tbuckley/cabot-search huggingface dataset:
Feasibility of triweekly docetaxel-based chemotherapy for elderly patients (age 75 and older) with castration-resistant prostate cancer.
Authors: N. Takaha, T. Iwata, T. Nakamura, F. Hongo, K. Kamoi, K. Okihara, A. Kawauchi, T. Miki
Journal: Journal of Clinical Oncology (2011)

e15092 Background:A survival benefit of tri-weekly docetaxel-based chemotherapy for castration-resistant prostate cancer (CRPC) patients was demonstrated by two trials, TAX327 and SWOG 99-16. Even though the management of elderly prostate cancer (PCa) patients is becoming a major public health concern in many countries, there are few reports regarding the optimal protocol of docetaxel for elderly CRPC patients, who are 75 years or older. The aim of this study is to evaluate the efficacy and safety of docetaxel-based chemotherapy for elderly metastatic CRPC patients at the age of 75 or higher. Methods:A total of 51 CRPC patients were treated by a regimen of docetaxel (70mg/m2) once every 3 weeks (3qw) in combination with oral dexamethasone or estramustine. Adjustment for docetaxel dosage and period per cycle was subject to investigator’s judgment. The efficacy and safety of 20 patients at the age of 75 or higher (older group) were compared to those of 31 patients younger than 75 years (younger group). Results:Median age was 72 years (55-88). The median relative dose intensity of both groups was 0.84 without any significant difference, while the median dose intensity and the number of treatment cycles of younger group and older group were, 14.6 vs 12.3 mg/m2/week (P=0.021), and 9 vs 8 cycles (P=0.15), respectively. In the older group of patients, PSA response rate was 50%, median time to biochemical progression was 7.5 months, and median survival time was 15.5 months, without any significant difference compared to those of younger group. No significant difference was demonstrated in the incidence of grade 3-4 adverse events observed in both groups. All these parameters for efficacy as well as discontinuation rate because of adverse events in this study are comparable to those reported previously for CRPC patients treated by a regimen of docetaxel 3qw. Conclusions:Treatment by docetaxel (70 mg/m2) 3qw with proper adjustment might contribute to maintaining the efficacy and safety of the treatment for elderly CRPC patients.
Integration of capecitabine (X) into adjuvant therapy comprising docetaxel (T) followed by 5-FU, epirubicin, and cyclophosphamide (CEF): Efficacy in patients with triple-negative breast cancer (BC).
Authors: H. Joensuu, P. Kellokumpu-Lehtinen, R. Huovinen, A. Jukkola-Vuorinen, M. Tanner, R. Kokko, J. Ahlgren, P. Bono, P. Auvinen, H. Lindman
Journal: Journal of Clinical Oncology (2010)

531 Background: Interim data from this phase III randomized trial (FinXX) evaluating the integration of capecitabine into anthracycline-/taxane-based adjuvant therapy for early BC were recently published (Lancet Oncol 2009); the present subgroup analysis explores the efficacy results in patients with triple-negative BC. Methods: 1,500 patients with axillary node-positive or high-risk node-negative (tumor size > 20 mm, progesterone receptor-negative) BC were randomized to the X-containing regimen: 3x XT (X 900 mg/m2 bid d1–14 and T 60 mg/m2 iv d1, q21d) followed by 3x CEX (C 600 mg/m2 iv d1, E 75 mg/m2 iv d1 and X 900 mg/m2 bid d1–14, q21d; n = 753), or the control regimen: 3x T (80 mg/m2 iv d1, q21d) followed by 3x CEF (C 600 mg/m2, E 75 mg/m2 and F 600 mg/m2 all d1, q21d; n = 747) in January 2004 to May 2007. The primary endpoint was recurrence-free survival (RFS) and the median follow-up time 3 yrs. Results: RFS was significantly increased with the X-containing therapy compared with control (92.5% vs. 88.9%; Cox proportional hazards model hazard ratio [HR] 0.66, 95% CI 0.47–0.94; p = 0.020). Overall, patients without triple-negative disease (n = 1,294) had longer RFS than those with triple-negative cancer (n = 202; HR 0.43, 95% CI 0.29–0.63; p < 0.001). Within the triple-negative BC subgroup, patients in the X arm (n = 93) achieved a longer RFS than those in the control arm (n = 109; HR: 0.43, 95% CI 0.21–0.90; p = 0.024; 3-yr RFS 87.7% vs. 76.6%, respectively), representing a 57% reduction in the risk of breast cancer recurrence or death. RFS of patients with triple-negative BC treated with the X-containing regimen did not differ significantly from RFS of the FinXX study participants whose cancer was not triple negative (HR: 0.74, 95% CI 0.38-1.41; p = 0.357). Conclusions: In this explorative analysis the integration of X into adjuvant combination chemotherapy reduced the risk of breast cancer recurrence substantially compared with a control regimen of standard agents in patients with triple-negative early BC. The result needs to be confirmed in studies that address adjuvant X-containing chemotherapy for triple-negative BC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Roche, sanofi-aventis Roche, sanofi-aventis
History of Keratinocyte Carcinoma and Risk of Melanoma: A Prospective Cohort Study
Authors: Shaowei Wu, Eunyoung Cho, Wen-Qing Li, Abrar A. Qureshi
Journal: JNCI Journal of the National Cancer Institute (2017)

