tbuckley/cabot-search huggingface dataset:
Triple-negative breast cancer with extracapsular extension of axillary lymph node metastasis: Prognostic value.
Authors: S. Maksimovic
Journal: Journal of Clinical Oncology (2010)

e11522 Background: Triple-negative breast cancers (TNBC) are defined by a lack of expression of estrogen, progesterone, and ERBB2 receptors. We compare the clinical features and prognosis of association of TNBC with extracapsular extension of axillary lymph node metastasis. Methods: From January 2000 to December 2009, 591 patients with breast cancer were operated on in General Hospital Sveti Vracevi in Bijeljina. We selected 301 (50.9%) patients with breast cancer who had metastases to axillary lymph nodes. Results: Extracapsular extension (ECM) was found in 122 (40.5%). Eighty-three patients (14%) were classified as TNBC. The patients were identified and divided into two groups: 22 patients with TNBC with extracapsular extension of axillary lymph node metastasis (TNBCECM) and 14 patients with TNBC without extracapsular extension of axillary lymph node metastasis (TNBCICM). 49 patients (40.1%) were identified with three or less lymph nodes involved, 30 patients (24.5%) patients four to six, 24 patients (19.6%) seven to nine, and 19 patients (15.5%) ten or more nodes, respectively. Total number of lymph nodes showing ECM were also significantly more in the TNBCECM (48 of 81, 59.25%) vs. (13 of 60, 21.66%) in the TNBCICM group (p < 0.001). With a median follow-up of 108 months factors with independent prognostic value for disease-free survival by multivariate analysis included TNBC with extracapsular extension (p < 0.005), pN category (p < 0.01), and presence of lymphovascular invasion (LVI; p < 0.005). An independent negative prognostic effect on overall survival was observed for TNBCECM (p < 0.05), pN category (p < 0.05), and presence of LVI (p < 0.005). The time between first relapse and death was also shorter in TNBCECM: 8.1 months vs. 21.5 months in TNBCICM (p = 0.03). Conclusions: New strategies in the search for effective treatment options for patients with TNBC have focused on both new chemotherapy regimens and targeted therapies. In patients TNBCECM prognosis was significantly worse compared with those who were TNBCICM. These findings have led to the conclusion that TNBC is associated with a more aggressive subtype of cancer. No significant financial relationships to disclose.
Use of preoperative tattooing to increase lymph nodes (LNs) retrieved in patients with locally advanced rectal cancer who receive preoperative chemoradiotherapy (CRT): A randomized controlled trial.
Authors: Kazutake Okada, Sotaro Sadahiro, Toshiyuki Suzuki, Akira Tanaka, Gota Saito, Akemi Kamijo
Journal: Journal of Clinical Oncology (2014)

561 Background: Retrieval of 12 or more LNs has been recommended for accurate staging of colorectal cancer. Patients with 12 or more LNs revealed better survival than those with less than 12 LNs. Preoperative tattooing has been reported to improve LNs retrieval in colorectal cancer. Preoperative CRT had been reported to decrease the number of LNs in rectal cancer. We conducted a randomized controlled study to validate whether preoperative tattooing increases the number of LNs in patients who receive preoperative CRT. Methods: Fifty patients with cStage II or III rectal cancer were randomly assigned to a group in which tattooing was performed at the time of colonoscopy one day before surgery (T group) or a group without tattooing (C group). Submucosal injection of India ink was performed into two sites at the lower tumor margin. All patients had received 40/45 Gy of radiotherapy in 20/25 fractions with concurrent oral UFT or S-1 chemotherapy. Mesorectal excision was performed 6 to 8 weeks after completion of CRT. Results: There were no significant differences in characteristics between the groups. The numbers of retrieved LNs (mean±SD) in T group and C group were 14±7 and 8±6, respectively (p &lt; 0.01). The number of patients with 12 or more LNs was greater in T group (56%) than in C group (20%) (p &lt; 0.01). The numbers of metastatic LNs were similar in both groups (0.5±1.2 and 0.5±1.4, respectively p = 0.92). In patients with poor histologic tumor regression (TRG grade 3 to 5), the number of LNs was significantly greater in T group (17±9) than in C group (6±5; p &lt; 0.01). However, in patients with good histologic response (TRG grade 1 or 2), the numbers of LNs in T group and C group were 11±5 and 9±6, respectively (p = 0.31). In T group, the numbers of LNs and metastatic LNs were significantly greater only in patients with poor histologic regression. Conclusions: Preoperative tattooing increases the number of retrieved LNs. In patients with poor histologic response following CRT, tattooing significantly increases the numbers of LNs. However, tattooing does not increase the numbers of retrieved LNs and metastatic LNs in patients with good histologic response. Clinical trial information: 11R-004.
