tbuckley/cabot-search huggingface dataset:
Metastatic ACTH-producing pituitary carcinoma managed with combination pasireotide and bevacizumab following failure of temozolamide therapy: A case report.
Authors: Lynda M. O'Riordan, Megan Greally, Niamh Coleman, Oscar S. Breathnach, Bryan Hennessy, Christopher J Thompson, William Grogan
Journal: Journal of Clinical Oncology (2013)

e13022 Background: ACTH-producing pituitary carcinomas (APPC) are malignant neuroendocrine tumors affecting the adenohypophysis. They are extremely rare, with a poor prognosis. They are poorly responsive to chemotherapy and radiotherapy. We report the case of a 25 year old female with a diagnosis of APPC, metastatic to bone, treated with temozolamide, followed by bevacizumab and the novel agent, pasireotide. Methods: The patient was diagnosed in 2002 with an ACTH-secreting pituitary macroadenoma causing Cushing’s disease. Despite two transphenoidal surgeries, bilateral adrenalectomies, craniotomy with excision of pituitary fossa tumour and radiotherapy she developed aggressive Nelson’s Syndrome. Following discontinuation of a somatostatin analogue in 2009 her ACTH levels rose dramatically causing progressive skin hyperpigmentation. Her disease continued to progress despite CyberKnife treatment. She was referred for temozolamide chemotherapy for treatment of the pituitary adenoma. At review, she had severe back pain. Investigations suggested metastatic disease and biopsy confirmed a diagnosis of metastatic APPC to bone.We commenced treatment with Temozolamide, however her disease progressed – ACTH levels were &gt;200,000pmol/l in June 2012. Molecular profiling completed on the patient’s tissue was negative. Pasireotide, a novel multi-somatostatin receptor analogue, was commenced concomitantly with the anti-angiogenesis agent bevacizumab. Results: Treatment response is being assessed with imaging, serial monitoring of serum ACTH levels and skin examination. Interval imaging has shown stable disease, ACTH levels have decreased to 113,000pg/ml. Conclusions: Pituitary carcinomas are extremely rare representing 0.1-0.2% of pituitary neoplasms. To date, there is no established standard treatment, although there are reports of response to temozolamide.Our patient exhibited a clinical improvement and a reduction in ACTH levels after 6 months of combination therapy with pasireotide and bevacizumab. This combination is a possible therapeutic option in patients with metastatic ACTH-producing pituitary carcinoma.
Correlation of interferon-g (IFN-γ) response with survival in a phase II hyperacute (HAL) immunotherapy trial for non-small cell lung cancer (NSCLC).
Authors: John Charles Morris, Gabriela R. Rossi, Nancy Harold, Lucinda Tennant, William Jay Ramsey, Nicholas N. Vahanian, Charles J. Link
Journal: Journal of Clinical Oncology (2012)

2571 Background: Lung cancer is the leading cause of cancer-related mortality. Patients progressing after initial systemic therapy have a poor prognosis. Thus, new therapies are needed. HAL immunotherapy exploits the hyperacute rejection of a xenotransplant as defense mechanism to initiate anti-tumor immune response by administering genetically modified allogeneic tumor cells expressing the αGal moieties on their cell surface. HAL immunotherapy utilizes αGal epitopes and natural human antibodies (Ab) against these targets as the proposed mechanism for anti-tumor immunity. Methods: We completed a phase II study of HAL immunotherapy in patients with metastatic or recurrent NSCLC, age ≥18, ECOG PS ≤2, ≤2 prior systemic therapies. Trial objectives were to determine response rate, safety and immunological responses. Patients received 300 x 10 6 HAL cells every 2 weeks for 8 doses. Response was determined using RECIST and adverse events were assessed using CTCAE v3. Immune responses were assessed by changes in serum anti-αGal titers and IFN-γ response. Results: Twenty-eight patients were treated. Eight (29%) demonstrated stable disease (SD) ≥16 wks including one patient that initially progressed and later regressed, surviving over 40 months. Median overall survival (OS) was 11.3 months (95% CI 3.8-21.9). Post vaccination, all patients responded by increasing anti-αGal Ab levels (2-100 fold) and 61% (11/18) of tested patients showed increases in IFN-γ levels (by ELISPOT). Interestingly, patients with increased IFN-γ responses after vaccination (&gt;10-500 fold-increase compared to baseline) had a median survival of 21.9 months compared to 5.5 months in patients with lesser IFN-γ responses after vaccination (p&lt;0.001). In addition, patients with higher IFN-γ responses showed reactivity to a NSCLC cell line that was not a component of HAL, suggesting cross-priming to shared tumor antigens. Conclusions: HAL immunotherapy is safe and feasible. The median survival compared favorably to that reported in patients receiving 2 nd line chemotherapy for relapsed or advanced NSCLC. The correlation between IFN-γ response and survival is highly encouraging.