Background: The association between history of keratinocyte carcinoma (KC, also known as nonmelanoma skin cancer) and risk of developing invasive melanoma has not been assessed comprehensively using prospective data. Methods: We followed 91 846 women in the Nurses' Health Study (NHS; 1984–2010), 114 918 women in the NHSII (1989–2011), and 48 946 men in the Health Professionals Follow-up Study (1986–2010) for diagnoses of KC and melanoma biennially. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma associated with history of KC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). All statistical tests were two-sided. Results: We documented 1949 melanomas, 38 842 BCCs, and 7462 SCCs over 6.4 million person-years of follow-up. After adjustment for other risk factors, a personal history of KC was associated with an increased risk of melanoma (meta-analysis HR = 2.22, 95% CI = 1.73 to 2.85). The association was more apparent among participants with a history of both BCC and SCC (HR = 3.40, 95% CI = 1.60 to 7.19) than among participants with a history of BCC only (HR = 2.20, 95% CI = 1.80 to 2.70) or SCC only (HR = 1.56, 95% CI = 0.98 to 2.46), and there was a strong risk-increasing trend associated with a higher number of reported KCs removed by surgery (Ptrend < .001). In women, KC history was more strongly associated with head/neck melanomas (HR = 4.17, 95% CI = 2.77 to 6.27) than with trunk or limb melanomas (both HRs < 2.50, Pheterogeneity = .04). Conclusions: Our results provide novel insights for the relationship between KC history and risk of developing melanoma, which may be important for melanoma prevention.
Prophylactic oophorectomy for patients with breast cancer with BRCA results.
Authors: J. C. Schink, K. M. Doll, C. B. Weldon, J. R. Trosman, H. H. Wetzel, T. J. Fallen, W. J. Gradishar
Journal: Journal of Clinical Oncology (2011)

1533 Background: Laparoscopic bilateral salpingo-ophorectomy (BSO) is playing an increasing role in the management of breast cancer in BRCA positive women. Those undergoing prophylactic BSO have decreased risk of breast cancer recurrence, ovarian cancer, and overall mortality (Domcheck et al., JAMA 2010;304(9)). We have previously reported that timing of BRCA testing impacts surgical approach in breast cancer management (Trosman JR, ASCO-Abstract-666-2010). The study goals are to review a cohort of breast cancer patients electing prophylactic BSO, and evaluate BRCA test results, timing of genetic counseling and prophylactic surgery. Methods: This is a retrospective medical record review of 302 breast cancer patients with BRCA testing and definitive surgery between July 1st 2006 and September 1st 2010. Following an IRB protocol, we reviewed the clinical characteristics of this population and used simple frequencies and Fisher's exact test to evaluate associations between BRCA results and salpingo-oophorectomy. Results: Sixty-seven women of a cohort of 302 (22%) underwent bilateral salpingo-oophorectomy, 49 of whom did so for primary prophylactic indications. Of these, 34 (69%) tested positive for the BRCA mutation. 79% (34/43) of BRCA positive women had salpingo-oophorectomy as compared to 6% (15/240) of BRCA negative patients, p<0.0001. Among BRCA positive women, 48% (11/23) counseled prior to breast cancer surgery had BSO compared to 66% (26/39) counseled afterward, p< 0.1840. Conclusions: Over 75% of BRCA positive women elected prophylactic bilateral salpingo-oophorectomy as compared to 6% of BRCA negative breast cancer patients. BRCA positive breast cancer patients counseled prior to breast cancer surgery were not more likely to opt for salpingo-oophorectomy than those counseled afterwards.
Using a statewide collaborative approach to improve tobacco cessation referral rates for cancer patients.
Authors: Jane Alcyne Severson, Hilary Baca, Douglas W. Blayney, Karen Brown, Grayce Galiyas, Mara Minasian, Anna Notier, Joan Schmidt, Graham Walter Warren
Journal: Journal of Clinical Oncology (2013)

