tbuckley/cabot-search huggingface dataset:
A phase II study of splited 5-fluorouracil and cisplatin (split FP) against advanced or metastatic hepatocellular carcinoma (HCC): Preliminary results
Authors: J. Jung, S. Park, J. Kwon, J. Kim, H. Kim, H. Song, H. Kim, D. Zang
Journal: Journal of Clinical Oncology (2008)

15636 Backgrounds: Most of the patients with hepatocellular carcinoma (HCC) are diagnosed at or progressed after local treatment to the status of an advanced stage for which effective local treatment is not available. We performed a phase II study of splited 5-fluorouracil (5-FU) and cisplatin (split FP) to evaluate the efficacy and safety in metastatic or advanced HCC. Methods: The patients with advanced or metastatic HCC, who were unavailable to local treatments, were enrolled. Eligible patients were proven by histology or diagnosed by radiologically (dynamic CT) or serologically (α-FP > 400) in high risk group. The previous local treatments and post-split FP salvage chemotherapy were allowed. The therapy consisted of intravenous administration of 750 mg/m2 5-FU over 12 hours on Days 1–4 and intravenous administration of 20 mg/m2 cisplatin on Days 1–4. The treatment was repeated every 4 weeks for a maximum of 6 courses with dose adjustments based on the observed toxic effects if there was no evidence of tumor progression or unacceptable toxicity. The primary endpoint was response rate. Results: The median follow-up duration was 9.03 (range 1.87–32.23) months. Of Seventeen enrolled patients (male/female 15/2, median age 56 (range 39–71), median ECOG PS 0 and median Child-Pugh score 5 and Class A), three (17.6%) (95% CI: 11.3–27.5%) patients achieved partial responses and four (23.5%) (95% CI: 16.4–39.5%) patients achieved stable diseases. The median time to progression was 14.3 months (range 1.3–14.3 months). Ten patients (58.8%) were remained as the status of progressive disease. The median survival time and 1-year survival rate were 13.7 months and 51.9%, respectively. The main grade 3 and 4 toxicities were neutropenia (8, 47.1%), leucopenia (6, 35.3%), anemia (2, 11.8%), thrombocytopenia (2, 11.8%). These were generally brief and reversible, with the exception of one death due to acute variceal bleeding. The febrile neutropenia was not observed. Conclusions: These preliminary results suggest that split FP regimen is active and relatively well tolerated in patients with advanced HCC. No significant financial relationships to disclose.
Number of lymph nodes recovered as an independent prognostic factor in predicting outcome in patients with pathologically node-negative rectal cancer following preoperative chemo/radiotherapy.
Authors: Sree Lakshmi Rodda, Amandeep Singh Dhadda, Peter D. Dickinson, Abed M Zaitoun, Eric M Bessell
Journal: Journal of Clinical Oncology (2012)

606 Background: To determine the importance of number of lymph nodes recovered on outcome in pathological node negative rectal cancer patients who had received chemo/radiotherapy prior to surgery. Methods: We retrospectively analysed data from 262 patients with locally advanced rectal cancer who received pre-operative chemo/radiotherapy at Castle Hill Hospital, Cottingham and Nottingham University Hospital between 2001 and 2008. Patients were treated with CT planned radiotherapy to a dose of 45-50 Gy in 25 fractions with concurrent fluoropyrimidine chemotherapy. Surgery was normally performed at an interval of 6-8 weeks. There were 152 patients who were found to be pathologically node negative for further analysis. Median follow-up was 51.5 months Patients were grouped into &lt; 10 nodes recovered or &gt; 10 nodes recovered. Disease free survival (DFS) and overall survival (OS) was assessed using Log rank test. Multivariate analysis was performed using Cox-regression analysis. Results: Of the 152 patients analysed, 67.1 % (n=102 ) had fewer than 10 nodes recovered and 32.8% (n=50) had greater than 10 nodes recovered. The median number of nodes recovered was 7 (range 0-39). There was a improvement in 5 year DFS and OS in group who had more than 10 nodes recovered compared to group with less than 10 nodes recovered ( DFS at 5yrs :86.5% vs. 61.5%, p=0.01, OS at 5 yrs : 77.8% vs. 67.4% , P =0.059). On multivariate analysis pathological T-stage , circumferential resection margin (CRM) status and number of lymph nodes recovered were found to be independent predictors of disease free survival (p=0.002). Conclusions: The number of lymph nodes retrieved following surgery for locally advanced rectal cancer patients following chemo/radiotherapy is an independent prognostic factor in pathologically node negative patients. This may need to be considered when making subsequent adjuvant chemotherapy decisions.
SBRT for early NSCLC: Markov model insight for optimal patient selection.
Authors: A. V. Louie, G. Rodrigues, M. Hannouf, D. Palma, G. Zaric, S. Senan
Journal: Journal of Clinical Oncology (2011)