Cancer Care Ontario’s lung disease pathway initiative: Building resources for lung cancer quality care.
Authors: William K. Evans, Yee Ung, Anna Chyjek, Angelika Gollnow, Carol Anne Sawka
Journal: Journal of Clinical Oncology (2013)

e17531 Background: Cancer Care Ontario (CCO) is the provincial agency mandated to improve the quality of cancer care in Ontario. CCO has driven quality improvement (QI) on a programmatic basis but in 2008, introduced Disease Pathway Management (DPM) as an additional QI approach. The lung cancer (LC DPM) began in 2009 as a two-year, phased initiative. Methods: The LC DPM team, consisting of clinicians, patients and system stakeholders, was organized into five groups and focused on aspects of the patient journey from diagnosis to end-of-life care, guided by draft pathway maps of the ideal state. 17 improvement concepts were identified of which 8 were selected for detailed development at a provincial consensus conference and validated as LC DPM’s Priorities for Action. 14 regional road shows presented region-specific performance and quality data to practitioners involved in LC patient care to promote ideas for improvement. Funding was provided to support both provincial and regional initiatives that addressed identified gaps. Results: Key outputs of the LC DPM initiative were: establishment of lung diagnostic assessment programs in 14 regions; completion of diagnostic and treatment pathways for NSCLC and SCLC which were grounded in evidence; 10 improvement projects on various stages of the cancer continuum; and 6 one-year Dyspnea Management Pilot Projects. For the dyspnea projects, each funded centre used different approaches and evaluated impacts on patient symptom burden, measured by Edmonton Symptom Assessment System (ESAS), patient satisfaction and quality of life. The learnings from each project have been summarized and will be shared with all regional cancer programs to facilitate knowledge transfer. Tools to support the patient experience include a LC Patient Pathway Map (PPM) and a document, Understanding Lung Cancer. The physician and patient pathways and related materials are available on CCO's website at https://www.cancercare.on.ca Conclusions: LC DPM has proven an effective strategy to accomplish system changes across a large geography that impact the quality of LC care, processes and patient experience. Indicator development and performance management will be used to sustain the gains achieved.
Training and skills assessment for MRI/TRUS fusion-guided prostate biopsy: End-fire vs. side-fire ultrasound probes.
