tbuckley/cabot-search huggingface dataset:
Use of elevated IL-1 to predict prognosis in patients with advanced pancreatic cancer with high IL-6 and wasting condition.
Authors: S. Mitsunaga, M. Ikeda, K. Nakachi, I. Ohno, S. Shimizu, H. Takahashi, H. Okuyama, M. Inagaki, J. Furuse, A. Ochiai
Journal: Journal of Clinical Oncology (2011)

e14604 Background: Pro-inflammatory cytokines have been implicated in disease progression in advanced pancreatic cancer (PC). This study aimed to characterize the impact of pro-inflammatory cytokines on prognosis and systemic weakness in patients undergoing chemotherapy for advanced PC. Methods: Patients who were treatment naïve for advanced PC and had no obvious infections were eligible. Serum pro-inflammatory cytokine levels including GM-CSF, IFNγ, IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-α were measured by electrochemiluminescence assay, and a high cytokine level was defined as a value greater than the median value. Body composition was evaluated using bioelectrical impedance analysis. Symptoms, such as fatigue, were rated numerically from 0 to 10 on the Japanese version of the M. D. Anderson Symptom Inventory. Results: From 2008 to 2009, 99 patients (male/female, 53/46; performance status (PS) 0/1/2/3, 68/29/1/1; median age, 66 years) were enrolled. All patients received systemic chemotherapy (GEM/GEM+S-1/GEM+other/S-1, 60/12/11/16). Median levels of serum IL-1 and IL-6 were 0.00 and 1.465 pg/mL. Multivariate analyses for overall survival time revealed that high IL-6 (HR, 2.98; P<0.001) and IL-1 (HR, 2.49; P=0.007) levels were independent poor prognostic factors. The high-IL-6/high-IL-1 group (N=20; HR, 7.26; P<0.001) showed poorer prognosis than the high-IL-6/low-IL-1 group (N=29; HR, 2.46; P=0.007) and low-IL-6 group (N=47; reference arm). Compared to the low IL-6 group, the high-IL-6/high-IL-1 and high-IL-6/low-IL-1 groups, respectively, showed worsened PS (P<0.001, P=0.028), elevated CRP (P<0.001, P=0.002), severe fatigue (P=0.093, P=0.017), decreased Alb (P<0.001, P<0.001), anemia (P<0.001, P<0.001), and loss of lean body mass (P=0.028, P=0.088). Serum CRP level was a good index for assigning patients to the low IL-6 (mean CRP, 0.29 mg/dL; 95%CI, 0.17-0.41), high-IL-6/low-IL-1 (mean CRP, 1.83 mg/dL; 95%CI, 0.61-3.06), or high-IL-6/high-IL-1 (mean CRP, 5.96 mg/dL; 95%CI, 3.28-8.65) groups. Conclusions: Elevated IL-1 predicts the poor prognosis of patients with high IL-6 and wasting condition in advanced PC. CRP was a good index of IL-6 and IL-1 status.
Frequency and current management of erlotinib-related skin effects
Authors: P. Souquet, G. Deplanque, N. Janus, V. Launay-Vacher, C. Robert, C. Mateus, B. Dréno, G. Deray, J. Morere
Journal: Journal of Clinical Oncology (2008)

