tbuckley/cabot-search huggingface dataset:
The <i>KRAS</i>-variant and cetuximab response in RTOG 0522.
Authors: Joanne B. Weidhaas, Jonathan Harris, Rita Axelrod, Adel K. El-Naggar, Anurag Singh, Thomas Galloway, David Raben, Dian Wang, Terence S. Herman, R. Jeffrey Lee, Rafael Ricardo Manon, Omar Yumen, Qiang Zhang, Christine H. Chung
Journal: Journal of Clinical Oncology (2014)

6000 Background: The KRAS-variant, a germ-line mutation in a microRNA-binding site in KRAS, predicts increased cancer risk and unique cancer biology for many cancers. RTOG 0522 is a phase III trial of cisplatin/radiation +/- cetuximab for patients with locally advanced head and neck cancer. Here we tested the hypothesis that the KRAS-variant would predict cetuximab response for these patients. Methods: Germline DNA was isolated from blood or buffy coat and tested for the KRAS-variant in Mira Dx's CLIA-certified laboratory. Hazard ratios (HR) were estimated by Cox model. Where proportional hazards assumption was invalid, models included time-dependent covariates. Results: 413/891 eligible patients on 0522 (46.4%) were tested for the KRAS-variant, and 70/413 were positive (16.9%). For progression-free survival (PFS) in the KRAS-variant group, there was a significant cetuximab benefit in year 1 (HR 0.31, p=0.04) and a significant interaction between treatment and time (p=0.02), confirming different effects in the first year and after. HR after year 1 was 1.76, but this did not reach statistical significance (p=0.29). The number of events in the KRAS-variant group (32) was too small for formal multivariate analysis, but HRs were stable after adjustment for single covariates (age, pack-years, Zubrod, site, p16, stage). In the KRAS-wildtype group, HRs for cetuximab effect were 1.00/1.07 with/without adjustment for covariates, similar to the overall trial (1.08). For overall survival (OS) in the KRAS-variant group there was a significant cetuximab benefit in years 1-2 (HR 0.19, p=0.03) and a significant interaction between treatment and time (p=0.02) confirming different cetuximab effects in years 1-2 and after. The HR after year 2 was 2.34, but this did not reach statistical significance (p=0.23). HRs were stable after adjustment for single covariates. In the KRAS-wildtype group, HRs for cetuximab effect were 0.90/0.93 with/without adjustment for covariates, similar to the overall trial (0.95). Conclusions: Our findings suggest that locally advanced head and neck cancer patients with the KRAS-variant appear to positively respond to cetuximab, resulting in better short-term PFS and OS. These results warrant further validation through a prospective study. Clinical trial information: NCT00265941.
Prevalence and differentiation of hereditary breast and ovarian cancer in Japan.
Authors: Seigo Nakamura, Takuji Iwase, Seiichiro Nishimura, Hideko Yamauchi, Tadashi Nomizu, Shozo Ohsumi, Masato Takahashi, Shinichi Baba, Tadao Shimizu
Journal: Journal of Clinical Oncology (2013)

1534 Background: Breast cancer is the most common female cancer, according to the Center for Cancer Control and Information Service in Japan. However, the lifetime breast cancer risk in Japan is markedly lower (one in 16) than in the U.S. or Europe. We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan. Methods: Our study of BRCA 1 and 2 (BRCA1/2) collected data at 8 institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March, 2012. Results: Among 260 proband cases, 46 (17.7%) were positive for BRCA1 and 35 (13.5%) were BRCA2 positive. Therefore, the total pathological mutation rate was 30.7%. Pathology data after breast surgery were obtained from 35 cases of BRCA1 mutation, 22 (62.9%) of which were triple negative and 10 (29.4%) were Luminal type. On the other hand, 24 cases (85.7%) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found 2 cases of large deletion detected by MLPA, comprising the first two reported cases in Japan. One was an entire deletion of exon 20 and the lacked exons 1-9. Eight cases of BRCA1 (3.1%) and 12 (4.6%) BRCA2 were uncertain variants. TN with a family history ovarian cancer were 14/20 (70%), TN under 40 y/o 17/23 (73.9%) and TN with one or more breast cancers in family history 19/32 (59.4%) showed higher incidences of BRCA1/2, especially BRCA1. Conclusions: HBOC may have nearly the same prevalence in Japan as in the U.S. or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to address these challenges: (1) To develop risk models for BRCA1/2 carriers in Japan (2) To identify the proper methods to detect cancer occurrence among Japanese BRCA1/2 carrier early (3) To differentiate whether uncertain mutation variants found in Japan are deleterious.
The Sub-Clonal Complexity of STIL-TAL1 T-ALL
Authors: Caroline L Furness, Marcela B Mansur, Victoria J Weston, Sarah Jenkinson, Frederik W van Delft, Lyndal Kearney, Ian Titley, Anthony M Ford, Rosemary E Gale, Pamela R Kearns, Adolfo A. Ferrando, Christine J. Harrison, Nicola E Potter, Mel Greaves
Journal: Blood (2014)
Abstract 591:Prognostic implications of PI3K mutation and amplification in curatively resected liposarcoma
Authors: Joo Hoon Kim, Hyo Song Kim, Jae Seok Lee, Ki Hyang Kim, Yong Jin Cho, Kyu Hyun Park, Soo Hee Kim, Joong Bae Ahn, Woo Ik Yang, Young Han Lee, Jin-Suck Suh, Kyoo-Ho Shin, Sun Young Rha
Journal: Cancer Research (2015)

