bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified-dose capecitabine + bevacizumab for the treatment of advanced/metastatic hepatocellular carcinoma (HCC): A phase II, single-arm study
Authors: Hsu C. , Yang T. , Hsu C. , Toh H. , Epstein R. J. , Hsiao L. , Cheng A. 
Published: March 2020

15190 Background: The oral fluoropyrimidine capecitabine (X; Xeloda®) has anti-tumor activity in metastatic colorectal, breast, gastric cancers and HCC. The humanized monoclonal antibody bevacizumab (A; Avastin®) targets VEGF and limits tumor angiogenesis. The combination of X+A is active in breast cancer xenografts and increases the objective response rate (ORR) in patients (pts) with anthracycline- and taxane-resistant breast cancer. X+A also appears to be highly active when administered with irinotecan as first-line treatment for metastatic colorectal cancer. We report data from a multicenter, Ensign’s 3-stage design, open-label phase II trial of X+A as first- line treatment for HCC. Methods: Pts with untreated, histologically confirmed advanced HCC received X 800mg/m2 orally bid d1–14 and A 7.5mg/kg i.v. infusion d1. Treatment was repeated q3w x6 cycles in the absence of disease progression or unacceptable toxicity. Pts without progressive disease after 6 cycles of X+A could continue on the same doses of X+A. Primary endpoint was ORR (RECIST); secondary endpoints were disease control rate, progression-free survival (PFS), overall survival, and safety. Results: 45 patients were enrolled. By Dec 2006 the 25 patients (male, 88%; median age 52 years; Child-Pugh A) enrolled in Stages 1 and 2 of the study had completed at least 6 months’ follow-up and were assessed for efficacy and safety. ORR (CR+PR) was 16% (95% CI 4.5–36.1%) and disease control rate (CR+PR+SD) was 60% (95% CI 38.7–78.9%). Median overall survival was 10.7 months (95% CI, 5.3–14.7) and median PFS was 4.1 months (95% CI, 1.6–6.2); the PFS rate (i.e. the event (PD or death) free rate) at 3 and 6 months was 64% (95% CI 45.2–82.8%) and 34% (95% CI 15.1- 53.2%), respectively. Median number of cycles per patient was 5 (range 1–6). The most common treatment-related grade 3 toxicities included hand-foot syndrome (n=2), nail changes (n=1), diarrhea (n=1), nausea/vomiting/hiccups (n=1), gastric ulcer hemorrhage (n=1). Conclusions: X+A appears to be both effective and well tolerated as first-line treatment for HCC, providing support for further evaluation of this combination in this difficult-to-treat cancer. No significant financial relationships to disclose.
Impact of risk-reducing oophorectomy on quality of life in women at risk for ovarian cancer
Authors: McArthur H. L. , Hensley M. , Brown C. L. , Chi D. S. , Offit K. , Hurley K. , Li Y. , Gemignani M. L. , Robson M. E. , Barakat R. R. 
Published: March 2020

1520 Background: Factors associated with quality of life (QOL) changes after risk-reducing salpingo-oopherectomy (RRSO) have not been clearly defined. We report the results of a prospective QOL study among women undergoing RRSO at the Memorial Sloan-Kettering Cancer Center. Methods: 101 women undergoing RRSO between April 2000 and April 2004 were included. Participants completed questionnaires evaluating perceived risk, symptoms, cancer-related worries/distress, sexual function and QOL at baseline, and at 6 and 12 months after RRSO. All questionnaires were adapted from validated, standardized instruments. Instrument score changes over time were evaluated by GLM repeated measures analysis. Results: The median age of the participants was 48y; 62.4% were post- menopausal; 47.5% had a deleterious BRCA mutation; 46.5% had a family history of OC; 73.3% had a personal history of breast cancer. 74.1% reported a perceived lifetime OC risk =25%. Mean total symptom and depression scores at baseline did not differ by menopausal status, BRCA mutation status, personal breast cancer history or OC family history. Menopausal subscale scores were significantly lower at baseline among pre-menopausal women. Baseline mean anxiety/distress scores and cancer-specific distress scores were significantly higher among mutation carriers than non-carriers. Among women who completed all 3 questionnaires (n=60), overall QOL measured by SF36 did not change over time. There was a significant interaction of menopausal status at surgery with the changes in total symptom and menopause subscale scores. There was a significant interaction between mutation status and post-operative decline in anxiety/distress scores. At 6 and 12 months, 24 (36.4%) and 22 (42.3%) of women, respectively, reported a worsened sex life and approximately 15% were dissatisfied with their decision to undergo RRSO. Conclusions: Most women perceived themselves at increased risk of OC and were satisfied with their decision to undergo RRSO. Mutation carriers demonstrated significant baseline OC-specific anxiety, but experienced a significant reduction post-RRSO. A significant increase in symptomatology was reported after RRSO, particularly among pre-menopausal women; however, there was no significant overall change in QOL. No significant financial relationships to disclose.
LCIS and tamoxifen use: A single institution review
Authors: Kirstein L. J. , Martei Y. , Roche C. , Smith B. L. , Specht M. C. , Gadd M. A. , Drohan B. , Lawrence C. , Michaelson J. , Hughes K. S. 
Published: March 2020

