tbuckley/cabot-search huggingface dataset:
Second primary malignancy in patients with long survival after esophagectomy for squamous cell carcinoma of the esophagus.
Authors: Kunihiko Hiraiwa, Kazuo Koyanagi, Hirofumi Kawakubo, Tai Omori, Toshihiro Kakefuda
Journal: Journal of Clinical Oncology (2012)

42 Background: Patients after esophagectomy for esophageal squamous cell carcinoma (ESCC) were reported to have a remarkably high risk of subsequent cancer of head and neck cancer (Matsubara, et al. J Clin Oncol 2003). The outcome was reported to be signiﬁcantly less favorable as a result of difﬁculty in early detection. However, magnifying endoscopy combined with narrow band imaging (NBI) system recently allowed early detection of head and neck cancer. This study was to assess the risk of subsequent malignancies after esophagectomy for ESCC for the establishment of an adequate follow-up program. Methods: Eighty patients with ESCC who had undergone radical esophagectomy at the Kawasaki Municipal Hospital from 2000 to 2006 were eligible for this study. Among the eighty patients, we analyzed 41 cases who survived more than 5 years after esophagectomy. Results: Median survival of the 41 patients was 7.1 years. Two patients who developed squamous cell carcinoma in the lung within 5 years after esophagectomy were not included in the group of subsequent second malignancies, because it was difficult to distinguish primary tumors from metastatic tumors. Second malignancies were found in 7 (17.1%) of 41 patients subjected to curative esophagectomy. Subsequent malignancies were most frequently found in the head and neck region (n = 4; 57.1%), followed by the residual esophagus (n = 1; 14.3%), colon (n = 1; 14.3%), and breast (n = 1; 14.3%). The subsequent cancers in head and neck, and residual esophagus were detected from 1 to 9 years after esophagectomy in an early stage with magnifying endoscopy combined with NBI system. They were curatively resected by endoscopic laryngo-pharyngeal surgery (ELPS) and endoscopic submucosal dissection (ESD). The subsequent cancers in colon and breast were also curatively resected by operation. Conclusions: Patients after esophagectomy for ESCC had a high risk of subsequent cancer of head and neck cancer. Minute postoperative surveillance with magnifying endoscopy combined with NBI system is strongly recommended even more than 5 years after esophagectomy. Early detection of second malignancies allowed less invasive treatment such as ELPS and ESD with favorable outcome.
Interim Analysis of the Randomized Eortc/Lysa/Fil Intergroup H10 Trial On Early PET-Scan Driven Treatment Adaptation in Stage I/II Hodgkin Lymphoma
Authors: Marc PE André, Oumedaly Reman, Massimo Federico, Théodore Girinski, Pauline Brice, Ercole Brusamolino, Christophe Ferme, Richard vander Maazen, Monica Bellei, Catherine Sebban, Franck Morschhauser, Elly Lugtenburg, Aspasia Stamatoulas, Catherine Fortpied, Michel Meignan, Annibale Versari, Martin Hutchings, John Raemaekers
Journal: Blood (2012)
Presentation, management, and outcome of the pregnant female with colorectal cancer.
Authors: E. L. Kachikwu, L. A. Leong, L. L. Lai
Journal: Journal of Clinical Oncology (2011)

