tbuckley/cabot-search huggingface dataset:
Changing law and clinical dilemmas
Authors: W D Weitzel
Journal: American Journal of Psychiatry (1977)

The author describes a case in which a severely depressed suicidal patient was treated with ECT despite her refusal to grant permission while involuntary commitment procedures were pending. He discusses the professional dilemmas caused by new, and sometimes conflicting, legal principles such as the right to treatment and the right to refuse treatment and suggests that psychiatrists work to clarify these principles while saftguarding themselves with the aid of appropriate legal counsel.
Gemcitabine (GEM) (day 1–8) plus carboplatin (CBDCA) (day 2) for the treatment of advanced non-small cell lung cancer (aNSCLC) in elderly or poor performance status (PS) patients (pts)
Authors: F. Sperandi, B. Melotti, A. A. Martoni
Journal: Journal of Clinical Oncology (2007)

18116 Background: Several studies have demonstrated that the combination of CBDCA plus GEM according to various regimens appears as effective as cisplatin (CP) containing regimens. CBDCA plus GEM regimens are associated with more haematological toxicity (G3–4 leucopenia 17–40.6%, G3–4 neutropenia 29–75%, G3–4 thrombocytopenia 21–57% and G3–4 anaemia 5–33%), but with lower non-hematological toxicity as compared to CP-based regimens. Methods: The primary objective of this trial was the evaluation of the overall survival, while the secondary objectives were assessment of objective response and toxicity in elderly or poor PS pts. The eligible pts had previously untreated aNSCLC not suitable for CP-based chemotherapy. Pts received each at 3-week intervals GEM 1000 mg/sq on day 1 and 8 plus CBDCA area under the curve of 5 on day 2. Between April 2004 and January 2007, 54 consecutive pts were accrued in the study. Pt characteristics were: 42 (78%) males and 12 (22%) females; median age 72 years (range: 56–84 years) with 67% of pts = 70 years; median Karnofsky PS 90 (range: 50–100) with 33% of pts = 80; stage disease: IIB not suitable for surgery in 1 (2%) pt, IIIA in 5 (9%), IIIB in 10 (19%), IV in 33 (61%) and recurrent disease in 5 (9%); histologic subtype: adenocarcinoma in 30 (56%) pts, epidermoid in 11 (20%), bronchioalveolar carcinoma in 2 (4%) and other histologic subtypes in 11 (20%). Results: A median of 4 courses was administered (range 1–8). Dose- intensity was 98.7% (range 50–100%) for CBDCA and 87.2% (range 60–100%) for GEM. Objective response according to intention-to-treat analysis was as follows: 15 (28%) pts had PR, 16 (29%) had SD, 14 (27%) had PD and 9 (16%) were not assessable because lost to follow-up or too early. Median overall survival was 10 months. WHO G3 leucopenia was observed in 5 (9%) pts, G3–4 neutropenia in 15 (28%), G3 thrombocytopenia in 7 (13%) and G3 anaemia in 2 (4%). No WHO G3–4 non-hematological toxicity was observed. Conclusions: This regimen is feasible and active in elderly or poor PS pts. It can be administered in a outpatient setting because toxicity is moderate and manageable. No significant financial relationships to disclose.
Phase I/II study of the association of sorafenib and temozolomide (extended schedule) in patients with metastatic melanoma: A new clinical response profile with massive tumor necroses
Authors: C. Robert, V. Lazar, L. Lacroix, F. Farace, N. Lassau, C. Dromain, V. Poirier, L. Zitvogel, J. Soria, C. Mateus
Journal: Journal of Clinical Oncology (2009)