20627 Background: The most common side effect of Erlotinib (Erl) is skin toxicity. However, there is still no consensus on its management. The French PRECEDE study (PRise En Charge des Effets Dematologiques sous Erlotinib) investigated incidence and management of Erl-related skin effects (ERSE) in lung cancer patients (pts). Methods: Data were retrospectively collected from the medical files of lung cancer pts treated with Erl in 7 cancer centers from January 2005 to December 2007. The preventive and curative management of ERSE and their evolution were recorded. Results: 234 pts were included. For 48.7%, information and education on ERSE was delivered and recorded in the medical file. 65% of the pts (152) developed ERSE: NCI CTC grade 1&2: 30.3 %, grade 3: 2%, grade not available: 67.8%. Among those pts, 32.9% had a dermatologic consultation, 6.6% had a reduction in Erl dosage, and 69.7% were treated with a total of 35 different drugs (204 prescriptions). The most prescribed drugs were oral doxycyclin (22.1% of prescriptions), local erythromycin (18.6%), topical emollient or similar (20.6%), and benzoyl peroxide (7.4%). ERSE improved or resolved in 86.2% of the 152 pts, among whom 64.9% were treated, and 3.9% had persistent skin disorders under treatment (mean duration of 4 months). Conclusions: ERSE are frequent but transient. Patient education and information on ERSE is recorded in the medical file for nearly half of the patients. In most cases, ERSE severity is not graded and referral to a dermatologist is infrequent. Furthermore, prescription habits may differ a lot since as much as 35 different drugs were used to treat ERSE. Clinical guidelines are thus needed to 1) help grading ERSE and 2) standardize their management. No significant financial relationships to disclose.
Evaluation of relapse-free survival in T3N0 colon cancer: The role of chemotherapy—A multicentric retrospective analysis.
Authors: Roberta Grande, Maurizio Cosimelli, Donatello Gemma, Fabrizio Ciancola, Domenico C. Corsi, Lorena Rossi, Isabella Sperduti, Maria Agnese Fabbri, Raffaello Mancini, Enzo Ruggeri, Flavia Longo, Silvia Quadrini, Germano Zampa, Sara Bianchetti, Teresa Gamucci
Journal: Journal of Clinical Oncology (2012)

e14082 Background: Use of adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients (pts) and disease characteristics. According to worldwide guidelines AC should be considered in high-risk (H) T3N0 pts. No data are available for better option in low-risk (L) pts. Aim of the study is to evaluate relapse-free survival (RFS) and disease-free survival (DFS) retrospectively in T3N0 CC pts related to treatment. Methods: RFS and DFS are evaluated with Kaplan Meier method. In order to find the optimal cut off for node number the receiver operating characteristics curve analysis and Maximally Selected Rank Statistics were performed. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15 respectively. Results: 1,000 pts with T3N0 CC were recruited. To date, data of 926 pts are available. Median age was 69 (29-93), M/F 513/413, Grading 1/2/3 46/668/158; 360 L (39%), 411 H (44%), 155 unknown (17%); 137 (15%) pts showed symptoms (S) at diagnosis: 51 pts had perforation (P) or bowel obstruction (BO). Median sampled lymph nodes (LN) were 15 (1-76); 383 (41%) pts were treated with AC. Median follow up (fu) was 5 years (yr) (range 3-24). Survival analysis was performed only for pts with a minimum fu of 3 yr and younger than 80 (80%). 5 yr RFS was 78% and 5 yr DFS was 76% At multivariate analysis S and AC were prognostic factors for RFS. AC is prognostic factor for all endpoints (data are shown in table). In L group 5 yr RFS was 88% in treated pts and 75% in non-treated pts (p 0.03); in H group was respectively 82% and 72% (p 0.006). Conclusions: Preliminary data confirmed the role of known prognostic factors and suggest the relevance of AC also in L stage II T3N0 CC pts. However, the highest risk in L subgroup should be identified to be submitted to AC. Data collection is ongoing, update results will be presented. [Table: see text]
Multicenter study validates PITX2 DNA methylation for risk prediction in tamoxifen-treated, node-negative breast cancer using paraffin-embedded tumor tissue
Authors: N. Harbeck, I. Bohlmann, J. S. Ross, R. Gruetzmann, G. Kristiansen, A. Margossian, A. Hartmann, T. Cufer, A. Paradiso, S. Maier
Journal: Journal of Clinical Oncology (2005)

