tbuckley/cabot-search huggingface dataset:
Comparing magnetic resonance imaging/ultrasound-fusion biopsy and systemic 12-core transrectal ultrasound biopsy for whole gland pathology.
Authors: Daniel Su, Arvin George, Minhaj Siddiqui, Soroush Rais-Bahrami, Lambros Stamatakis, Cheng William Hong, Jason Rothwax, Chinonyerem Okoro, Dima Raskolnikov, Nabeel Shakir, Annerleim Walton-Diaz, Richard Simon, Baris Turkbey, Bradford J. Wood, Peter L. Choyke, Peter A. Pinto
Journal: Journal of Clinical Oncology (2014)

84 Background: Historically, pathologic findings from standard 12-core prostate biopsies are upgraded in 25 to 33% of patients after radical prostatectomy (RP). MRI/US fusion prostate biopsy has been shown to upgrade prostate cancer compared to standard 12-core biopsy in 32% of patients. MRI/US fusion biopsy may offer a more accurate representation of whole gland pathology. We evaluate the rate of pathologic upgrade in standard 12-core biopsy and MRI/US fusion biopsy when compared with whole gland pathology from RP. Methods: Patients who underwent random prostate biopsy, fusion biopsy and subsequently RP for prostate cancer from 2012 to 2013 were included. Pathology was reviewed by a single pathologist. The cohort was divided into clinically significant high-grade (Gleason score 4+3 or higher) and clinically insignificant low-grade (Gleason score 3+4 or lower) sub cohorts. Pathological upgrade was defined as any increase in Gleason sum or primary Gleason score. McNemar’s test was used to compare the proportion of patients who were upgraded from random biopsy to RP versus the proportion that were upgraded from fusion biopsy to RP. Results: Sixty eight patients underwent 12-core and fusion prostate biopsy then subsequently RP. Mean prostate-specific antigen was 9.2ng/ml. There are total of 43 patients with clinically insignificant low-grade and 25 patients with clinically significant high-grade. Fusion biopsy upgraded 19 patients (28%) compared to 12-core biopsy, eight of these patients had negative 12-core biopsy. Pathology on the RP specimen upgraded 18 of the 12-core results (26%) compare to only eight fusion biopsy results (11%). (p =0.0095) 14 patients (20%) who had clinically insignificant low-grade disease on 12-core biopsy were upgraded to clinically significant high-grade on RP. Only two patients (3%) with clinically insignificant low-grade from fusion biopsy were upgraded on RP. (p&lt; 0.0005) Conclusions: Prostate cancer detected on MRI/US fusion prostate biopsy has significantly lower rates of pathologic upgrade than standard 12-core biopsy when both were compared to prostatectomy specimens. MRI/US fusion biopsy may represent whole gland pathology more accurately compared to 12-core biopsy.
Chemoradiotherapy for locally advanced head and neck cancers: Two-year survival and toxicity outcomes from a regional cancer centre in UK.