Process and outcome indicators for evaluation of surgical activity in a high-risk gastric cancer area.
Authors: O. Nanni, M. Altini, P. Morgagni, A. Rossi, E. Ciotti, F. Falcini, M. Maglie, A. Berardo, G. Vittimberga, P. Falasca, E. Prati, D. Garcea, D. Amadori
Journal: Journal of Clinical Oncology (2011)

e16537 Background: Numerous studies have been published on the relationship between hospital volume and quality of results in oncologic surgery. However, the relative importance of hospital volume in various surgical procedures is open to discussion because of study design heterogeneity. Differences in patients and provider characteristics can make volume appear to have a greater influence on outcome than it actually does. We aimed to identify appropriate process and outcome indicators to detect high quality providers and to assess the real role of hospital volume in clinical outcome in gastric cancer surgery procedures. Methods: We retrospectively collected data from 1680 gastric cancer patients who underwent total/subtotal gastrectomy in public/private hospitals in Romagna (population of about 1 million, 7 general hospitals and 8 private clinics, all with surgery units) from 2004 to 2008. Data on duration of hospitalization, patient characteristics, comorbidities, diagnosis, surgical intervention, lymph nodes removed and lymph node stations dissected were collected from electronic hospital records. Hospital performance indicators were hospital procedure volume and procedure volume for each surgical unit and for each surgeon. Provider factors were staffing levels and hospital facilities. Main clinical outcome measures were operative mortality, 30-day mortality, overall survival and complications. Results: 88.3% of the surgical activity was concentrated in general hospitals. More than 80% of patients were referred to their nearest general hospital. 30-day mortality rate was 7.26% and was inversely correlated with hospital volume. The median duration of hospitalization varied between 11 and 24 days and was lower in hospitals with a higher number of gastric cancer patients. Conclusions: Our results did not identify a reference center for gastric cancer surgery in Romagna but did highlight the need to improve the quality of surgical care, including increased health regionalization and development of common protocols for surgery procedures. A more complete analysis taking into account patient characteristics and hospital facilities is ongoing. Partially funded by Istituto Oncologico Romagnolo.