1527 Background: Results of the NSABP-P1 trial were published in 1998 showing a 50% reduction in breast cancer in the high- risk population with the use of tamoxifen. The use of tamoxifen is individualized, and depends on both patient and physician factors. We looked at the recommendations for and the use of tamoxifen in women with LCIS. Methods: A retrospective chart review at a single institution was performed from March 27, 1980 through September 19, 2005 for patients diagnosed with LCIS. Pathology and operative reports, as well as patient notes were reviewed for discussions about tamoxifen. Data was collected on whether a discussion took place, whether tamoxifen was or was not advised, whether the patient declined to take tamoxifen, whether they took it in the past or were currently on tamoxifen. We also examined the rate of DCIS and invasive cancer in this population. Results: There were 321 patients diagnosed with LCIS. Of those patients 193 were diagnosed after the publication of the P1 trial. Of these 193 patients we identified 104(54%) patients whose charts contained notes indicating a discussion about tamoxifen. The results of the discussion about tamoxifen are as follows: 21(20%) patients were currently taking tamoxifen, 16(15%) had taken it in the past, 37(36%) patients declined to take tamoxifen, and 17(16%) had not made a decision about taking tamoxifen. There were 13(13%) patients for whom tamoxifen was advised against. In the entire cohort of 321 patients, 15% went on to develop DCIS or invasive cancer in the first 12 years of follow up. We did not look at cancer rate Vs tamoxifen use due to the small numbers with available information. Conclusions: While the P1 trial recommends tamoxifen for breast cancer prevention in high-risk patients, in our experience, almost half of the patients did not have a documented discussion about the medication, and the majority of those who did decided not to take tamoxifen. This will likely have a large impact on the rate of DCIS and invasive breast cancer in this group. No significant financial relationships to disclose.
Comparison of weight loss with a National Cancer Institute diet and a plant-based olive oil diet in overweight women with invasive breast cancer
Authors: Flynn M. M. 
Published: March 2020

1532 Background: The risk of breast cancer increases with increasing body weight, higher blood levels of fasting insulin and triglycerides, and lower HDL-c. Weightloss and diet can affect these variables. While diets lower in fat are routinely recommended for weightloss and cancer prevention, there is no firm evidence that they have an advantage compared to diets higher in dietary fat. Further, lower-fat diets can adversely affect fasting blood levels of insulin, triglycerides and HDL-c. Methods: Overweight women diagnosed with invasive breast cancer after the age of 50 consumed a National Cancer Institute diet (NCI; total fat: ≥15% to <30%) and a plant-based, olive oil diet (PBOO; total fat: ≥35%, primarily from extra virgin olive oil) for 8 weeks each in a crossover trial with random assignment to order. Fasting blood samples at the end of each diet were analyzed for insulin, triglycerides and HDL-c. Results: Results for 14 subjects. Percent weightloss (NCI: 4.2 ± 2.3; PBOO: 6.2 ± 2.1) in this preliminary group exhibited a significant diet-order effect. Ten of the 14 had lower levels of fasting insulin while on the PBOO diet. Conclusions: These initial results suggest that weightloss can be achieved with a plant-based, higher-fat diet emphasizing extra virgin olive oil, and such a diet may have a metabolic advantage compared to the standard, lower-fat diet. [Table: see text] No significant financial relationships to disclose.
Impact of screening on presentation and survival of colorectal cancer
Authors: Beg M. S. , Gupta A. , Komrokji R. , Atiq M. , Ali S. , Safa M. 
Published: March 2020

