tbuckley/cabot-search huggingface dataset:
Second primary cancers in patients with stage III non-small cell lung cancer successfully treated with chemo-radiotherapy
Authors: T. Kawaguchi, M. Ogawara, M. Kawahara, S. Fukai, H. Komatsu
Journal: Journal of Clinical Oncology (2005)

7309 Background: The purpose of the current study is to assess the incidence of SPC and the impact of smoking status on the SPC in long-term survivors with stage III NSCLC after chemo-radiotherapy. Methods: Using the database from the National Hospital Study Group for Lung Cancer in Japan between 1985 and 1995, information was obtained on 62 patients who were more than 3 years diseases-free survivors. Details of clinical information and most smoking history were available from the questionnaire. Results: Nine of the 62 patients developed SPC 3.9–12.2 years (median, 6.2 years) after the initiation of the treatment. The site of SPC was 2 lung, 1esophagus, 2 stomach, 1 colon, 1 breast, 1 skin and 1 leukemia. Among these nine, three cancers occurred inside the radiation field. The relative risk of any SPC was 2.8 (95%CI, 1.3–5.3). In univariate analysis, the patients who were male, had more cumulative smoking and continued smoking had an increased risk of SPC (RR4.3, CI 1.1–5.3; RR3.0, CI 1.2–6.2; RR 5.2, CI 1.6–11.7, respectively). In multivariate analysis, factors including smoking status and histological type had no effect on the development of a SPC. Conclusions: The patients with stage III NSCLC successfully treated with chemo-radiotherapy were at risk for developing SPC and this risk increased with time. When compared with other published studies, there was little additional effect on developing SPC with treatment options such as chemo-radiotherapy, or with smoking status. No significant financial relationships to disclose.
Hypertension as a predictor of outcome and treatment response to cetuximab: A retrospective analysis of NCIC CTG CO.17.
Authors: Shelly Sud, Christopher J. O'Callaghan, Caleb Jonker, Christos Stelios Karapetis, Timothy Jay Price, Niall C. Tebbutt, Jeremy David Shapiro, Guy A. Van Hazel, Nick Pavlakis, Peter Gibbs, Mark Jeffery, Lillian L. Siu, Sharlene Gill, Ralph Wong, Derek J. Jonker, Dongsheng Tu, Rachel Anne Goodwin
Journal: Journal of Clinical Oncology (2016)

256 Background: Adrenergic receptor stimulation is involved in development of hypertension (HTN), and is implicated in progression and dissemination of metastases in tumour types such as colon cancer (CRC). Adrenergic antagonists, such as beta-blockers (BB), demonstrate inhibition of invasion and migration in CRC cell lines and have been associated with decreased mortality in advanced CRC. We examined the association of baseline HTN (BHTN) and use of BB on overall (OS) or progression-free survival (PFS) of pts with pre-treated, chemotherapy refractory, metastatic CRC (mCRC). We also examined BHTN and BB use as predictors of Cetuximab (CET) efficacy. Methods: Using data from NCIC CO.17 (CET vs. BSC), we coded BHTN and use of anti-HTN meds (Rx), including BB, for 572 pts. Chi-square test assessed association between these variables and baseline characteristics. Univariate and multivariate analyses of OS and PFS by BHTN diagnosis and BB use were performed using Cox regression models. Results: Pts with BHTN (149/572) and those using BB (60/572) were older, had diminished performance status, and higher creatinine levels. BHTN, BB use and anti-HTN Rx were not prognostic for OS and PFS, though a trend was noted between BB use and improved PFS (HR 1.38 [0.97- 1.96], p= 0.077). BHTN and BB use were not significant predictors of CET benefit. However, pts with BHTN tended to have a stronger treatment effect in PFS from CET (interaction p = 0.074). Conclusions: In chemo-refractory mCRC, BHTN and BB use are not significant prognostic factors. BHTN and BB use are also not predictive of CET benefit, though pts with baseline HTN may benefit from a stronger treatment effect with CET. Patients with chemo-refractory mCRC may be biologically selected and the impact of BB use in earlier lines may therefore still warrant investigation. [Table: see text]
How does parental status influence preferences for cancer treatment and palliative care?
Authors: Devon Check, Eliza Park, Katherine Elizabeth Reeder-Hayes, Deborah Mayer, Allison Mary Deal, Justin Yopp, Donald Rosenstein, Laura Hanson
Journal: Journal of Clinical Oncology (2014)