Authors: R. K. Dandamudi, L. Fresco
Journal: Journal of Clinical Oncology (2011)

e16020 Background: To evaluate the 2-year overall survival (OS), cause-specific survival and toxicities of locally advanced head and neck cancer patients treated with primary chemo-radiotherapy (CRT) over a two year period. Methods: Between June 2006 and May 2008, sixty patients with locally advanced head and neck cancers were treated (excluding skin and thyroid). Of these, seventeen (28.33%) were stage III, thirty nine (65%) were stage IVA and four (6.66%) were stage IVB. All received concurrent 3 weekly cisplatin (75-80 mg/m2) and radiotherapy dose of 66-70 Gy in 33-35 fractions, treated daily in three phases by conformal 3-dimensional CT-planning. Treatment response was assessed radiologically 3 months post primary CRT. Survival was calculated from the time of histological diagnosis and time to treatment tailure (TTF) from the completion of treatment. Results: The median age was 57 years (range 18-79) and M:F ratio was 3:1.The 2-year OS was 73.3 % and loco-regional control rate was 83.3 %. The treatment failure rate was 16.6 % (10/60 patients) with a median TTF of 5 months (range= 1 to 24 months). Sixteen patients (26.6%) died with in 2 years of treatment of which five (4%) died of progression from residual disease, six (4.8%) died of loco-regional recurrence and three (5%) died of distant recurrence. Rest of the three died of other causes and includes two (3.33%) from second primary (lung and oesophageal) cancers. The incidence of acute severe or persistent oral mucositis was 4% (RTOG grade 3) and none had grade 3/4 skin toxicity. The incidence of late toxicities was 4% for osteoradionecrosis (ORN) of the mandible, 3.2% for severe trismus and 2.4% had sinus/fistula formation. The incidence of severe oropharyngeal stenosis/total dysphagia was 3.2% and 3 patients (2.4%) were on long term (15-32 months) gastrostomy feeding tube for nutrition. One patient (0.8%) developed severe carotid artery disease in the RT field. None of the patients had treatment related death. Conclusions: Our results are on par with international standards published in the literature. This data will be followed up for long-term outcomes and can be used as a bench mark for comparison with current modern planning techniques like intensity modulated radiotherapy (IMRT).
Combination of Proteasome Inhibitor PS 341 (Velcade®) with Histone Acetylase Inhibitor (HDAC) PXD 101 Shows Superior Anti-Myeloma Activity and Inhibits Osteoclastogenesis.
Authors: Suzanne Lentzsch, Gulsum Anderson, Cuiling Li, Chandra P. Belani, Markus Y. Mapara, David Roodman
Journal: Blood (2005)
Multicenter, prospective, case-control, observational study on the influence of venous thromboembolism on patient outcome.
Authors: M. Mandala, R. Labianca, G. Agnelli, L. Crino, E. Maiello, A. Santoro, D. Fagnani
Journal: Journal of Clinical Oncology (2011)

1554 Background: The association between venous thromboembolism (VTE) and cancer is well known. VTE represents the second cause of death in cancer patients. In some retrospective analysis, carried out using population and hospital-based registries, it has been reported that patients with cancer and VTE have a worse survival than those with cancer without VTE. Methods: MASTER ONCOLOGY is a prospective, multicenter, national, observational, case-control study specifically designed to identify VTE risk factors and to evaluate the influence of VTE on outcome of cancer patients with locally advanced or metastatic solid tumours. Patients in case (cancer patients with VTE) and control (cancer patients without VTE) groups have been matched for gender, age, cancer site, cancer histology and extension of disease. Information on patients, tumour characteristics, concomitant diseases, treatments, risk factors were registered. Survival data have been prospectively collected at 10 months and assessed through both Kaplan Meier method and Cox proportional hazards regression. Results: 611 patients were enrolled in the study by 51 Italian Centers. Of these, 237 cases and 339 controls were evaluable. The mean age was 64.7 (range 23-84) and 64.5 (range 41-87) years in cases and controls groups, respectively; the percentage of males was 43.0% and 41.9%. The most frequent tumour sites were colon, breast, lung, pancreas and stomach. Overall survival was statistically better for control patients as compared to case patients (p=0.0021). The raw HR was statistically significant: case patients had a risk of death 1.56 larger than controls (95% CI 1.23-1.98). Considering the complete model (using backward selection), the HR, due to patients status after adjustment for covariates, was 1.29 (95% CI 1.01-1.66). Conclusions: The study results demonstrate, for the first time, in a prospective and specifically designed study, that patients with cancer and VTE have a reduced survival compared to cancer patients without VTE.
Salvage radiation therapy after radical prostatectomy: Contribution of a dose escalation to macroscopic local relapses.
