tbuckley/cabot-search huggingface dataset:
Phase III trial of carboplatin, etoposide and paclitaxel compared with 5-fluorouracil and folinic acid in adenocarcinoma of unknown primary
Authors: A. van de Wouw, H. F. P. Hillen, C. van der Heul, R. van Hoesel, R. L. H. Jansen
Journal: Journal of Clinical Oncology (2005)

9681 Background: To determine whether treatment with carboplatin, etoposide and paclitaxel (CEP) improves survival, response and toxicity profile in patients with AdenoCarcinoma of Unknown Primary (ACUP) compared to treatment with 5-Fluorouracil (FU) in a continuous schedule and Folinic Acid (FA) (FUFA). Methods: Chemotherapy-naïve patients with ACUP were randomly assigned to receive either CEP (n = 23; paclitaxel 200 mg/m2 and carboplatin AUC 6 iv on day 1 and etoposide alternating 50 and 100 mg orally on days 1 through 10, every 3 weeks) or FUFA (n = 23; folinic acid 500 mg/m2 followed by 5-Fluorouracil 2600 mg/m2 iv over 24 hours weekly for 6 weeks every 7 weeks) Results: Forty-six patients were enrolled; 23 in both treatment arms. Baseline characteristics were well balanced between both arms. No significant differences in survival were observed. The median survival for the CEP arm was 7.0 vs 6.4 months for the FUFA arm (p =0.76) and median time to progression was 3.5 vs 3.3 months (p =0.79). Eighty-three percent (38/46) of the above patients were evaluable for response. CR or PR in CEP vs FUFA arm was recorded in 39 vs 10% (p=0.036) and CR or PR or SD in 60 vs 48% (p=0.14). Two drug-related deaths were reported in the CEP and none in the FUFA arm. CEP caused more frequently grade 3 or 4 neutropenia (9 vs 1 patient), thrombocytopenia (5 vs 0 patient) and neutropenic fever (4 vs 0 patient). Incidences of anemia and nonhematological adverse events were similar in two groups. Remarkable was that 30% in the CEP and 26% in the FUFA arm were long survivors. Conclusions: This study indicates that the combination of CEP improves response rates but does not prolong overall survival or time to progression and is more toxic in patients with ACUP compared to FUFA. Further more there seems to be a subgroup of patients with ACUP who survive longer, independent of the therapy used. No significant financial relationships to disclose.
Prognostic value of Bcl-2 in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
Authors: L. M. Vargas-Roig, F. D. Cuello-Carrión, N. Fernández-Escobar, P. Daguerre, M. Leuzzi, J. Ibarra, F. E. Gago, S. B. Nadin, D. R. Ciocca
Journal: Journal of Clinical Oncology (2008)

602 Background: Bcl-2 has important roles in apoptosis, cell proliferation and cell differentiation in breast cancer. The value of Bcl-2 protein as predictive/prognostic factor to adjuvant treatment in breast cancer has been investigated. However, there are few analyses in a homogeneous group of patients treated with neoadjuvant chemotherapy. We analyzed Bcl-2 in pre- and post-chemotherapy biopsies and correlated its expression with clinical and pathological response, and with disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemotherapy. Methods: One hundred and ten patients were submitted to two different chemotherapeutic regimens: a) fluorouracil, doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) during 2 to 6 cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery (n=40) and b) doxorubicin (D) 75 mg/m2 or epirubicin (E) 120 mg/m2 during 4 cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and fluorouracil after surgey (n=70). Pre- and post-chemotherapy samples were immediately fixed and embedded in paraffin for studies (H&E, immunohistochemistry, TUNEL). Kaplan-Meier method, Wilcoxon signed rank test, Spearman´s rank correlation coefficient, Fisher's exact test, logistic regression and Cox models were used. Results: Bcl-2 expression did not change significantly after chemotherapy and was not related to clinical/pathologic response. The expression of Bcl-2, Bax and p53 evaluated before chemotherapy did not correlate with the clinical and pathologic response. In FAC/FEC group, Bcl-2 expression after chemotherapy correlated with better DFS and OS (p = 0.008 and p = 0.001), and ERα expression showed a tendency to correlate with longer DFS (p = 0.052) but not with OS (p = 0.08). In D/E group, Bcl-2 correlated with better DFS and OS (p = 0.03 and p = 0.054) in the post-chemotherapy biopsies, and ERα was associated with longer DFS (p = 0.004) and OS (p = 0.04). An unusual nuclear localization of Bax was observed in some biopsies, but this localization did not correlate with the tumor response or outcome of the patients. Conclusions: A high Bcl-2 expression had prognostic value in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. No significant financial relationships to disclose.
What do primary and recurrent ovarian cancer patients (OC) expect from their doctors? Final results of a German survey in 608 patients.
Authors: G. Oskay-Özcelik, S. Neubert, K. Münstedt, C. Liebrich, L. C. Hanker, R. Lorenz, P. Wimberger, S. Mahner, H. Hindenburg, J. Sehouli
Journal: Journal of Clinical Oncology (2010)