1535 Background: There is an increasing emphasis and utilization of colorectal cancer (CRC) screening. We evaluated the effect of screening on CRC presentation and outcome. Methods: We reviewed all the invasive CRC cases diagnosed between Jan 1995-Dec 2005 at the Cincinnati Veteran’s Affairs hospital. Individual case records were reviewed and the data collected including patient demographics, treatment, outcome, mode of presentation as well as whether CRC was detected as a result of screening. Results: Altogether 288 patients were diagnosed with CRC during the study period. The median age at presentation was 69.3 years and 18.8% were African-Americans. Early stage CRC was diagnosed in 63.4% cases (stage 1: 32.7%, stage 2: 30.8%) and 33.3% were diagnosed at advanced stage (stage 3: 18.1% and stage 4: 15.3%). Seventy seven (26.7%) CRCs were asymptomatic at presentation and were diagnosed as a result of screening. Predominant screening modalities included fecal occult blood testing (46.8%) and flexible sigmoidoscopy (22.1%). The proportion of screen- detected cases increased from 19% in 1995–1999 to 32% in 2000–05 (p = 0.047). Demographics, including age and race, as well as the site of CRC were similar to symptomatic cases. Screen-detected cancers presented early, with 77.9% presenting at early stage (stage 1: 55.8%, stage 2: 22.1%), compared to 51.5% (stage 1: 21.0%, stage 2: 30.5%) of symptomatic cancers (p <0.01). Only 1.3% of screen-detected CRC was found to be metastatic as compared to 21.0% of the symptomatic cases. The screen-detected cancers had significant survival advantage compared to symptomatic cases; with median survival being 81 months vs. 43 months in the latter (p =0.018). A proportional hazard regression analysis indicated that this improvement in survival was related to the fact that screening resulted in earlier stage at diagnosis. Only 20.3% of screen-detected CRC received adjuvant chemotherapy compared to 41.4% of symptomatic cases (p=0.002). Conclusions: An increasing proportion of CRC is being diagnosed as a result of screening. These cancers present at an earlier stage and are associated with a significantly improved survival. However, most CRC still presents symptomatically and more effective population screening is needed. No significant financial relationships to disclose.
Effects of letrozole on mammographic density (MD) in post-menopausal (PM) women at high risk for breast cancer (BC)
Authors: Andreopoulou E. , Ursin G. , Carapetyan K. , Utate M. , Alvear M. , Rosell M. , Muggia F. , Smith J. 
Published: March 2020

1548 Background: Letrozole BC chemoprevention is supported by reductions in contralateral cancer in aromatase inhibitor adjuvant BC trials. Decreased MD may be a surrogate for efficacy in prevention trials. Objective: to evaluate the effects of 12-mo letrozole on MD in PM women at high risk for BC. Methods: 20 healthy PM women had Gail model risk profile and baseline MD prior to letrozole 2.5/d for 1 y. MD was determined by a computer assisted method (Cancer Epidemiol Biomarkers and Prevention 2003;12:332–338) and read blindly (baseline, 6mo films and eventually also 12mo by GU). Health status, lipid profile, bone density, and cognitive function were monitored. Results: by December (<1y): 14 Caucasian, 1 Hispanic, 3 Asians, and 2 Blacks were accrued. The table shows changes in MD at baseline & 6mo in the first 6 women: * reader considered this MD technically unsatisfactory (insufficient contrast). Conclusions: One woman discontinued treatment at 3 mo due to muscle aches. Six and 12mo comparisons will be ready in June 2007. Concordant results and decrease in density are suggested by the available data. Acknowledgements: This work is supported in part by The Lynne Cohen Foundation. [Table: see text] [Table: see text]
A phase I trial of nordihydroguareacetic acid (NDGA) in patients with non-metastatic prostate cancer and rising PSA
Authors: Harzstark A. L. , Ryan C. , Diamond M. , Jones J. , Zavodovskaya M. , Maddux B. , Claros C. , Goldfine I. , Small E. J. 
Published: March 2020

