tbuckley/cabot-search huggingface dataset:
Dose titration of fentanyl pectin nasal spray in a broad range of patients for the treatment of breakthrough pain in cancer.
Authors: A. Nguyen, A. W. Burton, J. Conroy, N. Y. Gabrail
Journal: Journal of Clinical Oncology (2011)

e19659 Background: Randomized controlled studies have demonstrated that fentanyl pectin nasal spray (FPNS) provides superior pain relief compared with placebo and immediate-release morphine sulfate for the treatment of patients with breakthrough pain in cancer (BTPc). An ideal BTPc agent should also be easily titratable across a wide range of patient types. This report details the successful dose titration of FPNS in the clinical trial program. Methods: The FPNS clinical trial program enrolled 523 patients experiencing 1–4 BTPc episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for background pain. The open-label titration phase was designed to find an effective dose that successfully treated 2 consecutive episodes of BTPc without unacceptable adverse events (AEs). Results: Across the FPNS clinical trial program, a total of 2,417 episodes of BTPc were treated with FPNS in the dose-titration phase. This included a broad range of patient types: >28% were >60 years of age (mean age, 54.2), 48% were female, 55% were white, 56.6% had an Eastern Cooperative Oncology Group (ECOG) score = 1, and 21% were undergoing chemotherapy. Patients were successfully titrated to either 100 µg (17.7%), 200 µg (21.8%), 400 µg (32.0%), and 800 µg (28.5%) in a minimal number of steps (mean, 2.7). Successful titration was consistent across the 3 multinational, multicenter studies at sites across 13 countries and 4 continents. Dose distribution did not vary by age or by weight, although there was a slight tendency for men to titrate to higher doses. Titration failed for FPNS-related reasons in 42 (8.0%) patients: 15 (2.9%) because of AEs and 27 (5.2%) because of inadequate efficacy. Treatment-related AEs leading to withdrawal were primarily headache, nausea, and vomiting, consistent with the known effects of fentanyl; they were not dose related. Conclusions: FPNS provides an easy-to-use and convenient method of administration for the treatment of BTPc. Furthermore, FPNS is easily titrated to an effective dose in a broad range of opioid-tolerant cancer patients, with only 8.0% unable to titrate for FPNS-related reasons.
The use of stereotactic body radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma.
Authors: Aisling S Barry, Gonzalo Sapisochin, Moises Russo, Anthony M. Brade, James D. Brierley, Joon-Hyung J. Kim, Paul D Greig, David Grant, Laura A. Dawson
Journal: Journal of Clinical Oncology (2016)

418 Background: Approximately 30% of patients with hepatocellular carcinoma (HCC) on the wait list for liver transplant (LT) fall off the transplant list due to progressive HCC. Stereotactic Body Radiotherapy (SBRT) has been used as a “bridge” to LT in patients who are not amenable to RFA or TACE. Methods: Baseline patient characteristics, radiotherapy details and outcomes were reviewed in HCC patients who received SBRT as a bridge to LT. Results: Between July 2004 and Dec. 2014, 601 patients with HCC were listed for LT, of which 400 (66.5%) received bridging therapy. 38 patients, at high risk for HCC progression, were unsuitable for RFA or TACE, receiving SBRT as a bridging therapy. Median SBRT dose was 36Gy in 6 fractions (range 8.5-48Gy in 1 – 6 fractions), including 1 patient who was transplanted after receiving one fraction. 25 of 38 patients (67%) had all lesions treated (median number of lesions 2 {1-8}); 13 patients received SBRT only to the dominant lesion at highest risk of growing or rupturing. At the time of SBRT, 42% had HCC within Milan criteria, and median Child Pugh score was A6 (range A5-B8). 5 patients (13%) dropped off the transplant wait list due to development of metastatic disease (4) and macrovascular invasion with progressive disease (1). Median irradiated HCC volume was 60.5cc (range 7-216cc). Median liver volume (minus HCC) was 1491cc (737-2728cc). Median mean dose to the liver minus HCC was 11.2Gy (2.8-18.6Gy) and median effective liver volume irradiated was 28% (11-66%). 1 patient was admitted 2 months post SBRT with hepatic pain - possibly attributable to SBRT and another patient developed a rib fracture 8 months post SBRT (max rib dose 43Gy in 6 fractions). No other specific SBRT toxicity was noted. The 1-, 3- and 5-year disease free survival and actuarial survival of HCC patients treated with SBRT who went on to have transplant was 93%, 79% and 79%, and 89%, 76% and 76% respectively. Including patients who dropped off the transplant list, the intent-to-treat 1-, 3 - and 5-year survival was 89%, 65% and 65%. There was no reported increase in operative morbidity at the time of transplant in patients treated with SBRT. Conclusions: SBRT can be used safely and effectively in HCC patients as a bridge to liver transplant.
Incidence and prognostic significance of HER2 overexpression in gastric cancer (GC): A monoinstitutional retrospective analysis.
Authors: Ferdinando De Vita, Michele Orditura, Alessio Fabozzi, Maria Maddalena Laterza, Jole Ventriglia, Beatrice Savastano, Guido Giordano, Angelica Petrillo, Luigi Marano, Natale Di Martino, Floriana Morgillo, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello
Journal: Journal of Clinical Oncology (2014)

