tbuckley/cabot-search huggingface dataset:
Apoptosis and proliferation related-proteins in breast carcinoma with neoadjuvant chemotherapy
Authors: E. Adrover, G. Peiró, F. I. Aranda, C. Alenda, M. F. Peiro, A. Paya, J. Segui, S. Benlloch, M. Garcia-Franco
Journal: Journal of Clinical Oncology (2005)

838 Background: Apoptosis and proliferation deregulation plays a role in tumor pathogenesis and progression, and apparently in response to treatment. We studied whether the expression of proteins involved in these mechanisms can identify a subset of breast carcinoma (BC) patients who will respond to neoadjuvant chemotherapy (NACT). Methods: We selected 99 core needle biopsies (CNB) and the corresponding resection specimens from BC patients in NACT. Clinical response (CR) based on tumor size was classified as complete (100%), partial incomplete (>50%), minor (<50%) or progression. Tumor cellularity was assessed in CNB sections and specimens as the percentage invasive cells. Specimens were classified by a five-point grading system. Staining for Bcl2, Bad (pBad Ser136), cleaved Caspase-3, p53, Her2/neu and Ki67 was performed in CNB. All antibodies were scored based on the proportion except for pBad that was considered as negative (no/faint) or positive (moderate/strong). Results were correlated with CR, pathologic response (PR) and clinico-pathological factors. Results: Patients median age was 49 years (range 25–80). Median initial tumor size was 5.5 cm (range 1.5–12) and after treatment 3.2 cm (range 0–15) (p=0.02). 88% were of ductal type, 12% lobular and 63% grade 3. Overexpression of Bcl2 (>50%) or p53 (>20%) was observed in 51% and 41%, respectively; pBad was present in 44% tumors; activated caspase-3 (>50%) in 17% and Ki67 (>30%) in 27%. Complete CR was seen in 37% and PR and 17% (p=0.002). Tumor cellularity decreased from a median of 30% to 5% and 30% showed >90% reduction of the clinical size (p<0.000). Her2/neu was positive in tumors of older patients (p=0.02) with high Ki-67 (p=0.04) and predicted tumor reduction (p=0.03). Ki67 and p53 overexpression was seen in grade 3, with low Bcl2 (p30% (p=0.02) and as a trend with pBad (p=0.09). The grade of PR correlated with pathological size, cytological changes and lymph-node status (p<0.04), and as a trend with Bcl2 (p=0.07), Her2/neu (p=0.09) and Ki67 (p=0.11). Conclusions: In BC following NACT, Ki67 correlates with CR. The observed trend towards improved PR depending on the levels of Bcl-2, Her2/neu and Ki67 supports the idea that they may have predictive value. No significant financial relationships to disclose.
FDG PET/CT Findings of an Isolated Abdominal Wall Metastasis of Endometrial Carcinoma 4 Years After Primary Surgery
Authors: Guohua Shen, Huan Ma, Ying Wan, Minggang Su, Anren Kuang
Journal: Clinical Nuclear Medicine (2017)

The cancer relapses of endometrial carcinoma are most frequently localized in the vaginal cuff, pelvic and para-aortic lymph nodes, peritoneum, and lungs, whereas the abdominal wall, intra-abdominal organs, and central nervous system are unusual sites. We present 18F-FDG PET/CT appearance of a pathologically proven abdominal wall metastasis in a 51-year-old woman with a diagnosis of endometrial adenocarcinoma 4 years ago.
Efficacy of weekly cisplatin 40mg/m<sup>2</sup> in definitive and adjuvant chemoradiation of head and neck cancer: A retrospective analysis.
Authors: Z. A. Otty, S. S. Sabesan, M. buhrer Skinner
Journal: Journal of Clinical Oncology (2011)