Pharmacodynamic analysis of target receptor tyrosine kinase activity and apoptosis in GIST tumors responding to therapy with SU11248
Authors: D. W. Davis, D. J. McConkey, J. V. Heymach, J. Desai, S. George, J. Jackson, C. L. Bello, C. Baum, D. R. Shalinsky, G. D. Demetri
Journal: Journal of Clinical Oncology (2005)

3006 Background: Most GIST lesions contain activating mutations in the receptor tyrosine kinases, KIT and/or PDGFR. SU11248 is an oral, multitargeted tyrosine kinase inhibitor of KIT, PDGFR, and VEGFR-1, -2 and -3 active against imatinib-resistant GIST. We report here effects of SU11248 on endothelial and tumor compartments in GIST. Methods: Paired tumor biopsies were obtained from 19 GIST patients (pts) undergoing phase 1/2 therapy with SU11248 (Proc. ASCO 22:A3001, 2004). Biopsies were collected at baseline before and after at least 14d of treatment with SU11248 in the first cycle of treatment. Biopsies were examined using immunofluorescence coupled with laser scanning cytometry to quantify endothelial and tumor cell apoptosis, microvessel density (MVD), and the phosphorylation of PDGR-β and other RTKs. Results: Eight of 19 pairs of tumor samples came from patients who had clinical benefit (CB), defined as either partial response (PR) by RECIST criteria or stable disease (SD) for >6 months and 11 from pts with progressive disease (PD). Compared with baseline, tumors from pts with CB had a significant decrease of 15.0±0.03 % (SD; p=0.016, t-test) in phosphorylated PDGFR-β activity in the tumor cell compartment whereas tumors in non-responders had an increase in PDGFR-β activity of 11.0±0.17%. Two pts had PR and six had SD, corresponding to a 23 and 11% decrease in phosphorylated PDGFR-β activity, respectively (p<0.05). Overall, tumors in pts with CB displayed a 3.6- and 6-fold (p<0.05) increase in endothelial and tumor cell apoptosis, respectively. In contrast, tumors in pts with PD had little or no change in endothelial and tumor cell apoptosis from baseline. Conclusions: PDGFR-β phosphorylation was significantly decreased in tumor biopsies from GIST pts treated with SU11248 who had CB but not in those who had PD. Activities of other target RTKs are under investigation and will be presented. These data demonstrate that SU11248 inhibits PDGFR-β activity in addition to other RTKs in GIST. We hypothesize that SU11248 exerts direct antitumor and indirect antiangiogenic effects in GIST as the basis for its anticancer efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Academic Institutions, Pfizer Pfizer Inc.
Rate of infection and immunosuppression in two phase III studies of denileukin diftitox (DD) in cutaneous T-cell lymphoma (CTCL).
Authors: F. Lansigan, F. M. Foss
Journal: Journal of Clinical Oncology (2010)

e18515 Background: CTCL patients are at increased risk for infection because of the disruption of the skin barrier and immunosuppression due to the disease itself. Infection is the cause of death in 30%-60% of patients and cytotoxic chemotherapies used for advanced and refractory patients are associated with myelosuppression and further compromise of immune function. Methods: We evaluated immunosuppression and infections in 223 patients with stage Ia-III CTCL treated with DD or placebo (PBO) in two multicenter clinical trials. In both trials, DD was administered in doses of 9 or 18 μ g/kg IV, daily for 5 days, every 21 days for up to 8 courses. Evaluations included absolute lymphocyte count (ALC), absolute neutrophil count (ANC), and rate of infection in patients with mycosis fungoides (MF, n=201) and Sezary syndrome (SS, n=22). Results: Of 223 patients, 43 received PBO, 43 DD 9 μ g/kg, and 137 DD 18 μ g/kg. Repeated courses of DD were not associated with immunosuppression as manifested by fungal, viral, or bacterial infections. Infections experienced by CTCL patients with MF decreased steadily from course 1 to course 8: 1.347 to 0.086 events per patient, 1.293 to 0.059, and 0.452 to 0.125 for DD responders, DD nonresponders, and PBO nonresponders respectively. ALC decreased in DD patients during the first treatment course, then rebounded and remained at normal levels after course 2. ANC increased during the first course, but returned to normal thereafter. Adverse events generally showed a pattern consistent with the status of the CTCL disease. Conclusions: In these clinical trials, DD does not appear to be immunosuppressive by ALC and ANC. Infections experienced by CTCL patients did not increase in frequency with continued exposure to DD compared to placebo. DD does not further compromise immune function in CTCL patients. Median ALC and ANC for patients with MF PBO 9 μ g 18 μ g Cycle n ALC ANC n ALC ANC n ALC ANC Baseline 37 1.5 4.4 39 1.7 4.5 125 1.6 4.0 1 37 1.3 4.0 37 0.8 7.0 124 0.8 5.8 2 36 1.2 3.5 32 2.0 3.2 106 1.8 3.2 4 27 1.3 3.1 29 1.6 3.8 84 1.6 3.1 6 15 1.3 3.3 22 1.5 3.7 62 1.5 3.1 8 11 1.4 3.4 20 1.5 4.1 55 1.4 3.1 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai
Role of basal inflammatory status as a predictor of survival in bevacizumab-treated advanced non-small cell lung cancer (NSCLC) patients.