65 Background: When patients with metastatic cancer have dependent children, they may be less likely to acknowledge the terminal nature of their illness and more willing to accept toxic treatments for small improvements in survival, compared to patients without children. Our mixed methods study sought to clarify the role of parental concerns in treatment decision-making. Methods: We recruited 63 patients with metastatic cancer who have children &lt;18 to complete measures of physical and social wellbeing. 47 (75%) also participated in a semi-structured interview, which included questions about whether parental status influences patients’ decisions about anti-cancer treatment and whether patients would consider using palliative care, including hospice. We used univariable logistic regression to examine the relationship between patient and family characteristics and 3 outcomes: 1) influence of parental status on treatment decision-making, 2) interest in palliative care, and 3) interest in hospice. We used participants’ qualitative comments to describe the context for their preferences. Results: Average patient age was 44; average number of children was 2, and average child age was 13. 70% of patients reported that being a parent influences their treatment decisions. 64% cited parental status as motivation for life-extending treatment. 15% prioritized preserving parental functioning. Half of patients said they would consider using palliative care, and 57% said they would consider using hospice. Reasons for disinterest in palliative care and hospice included concerns about being perceived as giving up and children’s exposure to death at home. Parents with older children (OR 0.85, p=0.03), and those with increased social support (OR 0.96, p=0.05) had lower odds of reporting an influence of parental status on treatment decisions. Children’s age (OR 0.85, p=0.02) and low performance status (OR 4.3, p=0.02) were associated with palliative care interest. Conclusions: Parental concerns may influence treatment decision-making for metastatic cancer patients with children. Information about parental concerns may help oncologists to align treatment with patients’ priorities.
Effect of germ-line <i>BRCA</i> mutations in biochemical relapse and survival after treatment for localized prostate cancer.
Authors: Elena Castro, David Olmos, Chee Leng Goh, Ed Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Elizabeth Bancroft, Elizabeth Page, Tokhir Dadaev, Koveela Govindasami, Michelle Guy, Steve Ellis, Debra Frost, Susan Peock, Antonis C. Antoniou, Douglas Easton, Zsofia Kote-Jarai, Ros A. Eeles
Journal: Journal of Clinical Oncology (2013)

29 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter cause-specific survival (CSS). Germline BRCA mutations are associated with worse PrCa outcomes. In this study, we analyzed biochemical-progression free survival (bPFS) after conventional treatments for localized PCa in a cohort of BRCA patients from the UK. Currently, BRCA1/2 carriers are treated with the same protocols used for non-carriers. Methods: In this retrospective case-control study, each BRCA carrier (10 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by: age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment (RT or RP), androgen-deprivation therapy (ADT) and year of treatment (±5yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 176 patients (pts) were included. Median follow-up was 97 months (ms). Median age at diagnosis was 58.5 yrs (43-75). 80 pts received RT (16 BRCA2, 4 BRCA1, 60 NC) and 85% also received ADT≥6 ms. 96pts underwent RP (18 BRCA2, 6 BRCA1 and 72 NC). Following RT treatment, 5yrs-CSS was 96% in NC and 47% in BRCA carriers (p=2x10 -5 ), whilst no difference was seen after RP (5yrs-CSS was 98.5% in NC vs 93.3% in BRCA). Five-years bFPFS after RT was 74% in NC and 24% in BRCA (p=0.002). No difference was observed in 5yrs-bPFS between BRCA carriers and NC treated with RP (52% vs 66% , p=0.346). The adjusted MVA (including tumour stage, local treatment, ADT and BRCA status) confirmed the independent prognostic value of BRCA status for bPFS and CSS. Among BRCA carriers, the independent risk was greater when the analysis was limited to BRCA2 pts . Conclusions: Our results suggest that BRCA carriers have worse local disease control than NC when conventionally treated with RT. No differences in bPFS were observed in pts treated with RP after &gt;8 yrs median follow-up. These results may have implications for tailoring clinical management in these patients.
Changing trend in multiple myeloma therapy
Authors: A. Jajeh, D. Osafo, D. Tamkus, B. Yim
Journal: Journal of Clinical Oncology (2005)