e16039 Background: When chemotherapy is needed with radiotherapy for head and neck cancers, 3-weekly high dose cisplatin is the regimen that has been used in large randomised trials. Difficulties with this regimen include high rates of toxicities and need for overnight admissions for hydration. Weekly cisplatin has been used in our institute for concurrent chemo radiation (CRT) of head and neck cancers to reduce toxicity and improve compliance. Aim of this study is to examine the efficacy of this approach. Methods: Retrospective review of medical records was undertaken on patients who received radical chemo radiation with weekly cisplatin 40mg/m2 at Townsville Cancer Centre from 2003 to 2009. Statistical analysis was performed using SPSS- version17 and survival probabilities were estimated using the Kaplan-Meier method. Results: Out of the total 102 patients who were eligible for analysis, 62 received definitive CRT and 40 received adjuvant CRT. Median follow-up was 20.1 months (range 5 to 86 months).37.2 % of patients got all the 6 planned doses of cisplatin while 68.6% received at least 5 doses. Only 4 (6.4%) patients had interruption of radiotherapy. For definitive CRT group and adjuvant CRT group, estimated 3-year overall survival was 64.5% (95% CI 51 to 78) and 71.5% (95% CI 53 to 90), respectively. The estimated 3-year disease-specific survival in definitive and adjuvant CRT groups were 70.3 % (95% CI 57 to 84) and 81.6% (95% CI 69 to 94), respectively. The 3-year survival for patients who got 5 or more cycles of chemotherapy was 75.2% (95% CI 63 to 88) compared to 52.6% (95% CI 33 to 72) for those who got less than 5 cycles ( p value =0.018). Conclusions: Despite this being a small retrospective study, survival figures and toxicity profiles of low dose weekly cisplatin are comparable to historical controls using high dose regimens. In addition, radiotherapy interruptions are minimised and it is easy to administer in out patient setting.
Dual role of <i>TGFBR1 </i>as a modifier of colorectal cancer risk.
Authors: Michael J. Pennison, Qinghua Zeng, Phillip J. Buckhaults, Virginia G. Kaklamani, Noralane M. Lindor, John L. Hopper, Loic Le Marchand, Steven Gallinger, Polly A. Newcomb, Robert W. Haile, John A. Baron, Daniel O. Stram, Hong-Tao Zhang, Upender Manne, Jeffrey C. Edberg, Robert P. Kimberly, Jianfeng Xu, Kui Zhang, Nengjun Yi, Boris Pasche
Journal: Journal of Clinical Oncology (2015)

600 Background: Experimental and clinical evidence suggests that constitutively decreased Transforming Growth Factor Beta type I receptor (TGFBR1) signaling predisposes to colorectal cancer (CRC) development. However, associations between TGFBR1 variants and CRC risk in case-control studies have been inconsistent. Methods: We utilized 1,043 CRC cases and their 1,627 unaffected sibling controls obtained from the Colon Cancer Family Registry (C-CFR). Individuals were genotyped for twelve TGFBR1 haplotype tagging SNPs. SNPs associated with CRC risk were validated in 261 CRC cases and 531 controls of African American ancestry and 990 CRC cases and 3,427 controls of Han Chinese ancestry. Validated SNPs were functionally characterized with respect to TGFBR1 expression and TGF-β signaling. Results: The TGFBR1 rs7034462-TT genotype was associated with CRC risk in C-CFR participants (OR 3.80[1.46-9.85]) and African Americans (OR 8.16[2.07-32.08]) (see Table). The TT genotype was associated with stage III and stage IV at diagnosis in C-CFR participants (OR 2.99[1.15-7.81] and OR 9.38[1.54-57.28]) and African Americans (OR 5.89[1.15-30.02] and OR 12.75[1.88-86.33]), respectively. The rs7034462-CT genotype was associated with decreased risk for CRC in African Americans (OR 0.55[0.31-0.99]) and Han Chinese (OR 0.67[0.48-0.95]) (see table). Cells carrying the rs7034462-TT genotype exhibited decreased constitutive TGFBR1 expression, increased SMAD7 expression, and decreased TGF-β signaling. Conclusions: The TGFBR1 rs7034462-T allele has dual, opposite roles with respect to CRC risk. The rare rs7034462-TT genotype is a moderate penetrance genotype associated with risk for CRC and advanced stage disease at diagnosis. In contrast, the common rs7034462-CT genotype is associated with decreased CRC risk. [Table: see text]
Response to neoadjuvant chemotherapy in BRCA1- and BRCA2-related breast cancers
Authors: B. Arun, D. Atchley, J. Litton, L. Pusztai, V. Valero, G. N. Hortobagyi, C. T. Albarracin
Journal: Journal of Clinical Oncology (2008)