9062 Background: Recent progress in melanoma research identified a wide variety of different melanomas in term of biology, clinical behavior and chemosensitivity profiles. This phase I/II study of association of sorafenib (SOR) and temozolomide (TMZ) evaluates the safety and efficacy of this association in patients with metastatic melanoma and tries to correlate clinical responses to early biological and imaging parameters. We report the ph I results and preliminary results of the ph II (still recruiting pts). Methods: Safety was the primary objective of the phase I and three escalating dose levels were tested. Primary objective of the phase II is PFS at 12 weeks and 32 patients were recruited at the recommended (45 planned). Secondary objectives evaluate tumour vascularization by dynamic contrast enhanced ultrasonography (DCE-US), PK profile of TMZ, number and function of circulating lymphocytes, melanoma RNA expression profiles and mutational status (BRAF, NRAS, c-KIT, PTEN, PI3K, βcat), circulating endothelial and progenitor cells. Results: 13 evaluable pts were included in the phase I. The recommended doses are SOR: 400 mg bid and TMZ: 150 mg/m2 /d every other week. Toxicity was manageable. SOR did not influence TMZ PK. RECIST evaluation showed 1 CR (+ 12 months), 1 PR (+ 13 months), 3 SD, 8 PD. Among the 23 evaluable pts included in the phase II, 1 PR, 11 SD and 11 PD were observed. Five pts presented rapid and massive metastases necrosis with obvious tumour cavitation on CT which is very unusual during the course of melanoma treatment. Devascularization seen on DCE-US after 1 month was predictive of tumour response. Integrated correlative biological parameters are being analyzed and will be presented. Conclusions: SOR+TMZ association is well tolerated and gives promising results in some patients with metastatic melanoma. Unexpected major tumour necrosis has been observed in 5 patients. Early tumour devascularization observed by DCE-US seems predictive for tumour response. Extensive biological studies are being performed and might give useful clues allowing the identification of melanoma subtypes that are sensitive to this treatment regimen. No significant financial relationships to disclose.
A novel DNA marker associated with breast metastasis
Authors: H. Zhao, T. Ray, P. Robinson, C. Miyamoto, M. P. Achary
Journal: Journal of Clinical Oncology (2004)

681 Background: Differentiating primary breast tumors that are prone to develop metastasis (Group-I) from those that are not (Group-II) is critical to design appropriate treatments. Previously we isolated several metastasis associated DNA sequences (MADSs) and recently published that MADS-IX and -XI are informative in more than 60% of cases by PCR screening. Our previous attempts to supplement the PCR method with Fluorescence In Situ hybridization (FISH) for screening MADS-IX on primary tumor tissue sections were not consistent due to overlapping of cells and unclear cellular margins. Here we present our results with MADS-IX as a FISH probe in distinguishing the Group-I and Group-II primary breast tumors by screening tumor cell touch preparations. Methods: The DNA samples from primary and metastatic tumor cells isolated from 12 breast carcinoma patients had been compared with the matching normal cell DNA by the Representational Difference Analysis (RDA) and isolated 15 MADSs. Tumor cells were isolated by laser capture microdissection from archival samples whose clinical outcome was known. In the tumor cell touch preparation method, the tumor tissue material was exposed by trimming of the paraffin material from the block and then by touching the tumor tissue side at several places on a slide. Conventional methods were used to fix the cells followed by our FISH procedure. We used 3 cases of primary tumors that had positive lymph nodes (LN) and another 3 that had not (within 5 years of treatment). Results: The tumor touch preparations provided with clear and reproducible results. Group-I tumors with +ve LNs showed cells with no loss of MADS-IX in 54%; heterozygous loss in 38% and homozygous loss in 8%. Group-II tumors with –ve LNs, on the other hand showed cells with no loss of MADS-IX in 80%; heterozygous loss in 20% and none with homozygous loss. Conclusions: Basing on these studies, we propose that MADS-IX could be used as a candidate DNA marker to differentiate breast tumors that are prone to develop metastasis from the rest. This finding has a potential for better diagnostic grouping and treatment. Aside from screening additional breast tumors, cDNA expression profiling of the tumors are in progress. No significant financial relationships to disclose.
Phase I dose escalation study of continuous oral dosing of OSI-906, an insulin like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitor, in patients with advanced solid tumors
Authors: C. R. Lindsay, E. Chan, T. R. Evans, S. Campbell, P. Bell, A. W. Stephens, A. Franke, S. Poondru, M. L. Rothenberg, I. Puzanov
Journal: Journal of Clinical Oncology (2009)

