tbuckley/cabot-search huggingface dataset:
Are we improving the outcomes of metastatic breast cancer (MBC)? A single academic institution experience.
Authors: A. Florescu, S. Giilck, C. Victor, U. Zurawska, D. A. Baribeau, S. Verma
Journal: Journal of Clinical Oncology (2011)

1105 Background: Over the last two decades we have seen a tremendous improvement in the outcomes of patients with early stage breast cancer. There is limited literature if we are improving the survival of our patients with MBC. Methods: We conducted a chart review of two cohorts of MBC patients ≥ 18 years at a cancer centre in Canada. The early cohort comprised of women seen between 1997-2002; the late cohort consisted of women seen between 2007-2010. Tumor characteristics and survival between the 2 cohorts were compared. Results: A total of 295 cases were reviewed of which 274 met inclusion criteria. Of these, 126 belonged to the early cohort and 148 to the late cohort. Age at diagnosis was similar in the two groups (average age=58 years). Fewer cases in the late cohort had grade III disease (35.7% vs. 25.0%, p=0.007). With respect to BC subtypes, 73.1% of late cohort cases were ER+ (vs. 68.2%, p=0.400); 19.7% were Her2+ (vs. 16.3%, p=0.021); 14.5% were Triple Negative (vs. 15.8%, p=0.854). Chemotherapy use in the metastatic setting, anti-estrogen therapy and trastuzumab were similar in the 2 groups: 63.7% vs. 52.1% p=0.084, 66.1% vs. 68.3% p=0.791, and 8.1% vs. 11.8% p=0.409, respectively. Use of biologic agents was higher in the late cohort (0% vs. 6.9% p=0.002). Survival at 1 year was 82.5% in the early cohort and 88.4% in the late cohort (p=0.214) and 2-year survival was 63.9% and 77.8%, respectively (p=0.062). Overall survival was not significantly different between the 2 cohorts (chi square=2.79, p=0.102); survival in the first 24 months from diagnosis of MBC showed a trend towards benefit in the late cohort (chi-square=3.02, p=0.082). In multivariate analyses, being in the late cohort was associated with a 60% lower mortality rate compared to the early cohort (HR=0.40 95% CI 0.18-0.93, p=0.032) in the first 24 months after diagnosis, but this difference was not maintained at ≥30 months. Conclusions: Our institutional experience suggests that there appears to be a marginal improvement in outcome of MBC patients over the last decade, with an improved outcome at 1 yr and 2 yr survival rates but no significant improvement in the median overall survival.
Correlation of serum cytokines with clinical responses in patients treated with BPX-101, a drug-activated vaccine for metastatic castration-resistant prostate cancer (mCRPC).
Authors: D. M. Spencer, N. Lapteva, J. M. Levitt, M. Seethammagari, G. Sonpavde, J. D. McMannis, Y. Bai, J. M. Bull, K. M. Slawin
Journal: Journal of Clinical Oncology (2011)

167 Background: We report the correlation of clinical and immune monitoring results for subjects enrolled in a phase I/IIa clinical trial of BPX-101, a drug-activated dendritic cell vaccine for mCRPC. Methods: Men with progressive mCRPC were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and activating agent AP1903. BPX-101 was administered intradermally every 2 weeks for 6 doses, during the induction phase, and for non-progressing patients, every 8 weeks for up to 5 doses during the maintenance phase. AP1903 (0.4 mg/kg) was infused 24 hours after each BPX-101 dose. Blood samples for immune monitoring were collected weekly during the induction phase, and before and one week after each maintenance dose. GM-CSF, TNF-α, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, and RANTES levels were measured by Luminex microspheres, and IL-6 by ELISA. Results: Planned enrollment of 12 subjects is complete, including 3 each at 4 × 10 6 and 12.5 × 10 6 cells/dose, and 6 at 25 x 10 6 cells/dose. A pattern of spiking levels of serum cytokines one week after each dose, returning to baseline the following week, was observed in subjects with greater disease burden. In one low dose subject who experienced a PR after one year on study, panel cytokines spiked 4-fold on average after each induction phase dose, less than 2-fold after the first two boosters, and between 6-fold and 56-fold after the final three boosters. IL-6, which had declined during the induction phase to below 1 pg/mL through two boosters, spiked between 1,680-fold and 13,000-fold after each of the last three boosters. In a second, high dose subject (#1008), who experienced a near CR of multiple lung metastases with otherwise stable disease, panel cytokines spiked 150-fold on average during the induction phase. In both cases, TNF-α, MIP-1α and MIP-1β spiked the most, including a more than 1,000-fold average spike in TNF-α for subject 1008. Cytokine spikes were not associated with AEs. Conclusions: BPX-101 induces a spiking pattern of cytokine elevations after each dose. In patients who experienced measurable disease reductions, more dramatic spikes in serum inflammatory cytokine levels were seen. [Table: see text]
The influence of daily localization during treatment of prostate cancer on acute toxicity.
Authors: Peter john Rossi, Sherrie Cooper, Ashesh B. Jani
Journal: Journal of Clinical Oncology (2012)

