tbuckley/cabot-search huggingface dataset:
Residual pathologic stage at radical cystectomy and risk stratification of patients with pT2N0 bladder cancer
Authors: H. Isbarn, G. Sonpavde, S. F. Shariat, G. S. Palapattu, A. I. Sagalowsky, Y. Lotan, M. P. Schoenberg, G. E. Amiel, S. P. Lerner, P. I. Karakiewicz
Journal: Journal of Clinical Oncology (2009)

5076 Background: We hypothesized that in patients with pT2N0 transitional cell carcinoma (TCC) of the urinary bladder, residual muscle-invasive disease at radical cystectomy (RC) may confer poorer outcomes than residual non-muscle invasive disease due to larger tumor volume and/or biologically more aggressive disease. Patients with high-risk pT2N0 disease may be candidates for trials of adjuvant therapy. Methods: Patients from the BCRC database with pT2N0 stage (N = 208) at TUR (transurethral resection) whose tumors were organ-confined at RC (≤pT2N0) were analyzed. T1N0 patients (N=33) with pT2 disease at RC were also examined in order to include all pT2 patients. None of the patients had received perioperative chemotherapy. The effect of residual pT-stage at RC on outcomes was evaluated in Kaplan-Meier, as well as in univariable and multivariable Cox-regression models. Covariates consisted of age, gender, grade, lymphovascular invasion, concomitant carcinoma-in-situ (CIS), number of lymph nodes removed, and the year of surgery. Results: Among baseline T2N0 patients, residual pT-stage at RC was pT0 in 24 (11.5%), pTa in 9 (4.3%), pCIS in 22 (10.6%), pT1 in 35 (16.8%), and pT2 in 118 patients (56.7%). The median follow-up was 50.1 months. The 5-year recurrence-free survivals of patients with residual pT0/pTa/pCis, pT1 and pT2 were 100%, 85% and 75%, respectively. The 5-year cancer-specific survival rates for the same patient cohorts were 100%, 93%, and 81%, respectively. In multivariable analyses, the effect of residual stage &lt;pT2 at RC achieved independent predictor status for recurrence (adjusted HR 0.20; p = 0.002), as well as for cancer-specific survival (adjusted HR: 0.24; p = 0.02). Initial T1 patients who were pT2 at RC did not have statistically different outcomes compared to initial T2 followed by pT2 at RC. Conclusions: Patients with pT2N0 TCC of the urinary bladder with residual non-muscle invasive disease at RC have significantly better long-term outcomes compared to residual muscle-invasive disease. With further validation, these data may facilitate the risk-stratification of patients with pT2N0 disease and enable the selection of high-risk patients for trials of adjuvant therapy. No significant financial relationships to disclose.
Abstract 12148: Superiority of the Prognostic Value of Cardiac I-123 Metaiodobenzylguanidine Imaging to Heart Rate Recovery Testing in Patients with Chronic Heart Failure
Authors: Tadao Fujimoto, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takashi Naito, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Norihiro Yamamoto, Tsutomu Kawai, Satoshi Takahashi, Masatake Fukunami
Journal: Circulation (2012)

Background: Cardiac metaiodobenzylguanidine (MIBG) imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information in chronic heart failure (CHF) patients. Heart rate rec...
Pure tubular breast carcinoma: A study of outcomes from 1971–2004
Authors: G. Y. Yang, K. Wharton, T. D. Wagner, K. Donohue, P. Tripp, K. Khaghany, G. Tompson, J. Martin, G. Hare, W. Jaggernauth
Journal: Journal of Clinical Oncology (2005)

674 Background: Pure tubular breast carcinoma (ca) is widely thought to have a favorable prognosis, but questions remain regarding extent of treatment required. This study assessed the long term outcome for women with this rare histologic subtype. Methods & Materials: Between 1971 & 2004, 8832 patients (pts) were treated for breast cancer at our institution, and 27 (0.3%) were diagnosed with pure tubular ca. Tumors were considered tubular only if the pathology report explicitly identified the histology as tubular ca, and did not include any other histologic subtypes. All data for tubular ca pts were analyzed. Results: Median pt age was 55.4 years (range, 44–85). All patients were Caucasian. Twenty-one pts had stage I disease (78%), 5 pts stage IIA (19%), and 1 pt stage IIB disease. Eleven (41%) patients had a first-degree relative with breast or ovarian cancer. Median tumor diameter was 0.8 cm (range, 0.2–4.2 cm). Three pts (11%) had positive axillary lymph nodes. Fifteen pts were tested for estrogen receptor (ER) status, and all were positive. Twenty-one patients (78%) were treated using breast-conserving surgery (BCS), and 6 (22%) underwent modified radical mastectomy (MRM). Fifteen pts (56%) received post-operative radiation (RT) (14 BCS pts, 1 MRM pt). Among the pts treated with MRM, 4 pts received no further treatment, 1 received RT+ Tamoxifen (TMX)+chemotherapy (CT) & 1 received TMX alone postoperatively. Of BCS pts, 4 pts received no further treatment, 8 received RT alone, 5 received RT+TMX, 1 received RT+TMX+CT & 2 received TMX alone postoperatively. At median 5.3 years follow-up (range, 1–24), no pts had local or systemic recurrence, and no pts had died of breast cancer. Five-year disease-specific survival (DSS) & overall survival (OS) were 100%, & 89% respectively. Ten-year DSS & OS were 100%, & 70% respectively. Second cancer was diagnosed in 6 pts (22%), median 7.5 years after the diagnosis of tubular breast ca. Conclusions: Our study confirms the rare incidence of pure tubular ca, and its favorable biological behavior. Treatment selected, MRM or BCS, did not affect local control or DSS. BCS results in low rates of local recurrence & excellent DSS with or without further treatment. No significant financial relationships to disclose.
Safety and efficacy of ipilimumab with or without prophylactic budesonide in treatment-naive and previously treated patients with advanced melanoma
Authors: J. S. Weber, D. Berman, J. Siegel, D. Minor, A. Amin, J. A. Thompson, I. Ron, R. Ridolfi, H. Assi, O. Hamid
Journal: Journal of Clinical Oncology (2008)

9010 Background: Ipilimumab (ipi), an anti cytotoxic T-lymphocyte antigen-4 monoclonal antibody, has shown activity in small, phase I/II melanoma trials. The purpose of this study was to explore whether prophylactic budesonide (PB) would decrease the rate of diarrhea, a frequent immune-related adverse event (irAE), and assess clinical responses to the regimen. Methods: Patients (pts) with unresectable stage III or stage IV melanoma received ipi 10 mg/kg every 3 weeks (Q3W)×4 induction dosing in combination with placebo (Group A) or PB, an oral steroid with minimal systemic exposure used to treat inflammatory bowel disease (Group B; QD at 9 mg to Week 12, 6 mg to Week 14, and 3 mg to Week 16) in this randomized, double-blind, multicenter, phase II study. Pts were either treatment-naive or treated with prior systemic therapy for advanced melanoma. Eligible pts could enter maintenance treatment with ipi 10 mg/kg Q12W at Week 24. Response was assessed by an Independent Review Committee (IRC) using mWHO criteria. Follow-up tumor evaluation beyond progressive disease (PD) and before the administration of non-ipi anticancer therapy was permitted as per protocol. Results: 115 pts were treated. The rates [95% CI] of Grade 2+ diarrhea (regardless of causality) during the initial trial period were 35.1% [22.9 - 48.9] and 32.8% [21.0 - 46.3] for Groups A and B, respectively. Ipi was generally well tolerated; most pts had at least 1 irAE. There were no bowel perforations observed. There was no clinically meaningful difference in the best overall response rate (BORR), disease control rate (DCR), or safety events. BORRs were 15.8% and 12.1% in Groups A and B, respectively. Conclusions: Ipi is well tolerated and efficacious in pts with advanced melanoma. While therapeutic budesonide has activity in the management of low-grade gastrointestinal ipi-related irAEs, PB in advanced melanoma did not meaningfully impact the benefit to risk profile, and is not recommended. Group A (ipilimumab + placebo) Group B (ipilimumab + prophylactic budesonide) BORR (CR + PR) - % [95% CI] CR - n (%) 15.8 [7.5–27.9] 0 (0) 12.1 [5.0 - 23.3] 1 (1.7) DCR (CR + PR + SD) - % [95% CI] 35.1 [22.9- 48.9] 31.0 [19.5 - 44.5] Any irAE - % 84.2 81.0 Grade 3/4 irAE - % Any Gastrointestinal Hepatobiliary Endocrine Skin 38.6 22.8 8.8 5.3 0 41.4 24.1 6.9 5.2 5.2 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex Medarex
18-FDG-PET and somatostatin receptor scintigraphy (SRS) can predict disease progression and survival in patients with metastatic endocrine tumors: Results of a prospective study
Authors: J. Raoul, A. Devillers, A. de Lajarthe, M. Cuggia, E. Boucher, E. Garin
Journal: Journal of Clinical Oncology (2007)

4577 Background: Appropriate treatment for metastatic endocrine tumors (MET) depends on the aggressiveness of the disease. We wanted to know whether PET and SRS can predict early disease progression and patient survival. Methods: A prospective exploration protocol was applied for new cases of untreated MET diagnosed between September 2003 and January 2006 who gave their written informed consent. Explorations included: computed tomography (CT), SRS, PET, review of histological data (WHO grade, p53 and Ki67 IH); CT was repeated every three months to assess: disease-free survival (PFS), the risk of early (first 6 months) progressive disease (PD6m)and overall survival (OS). Results: The series included 38 patients (60±15y) with a primary digestive tract (n=24), lung (n=2) or unknown (n=12) tumor. Histologically, 4 patients had a high-grade tumor and 34 a low-grade tumor. Visual analysis of PET and SRS was positive in 15 and 27 patients respectively. The 2-year OS and DFS were 73% and 45%; 16 patients had PD6m. PET exhibited an excellent positive predictive value for PD6m (14/15 PET+ and 2/23 PET- were PD6m) and was correlated with DFS (p&lt;0.0001; at 2 yr 75% DFS for PET- and 0% for PET+) and OS (p&lt;0.0001; at 2 yr 95% vs 42%) even when considering only low-grade tumors. Positive SRS was associated with DFS (p&lt;0.001) and OS (p&lt;0.03). Among patients with positive PET, the SRS-positive patients had a better DFS than the SRS-negative patients. At univariate analysis DFS and OS were correlated with: PET, SRS, WHO grade, Ki67 and p53. At multivariate analysis only PET was predictive of DFS. Conclusions: PET and SRS exhibit excellent predictive value for rapid tumor progression. There results are correlated with DFS and OS even for histologically low-grade tumors. Tumors progressed within 6 months in 14/15 patients with a positive PET. These explorations should be included in the initial work-up for MET. No significant financial relationships to disclose.
TCT-835 Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation: is There Any Impact on Survival?
Authors: Jérôme Van Rothem, Thierry Lefèvre, Didier Tchetche, Kentaro Hayashida, Didier Carrié, Bernard Chevalier, Jean Fajadet, Marie-Claude Morice, Nicolas Dumonteil
Journal: Journal of the American College of Cardiology (2012)
Ancestral HLA haplotypes 62.1 and 8.1 as negative prognostic factors in patients with metastatic malignant melanoma
Authors: H. Helgadottir, E. Andersson, J. Hansson, R. Kiessling, G. V. Masucci
Journal: Journal of Clinical Oncology (2008)

9050 Background: Current methods to predict survival in patients with metastatic malignant melanoma are limited. Our objective was to determine the impact of Human Leukocyte Antigen-type (HLA-type) on prognosis in this patient group. HLA antigens are determinants for the efficacy of the immune response and loss of HLA and antigen processing machinery has been linked to tumour escape. Methods: An unbiased selection of melanoma patients (n=91), stage III (n=26) or IV (n=65) recorded by demographic and clinical data were analyzed for HLA-A, -B, -Cw and -DRB1 genotypes by the PCR/sequence-specific oligonucleotide hybridization method (PCR/SSOP). The frequencies of HLA alleles in the patients were compared to healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined by Kaplan Meier and Cox analysis. Results: The expression of Ancestral HLA Haplotypes (AHH) 62.1 [(A2)B15Cw3DRB1*04] and 8.1 [(A1)B8Cw7DRB1*03] in clinical stage III and IV patients was associated with the poorest survival rate (HR=2.08; C.I.=1.17–3.7; p=0.01) recorded from the appearance of metastasis. On the contrary, and in particular in stage IV patients, the period from the primary diagnosis to metastasis was the longest in patients with these haplotypes (HR=0.41; C.I.=0,20–0,85; p=0,01). Multivariate Cox analysis showed that AHH 62.1 and 8.1 are independent prognostic factors towards age, Breslow, Clark and clinical stage. Conclusions: AHH are inherited en bloc (MHC class I and II locus) and conserved more than can be expected by random within related populations. AHH 62.1 and 8.1 are common in Scandinavians and associated with higher incidence of autoimmune disorders. Melanoma patients in our cohort with the highly immunogenic 62.1 and 8.1 AHH have an initial strong anti tumour control with longer metastasis free period but at the appearance of metastasis they have a rapid progression and respond poorly to chemo- or/and immunotherapy, requiring intensive oncological care. This could be due to a selection of clones that are invisible to the immune system causing immune escape and rapid progression, thus different clinical approaches in follow up and treatment of these patients are mandatory. No significant financial relationships to disclose.
A phase II trial of biweekly administration of vinorelbine (V) and gemcitabine (G) in elderly patients (Pts) with advanced non-small cell lung cancer (NSCLC)
Authors: H. Kimura, K. Kasahara, K. Shibata, H. Shirasaki, K. Iwasa, A. Yoshimoto, T. Kita, M. Fuzimura, S. Nakao
Journal: Journal of Clinical Oncology (2004)

7331 Objective: The purpose of this phase II trial was to evaluate the activity and the toxicity in elderly NSCLC pts of biweekly administration of this combination. Pts and Methods: 45 elderly pts with advanced NSCLC were treated with V 25mg/m2 intravenously and G 1000mg/m2 intravenously every 2 weeks. Eligible pts had: age ≥ 70 yrs; measurable or evaluable disease; ECOG PS 0–2; adequate bone marrow, liver and renal function; no previous chemo- or radiotherapy; life expectancy ≥12 weeks; written informed consent. Results: From August 2001 to November 2003, 46 pts were enrolled and 44 pts were eligible: males/females 27/17; median age 76(range 71–84); PS 0/1/2 25/16/3; stage IIIA/IIIB/IV 5/14/25; adeno/squamous 31/13. A total of 194 cycles(median 6/pt, range 1–12) were given. Tumor response and safety were analysed by December 2003. Of the 40 pts evaluable for response, 11(27.5%) had partial response and 19(47.5%) had stable disease. At this writing, median time to progression is 160 days and median survival is 397 days and 21 pts(47.7%) are still alive. All pts were evaluable for toxicity. Toxicity was mild and mainly hematologic. Grade 3/4 toxicities were neutropenia in 35.3/17.6% of pts, leukopenia in 29.4/2.3%, anemia in 0/0% and thrombocytopenia in 0%/2.9%, respectively. 2 pts(4.5%) had febrile neutropenia. Only 5(11.6%) pts had grade 3 or 4 non-hematological toxicities which were mainly constipation. There was one death from sepsis with neutropenia. At 40th Annual Meeting, we will demonstrate the final results of this trial. Conclusions: This VG biweekly schedule shows an acceptable activity in elderly. The toxicity profile is favorable with mild myelotoxicity. No significant financial relationships to disclose.
Safety and tolerance of multiple weekly intracavitary injections of 131I-chlorotoxin (TM-601): Preliminary results of a prospective clinical trial in patients with recurrent glioblastoma multiforme
Authors: J. B. Fiveash, L. B. Nabors, A. N. Mamelak, N. G. Avgeropoulos, B. L. Guthrie, N. W. Salomon, J. Portnow, R. D. Bucholz
Journal: Journal of Clinical Oncology (2006)

1555 Background: 131I-chlorotoxin is a peptide originally derived from scorpion venom that will specifically bind to tumor cells targeting lamellipodia and produces a variety of secondary messenger effects through phosphatidyl inositol signaling. Preclinical studies suggest it is both a radiation and chemotherapy sensitizer. A previous phase I/II clinical trial defined the distribution and dosimetry of single injection intracavitary 131I-chlorotoxin and suggested clinical activity in patients with recurrent glioma. Methods: 15 patients with recurrent GBM after prior treatment (radiation therapy), were enrolled in this sequential, multiple-dose escalation study with re-resection and implantation of a ventricular access device (VAD) into the resection cavity. Dose limiting toxicity was defined as any grade 3 or greater toxicity judged probably related to study drug and occurring within 7–11 days of the last dose. Dosing cohorts of 3–5 patients were entered at each of the listed dose levels designed to maintain a constant drug specific activity. Results: One subject did not complete treatment due to thrombocytopenia possibly related to a VAD infection necessitating removal of the VAD following the initial dose of study drug. Eight serious adverse events (SAEs) were observed in 15 patients after study drug administration. These included seizure, cerebral edema, and gait disturbances. None were judged to be both unexpected and related to study drug. No dose limiting toxicity was observed. Two subjects experienced Grade 1/2 CTC 3.0 neutropenia. Conclusions: The safety profile of weekly intracavitary injections of 131I-chlorotoxin was acceptable. Dose limiting toxicity was not reached at the final planned dose level D (6 x 40 mCi/0.8 mg peptide, total 240 mCi), which is the maximum practical dose. Accrual to the randomized phase II portion of this trial comparing three vs. six weekly injections began 12/2005. [Table: see text] [Table: see text]
Risk-based treatment for nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) in patients under 30 years of age: Children’s Oncology Group study ARST0332.
Authors: Sheri L. Spunt, Lynn Million, James Robert Anderson, Cheryl M. Coffin, Beth McCarville, R. Lor Randall, David Parham, Simon C Kao, Andrea Anita Hayes-Jordan, Suzanne L. Wolden, Stephanie Alicia Terezakis, Jennifer Black, Fran Laurie, Ellen Kawashima, Rose Anne Speights, Stephen Skapek, William H. Meyer, Douglas S. Hawkins, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2014)

10008 Background: NRSTS comprise ~4% of childhood cancer but only 3 prospective clinical trials have been performed in the U.S. in the past 40 years. Tumor grade, size, resection potential, and extent of disease influence outcome. ARST0332 evaluated a risk-based treatment strategy for young NRSTS patients designed to limit therapy for low-risk disease and to test a combined chemoradiotherapy approach for unresected higher risk disease. Methods: Newly diagnosed NRSTS patients < 30 years old were assigned to 4 treatment arms based on risk: A (surgery only): grossly excised low-grade and ≤ 5 cm widely excised high-grade tumor; B (55.8 Gy radiotherapy [RT]): ≤ 5 cm marginally resected high-grade tumor; C (ifosfamide/doxorubicin chemotherapy + 55.8 Gy RT): > 5 cm grossly resected tumor ± metastases; D (neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery and an RT boost based on margins): > 5cm unresected tumor ± metastases. Results: 551 eligible patients were enrolled on Arm A (212), B (19), C (120), and D (200). Most common subtypes were synovial sarcoma (149), malignant peripheral nerve sheath tumor (60), and undifferentiated sarcoma (48). Tumors were 53% extremity, 72% high grade, 76% > 5 cm, and 14% metastatic. There were no toxic deaths; 2% had unexpected grade 4 adverse events. By treatment arm, at a median follow-up of 2.6 years, estimated 3-year event-free survival was: A 91%, B 79%, C 68%, D 52% and overall survival was: A 99%, B 100%, C 81%, D 66%. Conclusions: This novel risk-based treatment strategy segregated patients into clinically meaningful risk groups and produced outcomes similar to or slightly better than historical controls while using RT less frequently and at lower doses. This study defines the new standard of care for pediatric NRSTS against which future interventions should be compared. Clinical trial information: NCT00346164.
Novel genes mediating cisplatin resistance in head and neck cancer
Authors: M. Gasco, N. Syed, H. Coley, I. Colantonio, M. Merlano, T. Crook, T. Crook
Journal: Journal of Clinical Oncology (2009)

e22135 Background: Chemo-radiotherapy with cisplatin-based regimens offers the possibility of cure to a subset of patients with surgically non-resectable squamous carcinomas of the head and neck (HNSCC), but outcome is frequently limited by acquired drug resistance. We have sought novel genes mediating cisplatin resistance in HNSCC. Methods: We derived in vitro cisplatin resistant variants of the HN5 HNSCC cell line and performed micro-array anaylsis to identify differentially expressed genes. Differences in gene expression were confirmed by qPCR and /or western blotting. Methylation-dependent transcriptional silencing of down-regulated genes was studied by bisulphate sequencing and methylation specific PCR. Selected genes were further analysed in a cohort of stage III and IV HNSCC patients treated with cisplatin-based chemo-radiotherapy. Results: We have identified a panel of genes in which changes in expression occur with acquisition of cisplatin resistance both in vitro and, some cases, in vivo. Up-regulated genes include TAOK1, BZW1 and RECQL, whereas down-regulated genes include FAM83D, PAFAH1B2, DLL1, ABPA1 and FH. Conclusions: We report the identification of a novel panel of genes which function as determinants of cisplatin sensitivity. Analysis of expression and/or epigenetic regulation of these genes may have clinical utility in prediction of patients likely to respond to highly toxic combined modality chemo-radiotherapy. No significant financial relationships to disclose.