74 Background: Tobacco use by cancer patients decreases the effectiveness of cancer treatment, increases treatment toxicity, increases the risk of developing a second primary cancer, and increases mortality. Stopping tobacco use may reduce many of these adverse effects in cancer patients. Methods: The Michigan Oncology Quality Consortium (MOQC) collaborated with the Michigan Cancer Consortium (MCC) to implement the Tobacco Cessation Demonstration Project. This entailed designing a standard workflow and other lean tools to assist oncology practices in referring all cancer patients who use tobacco to the free Michigan Tobacco QuitLine or other cessation services. 19 practices participated in three learning sessions during which the following were provided: education by subject matter experts, use of data management and lean tools, and the sharing of barriers and successes. Results: Examination of baseline MOQC Quality Oncology Practice Initiative (QOPI) data demonstrated that &lt; 47% of patients who use tobacco were advised to quit or referred for tobacco cessation (n = 574 charts/44 sites), which was equivalent to the national QOPI mean in Fall 2012. Root cause analysis of this lack of action in tobacco cessation identified limited knowledge to the risks of continued smoking and the lack of available resources as barriers to adopting necessary change. Implementation of the MOQC/MCC Tobacco Cessation Demonstration Project increased total statewide referrals to the QuitLine by 30.9% over the first 2 months with an increasing proportion of patients (41%) being cancer patients referred by MOQC participating sites. Conclusions: Supplying scientific evidence, collaboration, and the use of lean tools improved the referral rate to a tobacco cessation program for oncology patients. [Table: see text]
Markers of sunitinib-resistance in clear cell renal cell carcinoma: A gene expression analysis.
Authors: Òscar Reig, Mercedes Marín-Aguilera, Juan José Lozano, Blanca Gonzalez, Carme Mallofré, Marc Campayo, Pedro Gascon, Begoña Mellado
Journal: Journal of Clinical Oncology (2014)

533 Background: Sunitinib is a standard first line treatment of metastatic renal cell carcinoma (ccRCC). Approximately 20% of patients experience primary resistance to therapy and no predictive biomarkers are available. The aim of our study is to discover novel biomarkers to predict response to sunitinib and to generate hypothesis about mechanisms of intrinsic resistance. Methods: Gene expression analysis was performed in formalin-fixed paraffin embedded (FFPE) samples from 44 patients with metastatic ccRCC treated with sunitinib in our institution. Affymetrix Human Gene 2.0 ST array was performed in primary tumors from 6 extremely sensitive (progression free survival (PFS) &gt; 24 months) and 8 refractory (progression disease as best response) ccRCC. Technical validation with qPCR (Fluidigm Dynamic 96.96 Array) was performed in the whole cohort. The ΔΔCt method was used to quantify the relative amount of mRNA. Clinical and pathological data were correlated with gene expression. Results: 330 genes were differentially expressed between refractory and sensitive patients (p≤0.05). Network analysis showed 16 significant networks represented. Gene expression of 96 selected markers was tested in 47 primary tumors and 24 metastases. We found IL8, VEGF and NOTCH pathways upregulated on refractory patients. Survival analysis showed that the overexpression of IL8 correlated with a worse PFS (HR: 2.42, 95%CI1.27 – 4.63, p=0.0075) and overall survival (OS) (HR: 3.42, 95%CI 1.50 – 7.79, p=0.0034). Overexpression of VEGFBcorrelated with a prolonged PFS (HR 0.52, 95% CI 0.28 – 0.98, p=0.0415). Conclusions: Our results confirm the predictive value of IL8 expression in a cohort of ccRCC patients treated with sunitinib and suggests novel biomarkers of response to sunitinib. These data will be further validated in an independent cohort of patients.
The importance of sequence in rescheduling bevacizumab and chemotherapy administration in the first-line treatment of metastatic colorectal carcinoma (mCRC).
Authors: Leonidas Chelis, Nikolaos Xenidis, Kiriakos Amarantidis, Nikolaos Diamantopoulos, Anastasios L. Boutis, Triantafyllia Koukaki, Prodromos Michailidis, Evagelos Christakidis, Athanasios Chalvatzis, Dimitrios Matthaios, Savas Deftereos, Nikos Courcoutsakis, Panagiotis Prassopoulos, Stylianos Kakolyris
Journal: Journal of Clinical Oncology (2014)