214 Background: Various localization techniques are used in clinical practice but little comparative effectivess data exists. The purpose of this investigation is to assess the impact of daily localization (L) of the prostate on toxicity during definitive treatment of prostate cancer with intensity modulated radiotherapy (IMRT). Methods: This study details an IRB approved retrospective review of three cohorts of patients treated for prostate cancer utilizing IMRT and different L technologies at four academic hospitals. Patients were treated with no technique (N), gold markers (G), or electromagnetic beacons [Calypso] (C) for daily L. Acute genitourinary (GU) and gastrointestinal (GI) toxicity was assessed according to RTOG toxicity criteria; toxicity rates between the groups were compared using the chi-square test. Ordered logit regression of all major demographic (age, race), disease (PSA, Gleason grade, and T-stage) and treatment (hormones, pelvic nodal treatment, total dose, and prior TURP) characteristics on GU and on GI toxicity were performed. Results: One hundred fifty four men who received definitive dose escalated IMRT (no brachytherapy or post-prostatectomy patients) for prostate cancer from 2006 to 2010 and were included (G: n=47; C: n=47; N: n=60). The cohorts were balanced except race (higher percentage of African Americans in the N group, due to hospital demographics) and higher grade and use of pelvic nodal treatment (which were more common in the G and C groups). Bladder V40 and V70 were higher in the N group (45.4%/24.3%) compared to C (27.9%/12.3%) and G (37.4%/18.4%) groups; however, rectal V40 and V70 were similar among all 3 groups. Toxicity results are shown in the Table; as shown the C and G groups had lower GU toxicity (p &lt;0.001) respectively compared to the N group; no significant differences in GI toxicity were seen among the 3 groups. Ordered logit regression showed only daily L (p=0.041) reached significance in lowering GU toxicity, and only pelvic RT use (p =0.008) reached significance in increasing GI toxicity. Conclusions: In patients treated with IMRT, daily L was associated with lower acute GU toxicity but not acute GI toxicity.
First-line sunitinib in patients with renal cell carcinoma (RCC) and von Hippel-Lindau syndrome (VHL).
Authors: A. Roma, U. Basso, A. Brunello, M. Maruzzo, V. Zagonel, M. Nardin, E. Bezzon, S. Zovato, G. Opocher
Journal: Journal of Clinical Oncology (2011)