389 Background: Most patients diagnosed with colorectal cancer (CRC) are older than 60 years old. However, there remains a population of women of reproductive age (17-49) who develop CRC. Few publications have described the presentation, management and outcome of patients who initially present while pregnant.The objective of this study is to assess the presentation, management and outcome of women aged 17-49 with a particular focus on the pregnant patient. Presenting symptoms, time from presentation to diagnosis, management of disease, and overall survival were the main endpoints of this study. Methods: A retrospective chart review was conducted of 72 women aged 18-49 who were treated for CRC between 2005 and 2009 at a single institution. We compared the non-pregnant women (n = 66, group A) with the pregnant women (n = 6, group B). Results: The median age at presentation was 43 and 36.5 years in group A and group B, respectively. All six patients in group B presented with significant anemia, severe abdominal pain, and bright red blood per rectum during pregnancy while 25% of group A were asymptomatic. Although all 6 of the group B patients presented while pregnant, five patients were diagnosed in the postpartum period. Only 1/6 patients were diagnosed while pregnant, in the 3rd trimester. Median time from presentation to diagnosis was 10 days in group A, and 175 days in group B. Definitive treatment for the group B women included resection with C-section (n = 1), resection followed by systemic chemotherapy (n = 3), and resection only (n = 2). 72% of group A and 100% of group B patients presented with advanced disease (stages III and IV). Median overall survival for the entire cohort was 24.4 months; 26.1 months for group A and 7.8 months for group B. There was one long-term survivor amongst the group B patients (5.3 years), who has had two recurrences. Conclusions: Overall, the majority of women aged 18-49 presented with advanced stages of CRC. Specifically, 5/6 pregnant women presented with stage IV disease. Given that many of the symptoms of CRC mimic symptoms of pregnancy, a higher index of suspicion of CRC may minimize the delay in diagnosis, decrease the proportion of higher stage cancers, and improve the cancer outcome in this cohort of patients. No significant financial relationships to disclose.
Biomarkers affecting metastasis and survival in paired tissues of 107 patients with metastatic breast cancer.
Authors: E. Kim, H. J. Lee, G. Gong, K. H. Jung, J. Ahn, B. H. Son, S. Ahn, H. Kim, S. Kim
Journal: Journal of Clinical Oncology (2011)

10630 Background: The chemokine, CXCL12, and its receptor, CXCR4, have been known to play important roles in metastasis of several kinds of carcinoma. In preclinical study, VEGF regulates both CXCR4 expression and invasiveness. Tumors with higher Ki67 and EGFR expression were more prone to recur or metastasis. CD44+/CD24- subpopulation of breast cancer cells has highly invasive properties and involves in early stage of metastasis. Methods: Between 1995 and 2009, among patients with breast cancer who underwent breast cancer surgery, during follow-up, patients who developed distant metastasis were screened for availability of metastatic sites tissue for immunohistochemistry (IHC) analysis. We reviewed patients’ medical records and assessed CXCR4, CXCL12, VEGF, Ki67, EGFR, PTEN, CD24 and CD44 by IHC for in primary sites and metastatic sites of these 107 patients. Results: The median age was 48 years (range, 26 to 70 years). Most tumors were invasive ductal carcinoma (IDC) (98/107, 91.6%) and more than 2cm (78/107, 72.8%). 56 patients were positive axillary lymph nodes (56/107, 52.3%). 103 patients were assessed for HER2 expression by IHC, 35 (35/107, 32.7%) patients showed HER2 expression. CXCR4 were significantly relevant to brain metastasis (OR 5.1 [CI 1.0-24.5], p=0.04). ER, PR expression and good histologic grade of tumor tissues were correlated significantly with longer overall survival (86.5 vs. 33.5, p=0.002, 84.4 vs. 41.5, p=0.005, 74.4 vs. 40.9, p=0.032). Conclusions: Higher CXCR4 in primary breast cancer sites was related to brain metastasis. ER, PR expression and good histologic grade were favorable prognostic factors for survival in patients with breast cancer.
Calculation of an immunoscore based on extensive flow cytometry analysis of PBMCs from metastatic breast cancer patients treated with docetaxel alone or in combination with vaccine.
Authors: Italia Grenga, Renee Nicole Donahue, Peter Sungwhan Kim, Brendan Dempsey, James L. Gulley, Christopher Ryan Heery, Ravi Amrit Madan, Jeffrey Schlom, Benedetto Farsaci
Journal: Journal of Clinical Oncology (2013)

