tbuckley/cabot-search huggingface dataset:
Doxorubicin and DTIC in organ transplant recipients with metastastic soft tissue sarcoma
Authors: D. Schoeler, B. Hildebrandt, U. Bachmann, P. Reichardt
Journal: Journal of Clinical Oncology (2006)

19502 Background: The development of cancer in organ transplant recipients is well known. Depressed immunosurveillance induced by the use of immunosuppressive agents for prevention of rejection is a causative factor. Kaposi’s sarcoma (KS), non-Hodgkin lymphoma and nonmelanoma skin cancers are more than 20-fold increased than in general population, EBV, HSV and HHV-8 seem to be causative. Other soft tissue sarcoma (STS) than KS are extremely rare post-organ transplantation tumours. Methods: Due to the fact that there is no “standard therapy” in organ transplanted STS patients we studied the feasibility, toxicity and response to a chemotherapy with doxorubicin (75 mg/m 2 , d1) and dacarbacine (DTIC, 300 mg/m 2 , d1–4). Two patients with metastatic disease (histology: poor differentiated uterine stromal sarcoma, poor differentiated malignant peripheral nerve sheath tumour, each n=1) were treated with up to 6 cycles of therapy. Results: One patient achieved a partial remission and dramatic improvement in life quality, the other patient achieved a stable disease after 2 cycles of therapy. Conclusions: Therapy with doxorubicin and DTIC is feasible in organ transplant recipients. Handling of the immunosuppression while chemotherapy is unproblematic. No significant financial relationships to disclose.
Expression of the Iron Regulatory Peptide Hepcidin Is Reduced in Patients with Chronic Liver Disease.
Authors: Greg Anderson, David M. Frazer, Kim R. Bridle, Graeme A. Macdonald, Jeffrey L. Smith, Bruno Turlin, Nathan Subramaniam, Darrell H. Crawford, Lawrie W. Powell, Grant A. Ramm
Journal: Blood (2005)
The role of octreotide imaging in detecting neuroendocrine tumors (NETs) in 2010: Do we still need it?
Authors: L. Saltz, M. Gollub, D. L. Reidy
Journal: Journal of Clinical Oncology (2010)

4032 Background: Somatostatin scintigraphy (OctreoScan, SRS) detects somatostatin receptors and images disease in patients with NETs. We sought to evaluate the utility of SRS when used in conjunction with modern CT or MRI and to determine if it added information to the CT or MRI. Methods: Electronic medical records identified all patients who underwent either a CT or MRI in addition to SRS within a 30-day time period at MSKCC (1/1/2003-6/11/2008). Reports of the SRS and CT/MRI were reviewed. Results: 104 patients were identified. 13 cases were nonevaluable and were excluded (1 merkel cell,1 unknown primary, 4 CT scans performed postsurgery with SRS performed pre-op, 3 patients with NET plus a second primary malignancy, 4 patients that had a limited CT for biopsy purposes). Of the 91 evaluable patients, 16 had functional tumors and 81 had metastatic disease. Nineteen were high grade, 7 intermediate grade, 56 low grade and 9 had no grade classification. There were 6 patients that had serial SRS plus either CT or MRI within a 30 day window. 18 patients had a negative SRS in the setting of clear metastatic disease on CT or MRI. Of those, 12 were high grade, 1 intermediate grade, 3 low grade and 2 unspecified. Notably, SRS missed hepatic metastases in 14 patients, in which, for 6 patients, this was their sole site of metastases. An additional 18 patients had findings on CT or MRI not seen on SRS and the liver was one of the most common sites missed. Four patients had positive findings on SRS that were not seen on CT or MRI imaging; all of these findings were bone lesions. None of the bone lesions were clinically relevant, defined as lesions that changed the clinical regimen, and all were in the setting of metastatic disease. Of the 6 patients who underwent serial SRS and CT or MRI, SRS did not detect any additional metastatic disease. Conclusions: Modern CT and MRI were able to identify soft tissue lesions with greater sensitivity than SRS. 5% of patients had clinically insignificant SRS avid bone metastases not seen on CT or MR. These data suggest that SRS is not a useful adjunct to defining extent of disease in NET tumors, and should not be used routinely for this purpose. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alchemia, Biothera, Delcath, ImClone Systems, Merck, Novartis, Roche Pfizer Amgen, Biothera, Bristol-Myers Squibb, Curetech, Genentech, ImClone Systems, Lilly, Merck, Pfizer, Roche, Tercica
Impact of age on treatment effect in locally advanced head and neck cancer (HNC): Two individual patient data meta-analyses
Authors: J. Bourhis, A. Le Maı̂tre, J. Pignon, K. Ang, J. Bernier, J. Overgaard, J. Tobias, M. Saunders, D. Adelstein, B. O’Sullivan
Journal: Journal of Clinical Oncology (2006)