160 Background: HER2 overexpression in GC is reported in 20% of cases; it is considered a negative prognostic factor with a positive predictive value of response to trastuzumab. We reviewed our case records analyzing its clinical significance. Methods: We retrospectively collected the data for patients (pts.) with histologically confirmed GC and tumor specimens. Results: From June 2011 to December 2012 we analyzed HER2 status in 76 pts with metastatic GC. (M/F 50/26, median age 64 years, ECOG performance status 0/1/2 = 59/12/5, G1/G2/G3 = 6.6%/22.4%/71%). In 36.8% of pts. gastric body was the primary tumor site. HER-2 overexpression was observed in 13 pts (17.1%). HER2-positive group had the following characteristics: M/F = 10/3, median age 63 years; Lauren’s histotype: 75% intestinal and 25% diffuse; G1/G2/G3 = 15.4%/30.8%/53.8%; T3-T4 tumors and N+ disease were observed in 46.1% respectively; the primary tumor site was: proximal 38.4%, distal 61.6%. 46.1% of pts with metastatic disease received a first line CT with a median progression free survival (mPFS) of 5 months (range, 3-7) and a median overall survival (mOS) of 9 months (range, 3-23). In HER2-negative group, (N= 63, M/F = 40/23, median age 64 years), 92.1% of pts. Lauren’s histotype: 45.5% intestinal and 54.5% diffuse; G1/G2/G3 = 4.8%/20.6%/74.6%; metastatic disease: 55.5%. T3-T4 tumors were assessed in 65.1% of pts and N+ disease in 61.9%. The primary tumor location was: proximal 38.1%, distal 61.9%. 57.1% with advanced disease received a first line CT with a mPFS of 5.5 months (range, 2-30) and a mOS of 10 months (range, 2-67). No statistically significant differences for mPFS (p: 0.08) and mOS (p: 0.06) were observed between HER2 positive and HER2 negative metastatic patients. Conclusions: According to our experience, HER2 overexpression doesn’t seem to correlate with a worse prognosis. In particular, it is not correlated with a worse histology and higher stage at diagnosis. Furthermore, no differences in terms of mPFS and mOS were observed between HER2 positive and HER2 negative metastatic pts.
Sequential Heart and Autologous Stem Cell Transplantation for AL Amyloidosis.
Authors: Martha Lacy, Angela Dispenzieri, Suzanne R. Hayman, Shaji Kumar, Robert Kyle, S. Vincent Rajkumar, Brooks S. Edwards, Richard J. Rodeheffer, Frantz P. Robert, Sudhir S. Kushwaha, Alfedo L. Clavell, Joseph A. Dearani, Thoralf M. Sundt, Richard C. Daly, Christopher G. A. McGregor, Dennis A. Gastineau, Morie Abraham Gertz
Journal: Blood (2006)
The availability versus accessibility gap in supportive care services at 40 NCI-designated cancer centers.
Authors: Kathryn Hutchins, Geoffrey Hamlyn, Abby Johnston, Rishonda Thomas, James Tian, Arif Kamal
Journal: Journal of Clinical Oncology (2016)