Authors: C. Botta, A. Guglielmo, E. Bestoso, S. Apollinari, A. Licchetta, P. Blardi, P. Tassone, G. Chiriaco, V. Barbieri, G. Mantovani, P. Tagliaferri, P. Correale
Journal: Journal of Clinical Oncology (2011)

7582 Background: At present, there is a great concern for the toxicity and costs associated with anti-VEGF Bevacizumab (Bv) mAb use in lung cancer treatment, underscoring the need of biomarkers predictive of Bv activity. We investigated the predictive value of several biologic parameters correlated with VEGF pleyotropic activity in NSCLC patients, enrolled in the ongoing phase II mPEBev trial (EUDRACT#2008-00-6051-40), who had received cisplatinum-based chemotherapy in combination with Bv (5mg/kg), between December 2008 and January 2010. Methods: Clinical and biologic variables from fifty-three metastatic NSCLC patients undergone frontline-ciplatinum-based chemotherapy and Bv were evaluated for their capability to predict longer progression-free-survival(PFS) and survival(OS). The Student-t test, Kaplan Meier survival curves and Cox regression analysis were performed to evaluate the correlation among variables and outcome. Results: These patients presented a 80% response rate and a median PFS and OS of 8 (CI 95% 6.192-9.808) and 15 (CI 95% 10.660-19.340) months, respectively. In our series, a specific inflammation profile, defined by baseline neutrophil counts >7500 cells/dl (9.53 vs 19.61 months; P=0.003); and monocyte counts >550 cells/dl (10.22 vs 18.00 months; P=0.018), resulted highly predictive of worse prognosis. A multivariate analysis showed a Hazard Ratio of 2.73 (CI 95% 1.086-6.871) for the first marker, and 2.39 (CI 95% 1.011-5.664) for the second. Furthermore, baseline Interleukin-10 concentration >10 mg/ml was also predictive of a worse survival (8.8 vs 20.76 months; p=0.007). Histotype, metastatic sites, sex, age, VEGF levels, lymphocyte and platelet counts did not show predictive value. Conclusions: The results of our study suggest that the baseline inflammatory status in NSCLC patients may affect Bv activity and patients’ survival and also identified three potential independent bio-markers able to predict the outcome of NSCLC patients receiving Bv which warrant prospective evaluation.
Further enhancement of natural killer (NK) activities and interferon (IFN)-gamma production by recombinant human interleukin-12 (rhIL-12) in the patients with renal cell carcinoma (RCC) during the treatment with IFN-alpha compared with before the treatment
Authors: N. Meguro, T. Kinouchi, O. Maeda, S. Saiki, M. Kuroda, M. Usami, T. Kotake
Journal: Journal of Clinical Oncology (2008)

16068 Background: We examined whether rhIL-12 may be immunostimulatory in vitro to the patients with RCC, and the prior treatment of IFN-alpha in vivo could enhance the antitumor immunity of rhIL-12 in vitro. Methods: The median age of 47 patients was 60 years (range, 42 to 79 years). The peripheral blood lymphocytes (PBLs) from patients were cultured with rhIL-12 at the concentration of 0.1 to 100 U/ml for 18 hours. The IFN-gamma in supernatants was measured by ELISA assay, and NK activity of PBLs was assayed against K562. Of 47 patients, NK activities and/or induction of IFN-gamma production before and 3 weeks after IFN-alpha therapy were assayed in 13 patients. Results: NK activities and IFN-gamma production were enhanced significantly by rhIL-12 in a dose dependent manner in 44 of 47 patients, and 34 of 40 