5106 Background: The following study was conducted to explore the information needs and preferences of OC patients with special focus on doctor-patient communication. Methods: A questionnaire was developed and validated in a phase-I study and was then administered to OC patients via internet (online) or as a print-version. Results: Between 01 and 11/2009 a total of 608 patients were interviewed (181 online, 427 print version). In the online group 97% had an own internet access, 49% in the print group. The median age of the online group was 48 years (range 19-73), for the print group 62 years (26-84). 76% of the patients had recurrent OC. The most effective and “patient-relevant” source of information and explanation of treatment options was the consultation with their physician (88%). All patients judged the therapeutic consultation by their physician on a likert scala (1:very bad,10:very well): Completeness: 8; understanding:8; response to questions: 9; competence of physician: 10; shared decision: 9 and involvement of relatives into therapy decision: 8. When asked to suggest areas for improvement, most frequent answers were: doctors should have more time for explanations (46%); no alopecia under treatment (35%); therapy should be made to be more effective (31%).The most stated answers to “How do you measure the success of a therapy?” were: based on my current well-being (55%); response of the tumour marker CA 125 (45%); based on the feedback that I receive from my doctor (38%). An independent second opinion centre was desired by 70% of the patients, but only 20% know such an institution. Conclusions: This study underlines the high need of ovarian cancer patients to discuss all details about treatment options and clinical management. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fresenius Biotech, GlaxoSmithKline, Medac
Phosphodiesterase type 5 inhibitors (PDE5i) and prostate cancer recurrence.
Authors: Stacy Loeb, Yasin Folkvaljon, David Robinson, Thorsten Schlomm, Hans Garmo, Pär Stattin
Journal: Journal of Clinical Oncology (2016)

55 Background: Phosphodiesterase type 5 inhibitors are commonly used for management of erectile dysfunction after prostate cancer (CaP) treatment. Single-institution studies have reported conflicting data on PDE5i use and recurrence after radical prostatectomy (RP). We re-evaluated the association between PDE5i use after RP and RT with biochemical recurrence in a nationwide, population-based registry. Methods: We performed a nested case-control study using data from the National Prostate Cancer Register of Sweden (including &gt;98% prostate cancer cases nationwide), linked to the national Prescribed Drug Register. Among men with localized CaP who underwent primary RT or RP from 2006-2007 with 5 years of follow-up, we identified those with biochemical recurrence (n=293 cases). For each case, we identified 20 controls who were recurrence-free at the event date of the index case, using incidence density sampling stratified by age and treatment (n=5,767 controls). Multivariable conditional logistic regression was used to examine the relationship between overall PDE5i use and cumulative pill number with biochemical recurrence. Results: Among men treated by RT, PDE5i were not associated with BCR (OR 0.97, 95% CI 0.48-1.94), adjusting for marital status, education, income, PSA, clinical stage, Gleason score, and proportion of positive biopsies. As shown in the table, PDE5i were not associated with biochemical recurrence after RP adjusting for clinical features (OR 0.79, 95% CI 0.60-1.05), or with additional adjustment for surgical pathology (OR 0.83, 95% CI 0.62-1.10). Men whose cumulative number of PDE5i pills was above the median had a slightly lower risk of biochemical recurrence in the clinical model, and no difference in risk of biochemical recurrence after adjustment for RP features. Conclusions: Our results from a population-based setting suggest against an increased risk of biochemical recurrence among men using PDE5i after CaP treatment. [Table: see text]
Measurement of distress in patients with nasopharyngeal carcinoma.
Authors: Y. Jiang, Y. Deng
Journal: Journal of Clinical Oncology (2011)