Authors: Imad Eddine Selmaji, Corina Udrescu, Tristan Brahmi, Hamza Samlali, Ariane Lapierre, Ciprian Enachescu, Alain Ruffion, Olivier Chapet
Journal: Journal of Clinical Oncology (2016)

e634 Background: Salvage radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer using 66 Gy may not be enough to treat macroscopic disease. The presence of a macroscopic nodule on the MRI could justify a focal dose escalation. This study evaluates the tolerance and efficacy of a new technique of irradiation including a focal boost to the nodule. Methods: Between 2011 and 2015, 14 patients, with a macroscopic relapse diagnosed on the MRI, underwent targeted MRI-guided biopsies. Three gold markers were implanted into the prostatic bed for a more accurate MRI/CT fusion and image guided IMRT. A dose of 60 Gy was delivered to the prostatic bed followed by a dose escalation to 72Gy on the macroscopic nodule. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated using the CTCAE v4. PSA level and late toxicities were assessed at 1 month and then every 6 months for 3 years. Results: The mean follow-up was 26.2 [18 – 36] months. Two patients had a biochemical failure after salvage RT (one bone metastasis and one lymph node recurrence). The local control rate was 100% and the biochemical control rate was 85.7%. Results for acute and late toxicities are summarized in the table. One patient presented with grade 2 urinary toxicity during the prostatic bed irradiation which lowered to grade 1 when the dose was focalized to the nodule. No grade 2 acute GI toxicity was seen. All late GI and GU toxicities were grade 1. Conclusions: Dose escalation to the macroscopic nodule visible on MRI is feasible using an IMRT-IGRT approach with gold makers. This technique allows a perfect initial local control at 3 years with a good tolerance. [Table: see text]
Predictors of quality radiation therapy completion after breast-conserving surgery.
Authors: Benjamin Daniel Powers, Maureen Patricia Daly, Alliric Isaac Willis
Journal: Journal of Clinical Oncology (2012)

210 Background: Quality radiation therapy completion (QRTC) is critical to quality breast conserving treatment (BCT). Our aim was to identify predictors of QRTC after BCT in an urban setting. Methods: Hospital Tumor Registry Data was collected for female BCT patients Stage I and II. Radiation therapy completion (RTC) was defined as 35 days or more of breast radiation. QRTC was defined as RTC of 35-49 days. Statistical analyses were performed with SPSS. Results: 346 patients were analyzed. Demographic data: Ethnicity: Black n=230 (66.5%), White n=63 (18.2%), Hispanic n=53 (15.3%); Age: &lt; 50 years n=74 (21.4%), 50 – 64 years n=152 (43.9%), &gt; 64 years n=120 (34.7%); Insurance: Medicare n=131 (37.9%), Private n=94 (27.2%), Medicaid n=121 (35.0%). Hispanics (60.4%) were more likely to have Medicaid versus blacks (33%) and whites (20.6%), p&lt;0.001. Majority (52%) of patients live within 3 miles of treatment. More blacks (66.5%) live &lt;3.0 miles than whites (7.9%) or Hispanics (41.5%), p&lt;0.001. There was no significant difference in mean days of RTC by ethnicity (black 46.8, white 46.4, and Hispanic 48.1 days; p=0.75) or total RTC % (black 88.2%, white 97.9%, Hispanic 93.3%; p=0.09). However, a substantial difference was seen in QRTC % by ethnicity (black 51.8%, white 79.2%, Hispanic 57.8%; p=0.03) Multivariate logistic regression of failure to achieve QRTC found associations with black race (OR=2.67), Medicare (OR= 3.46), Medicaid (OR=2.19), and age &lt;50 years (OR=4.13). Conclusions: This study demonstrates high overall % RTC; however, it identifies significant disparities in successful QRTC. Those at greatest risk of unsuccessful QRTC were younger, Medicare or Medicaid insured, and black ethnicity. Distance was not a significant factor in this urban population. Further studies should investigate the specific barriers that may contribute to disparities in QRCT among those at risk groups. [Table: see text]
Clinical implications of bone scan underuse for patients with high-risk prostate cancer (CaP).