Abstract Background: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutation/amplification in curative resected liposarcoma. Methods: A total of 125 liposarcoma tissue samples were collected over a 12-year period (2000-2012). PIK3CA mutation and amplification of gene copy number were analyzed by pyrosequencing method and fluorescence in situ hybridization (FISH). Results: Nine of the 105 liposarcoma patients (8.6%) showed activating PIK3CA mutation.PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic type vs well differentiated/dedifferentiated type (11.1% vs 88.9%, P = 0.044). In FISH analysis of PIK3CA, amplification of PIK3CA was detected in 31 of the 102 patients (30.4%) and histologic differences was not statistically significant in patients with PIK3CA amplification (48.4% vs 51.6%, p = 0.328). In survival analysis, PIK3CA amplified patients showed worse prognosis compared with PIK3CA-non amplified patients (median disease free survival (DFS) 119.2 vs 38.3 months p = 0.01). In multivariate analysis, positive PI3KCA amplification was an independent worse prognostic factor for DFS (p = 0.04; HR, 2.6; 95% CI 1.36 to 5.1). PIK3CA mutation was not associated with significant difference for DFS (p = 0.739) Conclusion: We demonstrated that histologic differences according to PIK3CA mutation or amplification status. PIK3CA amplification was an independent worse prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutation and amplification in liposarcoma. Citation Format: Joo Hoon Kim, Hyo Song Kim, Jae Seok Lee, Ki Hyang Kim, Yong Jin Cho, Kyu Hyun Park, Soo Hee Kim, Joong Bae Ahn, Woo Ik Yang, Young Han Lee, Jin-Suck Suh, Kyoo-Ho Shin, Sun Young Rha. Prognostic implications of PI3K mutation and amplification in curatively resected liposarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 591. doi:10.1158/1538-7445.AM2015-591
Survival outcomes associated with different sunitinib dosing regimens in metastatic renal cell carcinoma.
Authors: Winnie Cheng, Victoria Kletas, Mario Law De Lemos, Sally Man, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2014)

417 Background: Standard dosing regimen of sunitinib for metastatic renal cell carcinoma (mRCC) consists of 4 weeks treatment followed by 2-weeks rest (intermittent dosing, ID). Alternative regimens have been suggested, including continuous daily dosing (continuous dosing, CD) and non-conventional dosing (non-conventional dosing: e.g. 2 weeks on / 1-week off, ND) to provide more individualized therapy with less toxicities. It is unclear whether non-standard sunitinib dosing affects survival outcomes. Methods: mRCC patients treated with sunitinib between July 1, 2007 and July 1, 2011 were identified from the British Columbia Cancer Agency (BCCA) pharmacy database, a publicly funded cancer care organization. Medical records and dispensing data were reviewed retrospectively to categorize sunitinib dosing as ID, CD or ND. Primary outcome was to compare overall survival (OS) associated with varying regimens, with secondary outcomes of progression free survival (PFS) and incidence of treatment discontinuation due to adverse effects (AE). Results: A total of 180 patients were identified. Heng prognostic risk criteria were assessable in 162 patients. Of these, 34 (21%), 80 (49%) and 48 (30%) had low-, intermediate- and high-risk disease. Most patients received ID (120, 67%), followed by CD (32,18%) and ND (28,16%). Compared to ID, CD was associated with similar OS (median 9 vs. 13 months, HR 0.67, 95% CI 0.43-1.06, p=0.088) while ND was associated with significantly longer OS (median 9 vs. 23 months, HR 0.55, 95% CI 0.34-0.90, p=0.016). PFS was significantly better for CD (median 4 vs. 9 months, HR 0.61, 95% CI 0.40-0.94, p=0.025) and ND (median 4 vs. 10 months, HR 0.61, 95% CI 0.39-0.95, p=0.03) when compared to ID. Similar to prior sunitinib trials, a significant proportion of patients (20%) discontinued sunitinib therapy due to AE. Conclusions: In comparison to the standard ID regimen, dosing sunitinib with alternative regimens appears to be associated with improved OS and PFS in patients with mRCC. Presently, a prospective Canadian trial is underway investigating the efficacy and safety of individualized sunitinib dosing regimens.
Patient- versus physician-reported toxicities among survivors of head and neck cancer after chemoradiation: Prospective evaluation of screening methodologies.
Authors: Allen M. Chen, Carol Felix, Sophia Hsu
Journal: Journal of Clinical Oncology (2016)