505 Background: In hormone receptor positive, node-negative breast cancer, many patients receive chemo-endocrine therapy although endocrine therapy alone would have been sufficient in view of their excellent prognosis. In a microarray study, we recently reported that PITX2 methylation correlates strongly with the risk of recurrence after adjuvant tamoxifen. Here, we present results from a large multicenter study initiated to validate PITX2 methylation as an outcome predictor for adjuvant tamoxifen using paraffin-embedded tumor tissue. Methods: A real-time PCR assay was developed to test PITX2 methylation in paraffin-embedded tissue. Matched frozen and embedded samples (n=89) were analyzed to ensure comparability of Results: Then, we analyzed paraffin-embedded tumors of 422 node-negative patients from 9 clinical centers treated with tamoxifen alone; none of the patients had been included in the prior studies. Results: Results from the matched pairs indicated that the assay works well on paraffin-embedded material (correlation coefficient = 0.81). In the independent cohort, PITX2 methylation was strongly correlated with outcome (Cox proportional hazard model, p=0.025). In the group with low PITX2 methylation (45% of the cohort), 98% of the patients were metastasis-free after 10 years, compared to only 85% in the group with high PITX2 methylation. In a multivariate model, PITX2 methylation added significant information to conventional factors such as tumor size, grade, and age. Conclusions: This study validates PITX2 methylation as outcome predictor after adjuvant tamoxifen. Together with our previous studies, we have now analyzed over 750 patients, using two different Methods: In all studies, PITX2 methylation was consistently associated with poor outcome. Furthermore, we have now shown that PITX2 methylation can be reliably measured in paraffin-embedded tissue. The results provide substantial evidence that PITX2 DNA methylation is suitable for routine clinical use in order to predict outcome in node-negative, tamoxifen-treated patients, and to identify low-risk patients who can be spared the burden of additional cytotoxic therapy.
Ki-67 expression in residual triple-negative breast tumors after neoadjuvant chemotherapy to predict for recurrence-free survival.
Authors: Joseph A. Pinto, Franco F. Doimi, Justin M. Balko, Carlos L. Arteaga, Henry L. Gómez
Journal: Journal of Clinical Oncology (2012)

89 Background: Ki-67 expression in breast cancer has been described as predictive of pathological complete response and prognostic of recurrence free survival (RFS). Our aim was to evaluate in a retrospective cohort of triple negative breast cancer patients if tumor proliferation measured by ki-67 expression is correlated with the outcome. Methods: We evaluated a retrospective cohort of 109 cases of triple negative breast cancer (ER-, PR- and HER2- determined by immunohistochemistry). Ki-67 labeling index was determined in Formalin-Fixed, Paraffin-Embedded residual tumors after neoadjuvant chemotherapy. Patients were stratified in Ki67&lt;15% and Ki67≥15%. Clinicopathological data was retrieved from clinical records. RFS and overall survival (OS) were calculated using the Kaplan–Meier method and variables compared using the log-rank or Breslow test and Hazard Ratios (HR) estimated by the Cox regression. Results: The median age for patients was 47.5 years, 55 (50.5%) were premenopausal and 54 (49.5%) postmenopausal. Eight patients (7.3%) were clinical stages II and 101 (92.7%) stages III. Median of Ki-67 expression was 35.97% (0.96% - 77.7%). There was not association between Ki-67 expression (&lt;15% VS ≥15%) with tumor size, nodal involvement, clinical stage and menopausal status. After a median of follow of 21.6 months, 62 patients (56.9%) have relapsed and 53 (48.6%) have die. The median time for RFS and OS were 21.2 and 31.4 months, respectively. Median of RFS was 12.6 months for Ki67&lt;15% vs 21.2 months for Ki67≥15%, P=0.421 (HR=0.91). Median of OS was 34.9 months for Ki67&lt;15% vs 31.4 months for Ki67≥15%, P=0.755 (HR=1.18). Only nodal involvement was found predictor of shorter RFS (0 nodes, 25.2 months vs 1 -3 nodes, 26.1 months, vs &gt;3 nodes, 9.4 months, P=0.020). Conclusions: Ki-67 labeling index was not related with the outcome in terms of OS and RFS in patients with residual triple negative breast tumors that were treated with neoadjuvant chemotherapy.
Overcoming barriers to accrual: An assessment of 1,187 cancer patients’ (Pts) and caregivers’ awareness of and willingness to participate in cancer clinical trials (CCTs)
Authors: A. Umutyan, P. N. Lara, C. Chiechi, C. Turrell, M. S. Chen, D. A. Paterniti, T. Wun, S. Davis, J. Gonzalez, L. A. Beckett
Journal: Journal of Clinical Oncology (2005)