618 Background: Germline mutations in the BRCA1 and BRCA2 genes account for the major genetic predispositions to breast cancer. BRCA 1 and BRCA2 related breast cancers have distinct pathologic and gene expression profiles. Furthermore, some of the BRCA1 and BRCA2 proteins might be involved in response to certain chemotherapeutic agents. The objective of this study was to evaluate the pathologic response (PR) to neoadjuvant chemotherapy (CT) in breast cancer patients (pts) with or without deleterious mutations in the BRCA1 or BRCA2 gene. Methods: After obtaining IRB approval, a retrospective evaluation of PR to neoadjuvant CT in pts with breast cancer who underwent genetic testing at U.T. M.D. Anderson Cancer Center was performed. Pathologic complete response (pCR) was defined as no residual invasive cancer in the breast and negative lymph nodes after neoadjuvant CT. Fisher's exact test was used to evaluate variables in univariate and binary logistic regression model for multivariate analysis. Results: A total of 170 pts were identified who received neoadjuvant CT and also underwent genetic testing. 137 pts were BRCA negative, 23 BRCA1 positive, and 10 BRCA2 positive. 121 pts received anthracycline plus taxane based CT and 36 pts anthracycline based CT only. Statistically significantly more pts with BRCA1 mutations had grade 3 and estrogen receptor (ER) negative disease compared to BRCA negative pts (p=0.01, p=0.001, respectively). The pCR rate was higher at 41 % for pts with a deleterious BRCA 1 mutation versus 21% for BRCA negative pts (p= 0.05). Other variables associated with higher pCR included having grade 3 (p=0.01), ER negative (p=0.001), and HER-2/neu positive disease (p=0.001). In multivariate analysis ER, grade, and HER-2/neu remained significant, but not BRCA status. There was no correlation between type of CT and pCR rate in patients with BRCA 1 positive breast cancer. Conclusions: Patients with BRCA1 related breast cancer have a higher pCR rate to neoadjuvant CT compared to BRCA negative breast cancer. Even though in multivariate analysis this was no longer statistically significant, the cohort is too small to rule out more modest differences. Larger studies need to evaluate whether certain types of CT would further improve pCR rates and this would translate into improved survival rates. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Pharmacia, Roche Nuvena Biosciences AstraZeneca, Dako, Monogram Biosciences, Pfizer AstraZeneca, NCI, Pfizer
Variation in utilization of palliative surgery in patients with metastatic colorectal cancer.
Authors: Mark Andrew Healy, Hari Nathan, Scott E. Regenbogen, Samantha Hendren, Arden M. Morris, Pasithorn Amy Suwanabol
Journal: Journal of Clinical Oncology (2016)

120 Background: Twenty-five percent of patients with colorectal cancer will present with unresectable disease. Palliative surgery has been shown to improve symptom control and improve patient satisfaction as well as demonstrate improved cost and decreased healthcare utilization. However, it is unclear what factors influence use. We sought to determine patient and hospital factors associated with palliative surgery use in advanced colorectal cancers. Methods: Using the National Cancer Data Base (NCDB) Participant User File from 2006 to 2012, 162,967 patients with metastatic colorectal cancer were identified. Hierarchical regression was used to evaluate patient factors associated with use of palliative surgery. Hospitals were then categorized into quintiles based on palliative surgery utilization. Results: On multivariable analysis, factors associated with palliative surgery included rectal tumor site (OR 1.63, 95% CI 1.49 – 1.77), Asian/Pacific islander race, Medicaid/uninsured status, and longer duration from diagnosis to treatment (p &lt; 0.05 for all). After stratifying hospitals into quintiles of utilization, significant regional variation in use of palliative surgery was noted. The lowest likelihood of use of palliative surgery was the NCDB South Atlantic region (DC, DE, FL, GA, MD, NC, SC, VA, WV). Compared to this region, hospitals with high use of palliative surgery were more common in the Pacific (OR 2.08, 95% CI 1.9-2.26), West South Central (OR 2.60, 95% CI 2.39 – 2.84), East North Central (OR 4.15, 95% CI 3.86 – 4.46), Mountain (OR 4.72, 95% CI 4.22 – 5.27), West North Central (OR 5.30, 95% CI 4.83 – 5.83), East South Central (OR 5.42, 95% CI 4.97 – 5.92), Middle Atlantic (OR 6.75, 95% CI 6.24 – 7.30), and New England (OR 6.75, 95% CI 6.05 – 7.54) regions. Compared to community cancer centers, high utilization hospitals were more likely to be academic/research centers or comprehensive cancer centers. Conclusions: In metastatic colorectal cancer, race and socioeconomic status appear to play a role in use of palliative surgery. It appears that use is higher for patients at academic/research hospitals or comprehensive cancer centers. Significant regional variation also exists in use of palliative surgery.
Cost-effectiveness of zoledronic acid (ZOL) versus denosumab (Dmab) in prevention of skeletal-related events (SREs) in castration-resistant prostate cancer metastatic to the bone (mCRPC).
Authors: S. J. Snedecor, J. A. Carter, S. Kaura, M. Botteman
Journal: Journal of Clinical Oncology (2011)