Authors: Amit L Jain, Abhinav Sidana, Zachary Stanik, Mahir Maruf, Brian P. Calio, Dordaneh Sugano, Kai Hans Hammerich, Collier Wright, Mark Wayne Ball, Vladimir Valera, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2017)

e540 Background: Magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion-guided prostate biopsy (FBx) has rapidly proliferated in prostate cancer evaluation. FBx success may be dependent on multiple factors, including skills learned with user experience and the type of ultrasound (US) probe used. Our objective of this study was to compare the accuracy of the MRI/TRUS FBx technique utilizing an end fire versus a side fire US probe on an FBx platform. Methods: The participants of the study consisted of three different experience levels (expert ( &gt; 1000 FBx), Urology fellows with none to minimal FBx experience, Urology residents with no FBx experience). Each participant performed three trials of the FBx with the UroNav System in separate phantom models of the prostate. Each trial involved targeting the same set of fiducials through FBx platform and then using US only; first using an end fire US probe, and then using a side fire US probe. Fusion registration error (FRE) was defined as the distance between MR target and transformed core location from the US only biopsy. Results: Six users with 3 different experience levels performed the FBx. Mean FRE with the end fire probe for the residents, fellows, expert was 7.42(±0.11), 5.10(±0.73) &amp; 3.75(±0.75) respectively. Mean FRE with the side fire probe for the residents, fellows, expert was 6.08(±0.09), 4.76(±0.68) &amp; 3.46(±0.08) respectively. There was no significant difference between the FRE averages for end fire vs. side fire. There was an inverse relationship of mean FRE with user experience level (corr. coefficient (r) = -0.79, p = 0.011 for end fire; r = -0.84, p = 0.004 for side-fire). Conclusions: We report the results of a pilot study comparing the efficacy of side fire and end fire US probes in MRI/TRUS FBx. Our preliminary results suggest the type of US probe used does not significantly affect FRE and FBx performance. As expected, FRE decreases with increased user experience. A larger study with more participants will be needed to compare these probes with adequately powered analysis and will dictate the practice in clinical settings as minimization of FRE will improve diagnostic accuracy of this technique in detecting clinically significant cancer.
Liver metastases in germ cell tumors.
Authors: Suliman Boulos, Jonathan Shamash, Han Hsi Wong, Sarah Maria Rudman, Gary Doherty, Wendy Ansell, Daniel Berney, Marika Reinius, Peter Wilson, Linda Shephard, Danish Mazhar
Journal: Journal of Clinical Oncology (2017)

403 Background: Metastatic germ cell tumour (GCT) to the liver is considered rare and usually caries adverse outcomes. We aimed to determine the outcome of patients with metastatic GCT to the liver. Methods: We identified retrospectively 36 patients with metastatic germ cell tumour to the liver between the years 2001 and 2015, from which 34 were non-seminomatous germ cell tumours (NSGCT) and two seminomas. 35 patients had other sites of metastases including lungs, bones and brain. Elevated tumour markers were seen in the vast majority of patients (97.2%). 15 patients received treatment with dose intense regime including actinomycin-D, high-dose methotrexate, etoposide and cisplatin (GAMEC) every 14 days, 20 patients received the standard protocol of bleomycin, etoposide and cisplatin (BEP) every 21 days and one patient received POMB/ACE chemotherapy. 20 patients had an induction cycle of cisplatin, vincristine and bleomycin (Baby-BOP) prior to initial treatment. Results: 12 patients had radiological complete response (CR) and 19 patients had radiological partial response (PR) in the liver, with five patients having a CR in all sites with negative markers. Five patients underwent liver resection with no viable tumour seen. Three patients that underwent liver resection also had retroperitoneal lymph node dissection (RPLND) the histology from which was viable seminoma in one case, mature teratoma in one case and necrosis in the final patient.16 patients had marker negative PR, 10 patients had marker positive PR and 5 patients had a marker negative CR. 15 patients eventually relapsed and 10 died with only one liver relapse. Median Overall survival for patients that received BEP was 35.38 months (not reached for GAMEC) (p = 0.0147). The median progression free survival (PFS) for the BEP group was 24.45 months (not reached for GAMEC) (p = 0.22) and the 2-years PFS for the GAMEC and BEP groups were 73% and 55% respectively. Conclusions: Within this cohort, liver metastasis from germ-cell tumour had a good response to chemotherapy, with progression occurring mainly in extra-hepatic sites. There was also a suggestion that dose dense GAMEC regime may offer superior efficacy compared with BEP.These results also question the role of liver metastectomy after initial response to chemotherapy.
