tbuckley/cabot-search huggingface dataset:
Effect of ablative radiotherapy on survival in patients with inoperable intrahepatic cholangiocarcinoma: A dose response analysis.
Authors: Christopher H. Crane, Randa Tao, Priya Bhosale, Milind M. Javle, Rachna T. Shroff, Thomas A. Aloia, Ahmed Omar Kaseb, Eugene Jon Koay, Andrew Justin Bishop, Cameron Williams Swanick, Theodore S. Hong, Prajnan Das, Sunil Krishnan
Journal: Journal of Clinical Oncology (2016)

294 Background: Advances in radiotherapy (RT) techniques and image guidance (IGRT) have enabled ablative doses to be delivered to large liver tumors. We evaluated the effects of RT dose escalation in the treatment of intrahepatic cholangiocarcinoma (IHCC). Methods: 79 consecutive patients with inoperable IHCC were treated between 2002–2014. Median tumor size 7.9 cm (range 2.2–17 cm), 57% had nodes+ and 20% had metastatic disease. 89% received gemcitabine and cisplatin before RT (35–100 Gy, median 58.05 Gy) for a median biologic equivalent dose (BED) of 80.5 Gy (range 43.75–180 Gy). 57% were treated with concurrent capecitabine. CT on rails IGRT with gating were used to deliver higher doses. Results: Median FU was 33 months (range 11–93 ). Median overall survival rate (OS) after diagnosis was 30 months; 1, 2, and 3-year OS rates were 87%, 61%, 44%. The median duration of local tumor control (LC) was 23 months; 1, 2, and 3-year LC rates were 81%, 45% and 27%. RT dose was the most important prognostic factor. Higher doses correlated with improved LC and OS. The 3-year OS for a BED greater than 80.5 was 73% versus 38% for those receiving lower doses (P =0.017). Similarly, 3-year LC was significantly higher (78% versus 45%, P= 0.04). On multivariate analysis, RT dose was significant for LC (P= 0.004) and OS (P= 0.006). The majority of patients (32/36, 89%) whose cause of death could be determined died from liver failure related to intrahepatic disease progression. Only 4 patients (11%) died from distant metastatic disease. There were no significant treatment related toxicities. Conclusions: Higher doses of RT improve LC and OS in inoperable IHCC. A BED &gt; 80.5 Gy appears to be ablative for large IHCCs. Long term survival rates compare favorably to resection. RT schedules that achieve a BED &gt; 80.5, such as 67.5 Gy in 15 fractions and 75 Gy in 25 fractions, should be used. Solutions for internal organ motion and IGRT are necessary for safe delivery of high doses near bowel. These findings support the use of 67.5 Gy in 15 fractions (BED = 97.88 Gy) in the current phase III NRG-GI001 randomized trial evaluating whether the addition of RT to chemotherapy affects survival for inoperable IHCC patients.
Rural and urban disparities in the evolution of sentinel lymph node utilization in breast cancer.
Authors: Amanda Kathleen Arrington, Laura Kruper, Courtney Vito, John H. Yim, Steven L. Chen
Journal: Journal of Clinical Oncology (2012)