373 Background: VHL is a rare hereditary condition caused by germline alteration of VHL gene predisposing to multiple renal and other tumors. Since acquired dysregulation of VHL-dependent pathways is often present in patients with sporadic RCC treated with first-line sunitinib (SUN), there is a strong rationale to use the same drug in VHL patients with progressive disease in the kidneys or other sites. Methods: We performed a retrospective analysis of SUN therapy in genetically confirmed VHL patients treated at our Institution for multifocal or advanced RCC. Results: From February 2007 to October 2010, 9 VHL patients were proposed first-line SUN for RCC, mean age 44 yrs (26-60), F:M ratio 2:1. SUN was administered for a mean of 9 cycles (1-20). Eight of 9 pts received at least two cycles and were considered for response evaluation: all 8 were stable according to RECIST criteria, but decrease in radiological density of lesions was observed in 7 of 8 pts (87.5%). Density decrease was noted not only in renal and hepatic lesions but also in some pancreatic nodules; all CNS haemangioblastoma lesions remained stable (see table). Preliminary median PFS is &gt; 13 months (8 censored, 1 deceased). Conclusions: SUN treatment in VHL patients appears to achieve good disease control not only in renal tumors but also in synchronous VHL-related lesions, especially pancreatic solid nodules whose exact nature (metastatic RCC or neuroendocrine tumor) cannot be ruled out without invasive biopsies. [Table: see text] No significant financial relationships to disclose.
Planning the boost in early-stage breast carcinoma: Comparison of two methods.
Authors: Vanesa Krakobsky
Journal: Journal of Clinical Oncology (2012)

e11555 Background: When it comes to breast-conserving surgery the boost volume becomes a critical target: it has the highest risk of residual cancer cells. Failing this target may impact local recurrence outcomes. At our institution the most common methods to contour the tumor bed are: the scar-based planning guided by fluoroscopy (2DP) and the one that relies on the visualization of the seroma under CT (3DP). Since clips are not routinely used the boost demarcation becomes challenging. We evaluated the accuracy of the breast boost volume treated with 2DP compared with 3DP. Additionally we evaluated whether or not the lumpectomy scar is a suitable landmark to define the tumor bed. Methods: 20 patients diagnosed with breast cancer stage I-IIA underwent tumor bed boost planning using two techniques: 2DP and 3DP. CTV prescription dose: 16.2 Gy, 1.8 Gy/d. All the information concerning to the 2DP was reproduced in a radiotherapy planning system. Statistical analysis: match pair t-test and coefficient of variation were used to test for an association among the two planning techniques for tumor bed coverage. D95, D90, V15, volume, medium lung dose (MLD) and geographic miss (GM) were analyzed. Pearson correlation analysis was used to assess the relationship between CVS, date of surgery, age and previous chemotherapy. Other items taken into account were the match between the scar and the seroma and how good the visualization of the seroma was by using the CVS. Results: 2DP was inaccurate: the mean D95, D90 and V15 were 3.12 Gy, 4.6 Gy and 29% respectively (variation coefficient: 135%, 107% and 65% respectively) The mean D95, D90 and V15 for the 3DP were 14.34 Gy, 15 Gy and 88% respectively (variation coefficient: 6%, 3% and 7% respectively). The difference between the mean 2DP D95 and 3DP D95 was 11 Gy (95% CI, 9 Gy to 13 Gy, p&lt; 0.001). Percentage of GM was: 80% (95% CI, 63% to 97%). All the seromas were finely visualized There was no correlation between CVS, age, prior chemotherapy and date of surgery. Larger volumes and MLD 3DP: 373.1 cm 3 vs. 248.8 cm 3 and 0.27Gy vs. 0.14 Gy respectively. Only 45% of the lumpectomy scars matched the seroma. Conclusions: CT-based planning allows for optimal tumor bed coverage. The lumpectomy scar is often a poor indicator of the tumor bed.
The Impact of HLA Haplotype Matching for Mismatched Cord Blood Transplantation.
Authors: Satoshi Takahashi, Jun Ooi, Nobuhiro Tsukada, Seiko Kato, Aki Sato, Toshiro Kawakita, Yasuyuki Nagata, Maki Monna-Ooiwa, Arinobu Tojo, Takuhiro Yamaguchi, Satoko Morishima, Yasuo Morishima, Shigetaka Asano
Journal: Blood (2009)
Laboratory values and their relationship with short- and long-term outcome following transthoracic esophagectomy in patients with esophageal cancer.
Authors: Dirk Bosch, Maarten Nijsten, John Theodorus Plukker
Journal: Journal of Clinical Oncology (2012)