31 Background: Therapeutic vaccine is emerging as a potentially efficacious and safe treatment for cancer patients. However, markers are not available to identify patients more likely to benefit from this treatment. Aim of this retrospective study was to analyze before treatment immune subsets that correlated with clinical outcome in metastatic breast cancer patients treated with docetaxel alone or in combination with vaccine. Methods: We applied multi-color flow cytometry analysis of PBMCs harvested prior to treatment from patients (n=43) enrolled in a small randomized phase II study of docetaxel alone (n=20) or in combination with PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) encoding for the tumor-associated antigens CEA and MUC-1, along with a TRIad of COstimulatory Molecules (B7-1, ICAM-1, and LFA-3; called TRICOM) (n=23). Frequency of more than 200 immune sub-populations before treatment was measured by flow cytometry. Each of the resulting subsets was ranked in tertiles. For immune subsets that correlated directly with PFS, 2 points were assigned if the frequency fell in the highest tertile, 1 point if in the middle, and 0 if in the lowest tertile. For subsets that correlated inversely with PFS, the points were assigned in the opposite order. An immunoscore was calculated based on the sum of points assigned to each subset. Log-Rank analysis, with the cutoff based on the median of the immunoscores, was performed to evaluate differences in PFS between patients with a low and high immunoscore. Results: In vaccine plus docetaxel arm, 10 immune subsets from PBMCs before treatment correlated with PFS and were used for the calculation of the immunoscore. Patients with an immunoscore above the median showed a statistically significant longer PFS compared to those with lower score in vaccine plus docetaxel arm (p&lt;0.001, HR=0.1466, 95% CI= 0.0478-0.4375) but not in docetaxel alone arm (p=0.097, HR=0.418, 95% CI=0.147-1.172). Conclusions: Calculation of an immunoscore from PBMCs before treatment based on flow cytometry screening of immune subsets may identify patients that will most likely benefit from vaccine combination immunotherapy.
A predicitve algorithm for response to abiraterone in metastatic castration relapsed prostate cancer (CRPC).
Authors: Mehran Afshar, Fawaz Al-Alloosh, Nicholas David James, Helen Clarke, Sarah Pirrie, Emilio Porfiri
Journal: Journal of Clinical Oncology (2014)

238 Background: Numerous novel therapies for castration relapsed prostate cancer (CRPC) have led to a rapidly evolving approach to its management. Rationalisation of treatment combinations and sequencing of therapy requires identification of men who are more likely to benefit from a particular treatment. An unmet clinical need exists in this domain. We present the findings of a review of patients treated with abiraterone at our centre, and describe a novel predictive algorithm in this setting employing previously undefined pre-determinants of response. Methods: Patients with CRCP treated with abiraterone post-docetaxel at Queen Elizabeth Hospital between August 2010 and February 2012 were identified. Electronic patient records were utilised to extract variables including patient demographics, tumor characteristics, treatment history and other potential predictors of response such as prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP). Outcome measures included overall survival (OS), adverse events and PSA response rate. OS was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed on potential prognosticators. Multivariate Beta coefficients were used to generate a predictive algorithm to identify two distinct risk groups. Results: Sixty one patients met the inclusion criteria. From starting abiraterone, the median OS was 12.6m, and median duration of follow-up was 11.5m. In univariate analysis seven factors impacted OS: age, response duration to androgen deprivation therapy (ADT), Hb, time from diagnosis to starting abiraterone, and ALP. Subsequent multivariate analysis identified three independent predictors of OS: duration of response to ADT (HR: 0.95, p=0.006), performance status (HR: 0.71, p=0.013), and baseline Hb (HR: 0.47, p=&lt;0.001). A predictive algorithm dividing the cohort into high- and low-risk groups derived a diverging Kaplan-Meier curve without overlapping 95% CI’s. The low risk group did not reach median survival. Conclusions: This retrospective review has identified a predictive scoring algorithm for response to abiraterone in CRPC. We suggest that further analysis in the form of external validation is needed in order to justify its use in individualisation of patient management and stratification of patients for prospective clinical trials.
KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience
Authors: E. Van Cutsem, I. Lang, G. D'haens, V. Moiseyenko, J. Zaluski, G. Folprecht, S. Tejpar, O. Kisker, C. Stroh, P. Rougier
Journal: Journal of Clinical Oncology (2008)