71 Background: Sentinel lymph node biopsy (SLNB) has become the preferred method for axillary nodal staging. We examined SLNB utilization in urban versus rural settings as this procedure was adopted. We hypothesized that SLNB rates in urban centers quickly increased prior to 2000, while the technology shift and acceptance of SLNB was slower in rural centers. Methods: The SEER registry was used to identify patients with invasive ductal or lobular breast cancer from 1998-2008. Exclusion criteria included evidence of distant metastatic disease, T4 tumors, no curative-intent operation performed, or incomplete staging data. Residential setting was divided into three groups based on population density: rural, intermediate population, and urban. Results: The overall rate of SLNB increased with time (9.5% in 1998 to 72.7% in 2008). The adoption of SLNB was slower in rural settings than in urban populations (p&lt;0.001). By 2003, only urban areas were utilizing SLNB in over 50% of cases. When stratified by population density, there was a significant difference in SLNB rates according to type of surgery performed (lumpectomy vs mastectomy) as well as by T-stage, with lower T-stage positively correlating with the likelihood of SLNB usage in all categories. Overall, there was a two-year lag in the adoption of between the increases in SLNB utilization rates in these groups. Conclusions: Since 1998, the use of SLNB for breast cancer has slowly increased throughout the United States. Though widely accepted as the preferred staging method, the overall rate of SLNB remained near 50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1-T2 had increased to over 50% in all population categories. There was an overall 2-year lag in adoption of SLNB in less populated areas. While this may represent a more conservative approach as noted by the higher utilization in small tumors, the difference may be attributable to a shortage of experienced surgeons, lack of training, or lack of technological support at smaller institutions. The provision of continued training in emerging technologies for rural surgeons, such as SLNB, should remain a priority in continuing surgical education.
A Markov model for optimal intervals in prostate cancer screening programs in the era of individual baseline PSA values
Authors: T. Kobayashi, R. Goto-Watanabe, K. Ito, K. Mitsumori
Journal: Journal of Clinical Oncology (2005)

4618 Background: Once a prostate cancer screening program using prostate-specific antigen (PSA) has been established and is operational, the issue of the re-screening interval for patients with prior negative PSA results comes into question. We approached this issue using a decision-analytic model in which participants were stratified by baseline PSA values. Methods: Based on an actual contemporary screening program, we established a Markov decision analytic model of prostate cancer screening with different re-screening interval strategies determined by individual baseline PSA levels. Cost-effectiveness analysis was performed to determine the incremental cost-effectiveness ratio (ICER; costs per quality-adjusted life years) for each strategy. Results: Re-screening strategies with biennial PSA testing in men with PSA levels ≤3.0 and ≤4.0 ng/ml are dominated by biennial screening in men with PSA ≤2.0 ng/ml, which is the most cost-effective strategy. ICERs for annual screening and biennial screening strategies in men with PSA ≤1.0 were US$25,220 and US$10,557, respectively, with respect to strategies with biennial screening in men with PSA ≤2.0 ng/ml. On sensitivity analyses, ICER for annual screening with respect to biennial screening in men with PSA ≤2.0 ng/ml will be larger under conditions with a lower biopsy participation rate in PSA-positive participants, or a lower cancer detection rate on biopsy. It was also observed that ICER for an annual screening strategy is larger in an initial age cohort of men in their 50’s and 70’s than in their 60’s. Conclusions: Our model shows that cut off of baseline PSA for annual PSA testing in prostate cancer mass screening should be determined as 0.0 to 2.0 ng/ml based on clinical and economical variables in view of the budget of each society. No significant financial relationships to disclose.
Recombinant adeno-viral human p53 gene combined with FOLFOX4 in the treatment of advanced colorectal cancer.
Authors: Zhong-guo Zhang
Journal: Journal of Clinical Oncology (2012)