6745 Background: Newer agents has been incorporated in the treatment of multiple myeloma either as a single agent or in combination with other agents. Thalidomide has caused a change in the treatment of multiple myeloma at our insitution which is an urban inner city teaching hospital. Methods: Retrospective analysis of patients diagnosed with multiple myeloma in the last two years was conducted. The diagnosis was based on bone ma rrow biopsy, serum protien electrophoresis, quantitative serum immunogobulin, immunofixation, twenty four hours urine collection for protien and electophoresis and skeletal survey revealed eighty three patients with established diagnosis. Review of the staging, beta 2 microglobulin, LDH, serum albumin, treatment strategy and out come of treatment objectives were analized. Results: Thirty patients recieved thalidomid either alone or with Dexamethazone (30%). Ninety percent of patients has failed or were refractory to many lines of treatment. Twenty six patients had combination treatment with Doxil, Vincristine and four days of pulse Dexamethazone (DVd), nineteen patients (73%) were newely diagnosed. Six patients recieved Bortizomibe. Response rate is 65% for the Thalidomide therapy. Seventy percent of patients are alife with good response (CR complete response and PR partial respone with medium follow up of 18 months in the Thalidomide therapy. Eighty three percent of patients in the DVd treatment achieved CR, PR. However, seventy five percent has relapsed with in less than two years of follow up. Five patients in the DVd therapy underwent autologous bone marrow transplant. More than 65% patients were blacks, twenty percents hispanics, ten percent white and five percent were others. More than sixty percent of patients has advanced stages and high risk factors. Mean beta 2 microglobulin level is 4.3 (range0.9–9.5). normal 0.04–2.3mg/dL. Seven patients recieved infusional VAD treatment. Melphan and prednison were given to ten newly diagnosed patients as a first line therapy. Conclusions: The above retrospective analysis has shown a clear shift in the trend of selecting therapy in patient with multiple myeloma. Thalidomide has shown superior results considering the high risk presentation and minority status of our patients population No significant financial relationships to disclose.
Amuvatinib (MP-470), an oral dual inhibitor of mutant kinases and DNA repair: Final results from a 100-patient, 5-arm phase Ib trial in combination with five standard of care (SOC) anticancer regimens.
Authors: K. K. Sankhala, A. W. Tolcher, M. M. Mita, M. S. Gordon, L. S. Rosen, K. P. Papadopoulos, A. Patnaik, R. L. Drengler, A. C. Mita, J. Sarantopoulos, R. G. Bristow, G. Fine, G. S. Choy, M. Azab
Journal: Journal of Clinical Oncology (2011)

3074 Background: Amuvatinib is an oral multi-targeted TKI which inhibits the mutant forms of c-kit, and PDGFRα. It also disrupts DNA repair probably through suppression of Homologous Recombination protein Rad51. Methods: Adults with cancer diagnosis appropriate for one of the 5 SOC regimens to be studied received amuvatinib (dry-powder capsules) in combination with SOC. The 5 SOC regimens were: paclitaxel/carboplatin (PC), carboplatin/etoposide (CE), topotecan (T), docetaxel (D), and erlotinib (E). Amuvatinib doses were escalated until the MTD of the drug in combination with SOC agents was reached. The primary objectives of the study were to determine the MTD, DLTs, and quantify the effects of amuvatinib on the PK of SOC agents. Other objectives included pharmacodynamic parameters and tumor response. Results: 100 patients, mean age of 58 (range, 25–84) years were enrolled. M/F:35/65. ECOG PS 0/1/2:15/78/7, respectively. 90% of patients had prior cancer treatment. Patients were treated with amuvatinib plus: PC (23 patients); CE (22); T (20); D (15), and E (20). Amuvatinib doses were escalated from 100 mg PO QD to 400 mg PO BID on a continuous basis. Amuvatinib did not alter the PK of SOC agents, except D. The MTD was not reached and amuvatinib-related DLTs were not identified in this study. Most common (≥ 15% of patients) adverse events (AEs) related to treatment were expected AEs of SOC: neutropenia, fatigue, alopecia, diarrhea, thrombocytopenia, and anemia. Overall, 12 PRs and 44 SDs by RECIST criteria were observed for an overall disease control rate of 56% (95% CI, 46–66). The PC and CE combination arms with amuvatinib showed the most activity with 6 and 5 PRs, respectively. Small Cell Lung Cancer (SCLC) and Neuroendocrine (NE) tumors were the most sensitive with 5 of 11 SCLC or NE patients achieving PR. Rad51 modulation and increased DNA damage (53BP1 foci) was observed in skin punch biopsies. Conclusions: Amuvatinib is well tolerated in combination with 5 SOC regimens. Several PRs were observed. The results support further investigation of amuvatinib in combination with CE or PC in SCLC and NE tumors.
Analysis of polymorphisms in sodium channel, voltage-gated, type I, alpha subunit (SCN1A) as predictors of clinical outcome and toxicity in advanced ovarian cancer patients enrolled in a phase III trial treated with patupilone.
Authors: Y. Ning, W. Zhang, D. Yang, D. Weber, F. Souami, P. O. Bohanes, A. Gerger, M. J. Labonte, L. Benhaim, H. Lenz
Journal: Journal of Clinical Oncology (2011)

