to concerns that these patients are too ill to participate. We assessed the feasibility and safety of implementing a PA intervention among patients with advanced pancreatic cancer. Methods: Patients with unresectable locally advanced or metastatic disease were randomized to a 12-week walking program (intervention; n = 19) or usual care (UC; n = 18). All patients met with a health educator to complete baseline assessments of QOL, symptoms, and physical functioning. Intervention participants were also instructed on how to complete the walking program and received a program booklet, a walking log, and a pedometer. Both intervention and UC patients were contacted every 4 weeks by phone to assess symptoms and changes in medical status. At 12-weeks post-baseline (intervention end), all patients completed assessments again. Results: 70 patients were approached; 37 enrolled on study (53% acceptance rate). Patients’ mean age was 63.5 years; 49% were male. There were no differences in overall QOL, symptoms, or functioning between groups at baseline. 25 of 37 patients completed the study (68%); 11 in the Intervention group and 14 in UC. Primary reason for study drop-out was declining health. Compared to UC, the intervention group reported a significant increase in average duration of physical activity from baseline (11 min/day) to follow-up (35 min/day) (p &lt; 0.05), and improvement in symptoms as assessed by the FACT-Hep (p = 0.06). Importantly, no adverse events were reported among study participants. Conclusions: Despite advanced disease, patients with pancreatic cancer are willing and interested in participating in a PA intervention. Preliminary results suggest that intervention participants increased their PA and reported symptom improvement. Recruitment is ongoing, and clinical outcomes will be explored. In sum, this pilot study suggests that a home-based walking program is feasible and safe among patients with advanced pancreatic cancer. Clinical trial information: NCT02442323.
Gene expression profile of primary cutaneous melanomas to distinguish between low and high risk of metastasis.
Authors: David H. Lawson, Maria Russell, Jeffrey Wilkinson, Rodabe Navroze Amaria, Rene Gonzalez, Pedram Gerami, Stephen Lyle, Gilchrist L. Jackson, Anthony Greisinger, Clare Johnson, Kristen M. Oelschlager, John F Stone, Derek Maetzold, Robert W. Cook, Keith A. Delman
Journal: Journal of Clinical Oncology (2013)

9022 Background: Wide variability exists in metastatic rates of primary cutaneous melanoma (CM), even within TNM stage groupings. We developed an RT-PCR based gene expression profile (GEP) test to predict distant metastases in early stage CM. Methods: RNA was isolated from formalin-fixed, paraffin embedded biopsies or wide excisions of primary CM from patients with stage 1-4 CM (87% stage 1-2) converted to cDNA and analyzed using RT-PCR. All analyses were done using JMP Genomics and WinSTAT. Radial Basis Machine (RBM) modeling was used to predict metastasis-free survival (MFS) for the training set of 149 samples. Independent validation was performed on an additional 107 CM samples. RBM reports a binary Class 1 (low risk) and Class 2 (high risk). Results: Analysis of the training set resulted in a model with 85% receiver operating characteristic (ROC) and sensitivity of 82%. Prediction of metastatic risk for the validation set resulted in a 90% ROC and sensitivity of 89%. 30 of 33 stage 1-3 cases with a known metastatic event were accurately called Class 2. Kaplan-Meier analysis showed 5-year MFS rates of 88% and 25% for predicted Class 1 and Class 2, respectively, in the training set (p&lt;0.0001, overall MFS=60%). Similarly, MFS was 95% and 26% for Class 1 and Class 2, respectively, in the independent validation set (p&lt;0.0001, overall MFS=67%). Univariate Cox regression analysis of the validation set revealed that GEP, AJCC stage, Breslow thickness, and ulceration were each predictors of metastatic risk (HR=27.2, 11.4, 3.0, and 11.6, respectively, p&lt;0.002 for each). Multivariate analysis showed GEP and AJCC stage were independent predictors of risk (HR=8.4 and 6.4 respectively, p&lt;0.007 for both). Conclusions: This GEP signature provides an accurate stratification of metastatic risk in the training and validation samples independent of all other histologic factors. This test may serve as a prognostic tool for outcomes in patients with melanoma and for stratifying patients for clinical trials.
First results of a phase 2 study using a 10-day subcutaneous (SC) regimen of the novel hypomethylating agent (HMA) SGI-110 for the treatment of relapsed/refractory acute myeloid leukemia (r/r AML).