4581 Background: A phase III trial found that Dmab reduced the proportion of mCRPC patients (pts) developing ≥1 SREs by 4.7 absolute percentage points vs. ZOL (from 40.6% to 35.9%). However, overall survival, disease progression, serious adverse events, and bone pain were similar across treatments. In the United States (US), the acquisition cost of Dmab ($1650) per injection is nearly 2x that of ZOL's ($887). This analysis assessed the cost-effectiveness of Dmab vs. ZOL in mCRPC from a US managed care perspective. Methods: A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug and administration (Dmab=$32.46; ZOL=$153.86) costs for mCRPC pts receiving Dmab or ZOL for 27 months. Model inputs were selected to reproduce the phase III trial outcomes. QALYs were estimated by assigning utilities to health states (prior to SRE; SRE; post-SRE, and death). Cost for individual SREs ranged from $4,039 to $20,734. Future outcomes were discounted at 3%/year. Results: Compared to ZOL (Table), Dmab resulted in fewer SREs, more QALYs, and lower SRE-related costs, but higher drug-related and total costs ($5,313). Overall, Dmab resulted in an incremental cost of $1,250,000 per QALY gained. Conclusions: The use of Dmab in mCRPC is predicted to result in an incremental cost per QALY gained of $1.25 million. This high cost per QALY is attributed to Dmab having a higher drug acquisition cost, limited prevention of SREs, and no additional overall survival or disease progression benefits vs. ZOL. The cost per QALY of Dmab in this setting is far higher than what is considered in the US to be good value for a medical intervention ($50,000 to $100,000 per QALY), thus raising questions about the value of using Dmab in mCRPC. ZOL Dmab Difference SREs/pt 1.29 1.04 -0.25 Discounted QALYs/pt 0.93 0.94 +0.00493 Discounted costs Drug, administration, monitoring $12,963* $20,277 $+7,313 SREs $9,528 $7,604 $-1,924 Total $22,491 $27,881 +5,390 Cost/QALY gained $1,248,051 * Costs in 2010 U.S. dollars.
EGFR and <i>ABCG2</i> polymorphisms as prognostic and predictive markers in the NCIC CTG BR.21 trial of single-agent erlotinib in advanced non-small cell lung cancer (NSCLC).
Authors: G. Liu, D. Cheng, A. Le Maitre, N. Liu, Z. Chen, L. Seymour, K. Ding, F. A. Shepherd, M. S. Tsao
Journal: Journal of Clinical Oncology (2010)

7538 Background: EGFR and ABCG2 polymorphisms have been evaluated in small nonrandomized studies of EGFR tyrosine kinase inhibitors as markers of clinical outcome. BR.21 is a double-blind, placebo controlled trial of erlotinib as second/third line treatment in Stage IIIB/IV NSCLC. Methods: Normal tissue (± tumor) DNA was extracted from 242 paraffin tissues of 731 enrolled patients. Genotyping involved sequencing (EGFR -216 G>T [EGFR 216], EGFR -191 C>A [EGFR 191]), microsatellite length analysis (EGFR intron 1 CA dinucleotide repeat [CADR]) and allelic discrimination (ABCG2 421 C>A [ABCG2]). Cox proportional hazard and logistic regression models compared genotypes to overall survival (OS), progression-free survival (PFS), and skin toxicity (presence/absence). Results: In a 30 patient subset, genotyping concordance rates were > 93% between normal and corresponding tumor tissue DNA. Subgroups of genotyped and non-genotyped patients had similar OS/PFS and benefited similarly from study treatment. Genotyping technical success rates exceeded 92%. In the prognostic evaluation of patients on placebo (n = 86), carrying at least one short CADR allele (< 16 repeats) was associated with longer PFS compared with carrying all long (adjusted hazard ratio [aHR] 0.6, 95% confidence interval [CI] 0.3-1.0). In the predictive evaluation, no interaction was demonstrated between treatment arm and CADR (interaction p = 0.76). For OS, the heterozygous variant of EGFR 191 was predictive of lack of benefit from study treatment (HR 1.97, 95% CI 0.6-6.5) in univariate, but not multivariate analyses; EGFR 191 was not predictive of PFS or skin toxicity. EGFR 216 and ABCG2 421 polymorphisms were neither prognostic nor predictive of survival/skin toxicity outcomes. Conclusions: Carrying shorter alleles of the EGFR CADR polymorphism is associated with longer PFS, but is not predictive of survival benefit from erlotinib treatment or skin toxicity. EGFR and ABCG2 polymorphisms do not appear to aid in the selection of EGFR TKI therapy in advanced NSCLC patients who have failed platinum-based therapy. Supported by CCS, OICR research grants, Alan Brown and CCO Chairs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Roche
Transplantation from Matched Unrelated Donors (MUD) for Thalassemia and Other Congenital Red Cell Disorders.
Authors: Kathryn S. Leung, Ingrid Kuehnle, Stephen Gottschalk, Catherine M. Bollard, Dean A. Lee, Helen E. Heslop, Malcolm K. Brenner, Robert A. Krance
Journal: Blood (2005)
Treatment patterns for patients with localized (T1-T2) penile squamous cell carcinoma in the United States.
Authors: Brittney Diane Barbosa, Laura H. Hendrix, Kevin Alexander Pearlstein, Ronald C. Chen
Journal: Journal of Clinical Oncology (2013)