patients, respectively. There was not a significant difference among the variables including sex, PS, histological grade, tumor stage, and the presence of metastasis between the positive group and negative group. The NK activities of 34 patients with IFN-gamma production were significantly higher than those of 6 patients without IFN-gamma production. Among 13 patients treated with IFN-alpha, NK activities after IFN-alpha treatment were further enhanced by the addition of rhIL-12 than those at the same concentrations before IFN-alpha treatment. The induction of IFN-gamma production before and after IFN-alpha treatment was assayed in 5 patients, and 3 patients were induced to produce IFN-gamma by rhIL-12 before IFN-alpha treatment, but other 2 patients who were not before IFN-alpha treatment, were induced significantly to produce IFN-gamma by rhIL-12 after IFN-alpha treatment, and also the NK activities of these 2 patients were enhanced by rhIL- 12 after IFN-alpha treatment compared with those before IFN-alpha treatment. Conclusions: We demonstrated that rhIL-12 could enhance the antitumor activities in patients with advanced RCC, and suggest the combined treatment of rhIL-12 and IFN-alpha might be feasible in the clinical setting. No significant financial relationships to disclose.
Dosimetric study of 3-dimensional conformal radiotherapy, electronic compensator technique, intensity modulated radiation therapy, and volumetric arc therapy in whole-breast irradiation.
Authors: Chonnipa Nantavithya
Journal: Journal of Clinical Oncology (2015)

44 Background: Whole breast irradiation is an essential treatment after breast conserving surgery (BCS). Adverse effects are from inhomogeneity of PTV and excessive dose to normal tissues. Aim of this study is to compare dosimetry among standard technique, three-dimensional Conformal Radiotherapy (3D-CRT) and advanced techniques, Electronic Compensator (ECOMP), Intensity Modulated Radiation Therapy (IMRT) and Volumetric Arc Therapy (VMAT). Methods: Images from CT simulation of patients who underwent BCS were replanned. Clinical Target Volume (CTV) was contoured followed RTOG atlas as breast only and breast with chest wall respectively. Planning Target Volume (PTV) was expanded 0.7 cm from CTV. Each patient was replanned with all four techniques. Dose prescription was 50 Gy in 25 fractions. Results: Twenty five patients underwent CT simulation from November 2013 to November 2014 were included. Six patients with node positive were planned for breast with chest wall irradiation and 19 patients with node negative were planned for breast only irradiation. Primary outcome, homogeneity index (HI) of 3D-CRT, ECOMP, IMRT and VMAT were 0.865, 0.889, 0.890 and 0.866 respectively which ECOMP and IMRT were significant higher than 3D-CRT (p values &lt; 0.001). Secondary outcome, conformity index (CI), Mean heart dose (MHD), heart V25, heart V30, mean lung dose (MLD), mean ipsilaterallung dose (MILD), mean contralateral lung dose (MCLD) and mean contralateral breast dose (MCBD) of advanced techniques were significant better than 3D-CRT technique. Conclusions: HI of ECOMP and IMRT were statistically significant higher compared with 3D-CRT technique. Advanced techniques showed statistically significant superior in CI dose to heart, lungs and contralateral breast.
Retrospective cohort study of patients with anal cancer treated over a 12-year period at a large Canadian cancer center.