Identification of chromosomal abnormalities in prostate cancer by array CGH
Authors: Prasad Dhulipala, Greg Kaput, Wendell Fortson, Shyam Reddy
Journal: Cancer Research (2007)

LB-55  Genetic alterations are the hallmark for various diseases like cancer, mental retardation and birth defects. Identifying these alterations and the genes they contain will provide molecular targets for diagnosis and therapy.  Genomic DNA was isolated from LNCaP, a human prostate cancer model cell line. Labeled genomic DNA probes were generated from LNCap cells and normal female genomic DNAs using CyScribe™ Array CGH Genomic Labeling Kit (GE Helathcare) and BioPrime™ Array CGH Genomic Labelling System (Invitrogen). The labeled fragments were hybridized on to a Spectral Chip™ 2600 used for whole genome scanning and Constitutional Chip™ 3.0 containing clones for 48 constitutive diseases. Image analysis was performed by Axxon GenePix® Pro 6.0 software and chromosomal abnormalities were identified using web-based Spectral Ware™. Higher dye labeled DNA yields (>16%) and CyDye dCTP-nucleotide incorporation (10%) were achieved with Amersham CyScribe Array CGH Genomic Labeling Kit. Analysis of hybridization data showed similar signal intensities, log2 ratios and signal to noise ratios for the two kits. Both kits identified loss in 2p22.3-2p14; 10q23.1-10q24.33; 13q21.1-13q22.1 chromosomal regions and strong gain in Yq11.2 region that were previously detected by conventional CGH.
Evaluation of parameters for treatment duration of sunitinib in metastatic renal cell carcinoma.
Authors: Ellen Kossoff, Nicolas Batty, Alice C. Ceacareanu, Kristopher Attwood, Dustyn Miller, Jonathan Rabey, Charlene Lee, Ahmad Ahmad, John M. Ebos, Thomas Schwaab, Saby George, Roberto Pili
Journal: Journal of Clinical Oncology (2012)

e15042 Background: In metastatic renal cell carcinoma (mRCC), there is a need for predictive indicators for treatment duration (TD) of sunitinib. Our study evaluates parameters that may be associated with TD of sunitinib. Methods: From 01/2007-12/2011, consecutive mRCC patients (pts) were reviewed. Responders (R) were defined as having either complete response (CR) or partial response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, while non-responders (NR) were defined as having either stable disease (SD) or progressive disease (PD). Long term duration (LTD) was defined as therapy with sunitinib ≥ 18 months (mos). Hazard ratios (HR) and 95% confidence interval (95CI) representing the association between TD and specific parameters were computed with Cox proportional hazard model. Results: After a median follow-up of 9.8 mos (&lt;1 - 63.8) of 128 mRCC pts, 57 (45%) received sunitinib. Responses were CR, PR, SD, PD of 3, 13, 8 and 33 pts, respectively. LTD was observed in 9 pts (21%). Hemoglobin &lt; 12.5 g/dL (p = 0.048), prior nephrectomy (PN) (p = 0.001), prior therapies (p = 0.016), dose reduction (DR) (p = 0.001), an increased skin toxicity (p = 0.025) and low/intermediate (LI) Memorial Sloan-Kettering Cancer Center (MSKCC) risk-groups (p = 0.003) were associated with longer TD and a higher ANC (p &lt; 0.0001) with shorter TD. In the multivariate analysis, PN was the only significant prognostic factor [HR 0.3 (95CI 0.12 -0.72) p = 0.007] that was associated with prolonged TD. Pts with LTD had a lower baseline ANC (p= 0.037), a LI MSKCC (p = 0.026), higher frequency of DR (p = 0.007), increased skin (p = 0.017) and endocrine (p = 0.015) toxicities and an increase of body mass index (BMI) from baseline (p = 0.008). When adjusted for BMI and performance status, results were maintained. Progression free survival (PFS) and overall survival (OS) of pts with LTD were not reached. However, both PFS and OS of R with TD &lt; 18 mos, were 19.5 mos 95CI (3.4 - 27.9). Conclusions: PN, lower baseline ANC, DR, an increase of BMI from baseline, skin and endocrine toxicities were associated with prolonged TD of sunitinib in mRCC. There is a need for prospective studies to develop a predictive TD model in this setting.