15500 Background: NDGA is a butanediol with effects on tumor cells, including inhibition of insulin growth factor receptor (IGF-1R) autophosphorylation. In vitro studies suggest that NDGA attenuates androgen-mediated prostate cancer growth without competitive androgen receptor blockade. Its effects on PSA in pts were studied. Methods: Eligible pts included men with recurrent prostate cancer following definitive local therapy with a rising PSA and no metastasis. Both androgen dependent prostate cancer (PSA rising with a normal tesosterone - ADPC) and androgen independent prostate cancer (PSA rising with castrate level of testosterone - AIPC) was allowed. Treatment consisted of continuous oral daily dosing of NDGA according to a planned dose escalation of 750, 1,250, 1,750, 2,250 and 2,500 mg. Pts were followed for safety and changes in PSA and PSA doubling time (PSADT). Results: 15 pts were enrolled: 11 pts with ADPC and 4 pts with AIPC. Median baseline serum PSA was 3.6 ng/mL in ADPC pts and 5.74 mg/mL in AIPC pts. Median age was 66 (range 48–81). Following a median of 5.5 cycles (range 1–13), transaminase elevations occurred in five pts (33%): 1 gr 1, 1 gr 2 and 3 gr 3- all occurring in month 3 or later. Transaminase elevations resolved after drug discontinuation but recurred with repeated dosing. Doses up to 2,500 mg/day were otherwise well- tolerated. The median baseline PSADT was 6.1 months for ADPC and 6.7 months for AIPC and was and 8.4 months on therapy (p=0.12) for ADPC and 4.2 months for AIPC. Of 11 ADPC pts, one (9%) had a decline in PSA by >50% compared to baseline and one (9%) had a decline of 3 fold increase in PSADT while on therapy, one from 11 to 46 months (750 mg), one from 9.5 to 49.5 months (1,750 mg), and one from 5.9 to 46.2 months (2,500 mg). There were no PSA reductions in the AIPC pts, however one pt had a >3 fold increase in PSADT (from 1.4 to 7.5 months). No significant effects on testosterone, adrenal androgen or estradiol levels were observed while on study. Conclusions: NDGA is well tolerated with the exception of transaminase elevations which occur after approximately 3 cycles in a minority of patients. Combined with preclinical data, the modest effects on PSA kinetics suggest that further study on androgen dependent tumors is justified. No significant financial relationships to disclose.
Phase II trial of the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in patients (pts) with advanced papillary renal cell carcinoma (pRCC)—SWOG S0317
Authors: Pan C. , Hussey M. , Lara P. , Mack P. C. , Nagle R. B. , Dutcher J. , Samlowski W. , Clark J. , Crawford E. D. , Gordon M. S. 
Published: March 2020

15516 Background: Clear cell RCC often has mutations of the von Hippel-Lindau (vHL) gene and over expression of vascular endothelial growth factor (VEGF). pRCC has mutations of c-met and not vHL. Pre-clinically, normal vHL expression is associated with greater activity of EGFR inhibitors in clear cell RCC (Clin Can Res 6:1518, 2000). PRCC has no effective treatment. Given the absence of vHL mutations we undertook a study of E in pts with pRCC. Methods: Pts with histologically confirmed advanced or metastatic pRCC with measurable disease received E 150 mg PO QD from day 1 to disease progression, pt refusal, unacceptable toxicity, or a delay of therapy >3 wks. Central path review and tissue submission for vHL gene analysis were required. The primary endpoint was response. Further study of this regimen would be considered if the observed response rate (RR) was =20% (i.e. 5+ observed responses). Results: 52 pts from 27 SWOG and 2 ECOG institutions were registered. 7 pts were ineligible (no path submission-3; incorrect histology-1; no measurable disease-2; scans outside timeframe-1). Central path review is ongoing for 7 pts, leaving 39 pts evaluable for response including 30M/9F with a median age of 60.2 y (range 27.9 to 82.3). Median follow-up was 12.8 months (range 1.5 to 35.4 m). 4 pts had confirmed PRs for a RR of 10% (95% CI: 3 - 24%). Five evaluable patients with inadequate response assessment were assumed to be non-responders. Median OS was 26.9 months (95% CI lower limit 12.8 m, upper limit not yet estimable). Probability of freedom from treatment failure at 6 m is 30% (95% CI: 15–45%). There was one Grade 5 adverse event (AE) of pneumonitis thought to be possibly drug-related and one Grade 4 thrombotic AE. 8 pts experienced Grade 3 AEs common to E including rash, anorexia, diarrhea and fatigue. vHL mutation was observed in two patients with stable disease. Conclusions: Though the observed RR in pts with pRCC receiving E is similar to pts with clear cell RCC we did not see enough responses to warrant further study. As this is the first phase II trial reported (to our knowledge) for the subset of pts with pRCC we have demonstrated that less common and distinct histological subtypes can be independently studied in the cooperative group setting. [Table: see text]
Evaluation of VEGF targeted therapy efficacy in mRCC after sorafenib failure or intolerance
Authors: Hajdenberg J. , Oberoi S. , Cohen N. , Kayaleh O. , Harding D. , Tseng J. 
Published: March 2020