6057 Background: We developed a Markov model to simulate outcomes in different sub-groups of patients with stage I NSCLC to help define the role of SBRT in this disease. Methods: We modeled the 5 year clinical history of (i) operable stage I NSCLC patients treated with either SBRT or lobectomy, and (ii) patients aged ≥75 years with COPD who undergo SBRT or best supportive care (BSC). Parameters for recurrence rates and Markov state utilities for appropriate AJCC stages of NSCLC were extracted from the literature and adapted to monthly time intervals. For operable patients, age- and sex-specific rates of death from all other causes were extracted from standard life tables and varied according to smoking habit. Surgical outcomes from the model were compared to Adjuvant! Online (AO). Elderly COPD patients were stratified into 4 classes according to T stage and COPD GOLD score. We report various treatment strategy overall and quality adjusted survival stratified by age, sex, smoking history, COPD, and T-stage. Sensitivity analyses on Markov utilities, treatment-related death, and the proportion of patients with recurrent disease treated radically were performed to determine thresholds for treatment modality preference. Results: For surgical patients, the 5-year overall survival, cancer specific survival, and other causes of death as predicted by our model correlated closely with AO, ranging from 0.0% to 3.8%. Differences between surgery and SBRT ranged from 2.2% to 3.0% in 5-year overall survival and 0.07 to 0.09 in quality adjusted life years, both in favor of surgery. The SBRT utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to the SBRT utility, the proportion of recurrences treated radically, and the surgical and SBRT treatment related mortalities. For high risk patients, our model predicted for a benefit in 5-year overall survival of 4.0% to 38.2% and 8.8 to 17.4 quality-adjusted life months in favor of SBRT over BSC for the 4 classes. Outcomes were not sensitive to the SBRT utility or disease progression. Conclusions: Withholding SBRT based on age and/or COPD severity may be unjustified. SBRT may offer comparable overall survival and quality adjusted life expectancy compared to surgical resection in operable cases.
Cytoreductive radical prostatectomy in patients with prostate cancer and low-volume skeletal metastases: Results of a feasibility and case-control study.
Authors: Axel Heidenreich, Daniel Porres, T Kuru, David J. K. P. Pfister
Journal: Journal of Clinical Oncology (2015)