283 Background: Many cancer centers have developed and fostered several supportive care services to ease the stress of a cancer diagnosis. The availability of such services is key to Commission on Cancer (CoC) for accreditation, which many cancer centers pursue and patients seek as a measure of quality. Despite the stated availability of supportive care services, we wondered how easily new patients could access these services when first contacting a major cancer center. Methods: We used a ‘mystery shopper’ format to simulate calls made by a family member of a recently diagnosed patient to 40 NCI-designated cancer centers. We called each center four times on different days, twice with the caller reporting Medicaid insurance, twice with private insurance. We evaluated quantitative and qualitative components of the call, including time to next available appointment and reported availability of the 7 supportive services reported to the CoC. Descriptive statistics were calculated for each quantitative measure. Results: We placed 160 calls to 40 NCI-designated cancer centers. 38.2% of callers were unable to receive complete information about the number of supportive care services offered, whether because they were unable to reach a person or because the person they reached did not know whether one or more of the services was offered. Overall, only 37.6% of callers (60.8% of those who reached a person who could answer their questions) were told that all seven supportive care services were offered. Call recipients responded with an answer other than yes to whether the cancer center offered a multidisciplinary team approach (14.6%), patient navigation services (12.1%), genetic assessment/counseling (9.5%), palliative care (9.5%), counseling/psychological services (7.6%), or cancer education services (6.4%). Conclusions: Despite the stated availability of seven key supportive care services, we were unable to access all services during a call to establish an appointment about one-third of the time. For individual services, about 10% of the time we were told such services did not exist at the cancer center. Further research is needed to close the availability vs. accessibility gap in oncology supportive care.
Can Twitter social media be an effective tool for breast cancer survivor support and education?
Authors: Deanna J. Attai, Jeffrey Landercasper, Jody M Schoger, Alicia C Staley, Michael S Cowher
Journal: Journal of Clinical Oncology (2014)

130 Background: Despite reported benefits, approximately 60% of women do not attend breast cancer support groups. Many online resources for support exist, but information regarding the effects of participation is lacking. We report the results of a Twitter breast cancer support community participant survey. Methods: The Breast Cancer Social Media (#BCSM) Twitter support community began in July 2011. IRB approval with waiver of informed consent was obtained for a de-identified survey which was posted for two weeks on Twitter and on the #BCSM blog and Facebook page. Results: There were 206 respondents, with a median age of 45-54 and 93% being female. 74% were from the United States. 92% were Caucasian. 83% completed a 4-year college degree. 69% had been treated for breast cancer. 14% reported living with metastatic breast cancer. 72% became aware of #BCSM through Twitter. 45% had been participating in the chats for &gt; 12 months. 81% of respondents reported increased overall knowledge about breast cancer. Increased knowledge through #BCSM was reported in all the following specific domains: 86% survivorship, 80% metastatic breast cancer, 70% cancer types and biology, 66% clinical trials and research, 56% treatment options, 56% breast imaging, 54% genetic testing and risk assessment, and 43% radiotherapy. 31% reported that participation led them to seek a second opinion or bring additional information to the attention of their treatment team. 73% percent reported plans to increase their outreach and advocacy efforts as a result of participation. Levels of reported anxiety before and after participation were analyzed. 29 of 43 patients (67%) who initially reported “high or extreme” anxiety reported “low or no” anxiety after participation (p &lt; 0.001). Also, no patients initially reporting “low or no” anxiety prior to participation reported an increase to “high or extreme anxiety” after participation. Conclusions: While many online breast cancer patient resources exist, data documenting patient educational benefits of participation are lacking. This study demonstrates that breast cancer patients’ perceived knowledge can be increased and that their anxiety can be decreased by participation in a Twitter social media support group.
Characterization of breast cancer resistance protein (BCRP) in epithelial ovarian cancer (EOC)
Authors: R. Sayer, J. Turner, D. Sullivan, J. Fiorica, J. Lancaster
Journal: Journal of Clinical Oncology (2005)