e14036 Background: Metastatic or recurrent colorectal cancers generally become unresectable and will not respond to radio- or chemo-therapy. Studies showed that p53 has a synergic effect with radio- or chemotherapy. This study is to determine the efficacy and safety of recombinant adenoviral human p53 gene (rAd-p53) combined with standard FOLFOX4 regimen in treatment of advanced colorectal cancer. Methods: From July 2008 to Dec. 2011, 56 patients with an advanced colorectal cancer or local recurrent disease were treated with rAd-p53 and standard FOLFOX4 regimen. For local tumor, 1-4×10 12 viral particles (VP) of rAd-p53 diluted into 5 ml of saline solution was injected into tumor at multiple directions, once a week for 6 weeks. If tumor spreading into abdominal cavity, 4×10 12 VPs diluted in 500 ml of saline solution were injected inraperitoneally, twice in 2 weeks. If having lung or liver metastasis, 2×10 12 VPs diluted into 100 ml of saline solution were given intravenously twice in 2 weeks. Three days after the first gene therapy, the standard FOLFOX4 regimen was given for six cycles. Results: The follow-up time was 3~38 months with a median of 19.5 months. Among these patients, 8 (14.3%) patients were assessed as complete response, 31 (55.4%) as partial response and 11 (19.6%) as stable disease. After the combined treatment, a radical resection was successfully performed in 18 cases with local recurrent disease. All these patients were still alive at the last follow-up. Common adverse events were 38.4~40.5 o C self-limited fever, occurring in 86% patients. No serious adverse events were observed. Conclusions: rAd-p53 combined with FOLFOX4 is a safe and effective treatment for advanced colorectal cancer or local recurrent disease.
DECREASE OF HEPARAN-SULFATE STAINING IN THE GLOMERULAR-BASEMENT-MEMBRANE IN MURINE LUPUS NEPHRITIS: CORRELATION WITH ALBUMINURIA AND GLOMERULAR IMMUNOGLOBULIN DEPOSITS
Authors: Mcj Vanbruggen, C Kramers, Mn Hylkema, J Vandenborn, Mah Bakker, Kjm Assmann, Rjt Smeenk, Jhm Berden, Machteld Hylkema
Journal: Kidney International (1995)
Clonal heterogeneity in platinum-resistant metastatic urothelial cancer.
Authors: Bishoy Faltas, Himisha Beltran, Kenneth Eng, Chantal Pauli, Brian D. Robinson, Juan Miguel Mosquera, David M. Nanus, Scott T. Tagawa, Olivier Elemento, Mark A. Rubin
Journal: Journal of Clinical Oncology (2015)

290 Background: Beyond platinum-based chemotherapy, there are currently no approved therapies for advanced PRUC. Our objective was to generate the first detailed genomic profile of metastatic PRUC to identify molecular changes critical to platinum-resistance and metastasis development. Methods: Following informed consent, we collected 50 urothelial cancer (UC) tissue samples, from 23 patients. Metastatic tumor samples were obtained from biopsies or metastatectomy. Germline samples were prospectively collected and matched archival formalin-fixed paraffin-embedded primary tumors from the same patients were retrieved. Our cohort comprises 23 metastatic samples, 37 PRUC samples and 18 trios of matched primary, metastatic and germline samples including 2 rapid autopsies yielding tumor samples from multiple sites. We performed whole exome sequencing of all tumor and germline samples followed by integrated analysis of somatic single nucleotide variants and copy-number alterations and to analyze clonality. We utilized DAVID bioinformatic tool for pathway analysis. Results: Advanced PRUC samples were enriched for several molecular alterations, we identified 414 recurrently mutated genes including common genes such as TP53 (45%) as well as actionable alterations in PIK3CA (11%) and TSC1 (19%). We also identified frequent alterations in novel genes such as DPCR1 (38%) and NIN (28%). Frequent copy number alterations included CDKN2A deletion (33%), E2F3 amplification (10%) and ERBB2 amplification (7%). Pathway analysis showed enrichment of mutations in the apoptosis (p=1.0E-7) and cell cycle regulation (p=1.6E-2) pathways compared to TCGA primary UC dataset. We reconstructed phylogenetic trees from matched primary, metastatic and germline trios. Variant allele frequencies of certain shared mutations increased from primary tumors to lymph node and visceral metastases revealing clonal selection of mutations present in primary tumors. Conclusions: This study generates a detailed profile of the genomic landscape of advanced PRUC revealing extensive heterogeneity and clonal selection underlying platinum-resistance and metastatic spread.
Causes of Discontinuation and Long-Term Outcomes of Patients with CLL after Discontinuing Ibrutinib
Authors: Preetesh Jain, Philip A Thompson, Michael Keating, Zeev Estrov, Alessandra Ferrajoli, Nitin Jain, Hagop M. Kantarjian, Jan Burger, Susan M. O'Brien, William G. Wierda
Journal: Blood (2016)
Induction chemotherapy (ICT) containing docetaxel, platinum, and 5 fluorouracil (DPF) regimen in a sequential treatment of locally advanced nasopharyngeal cancer (LANPC): Retrospective analysis from a single institution.
Authors: U. P. Hegde, R. Dowsett, J. Spiro
Journal: Journal of Clinical Oncology (2011)