2 Background: Efficacy analyses of the randomized phase III CRYSTAL trial have shown a significant improvement in progression-free survival (PFS), overall response, and curative surgery rate when adding cetuximab to FOLFIRI in the first-line treatment of mCRC. Furthermore, KRAS mutation status has recently been shown to relate to outcome in mCRC patients (pts) treated with cetuximab as a single agent or in combination with irinotecan. Efficacy analyses have been repeated to evaluate the influence of KRAS mutation status in first-line pts treated with FOLFIRI with or without cetuximab under controlled study conditions. Methods: Blocks from archived tumor material were available from 587 of 1198 of the total pt population. Isolation of genomic DNA was performed directly from slides (3×10 μm). Determination was done by qPCR-based KRAS mutation analysis of codons 12/13. The KRAS-evaluable pts (n=540) were analyzed statistically to evaluate treatment effect stratified by KRAS mutation status (wild-type [wt] or mutation [mt]) and the given randomization strata using Cox regression for PFS time (primary IRC evaluation) and the CMH test for best overall response. Results: The population with available tissue for KRAS analysis was representative of the overall ITT population. KRAS mt were detected in 35.6% (192/540) of pts with evaluable samples. A statistically significant difference in favor of cetuximab was seen in KRAS wt pts for PFS (p=0.0167; hazard ratio [HR] estimate 0.68 [95% CI: 0.051–0.934]) and best overall response (59.3% [cetuximab + FOLFIRI] vs 43.2% [FOLFIRI], p=0.0025). Subgroup analyses by KRAS mt status for cetuximab + FOLFIRI vs FOLFIRI showed no significant differences between treatment groups for PFS (p=0.75; HR estimate 1.07 [95% CI: 0.71–1.61]) or best overall response (p=0.46). Conclusions: This large analysis shows the predictive value of KRAS mutation status for treatment with cetuximab plus FOLFIRI in the first-line treatment of mCRC. The data demonstrate that treatment effect of cetuximab in pts with KRAS wt is significantly enhanced compared with standard chemotherapy alone, whereas pts with KRAS mt could not be shown to benefit from cetuximab treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck Merck Merck
The enhanced antitumor effect of combined triptolide and paclitaxel on pancreatic cancer cell lines.
Authors: Wei Wang, Wenjie Lin, Qingda Wang, Xin Zhuang, Jinbing Luo
Journal: Journal of Clinical Oncology (2014)

335 Background: Pancreatic cancer is a disease with dismal prognosis and its treatment options are limited. Recently albumin-bound paclitaxel (nab-paclitaxel) was approved by FDA for advanced pancreatic cancer patients. This study aims to explore the enhancement of therapeutic effect on human pancreatic cancer cell lines (AsPC-1 and PANC-1) via the combination of triptolide, derived from the herb Tripterygium wilfordii, and paclitaxel. Methods: Pancreatic cells were treated with paclitaxel or triptolide alone, and the combination of them. Cell proliferation was measured by sulforhodamine B (SRB). Apoptotic cells were assessed by flow cytometry and western blot for cleaved caspase-3, 8, 9 and PARP. To explore the role of nuclear factor kappaB (NF-kB) activity in pancreatic cancer cell lines, AsPC-1/IkBaM and PANC-1/IkBaM cells (NF-kB activity of cells was silenced by IkB-a mutation) were treated with triptolide plus paclitaxel and NF-kB activity were analyzed. Results: Triptolide demonstrated cytotoxicity on pancreatic cancer cell lines with the IC 50 of 25-40nM. The combination of triptolide (IC 30 concentration) and paclitaxel enhanced the cytotoxicity significantly . Combination index (CI) indicated that the effect of triptolide plus paclitaxel was synergistic. Furthermore, pancreatic cancer cells treated with triptolide plus paclitaxel exhibited increased apoptosis, as evidenced by stronger Annexin V/ PI staining, higher levels of pro-apoptotic proteins including cleaved caspases and activated PARP compared to cells treated with paclitaxel or gemcitabine alone. In the mechanism study, the combination of triptolide and paclitaxel did not demonstrate synergistic effect on AsPC-1/IkBaM and PANC-1/IkBaM cells. It indicated that the enhanced effect of triptolide plus paclitaxel was correlated with NF-kB activity. Conclusions: (1) the combination of triptolide and paclitaxel enhances the apoptosis in vitro, low concentration of triptolide showed synergistic effect with paclitaxel; (2) the antitumor effect of triptolide plus paclitaxel on pancreatic cancer is mediated by the induction of apoptosis and triptolide enhances paclitaxel-mediated apoptosis via suppression of NF-kB activity.
Causality attribution of adverse events (AEs) as reported in two industry-sponsored phase III placebo-controlled clinical trials.
Authors: J. Hui, K. D. Holen, G. B. Gordon, K. Obermeyer, J. Qian
Journal: Journal of Clinical Oncology (2011)