5547 Background: Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and parts of Southeast Asia, but it is rare in Western countries. Few studies have focused on the distress status in NPC patients. The distress thermometer (DT) is a single-item rapid distress screening tool. The objective of this study was to determine the optimum DT cut-off score that would identify significant distress in NPC patients thus validating its use. Methods: The DT was administered with the Hospital Anxiety and Depression Scale (HADS) in a sample of 156 NPC patients. HADS served as the gold standard against which the DT was compared. Results: The mean distress score for all included 156 NPC patients was 3. Nearly one third NPC patients (36.5%) had distress scores ≥4. Receiver Operating Characteristic (ROC) analysis indicated a DT cut-off score of 3/4 had best sensitivity (0.71) and speciﬁcity (0.83) against HADS. With this cutoff score, DT gave a sensitivity of 0.78, specificity of 0.76 for detecting anxiety against the HADS anxiety scale. And for detecting depression, DT had a sensitivity of 0.75, specificity of 0.75 against the HADS depression scale. The main factors associated with distress were ‘emotional problems’ in the problems list. No demographic or clinical variables were significantly associated with DT score (P<0.05). Conclusions: This study reports on the first validation of the DT as a screening instrument for psychological symptoms in NPC patients. Nearly one third NPC patients had distress scores ≥4.
The status of epidermal growth factor receptor (EGFR) mutations at exon 19 and 21 in Chinese patients with NSCLC
Authors: L. Zhang, X. Zhang, X. Wang, Z. K. Pan, N. Li, J. H. Chang, Z. Z. Guan
Journal: Journal of Clinical Oncology (2005)

7097 Background: Recently, two studies by Paez and Lynch show that somatic mutations in EGFR tyrosine kinase(TK) domain are associated with sensitivity of NSCLC to gefitinib. The mutations were clustered around ATP-biding pocket of the TK domain. Mutations were more frequent in women, adenocacinomas or bronchoalveolar carcinoma (BAC) and non-smoker patients. Interestingly, these studies showed the frequency of mutations is 2%–8% in Caucasian patient population compared to 26% in Japanese patients. Pao also report that 88% of these mutations are located at two “hotspots”(exon 19 and 21). This result also prompted us to perform analysis of EGFR mutations particularly on exon 19 and 21 in Chinese patients. Methods: All patients were pathologically confirmed NSCLC who had not been exposed to gefitinib. Fresh frozen tumor specimens and matched normal tissue were obtained from 56 consecutive patients during surgical operation. DNA was isolated by Proteinase K digestion, followed by traditional Phenol-chloroform extraction procedures. PCR was performed using the Takara Taq™ system (Takara Bio, Otsu, Japan). PCR amplification fragments were then sequenced and analyzed in both sense and antisense directions, using Beckman Coulter CEQ8000 Genetic analysis system and the CEQ™ DTCS Quick Start Kit (Beckman Coulter). Results: Somatic mutations in the TK domain of EGFR were identified from 9 of 56 (16.1%) patients. Among the 9 mutants, 6 showed in-frame deletions in exon 19 (delE746-A750 and delL747-S752). Another 3 showed substitutions leucine to arginine at position 858 (L858R) in exon 21. Mutations were more frequent in BAC (40%) and adenocarcinoma (28%) than in squamous carcinoma (0%), more frequent in women (21.4%) than in men (14.3%), and more frequent in non smokers (23.8%) than in smokers (11.4%). The highest fraction of mutations was detected in women with adenocarcinoma (42.9%). Conclusions: The status of EGFR mutations on exon 19 and exon 21 in Chinese patients with NSCLC are similar to Japanese patients, and the frequency of EGFR mutations in Chinese patients is higher than that in Caucasian patients (16.1% vs 2–8%). No significant financial relationships to disclose.
Effect of VEGF and VEGFR polymorphisms on clinical outcome and response in patients with advanced renal cell carcinoma receiving first-line treatment.
Authors: Maristella Bianconi, Mario Scartozzi, Luca Faloppi, Cristian Loretelli, Antonio Zizzi, Riccardo Giampieri, Alessandro Bittoni, Michela Del Prete, Luciano Burattini, Rodolfo Montironi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2013)