Impact of cytoreductive nephretomy on timing of systemic therapy in metastatic kidney cancer.
Authors: Liam Connor Macleod, Atreya Dash, George Schade, Jonathan D. Harper, Daniel W. Lin, Scott S. Tykodi, John L. Gore
Journal: Journal of Clinical Oncology (2017)

503 Background: High rates of disease control with systemic therapy (ST) in the post-cytokine era for metastatic renal cell carcinoma (mRCC) cause apprehension that cytoreductive nephrectomy (CN) may delay effective therapy. We therefore evaluated factors associated with early mortality and time to ST after CN. We hypothesized markers of poor performance status and morbid CN would be associated with postoperative mortality and therapeutic delays. Methods: The National Cancer Database was screened for adult mRCC cases having CN followed by ST, years 2006-2013. We classified a delay in systemic therapy as interval &gt; 45 days (median time to ST in the cohort). Multivariable logistic regression was performed, identifying factors associated with perioperative mortality and delays to initiation of ST. Results: Of 10,913 patients with initial CN (45% of mRCC), 30- and 90-day mortality were 3% and 11%, respectively. 6,362 later received ST (87% targeted therapy, 13% immunotherapy), median start was 45 days post-operatively (IQR 9-72), with 73% receiving ST within 30 days of CN. Multivariable factors associated with 30-day mortality included, older age, (OR 2.3, 95% CI 1.5-3.5 for those &gt;75 [referent &lt; 55 years]), Charlson index &gt;0 (OR 1.3, 95% CI 1.0-1.6), lack of insurance (OR 1.9, 95% CI 1.2-2.8 [referent private payer]), node-positive disease (OR 1.4 95% CI 1.1-1.7), length of stay &gt; 90 th percentile (&gt; 10 days, OR 3.2, 95% CI 2.0-5.3), larger tumor size (T4 lesion OR 1.7, 95% CI 1.2-2.5 [referent T1]). Delayed ST was associated with travel burden &gt; 50 miles (OR 1.2, 95% CI 1.0-1.4), concurrent metastasectomy (OR 1.3, 95% CI 1.2-1.5), and length of stay &gt; 90 th percentile (OR 1.5, 95% CI 1.1-2.3). Conclusions: These data suggest that markers of frailty, more progressive disease, and surgical morbidity may contribute to surgical-related deaths or hinder patients receiving potentially disease-controlling therapy when treated with initial CN in mRCC. Going forward, existing surgical prognostic models could incorporate risks of surgical-related mortality and delay to ST when considering CN.
A randomized phase II study of OGX-427 plus prednisone (P) versus P alone in patients (pts) with metastatic castration resistant prostate cancer (CRPC).