2020 Purpose: While the majority of patients with advanced EOC achieve an initial response with current chemotherapy regimens, most eventually relapse with resistant disease. One of the cellular mechanisms of drug resistance is over-expression of BCRP, a drug efflux pump that selectively pumps chemotherapeutic drugs out of cells. The objectives of this study are to characterize BCRP in EOC cell lines and investigate the relationship between BCRP expression and clinicopathological parameters in advanced EOC. Methodology: BCRP expression and cellular localization were evaluated in 10 EOC cell lines using QRT-PCR and fluorescence microscopy. Functional analysis was performed measuring topotecan efflux by flow cytometry in the presence and absence of Trypostatin-A, a specific BCRP inhibitor. A topotecan-resistant cell line was treated with DES (a known inhibitor of BCRP) and efflux of topotecan was measured by flow cytometry. BCRP expression was measured in 101 untreated primary EOC tissues using QRT-PCR. Statistical correlations between BCRP expression and clinicopathological parameters were analyzed using chi square test, log-rank test, and Cox proportional hazards models. Results: EOC cell lines exhibited varying degrees of BCRP expression. mRNA expression was correlated with protein levels and function. DES was able to reverse BCRP-mediated topotecan resistance in EOC cell lines. BCRP mRNA expression in EOC patient tissues was widely dispersed. No correlation was found between BCRP expression and age, stage, grade or debulking status. A significant correlation was demonstrated between BCRP expression and chemotherapeutic response (CR/PR vs. SD/PD, p=2.75x10–14). Comparison of survival (<24 vs. >24 months) showed a trend of decreased survival with high BCRP expression (p=0.076). Conclusions: BCRP is both present and functionally active in EOC cell lines. Further, preliminary studies with DES have shown a dose-dependent reversal of topotecan uptake. Additionally, we have demonstrated a highly significant association between elevated BCRP expression and poor chemotherapeutic response in patient samples. BCRP may serve as a molecular target for reducing drug resistance to chemotherapy in advanced EOC. No significant financial relationships to disclose.
Effect of Wnt-1 induced signaling protein-2 (Wisp-2/CCN5) on angiogenesis and invasion in prostate cancer.
Authors: Yasunobu Hashimoto, Rajendra Singh, Bal L. Lokeshwar
Journal: Journal of Clinical Oncology (2013)

164 Background: The Wnt-Induced Signaling Protein-2 (Wisp-2/CCN5) is a secreted protein implicated in modification of extracellular matrix, invasion, and angiogenesis. The regulation of Wisp-2 and its function in CaP is poorly explored although it is highly expressed in advanced CaP cells. We discovered recently that a pro-inflammatory chemokine, Interleukin-8 (IL-8) strongly modulates Wisp2 expression in CaP cells. Since chronic inflammation is thought to be significant in CaP metastasis and IL-8 is a major effecter of inflammatory pathway, we investigated the physiological consequence of Wisp-2 modulation in CaP cells. Methods: Quantitative PCR was used to determine the expression of Wisp-2 mRNA and other mRNA in prostate epithelial and cancer cells. Wisp-2 mediated-VEGF secretion was determined by ELISA and endothelial tube formation assay using human vascular endothelial cells. Invasive activity and their attributes were determined using gelatin-zymography for matrix metalloproteinases (MMPs), Matrigel invasion assay and chemotaxis assay. Results: Wisp2 RNA was strongly expressed in two highly metastatic CaP cell lines, DU145 and PC-3 and moderately in less invasive LAPC4 and LNCaP cells. Constitutive autocrine expression or external addition of IL-8 increased Wisp-2 mRNA by ≥15.2 times in LNCaP, and 7.4 times in LAPC4 cells. Depleting Wisp-2 by RNA interference caused 82% reduction of Wisp2 in DU145, and 75% in PC-3. Depletion of Wisp2 did not affect cell proliferation in DU145 and PC3 but it reduced expression of VEGF mRNA by 64% in DU145 and 43% in PC3. Secreted VEGF protein in cultures of DU145 and PC-3 cells showed a decrease of 62% in DU145 and 30% in PC3. Condition medium of Wisp-2 depleted DU145 cell cultures showed 20% decrease in proliferation and vessel formation activity in HUVEC cells. Further, Wisp-2 depletion in DU145 cells resulted in significant decrease in chemoinvasion activity (28%) and secretion of MMP-9 (25%). Conclusions: These results show that Wisp2 is down stream effector of IL-8 and is an important modulator, affecting extracellular matrix to stimulate angiogenesis and invasiveness in CaP cells. Suppression of Wisp-2 in CaP may reduce their metastatic potential.
Efficacy and safety of regorafenib in Korean patients with advanced gastrointestinal stromal tumor after failure of imatinib and sunitinib: A multicenter study based on the management access program.
Authors: Myoung Kyun Son, Min-Hee Ryu, Joon Oh Park, Seock-Ah Im, Baek-Yeol Ryoo, Sook Ryun Park, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2015)