e16533 Background: Hillman et al have reported on the limited usefulness of causality in randomized placebo-controlled cooperative group studies [Hillman JCO 2010]. The merits of reporting causality for AEs to test drugs in clinical trials was investigated by analyzing AE data from two industry supported phase III studies - atrasentan vs. placebo in men with non-metastatic (M00-244) or metastatic (M00-211) prostate cancer. Methods: All AEs, including all grades of severity, from pts in the atrasentan and placebo arms of these two trials were analyzed. The investigator rated the severity of each AE according to the CTC v2.0, and assessed the relationship of the AE to the use of study drug as probably, possibly, probably not, or not related. AEs were summarized using the MedDRA (version 9.0). A subject with more than 1 AE reported for the same MedDRA term is counted once. The method described by Hillman was used to evaluate the effect of physician-reported causality of the AE rates in these trials. Results: In M00-244, 99% (459/462) of pts in the atrasentan arm and 97% (454/470) in the placebo arm experienced at least one AE. The corresponding incidences in the M00-211 trial were 99% (398/404) and 97% (386/397). The incidence rate of Grade 1 or 2 AEs is more than 10% higher than that of Grade 3 or 4 AEs. AEs rated as grades 3 and 4 were reported by a similar percentage of pts in each arm in both trials. Analysis of these data showed that there was no consistent pattern for causality attribution of AEs, and the knowledge that the test drug may increase the risk of heart failure in subjects with a history of cardiac disease and chronic pulmonary conditions did not affect the causality attribution by the investigators. The incidence of probably or possibly related (to study drug) AEs involving respiratory, blood and lymphatic systems were found to be over-reported in the M00-244 study and under-reported in the M00-211 study. Conclusions: This analysis from an industry database suggests that AE causality is difficult to determine, may not be reliable, and can be influenced by physicians’ preconceptions. The limited utility of causality assessment in placebo-controlled randomized studies needs to be further substantiated.
A prospective, observational study of medication use among outpatients with common solid tumors.
Authors: M. Weiss, J. Manola, M. A. Thompson, M. L. Thomas, M. Fisch
Journal: Journal of Clinical Oncology (2011)

9055 Background: In addition to treatment for their primary disease, cancer patients (pts) receive medications (meds) for relief of symptoms arising from the disease or its treatment and for prevention and treatment of other concurrent conditions. As part of the ECOG Symptom Outcomes and Practice Patterns study (SOAPP), we explored the number and type of agents pts receive and examined factors associated with taking more than 10 meds. Methods: Eligible pts were seen in outpatient academic or community cancer clinics and agreed to complete a survey at two time points 28 to 35 days apart. Data on current meds were collected through health care providers at both time points. Descriptive statistics, Fisher's exact test, and logistic regression (LR) were used to summarize the findings. Results: In 2,795/3,106 evaluable pts responding to the question at baseline (90% response rate), 32% were taking 0-4 meds, 43% were taking 5-9 meds, and 25% were taking >10 meds. The 5 most frequently prescribed categories of med among 3099 pts with available data were anti-hypertensives (46%), non-opioid pain meds (38%), GI meds other than antiemetics (38%), psychiatric meds (35%), antiemetics (32%). In addition, 48% of pts were taking nutrition supplements. A multivariable LR model showed that Non-Hispanic white pts, older pts, pts with poor ECOG performance status, pts with diagnoses of lung and prostate cancer, and pts with advanced stage of disease were more likely to be taking 10 or more meds. These pts were as prevalent in community practices as in academic settings (p=0.63). Conclusions: Outpatient management of solid tumor patients is complex due to co-morbidities and the need for pharmaceutical intervention of both symptoms of disease and side effects of treatment. The strongest predictor of polypharmacy is race/ethnicity. Factors asssociated with > 10 meds Odds ratio 95% CI P Female 1.13 0.89 – 1.43 0.31 White/non-Hispanic 2.84 2.15 – 3.76 <0.0001 Primary site lung/prostate 1.78 1.40 – 2.25 <0.0001 ECOG PS 2-4 vs PS 0 1.63 1.13 – 2.34 0.001 ECOG PS 2-4 vs. PS 1 1.17 0.83 – 1.64 0.43 Advanced disease 1.41 1.15 – 1.72 0.001 Age > 65 1.72 1.40 – 2.12 <0.0001 Number of moderate to severe symptoms 1.06 1.06 – 1.12 <0.0001