617 Background: One of the proposed mechanisms of action for bevacizumab is by reducing the interstitial fluid pressure (IFP) allowing an increased penetration and uptake of chemotherapy agents in tumors. Clinical and laboratory data suggest that the decrease of IFP occurs after a few days of bevacizumab administration and intratumoral delivery of chemotherapy increase when bevacizumab precedes chemotherapy. We hypothesized that altering the schedule of BEV/FOLFOX regimen would improve the efficacy of the regimen and increase objective response rate. Methods: Patients (pts) with mCRC or locally advanced colorectal cancer, with ECOG PS 0-2 were eligible. The treatment schedule was Bevacizumab 5mg/Kg on day 1, standard FOLFOX-4 regimen on days 8-9 at cycles repeated every 14 days. Prior 5-FU/oxaliplatin adjuvant treatment was allowed. The pts were treated for 6 months or until reaching a plateau of response. Standard RECIST v1.1 response evaluation criteria were used. Primary endpoint of the study was the percentage of objective response rate, PR+CR (ORR), secondary end points were PFS, OS and toxicity. A Simon two step, minimax, statistical design was used: the minimum accepted ORR was 45% (p0) and the estimated ORR was 65% (p1). Results: Thirty (n=30) pts were enrolled. The median age was 69.5 years, the performance status was 0 (40%), 1 (40%), 2 (20%), the median follow up was 20.75 months and the K-RAS status was wild type for 63.5% and mutant for 36.5%. Seven pts (23.3%) had received prior adjuvant chemotherapy. Five pts had convertible metastatic disease. Four CR (13.33%), 18 PR (60%), 7 SD (23.33%), and one PD (3.3%) were observed for a total ORR of 73.3% and disease control rate (CR+PR+SD) of 96.7%. Four out of five (80%) pts with convertible disease achieved a R0 resection. The PFS was 12.8 months and OS has not been reached yet. One patient experienced a grade 4 event (febrile neutropenia). The study met its primary endpoint and therefore is considered positive. Conclusions: Delivering bevacizumab before chemotherapy in the first-line treatment of mCRC represents a very effective and promising schedule which warrants further investigation in randomized clinical trials.
Survival trends in unresectable hepatocellular carcinoma and the effect of DEB-TACE: SEER versus tertiary cancer center.
Authors: Minzhi Xing, Hasmukh J. Prajapati, Nima Kokabi, Juan C. Camacho, Bassel F. El-Rayes, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2014)

308 Background: Long-term survival in patients with advanced unresectable hepatocellular carcinoma (HCC) treated with drug-eluting bead transarterial chemoembolization (DEB-TACE) vs. best supportive care has not been investigated in large-scale population studies. Methods: Under IRB approval, our institute’s cancer registry was queried for patients with advanced unresectable HCC diagnosed from Sept 2005 to Dec 2010, treated with DEB-TACE. Eighteen registries of the U.S. Surveillance, Epidemiology and End Results (SEER) database were queried for patients with advanced HCC not amenable to surgery/radiation diagnosed in the same time period. Baseline characteristics, median overall survival (OS) from HCC diagnosis and median OS from first DEB-TACE were stratified by national/state cohorts. Survival analysis and 95% confidence intervals (CI) were calculated using Kaplan-Meier estimation. Results: A total of 231 patients who underwent DEB-TACE for unresectable HCC (Group A) and 20,897 patients with unresectable HCC who received neither radiation nor cancer-directed surgery (Group B) were included. Both groups were similar for mean age at diagnosis, gender, race, bilobar disease, portal vein thrombosis and mean largest tumor size (p&gt;0.05). Median OS from HCC diagnosis was 21.8 months (Group A; 95% CI, 18.1-25.4) and 4.0 months (Group B; 95% CI, 3.9-4.1), p&lt;0.001. Median OS from first DEB-TACE was 15.0 months (Group A; 95% CI, 9.6-20.4). Interval survival rates from HCC diagnosis for Group A vs. B were: 99% vs. 65% (1 month), 92% vs. 49% (3 months), 75% vs. 36% (6 months), 58% vs. 35% (1 year), 36% vs. 9% (2 years), and 20% vs. 4% (3 years). Conclusions: DEB-TACE in patients with unresectable HCC demonstrated significantly greater median OS and favorable long-term survival rates compared to best supportive care in a population-based study. [Table: see text]
Facilitators of quality breast cancer screening and diagnosis in an urban environment.
Authors: C. B. Weldon, J. R. Trosman, D. Dupuy, R. Alvarez, E. A. Marcus, J. C. Schink, A. M. Murphy
Journal: Journal of Clinical Oncology (2011)