Authors: Kim N. Chi, Sebastien J. Hotte, Susan Ellard, Joel Roger Gingerich, Anthony Michael Joshua, Evan Y. Yu, Martin Edwin Gleave
Journal: Journal of Clinical Oncology (2012)

4514 Background: Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone protein that regulates cell signaling and survival pathways implicated in cancer progression. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a 2nd generation antisense oligonucleotide that inhibits Hsp27 expression with in vitro and in vivo efficacy and was well tolerated with single agent activity in phase I studies. Methods: Chemotherapy-naïve pts with no/minimal symptoms were randomized to receive OGX-427 600 mg IV x 3 loading doses then 1000 mg IV weekly with P 5 mg PO BID or P only. Primary endpoint was the proportion of pts progression free (PPF) at 12 weeks (PCWG2 criteria). A 2-stage MinMax design (H 0 = 5%, H A &gt;20%, α=0.1, β=0.1) with 32 pts/arm provides 70% power to detect the difference at 0.10 1-sided significance. Secondary endpoints include PSA decline, measurable disease response, and circulating tumour cell (CTC) enumeration. Results: 38 pts have been enrolled; 1st stage of accrual completed with 2nd stage accruing. In the 1st 32 pts randomized (17 to OGX-427+P, 15 to P), baseline median age was 71 years (53-89), ECOG PS 0 or 1 in 66% and 34% of pts, median PSA 66 (6-606), metastases in bone/lymph nodes/liver or lung was 75/56/9%, 31% had prior P treatment, and 93% had ≥5 CTC/7.5 ml. Predominantly grade 1/2 infusion reactions (chills, diarrhea, flushing, nausea, vomiting) occurred in 47% of pts receiving OGX-427+P. One pt on OGX-427+P developed hemolytic uremic syndrome. A PSA decline of ≥50% occurred in 41% of pts on OGX-427+P, and 20% of pts treated with P. A measurable disease partial response was seen in 3/8 (38%) evaluable pts on OGX-427+P and 0/9 pts on P. CTC conversion from ≥5 to &lt;5/7.5 ml occurred in 50% of pts on OGX-427+P and 31% treated with P. Thus far, in 26 evaluable pts the PPF at 12 weeks was 71% (95% CI: 42-92) in OGX-427+P treated pts and 33% (95% CI: 10-65) in pts on P. Conclusions: These data provide clinical evidence for the role of Hsp27 as a therapeutic target in prostate cancer and support continued evaluation of OGX-427 for pts with CRPC. Funded by a grant from the Terry Fox Research Institute.
Breast cancer following spinal radiotherapy for a childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Chaya S. Moskowitz, Jyoti Malhotra, Joanne F. Chou, Suzanne L. Wolden, Marilyn Stovall, Gregory T. Armstrong, Wendy M. Leisenring, Joseph Philip Neglia, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2014)

10082 Background: Small dosimetry-based studies suggest females treated with spinal radiotherapy (RT) for a pediatric malignancy may have an increased risk of subsequent breast cancer (BC) due to scatter radiation to breast tissue. However, BC risk in this population has not been assessed in well-characterized survivor cohorts with long-term follow-up. Methods: In the CCSS cohort, we estimated BC incidence in 363 5-yr survivors of leukemia (n=195) and central nervous system (CNS) tumors (n=168) diagnosed 1970-86 prior to age 21 and treated with spinal RT. The median delivered dose of spinal RT for leukemia survivors was 1800 cGy (range 150-4175 cGy) and for CNS tumor survivors was 3453 cGy (range 475-6500 cGy). BC risk compared with the general population was evaluated with standardized incidence ratios (SIRs) estimated using the Surveillance, Epidemiology, and End Results (SEER) Program. Cumulative incidence was estimated treating death as a competing risk. Results: With a median follow-up time of 27.5 yrs (range 9-38) and a median attained age of 35 yrs (range 10-53), 3 women were diagnosed with BC at ages 31, 41 and 41 yrs. All were leukemia survivors with spinal RT doses of 1800, 2000, and 2588 cGy; none had a known family history of BC (1 was adopted). BC cumulative incidence by age 40 was 0.5% (95% confidence interval (CI) 0-2.5%). The SIR was 1.2 (95% CI 0.8-7.8) for all survivors treated with spinal RT, 3.9 (95% CI 1.3-12.1) for leukemia survivors, and 0 for CNS tumor survivors. Conclusions: We did not find convincing evidence that spinal RT for a childhood cancer is associated with an increased BC risk. The increased risk in leukemia survivors who were treated with lower doses of RT relative to CNS tumor survivors may be due to other factors including a genetic predisposition.