tbuckley/cabot-search huggingface dataset:
Association of reduction of tumor metabolism with prognosis of advanced gastric cancer patients treated with palliative chemotherapy: Prospective cohort study.
Authors: Seongyeol Park, Seunggyun Ha, Hyun Woo Kwon, Woo Hyoung Kim, Tae-Yong Kim, Do-Youn Oh, Gi Jeong Cheon, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2016)

31 Background: Although tumor metabolism can be measured by 18 F-FDG PET, the meaning of metabolic response by chemotherapy in gastric cancer patients has not been well studied. The purpose of this study is to identify prognostic value of tumor metabolic response in gastric cancer. Methods: Advanced gastric cancer patients were enrolled in this prospective cohort study before initiation of palliative chemotherapy. At the baseline and at the first tumor response evaluation, 18 F-FDG PET was taken to measure tumor metabolism. We measured maximum standardized uptake value (SUVmax), and total lesion glycolysis (TLG) calculated as multiplying mean SUV by metabolic tumor volume (MTV) using threshold SUVs of 2.5 (TLG2.5) in each patients. Correlation of clinicopathological factors and survival were analyzed. Results: A total of 87 patients were enrolled. Baseline high SUVmax and TLG2.5 were associated with HER2 positivity, histologic differentiation and tumor size. High SUVmax and TLG2.5 were also associated with worse overall survival (OS) (HR 2.14, P = 0.025; HR 2.23, P = 0.037, respectively). Comparing RECIST evaluation, 30% of the reduction of sum of target lesions was correlated with 50% reduction of SUVmax, and 50% reduction of TLG2.5. The larger reduction of SUVmax (HR 0.43, P = 0.006 for Progression-free survival (PFS); HR 0.38, P = 0.007 for OS), and TLG2.5 (HR 0.27, P &lt; 0.001 for PFS; HR 0.27, P = 0.001 for OS) was associated with better OS. In multivariate analysis, SUVmax and TLG2.5 were independent prognostic factors along with age, histologic type, gastrectomy history and HER2 status. Conclusions: Tumor metabolic response measured by SUVmax or TLG2.5 was associated with prognosis of advanced gastric cancer patients treated with chemotherapy.
Phase II trial of abiraterone acetate (AA) treatment for metastatic prostate cancer (PC) patients with a PSA of more than four following initial androgen deprivation therapy: SWOG S1014.
Authors: Thomas W. Flaig, Catherine M. Tangen, Maha Hussain, Neeraj Agarwal, Nicholas Mitsiades, Hari Anant Deshpande, Ulka N. Vaishampayan, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2015)

152 Background: Metastatic PC patients with a poor response to initial androgen deprivation therapy (ADT) as reflected by a PSA &gt; 4 ng/ml after 7 months of ADT have a poor prognosis. In the S9346 trial, about 25% of all enrolled patients had a PSA &gt; 4 ng/ml after 7 months of ADT with a subsequent median survival (OS) of 13 months. S1014 examined the efficacy of AA in this setting. Methods: Eligible patients with metastatic PC and a PSA of &gt; 4ng/ml between 6-12 months after starting ADT were treated with 1,000 mg of AA daily + 5 mg of prednisone twice daily. PSA could be rising or falling at the time of enrollment, but had to be &gt; 4 ng/ml. No chemotherapy or secondary hormonal therapies were allowed, except in patients receiving an anti-androgen at the time of enrollment, who were continued on this therapy. The primary endpoint was a PSA of ≤ 0.2ng/ml within 12 months of starting AA. The null hypothesis was a 5% rate and alternative was 20%, requiring 6 or more patients with PSA &lt; 0.2 ng/ml to conclude the regimen is promising (one-sided α=0.048, power=0.92). Results: Forty-one patients were enrolled between 7/2012 and 7/2013. One patient was deemed not analyzable due to not receiving any protocol treatment. Fourteen patients remain on treatment. Five (13%) patients achieved an undetectable PSA of ≤ 0.2ng/ml (95% CI 4%, 27%). Nine (23%) additional patients had PSA level &gt; 0.2 but &lt; 4 ng/ml. Twenty-one patients had no PSA response and six were not assessable and assumed to be non-responders. The median progression-free survival (PFS) was 17.4 months. There was one incident each of Grade 4 ALT elevation and rectal bleeding. Twelve patients reported Grade 3 adverse events as their worst level of severity. Conclusions: Although encouraged by 5 patients attaining “undetectable” PSA responses to AA in this poor prognosis setting, this study did not reach the protocol pre-specified level of 6 responses. OS and PFS will be updated with further follow-up. The therapy was generally well tolerated, without any clear signal of any unexpected toxicity. Clinical trial information: NCT01309672.
Ten fractions of preoperative radiotherapy for advanced rectal cancer: Is it a new protocol to follow?
Authors: J. Gu
Journal: Journal of Clinical Oncology (2011)