175 Background: GRID phase III trial showed that regorafenib improves progression free survival (PFS) in patients (pts) with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib. This study aims to confirm the efficacy and safety of regorafenib for advanced GIST in Korean pts. Methods: Clinical records were reviewed from 57 Korean pts with advanced GIST who failed both imatinib and sunitinib and were treated with regorafenib under MAP between December 2012 and November 2013. Pts received regorafenib 160mg p.o. once daily in a 3 weeks on/1 week off schedule, every 4 weeks until intolerable toxicities or disease progression with no benefit by physician’s discretion. Results: Out of total 57 pts, none achieved a complete or a partial response whereas 25 pts (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 8.6 months (range, 0.2-15.3), median PFS and overall survival (OS) were 4.5 months (95% CI, 3.8-5.3) and 12.2 months (95% CI, 10.1-14.3), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of cancer-related symptoms (abdominal pain in 8 and abdominal distension in 5) during the rest period of regorafenib, which were reduced with resumption of regorafenib. The most common grade 3 or 4 adverse events were hand-foot skin reaction (25%), hypertension (7%), and skin rash (7%). The dose of regorafenib was reduced in 44 patients (77%) because of toxicities, mainly due to hand-foot skin reaction (n=31). There was no treatment-related death. Conclusions: We could confirm the efficacy and safety ofregorafenib for advanced GIST after failure of imatinib and sunitinib reported in GRID trial in Korean pts. Considering exacerbation of cancer-related symptoms during rest periods, continuous dosing schedule of regorafenib needs to be explored in future clinical trials.
Racial differences in suicide deaths after cancer diagnosis: A SEER-based analysis of 2,336,949 patients.
Authors: Yu-Wei Chen, Chao-Ping Wu, Yu-Han Chiu, Angela Y. Chang, Chen-Hao Chen, Yen-Chen Feng, Sheng-Hsuan Lin, Yi-Han Sheu, Yen-Feng Lin
Journal: Journal of Clinical Oncology (2015)

244 Background: Risk of suicide is increased after cancer diagnosis. Our study aims to investigate the racial differences on risk of suicide after cancer diagnosis in a nationwide cohort of U.S. patients. Methods: Patients ≥ 18 years and diagnosed with breast (n = 616,099; 26.4%), lung (n = 585,978; 25.0%), colorectal (n = 429,060; 18.4%), or prostate cancer (n = 705,812; 30.2%) from 1988-2010 in Surveillance, Epidemiology and End Results Program (SEER) were identified. A Cox-proportional hazard model was used to compare the suicide mortality of the races (Hispanic white, African American, Asian/Pacific Islander, American Indian/Alaska Native) to non-Hispanic white patients adjusting for age, sex, marital status, household income, education level and cancer sites. Results: A total of 2,336,949 patients were identified, and there were 3,406 suicide death events. Fifty percent of suicide deaths were within 32 months after cancer diagnosis (interquartile range: 66 months). After a median follow-up of 49 months, the suicide mortality was lower in African American (HR: 0.29, 95% CI: 0.25-0.35, p value &lt;.0001), Hispanic white (HR: 0.49, 95% CI: 0.41-0.58, p value &lt;.0001), Asian/Pacific Islander (HR: 0.67, 95% CI: 0.57-0.79, p value&lt;.0001). The suicide mortality was the same comparing American Indian/Alaska Native to non-Hispanic white patients (HR: 1.01, 95% CI: 0.62-1.65, p value: 0.97). Conclusions: After adjusting for sociodemographic factors, non-Hispanic white cancer patients still had higher risk of suicide death after cancer diagnosis. Future studies should address the racial differences of psychological stress after cancer diagnosis. [Table: see text]