Authors: Aaron David Falchook, Laura H. Hendrix, Ronald C. Chen
Journal: Journal of Clinical Oncology (2014)

124 Background: National practice guidelines recommend bone scans during workup of high-risk CaP patients. Omission of bone scans may lead to aggressive and futile treatments in patients with undiagnosed metastatic disease. We hypothesized that patients who did not vs. did have a bone scan have inferior survival after treatment. Methods: Patients in the Surveillance Epidemiology and End Results (SEER)-Medicare database diagnosed from 2004-07 were included. Prevalence of bone scan use in patients with apparent high-risk CaP (N=19,885) was calculated, without consideration of M-stage which is a downstream result of the scan. Then, we excluded patients with M1 disease and compared prostate cancer specific mortality (PCSM) among 17,450 patients with apparent M0 cancer who received vs. did not receive a staging bone scan. Kaplan-Meier estimates and Cox multivariate models were used. Results: Only 60% of high-risk patients received a bone scan. In patients with apparent M0 disease, 58% of those who did not receive a bone scan received curative-intent treatment – either surgery or radiation (Table). With median follow-up of 3.3 years, PCSM was higher in patients who did not receive a bone scan (4-year 22% vs. 18%, p&lt;.001). When stratified by treatment, a significant PCSM difference was seen among radiation patients (4-year PCSM 19% no bone scan vs. 14% bone scan, p=.006), but not in surgical or no treatment/hormone only patients. On multivariate analysis controlling for age, race, marital status, comorbidity, diagnosis year, regional socioeconomic status, geographic region, and population density, PCSM difference in radiation patients remained significant (hazard ratio 1.36 for no bone scan, p=.04). Conclusions: 40% of high risk CaP patients did not receive recommended bone scan during workup. Patients with apparent non-metastatic CaP but did not receive a staging bone scan often received curative-intent treatments. A worse survival among patients without bone scan suggests a potential overtreatment in patients with undiagnosed metastatic disease. [Table: see text]
Bcl2 expression and prediction of outcomes to anthracycline-based neoadjuvant chemotherapy in ER-positive breast cancer and to nonanthracycline adjuvant therapy.
Authors: P. D. Dickinson, T. M. A. Abdel-Fatah, A. R. Green, P. Moseley, J. S. Reis-Filho, I. O. Ellis, S. Chan
Journal: Journal of Clinical Oncology (2011)

589 Background: Only 20% of patients with breast cancer (BC) benefit from their treatment and there is an urgent need to identify biological markers which could be used to tailor treatment to individual patients, thereby avoiding unnecessary toxicity. Most chemotherapy agents preferentially target continuously cycling cells, which results in mitotic catastrophe and apoptosis. We therefore hypothesized that the level of Bcl2 protein, which is a cell cycle/apoptosis regulator, could predict response and clinical outcome, following chemotherapy for BC. Methods: Bcl2 expression was immunohistochemically evaluated in 2650 patients with primary BC, who received neoadjuvant and/or adjuvant therapy, from four independent series; a) 240 locally advanced primary BC patients treated with an anthracycline-based combination b) 245 BC patients treated with surgery followed by anthracycline-based chemotherapy, c) 145 patients with BC with HER-2 overexpression treated with surgery followed by trastuzumab and d) 2000 consecutive cases of primary BC in which adjuvant CMF and/or tamoxifen therapies were prescribed. Results: Low Bcl2 expression was associated with poor clinical outcome in patients who received CMF, tamoxifen and/or trastuzumab compared to high Bcl2 expression (p=0.01). After anthracycline-based neo-adjuvant chemotherapy, 18/58 (31%) of low Bcl2 expression BC achieved pCR vs. 8/97 (8%) of high Bcl2 expression BC (p=0.00023). In a multivariate analysis, Bcl2 expression remained an independent predictor for pCR (p<0.02). In the ER+ subgroup, 4/11 (36%) of low Bcl2 expression BC achieved a pCR compared to 3/70 (4%) of high Bcl2 expression BC (p=0.0004) and the progression free survival of low and high Bcl2 expression BC was similar despite on-going treatment with adjuvant hormonal therapy. Conclusions: Anthracycline based neo-adjuvant chemotherapy is an effective treatment for low Bcl2 expression BC, even in ER+ tumours. Bcl2 expression should be included in the prognostic and predictive panel of markers for management of BC. Clinical trials based on Bcl2 expression are warranted.