439 Background: This study is a retrospective analysis to investigate the efficiency of short-course preoperative radiotherapy following standardized total mesorectal excision (TME) for locally advanced rectal cancer. Methods: Clinical data of locally advanced mid-low rectal cancer who received TME in Beijing Cancer Hospital from 2001 to 2005 were collected retrospectively. Survival analysis was performed between patients who had TME following short-course preoperative radiotherapy (biological equivalent dose: 36Gy) or TME alone at the corresponding period. Results: Two hundred and sixty-three patients were eligible for analysis including 101 patients who received TME plus preoperative radiotherapy (PRT group) and 162 patients with TME alone (TME group). The occurrence of TNM downstaging in PRT group was 49.5%, including five percent who had complete response. The local reccurence rate was 4% in PRT group and 8.4% in TME group, with statistically different (p=0.04). An significant improved 5-year overall survival and disease-free survival was obtained in PRT group comparing with TME group (77.2% vs. 69.8%, p=0.04; 76.2% vs. 67.3%, p=0.03). Conclusions: Improved local control and survival benefits could be achieved by short-course preoperative radiotherapy on the basis of standardized TME for locally advanced rectal cancer. No significant financial relationships to disclose.
Potential predictors of pancreatic cancer: A population-based screen.
Authors: E. Ragulin-Coyne, J. K. Smith, S. Ng, T. P. McDade, S. A. Shah, J. F. Tseng
Journal: Journal of Clinical Oncology (2011)

164 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer-related death in the U.S. Unfortunately, PC is usually diagnosed at late stages. We hypothesized that certain diagnoses may precede PC diagnosis and assist in early identification of pancreatic cancer patients. Methods: SEER-Medicare 1991-2005 was used to identify PC patients. PC and prePC diagnoses were identified using ICD9 codes. We then examined pre-pancreatic cancer (prePC) diagnoses and compared the frequency of those diagnoses by PC stage at time of cancer diagnosis. Stepwise logistic regression was used to assess potential PrePC diagnoses. Risk factors were compared by stage at diagnosis using Kruskal-Wallis test, stratified univariate analysis and logistic regression. Time to diagnosis was calculated for each PrePC diagnosis. Results: 19,801 PC patients were identified. Significant (p&lt;0.05) prePC diagnoses included acute pancreatitis, chronic pancreatitis, cyst/pseudocyst, other pancreatic disease, bile duct obstruction, diabetes, weight loss, jaundice, abdominal pain, hepatomegaly. Median time (months) and interquartile range percentiles (25th-75th) before PC diagnosis were as follows: acute pancreatitis 0.97 (0.33-8.6), chronic pancreatitis 1.56 (0.37-11), cyst/pseudocyst 0.83 (0.3-3.5), other pancreatic disease 0.47 (0.2-1.2), bile duct obstruction 0.4 (0.17- 0.83), diabetes 30.6 (11.3-59.8), weight loss 1.16 (0.43-5.1), jaundice 0.43 (0.2-0.8), abdominal pain 16 (1.07-55.5), hepatomegaly 1.06 (0.33-1.07). Patients diagnosed at AJCC stage 0 had a mean of 3.53 prePC diagnoses (±SD 1.42); stage IA, 2.80 (1.68); stage IB, 2.42 (1.57); stage IIA, 2.44 (1.63); stage IIB, 2.46 (1.64); stage III, 2.33 (1.59); and Stage IV, 1.79 (1.40) (p&lt;0.001). Conclusions: PC patients who presented at later stages were less likely to have prePC claims identified prior to PC diagnosis compared with patients diagnosed at earlier stages. This analysis of potential prePC diagnoses suggests that access to care and earlier identification of PC related conditions may factor into the stage at which this lethal disease is identified. Further studies need to be conducted to identify and analyze additional predictors of PC and better screen individuals at risk. No significant financial relationships to disclose.
Undetectable PSA after radiotherapy for biochemical progression after radical prostatectomy as a predictor of biochemical outcome: Results of a retrospective study
Authors: T. Wiegel, G. Lohm, D. Bottke, S. Hoecht, K. Miller, K. Neumann, W. Hinkelbein
Journal: Journal of Clinical Oncology (2008)