176 Background: Androgen deprivation (ADT) represents the standard treatment for PCA with osseous metastases. We explored the role of cytoreductive radical prostatectomy in PCA with low volume skeletal metastases in terms of a feasibility study. Methods: 32 patients with biopsy proven PCA, minimal osseous metastases (≤ 3 hot spots on bone scan), absence of visceral or extensive lymph node metastases and PSA decrease to &lt; 1.0 ng/ml after neoadjuvant ADT were included in the feasibility study. 38 men with metastatic PCA who were treated by ADT without local therapy served as control group (group B). Surgery-related complications, biochemical progression-free, symptomatic-free, cancer-specific and overall survival were analyzed using descriptive statistical analysis. Results: Mean age was 61 (42-69) and 64 (47-83) years in group A and B, respectively, with similar patient characteristics in terms of initial PSA, biopsy Gleason score, clinical stage, extent of metastatic disease. The mean follow-up was 40.6 (3-71) and 44 (24-96) months in group A and B, respectively. Pathohistology revealed vital PCA with metastatic potential in all 32 patients despite neoadjuvant ADT. 12% of pts in group A developed Clavien grade III complications. According to the ICSmaleSF questionnaire 30/32 (93.7%) pts were continent. Patients in group A experienced significantly better bPFS (36.8 versus 23.1 months, p=0.042), clinical PFS (38.6 versus 26.5 months, p=0.032) and cancer specific survival rate (95.6% versus 84.2%, p=0.043) whereas the overall survival was similar. 0% and 29% of men in group A and B, respectively, underwent palliative surgical procedures for locally progressing PCA. Conclusions: CRP is feasible with good functional and oncological results in well selected men with metastatic PCA who respond well to neoadjuvant ADT. These men have a long life expectancy and CRP reduces the risk of locally recurrent PCA and local complications. CRP might be a treatment option in the multimodality management of PCA with minimal osseous metastases.
Haploinsufficiency and Deletions of G3BP1 on Chromosome 5q Result in Induction of TP53
Authors: Naoko Hosono, Mahfouz Reda, Bartlomiej P Przychodzen, Chantana Polprasert, Latifa Zekri, Michael J. Clemente, Jamal Tazi, Yogen Saunthararajah, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Hideki Makishima
Journal: Blood (2014)
The clinical characteristics and potential prognostic factors of patients with liver metastasis from breast cancer
Authors: J. Wang, B. Xu
Journal: Journal of Clinical Oncology (2008)

12030 Background: To analyze the clinical characteristics, efficiacy of treatment and potential prognostic factors of patients with liver metastasis from breast cancer(BCLM). Methods: Retrospective analysis of clinical characteristics, response to treatment and survival were statistically carried out in 152 breast cancer cases with liver metastasis by SPSS 11.5. Results: The median diseases free survival (DFS) from initial diagnosis to recurrence was 21 months. The median survival from the time of recurrence (MSR) was 16 months with 1 year survival rate at 60.5%. The time to tumor progression was 7.4 months. The response rate was higher in chemotherapy group than in TACE group (38% vs. 51%, P=0.045). Compared to non-taxanes-encompassing regimen, the TTP was longer (7m vs.10m, P=0.048) and the response rate was higher (61% vs.45%, P=0.048) in taxanes-based chemotherapy. The MSR is longer in patients with single liver metastases receiving TACE than receiving chemotherapy (16m vs. 30m,P=0.0052), but no statistically significant difference in MSR was observed for multiple metastases. On the univariate analysis, Pathological tumor size (PT) at diagnosis, axillary lymph node status at diagnosis, negative estrogen receptor (ER) status, abnormal ALT after liver metastasis, metastasis tumor size were significantly associated with shorter survival from liver metastasis. On the multivariate analysis, only the axillary’s lymph node status at diagnosis and ER status remained independently associated with decreased MSR after liver metastasis. Conclusions: Young women, short of DFS and with consecutive metastastsis in lung and bone are the characteristics of patients with BCLM. The effective chemotherapy (especial taxane- containing regimens) and TACE may improve outcome for patients with BCLM. The median survival time 1 or 2 year survival rate are higher than those of 10 years ago. No significant financial relationships to disclose.
Relationship of ethnicity and overall survival (OS) in Asian patients (pts) on sorafenib for advanced hepatocellular carcinoma (HCC) in British Columbia, Canada.
Authors: Renata D'Alpino Peixoto, Daniel John Renouf, Sharlene Gill, Winson Y. Cheung, Hagen F. Kennecke, Howard John Lim
Journal: Journal of Clinical Oncology (2014)

