tbuckley/cabot-search huggingface dataset:
Prognostic significance of positive lymph node ratio in resected esophageal cancer.
Authors: R. Thota, T. Tashi, W. Gonsalves, A. R. Sama, P. T. Silberstein, P. Townley, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

100 Background: Nodal involvement in esophageal cancer is associated with poor survival. We aim to determine whether the ratio of metastatic to examined lymph nodes (the lymph node ratio [LNR]) is a better predictor of survival as compared to the number of positive lymph nodes in resected esophageal cancer. Methods: 1,149 patients with resected esophageal cancer from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. The patients were further characterized to 3 lymph node quartiles based on LNR and their median survivals were calculated using the Kaplan-Meier method. Results: Out of 1149 patients 26.4% patients (303) had squamous cell carcinoma and 73.6% (846) were of adenocarcinoma histology. Median age of diagnosis is 63 years. 353 (31%) are stage 1, 384 (33%) are stage 2, and 412 (36%) are stage 3. Majority of them 71% arise in lower third of esophagus followed by 13% in middle third, 4% in upper third and 12 % had unknown site of origin. The group was subdivided into 3 quartiles with 62.7% in LNR1 (0.0-0.1), 25.6% in LNR2 (0.1-0.5) and 11.7% in LNR3 (0.5-1.0). 13.7% had less than 2 nodes removed, 29.3% had 3-6 nodes and 57% had &gt;7 nodes examined. 28% of them had tumor invading sub mucosa, 23.5% had tumor invading muscularis mucosa, 43.2% had involvement of adventitia and 5.3% had penetrating tumor at the time of diagnosis The 5 year survivals based on number of lymph nodes examined, number of positive lymph nodes and positive lymph node ratio are listed in the table. The median overall survival for resected esophageal cancer based on LNR quartiles was 37 vs 14 vs 11.5 months (p&lt;0.0001). Conclusions: Number of positive lymph nodes and positive lymph node ratio correlated with survival outcomes but number of lymph nodes retrieved did not predict any survival differences. However LNR was a better predictor of survival when compared to number of positive nodes. Further validation of this observation needs to done in large multicenter studies. [Table: see text] No significant financial relationships to disclose.
Clinical differences between African-Americans (AA) and Caucasians (CA) with and without family history (FH) of prostate cancer.
Authors: Cathryn E. Garvey, Patrick Cotogno, Emma M. Ernst, Elisa M. Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2016)

279 Background: Prostate cancer is one of the most common adult malignancies. Two well characterized risk factors for prostate cancer (PCa) are family history (FH) and race. The goal of this study was to distinguish the influence of family history and race with regards to clinically relevant covariates. Methods: In this single-institution study, 497 PCa patients from Tulane Hospital were clinically annotated and FH was evaluated. FH was defined as having ≥ 1 first degree relative affected with PCa and/or ≥ 2 affected second or third degree relatives. There were 147 AA and 350 CA patients; 66 AA and 120 CA reported PCa FH. The following clinical factors were documented: age and PSA at diagnosis (dx), Gleason score (biopsy or radical prostatectomy), and presence of metastasis (at any time). Chi-square, ANOVA, and odds ratio tests were performed to identify potential clinical correlates with regard to FH and race. Results: Results indicate that race and FH are not independent (p = 0.0266), where AAs were 1.5 times more likely to have a FH of PCa than CAs (95% CI 1.0543-2.3133). On average, men with a FH of PCa were younger at dx (p = 0.0063). FH significantly impacted age at dx for AAs (p = 0.036) but not CAs. No difference in age of dx was detected between race. FH of PCa did not influence PSA at dx in either CA (6.5, 1.2-681) or AA (19.2, 1.7-500) men, however race did (p = 0.004). CAs with FH of PCa were more likely to be diagnosed with low or intermediate risk PCa (Gleason score ≤ 7, p = 0.03). Gleason scores were not significantly different between races. Overall, FH did not influence metastasis. Although, AAs (n = 19) were 1.61 times more likely to develop metastatic disease compared to CA men. Conclusions: For AAs, FH lowered age at dx but did not have influence on development of metastatic disease, Gleason score or PSA. For CAs, Gleason score was lower in men with a FH. Overall AAs, as compared to CAs had more metastatic disease and higher PSAs at dx. Continuing to track clinical differences between AAs and CAs with a FH of PCa may provide additional insights into underlying racial and clinical disparities.
Efficacy of SAR302503, a JAK2 Inhibitor, in the Treatment of a Primary Xenograft Model of Human Acute Myeloid Leukemia,
Authors: Weihsu Claire Chen, Andreea C. Popescu, Yan Xing, Gitte Gerhard, Julie S. Yuan, Mark D. Minden, Cynthia Guidos, Donna E. Hogge, Jean C.Y. Wang, John E. Dick
Journal: Blood (2011)
Second-Line Treatment In Steroid Refractory Acute Graft Versus Host Disease During a 10-Year Period: A Single Centre Experience Comparing 4 Strategies
Authors: Alienor Xhaard, Raphael Porcher, Vanderson Rocha, Regis Peffault de Latour, Benjamin Bueno, Julien Lenglet, Anna D. Petropoulou, Patricia Ribaud, Gérard Socié, Marie Robin
Journal: Blood (2010)
Prognostic factors determining long term survival of patients with unresectable stage III and stage IV metostatic melanoma (MM) treated with combination therapy or IL-2 based biochemotherapy (BCC)
Authors: A. Y. Bedikian, M. M. Johnson, L. D. Broemeling, N. E. Papadopoulos, K. B. S. Kim, L. H. Camacho, P. Hwu
Journal: Journal of Clinical Oncology (2005)