siRNA library screening to define esophageal adenocarcinoma cell survival factors.
Authors: Shane P Duggan, Catherine Garry, Fiona Behan, Murat Kirca, Sarah MacGarrigle, Hiromi Kudo, Robert D Goldin, Marina Botto, Aideen Long, Dermot P Kelleher
Journal: Journal of Clinical Oncology (2015)

70 Background: There is a pressing need to identify new therapeutic targets for esophageal adenocarcinoma (EAC). Hence, we utilized siRNA-screening libraries to identify genes impacting on EAC cancer cell growth to identify potential therapeutic targets. Methods: A “druggable genome” library (6,022 individual siRNAs) was utilized to examine EAC cell survival using the MTT assay. Statistical analysis combined the use of Z-factor, t-test and SSMD. EAC cell lines GohTRT, SKGT4 and OE33 were utilized. Functional validation of the resulting siRNAs utilized RT-PCR, Western Blot, ELISA and TOPFLASH assays. Results: siRNA library screening resulted in positive quality metrics (Z-factor&gt;0.5) confirming its validity and further identifying 118 high confidence gene targets affecting EAC cell growth. Verification of these siRNA targets in multiple cell lines indicated a good level of concordance with the primary screening data. Bioinformatic and pathway mapping approaches of these targets emphasized links between EAC cell proliferation and regulators of inflammation and “immune cell processes” (LIF, C1Qa, C1r, C1s, GDF15, IL9R and TREM2). Pathological and transcriptomic studies demonstrated that LIF (FC=96.7; P&lt;0.0001), GDF15 (EAC: FC=74; P&lt;0.0001), C1Qa and TREM2 may be up-regulated in EAC biopsies. In functional work, exposure of EAC cell lines to recombinant or native proteins of C1q, LIF and GDF15 rescued the observed effects of their respective silencing in EAC cells (&gt;90%,p0.001) and acted as potential growth promoters (&gt;40%, p0.01). Auto-regulatory feedback loops were discovered in response to treatment with exogenous C1q and LIF in EAC cells. Signal transduction could be induced through b-catenin stabilization and STAT3 pathways in response to C1q and LIF treatment respectively. GDF15 was observed to act in a similar fashion to TGFb in scratch wound assays and additionally regulate Th17 type T-cell differentiation. Conclusions: Genes regulating EAC proliferation have been defined by siRNA library screening. We have identified secreted immune factors, not previously associated with EAC biology, capable of regulating EAC cell survival.
The effect of body mass index (BMI) and nutrition on morbidity and mortality in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).