311 Background: Although both the SHARP and the Asian-Pacific trials showed improved OS for sorafenib when compared to placebo, the magnitude of benefit was substantially less for Asian pts, who have a higher prevalence of hepatitis B (HBV) infection. Whether the worse prognosis is related to ethnicity or to the etiology of HCC remains unclear. BC has a sizeable Asian population that can provide a good comparison to Caucasian pts with HCC. The aim of this study was to identify prognostic factors among pts with HCC who received sorafenib. Methods: 257 consecutive pts with advanced HCC who initiated sorafenib from January 2008 to February 2013 were identified using our pharmacy database. Clinicopathological variables and outcomes were retrospectively collected. Prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank tests) and multivariate analyses (Cox proportional hazards models). Results: Median age was 62 years (range 22-93), 80.5% were men, and 37.7% were Asian. Among them, 34.2% had HBV and 29.6% had hepatitis C (HCV). In addition, 68.4% had cirrhosis and 46.3% had liver-limited disease. Median progression-free survival (PFS) was 3.7 months (95% CI 3.2-4.1). Median OS from initiation of sorafenib to death was 7.4 months (95% CI 5.7-9.1). On univariate analysis, good ECOG PS, AFP &lt; 250 and history of HCV were associated with better OS (p &lt; 0.001, 0.002 and 0.025, respectively). Ethnicity, age, gender, HBV, cirrhosis and extra-hepatic metastases were not significantly associated with OS. On multivariate analysis, good ECOG PS, AFP &lt; 250 and HCV positivity correlated with better OS (p &lt; 0.001, 0.001 and 0.006, respectively), while ethnicity did not. Conclusions: When treated with sorafenib at the same institution, Asians and Caucasians with advanced HCC had similar OS. ECOG PS, AFP and HCV were the only significant prognostic factors. A higher proportion of HCVpositivity might explain why the SHARP trial achieved better OS when compared to the Asian-Pacific trial.
Efficacy of physician and self skin-examination practices for early melanoma detection
Authors: S. M. Swetter, R. A. Pollitt, D. R. Brooks, T. M. Johnson, E. R. Park, A. C. Geller
Journal: Journal of Clinical Oncology (2008)

9037 Background: Early detection of invasive melanoma is critical for successful treatment, and most cutaneous melanomas are visible on the skin surface. Recent literature has emphasized the value of the clinical skin examination and skin self-examination (SSE) in reducing melanoma mortality. However, the efficacy of skin examination practices in early melanoma detection remains poorly understood. Methods: Individuals ≥18 years with a diagnosis of invasive primary melanoma were surveyed within 3 months of diagnosis at Stanford/VA Palo Alto and University of Michigan regarding predictors of early melanoma discovery. Data were analyzed (SAS 9.1) to determine age-adjusted associations between skin examination, sociodemographic measures, and melanoma thickness at diagnosis. Results: The 223 patients (57% male; mean age 56.4 years, SD 16.7 years) had a mean tumor depth of 2.06 mm (SD 2.19). Receiving a physician skin examination within the last year (48%) was associated with significantly thinner tumors at diagnosis (1.57 mm vs. 2.42 mm, p=0.006). Patients who examined all of their own moles most frequently (at least every six months) (34%) had slightly thinner tumors (1.76 mm vs. 2.22 mm; p=0.142) than those who did not. Individuals routinely examining their skin on 7 or more of the 13 body areas assessed (49%) had a mean tumor depth of 1.91 mm, versus 2.21 mm among those who did not (p=0.298). Use of a melanoma picture as an aid in SSE (30%) was associated with significantly thinner tumors (1.50 mm vs. 2.30 mm, p= 0.013). Conclusions: Physician skin exam was a strong predictor of earlier melanoma detection, supporting the current emphasis on physician skin examination for secondary prevention. Selected SSE practices were also associated with thinner tumors at diagnosis. Measures of frequency of mole self-examination and proportion of overall skin area examined during SSE were modest predictors of earlier melanoma diagnosis. A more specific measure of behavior during SSE (use of a melanoma picture aid) was strongly associated with thinner tumors. While thorough SSE appears to be important in early melanoma detection, more precise definitions of vigilant SSE are required. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough
A pilot study of immune checkpoint inhibition (tremelimumab and/or MEDI4736) in combination with radiation therapy in patients with unresectable pancreatic cancer.
Authors: Austin G. Duffy, Oxana V. Makarova-Rusher, Drew Pratt, David E Kleiner, Christine Alewine, Suzanne Fioravanti, Melissa Walker, Stephanie Carey, William Douglas Figg, Seth M. Steinberg, Victoria Anderson, Elliot Levy, Venkatesh Krishnasamy, Bradford J. Wood, Jennifer Jones, Deborah E. Citrin, Tim F. Greten
Journal: Journal of Clinical Oncology (2016)