e16037 Background: Concurrent chemotherapy and radiation therapy (CCRT) is the standard treatment of patients (pts) with advanced nasopharyngeal cancer (LANPC). Sequential treatment strategy with ICT helps improve local function, pain control and reduction of systemic failure. We report our limited experience of ICT with DPF regimen in a sequential treatment strategy of patients with LANPC. Methods: The data was recorded following chart review of pts treated for LANPC at the University of Connecticut Health Center between 2004-2010 following approval by the Institutional Review Board. Analysis included age of the pt, stage of the cancer, histological diagnosis; number of ICT cycles, response to treatment as complete disappearance of disease (CR) or more than 50% reduction of the disease (partial response PR), assessed both clinically and with imaging studies. Overall survival (OS) was defined as time from diagnosis to the last follow up, disease free survival (DFS) was defined as time from complete remission of the disease to the last follow up in CR. Results: 5 pts with LANPC were treated sequentially with DPF regimen followed by CCRT. The median age is 55 years, 4 males and one female. All pts had stage IV B, non keratinizing poorly differentiated histology. Average number of DPF ICT was 3. 4 out of 5 pts achieved CR while one pt achieved PR. With a median follow up period of 24 mths, four pts are alive in CR and one pt in PR died of tumor progression. The median DFS in four pts in CR is 16 mths (range 8-70 mths) and overall survival is 24 mths (range 12-74). Conclusion: DPF is well tolerated and effective ICT regimen in patients with LANPC. More studies will help understand the clinical relevance of this regimen as ICT in a sequential treatment of LANP.
The effect of hepatic insufficiency on the pharmacokinetics of ridaforolimus.
Authors: J. B. McCrea, M. Stroh, X. Li, V. Schulz, J. Talaty, K. W. Orford, M. Trucksis, K. Lasseter, N. Agrawal, J. A. Wagner, M. Iwamoto
Journal: Journal of Clinical Oncology (2011)

e13001 Background: Ridaforolimus (RIDA) (AP23573; MK-8669), a unique rapamycin analog and a potent inhibitor of mTOR signaling, is being developed for the treatment of solid tumors. The study aims were to assess the safety and whole blood pharmacokinetics following single 10 mg doses of RIDA in patients with moderate hepatic insufficiency (Child-Pugh [CP] score of 7-9). Methods: This was an open-label study comparing the pharmacokinetics after administration of a 10 mg single dose of RIDA to patients with moderate hepatic insufficiency (assessed by the CP scale) with healthy matched controls. Nineteen (19) males and females of non-childbearing potential were enrolled: ten (10) patients with moderate hepatic insufficiency (CP score of 7-9) and 9 healthy matched control subjects (race, age [±5 years], gender, BMI [±3.3 units]). Results: A summary of the blood pharmacokinetic parameters of RIDA administered to patients with moderate hepatic insufficiency and to healthy matched control subjects is presented below. RIDA was generally well tolerated and no patients were discontinued due to drug-related AEs. Conclusions: RIDA exposure in patients with moderate hepatic insufficiency was approximately 2-fold higher than in healthy matched controls. Since RIDA is being studied in phase III at the maximally tolerated dose of 40 mg, this finding is likely to be clinically meaningful and caution should be exercised when dosing patients with moderate hepatic insufficiency. Moderate hepatic insufficiency Healthy matched control Moderate hepatic insufficiency/ healthy matched control Pharmacokinetic parameter N# GM 95% CI N GM 95% CI GMR 90% CI AUC0-∞ † (ng/ml·hr) 10 1168 (669, 2,039) 9 589 (315, 1,100) 1.98 (1.06, 3.71) Cmax † (ng/ml) 10 53.9 (25.5, 114.2) 9 41.4 (17.8, 96.0) 1.30 (0.56, 3.03) Tmax ‡ (hr) 10 6.0 (3.0, 8.0) 9 4.0 (4.0, 8.0) Apparent t1/2 § (hr) 10 111.4 28.0 9 75.0 41.0 Abbreviations: GM, geometric mean; GMR, geometric mean ratio; CI, confidence interval. † Geometric mean computed from least squares estimate from an ANCOVA performed on the natural-log transformed values. ‡ Median [Min, Max] reported for Tmax. § Harmonic mean, jack-knife standard deviation (SD) reported for t1/2. # AN 0003 who discontinued had sufficient PK to be included in the primary analysis.
Stereotactic radiotherapy (SRT) for primary and metastatic liver tumors with functional treatment planning.
Authors: Alexander V. Kirichenko, Ngoc Thai, Erik Lappinen, Olivier Gayou, Ellen Day, Katherine Kotinsley, Susan Gott
Journal: Journal of Clinical Oncology (2013)