7544 Background: The impact of systemic therapy on long-term (l-t) survival (S) of pts with MM remains uncertain. The objective of this study was to evaluate the S of pts treated with regimens including cisplatin (C), Vinblastine (V), DTIC (D), Taxol (T), Tamoxifen (Tam), interferon Alfa (IFN) and interleukin-2 (IL-2). We also wanted to identify the prognostic factors that predicted l-t S. Methods: The databases of 616 pts with MM treated on 8 Phase II/III clinical trials conducted between 1987 and 2001 were reviewed. They included MM of Skin (498 cases), unknown primary (81) mucosal (21) and choroidal MM (16 cases). Results: The characteristics of the pts who received IL-2 based biochemotherapy (BCC) and non-BCC regimens were compared. The 2 groups were similar in terms of median age, gender, sites of primary, serum LDH, and number of Stage M1C cases. Pt characteristics favored (p < 0.001) the 264 pts who received BCC in terms of younger age, pts with no bone metastasis and normal serum albumin level, and favored the 352 pts who received non-BCC regimens in terms of pts with no brain metastasis and Performance Status (PS) = 0. The 5-year and 10-year overall S rates of BCC and non-BCC, not corrected for non-cancer related deaths, were 14.51% and 7.95% (p= 0.020) and 11.94% and 4.47% (p= 0.002) respectively. In the non-BCC group, the S of 264 pts treated with 3-drug regimens CVD or CTD was not statistically significantly different than that of the 108 pts who received CVD+IFN±Tam. The response rate and median S of the BCC group were 49.2% and 12.7 months respectively compared with 33.5% and 9.6 months for the non-BCC group. Multivariate analysis revealed that treatment with biochemotherapy (p = 0.001), normal serum albumin level (p < 0.001), normal LDH level (p <0.001), PS = 0 (p = 0.03), and one visceral metastasis (p = 0.02) were favorable prognostic factors for l-t S. Conclusions: IL-2 based BCC is associated with superior l-t S than regimens not containing IL-2. Treatment with BCC, response to treatment, normal serum albumin level, normal LDH, PS = 0 and number of < 2 visceral metastatic sites were identified as significant predictive factors of l-t S. No significant financial relationships to disclose.
Immunotherapy in high-risk, chemotherapy-resistant patients with metastatic solid tumors and hematologic malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: A phase II study.
Authors: S. Slavin
Journal: Journal of Clinical Oncology (2010)