37 Background: Surgical resection in esophageal cancer patients remains the mainstay of therapy, but carries a considerable risk of post-operative complications. Deranged laboratory data in the early post-operative period could provide guidance in decision making for further treatment strategy. Therefore we related standard laboratory measurements on 90-day and 1-year mortality after esophagectomy. Methods: Esophagectomy with curative intent was performed in 226 consecutive patients with cancer of the esophagus between January 2000 and December 2009. Prognostic analyses for albumin, lactate dehydrogenase (LDH), ALAT, ASAT, gGT, urea, creatinine, C-reactive protein (CRP), white blood cell count (WBC) and platelet count were performed with a Mann-Whitney U-test (p&lt;0.05) and ROC curve (area under the curve (AUC) &gt;0.7) for postoperative day (POD) 1, 2, 3, 4, 5, 10 and 15. Extreme laboratory values (cutoff points) were calculated (5 th or 95 th percentile) in the case of significant outcomes. Results: Laboratory measurements between survivors and patients deceased within 90-days (n=16) were significantly different in the case of albumin on POD 1, 3, 5, 10 and 15 (5 th percentile between 10-13.02, AUC: 0.761), CRP on POD 3, 4, 5, 10 and 15 (95 th percentile between 228.8-324.7, AUC: 0.861) and LDH in the late postoperative period on POD 4, 10 and 15 (95 th percentile between 387.1-512.2, AUC: 0.864). The other laboratory values showed no systematic differences. For one-year mortality (N=36), only albumin and CRP showed to have significant differences for non-survivors: albumin on POD 10 and 15 (5 th percentile between13.2-13.75, AUC: &lt; 0.7) and CRP on POD 3, 4 and 10 (95 th percentile between 220.9-319.5, AUC: &lt; 0.7). Conclusions: Albumin and CRP are the strongest prognostic measurements in predicting 90-day and one-year mortality after esophagectomy.
Phase I Study of Eltrombopag for Promoting Thrombopoiesis in Patients Undergoing Stem Cell Transplantation After Total Body Irradiation,
Authors: Jane L. Liesveld, Gordon L. Phillips, Michael W. Becker, Louis Constine, Jonathan Friedberg, Jeffrey Andolina, Laurie Milner, Jessica DeBolt, Ollivier Hyrien, Katie L Dawson, Yuhchyau Chen
Journal: Blood (2011)
Whole brain radiotherapy for brain metastases
Authors: Paul D Brown
Journal: BMJ (2016)

Optimising its use and application in the context of new treatments 

A recent large non-inferiority trial reported that whole brain radiotherapy did not improve survival or quality of life in adults with brain metastases from non-small cell lung cancer, when compared with corticosteroids and supportive care.1 QUARTZ (Quality of Life after Treatment for Brain Metastases) was a pragmatic trial with broadly inclusive eligibility criteria, but the 538 patients were all unsuitable for surgery or stereotactic radiosurgery and were recruited only when both the treating clinician and the patient felt uncertain about the potential benefit of whole brain radiotherapy. Many participants had a poor performance status, functioning in their daily lives at a level that typically would exclude them from clinical trials.

Although reported baseline characteristics were similar between the two groups, several key prognostic factors were not reported, including the presence of symptomatic or asymptomatic metastases, controlled …
In Vitro Characterization of Umbilical Cord Blood CD133+ and In Vivo Functionality in Response to Ischemia in a Murine Hind-Limb Injury Model.
Authors: Marcie R. Finney, Nicholas G. Greco, Matthew E. Joseph, Daniel G. Winter, Shyam Bhakta, Laura R. Fanning, Margaret Kozik, Jason Banks, Ying Huang, Vincent J. Pompili, Mary J. Laughlin
Journal: Blood (2005)
T-Cell Depletion Improves the Composite End Point Graft-Versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Federico Simonetta, Stavroula Masouridi-Levrat, Yan Beauverd, Olga Tsopra, Yordanka Tirefort, Caroline Stephan, Karolina Polchlopek, Riccardo Favale, Carole Dantin, Marc Ansari, Eddy Roosnek, Yves Chalandon
Journal: Blood (2015)
Robert Lockhart Johnston
Authors: John Ferris
Journal: BMJ (2016)