5161 Background: Salvage radiotherapy (SRT) is used to treat patients with biochemical failure after radical prostatectomy. A biochemical response in about 65% of patients was demonstrated, but a significantly lower rate achieve an undetectable PSA range. Long-term response is about 25 %. The purpose of this study was to determine prognostic factors with impact on achieving the undetectable PSA-range after SRT and to define the role of this endpoint. Methods: Between 1997 and 2004, 162 patients received SRT without hormonal treatment at the Charité Universitätsmedizin, Berlin. We analysed the impact of several clinical factors on achieving an undetectable PSA after SRT and on biochemical relapse free survival (bNED). Results: Median follow-up time was 41.5 months and median PSA pre-SRT was 0.33 ng/ml. 60% of the patients achieved an undetectable PSA after SRT. Univariate analysis demonstrated significant predictors of biochemical progression after SRT: Gleason-Score (p=0.01), PSA pre-SRT (p=0.031), tumour stage (p=0.047) and persistent PSA after RT (p<0.00005). In multivariate analysis, margin status (p=0.017) and PSA pre-SRT (p=0.002) were predictors of an undetectable PSA after SRT. The most significant independent predictor of bNED was “PSA undetectable after RT” (p<0.0005) with a hazard ratio of 8.4. The calculated bNED at 4 years was 78% compared with 18% for those without achieving an undetectable PSA after SRT. Conclusions: Our findings suggest that, achieving an undetectable PSA after SRT is important to predict biochemical outcome. Patients with a low PSA pre- SRT, positive surgical margins and low tumour stage are best candidates for SRT. No significant financial relationships to disclose.
Pushing palliative care upstream: Integration into a community-based oncology practice.
Authors: Jennifer Blechman, Janet Bull
Journal: Journal of Clinical Oncology (2015)

134 Background: It is now well established that palliative care is an integral part of cancer treatment, recommended by the National Cancer Comprehensive Network for evidence based practices. Palliative care in this setting has been shown to improve symptom burden, enhance quality of life, reduce cost, and extend survival. Partners in Care is a non-profit, community-based hospice/home health agency in Bend OR, and consistent with national trends, receives late oncology referrals to hospice. Partnership with a multispecialty group was established to allow for a palliative care specialist to be embedded into their oncology clinic. Methods: Palliative care consults are offered 2 days/week in the oncology clinic. Triggers have been created to facilitate consultation. Quality metrics have been carefully tracked and include symptom scores, advance care planning, and transition and length of stay for hospice referrals. Financial support has been provided through grant funding from local insurance and community foundations. Results: In the first 10 months, 116 new oncology patients were seen, and had an average 1.9 visits. Documented ACP discussions occurred in 85% patients. Of patients with moderate to severe pain and dyspnea, scores improved by 65% and 50% respectively. Length of stay on hospice increased from 26 to 36 days. All of the patient respondents surveyed would recommend our service to others. Provider respondents 100% strongly agree that objectives were met when they requested a palliative care consult. Conclusions: Palliative care has been successfully integrated into a community-based oncology practice, resulting in increased access to palliative care, increased utilization of and length of stay on hospice, improved symptom management, increased use of ACP, and enhanced patient/family satisfaction. Having palliative care embedded in the clinic has resulted in better coordination of care and ease of communication. Future directions include using QDACT (Quality Data Collection Tool) to better track quality measures, inclusion of a social worker, and alignment with insurers and ACOs for cost support and data analytics.
Intraoperative margin assessment with the MarginProbe at different mammographic breast densities.
Authors: Alice Police, Erin Lin, Karen Lane
Journal: Journal of Clinical Oncology (2015)