15517 Background: Sorafenib, a multi kinase targeted agent with raf and VEGF receptor (VEGF-R) inhibitory properties, has been recently approved for the treatment of metastatic renal cell carcinoma (mRCC). Two other VEGF pathway targeted agents, sunitinib and bevacizumab, have documented efficacy in mRCC. It is not known whether these agents will exhibit biological or clinical activity after prior VEGF directed treatment. Methods: Eligibility applied to patients with mRCC treated with sorafenib within an expanded access program (EAP) at our institution that were later switched to either bevacizumab or sunitinib due to tumor progression or sorafenib intolerance. All patients had measurable disease. Patients were evaluated for response rates (RECIST), treatment duration and progression free survival (PFS). Results: 35 patients that participated in the EAP were identified. 10 patients fulfilled the entry criteria and all of them had clear cell histology. Median age was 66; sex distribution was 70% male-30% female. 6 (60%) received sunitinib and 4 (40%) received bevacizumab. Median treatment duration was 5.5 months (range: 1–15). Of the patients evaluable for response: 5 have SD (50%), 1(10%) had a PR and 1(10%) progressed. 3 are too early to be evaluated. Median PFS was 7 months. Conclusions: Despite the limitations of a small patient sample, the VEGF targeted therapies sunitinib and bevacizumab exhibited a median PFS and reponse rate similar to those reported by other authors as a first line anti-VEGF therapy. Second line anti-angiogenic activity appears to retain efficacy in clear cell mRCC priorly treated with the multi- kinase targeted agent sorafenib. This may provide hypothetical justification for sustained anti-angiogenic therapy after progression. Prospective evaluation of serial and combination approaches is ongoing. No significant financial relationships to disclose.
Optical coherence tomography guided cystoscopy in diagnosis and management of clinical bladder tumors
Authors: Lee C. S. , Mishail M. , Waltzer W. C. , Liu J. , Wang Z. , Pan Y. 
Published: March 2020

15518 Background: Optical coherence tomography (OCT) is a novel tool that permits high-resolution cross-sectional imaging of bladder urothelium during cystoscopy. OCT delineates morphological features of the bladder urothelium, the lamina propria, and the muscularis layer based on their backscattering patterns. We hypothesize that application of microelectromechanical systems (MEMS) mirrors for OCT can improve cross-sectional image resolution of bladder lesions. We report preliminary results from our prospective non-randomized study using MEMS mirror OCT imaging during cystoscopy. Methods: Following our institutional IRB approval, a prospective correlative study was performed evaluating the role of cross-sectional OCT in diagnosis and treatment of bladder cancers. OCT cystoscopy was performed in thirty patients undergoing cystoscopy or transurethral resection for suspected bladder tumors. Any suspicious lesions or tumors seen on cystoscopy were either biopsied or resected as per standard of care. The primary endpoints were patient safety and the correlation between OCT images and histology. Results: Bladder cancer was identified in twenty five patients by pathological evaluation. Twenty four out of twenty five patients were correctly diagnosed with cross-sectional OCT imaging. Four out of five patients with benign lesions were correctly identified. There was one false positive and one false negative in our series. Overall sensitivity and specificity of cross-sectional OCT in diagnosing bladder cancer was 96 and 80%, respectively. There were no complications related to OCT cystoscopy. Axial and lateral resolutions were 10 and 12 microns, respectively. The field of view was measured at 4.5 mm with the depth of penetration measured to be 2 mm. Conclusions: OCT cystoscopy is a promising new tool in diagnosis of bladder cancer. Our preliminary data suggests OCT with MEMS mirrors resulted in high resolution images that may aid in the diagnosis of bladder cancer during cystoscopy. Application of OCT cross sectional imaging may have additional benefits: improved diagnosis, identification of surgical margins, and more complete resection of bladder tumors. No significant financial relationships to disclose.