The son of a general practitioner and a professor of surgery, and one of five siblings, Robert Lockhart Johnston (“Rob”) graduated from Bristol University in 1989. His ophthalmology training was at Cheltenham General Hospital, St Thomas’ Hospital, and Moorfields Eye Hospital, followed by vitreoretinal fellowships in Melbourne and at Moorfields. He was appointed to a medical retina and vitreoretinal consultant post in Cheltenham in 2001.

Rob had extraordinary vision, creativity, and drive—attributes that resulted in his becoming one of the most influential ophthalmologists of his generation. As a registrar he was inspired by one of his trainers to develop an electronic tool to audit cataract surgery outcomes. Despite the enormity of the task and the numerous obstacles placed in his path, Rob’s primary focus never deviated from his original vision of using this tool to improve the quality of patient care.

In 1995 Rob and his brother, David, formed …
Benefit of the Adjunction of Rituximab in Salvage Regimen before Autologous Stem-Cell Transplantation (ASCT) in Follicular Lymphoma at Relapse. A Single Institution Study.
Authors: Karim Belhadj, Yosr Hicheri, Cécile Pautas, Taoufik El Gnaoui, François Hémery, Christiane Copie-Bergman, Jean-Louis Beaumont, Marie-Hélène Delfau-Larue, Jehan Dupuis, Isabelle Gaillard, Marine Diviné, Félix Reyes, Corinne Haioun
Journal: Blood (2005)
Identification of Prognostic Factors in Patients with Early Stage Unfavorable Hodgkin’s Lymphoma: An Individual Patient Data Meta-Analysis.
Authors: Julia Bohlius, Heinz Haverkamp, Volker Diehl, Houchingue Eghbali, Jeremy Franklin, Beate Pfistner, John Raemaekers, Andreas Engert, Michel Henry-Amar
Journal: Blood (2005)
Correlation of CD30 Expression on Neoplastic Mast Cells in Systemic Mastocytosis Assessed By Immunohistochemistry Versus Multiparameter Flow Cytometry and Correlation to Clinical Parameters
Authors: Frauke Bellos, Karl Sotlar, Susanne Schnittger, Claudia Haferlach, Torsten Haferlach, Wolfgang Kern
Journal: Blood (2015)
A multidisciplinary protocol for planned skin-preserving delayed breast reconstruction for patients with locally advanced breast cancer requiring postmastectomy radiation therapy: 3-year follow-up.
Authors: S. J. Kronowitz, W. Tereffe, K. Hunt, H. M. Kuerer, V. Valero, G. L. Robb, L. Feng, T. A. Buchholz
Journal: Journal of Clinical Oncology (2011)