47 Background: Mammographic breast density (BD) is known to affect breast imaging. MarginProbe is an RF Spectroscopy intraoperative margin assessment tool. We looked at the effect of mammographic breast density (BD) on the performance of the device. Mammographic density was assigned by Breast Imaging-Reporting and Data System (BI-RADS) classification prior to breast conserving surgery with the MarginProbe. Methods: For the current study we analyzed MarginProbe device arm data from the MarginProbe Pivotal Trial for which BD data was available. Clear margins of the main specimen, which is where the MarginProbe was applied, were defined as no tumor on ink. Clinical benefit was defined as clearing positive main specimen margins or cancer in the shaving. Analysis was performed based on logistic and linear regression, with univariate analysis. Results: The dataset for the analysis included 196 patients for which preoperative BD data was available. With higher BD, there was an increase in the rate of main lumpectomy specimen with positive margins (OR 1.65 per change in density category, p=0.025). The rate of shavings with clinical benefit showed an upward trend, with increasing BD. The number of shavings per patient increased with BD, however the overall volume of shavings did not increase. There was an increase in the per patient relative clinical benefit as BD increased (OR 1.6 per change in density category, p=0.024). Conclusions: With higher breast density patients and surgeons face an increase in risk for main specimen positive margins. With the increased BD and main specimen positivity more shavings were removed, but shavings volume did not increase as average shaving volume decreased with higher BD. Higher level of patient clinical benefit was observed with higher BD.
Secondary leukemia 15 years or more after treatment for childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: K. Nottage, J. Lanctot, Z. Li, J. P. Neglia, S. Bhatia, S. Hammond, W. Leisenring, A. T. Meadows, D. K. Srivastava, L. L. Robison, G. T. Armstrong
Journal: Journal of Clinical Oncology (2011)

9577 Background: Previous evaluations of survivors of childhood cancer suggest that the cumulative incidence of secondary leukemia plateaus at ~2% 10-15 years after primary cancer therapy. Risk beyond 15 years has not been comprehensively assessed, in part because of the lack of comprehensive long-term follow-up of previous cohorts beyond this time period. Methods: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study of 5-year survivors of childhood cancer treated between 1970 and 1986. Self-reported secondary leukemias >5 years from primary diagnosis were confirmed by pathology report or medical records. Diagnostic bone marrow samples were acquired and centrally reviewed. The standardized incidence ratio (SIR) was derived using age, gender, and calendar year specific rates from surveillance epidemiology and end results data. Results: Of 14,358 5-year survivors, 43 developed subsequent leukemia >5 years from primary diagnosis with 13 cases of leukemia occurring ≥ 15 years from diagnosis. Five were AML (2 with confirmed preceding MDS), 4 ALL (2 pre-B lineage, 1 T-cell, 1 unknown), 2 were APL with t(15;17). Two AML cases had 7q- deletion. One ALL had a complex karyotype including t(9;22) and another a p53 mutation. The mean age at diagnosis of leukemia was 31.6 years (range 18 to51), and occurred after a latency of 21.6 years from diagnosis. Sarcomas (n=5) and Hodgkin lymphoma (n=4) were the most common primary diagnoses. Six of the 13 patients received radiation therapy, while only 5 received alkylating agents, and none received epipodophyllotoxins. The SIR for leukemias occurring ≥ 15 years from diagnosis was 3.5 (95% CI 1.9 - 6.0). Eight of 13 are deceased with a median survival of 2 years after diagnosis of leukemia. Conclusions: This is the first description of increased risk of secondary leukemia ≥ 15 years from primary malignancy, demonstrating a 3.5-fold increased risk above that of the general population. Radiation was the most common treatment exposure. These findings indicate a high level of suspicion should be maintained for subjects who received radiation or alkylators and develop pancytopenia to facilitate early detection and intervention.
Immune response and its correlation with the disease activity in patients with advanced colorectal cancer (aCRC): Results from a prospective observational study.
Authors: Shahid Ahmed, Guojian Wei, June Lim, Florence Pilar M. Plaza Arnold, Tahir Abbas, Nayyar Iqbal, Lynn Dwernychuck, Amer Sami, Kamal Haider, Sunil Yadav, Peter Bretscher
Journal: Journal of Clinical Oncology (2014)