150 Background: This study sought to compare the incidence of late toxicities among survivors of head and neck cancer treated by definitive chemoradiation using patient-reported versus physician-reported methodologies. Methods: Two validated quality of life instruments, the University of Washington Quality of Life questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy for Head and Neck questionnaire (FACT-H&amp;N) were administered to patients returning for follow-up after chemoradiation for head and neck cancer. Only patients who had been clinically without evidence of disease for greater than 6 months were sampled. Scores were compared to physician-reported toxicities, which were recorded blindly and independently after each patient visit, using the National Cancer Institute’s Common Toxicity Criteria (version 4.0). Two by two contingency tables were constructed to assess differences between patient- and physician-reported responses using Fisher’s exact test. Results: Fifty patients (35 male; 15 females) completed both instruments. While 78% of patients reported an inability “to swallow certain solid foods” and 70% reported difficulty to “swallow naturally and easily” using the self-reported UW-QOL and FACT-H&amp;N surveys, respectively, the incidence of grade 2+ esophageal dysfunction as reported by physicians was only 48% (p &lt; 0.001). While 60% of patients reported “too little saliva” and 50% acknowledged having problems with "voice quality and strength" using the UW-QOL and FACT-H&amp;N surveys, only 20% and 30%, respectively, were scored as having grade 2+ xerostomia and laryngeal toxicity. Significant discordance was also observed between patient- and physician-reported toxicities with respect to the domains of appearance (p = 0.02), pain (p = 0.01), activity/energy (p &lt; 0.001), and mood (p = 0.001). Conclusions: Late toxicities are frequently under-reported by physicians after chemoradiation for head and neck cancer. The true incidence and severity of these treatment-related toxicities, with respect to both functional and psychosocial impairment, among survivors may be better evaluated by patient-reported methods.
Risk of leukaemia is no higher in children living near UK nuclear sites, finds report
Authors: Susan Mayor
Journal: BMJ (2016)

Children living near two nuclear sites in the United Kingdom, Sellafield and Dounreay, showed no increase in risk of leukaemia or non-Hodgkin’s lymphoma, a new analysis of cancer rates from 1991 to 2006 has shown.1

The report’s authors said that the increased incidence of these cancers found in earlier years may have been associated with exposure to infections as people from elsewhere moved into these previously isolated rural areas.

The Committee on Medical Aspects of Radiation in the Environment (COMARE) has been investigating possible cancer clusters around nuclear installations for the past 30 years. A report in 1984 found an increased incidence of leukaemia in under 25s living in Seascale, a village near the Sellafield nuclear site in northwest England. A second report in 1988 found higher rates of leukaemia in children and young people living near the Dounreay nuclear site in Caithness, Scotland, compared with the …
A phase II randomized, double-blind placebo-controlled trial of an antiemetic, 6-gingerol in solid tumor patients receiving moderately to highly emetogenic adjuvant chemotherapy.
Authors: Jitprapa Konmun, Kwanjit Danwilai, Nuttapong Ngamphaiboon, Aumkhae Sookprasert, Ekaphop Sirachainan, Suphat Subongkot
Journal: Journal of Clinical Oncology (2014)