2510 Background: Feasibility and safety of immunotherapy mediated by intentionally mismatched rIL-2 activated killer lymphocytes (IMAK) with no prior stem cells engraftment was investigated in patients with advanced chemotherapy-resistant hematological malignancies and metastatic solid tumors. Treatment with IMAK was designed to accomplish 3 major goals: (1) improve anti-cancer activity of donor lymphocytes by using intentionally mismatched donors; (2) amplify killing of cancer cells by activation of donor lymphocytes with rIL-2 in vitro and in vivo following conditioning with low dose cyclophosphamide or fludarabine, CO×2 inhibitors and alpha interferon; and (3) avoid the risk of acute and chronic graft-versus-host disease (GVHD) by timely mandatory rejection of alloreactive donor lymphocytes. Methods: Treatment consisted of outpatient conditioning with 5 days of fludarabine 25mg/m2 or a single dose of cyclophosphamide 1,000mg/m2, 2 subcutaneous injections of alpha interferon (IFN) 3=106 and CO×2 inhibitors, followed by administration of IMAK in conjunction with low dose subcutaneous rIL-2 for 5 days for continuous activation of anticancer effects mediated by alloreactive donor lymphocytes prior to their anticipated rejection. Results: Results of phase II clinical study data in a cohort of 40 high-risk patients with metastatic solid tumors and hematological malignancies indicate that the outpatient procedure was reasonably well tolerated. Progression-free survival of >10 to >93 months was recorded in 5 of 31 evaluable patients with additional 5 with stable or progressive disease alive >6 to >24 months. A total of 4 out of 5 with high-risk hematologic malignancies were disease free >63 to >88 months. No patient developed clinical signs of GVHD. Conclusions: Allogeneic cell therapy with IMAK is feasible, safe, and potentially effective, with some otherwise resistant cancer patients apparently cured, thus justifying larger phase III studies in patients with hematologic malignancies and solid tumors, preferably at a stage of minimal residual disease at an early disease stage. No significant financial relationships to disclose.
Experience of weight loss and its burden in patients with non-small cell lung cancer: Results of an online survey.
Authors: Ana Maria Rodriguez, Elizabeth M Duus, John Friend
Journal: Journal of Clinical Oncology (2016)

71 Background: The main objectives of this study were to characterize and compare the burden of non-small cell lung cancer (NSCLC) patients who reported considerable weight loss ( ≥ 5% of their body weight in the past 6 months or ≥ 2% for a BMI less than 20 kg/m 2 ) to those who did not. Methods: 95 advanced NSCLC patients were surveyed from the online patient-powered community PatientsLikeMe. Self-reported demographic and clinical characteristics were recorded. Appetite, distress and concerns, health-related quality of life (QLQ-C15-PAL) and anorexia-cachexia symptoms/concerns (FAACT A/CS) were summarized. The results obtained between patients who lost considerable weight and those who did not were compared, using a two-tailed t-test or a Kruskal-Wallis test. Patients with weight loss were additionally asked open-ended questions on burden and concerns. Results: 35 (37%) patients were classified as having considerable weight loss at the time of the survey and 60 (63%) where classified without. Most patients were female (81%), American (81%), and mean age was 59 years. 61% of patients indicated not receiving either chemotherapy or radiotherapy at the time of the survey. Patients with weight loss reported significantly (p &lt; 0.05) lower overall quality of life (55.2 vs. 66.9), worsened anorexia-cachexia symptoms/concerns (30.7 vs. 36.0), and higher symptomology, specifically fatigue (64.8 vs. 49.1), nausea (19.5 vs. 9.2), and appetite loss (41.0 vs. 23.9) – than patients without weight loss. In addition, significantly more patients who lost weight reported moderate/high distress levels than patients who did not (71% vs. 38%). For patients with weight loss, change in food taste, fatigue, and decrease in appetite were the most frequently reported symptoms with the greatest impact on their lives. Conclusions: Our results support that weight loss negatively affects cancer patients’ quality of life and is associated with more distress and symptoms—particularly fatigue, and appetite loss. Weight loss-related symptoms also significantly impact their lives. Interventions targeted at maintaining/increasing body weight may help to improve well-being and reduce key symptoms in advanced NSCLC patients with considerable weight loss.
A new strategy for the early detection of colorectal cancer recurrence.
Authors: Afsaneh Motamed-Khorasani, Andrea Lee Small-Howard, Hooman Etemadi
Journal: Journal of Clinical Oncology (2012)