1124 Background: We examined the safety and complication rates with a protocol for planned skin-preserving delayed breast reconstruction after postmastectomy radiotherapy (PMRT) for patients with locally advanced breast cancer (LABC, stages IIB and III). Methods: We identified 47 patients with preoperatively known indications for PMRT who were treated according to our protocol for skin-preserving delayed reconstruction after PMRT with placement of a tissue expander between December 2003 and May 2008 (protocol group). We matched these patients on the basis of disease stage with 47 control patients who underwent standard delayed reconstruction after PMRT (no skin preservation or tissue expander) during the same period. Results: In the protocol group, complication rates were 21% for skin-preserving mastectomy and placement of the tissue expander (stage 1), 5% for PMRT, 25% for expander reinflation after PMRT, and 24% for skin-preserving delayed reconstruction. The standard-delayed-reconstruction control group had a 38% complication rate. Tissue expander loss rates were 32% overall, 9% for stage 1, 5% for PMRT, and 22% for reinflation after PMRT. Wound healing complications after reconstruction were 3% in the skin-sparing protocol group and 10% in the standard-delayed-reconstruction control group. The median follow-up time for the patients who were still alive at the last follow-up was 40 months (range: 8.5-85.3). The 3-year RFS was 92% (95% CI, 83-100) and 86% (95% CI, 76-98) for the protocol group and standard delayed reconstruction, respectively (p = 0.87). Conclusions: In patients with LABC, skin-preserving mastectomy with a deflated tissue expander on the chest wall during PMRT does not increase locoregional recurrence risk and is associated with lower complications rates of definitive reconstruction.
Long Term Clinical Outcome of Hematopoietic Cell Transplantation for Intermediate to High-Risk Adult AML in Complete Remission; Can We Enhance the Survival Outcome Using Alternative Donor Types?
Authors: Jae-Ho Yoon, Hee-Je Kim, Young-Woo Jeon, Seung-Ah Yahng, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
Journal: Blood (2015)
The Use of Sirolimus Combined with Tacrolimus and Low-Dose Methotrexate Is Effective in Preventing Graft-Versus-Host Disease after Unrelated Donor Hematopoietic Stem Cell Transplantation.
Authors: Ryotaro Nakamura, Roberto Rodriguez, Auayporn Nademanee, Joycelynne Palmer, David Senitzer, David Snyder, Jasmine Zain, Vinod Pullarkat, Stephen J. Forman, Pablo Miguel Parker
Journal: Blood (2006)
Multiplex panel of metabolomic markers for early detection of prostate cancer.
Authors: S. K. Vareed, J. Siddiqui, V. Putluri, N. Putluri, T. M. Rajendiran, J. T. Wei, M. K. Terris, A. Chinnaiyan, G. Michailidis, A. Sreekumar
Journal: Journal of Clinical Oncology (2011)

13 Background: Prostate cancer (PCa) is the second leading cause of cancer deaths among men in US. Prostate specific antigen (PSA) the clinical standard for early detection of PCa is not specific for the disease necessitating development of additional markers. Metabolites are stable, measurable in biological fluids and function as physiological indicators of the individual. Earlier we described the metabolomic alteration in PCa and nominated sarcosine as a tissue marker for PCa progression. Further, elevated sarcosine levels were seen in cancer urine. The current study describes a multiplex panel of metabolomic markers in urine that include sarcosine, for early detection of PCa. Methods: A sensitive liquid chromatography- mass spectrometry based assay was used to quantify relative levels of tissue specific metabolites in urine of PCa patients. The urine specimens examined in this study were collected at University of Michigan from post DRE and pre-biopsy from clinically challenging patients with PSA between 4-10 ng/mL where biopsy was either positive or negative for tumor. The urine supernatants were recovered post-centrifugation, adjusted to have an osmolarity between 350-400 mOsm/kg, spiked with defined amount of internal standards and evaluated by multiple reaction monitoring (MRM) using a triple quadrupole mass spectrometer. The MRM data was examined using random-forest (RF)-to generate a panel of discriminatory compounds that were validated in an independent test set. Results: A panel of 11 metabolites (glutamic acid, sarcosine, spermidine, histidine, methionine, adenosine, inosine, thymine, hydroxyphenyl lactic acid, acetyl valine and lauric acid) when employed in a RF-based 2-stage training model (n=63) delineated PCa and benign with a cross-validated (out-of-bag validation based on 20000 decision trees) accuracy of 76 %. When applied to an independent set of test samples (n=98) from the same cohort the accuracy, sensitivity, specificity, positive predictive value and negative predictive values were 72 %, 77.5 %, 62.5 %, 67.8 % and 73.2 % respectively. Conclusions: The study describes a first-generation multiplex panel of metabolic markers for early detection of PCa in urine supernatants. No significant financial relationships to disclose.
Therapeutic Drug Monitoring (TDM) of IV Busulfan in Patients with Severe Obesity.
Authors: Donald A. Hutcherson, Jolynn K. Sessions, Ronald A. Mihelic, Katherine Sanvidge, Stephen R. Stricker, Amelia Langston, Christopher Flowers, Mary Jo Lechowicz, Ned Waller, Sagar Lonial
Journal: Blood (2007)