332 Background: The standard treatment for patients with localized penile squamous cell carcinoma is penectomy, which is associated with high psychosocial morbidity. Organ preservation using radiation therapy is an alternative. To our knowledge, this is the first population-based patterns of care study in this disease for a modern cohort of men. Methods: Caucasian (CA, N=1,270) and African American (AA, N=139) patients diagnosed with localized cancer from 2000-2009 were included from the Surveillance, Epidemiology and End Results (SEER) database. Treatments were categorized into ablative therapies (e.g. laser, electrocautery), surgical resection, or radiation therapy (including external beam and brachytherapy). Multivariate logistic regression assessed factors associated with receipt of radiation therapy as primary treatment. Results: 57% of patients were married. The vast majority of patients receive surgical resection, with about 1% receiving primary radiation therapy (Table). Patterns of care were not significantly different among AA and CA patients (p=.95). Multivariable analysis including diagnosis year, marital status, age, race and SEER region did not show any covariate significantly associated with receipt of primary radiation treatment. Conclusions: Surgical resection is the predominant treatment for patients with localized penile cancer in the United States, with very few patients receiving primary radiation therapy. [Table: see text]
Influence of <i>KRAS </i>G13D mutations on outcome in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without cetuximab.
Authors: S. Tejpar, C. Bokemeyer, I. Celik, M. Schlichting, U. Sartorius, E. Van Cutsem
Journal: Journal of Clinical Oncology (2011)

3511 Background: Addition of cetuximab (cet) to first-line chemotherapy (CT) was shown to significantly improve clinical benefit in patients (pts) with KRAS wild-type (wt) mCRC. Pts with KRAS codon 12 or 13 mutations are excluded from cet treatment. Studies suggest that not all KRAS mutations are equivalent in their biological effects. We investigated the influence of the KRAS codon 13 mutation G13D on clinical outcome compared with pts with other KRAS tumor mutations or KRAS wt tumors in a pooled analysis of pts from the CRYSTAL and OPUS studies. Methods: Variation of the treatment effect by KRAS mutation status, and the effect of KRAS mutation status within each treatment group for response, progression-free (PFS) and overall survival (OS) was investigated. Results: There were 689 pts in each treatment arm: 447 vs 398 pts had KRAS wt tumors, 41 vs 42 pts had KRAS G13D mutant tumors and 201 vs 249 pts had tumors with other KRAS mutations, for the CT and CT+cet arms, respectively. Heterogeneous treatment effects were seen for all endpoints across the mutation types with significant treatment interaction by KRAS mutation status for response (p<0.0001), PFS (p<0.0001) and OS (p=0.0219). Compared with pts with KRAS wt tumors those with G13D mutations had a similar relative treatment effect but at a much lower effect level (Table). Conclusions: These observations suggest a heterogeneous treatment effect according to tumor KRAS mutation status. Pts with KRAS G13D mutant mCRC appear to benefit from the addition of cet to first-line CT. Further prospectively generated clinical investigations are necessary to confirm these data. N Response % PFS mo OS mo CT CT+cet CT CT+cet CT CT+cet KRAS wt 845 38.5 57.3 7.6 9.6 19.5 23.5 Odds ratio/HR* [95% CI] P value 2.17 [1.64–2.86] <0.0001 0.66 [0.55–0.80] <0.0001 0.81 [0.69–0.94] 0.0063 KRAS G13D 83 22.0 40.5 6.0 7.4 14.7 15.4 Odds ratio/HR* [95% CI] P value 2.41 [0.90–6.45] 0.0748 0.60 [0.32–1.12] 0.1037 0.80 [0.49–1.30] 0.37 KRAS other mutations 450 43.8 30.5 8.5 6.4 17.7 15.5 Odds ratio/HR* [95% CI] P value 0.56 [0.38–0.83] 0.0037 1.42 [1.10–1.83] 0.0069 1.14 [0.93–1.40] 0.1964 * Odds and HRs are for CT+cet vs CT groups. Abbreviation: HR, hazard ratio.