2559 Background: OSI-906 is a potent small molecule inhibitor of IGF-1R, a receptor tyrosine kinase activated by insulin like growth factor, which is overexpressed in numerous malignancies and implicated in resistance to chemotherapy. Methods: Patients with advanced cancer entered escalating dose cohorts of OSI-906. Study objectives included assessment of: safety; determination of MTD; pharmacokinetics (PK), pharmacodynamics (PD) including IGF-1R levels in peripheral blood cells; and tumor response (RECIST). Results: To date, 32 pts have been treated (22M/10F, median age 62y) at 10, 20, 40, 75, 150, and 300 mg QD and at 20, 40 mg and 75 mg BID. Median number of weeks on trial was 6 (range 0–44). No DLTs have been observed. Hyperglycemia (5/20 pts) related to OSI-906 was transient and mild (grade 1 only). In addition to hyperglycemia, grade 1–2 nausea and vomiting (5/20 pts) were the most frequent related adverse events (AEs). There was grade 3 elevated lipase in 1 pt. At doses of 10–150 mg, OSI-906 exhibited linear PK, median terminal t 1/2 ranged from 2.18–4.30 hr, AUC 0-inf from 284–10200 ng.hr/mL, and C max 76.6–1440 ng/mL. There was no relationship between glucose or insulin levels and OSI-906 plasma concentrations. Stable disease &gt; 12 weeks was seen in 7/20 pts (range 12–34 weeks), including 1 pt each with thymic (27 w), adrenocortical (28w), and colorectal (34w) cancer. PD data on IGF-1R phosphorylation will be presented. Conclusions: Plasma concentrations of OSI-906 achieved in this trial exceed concentrations required for antitumor efficacy in preclinical models. PD target modulation and preliminary anti-tumor activity have been observed. It is interesting to note that clinically meaningful hyperglycemia has yet to occur. Minimal toxicity was observed and further dose escalation is in progress. [Table: see text]
Testosterone recovery after permanent prostate seed implantation in patients with neoadjuvant hormonal therapy.
Authors: N. Hayashi
Journal: Journal of Clinical Oncology (2011)

e15067 Background: The PSA kinetics in patients undergoing prostate brachytherapy with neoadjuvant hormonal therapy (NHT) is dependent on the recovery of serum testosterone(T) levels. When NHT was done, determination of PSA nadir is sometimes very confusing because of variety pattern of testosterone recovery. In this study, we assessed the duration of testosterone recovery and its effect on PSA kinetics in Asian (Japanese) men. Methods: From March 2004 to September 2010, 612 patients underwent I125 seed implantation in our institution. The records of 306 patients with NHT and a minimum of 2 years of follow-up were reviewed. Among those, 243 had serum testosterone level measurement every 3-6 months. All patients had at least 2 years of follow-up and were ceased androgen ablation after seed implantation. Prognostic factors for testosterone recovery were examined using multivariate Cox regression analysis. Results: Of 243 patients (age 48-81) with T1-T2 N0M0 prostate cancer, 207 had appropriate data. NHT included maximum androgen blockade (MAB) in 47 patients (22.7%), LHRH analog (LHRHa) in 157 (75.8%) and anti-androgen agent in 3(1.5%). The median duration of NHT was 11 months (range 3-72M). 94.7% of patients (n=196) recovered normal T levels (7.2 nmol/l) and median time to recover was 6.9 months (MAB group 9.0M, LHRHa group 6.5M). When PSA nadir was defined after 6.9M (207 days) of brachytherapy, 2 patients (4.3%) had biochemical failure (BF; nadir+2ng/dl) and 2 (4.3%) had PSA bounce (PB) in MAB group while 3 patients (1.9%) had BF and 7 (4.5%) had PB in LHRHa group. Total BF free rate was 5.8% and PSA bounce rate was 16.0%. 11 patients (5.3%, median NHT duration 10 months) did not recover normal T levels. On multivariate analysis, younger age (p=0.016, 95% C.I. 0.945-0.994) and the use LHRHa as compared with MAB (p=0.004. 95% C.I. 0.028-0.504) could be the prognostic factors for testosterone recovery. The duration of NHT was not significant (p=0.211) in this study. Conclusions: 78.3% and 95.4% of patients recovered normal serum testosterone levels within a year and 2 years, respectively. Defining PSA nadir according to T recovery seems useful in appropriate follow-up of patients undergoing brachytherapy with NHT.
CEA radioimmunotherapy of post-salvage resected colorectal cancer liver metastases is safe and potentially effective in extending survival
Authors: T. Liersch, T. M. Behr, J. Meller, P. Schüler, P. Markus, C. Ding, J. Kovacs, I. Horak, H. Becker, D. Goldenberg
Journal: Journal of Clinical Oncology (2004)