Authors: Michael J. Abunassar, Jordan Reinders, Derek J. Jonker, Timothy Asmis
Journal: Journal of Clinical Oncology (2014)

606 Background: While optimal management of anal cancer has become better defined in light of recent clinical trials including selected patients, the outcomes in an unselected population are less well defined. We reviewed the outcomes of anal cancer patients in a population referred to a sole-provider regional cancer program at the Ottawa Hospital over a 12 year period (2000 to 2011). Methods: Patient data was collected from hospital records, including demographic, treatment and outcome. Outcomes of interest included overall and recurrence free survival, as well as colostomy free survival. Results: Patients were 72% (n = 130) female and 28% (n = 50) male, 6.6% (n = 12 males) HIV positive, 60% (n = 108) ever smokers, mean age 62 [range 35-90] years. Most frequent presenting symptoms were blood per rectum (87%) and anal pain (80%). Treatment intent was curative in 87%. Treatment included radiotherapy (94%), brachytherapy (26%), chemotherapy (73%). Combined chemoradiotherapy was received by 71%, including MMC-5FU (n = 87) and cisplatin+5FU (n = 41). Among patients treated with curative-intent, 72% had a complete response, 31% local/regional recurrence, 16% required salvage surgery and 21% had distant recurrence. Colostomy rate was 23%. 5 year overall survival (OS) was not significantly different for patients by HIV status; 52 vs. 60% for HIV positive vs negative, respectively, HR 1.36, p = 0.47. Survival was superior if MMC+5FU was used first vs. Cisplatin+5FU; 5yOS 73 vs 46% respectively, [HR 0.45 (95%CI 0.25 – 0.83), log rank p = 0.013]. Conclusions: The outcomes of patients in this large retrospective cohort study are similar to the outcomes of patients in highly selective clinical trials. Five year overall survival and colostomy free survival are encouraging. MMC +5FU was found to be superior to Cisplatin +5FU. Further study is required to improve outcomes for patients with metastatic disease.
Mutational load distribution analysis of colorectal and pancreatic carcinoma by next generation sequencing platform.
Authors: Adriana Lopez-Doriga, Daniel Azuara, Mireia Morell, Javier de Oca, Francisco Rodriguez-Moranta, Joan Fabregat, Jaume Boadas, William Larochelle, Gabriel Capella, Jose Costa
Journal: Journal of Clinical Oncology (2012)

57 Background: It has been suggested that the sequential analysis of the mutational spectra at loci involved in the pathogenesis of tumors (mutational load distribution analysis [MLDA]) may reflect the biology of the tumor and/or the risk of cancer before the tumor emerges. Metrics derived from MLDA could assist quantifying risk, in early diagnosis, and in monitoring response to therapy. The aim of this study was to assess the efficacy of the NGS platform to obtain clinically relevant metrics derived from MLDA. Methods: Two sets of DNA samples were assessed: (i) 6 paired tumor/normal colorectal carcinomas and 8 colorectal adenomas; and (ii) 21 pancreatic carcinoma and 6 non-matched normal pancreas. Thirty amplicons from 6 genes (KRAS, BRAF, EGFR, CDKN2A, TP53, and PI3KCA) were sequenced using the Roche 454 GS FLX-TI platform. Data analysis was carried out by Variant Identification Pipeline (VIP) software and R (computing environment) commands. Total mutational load (TML) was calculated as the sum of all variants frequency for each sample. Results: In all, 18,626 variants were identified. Optimal filters applied to discard false positives were: (1) variants with an absolute frequency &lt; 10x, (2) variants in homopolymer (HP) ≥ 6 nucleotides, (3) insertions and deletions (INDELs) in HP ≥ 5 nucleotides, and (4) INDELs in only one strand. Filtering yielded 870 variants from all samples remained as valid, 92 being unique. After discarding polymorphisms, variants classified as neutral by the Condel software and variants preferentially detected in normal tissues, 46 variants were used to compute TML. TML in colonic carcinomas and adenomas was higher than normal mucosa (0.83 vs. 0.607 vs. 0.128, p = 0.01). In pancreatic disease, TML for pancreatic carcinoma was higher than normal pancreas (0.716 vs. 0.135, p = 0.01). KRAS and TP53 analysis provide most of the information in both tumors, while PI3KCA adds information for colorectal carcinomas exclusively and CDKNA2 is informative in pancreatic samples. Conclusions: NGS provides a robust and quantitative measure of genetic alterations in tumor samples. MLDA is an effective tool for the classification of GI tumors.