222 Background: We report on outcomes and toxicity of liver SRT/SBRT based on 3D-CT/SPECT treatment planning with conformal avoidance of well perfused functional normal liver volumes (FNLV). Methods: 51 patients with unresectable metastatic (36) or primary (15) hepatic tumors (65 targets) completed SRT planning with 99m Tc sulfur colloid 3D-SPECT/CT to define FNLVs. Various degrees of FNLV retraction as a result of hepatic cirrhosis or systemic or intrahepatic chemotherapy were observed. For conformal avoidance of the residual FNLV, total dose and fractionation were adapted to FNLV constraints. 4D-CT and SPECT-based dosimetry were compared and treatment outcomes and toxicity were analyzed with medium followup 14.5 months (3-36months). Results: The in-field local control rate was 95%, hepatic failure free survival - 88%, hepatic progression free survival - 78% and overall survival - 70%. 25% patients developed Grade ≤ 2 elevation of liver enzymes with no incidence of “classic” radiation-induced liver disease. No patients with hepatic cirrhosis had Child-Pugh score progression. The most common toxicity was Grade ≤ 2 fatigue. For the group, FNLVs were significantly reduced compared to CT-derived NLV (p&lt;0.01) with marked FNLV contraction in patients with Child-Pugh ≥ B cirrhosis, those who completed hepatic resections or received TACE within 2 months prior to SRT. Treatment planning with incorporated SPECT/CT helps to reduce volumes of functionally active liver parenchyma receiving doses above prescription threshold in patients with HCC compared to conventional 4D-CT treatment planning (p&lt;0.01). There was no such correlation for non-HCC patients. Conclusions: 3D-SPECT/CT treatment planning allows identification and conformal avoidance of FNLV from high radiation doses facilitating safety of liver SRT in patients with preexisting liver disease. Outcomes are favorable, however participation in prospective Phase III trial would estimate true value of this method.
Breast ductal lavage (DL) and P16 immunocytochemistry.
Authors: C. Casadio, S. Di Vincenzo, L. Chiapparini, B. Bonanni, M. Cazzaniga
Journal: Journal of Clinical Oncology (2011)

1587 Background: The low sensitivity in detecting high-grade atypical cells makes cytologic evaluation of DL specimens a low-yield tool for assessing risk or identifying intraepithelial neoplasia. Following the uterine cervix carcinogenesis model, the hypotheses on some viral role and the loss of p16 function as a pivotal trigger for cell to progress to malignancy, we tested the overexpression of p16 by immunostaining in order to test the possibility of improving cytology sensitivity in DL by means of p16 immunocytochemistry. Methods: 102 DLs and 8 random periareolar fine needle aspiration cytology (FNAC) performed on volunteer women at increased risk for breast cancer (history or presence of controlateral breast cancer or BRCA1/2 mutation carriers or >10% of risk of mutation according to the BRCAPRO model) were retrieved from our institutional files and submitted for p16 immunostain. The morphological diagnosis were: C2 in 77 DLs and in all random FNAC, C3 in 22 DLs and C4 in 7 DLs. Ten cases of routine FNAC positive (C5) for tumor cells were tested too. Results: 5 DLs resulted inadequate for p16 staining, 81 (83.5%) negative, 11 (11.3%) ambiguous, 5 (5.2%) positive (morphologically diagnosed as C2). 6 random FNAC resulted negative for p16 staining, 1 ambiguous and 1 positive (morphologically diagnosed as C2). 8 routine FNAC tumor cells stained for p16 while 2 resulted negative. No relationship was found with DLs of the 26 BRCA mutation carriers. Conclusions: In a different way from what happens for Pap test, p16 does not seem to significantly improve the sensitivity of DL cytology in our series.
Molecular Imaging in Neuroendocrine Differentiation of Prostate Cancer
Authors: Sharjeel Usmani, Najeeb Ahmed, Fahad Marafi, Rashid Rasheed, Henney G. Amanguno, Fareeda al kandari
Journal: Clinical Nuclear Medicine (2017)