416 Background: Several biological markers have been tested for colorectal cancer (CRC) including CEA; however, they are of limited use for recurrence diagnosis due to low sensitivity. Almost 50% of CRC cases experience recurrence and more than 50% of them have low values not detectable by CEA. Therefore, an effective marker for detection of recurrence will vastly increase the quality of life and survival rate. Onko-Sure is an FDA-cleared blood test that is used for the monitoring of treatment/recurrence of CRC. This ELISA assay measures the accumulation of Fibrin/Fibrinogen Degradation products in the serum using an antibody against the DR-70. The goal of this study was to determine whether the combined usage of DR-70 and CEA will improve the sensitivity for detecting recurrences. Methods: A total of 75 serum samples were retrospectively recruited through a serum bank in two arms including the confirmed healthy control (n=39) and biopsy-confirmed recurrent CRC (n=36) groups. For each patient, the serum sample was tested for DR-70 and CEA concentrations. Results: The results showed sensitivity of 75% and specificity of 58.97% for DR-70 and CEA combined. The cut points were calculated as 1.3ug/ml for DR-70, and 3 or 5ng/ml for CEA for non-smokers and smokers; respectively. For the combined analysis, if either CEA or DR-70 was positive, the test was considered positive and if both tests were negative, the result was considered negative. The sensitivity for the combined test was much better than that of each of the markers alone (35% higher than that of CEA). Conclusions: The combined usage of DR-70 and CEA in monitoring of CRC recurrence showed a significant clinical advantage in terms of sensitivity over each marker alone. Improvement in detection of recurrence has important implications to patient treatment options and prognosis. Should an IVD increase early detection of CRC recurrence when used adjunctively with other available diagnostic markers, the annual deaths due to CRC recurrence could be reduced due to the increase in early detection and the survival rate of those early detections.
A local enrichment of regulatory T cells within the tumor tissue might suppress an effective anti-tumor T cell response in patients with head and neck cancer
Authors: Y. Cao, S. Hegewisch-Becker, I. Blum, K. Bartels, C. Faltz, R. Leuwer, D. Atanackovic
Journal: Journal of Clinical Oncology (2005)

9666 Background: Head and neck cancer has traditionally been regarded as a tumor type exerting a suppressive effect on the T cell-mediated immune system. Here, we examined the expression of a variety of tumor-associated antigens as possible targets for a T cell response in tumors of patients with head-and-neck cancer. Next, we analyzed whether a local accumulation of regulatory T cells within the tumor might contribute to a suppression of an effective immune response. Methods: We analyzed the expression of cancer testis (CT) antigens NY-ESO-1, MAGE-A3, MAGE-C1, MAGE-E1, SSX-1, SSX-2, ADAM2 (CT15), LIP1 (CT17), and HOM-TES-85 in tumor samples and adjacent healthy tissue of patients with head and neck cancer (N=35) using rt-PCR. Furthermore, we analyzed the expression of Foxp3, a marker gene for regulatory T cells (Treg), in tissue samples of the same patients using real-time PCR. For comparison, quantitative PCR for Foxp3 expression was also applied to non-malignant tissue derived from inflamed tonsils of patients who had undergone tonsillectomy (N=11). Results: We observed expression of a variety of CT antigens in tumor tissue derived from patients with head and neck cancer. MAGE-A3 was expressed in 60%, SSX-1 in 37%, MAGE-C1 in 17%, MAGE-E1 in 14%, and SSX-2 in 11% of cases. CT antigens less frequently expressed were HOM-TES-85 in 9%, NY-ESO-1 in 6%, and CT17 in 3% of cases. CT15 was not expressed in any of the tumor samples. None of the healthy tissue samples adjacent to the tumor expressed any CT antigens. Real-time PCR revealed a higher expression of Foxp3 within tumor tissue than within adjacent healthy tissue (p<0.05). Importantly, expression of Foxp3 was not increased in tissue derived from inflamed tonsils, pointing to a specific homing of regulatory T cells into the tumor. Conclusions: Tumors of patients with head and neck cancer express a variety of CT antigens which might serve as targets for a T cell-mediated anti-tumor response. However, a local enrichment of regulatory T cells expressing Foxp3 might contribute to the suppression of such a T cell response. We are currently investigating which local factors lead to an enrichment of regulatory T cells within the tumor. No significant financial relationships to disclose.
Correlation of high density of CD8+and FoxP3+ lymphocytes with overall survival in intestinal-type periampullary adenocarcinoma.
Authors: Carl Fredrik Warfvinge, Jacob Elebro, Margareta Heby, Bjorn Nodin, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2016)