9647 Background: Several studies showed that ginger powder could reduce chemotherapy-induced nausea and vomiting (CINV). 6-gingerol is a natural compound extracted from ginger. It has an antagonistic activity to NK1, serotonin, and dopamine receptors. Methods: Patients who received moderately to highly-emetogenic chemotherapy were randomized to 6-gingerol 10 mg or placebo PO BID continuously, started 3 days prior to chemotherapy and continued for 4 cycles. 5-HT3 receptor antagonist and dexamethasone were given to all patients. The Likert scale was used to evaluate severity of nausea and loss of appetite. Vomiting was graded according to the CTCAE v.4. Quality of life (QoL) was measured by the FACT-G score. All parameters were evaluated at baseline and before each cycle. Primary endpoints were severity of acute (≤24 hours after chemotherapy) and delay (>24 hours) CINV between 2 groups. Results: 87 patients (median age of 53) were enrolled. Patient characteristics were equally distributed between 2 groups. Most patients received anthracyclines (64%) and platinum-doublets (20%). 6-gingerol group had significantly less CINV, improved QoL and appetite, correlated with cytokine changes (see Table). Conclusions: 6-gingerol significantly reduces CINV, improves appetite and QoL. A larger clinical trial is warranted to confirm these results. 6-Gingerol N=41 (%) Placebo N=46 (%) p-value Acute vomiting None Gr.1-2 Gr. 3-4 35 (85) 5 (12) 1 (2) 26 (57) 18 (39) 2 (4) 0.013 Delay vomiting None Gr.1-2 Gr. 3-4 31 (76) 9 (22) 1 (2) 5 (11) 22 (48) 9 (20) <0.001 Acute nausea None Mild Moderate Severe 22 (54) 14 (34) 3 (7) 2 (5) 3 (6) 10 (22) 16 (35) 7 (15) 0.002 Delayed nausea None Mild Moderate Severe 10 (24) 23 (56) 5 (12) 3 (7) 4 (9) 9 (19) 17 (37) 16 (35) <0.001 Mean FACT-G Score Cyc2 Cyc4 82.5 86.2 77.1 72.4 0.124 <0.001 Mean super oxide dismutase (unit/mL) Cyc2 Cyc4 638 786 496 448 0.033 <0.001 Mean catalase (Kunit/mL) Cyc2 Cyc4 61.2 66.0 47.9 48.5 0.001 0.001 Mean glutathione (unit/mL) Cyc2 Cyc4 18.5 21.8 13.2 13.6 0.016 0.001 Mean thiobarbituric acid reactive substance (nmol/mL) Cyc2 Cyc4 5.2 5.2 6.1 6.8 0.082 0.002 Mean appetite score Cyc2 Cyc4 2.0 2.3 3.6 5.3 0.008 <0.001
Different components of blood pressure are associated with increased risk of atherosclerotic cardiovascular disease versus heart failure in advanced chronic kidney disease
Authors: Nisha Bansal, Charles E. McCulloch, Feng Lin, Cassianne Robinson-Cohen, Mahboob Rahman, John W. Kusek, Amanda H. Anderson, Dawei Xie, Raymond R. Townsend, Claudia M. Lora, Jackson Wright, Alan S. Go, Akinlolu Ojo, Arnold Alper, Eva Lustigova, Magda Cuevas, Radhakrishna Kallem, Chi-yuan Hsu, Lawrence J. Appel, Harold I. Feldman, Alan S. Go, Jiang He, John W. Kusek, James P. Lash, Akinlolu Ojo, Mahboob Rahman, Raymond R. Townsend
Journal: Kidney International (2016)
Updated Results of the PRIMA Study Confirms the Benefit of 2-Years Rituximab Maintenance In Follicular Lymphoma Patients Responding to Immunochemotherapy.
Authors: Gilles Andre Salles, John Catalano, Pierre Feugier, Fritz C Offner, Reda Bouabdallah, Dolores Caballero, Pauline Brice, Lars Moller Pedersen, Corinne Haioun, David Belada, Alain Delmer, David Simpson, Herve Tilly, Sirpa Leppa, Pierre Soubeyran, Anton Hagenbeek, Olivier Casasnovas, Tanin Intragumtornchai, Christophe Fermé, Maria Gomes da Silva, Catherine Sebban, Andrew Lister, Jane A Estell, Gustavo Milone, Anne Sonet, Armando Lopez-Guillermo, John Francis Seymour, Luc Xerri
Journal: Blood (2010)
A phase II study of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01): Report of interim analysis.
Authors: Mitsukuni Suenaga, Nobuyuki Mizunuma, Yoshiya Fujimoto, Masashi Ueno, Satoshi Matsusaka, Eiji Shinozaki, Yosuke Fukunaga, Satoshi Nagayama, Toshiharu Yamaguchi
Journal: Journal of Clinical Oncology (2012)