e16584 Background: The death rate from breast cancer for black women in Chicago, Illinois is 62% higher than for white women, and is much higher than the U.S. disparity of 41% and the New York City disparity of 27% (Sinai Urban Health Institute, 2010). The Chicago Breast Cancer Quality Consortium, funded by Susan G. Komen for the Cure Foundation, previously collected data from 43 Chicago hospitals identifying the potential for significant quality deficits in breast cancer screening and treatment (Chicago Breast Cancer Quality Consortium, 2010). Our aim is to identify facilitators of high quality breast cancer screening and diagnosis for black women to implement in local hospitals. Methods: We conducted semi-structured interviews (n=35) with cross-discipline providers in breast cancer care from 1 academic, 2 public, 5 community hospitals, and 1 support group in Chicago, with black women averaging 50% of their population. Interviews were transcribed and thematic analysis according to the framework approach was performed. Results: Theme analysis identified 7 facilitators to improve breast cancer screening and diagnostic quality across sites: 1. Implement referral structure by geographic area based on capacity and volume, e.g.; screening referrals to diagnostic/treatment centers (32/35). 2. Incentives and measures to encourage cooperation across sites (34/35). 3. Direct patient contact for follow up on abnormal screen or diagnostic; or centralized patient follow-up and tracking to support low-resource site operations (31/35). 4. Public awareness of accessible, affordable screening resources (28/35). 5. Acceptance of self referrals/direct access and standing orders for screening mammography (27/35). 6. Timely transfer of images between sites (23/35). 7. Same day results to patient for diagnostics and when indicated same day biopsy (14/35). Conclusions: We found that capacity based referrals, cooperation among sites, awareness of public programs and more accessible screening and diagnostic processes may facilitate improvement of breast cancer screening and care for Chicago patients, including black women. These results inform our further examination of additional sites and development of solutions for implementation.
Immediate or Delayed Nephrectomy in Patients With Metastatic Renal Cancer Who Are Receiving Targeted Agents: Is the Analysis at Risk for Guarantee-Time Bias?
Authors: Consuelo Buttigliero, Marcello Tucci, Francesca Vignani, Massimo Di Maio
Journal: Journal of Clinical Oncology (2017)

Background First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity.This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatinineligible patients. MethodsFor this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible.Patients were given 1200 mg intravenous atezolizumab every 21 days until progression.The primary endpoint was independently confi rmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (central review), assessed in prespecifi ed subgroups based on PD-L1 expression and in all patients.All participants who received one or more doses of atezolizumab were included in the primary and safety analyses.This study was registered with ClinicalTrials.gov,number NCT02108652.Findings Between June 9, 2014, and March 30, 2015, we enrolled 123 patients, of whom 119 received one or more doses of atezolizumab.At 17•2 months' median follow-up, the objective response rate was 23% (95% CI 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing.Median response duration was not reached.Responses occurred across all PD-L1 and poor prognostic factor subgroups.Median progression-free survival was 2•7 months (2•1 to 4•2).Median overall survival was 15•9 months (10•4 to not estimable).Tumour mutation load was associated with response.Treatment-related adverse events that occurred in 10% or more of patients were fatigue (36 [30%] patients), diarrhoea (14 [12%] patients), and pruritus (13 [11%] patients).One treatment-related death (sepsis) occurred.Nine (8%) patients had an adverse event leading to treatment discontinuation.Immune-mediated events occurred in 14 (12%) patients.Interpretation Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer.