tbuckley/cabot-search huggingface dataset:
Clinical features, treatment, and outcome in 108 patients with localized, high-grade synovial sarcoma (SS)
Authors: A. A. Gupta, H. Al-Hussaini, C. Yu, A. Griffin, V. Tsung, D. Stephens, M. Blackstein, D. Hogg, P. Ferguson, J. Wunder
Journal: Journal of Clinical Oncology (2009)

10584 Background: There remains ongoing controversy in the treatment of localized SS, with no clear consensus on routine use of chemotherapy. Methods: Between 1986 and 2007, 93 adult (AP) and 15 pediatric (PP) patients were diagnosed with high grade, localized SS at 2 centres in Toronto. Clinical records and pathology reports were examined. Survival distribution functions were estimated by Kaplan-meier and compared using Log-rank test. Results: Median age for AP and PP was 36 (range 14–76) and 14 (range 0.4–18) years, respectively. Sixty-six (61%) patients had large tumours (&gt; 5 cm), 7 (6.5%) had neuro-vascular invasion, and 10 (9.3%) had bone invasion. 76 (82%) AP and 8 (53%) PP received radiation (RT). 16 (17%) AP and 13 (87%) PP received chemotherapy. All patients underwent definitive surgery with gross total resection; 9 patients (8 PP) had positive margins. Some patients received neoadjuvant chemotherapy, and response was evaluable in 15 patients: 10 SD, 2 PR, 1 CR, 1 PD. Relapse occurred in 32 patients: 28 distant, 3 local only, 1 local + distant. With a median follow-up of 5.6 years, EFS and OS was 72 ± 4.6% and 82 ± 4.2%, respectively and was similar for AP and PP. Patients with tumours &gt; 5 cm had significantly worse EFS (63 ± 6.5%) compared to patients with small tumours (88 ± 5.4%, p=0.02), as did those with bone invasion (47 ± 18 vs.75 ± 4.9, p=0.05). The effect of chemotherapy was assessed in the entire cohort. Of 29 who received chemotherapy, 9 (31%) relapsed, and of 79 who did not receive chemotherapy, 23 (29%) relapsed. In patients with tumours &gt;5 cm, relapse occurred in 41% (7/17) of those who received chemotherapy compared to 37% (18/49) in those that received no chemotherapy. Conclusions: Patients with SS &lt; 5 cm have an excellent chance of cure with surgery and RT. Large tumours and those with evidence of bone invasion have a poor outlook. It is unlikely that chemotherapy contributes to an improvement in survival in SS. No significant financial relationships to disclose.
A novel bispecific antibody (bsMAb) construct for nuclear imaging of pancreatic cancer
Authors: D. Gold, H. Karacay, C. Chang, E. Rossi, W. McBride, D. Goldenberg, R. Sharkey
Journal: Journal of Clinical Oncology (2007)

4564 Background: The initial diagnosis of pancreatic cancer is difficult at best. We developed MAb-PAM4 reactive with a unique epitope within MUC1 that is expressed in most pancreatic cancers, but not in normal or inflammatory pancreas, nor most other normal and neoplastic tissues. Our current focus is the development of a pretargeting procedure that can greatly enhance targeting sensitivity while retaining the MAb’s high specificity. Methods: TF10 is a novel humanized recombinant bsMAb with divalent binding to PAM4-defined MUC1 and monovalent binding to histamine-succinyl-glycine (HSG). TF10 is a 157 kDa protein having &gt;85% binding to MUC1 and &gt;90% with HSG. Athymic nude mice bearing CaPan1, human pancreatic cancer, were injected with 125 I-TF10 to assess biodistribution. Other animals were given varying doses of TF10 followed 16 h later with 111 In-IMP-288, a divalent-HSG-peptide. These animals were imaged 3 h after the 111 In-IMP-288-injection and then necropsied. Results: 125 I-labeled TF10 cleared rapidly from the blood, with blood levels &lt;0.25 ± 0.02 %ID/g at 16 h, and no accumulation in any normal tissues. Tumor uptake was 7.16 ± 1.10, 3.47 ± 0.66, and 1.65 ± 0.57 % ID/g at 6, 16, and 48 hrs, respectively. These data confirmed that for a pretargeted imaging study a 16-h interval is sufficient to clear the blood so that 111 In-IMP-288 could be administered. At 3 h, the imaging studies showed intense uptake of radiolabeled peptide within the tumors (avg. 0.5 cm3 - 0.3 g at necropsy) with no evidence of uptake in any normal tissues, while no targeting was seen in animals given the 111 In-IMP-288 alone. At necropsy, tumor uptake of the 111 In-IMP-288 in the TF10 pretargeted animals was 24.3 ± 1.7 % ID/g, while for 111 In-IMP-288 alone tumor uptake was only 0.012 ± 0.002 % ID/g. Tumor/blood, liver, lungs, and kidney ratios averaged 2800:1, 139:1, 184:1, and 14.2:1, respectively, in the pretargeted animals. Conclusions: These results demonstrate that this novel PAM4-based pretargeting agent targets and images xenografted human pancreatic cancer with high signal-to-background ratios. In addition to imaging, TF10 may prove useful for pretargeted therapy of pancreas cancer. (Supported in part by grant CA115755 from the NIH.) No significant financial relationships to disclose.
Occult cervical cancer after extrafascial hysterectomy: The role of radical parametrectomy as a treatment option
Authors: W. D. Joo, D. Y. Kim, D. S. Kim, J. H. Kim, Y. M. Kim, Y. T. Kim, J. E. Mok, J. H. Nam
Journal: Journal of Clinical Oncology (2005)

5076 Background: To investigate clinical outcome of occult cervical cancer diagnosed after extrafascial hysterectomy(EH) and to assess an efficacy of radical parametrectomy(RP) as a treatment option in stage Ib occult cervical cancer. Methods: We performed retrospective chart review and 70 patients were identified, who were diagnosed at or transferred to Asan Medical Center due to occult cervical cancer diagnosed after EH from June 1989 to June 2004. Data were collected on tumor stage, histology, indication for hysterectomy, adjuvant treatment, recurrence and survival. Results: Median age of patients was 42.5 years(range 28–74). Number of patients were 44 in stage Ia1(63%). 5 in stage Ia2(7%), 18 in stage Ib(26%), 2 in stage IIa(3%), and 1 in stage IIIb(1%). The most common indication for EH was CIS of the cervix(76%). In the stage Ia1 and Ia2, 44 patients had no further treatment and 5 patients had adjuvant radiotherapy(RT). No recurrence was observed in the stage Ia. In the stage Ib, 7 out of 18 patients had RP and pelvic and/or para-aortic lymphadenectomy. One patient(14%) had metastasis to the pelvic lymph node at the time of RP. 5 patients had no further treatment and 2 patients had adjuvant chemotherapy or concurrent chemoradiaton(CCRT). All are alive (median follow-up 30 months, range 7–65) and 2-year disease free survival rate(DFSR) was 100%. 11 patients who did not have RP had RT(7 patients), chemotherapy(2 patients) or CCRT(1 patient) and one patient had no further treatment. There was one recurrence. The patient was stage Ib2 and had adjuvant chemotherapy. Median follow-up of non-RP group was 44 months (range 9–144 months) and 2-year DFSR was 87.5%. There was no significant difference between two groups in 2-year DFSR(p=0.480). In the stage IIa or higher, 2 patients had RT and 1 patients had CCRT. No recurrence was observed among them. Conclusions: RP showed comparable results to that of RT or CCRT as a treatment option. There is no evidence until now that RP shows a better survival than RT or CCRT. But, RP is an attractive option, especially for young women to preserve ovarian function. No significant financial relationships to disclose.
Impact of homozygote variant of bleomycin hydrolase (BLMH) gene on survival after chemotherapy for testicular cancer (TC)
Authors: E. C. de Haas, N. Zwart, C. Meijer, H. M. Boezen, G. van der Steege, D. T. Sleijfer, J. A. Gietema
Journal: Journal of Clinical Oncology (2007)

5022 Background: With bleomycin, etoposide and cisplatin, cure of disseminated TC exceeds 80%. Next to tumor characteristics, response to chemotherapy may be determined by polymorphisms of genes involved in metabolism or target pathways of cytotoxic drugs. We investigated whether the A1450G polymorphic site in the gene for BLMH, an enzyme that inactivates bleomycin, is associated with differences in survival. Methods: Data were collected on survival of non-seminomatous TC patients treated with bleomycin and platinum from 1977–2003. BLMH genotype was determined from genomic DNA by PCR + restriction fragment length polymorphism analysis. The 3 genotypes [AA (wild-type), AG (heterozygote variant) and GG (homozygote variant)] were compared for patient characteristics, prognostic factors and received chemotherapy (Mann-Whitney U or χ 2 test) and survival (Kaplan-Meier + log-rank test and Cox regression). Results: Data on BLMH genotype and survival were available for 304/372 patients (82%) with median follow-up of 10 yrs (range 0–27). The 3 genotypes AA (n=140), AG (n=133) and GG (n=31) did not differ significantly with respect to age, IGCCC prognosis, creatinine clearance and received dose of bleomycin and platinum. Overall survival of the GG genotype (61%) was worse than the overall survival of AA and AG combined (83%) (p=0.004), due to worse TC related survival of GG (71%) compared to AA + AG (90%) (p=0.001). Homozygote variants (GG) had a significantly increased risk for TC related death (odds ratio (OR) = 4.97) compared to wildtypes (AA) ( table ). Conclusion: Germline presence of the homozygote variant (GG) of the BLMH gene appears to be an unfavorable prognostic factor for TC related death after chemotherapy, in addition to the commonly used IGCCC prognosis. It is unclear whether this is due to alterations in metabolism or target pathways of bleomycin or other cytotoxic agents, or linkage disequilibrium to a yet unknown involved gene. This needs to be unraveled in future research. [Table: see text] No significant financial relationships to disclose.
Concordance of FDG-PET scan and MRI- spectroscopy in primary and metastatic intracranial tumors
Authors: S. M. Kurian, E. B. Crowell
Journal: Journal of Clinical Oncology (2004)

1551 Background: Functional imaging techniques that utilize altered metabolic characteristics like glycolytic activity (PET scan) and catabolic metabolites (spectroscopy) in neoplastic tissues are powerful tools that add to our ability to non-invasively characterize intracranial lesions. We are presenting the results of a single institution experience, evaluating the concordance between PET scan and MRI spectroscopy and analyzing the relative contributions of these two imaging modalities. Methods: Thirteen patients with intracranial mass underwent both MRI spectroscopy and FDG-PET scan in our institution. The median interval between these two studies was two weeks. The presence of a high SUV hypermetabolic activity was considered as positive PET result and reversal of choline:creatinine ratio exceeding 2 was considered as positive spectroscopic result. Results: Concordance between the two modalities was found in eight (both tests positive in four, both tests negative in four ) patients out of the total thirteen patients. Further follow-up with tissue diagnosis of patients with double positive results showed that these results correlated accurately with their subsequent pathological diagosis of a malignant intracranial neoplastic process. Patients with both results negative had non-malignant process (multiple sclerosis, toxoplasmosis). In the five patients with discordent results, PET scan alone was positive in three patients (metastatic lung cancer with brain metastasis-2, radiation necrosis-1). In the other two patients with discordant results, only spectroscopy was positive, and they were diagnosed with low grade primary malignant gliomas. Conclusions: Concordance between these two tests correlated with accurately predicting neoplastic nature of the tumor. PET scan was relatively more accurate in detecting metastatic lesions to brain. Spectroscopy was more reliable in detection of primary brain neoplasm including low grade tumors and in the differentiation of radiation necrosis. These two techniques can be used as complementary imaging modalities to improve the non-invasive diagnostic yield in patients with intracranial lesions. No significant financial relationships to disclose.
A phase II study of RAD001 (R) (everolimus) monotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy (C) or prior C and EGFR inhibitors (EGFR-I)
Authors: V. Papadimitrakopoulou, J. C. Soria, J. Y. Douillard, G. Giaccone, J. Wolf, L. Crino, F. Cappuzzo, S. Sharma, S. H. Gross, F. A. Shepherd
Journal: Journal of Clinical Oncology (2007)

7589 Background: R is an oral inhibitor of mammalian target of rapamycin (mTOR) with anti-tumor activity. Single-agent R and in combination with other anticancer agents showed efficacy in in vitro and in vivo NSCLC models. In a phase I study, 4 disease stabilizations (SD) and 1 partial response (PR) were reported from 14 NSCLC pts treated with R monotherapy. Methods: Advanced NSCLC pts with adequate organ function, performance status ≤ 2, failing either ≤ 2 C (arm 1) or ≤ 2 C and an EGFR-I (arm 2) were treated with R at 10 mg qd if tolerable until progression (PD). Study applied a Simon-2-stage design with primary endpoint of objective tumor response rate (RR) according to RECIST. CT scans were performed every 28 days until month 4 and then every 2 months thereafter. Adverse events (AE) were assessed using NCI CTC v. 2.0. Results: This analysis is based on data acquired up to 20 Sep 2006. 85 pts were enrolled between 08/2005 and 05/2006. Demographics and patient disposition were (arm 1/arm 2): 42/43 (7 pts ongoing), female 38.1%/51.2%, never smoker 14.3%/44.2%, adenoca. 57.1%/62.8%, squamous cell ca. 21.4%/14.0%, BAC 2.4%/16.3%, others 19.1%/6.9%. Median age was 60 years (range 21–74). R was given on arm 1 as 2nd line therapy in 64.3% of pts., as 3rd line in 35.7% and on arm 2 as 3rd line in 58.1%, as 4th line in 41.9%. 90.6% pts had stage IV disease. The trial did not proceed to stage 2 based on RR for 74 pts in the efficacy population. Best overall tumor response (arm 1/2 in %): confirmed PR (5.3/2.8), SD (44.7/44.4); SD ≥ 12 weeks (34.2/41.7), duration of SD in days arm 1 (58 –267) and arm 2 (68 –231). Median PFS on arm 1 is 11.3 weeks (95% CI: 8.1; 12.4) and on arm 2 is 9.7 weeks (7.3; 13.0). Most frequent AEs (pts, all grades/grade 3 and 4): stomatitis/mucositis (43/5), cough (27/1), dyspnea (33/8), rash (26/0), fatigue (25/10), anorexia (25/1), nausea (20/0), anemia (18/3), epistaxis (18/0), diarrhea (17/2). Analyses of molecular markers in tumor tissue samples are ongoing. Conclusions: 10 mg qd R monotherapy is well tolerated and shows limited activity in pretreated advanced NSCLC pts. Combination trials with both standard chemotherapy and targeted agents are in progress. No significant financial relationships to disclose.
Oropharyngeal squamous cell cancers (OSCC) bearing transcriptionally active human papillomavirus (HPV) display distinct protein expression profile
Authors: P. Weinberger, P. Kountourakis, C. Sasaki, B. Haffty, R. Camp, D. Rimm, A. Psyrri
Journal: Journal of Clinical Oncology (2006)

10028 Background: It is known that among HPV DNA+ OSCCs only the transcriptionally active ones are biologically and clinically relevant. pRb downregulation by HPVE7 results in p16 upregulation. We previously showed (JCO, Feb 2006) that p16 expression defines transcriptionally active HPV+ tumors. Thus, OSCC tumors can be Class I: HPV−/p16−, Class II: HPV+/p16−, or Class III: HPV+/p16+. We hypothesized that tumors classified by these criteria would show different protein expression profiles. Methods: Following institutional review board approval, paraffin-embedded specimens from 77 patients were collected from Yale-New Haven Hospital archives. Patients with OSCC treated with radiotherapy (RT) or surgery and RT were eligible. We used real-time polymerase chain reaction for HPV 16 and immunohistochemistry for p16 protein expression to classify 77 patients with OSCC. Tumors were classified into a 3-class model based on p16 expression and HPV DNA presence: Class I (HPV−, p16−) Class II (HPV+, p16−) and Class III (HPV+, p16+). A tissue microarray including these cases was constructed and examined for 13 target proteins with known involvement in tumor suppression or progression. We used a method of in-situ automated quantitative protein expression analysis (AQUA). Protein signal (AQUA score) was scored on a scale of 0–255.Protein expression between groups was analyzed by analysis of variance (ANOVA). Results: Thirty tumors were class I (39%), 29 were class II (38%), and 18 were class III (23%). There were significant differences for protein expression of Met (p=0.005), β-catenin (p=0.009), pRb (p=0.001), p53(p=0.026), epidermal growth factor receptor (EGFR) (p=0.009) and Vascular Endothelial Growth Factor (VEGF) (p=0.028). There was no difference for ki-67, COX2, p27, p21 or Cyclin D1 expression, while ERK2 and p14 trended towards significance (p=0.09 and 0.054, respectively). Conclusions: We demonstrated that tumors classified by HPV DNA presence and p16 expression status have different molecular phenotypes. Of particular note, class III tumors demonstrated increased expression of Met, β-catenin, EGFR and VEGF. These findings may prove useful for patient selection for molecular-targeted therapies. [Table: see text]
Phase Ib study of RAD001 (R) with pegylated-liposomal doxorubicin (PLD) in patients with advanced solid tumors.
Authors: A. Perotti, C. Sessa, N. Colombo, G. Del Conte, A. Delmonte, T. Diena, M. Lapresa, G. Parma, L. Viganò, L. Gianni
Journal: Journal of Clinical Oncology (2010)

5050 Background: Based on synergism between mTOR inhibitor R and doxorubicin, a dose finding study of R with PLD was designed. Methods: Eligibility required: progressive advanced solid tumor, ≤ 2 prior chemotherapies for advanced disease, no anthracyclines within 12 months (cumulative dose ≤ 360 mg/m2) ANC ≥1.5 × 109/L, platelets ≥ 100 × 109/L, normal liver/renal function. PLD at 40 mg/m2 on day 1 q28 days and R for 3-4 weeks at 2.5-5-7.5-10 mg/d were given. The recommended dose (RD), defined as one level below the maximum tolerated dose (MTD), was tested in pts with ovarian and endometrial cancer. Pharmacokinetic (PK) sampling for PLD plasma disposition was obtained concomitantly (cycle 1) or 48 hrs before R (cycle 2), and for R concentration at steady state (Css) on days 8 and 15. Tumor response (RECIST) was evaluated every 2 cycles; adverse events during each cycle (CTCAE-NCI v3.0). Results: 48 patients were enrolled: median age 51.5 (range 21-72), ECOG PS 0 96% pts; tumor types: 30 ovarian (16 platinum resistant), 15 endometrial, 3 other. Dosing of R was shortened to 3 weeks after the 2.5 mg/d level due to mucositis (G2) leading to R discontinuation in 3 pts. MTD was defined at 10 mg/d due to 1/6 DLT (10 R doses missed due to stomatitis [G2]). Frequent toxicities were: stomatitis (G1-2 88.6%), nausea (G1-2 40%), palmar- plantar erythrodysesthesia (G1-2 31.4%), rash (26% G1-2; 5% G3). The concentrations at steady state (Css) of R on day 15 increased proportionally with dose up to 7.5 mg/day, while a disproportionate increase was observed at 10 mg/day. There was no evidence of PK interaction with PLD. A trend towards a minor decrease of the apparent PLD clearance on cycle 2 could also be due to accumulation of the drug in view of its long persistence in the blood. Among the 30 ovarian cancer pts 6 confirmed and 1 unconfirmed PR were observed. Three confirmed responses were in platinum-resistant pts. Among the 12 evaluable pts with endometrial cancer, 1 unconfirmed PR was observed. Conclusions: R (7.5 mg/d for 3 wks) with PLD (40 mg/m2) q 28 days is feasible without obvious PK interactions. Responses in ovarian cancer (20%) including cases with platinum resistant disease justify further testing of the combination. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration SENDO Foundation Genentech, GlaxoSmithKline, Novartis, Pfizer, Roche, Schering-Plough, Wyeth Schering-Plough
The accuracy of the HPV-associated diseases risk assessment inventory for detecting cervical dysplasias in medically underserved women in the United States.
Authors: M. S. Cyrus-David, W. Wang, G. Siddiqui
Journal: Journal of Clinical Oncology (2010)

1560 Background: Cervical cancer remains prevalent among medically underserved women in the United States, and in women in developing countries. Not all women who are exposed to HPV subsequently develop HPV-associated diseases (HPV-ADs). Further, mass vaccination of all eligible females in most developing countries is currently not tenable due to the prohibitive costs. Thus, the HPV-ADs Risk Assessment Inventory (RAI) was developed as a cheap, easy-to-use, method of detecting older adolescents or young women who are at high-risk of persistent HPV infections, who may subsequently develop HPV-ADs, for targeted preventive interventions. Methods: A panel of experts and lay women assessed the content validity. Criterion validity was retrospectively assessed on a consecutively recruited study sample of 116 sexually active young women, of low SES and medically underserved, who visited the Dysplasias Clinic of the Planned Parenthood of Houston Texas between 2007 and 2008. Each of the 17 items in the HPV-ADs RAI was assigned a risk score (i.e. with a range 0 for 'not at high-risk,“ to 1 or 2 for “at high-risk“ [i.e., depending on the severity] of cervical dysplasia). Then, a total score was computed for all subjects. The accuracies of the inventory as a predictor of cervical dysplasia or worse versus chance were assessed using standard statistical procedures. The investigators were blinded to the histopathologic diagnoses and did not administer the inventories. Results: The mean age of the subjects was 25 years. At an optimal cut-point of 5.0 for the inventory scores, the sensitivity, specificity, PPV, and NPV were 85%, 78%, 90%, and 70% respectively. The area under the receiver-operating characteristics curve was 0.97. Conclusions: Based on our findings, the HPV-ADs RAI is a useful tool for detecting cervical dysplasias, and would adequately triage eligible females for cervical cancer prevention programs in resources-poor settings. No significant financial relationships to disclose.