6016 Background: Only 3% of pts participate annualy in CCTs. Barriers to accrual include lack of CCT awareness and uncertain third party payer coverage. In January 2002, a new California law (Senate Bill 37 [SB37]) required all third party payers to reimburse pt care costs related to CCTs. We evaluated the level of awareness of pts and/or their caregivers regarding CCTs and SB37. Methods: We employed both a written survey for pts and/or caregivers seen for the first time in an oncology clinic within the UCDCC catchment area, and a verbal telephone version for callers to the CIS. We used Spearman’s correlation and Pearson’s Chi-Square to test for correlations between CCT “awareness” (subjects had heard of CCT and agreed that it tests the safety and usefulness of a new drug)/SB37 knowledge, and willingness to participate in CCTs. Logistic regression was performed to assess predictive variables for awareness and willingness to participate. Results: Of the 1,187 respondents, 59% were aware of CCTs, 19% knew of SB37, and 33% were very likely to consider a CCT. There were significant positive correlations between CCT awareness and willingness to participate (p<0.0001, Spearman), and between SB37 knowledge and willingness to participate (p=0.0012, Pearson Chi-square). Reduced awareness of CCTs was seen in respondents who were either Black (odds ratio [OR] 0.44, p=0.0036), Hispanic (OR 0.56, p=0.03), had an annual income <$25,000 (OR 0.38, p<0.0001), or had less than a college degree (OR 0.12 to 0.53, p<0.0001 to 0.013). Reduced willingness to participate in CCTs was seen in respondents who were either Black (OR 0.38, p<0.0001), or Asian (OR 0.44, p<0.0057). Conclusions: Improving clinical trial awareness and SB37 knowledge, especially among lower income, less educated, and minority pts, may potentially overcome barriers to CCT participation and subsequently increase accrual in California. (R21 CA10172; VANCHCS; ACS CRTG 00197101CCE to PNL) No significant financial relationships to disclose.
Vinorelbine plus oxaliplatin in unfit patients (pts) with stage IV non-small cell lung cancer (NSCLC)
Authors: O. Mir, J. Alexandre, S. Ropert, J. Durand, I. Martin, V. Montheil, F. Goldwasser
Journal: Journal of Clinical Oncology (2008)

19064 Background: Most pts with stage IV NSCLC are unfit for cisplatin-based chemotherapy. We investigated the feasibility of a combination of weekly vinorelbine and biweekly oxaliplatin in this population, with an increased dose-intensity (DI) of vinorelbine in comparison with the previous multicenter phase II study (Monnet I. et al. Ann Oncol 2002; 13(1):103–7.). Methods: From Oct. 2003 to Oct. 2007, 55 chemo-naive pts (40 males, median age 60 yrs, range 43–84) received, in the outpatient setting, every 2 weeks: vinorelbine 26 mg/m2 IV d1 and 60 mg/m2 p.o. d8, oxaliplatin 85 mg/m2 IV d1. They were unfit for cisplatin because of PS ≥ 2 (30 pts), impaired renal function (17 pts) or severe comorbidities (8 pts). 22 (40%) pts had ≥ 2 metastatic sites and 14 (25%) had brain metastases. Results: 288 cycles were given (median per pt: 4, range 1–11). The planned vinorelbine DI was given in 65% of pts. One complete and 13 partial responses were observed, providing an objective response rate of 25% [95% confidence interval (CI) 14.6–38.3]. The median progression free survival and overall survival were 3.5 months and 9.5 months, respectively. The 1-year survival rate was 24% (95%CI: 12.7- 42.5). The main grade 3/4 toxicities were: neutropenia (15 pts, 27%), anemia (12 pts, 22%) and peripheral neuropathy (8 pts, 15%). Three patients (5.5%) experienced febrile neutropenia. Conclusions: Thevinorelbine-oxaliplatin doublet is active in poor prognosis NSCLC pts. This combination allows increased DI of vinorelbine in unfit pts. No significant financial relationships to disclose.
Correlation of postoperative CEA trends with survival and patterns of recurrence after hepatectomy for colorectal cancer metastases.
Authors: Lawrence Andrew Shirley, Megan McNally, Justin Huntington, Natalie Jones, Lavina Malhotra, Mark Bloomston, Carl Richard Schmidt
Journal: Journal of Clinical Oncology (2012)