Authors: Elizabeth A. Griffiths, Hagop M. Kantarjian, Gail J. Roboz, Patricia Lamont Kropf, Casey Lee O'Connell, Karen W. L. Yee, Guillermo Garcia-Manero, Elias Jabbour, Eric Jay Feldman, Katherine Jean Walsh, David Rizzieri, Wendy Stock, Scott D. Lunin, Sue Naim, Gavin S. Choy, Pietro Taverna, Yong Hao, Mohammad Azab, Woonbok Chung, Jean-Pierre J. Issa
Journal: Journal of Clinical Oncology (2014)

7030 Background: SGI-110 is a novel HMA administered as a small volume injection which results in extended decitabine exposure. We previously reported an Overall Complete Remission (OCR=CR+CRi+CRp) rate of 16% in 50 patients with r/r AML using SGI-110 daily x 5 regimen with either 60 or 90 mg/m2/d (Kantarjian et al, 2013). We report here the first results of the daily x 10 Q 28 days regimen using 60 mg/m2/d. Methods: Patients with AML who relapsed or progressed following prior treatment were enrolled. There was no limit on the number of prior treatment regimens, total WBC, or blast %. The primary endpoint was OCR using modified IWG 2003 criteria. Secondary efficacy endpoints included duration of response, and Overall Survival. Safety was assessed using the CTCAE Version 4. After 2-4 cycles, investigators were allowed to consolidate with daily x 5 at 60 mg/m2/d regimen until progression. Results: The study completed enrolment with 53 patients treated. Patients had a median age of 57 years (range 29-82), 51% were male, 83% had ECOG PS of 0-1, and 17% had ECOG PS 2. Median number of prior regimens was 2 (range 1-7); 13% of patients had prior HMA treatment. The primary efficacy endpoint of OCR was reported in 16 patients (7 CR, 6 CRi, and 3 CRp) or an OCR rate of 30% (95% CI: 18.3%, 44.3%). Seven patients are still on treatment. 30-day and 60-day mortality were 1.9% and 11.3% respectively. Of 162 total number of cycles given at the data cutoff, 149 (92%) were given using the 10-day regimen and 13 (8%) were given using the daily x 5 consolidation. The most common drug-related Grade ≥3 AEs were: anaemia and thrombocytopenia (19% each), neutropenia and febrile neutropenia (5.7% each). Conclusions: SGI-110 given as a daily x 10 SC regimen at a dose of 60 mg/m2/d was clinically active in heavily pretreated population of r/r AML with an acceptable safety profile. The results appear to compare favorably with our previously reported complete remission response rate in a similar patient population using the daily x 5 regimen at doses of 60 or 90 mg/m2/d. These results warrant further investigation of this regimen for the treatment of r/r AML. Clinical trial information: NCT01261312.
ABEL trial: A phase II randomized trial adding bemiparin (B) to chemo-radiotherapy (CT-RT) in limited-stage small cell lung cancer (SCLC)—Final results.
Authors: Bartomeu Massuti, Ramon Lecumberri, Guillermo M Lopez Vivanco, Albert Font, Enrique Gonzalez-Billalabeitia, Juan Luis Marti-Ciriquian, Jose Gómez-Codina, Manuel Domine, Isabel Bover, Dolores Isla, Antonio Galan, Alfonso Gurpide, Vicente Vicente, Rafael Rosell, Mayte Monreal, Eduardo Rocha
Journal: Journal of Clinical Oncology (2012)

7095 Background: Low molecular weight heparins (LMWH) could improve therapeutic outcomes in patients with advanced cancer. Heparin binding growth associated molecule is a member of growth factors involved in proliferation, angiogenesis and metastases in SCLC. LMWH associated with CT increase survival in cancer patients (Cochrane DB Systematic Reviews 2011). LMWH do not increase hemorrhagic events when used in neoplastic patients. Methods: Open randomized phase II multicentric trial to assess efficacy and safety of adding bemiparin to standard CT-RT in patients with SCLC with limited disease. CT: Cis/carboplatin + etoposide x 4-6 cycles. Concurrent early thoracic RT (45-50 Gy) and prophylactic cranial irradiation in case of response. Patients (p) were randomly allocated to addition of B at daily subcutaneous dose of 3.500 UI during 26 weeks. Primary end-point: progression free survival (PFS). Secondary end-points: response (RECIST), safety profile (CTC), venours thromboembolic (VTE) and hemorrhagic events incidence and overall survival (OS). Sample size 130 p. Preplanned interim analysis after inclusion 30 p. Results: From October-05 to January/10 39 p were included. Study was closed after interim analysis due to poor recruitment. 