3155 Background: Radioimmunotherapy (RAIT) was performed in the setting of post-salvage-resection of colorectal cancer metastases to the liver. Methods: Nineteen pts were studied in an exploratory Phase-II trial with 131I-hMN-14 (131I-labetuzumab), a humanized antibody against carcino-embronic antigen (CEA). Safety and efficacy of RAIT were evaluated, with time-to-recurrence and overall survival being determined using the Kaplan-Meier product-limit method. Results: The 19 pts were 12 males, 7 females; 17 were 70 years or younger; the primary disease site was colon in 7, rectum in 10, and both in 2; 10 had lymph node involvement and 9 didn't; after surgery of primary colorectal cancer, 10 had <12 months disease-free intervals and 9 were longer; 7 had 1 tumor in the liver and 12 had more. Eighteen pts received 1 infusion of the RAIT regimen at a dose level of 50–60 mCi/m2 and 2 pts received a second infusion after the initial RAIT. Six pts had grade 3/4 hematological toxicities (WBC, platelets, and ANC) without spontaneous bleeding during the first 10 weeks after RAIT, full bone marrow recovery and no other major treatment-related events. The median time-to-recurrence was 18.4 mos; median survival from liver resection was 54 mos as of November 30, 2003 (8 deaths). Current survival rates are: >1 year: 95%; >2 yrs: 84 %; >3 yrs: 68 %; >4 yrs: 58%. Conclusion: This is the first study of RAIT in this setting, and showed both a good safety profile of the 131I-hMN-14 humanized antibody and promising median survival results in patients with salvage resection of colorectal metastases to the liver. No significant financial relationships to disclose.
Multiparametric prostate MRI and MRI/ultrasound fusion biopsy as tools to follow prostate cancer progression for men on active surveillance.
Authors: Nabeel Shakir, Annerleim Walton-Diaz, Soroush Rais-Bahrami, Baris Turkbey, Jason Rothwax, Cheng William Hong, Lambros Stamatakis, Arvin George, Chinonyerem Okoro, Dima Raskolnikov, Minhaj Siddiqui, Daniel Su, Richard Simon, Bradford J. Wood, Peter L. Choyke, Peter A. Pinto
Journal: Journal of Clinical Oncology (2014)

63 Background: Active surveillance (AS) is an option for patients with low risk prostate cancer (PCa); however, determining disease progression is challenging. At the NCI, multiparametric MRI (MP-MRI) with our biopsy protocol (MR-US fusion-guided plus 12 core extended sextant biopsy) has been used to confirm eligibility for AS. We evaluated the utility of these modalities in monitoring patients on AS. Methods: Patients who underwent MP-MRI of the prostate with biopsy per our protocol between 2007-2012 were reviewed. We selected a subset who met Johns Hopkins criteria for AS (Gleason score≤6, PSA density≤0.15, tumor involvement of ≤2 cores, and ≤50% of any single core) by outside 12−core TRUS biopsy. Patients with Gleason score≤6 confirmed at first NCI biopsy session were followed with annual MP-MRI and biopsy. MRI progression was defined as an increase in MP-MRI suspicion level, lesion diameter, or number of lesions. Pathologic progression was defined as an increase to Gleason score≥7 in either 12-core or MR-fusion biopsy. We determined the association between MRI and pathologic progression. Results: 129 patients met JHU criteria for AS by outside biopsy. Mean age was 61.6 years and mean PSA 5.16ng/mL. 28/129 (21.7%) patients had Gleason score ≥7 at first NCI biopsy session.31 patients had at least two biopsy sessions (mean follow up 18 months, range 12-54 months) of which 9/31 (29%) increased in Gleason score, all to 3+4=7. Fusion biopsy detected more pathologic progression than did standard biopsy (Table). The positive predictive value of MP-MRI for pathologic progression was 50%, while the negative predictive value was 84%. The sensitivity and specificity of MP-MRI for increase in Gleason score was 67% and 73%, respectively. Conclusions: Stable findings on MP-MRI are associated with Gleason score stability in patients with low-risk PCa choosing AS. The majority of patients who had pathologic progression were detected on fusion biopsy, which may suggest that random biopsies are unnecessary in this population. Larger studies are needed to validate these findings. [Table: see text]
Biological factors in human cutaneous melanoma correlated to disease stage
Authors: E. G. Elias, B. K. Sharma, J. H. Hasskamp, A. M. Avergas, S. L. Beam, J. N. Broussard, J. L. Zapas, E. C. McCarron, W. J. Culpepper
Journal: Journal of Clinical Oncology (2009)

9053 Background: Cutaneous melanoma cells express a variety of cytokines and growth factors (C/GF) as the tumor progresses. This study was undertaken to identify various C/GF at different stages of the disease with the hope of identifying prognostic factors. Methods: Immunohistochemical (IHC) studies were performed on 62 specimens of parafinized human melanoma comprised of 12 primaries, 10 local recurrences, 6 intransit, 15 regional lymph node and 19 distant metastases. Staining for 17 C/GF was performed using commercially available antibodies on Bond-Max automated IHC system. Results: The overexpression of C/GF in primary lesions was compared to distant metastases with regard to intensity and extent of staining. Data was dichotomized as positive (dark staining) or negative (lesser or no staining). There was simultaneous intense staining of 4–15 C/GF in primaries and 3–14 C/GF in metastatic lesions. Comparing primaries to metastases by Chi-Square using Fisher's exact test, statistical differences were seen in intensities of transforming growth factor-β (p&lt;0.001), β-catenin (p&lt;0.01), Bcl-2 (p&lt;0.01). Staining intensities of IL-8 approached significance (p&lt;0.058). Statistical differences in extent of staining between primaries and metastases were found for insulin-like growth factor-1 (p&lt;0.01), fibroblast growth factor-basic (p&lt;0.05) and IL-15 (p&lt;0.05). Conclusions: Potential dynamic changes in overexpression or loss of expression of C/GF in metastatic melanoma is not clearly understood and may reflect on mutations. Melanoma is an extremely heterogeneous tumor and no single targeted therapeutic agent can control this disease. No significant financial relationships to disclose.
Clinical predictors of response to sorafenib in patients with hepatocellular carcinoma.
Authors: Sara Marinelli, Alessandro Granito, Eleonora Terzi, Simona Leoni, Fabio Piscaglia, Laura Venerandi, Luigi Bolondi
Journal: Journal of Clinical Oncology (2013)

e15149 Background: Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). Little is known about clinical-laboratoristic parameters predicting treatment benefit. Methods: Between 2008-2012, 94 consecutiveclinically compensatedcirrhoticpatients [M/F=85/9, median age 69-years (38-88)] with advanced HCC (BCLC-C, n=57) and those with an intermediate HCC (BCLC-B, n=37) who failed to respond or not eligible to locoregional therapies, received sorafenib. Clinical-laboratoristic data were reviewed. RECIST criteria were used to assess objective benefit. Toxicities were classified using NCIC Toxicity Criteria v-3.0 and treatment managed according to drug label. Results: The median treatment duration (TD) was 3.9 months (range 0.1-48). The median survival was 9.2 months (range 0.4-45). On the basis of TD we identified two groups of patients with a significant different overall survival (OS): group A (TD&gt;6.6 months, median-TD 11.4, 33 patients) and group B (TD&lt;6.6 months, median-TD 2.3, 61 patients). Median OS in group A and B was 20.6 and 6.6 months, respectively (p&lt;0.001). CPT score, BCLC stage and neoplastic portal vein thrombosis were similar in the two groups. On univariate analysis, group A showed an higher rate of ECOG-PS 0 (75% vs 50%, p=0.034), lower basal serum levels of alfa fetoprotein (best cut-off: AFP&lt;19 ng/dl, p=0.006). Fatigue and nausea were more frequent in group B (67.2% vs 43.8%, p=0.044; 19.3% vs 3.2%, p=0.05, respectively). ECOG-PS 0, AFP serum levels and nausea were significantly associated with a longer OS (p=0.003; p=0.006; p=0.008, respectively, log-rank test). On multivariate analysis, basal AFP levels (&gt;19 ng/ml) remained predictor of shortened OS (p=0.028, OR=4). Conclusions: Development of nausea and fatigue on sorafenib is associated with poorer OS. AFP basal levels &lt;19 ng/ml indipendently predict a better survival. Clinical-laboratoristic parameters may be useful to identify patients more likely to benefit from sorafenib.