266 Background: Periampullary cancers can be divided into different morphological subtypes where those having an intestinal-type (I-type) morphology have a better prognosis than those with a pancreatobiliary-type (PB-type) morphology. In recent years much focus of antineoplastic research has been directed towards the central role played by various subsets of T-lymphocytes. Yet, very little is known of their role in different subtypes of periampullary cancer. Therefore, the aim of this study was to analyze the density of CD8+ (cytotoxic) and FoxP3+ (regulatory) T-cells in periampullary cancer, with particular reference to their relationship with survival by morphological subtype. Methods: Immunohistochemical expression of CD8 and FoxP3-positive tumor-infiltrating lymphocytes (TILs) was analyzed in tissue microarrays with tumors from 175 consecutive cases of periampullary adenocarcinoma, 110 of PB-type and 65 of I-type morphology, treated with pancreaticoduodenectomy. Kaplan-Meier and univariable and multivariable Cox regression analysis, adjusted for age, T-stage, N-stage, grade, sex, invasion of blood vessels, lymphatic vessels, adjuvant chemotherapy and resection margins were applied to determine the impact of CD8 and FoxP3 expression on 5-year overall survival (OS). Results: In I-type tumors, a high density of CD8+ as well as FoxP3+ TILs was significantly associated with a prolonged overall survival (HR = 0.39, 95% CI 0.19-0.80 and HR = 0.32, 95% CI 0.15 –0.67). The association between high density of FoxP3+ TILs and survival remained significant in multivariable analysis (HR = 0.37, 95% CI 0.17-0.84) while the association between CD8+ TILs and survival did not. The density of CD8+ and FoxP3+ TILs was not prognostic in PB-type tumors. Conclusions: High density of CD8+ and FoxP3+ TILs correlates with a prolonged overall survival in I-type but not in PB-type periampullary adenocarcinomas. Thus, morphological subtype appears to be an important determinant of the prognostic and predictive impact of the inflammatory microenvironment in periampullary carcinoma, and should be considered in future studies.
TH-302 plus gemcitabine (G+T) versus gemcitabine (G) in patients with previously untreated advanced pancreatic cancer (PAC).
Authors: David P. Ryan, Shantan G. Reddy, Nathan Bahary, Hope Elizabeth Uronis, Darren Sigal, Allen Lee Cohn, William R. Schelman, Joe Stephenson, Clarence Eng, Mitesh J. Borad
Journal: Journal of Clinical Oncology (2013)

325 Background: TH-302 is a hypoxia-targeted drug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G+T to standard dose G as first-line therapy of PAC. Methods: An open-label multi-center study of two dose levels of TH-302 (240 mg/m 2 or 340 mg/m 2 ) in combination with G versus G alone (randomized 1:1:1). G (1,000 mg/m 2 ) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G+T arm. The primary efficacy endpoint was a comparison of PFS between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Overall survival (OS) was a secondary endpoint. Results: 214 pts were treated; 163 (76%) Stage IV and 51 (24%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 38% ECOG 0/62% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G+T240; 55% G+T340. Median PFS was 3.6 mo in G vs 5.6 mo in G+T240 (p=0.06) and 6.0 mo in G+T340 (p=0.01). Median OS was 6.9 mo in G vs 8.7 in G+T240 (p=0.83) vs 9.2 mo in G+T340 (p=0.80). 6-mo OS was 57% in G vs 69% in G+T240 (p=0.12) and 73% in G+340 (p=0.04); 12-mo OS was 26% in G vs 37% in G+T240 (p=0.18) and 38% in G+340 (p=0.13). RECIST best response was 10% in G vs 17% in G+T240 and 26% in G+T340. 14 and 12 pts in G crossed over to T240 and T340, respectively. Median post crossover PFS was 1.8 mo in T240 vs 2.9 mo in T340 (p=0.13). Median post crossover OS was 2.6 mo in T240 vs 13.4 mo in T340 (p=0.01). AEs leading to discontinuation were: 16% G, 17% G+T240 and 12% G+T340. Rash (47% in G+T340) and stomatitis (42% in G+T340) were greater in combination, 3 pts Grd 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G+T240 and 63% G+T340 and Grd 3/4 neutropenia were 31% G, 56% G+T240 and 60% G+T340. Conclusions: The combination of G plus TH-302 improved the PFS of G. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. A phase 3 study of TH-302 (340 mg/m 2 ) in combination with G is planned with OS as the primary efficacy endpoint. Clinical trial information: NCT01144455.