436 Background: Pre-operative carcinoembryonic antigen (CEA) level is associated with outcome after hepatectomy for colorectal cancer metastases. In this study we sought to determine the relationship between post-operative CEA and outcome after hepatectomy. Methods: A single institution retrospective review of hospital records from 1993 to 2010 found 339 patients who underwent a liver resection for CRC metastases. Of these, 140 had CEA levels drawn pre-operatively, post-operatively, and at least once more in follow-up. A ΔCEA level was calculated by subtracting the initial post-operative CEA level from the highest CEA level drawn in follow-up. Outcomes were compared between patients with ΔCEA less than 5 and greater than 5. Results: Of 140 patients, 61 had ΔCEA less than 5 and 79 had ΔCEA greater than 5. Patients with low ΔCEA had improved median overall survival (OS) (70.2 months) compared to those with high ΔCEA (38.7 months, P=0.0001). However, there was no significant difference in progression-free survival (PFS) (13.0 months vs. 12.3 months, P=0.982). 100 patients had recurrence after hepatectomy, 69 with high ΔCEA and 31 with low ΔCEA. Patients with low ΔCEA were more likely to have a single site of recurrence (77.4% vs. 53.6%, P&lt;0.0001). Conclusions: Although a rising CEA after hepatectomy for CRC metastases is associated with worse overall survival, there is no difference in progression-free survival between patients with rising CEA and those with stable-to-decreasing CEA. Patients with stable-to-decreasing CEA have patterns of recurrence more amenable to locoregional therapy. Post-operative CEA values are an important component of oncologic surveillance, and patterns of rise and fall may indicate patterns of recurrence.
Outcomes in patients with high-risk prostate cancer treated with definitive versus adjuvant radiation therapy.
Authors: Vasu Tumati, Corbin Jacobs, James Ying, Claus G Roehrborn, Yair Lotan, Vitaly Margulis, David A. Pistenmaa, Dong W. Kim, Raquibul Hannan
Journal: Journal of Clinical Oncology (2016)

133 Background: 20% of men with prostate cancer (PCa) are diagnosed with high-risk disease. The optimal therapy for these patients, prostatectomy followed by adjuvant radiation therapy (ART) or definitive radiation with androgen deprivation (DRT), is still unclear. Previous randomized trials failed to accrue; therefore we sought to answer this using an IRB-approved retrospective cohort study. Methods: High-risk PCa was defined using NCCN criteria. Adjuvant radiation was defined as radiotherapy started within 6 months of prostatectomy. Biochemical progression-free survival (BPFS), castrate resistance-free survival (CRFS), distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were calculated using Kaplan-Meier estimates. Biochemical failure was defined using the AUA definition in the ART group and by the Phoenix definition in the DRT group. Castrate resistance was defined as ≥2 episodes of rising PSA with testosterone &lt;50 ng/ml or rising PSA despite second line anti-androgen. Statistical analysis was performed using log rank and Cox testing. Results: 60 men with high-risk PCa treated between 1992-2011 were included in the ART group and 154 men were included in the DRT group. 58% of men in the ART group received short course of androgen depravation therapy (ADT). Nearly all men received 2 years of ADT in the DRT group. The median follow up for the ART group was 62 months and 55 months for the DRT group. Men in ART group were younger (p&lt;0.0001) and had a lower pre-treatment PSA (p=0.0338). Log rank testing revealed the ART group had worse BPFS (5 year: 57% vs. 71%; p=0.008), but there was no difference in the other endpoints including CRFS (p=0.9693), DMFS (p=0.7345), PCSS (p=0.5481), or OS (p=0.2557). On multivariable analysis ADT use, ADT length, type of treatment, and stage were not predictive of BRFS whereas Gleason score was (p=.0001). Conclusions: This study suggests that for high-risk PCa patients there is no difference between DRT and ART with regards to BPFS, CRFS, DMFS, PCSS, or OS. Therefore, over a short follow-up period, there does not appear to be a difference between these approaches. Prospective trials are required to validate this finding.
Antiandrogen withdrawal (AAWD) in patients (pts) with prostate cancer (PCa): Retrospective analysis of data from the South Australian Prostate Cancer Clinical Outcome Collaborative (SA-PCCOC).
Authors: Sina Vatandoust, Ganessan Kichenadasse, Michael E O'Callaghan, Tina Kopsaftis, Scott Walsh, Martin Borg, Christos Stelios Karapetis, Kim L Moretti
Journal: Journal of Clinical Oncology (2015)

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p&lt;0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p &lt;0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p&lt;0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.