Authors: Komal Patel, Joseph B Oliver, Ravi Chokshi, Jimmy S Patel, Kevin Spiegler
Journal: Journal of Clinical Oncology (2016)

765 Background: In patients with peritoneal malignancies undergoing CRS-HIPEC, their weight and nutritional factors may be affected by the presence of cachexia or obesity. With the potential morbidity of these radical operations, the selection of patients is paramount. BMI and albumin have long been utilized to predict outcomes in surgical patients. Our study evaluated whether BMI and albumin had an impact on CRS-HIPEC morbidity and mortality. Methods: Demographics, comorbidities, intraoperative variables and post-operative outcomes were analyzed using a retrospective database comprising of 28 patients undergoing CRS-HIPEC at our institution from 2012 to 2015. Median BMI of 25 and median albumin of 3.8 were used to compare the 2 groups. Primary outcome was overall survival, while secondary outcomes included complications, length of stay and intraoperative variables. Results: Patients were organized into 2 groups: &lt; 25 BMI (n = 13) and &gt; 25 BMI (n = 15). Albumin levels were assigned to each group and demonstrated similar values (4.0 vs 3.8, p = 0.44). Demographic data described similarly aged (54 vs 56 years, p = 0.42), gender (92% vs 93% females, p = 0.92), and peritoneal carcinomatosis index (21 vs 18, p = 0.60). The &gt; 25 BMI group had slightly higher number of comorbidities (Charlson Comorbidity Index &gt; 0 in 23% vs 60%, p = 0.04). Both had similar operative times (566 vs 549 minutes, p = 0.73), blood loss (700 vs 550 ml, p = 0.96) and median numbers of organs removed during cytoreduction (4 vs 3, p = 0.28). Length of stay was no different between the 2 groups (11.5 vs 10.5 days, p = 0.86). Six of the thirteen &lt; 25 BMI individuals died during follow up (mean 5.6 months) compared to only two of the fifteen &gt; 25 BMI individuals (mean 10.2 months) (p = 0.01). Conclusions: In our single center series, patients &gt; 25 BMI had a better survival when compared to &lt; 25 BMI patients. However, the analysis of the albumin levels did not demonstrate a statistically significant difference. There were no other significant differences in preoperative, intraoperative or other post-operative outcomes. Higher powered studies with longer follow-up are needed to confirm our results.
Racial disparities in prostate cancer treatment: The contribution of inappropriate care.
Authors: C. J. Presley, A. C. Raldow, L. D. Cramer, P. R. Soulos, J. B. Long, D. V. Makarov, J. B. Yu, C. P. Gross
Journal: Journal of Clinical Oncology (2011)

4544 Background: Racial disparities persist in curative therapy (CTx) for clinically localized prostate cancer (CaP). This study explores disparities across strata of treatment appropriateness as defined by potential for clinical benefit. Methods: Using the SEER-Medicare dataset, we identified 64,192 men (54,420 white and 5,933 black) aged 67-85 years diagnosed with localized CaP 1996-2005. Life expectancy (LE) was estimated based on age and comorbidity burden using a life table approach. Low benefit patients were defined as men with low-risk tumors and LE <10 years, intermediate benefit as moderate-risk tumors and LE <10 years or low-risk tumors and LE >10 years, and high benefit as moderate-risk tumors and LE >10 years. CTx was defined as either radical prostatectomy or radiation. Bivariate associations between race and independent variables (demographics, tumor risk, year of diagnosis, SEER registry) were explored using chi-squared tests. Logistic regression was used to model the association between race and receipt of CTx, as well as to test the interaction between race and clinical benefit category. Results: Approximately 66% of white and 56% of black patients received CTx. Although black patients were significantly less likely to receive CTx in each benefit group, the magnitude of the racial disparity varied with the degree of potential clinical benefit. In the low benefit group, the adjusted predicted probability of receipt of CTx was 44% for black compared to 48% for white patients, 58% vs. 69% in the intermediate group, and 65% vs. 81% in the highest benefit group. The largest racial disparity existed in the highest benefit group (adjusted odds ratio (OR) for CTx for black vs. white patients 0.57; 95% CI: 0.49, 0.65); among patients in the low benefit group, the OR for black vs. white patients was 0.77; 95% CI: 0.68,0.88. The interaction between race and clinical benefit group was significant (p<0.001). Conclusions: The magnitude of racial disparities in the receipt of CTx for CaP varies substantially according to clinical benefit. Improving racial disparities should focus on increasing CTx of black CaP patients of the highest clinical benefit.