388 Background: For the last few years, sunitinib has been considered the standard treatment for first-line metastatic renal cell carcinoma, but in 2010 a new drug pazopanib had been approved for treatment in this setting. Recent data from the COMPARZ and PISCES study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS and a patients’ preference for pazopanib if we consider quality of life parameters. The aim of our study is to investigate whether polymorphisms of VEGF and VEGFR can influence PFS and OS when patients are treated either with sunitinib or pazopanib as first-line treatment. Methods: 97 histologic samples of mRCC patients were tested for VEGF-A, VEGF-C, and VEGFR-1, 2, 3 single nucleotide polymorphisms (SNPs). Patients’ progression free survival (PFS) and overall survival (OS) were analyzed for first-line treatment. Results: In patients treated with sunitinib VEGF-A rs833061 resulted significant in PFS (CC+CT vs TT, p &lt; 0.0001) and OS (p &lt; 0.0001). VEGF-A rs699947 was significant for PFS (AA+AC vs. CC) p = 0.0001) and OS (p &lt; 0.0001). VEGF-A rs2010963 was significant in PFS (CC vs. CG vs. GG, p = 0.0001) and in OS (p = 0.0045). VEGR3 rs6877011 was significant in PFS (CC vs. CG, p = 0.0075) and OS (p = 0.0001). At multivariate analysis rs833061, rs2010963, and rs68877011 were significant in PFS. rs833061 and rs68877011 were independent factors in OS. In the pazopanib treated groups of patients VEGF-A rs833061 resulted significant in PFS (TT+CT vs. CC p = 0.027) Conclusions: In our analysis patients with CC or CT polymorphism of rc833061 had a favourable PFS and OS if treated with sunitinib instead patients treated with pazopanib seems to have benefit if CT+TT polymorphism, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line with sunitinib. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first-line therapy with sunitinib. Our data seem to suggest that biology could have a role in the choice of first-line treatment for mRCC patients. Further data will be presented at the Symposium.
Back pain and hip pain among survivors of childhood acute lymphoblastic leukemia.
Authors: D. C. Bowers, T. Griffith, L. Gargan, C. Cochran, B. Kleiber, A. Foxwell, A. Farrow-Gillespie, A. Orlino, J. N. Germann
Journal: Journal of Clinical Oncology (2011)

9562 Background: The objective of this study is to determine the prevalence and relative risk (RR) of back pain and hip pain among childhood leukemia survivors and to identify possible risk factors for this pain among childhood acute lymphoblastic leukemia (ALL) survivors. Methods: Surveys were mailed to 5+ year survivors of childhood ALL aged 13 – 25 years. Survivors’ siblings were also invited to participate in the study to serve as a comparison group. Prevalence of back pain and hip pain among ALL survivors was determined and compared with the sibling cohort. Gender, obesity, physical activity, and treatment with radiation therapy were examined for a possible association with back pain and hip pain. Results: 44 of 99 (44.4%) ALL survivors reported experiencing back pain compared with 11 of 52 (21.2 %) siblings (p value = 0.007; RR = 2.01; 95% CI = 1.15 – 3.56). In contrast, 10 of 99 (10.1 %) ALL survivors reported experiencing hip pain compared with 1 of 52 (2.0%) siblings (p value = 0.07; RR = 4.95 (0.65 – 37.57). 60.5% of female ALL survivors reported back pain compared with only 14.3% of female siblings (p = < 0.001; RR = 4.23, 95% CI = 1.66 – 10.82). In comparison, 32.1% of male ALL survivors reported back pain compared with 31.8% of male siblings (p = 0.978; RR = 1.01, 95% CI = 0.049 – 2.08). 20 (45.4%) of 44 ALL survivors who reported back pain and 29 (52.7%) of the 55 survivors who reported no back pain were overweight or obese (p = 0.54). Rates of ALL survivors who reported CDC definitions of moderate and vigorous physical activity were low and were not more frequent among survivors reporting back pain. Treatment with radiation therapy was not associated with back pain. Conclusions: Survivors of childhood ALL have an increased prevalence of back pain. Female survivors appear to be at especially high risk. Future studies are needed to better define the causes of chronic back pain among childhood ALL survivors.
Phase II study of axitinib for downstaging cT2a to cT1 renal tumors for allowing partial nephrectomy (AXIPAN).
Authors: Jean-Jacques Patard, Jean-Christophe Bernard, Karim Bensalah, Herve Baumert, Herve Lang, Didier Jacqmin, Brigitte Duclos, Alain Ravaud, Brigitte Laguerre, Laurence Albiges, Armelle Arnoux, Bernard Escudier
Journal: Journal of Clinical Oncology (2016)