471 Background: Currently limited biomarkers are available to monitor disease status in cancer patients. Although host factors are critical in regulating cancer, the role of immune responses in aCRC is less clear. A predominant T helper 1 (Th1) response may be more effective to contain cancer than one with a substantial Th2 component. The Th1/Th2 phenotype can be inferred from relative prevalence of IgG isotypes among anti-cancer antibodies and may provide an innovative way to assess disease activity. The study aims to develop an ELISA assay to monitor IgG 1 :IgG 2 and its utility in predicting disease status in aCRC. Methods: A validated ELISA assay (Bertech Pharma) utilizing CRC cell lines was developed to measure IgG 1 (Th2) and IgG 2 (Th1) levels. A sample size of 44 (24 CRC and 20 healthy control [HC]) was estimated to achieve 80% power and α error of 0.05 assuming that the assay correctly detect CRC specific antibody in &gt; 80% cases. The IgG 1 :IgG 2 was compared between/within groups with HC and aCRC. Results: Samples were collected from 62/66 individuals recruited at 2:1 over 1 yr. 43 CRC patients had median age of 65 yrs (39-86) and M:F 2.3:1. 25 had &gt;1 metastatic site, 31 underwent primary tumor resection and 37 received chemotherapy. Using standard criteria, 14/43 (33%) CRC patients had elevated 1gG 1 titer compared with 2/19 (10%) HCs (p = 0.06). Mean IgG 1 of CRC group was 0.18±0.05 compared with 0.15±0.01 in HC (p = 0.01). Conversely, mean IgG 2 level of CRC group was 0.26±0.11 compared with 0.38±0.15 in HC (p = 0.003). Mean IgG 2 :IgG 1 of CRC group was 1.5±0.35 compared with 2.5±0.97 in HC (p &lt; 0.001). Among 43 CRC patients, 7/12 (58%) with disease progression (DP) had elevated IgG 1 compared 7/31 (23%) with stable disease (p = 0.03). Strikingly, 9/12 (75%) patients who died had elevated IgG 1 compared with 5/31 (16%) who were alive during the follow up, p = 0.001. Logistic regression revealed positive association among elevated IgG 1 and DP, HR:4.8 (95% CI:1.2-19.9) and mortality, HR:15 (95% CI:3.1-78.8). Conclusions: Our results revealed that patients with aCRC have abnormal IgG 1 :IgG 2 compared with HC and elevated IgG 1 (a predominant Th2 response) levels in aCRC correlate with DP and mortality.
Randomized phase II study of the safety, efficacy, and immune response of GVAX pancreas (with cyclophosphamide) and CRS-207 with or without nivolumab in patients with previously treated metastatic pancreatic adenocarcinoma (STELLAR).
Authors: Dung T. Le, Todd S. Crocenzi, Jennifer N. Uram, Eric R. Lutz, Dan Laheru, Elizabeth A. Sugar, Robert H. Vonderheide, George A. Fisher, Andrew H. Ko, Aimee L. Murphy, Katherine McDougall, Sandy Ferber, Dirk G. Brockstedt, Elizabeth M. Jaffee
Journal: Journal of Clinical Oncology (2016)

TPS486 Background: A heterologous prime-boost vaccination strategy using GVAX pancreas and CRS-207 is showing promise in patients with pancreatic adenocarcinoma (PDA) (Le, JCO 2015). Furthermore, blockade of the immune checkpoint programmed death-1 (PD-1) is active in some cancers. Combinatorial strategies aimed at priming tumor antigen-specific T cells while simultaneously blocking negative checkpoints may be necessary to improve outcomes in PDA. GVAX is composed of allogeneic pancreatic cancer cells modified to express GM-CSF and induces a broad response against multiple tumor antigens. GVAX is given with low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and is unique in its capacity to stimulate both innate and adaptive immunity by activating T cells and NK cells. Nivolumab is an antibody against PD-1. Methods: This is a phase 2 study comparing CY/GVAX and CRS-207 with or without nivolumab in subjects with PDA who failed only one chemotherapy regimen for metastatic disease. Subjects are randomized in a 1:1 ratio to receive either 2 doses of CY/nivolumab/GVAX and 4 doses of nivolumab/CRS-207 (Arm A) or 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm B). The primary objective is to compare OS between Arms A and B. Secondary/exploratory objectives include: assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with OS, progression-free survival and best overall response. Clinical trial information: NCT02243371.