We report on a 62-year-old man with metastatic prostate cancer (cT3b N1) diagnosed in 2011, treated with total androgen blockage with flutamide and goserelin acetate (Zoladex). He presented with left suprascapular swelling and low-back pain after being asymptomatic for 5 years. His prostate-specific antigen was 0.049 ng/mL. F-NaF PET-CT and Ga-PSMA scan were negative, whereas Ga-DOTA NOC scan done after 10 days showed multiple somatostatin-avid hepatic and lymph node metastasis.
Impact of a multidisciplinary home palliative care unit in the place of death of patients diagnosed with cancer.
Authors: Borja Lopez De San Vicente, Juan Fernando Arango, Jacinto Batiz, Julio Gomez, Virginia Arrazubi, Kepa San Sebastian, Matxalen Aguilo, Nany Perez-Hoyos, Miriam Oliver, Maria Angeles Sala Gonzalez, Pilar Ruda, Elena Galve Calvo, Aiala Gandiaga, Patricia Novas, Teresa Abad, Laura Sande, Ane Zumarraga, Maria Lopez Santillan, Purificación Martínez del Prado
Journal: Journal of Clinical Oncology (2015)

45 Background: Home death rate is increasingly being used as a quantifiable indicator of the effectiveness of palliative care services. Intensifying home care and training of the end-of-life care practitioners, seems to be the way to improve the correlation between patient preferences and actual place of death. The objective of this study is to measure the impact of a multidisciplinary home palliative care unit (HPCU) (including medical, nursery, and psycological care, and social worker counselling) on the place of death of patients treated in a single oncology service. Methods: A retrospective case-control study was performed. HPCU patients consecutively admitted from January 2014 to June 2015 (cases) were matched with contemporary patients from the same center who could be followed by independent support services (Home Hospitalization, Psicooncologists and General Practitioners) (controls) by diagnosis, sex, age group ( &lt; 60 years, 61-75y and &gt; 75y) and oncologist physician. Place of death was registered. Odds ratio (ORR) and relative risk was analysed with SPSS for Windows ver.22.00. Results: Seventy four patients (p) admitted in a HPCU and their controls were included; 54% men; Average of age in cases 69.7years (y) (SD 10.8) and controls 68.5 y (SD 10.41), diagnosed of lung cancer 20p (27%), breast cancer 6p (8%), gastrointestinal noncolorectal cancer 16p (22%), colorectal cancer 10p (13.5%), head and neck cancer 5p (6.8%), genitourinary cancer 12p (16%), metastatic melanoma 2p, advanced sarcoma 2p and unknown primary cancer 1p. Place of death: home (cases 43p [59%], controls 8p [10%]); emergency service (1p [1.4%] vs 3p [4.1%]); in acute hospital in-patient-care (AH) (11p [15.1%] vs 29 p [39.2%]) and at a hospitalized palliative care unit (18p [24.7%], vs 34p [45.9%]); 1p of case group was lost during follow-up. The ORR for dying at home for HPCU patients was 11.82 (IC 95% 4.95-28.02) and a reduction in risk of die in an AH was seen (0.38, IC 95% 0.21-0.67). Conclusions: Death at home seems to be more feasible if cancer diagnosed patients have a proper follow-up by a multidisciplinary home palliative care unit, and it also reduce the possibility of dying in an acute hospital in-patient-care.