e14145 Background: Perioperative chemotherapy combined with surgery for liver metastases is regarded as active strategy in metastatic colorectal cancer (mCRC). However, its impact on initially unresectable or potentially resectable previously untreated advanced CRC (ACRC), regardless of concurrent metastases, remains to be clarified. Methods: A phase II study to evaluate safety and efficacy of perioperative FOLFOX4 plus bevacizumab (BEV) for initially unresectable ACRC was conducted at a single institute in Japan. Previously untreated advanced colon or rectal (Rs-Ra) cancer and initially considered as unresectable ACRC (TNM: Stage IIIb, IIIc or IV) indicating potentially resectable after neoadjuvant chemotherapy (NAC) were eligible for this study. All patients provided their written informed consent. Patients received neoadjuvant FOLFOX4 plus BEV for six cycles. The sixth cycle did not include BEV. Duration between the last administration of BEV and surgery needed at least five weeks. Adjuvant FOLFOX4 plus BEV for six cycles were given after surgery. Completion rate of NAC and possibility of curative surgery were primary end point. Interim analysis of completion rate of NAC was planned at the end of NAC in the twelfth patient. Results: Characteristics of patients were as follows: gender, 8 male and 4 female: location, Sigmoid in 3, Ascending in 1 and Ra in 8: Stage, III in 8 and IV in 4 (liver or lymph node). All patients completed six cycles of NAC. No tumor-related severe adverse events or death were observed. Median duration between last administration of BEV, FOLFOX4 and surgery were 51 days and 34 days, respectively. Objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection including metastatic lesion. Conclusions: The interim analysis met primary end point and suggests that neoadjuvant FOLFOX4 plus BEV is well tolerated and promise high response rate leading to curative surgery. These data indicate potential survival benefits from perioperative addition of BEV to the FOLFOX4 for initially unresectable ACRC if concurrent metastatic lesion.
Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors
Authors: Yongkun Sun, Wei Niu, Feng Du, Chunxia Du, Shuting Li, Jinwan Wang, Li Li, Fengqing Wang, Yu Hao, Chuan Li, Yihebali Chi
Journal: Journal of Hematology & Oncology (2016)

Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Anlotinib (5–16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1). Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. On the 4/0 schedule, dose-limiting toxicity (DLT) was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma) were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.
Brief Report: Causes of Stillbirths in Women With Systemic Lupus Erythematosus
Authors: Évelyne Vinet, Geneviève Genest, Susan Scott, Christian A. Pineau, Ann E. Clarke, Robert W. Platt, Sasha Bernatsky
Journal: Arthritis & Rheumatology (2016)

Objective There are few precise or recent estimates of the risk or causes of stillbirths in women with systemic lupus erythematosus (SLE). Thus, we undertook the present study to examine causes of stillbirths in mothers with SLE versus those without SLE. Methods The Offspring of SLE Mothers Registry (OSLER) is a large population‐based cohort, identified through Quebec's health care databases (1989–2009), including all women who had ≥1 hospitalization for delivery after SLE diagnosis, and a randomly selected control group of women matched for age and year of delivery. We identified stillbirths and ascertained the cause of death as indicated on death certificates. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and multivariate logistic regression analysis was performed to estimate the risk of stillbirth in women with SLE versus controls. Results In our cohort, 509 women with SLE had 729 births, including 9 stillbirths, while 5,829 matched controls had 8,541 births, including 47 stillbirths. We observed more stillbirths in mothers with SLE than in controls (1.24% versus 0.55%, difference 0.69% [95% CI 0.03, 1.88]). Women with SLE had an increased risk of stillbirth compared to controls (adjusted OR 2.13 [95% CI 1.02, 4.45]). We also observed a trend toward more stillbirths due to placenta‐mediated pregnancy complications in mothers with SLE than in controls (44% [95% CI 14, 79] versus 15% [95% CI 6, 28]). Conclusion Compared to women from the general population, women with SLE have an increased risk of stillbirth. Stillbirths in women with SLE might be more often caused by placenta‐mediated pregnancy complications compared to stillbirths in mothers without SLE.