5501 Background: The Meta-Analysis of Radiotherapy in Carcinomas of Head &amp; Neck (MARCH; Bourhis J, ASTRO 2002) showed that altered fractionation radiotherapy (Alt-RT) could improve survival as compared to standard RT in patients with locally advanced HNC (pooled hazard ratio - HR -: 0.92, 95% confidence interval: 0.86–0.97). The Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC; Bourhis J, ASCO 2004) demonstrated that concomitant chemotherapy (CT), added to RT, improved survival (HR: 0.82, 95% CI: 0.78–0.86). This study considers age as a potential modifier of the treatment effect. Methods: 15 randomized trials with 6,515 patients were included in MARCH (median follow up: 6.0 years), and 50 with 9,471 patients in concomitant part of MACH-NC (median follow up: 5.6 years). The interaction between age and treatment effect, using HR of death, was tested with heterogeneity test. Effect of prognostic factors on the interaction was analysed using Cox model. Results: The effect of Alt-RT in MARCH and of concomitant CT in MACH-NC on overall survival decreased with increased age ( table ). Patients aged 71+ had a lower performance status, less advanced stage, and more often laryngeal cancer than the younger patients; there were more women in the oldest patients group. However, adjusting on covariates did not modify the results. Causes of death was available in MARCH and in recent (1994–2000) trials of MACH-NC. The proportion of deaths not due to HNC increased with age, from 18% at age 50 to 41% at age 71+ in MARCH, and from 15% to 39% in MACH-NC. Conclusions: Treatment benefit decreases with increasing age. Patients aged 71+ did not benefit from Alt- RT nor from concomitant CT. The increasing risk of death from other causes with age may explain part of these observations. Supported by PHRC, ARC, LNCC [Table: see text] No significant financial relationships to disclose.
Targeted immune depletion prior to reduced-intensity allogeneic stem cell transplantation results in rapid and complete donor chimerism with low treatment-related mortality
Authors: R. M. Dean, D. H. Fowler, S. M. Steinberg, J. Odom, J. Gea-Banacloche, C. Sportes, N. Hardy, S. Pavletic, R. E. Gress, M. R. Bishop
Journal: Journal of Clinical Oncology (2006)

6540 Background: Significant variation in host immune status may influence outcomes after reduced-intensity (RI) allogeneic stem cell transplantation (alloSCT). We have investigated a strategy of targeted immune depletion (TID) with conventional chemotherapy to deplete host T cells and achieve a minimal disease state prior to RI alloSCT. The aim of TID is to rapidly establish complete donor chimerism after RI alloSCT in order to potentiate a graft-versus-tumor (GVT) effect. In a prospective phase II trial (NIH 03-C-0077), we evaluated the effect of TID on donor chimerism, acute graft-versus-host disease (GVHD), and clinical outcome. Methods: Thirty-one patients (pts) with relapsed and refractory hematologic malignancies (NHL = 16; HL = 4; CLL/PLL = 4; MDS/AML = 3; other = 4) were enrolled. Median age was 57 years (range: 31–71). All pts received EPOCH-F (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine) ± rituximab (R) as TID to deplete host CD4+ cells &lt;100/μL. All pts then received a RI conditioning regimen consisting of fludarabine and cyclophosphamide followed by a T-cell replete allograft from HLA-matched siblings. GVHD prophylaxis consisted of cyclosporine plus short-course mini-methotrexate. Results: EPOCH-F(R) achieved the target host T-cell level in 74% of pts. All 31 pts engrafted after RI alloSCT. Complete donor chimerism (&gt; 95%) was observed in 74% and 81% of pts at day +14 and +28 post-transplant, respectively. The incidence of grade II-III acute GVHD was 42% with no cases of grade IV acute GVHD. The median potential follow-up from transplant is 25 months. Actuarial treatment-related mortality at 1 and 2 years was 3% and 8%, respectively. Event-free survival probabilities at 1 and 2 years post-transplant are 65% and 49%, respectively. Ten pts are alive and event-free &gt;24 months post-transplant. The overall survival probabilities at 1 and 2 years are 84% and 64%, respectively. Conclusions: TID prior to RI alloSCT results in rapid, complete donor engraftment and may potentiate GVT effects. This treatment strategy was associated with very low TRM and favorable outcomes in an older patient population with advanced hematologic malignancies. No significant financial relationships to disclose.
The psychiatric uses of cold wet sheet packs
Authors: D R Ross, R Lewin, K Gold, H S Ghuman, B Rosenblum, S Salzberg, A M Brooks
Journal: American Journal of Psychiatry (1988)

The cold wet sheet pack is a treatment that is seldom discussed anymore. The authors present results of a national survey which demonstrated that this treatment is rarely used in modern American psychiatry. They retrospectively review its recent use for 46 hospitalized psychiatric patients and conclude that the treatment is safe and has interesting and useful effects that go beyond the concept of simple restraint. Further study of treatment with cold wet sheet packs is recommended before it disappears altogether.
Alternatively spliced truncated BCR-ABL1 protein in CML patients with resistance to kinase inhibitors
Authors: J. Bruey, H. Kantarjian, W. Ma, C. Yeh, R. Peralta, T. Lee, S. O'Brien, Z. Estrov, J. Cortes, M. Albitar
Journal: Journal of Clinical Oncology (2009)

7026 Background: We have reported that some patients with imatinib-resistant chronic myeloid leukemia (CML) express an alternatively spliced BCR-ABL mRNA with a 35-bp insertion (BCR-ABL1 35INS ), resulting in the addition of 10 residues and truncation of 653 residues. Molecular dynamic simulation suggested that this truncation and insertion of new 10 AA results in structural changes similar to those seen in BCR-ABL with T315I mutation. Here we evaluate the prevalence of BCR-ABL1 35INS in imatinib-resistant CML, examine the effect of this mutation on resistance to compared the efficiency of various kinase inhibitors in vitro, and suggest a model for persistent CML and a possible strategy to eradicate residual disease. Methods: Using a sensitive PCR method, we determined the prevalence of the alternatively spliced BCR-ABL1 35INS mRNA in 288 patients with chronic-phase CML resistant to imatinib. Expression of truncated protein was confirmed by Western blot. We then tested the effectiveness of various kinase inhibitors on human K562 CML cells expressing different levels of BCR-ABL1 35INS along with wild-type BCR-ABL1. Results: BCR-ABL1 35INS mRNA was detected in 210 (73%) of the 288 patients. Only 25% of BCR-ABL1 35INS positive cases showed coexistance of ABL1 kinase point mutation. Immunoprecipitation studies demonstrated that expression of the predicted 143-kD BCR-ABL1 35INS protein at levels proportional to those predicted by mRNA. Expression of BCR-ABL1 35INS in K562 cells was sufficient to conferred resistance to imatinib, dasatinib, and nilotinib in a dose-dependant fashion. However, no resistance was detected using aurora kinase inhibitor (MK 0457) or homoharringtonine (HHT). BCR-ABL1 35INS suppressed imatinib, nilotinib, and dasatinib-mediated dephosphorylation of CRKL, LYN, SRC, and STAT5, but had no effect on MK 0457-mediated dephosphorylation. The combination of imatinib with nilotinib or HHT showed strong synergy, overcoming BCR-ABL1 35INS -induced resistance in vitro. Conclusions: These findings emphasize the importance of the overlooked alternatively spliced BCR-ABL1 35INS protein and may provide a strategy to treat resistant disease and eradicate residual CML. No significant financial relationships to disclose.
Estimation of the epidemiological effect of trastuzumab over 10 years in 5 European countries
Authors: U. Weisgerber-Kriegl, A. Cirrincione, P. McNiven
Journal: Journal of Clinical Oncology (2008)

6589 Background: Trastuzumab (T) is now approved for the treatment of HER2-positive early breast cancer (EBC) in most European countries. Approval was based on the results of the HERceptin Adjuvant (HERA) trial, in which distant recurrence-free survival was reduced by half. The model assesses the long-term impact of T treatment in EBC on the annual number of patients entering the metastatic setting between 2005 and 2015 in five European countries. Methods: Annual EBC incidence for 2005–2015 was projected by applying stage-specific proportions for stages I-III, according to regional cancer registry data, to published female breast cancer incidence rates from 1990–2002. Age-specific rates for 2002 were then applied to United Nations population projections for 2003–2015. The annual number of patients with HER2-positive metastatic breast cancer (MBC) includes annual de novo MBC incidence plus patients with breast cancer recurrence. The baseline 10-year recurrence rate for standard treatment was estimated as 37%, based on 4-year follow-up in the control arm of a combined trial analysis in patients with HER2-positive breast cancer and the long-term timing of recurrence in all patients with breast cancer. To model recurrence in T-treated EBC patients, the hazard ratio (HR) from the HERA trial (0.49; 95% CI: 0.38, 0.63) was applied, resulting in an estimated 10-year recurrence rate of 18.1% (95% CI: 14.0, 23.3). Results: In 2004, prior to approval of T in EBC, the pool of de novo and relapsed MBC patients in the five countries was estimated to be 16,156. Between 2005 and 2015, the model predicts that the use of T will result in an annual decline of 2.5% (95% CI: 1.7, 3.2). The total number of patients saved from developing metastases over 10 years is projected to be 27,727 (95% CI: 20,116, 33,709). Conclusions: T treatment of HER2-positive EBC is expected to prevent nearly 28,000 women from developing metastases over a 10-year period in five countries alone, which may result in a similar number of breast cancer deaths being avoided. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration F. Hoffmann-La Roche Ltd F. Hoffmann-La Roche Ltd
Outcome of wire localized lumpectomies for nonpalpable breast lesion following neoadjuvant chemotherapy.
Authors: Samreen umer Khan, Syed Adil Asif Zaidi, Zoona Feroza, Sohaib adil Fiaz, Huma Majeed Khan, Mohammad Zulqarnain Chaudhary, Amina Iqbal Khan
Journal: Journal of Clinical Oncology (2014)

96 Background: Wire localized lumpectomies for non-palpable breast lesions is not yet a widespread practice in Pakistan. Shaukat Khanum Memorial Hospital is one of the few centers practicing this technique. It remains an effective and cost efficient procedure .The aim of this study is to evaluate wire-guided localization for nonpalpable breast cancer following neoadjuvant chemotherapy focusing on post-operative outcome and survival rate. Methods: It is retrospective analysis of consecutive series of patients treated at SKMH with BCS after wire localization for nonpalpable breast cancer following neoadjuvant chemotherapy from August 2005 to December 2011.The records were reviewed for patient, radiological, histological and surgical characteristics. The tumor volume analysis was calculated according to the Krekel et al method. Data was analyzed using SPSS (Version 19). Kaplan Meier curves were used to conduct survival analysis with respect to stage at presentation and pathological response to therapy. Results: A total of 195 patients were reviewed. The rate of positive margins; taken as less than 2mm, following initial BCT was 9.7%. Out of the 19 patients with positive margins 13 had re-excision of margins and 2 had completion surgery. One patient refused completion surgery. The rate of local recurrence was 6.6% and distal recurrence 17.9%.Out of 49 patients with recurrence 6 patients (12.24%) had both loco-regional and distal recurrence. The median resection ratio was 16.39. The median survival was 44 months (SD 17.162). There was a significant survival benefit (p = 0.03) in patients presenting at an early clinical stage whereas some clinic yet statistically non-significant survival advantage in patients undergoing surgery following complete radiological response after chemotherapy. Conclusions: Wire localized lumpectomies in post neoadjuvant chemotherapy patients at our institution has a low recurrence rate and an internationally acceptable re-excision rate. The size of the specimen can be optimized further. Early detection and management remains the mainstay of treatment for breast cancer. Patient education and screening are goals that are yet to be achieved on the grand scale in Pakistan.
Randomized, phase II trial of NGR-hTNF and chemotherapy in chemotherapy-naive patients with non-small cell lung cancer (NSCLC): Preliminary results.
Authors: V. Gregorc, N. Zilembo, F. Grossi, G. Rossoni, F. Pietrantonio, E. Rijavec, A. Bulotta, M. Vitali, G. Barletta, L. Bergamaschi, M. Platania, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2011)

7568 Background: NGR-hTNF is a highly selective vascular targeting agent, that binds CD13 overexpressed on tumor blood vessels, obtained by adding the NGR peptide to the human tumor necrosis factor (hTNF). By damaging tumor vasculature and decreasing interstitial pressure, NGR-hTNF improves penetration of cytotoxic agents within the tumor. Methods: Chemo-naive, stage IIIb-IV NSCLC patients (pts), stratified by histology (nonsquamous v squamous) and PS (0 v 1), were randomly assigned to receive either chemotherapy (CT) plus NGR-hTNF 0.8 μg/m2 day 1 (arm A) or CT alone (arm B). Brain lesions were included. Study regimens for both arms consisted of cisplatin 80 mg/m2 day 1 plus either gemcitabine 1,250 mg/m2 days 1,8 for squamous or pemetrexed 500 mg/m2 day 1 for nonsquamous histology, every 3 weeks up to 6 cycles. In arm A, NGR-hTNF was administered until progression (PD). Primary endpoint was progression-free survival (PFS). Assuming 15% increase in PFS rate (β=20% and α=20%), a sample size of 102 pts was calculated. Results: 82 pts have been enrolled so far and 64 (32 in each arm) were assessed for safety and preliminary activity. Baseline characteristics were (arm A/B): median age: 63/62 yrs; PS 1: 11/9; squamous: 8/8; men: 21/20. A total of 180 (1-17) and 133 cycles (1-6) were administered in arm A and B, respectively. Grade 3-4 toxicities for arm A v B were 23 v 34% for all events, listed as follows: neutropenia 13 v 15%; thrombocytopenia 3 v 6%; fatigue 3 v 12%; renal or respiratory failures 0 v 6%; thromboembolism 6 v 0%. Grade 1-2 hypertension was 3% in arm A v 11% in arm B. No grade 3-4 toxicities related to NGR-hTNF were noted, while 31% of pts had NGR-hTNF-related grade 1 transient chills. Median follow-up was 8.6 months in arm A and 5.5 in arm B. In nonsquamous pts (n=48), PFS at 8 months was 38% in arm A and 18% in arm B, whereas in pts who experienced disease control (n=36), including partial response (PR) plus stable disease (SD), was 51% in arm A and 21% in arm B. In squamous pts (n=16), 2 PR, 5 SD and 1 PD were noted as best responses in arm A and 1 PR, 4 SD and 3 PD in arm B. Conclusions: NGR-hTNF can be safely combined with chemotherapy in NSCLC, regardless of histology and with promising activity.
Editorial
Authors: Antony J. Workman, Andrew C. Rankin
 *
Journal: Cardiovascular Research (1998)

Serotonin (5-hydroxytryptamine, 5-HT) has a wide load, calcium oscillations and triggered activity.A further diversity of actions throughout the body, including the arrhythmogenic mechanism is suggested in the paper by nervous, gastrointestinal and cardiovascular systems., which describes the action of vances have been made in our understanding of the serotonin on the hyperpolarisation-activated current, I , in f
International Guidelines for the Definition of Time to Event Endpoints (Tee) in Renal Cell Cancer (Rcc) Randomised Clinical Trials (Rct): Results of the Datecan Project
Authors: A. Kramar, T. Filleron, R. Sylvester, B. Escudier, S. Joniau, P. Mulders, S. Negrier, T. Powles
Journal: Annals of Oncology (2014)
Japanese D3 lymph node dissection in low rectal cancer with inferior mesenteric lymph node and/or lateral lymph node metastases.
Authors: Mamiko Ubukata, Michio Itabashi, Shimpei Ogawa, Tomoichiro Hirosawa, Yoshiko Bamba, Sayumi Nakao, Shingo Kameoka
Journal: Journal of Clinical Oncology (2015)

530 Background: The current Japanese Classification of Colorectal Carcinoma defines inferior mesenteric lymph nodes (IMLN) and lateral lymph nodes (LLN) as regional lymph nodes in rectal cancer. It states that these lymph nodes should be dissected when performing D3 dissection for rectal cancer. However, there is currently no consensus on the significance of Japanese D3 lymph node dissection in low rectal cancer. A retrospective study involving a large number of patients was conducted. Methods: The subjects were 2,743 patients registered in the multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum. The data were analyzed for outcomes in R0 cases with IMLN and/or LLN metastasis (IMLN(+)LLN(-) or IMLN(-)LLN(+) or IMLN(+)LLN(+)). Results: In the control group, 67 patients (2.7%) were considered positive for IMLN metastasis, 181 patients (7.4%) for LLN metastasis, and 34 patients (1.4%) for IMLN + LLN metastasis. The outcomes in the R0 cases with IMLN and/or LLN metastasis were 52.8% for 5-year RFS and 63.1% for 5-year OS, which were each better than for R1+R2 cases (5-year RFS 26.2%, p&lt;0.0001; 5-year OS 30.5%, p&lt;0.0001). Including only those with a total of seven or more metastatic lymph nodes, the outcomes in the R0 cases with IMLN and/or LLN metastasis were 53.6% for 5-year RFS and 64.9% for 5-year OS, which did not differ significantly from those for IMLN(-)LLN(-) cases (5-year RFS 54.4%, 5-year OS 55.2%) (RFS: p=0.9718, OS: p=0.4049). Conclusions: We confirmed that cases of IMLN and/or LLN metastasis in low rectal cancer tend to have a large total number of metastatic lymph nodes, but a good outcome can be expected if curative resection can be performed. These results demonstrate the value of radical Japanese D3 lymph node dissection in low rectal cancer with IMLN and/or LLN metastasis.
High-Dose Methotrexate Seems to Benefit Only to Standard-Risk BCP-ALL Patients with Good Early Response to Chemotherapy: Final Analysis of the FRALLE93B Study
Authors: Thierry Leblanc, Judith Landman-Parker, Marie-Françoise Auclerc, Krystell Desseaux, Christiane Vermylen, Claudine Schmitt, Virginie Gandemer, Odile Lejars, Jean-Pierre Vannier, François Demeocq, Christian Berthou, Gérard Couillault, Brigitte Pautard, Claire Berger, Lionel De Lumley, Marianne Debré, Gérard Michel, Yves Perel, Guy Leverger, Andre Baruchel
Journal: Blood (2008)