TPS470 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. MEDI4736 is a human monoclonal antibody directed against PD-L1. Blockage of ligation between PD-L1 and PD1 induces local immune activation and prevents anergy and exhaustion of effector T-cells. Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation. The underlying hypothesis of this study is that the effect of immune checkpoint inhibition (accomplished via tremelimumab and/or MEDI4736) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma. Whilst radiation treatment in pancreas cancer is commonly employed in limited or early stage disease, if radiation can enhance the effect of immune checkpoint inhibition to produce systemic anti-tumor effects the combination could become an effective treatment modality for patients with advanced disease. Methods: Patients with histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) disease are being enrolled to this pilot study. The primary objectives are to determine the safety, tolerability and feasibility of immune checkpoint inhibition [comprising either MEDI4736 alone (Cohort A), Tremelimumab (Cohort B) or combined MEDI4736 and Tremelimumab (Cohort C)] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer. Select eligibility criteria are as follows: at least 1 measurable metastatic lesion by RECIST 1.1 criteria and accessible for biopsy. No prior radiation therapy to the pancreas allowed. There is no limit to the number of prior chemotherapy regimens received; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active or prior documented autoimmune or inflammatory disorders. Clinical trial information: NCT02311361.
Vorinostat (V) and bortezomib (B) as third-line treatment in patients with advanced non-small cell lung cancer (NSCLC): A Wisconsin Oncology Network Phase II Study.
Authors: M. W. Jones, C. Zhang, K. R. Oettel, J. H. Blank, E. G. Robinson, H. G. Ahuja, R. J. Kirschling, P. H. Johnson, M. S. Huie, J. Kolesar, M. B. Wims, H. Hernan, T. C. Campbell, A. M. Traynor, T. Hoang
Journal: Journal of Clinical Oncology (2011)

7567 Background: Third-line treatment option for advanced NSCLC patients is very limited with a lack of effective drugs and specific trials targeting this patient population. V+B combination was previously investigated in a phase I study at our institution, which suggested anti-tumor activity in NSCLC. We conducted this phase II trial to evaluate the efficacy and tolerability of this combination as third-line therapy in advanced NSCLC. Methods: Eligibility included: recurrent/metastatic NSCLC, receiving 2 prior systemic regimens, and performance status 0-2. Stable, treated brain metastasis was allowed. Patients received V 400 mg PO daily D1-14 and B 1.3 mg/m2 IV D1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS). Secondary endpoints were response, survival, toxicity, B-induced neuropathy, and correlates. This study followed two-stage minimax design (n=18+15=33). Results: From 01/2009 to 03/2010, 18 patients were enrolled in the first stage. Median age was 59; half were women. Histology included adenocarcinoma (50%), NSCLC-NOS (33%) and squamous cell (17%). All patients had platinum-based doublets involving taxane or pemetrexed as first-line treatment. Second-line therapy included pemetrexed (50%), erlotinib (22%), or other agents (28%). Patients received a median of 2 treatment cycles (range: 1-6). The most common reason for treatment discontinuation was disease progression. Efficacy results: median PFS was 1.43 months (95% CI 1.15-2); 3m-PFS 13% (95% CI 0-0.294); and median overall survival 4.7 months (95% CI 3.15-8.64). There was no response; stable disease was observed in 5 patients (28%). Most common grade 3/4 toxicities were: thrombocytopenia (8/1), lymphopenia (3/1), and fatigue (5/1). Grade 3 peripheral sensory neuropathy was seen in 1 patient. Conclusions: This phase II trial demonstrated that V+B combination was well tolerated in this patient population. However, due to lack of efficacy observed in the first stage, the study was terminated. Analysis results of histone acetylation, p21, HSP70 gene expression, and 20S proteasome inhibition will be presented at the time of the meeting.