575 Background: Laparoscopic Radical nephrectomy (RN) is the current standard of care for large organ confined renal tumors while partial nephrectomy (PN) is recommended for tumor sizes up to 7 cm. PN preserves long term renal function with possible effect on overall survival. Axitinib, a potent VEGFR TKI can reduce the size of primary tumor in metastatic setting. Our primary objective was to test the ability of axitinib to reduce the size of large tumors for shifting from a RN to a PN indication. Methods: Patients with localized (cT2N0M0) RCCs were enrolled in a prospective phase II trial assessing the effect of neoadjuvant axitinib prior to surgery (PN or RN). Main inclusion criteria were: age ≥ 18, histologically proven clear cell RCC, MDRD creatinine clearance ≥ 60 ml/min, cT2a N0NxM0 tumors ( Ø&gt; 7cm; ≤ 10 cm). Medical treatment consisted in axitinib 5 mg up to 10 mg tw/d during 2 to 6 months prior surgery according to radiological response. Results: A total of 18 patients including 11 men (61%) and 7 women (39%) with a median age of 60 yrs were enrolled. Median baseline tumor size, R.E.N.A.L. score, serum creatinine and MDRD estimated GFR were: 7.5 cm, 11, 0.8 mg/dl and 96.5 ml/min respectively. Duration of treatment was 2, 4 and 6 months in 12 (66%), 3 (17%) and 3 cases (17%), respectively. After neoadjuvant treatment median tumor size and RENAL score decreased to 5.9 cm and 10. 93 % of patients presented a decrease in maximum tumor diameter, with median size reduction of 21.7%. Out of the 17 patients who were operated, 16 (94%) underwent a PN (9 robotic and 7 open), including 84% of the cases which were performed for tumors ≤ 7cm. At 1 month from surgery, median serum creatinine and MDRD estimated GFR were 0.88 mg/dl and 88 ml/min, respectively. Medical and surgical complications rate was 11% including 1 embolization for severe bleeding and 1 Clavien V complication at 1 month after surgery due to massive myocardial infarction. Conclusions: Neoadjuvant axitinib in cT2renal tumors allowed cT1 downstaging and nephron sparing surgery in more than 80% of the cases. However, PN procedures remained high complexity cases requiring adequate surgeon expertise and information of the patients for possible morbidity of these procedures. Clinical trial information: RECF2256.
An analysis of altered melanoma matrix metalloproteinase-23 (MMP-23) expression and response to immune biologic therapy.
Authors: M. Krogsgaard, M. W. Ma, E. B. Friedman, E. Vega-Saenz de Miera, F. Darvishian, A. Perez-Garcia, R. S. Berman, R. L. Shapiro, P. J. Christos, I. Osman, A. C. Pavlick
Journal: Journal of Clinical Oncology (2011)

8541 Background: MMP-23, characterized by its unique ShK and immunoglobulin-like domains, has been shown to downregulate the immune response. The ShK domain selectively blocks the voltage-gated potassium channel Kv1.3 on activated T cells, suppressing T cell proliferation. We hypothesize that increased melanoma MMP-23 expression blunts the anti-tumor response and is associated with poor response to immunotherapy and worse clinical outcome. Methods: Melanoma tissues were obtained from patients treated with immunotherapy and enrolled in a prospective database at New York University Medical Center. Tumor MMP-23 expression was detected by immunohistochemistry and scored for staining intensity (0–3)/distribution (0–2), which were summed to create a composite score (0–5). FACS analysis was used to detect peripheral blood T cell Kv1.3 expression in a subset of patients and scored 0–2. Associations between tumor MMP-23 expression, T cell Kv1.3 expression, clinicopathologic variables, and outcome were evaluated in univariate models. Results: 85 patients (median follow-up: 5.9 years for survivors) with pre-immunotherapy primary tissues available were studied. Dendritic cell vaccines, immune biologics: interferon, GM-CSF, or anti-CTLA-4 therapy were given after primary resection (n=37), at recurrence (n=42), or in both settings (n=6). Primaries with higher MMP-23 composite scores were more mitogenic (p=0.03) and had a lower prevalence of tumor-infiltrating lymphocytes (p=0.05). A weak positive correlation was observed between the tumor MMP-23 composite score and both peripheral blood CD4 and CD8 T cell Kv1.3 expression (r=0.21). Stratified analysis of recurrence risk by immunotherapy type as primary adjuvant treatment showed that higher MMP-23 staining intensity (p=0.02), distribution (p=0.04), and composite score (p=0.004) are associated with a greater risk of recurrence among patients treated with immune biologics but there was no difference among those given dendritic cell vaccines. Conclusions: Our results suggest that tumor MMP-23 expression constitutes a new immune escape mechanism. Data also support its potential utility in guiding immunotherapy selection.