38 evaluable p. ITT analysis: 20 CR-RT + B vs 18 CT-RT. No significant disbalance in patient characteristics and prognostic factors. Median PFS 58.6 weeks (CT-RT+B) vs 38.8 w (CT-RT) (HR 2.576; Log-rank p=0,018). RR: 65% (CT-RT+B) vs 55% (CT-RT) (NS); Median OS 161.8 w (CT-RT+B) vs 49.3 w (CT-RT) (HR 2.96; Log-rank p=0,012). 2-year survival rate: 68.6% (CT-RT+B) vs 29.4% (CT-RT) (p=0,0042). Safety: G3-4 AE: 50% vs 67%; bleeding events: 10% vs 27% (NS); thrombocytopenia 15% vs 50% (p=0.024); VTE: 0 vs 22% (p=0.041). Conclusions: Addition of B (3.500 u/daily s.c. during 26 w) to CT-RT in SCLC with LD significantly increases PFS and OS. B does not increase hemorragic events and significantly reduces VTE. In spite of early closure of the trial due to poor accrual, these results warrants further research in this approach trying to improve current outcomes of SCLC. ClinicalTrials.gov Id: NCT00324558.
Responses to romidepsin in patients with cutaneous T-cell lymphoma (CTCL) with tumors and/or folliculotropic involvement.
Authors: Francine M. Foss, Madeleine Duvic, Adam Lerner, Alain Rook, Sean Whittaker, Ellen J. Kim, Youn H. Kim
Journal: Journal of Clinical Oncology (2014)

8575 Background: CTCL is a heterogeneous group of non-Hodgkin lymphomas that arises in the skin (patches, plaques, tumors, and/or erythroderma) but can involve the lymph, blood, and/or viscera. Additionally, patients with cutaneous tumors or folliculotropic involvement typically have poor prognoses. Romidepsin is a histone deacetylase inhibitor approved by the US FDA for the treatment of patients with CTCL who have received ≥ 1 prior systemic therapy. Durable responses (objective response rate [ORR; complete [CR] + partial responses] of 34% and median duration of response of 15 mo) and tolerability with extended dosing have been reported. To examine responses to romidepsin in these less favorable prognostic subsets, patients with tumors or folliculotropic involvement in the pivotal study of romidepsin for the treatment of CTCL were analyzed. Methods: Patients with CTCL (N = 96) who had ≥ 1 prior systemic therapy received romidepsin 14 mg/m2on days 1, 8, and 15 every 28 days. Responses were determined by a rigorous composite endpoint that included changes in the skin, blood, and lymph. Patients with cutaneous tumors or folliculotropic involvement were identified by reviewing diagnosis and histology reports. Results: Of 96 patients with CTCL, 20 had tumors, and 10 had folliculotropic involvement (2 had both). All but 2 patients with tumors and 1 with folliculotropic involvement achieved ≥ stable disease (SD) with romidepsin (Table). Time to response and DOR ranged from 0.9-4.7 mo and 1.4-18.7+ mo, respectively, for patients with tumors and 1.0-8.3 mo and 2.1-5.0+ mo for patients with folliculotropic involvement. Discontinuation due to an adverse event occurred in 1 patient with tumors (fatigue) and 0 with folliculotropic involvement. Conclusions: In the pivotal study of romidepsin for the treatment of CTCL, patients with cutaneous tumors or folliculotropic involvement commonly responded to therapy. Additionally, despite rapid onset of response, patients with tumors rarely discontinued romidepsin due to adverse events, with the longest duration of response ongoing at 18.7 mo. Clinical trial information: NCT00106431. Best response, n (%) Tumors (n = 20) Folliculotropic involvement (n = 10) ORR 9 (45) 6 (60) CR 2 (10) 1 (10) SD 9 (45) 3 (30)
A Prognostic Scoring Model for the Utility of Induction Chemotherapy Prior to Neoadjuvant Chemoradiotherapy in Esophageal Cancer
Authors: Mian Xi, Zhongxing Liao, Weiye Deng, Cai Xu, Ritsuko Komaki, Mariela Blum, Wayne L. Hofstetter, Linus Ho, Steven H. Lin
Journal: Journal of Thoracic Oncology (2017)