5051 Background: Patupilone (P) is a potent member of a class of microtubule-stabilizing cytotoxic agents known as epothilones. Recently, a phase III trial fail to show a significant overall survival advantage in platinum refractory recurrent ovarian, primary fallopian tube and primary peritoneal cancer patients (pts) treated with P compared to pegylated liposomal doxorubicin (PLD). Our previously data demonstrated 2 SCN1A polymorphisms [T1067C (rs2298771) and IVS5_91 (rs3812718)] were associated with clinical outcome and toxicity in mCRC pts enrolled in a phase II study treated with Celebrex and P. Here we tested the hypothesis whether these 2 SCN1A polymorphisms may predict clinical outcome and toxicity in advanced ovarian cancer pts enrolled in a phase III trial. Methods: A total of 829 pts enrolled into P clinical trial between Nov 2005 and Feb 2010. 347 pts’ extracted DNA samples were available for current pharmacogenetic study. 181 samples came from P arm, and the other 166 came from PLD arm. The clinical and pathological characteristics of these 347 pts were not statistically significantly different from pts (n=482) enrolled in the trial but no DNA samples available. PCR-based direct sequencing was performed on genomic DNA samples. Results: In univariable analysis, pts with SCN1A 1067 TT genotype (n=86) had trend shorter median OS=10.7 (95% C.I 8.1, 12.8) months compared to pts harboring C allele (TC+CC) (n=94), median OS=15.3 (95% C.I 11.6, 17.9) months (HR: 0.72, 95% C.I 0.51, 1.02; P=0.059, log-rank test). In combined haplotype (T1067C/IVS5_A91G) analysis, pts with C/G haplotype had lowest risk of dying (HR 0.741(95% C.I 0.555, 0.991) compared to T/A and T/G haplotype. (p=0.043, Wald test). Also, pts with T/G haplotype had lowest grade 3-4 diarrhea risk (HR 0.476(95% C.I 0.234, 0.966) compared to T/A and C/G haplotype (p=0.04,Wald test). Conclusions: Our preliminary results suggest germline polymorphisms in SCN1A gene may be associated with overall survival and toxicity in advanced ovarian cancer pts treated with P. Prospective trials based on these correlative studies are warranted.
The prognostic value of lymphadenectomy in the revised 2009 FIGO staging system for endometrial cancer: A multicenter study.
Authors: J. W. Kim, H. Kim, C. Park, J. Lee, J. Lee, C. Cho, S. Kim
Journal: Journal of Clinical Oncology (2011)

e15568 Background: We sought to evaluate whether pelvic or para-aortic lymphadenectomy increases the prognostic value of the revised 2009 FIGO staging system in patients with endometrial cancer (EC). Methods: We reviewed 786 patients with EC from 6 tertiary medical centers between July 1996 and June 2008. All patients were classified according to the 1988 FIGO staging system for EC: IA (n=234); IB (n=270); IC (n=109); IIA (n=35); IIB (n=29); IIIA (n=37); IIIB (n=3); IIIC (n=69), and the revised 2009 FIGO staging system was also applied to classify them: IA (=542); IB (=125); II (n=29); IIIA (n=18); IIIB (n=3); IIIC1 (n=43); IIIC2 (n=26). Results: In all patients, the 1988 FIGO stage IC, IIB, IIIA+IIIB and IIIC diseases (adjusted HRs, 8.39, 10.79, 12.30 and 15.41; 95% CIs, 1.67-22.15, 1.75-36.62, 1.95-46.16 and 2.94-50.88), and the revised 2009 FIGO stage IB, II, IIIA+IIIB and IIIC2 diseases were poor prognostic factors for PFS (adjusted HRs, 3.39, 4.37, 2.46 and 10.33; 95% CIs, 1.29-8.91, 1.23-15.59, 1.48-12.56 and 3.50-30.46), whereas the 1988 FIGO stage IIB and IIIC diseases (adjusted HRs, 18.92 and 20.93; 95% CIs, 1.54-43.21 and 2.01-40.92), and the revised 2009 FIGO stage II, IIIA+IIIB and IIIC2 diseases were unfavorable prognostic factors for OS by multivariate Cox proportional hazard analyses (adjusted HRs, 9.10, 3.86, 3.86 and 20.14; 95% CIs, 1.67-29.61, 1.37-20.45 and 3.98-41.81). Although these results are similar to those in 595 patients who underwent pelvic or para-aortic lymphadenectomy, the revised 2009 FIGO stage IIIC1 disease was an additional prognostic factor for PFS and OS (adjusted HRs, 4.19 and 11.25; 95% CI, 1.39-12.60 and 2.23-36.74, respectively). Conclusions: These findings suggest that the revised 2009 FIGO staging system may be more prognostic than the 1988 FIGO staging system for EC, and pelvic or para-aortic lymphadenectomy may increase the prognostic value of the revised 2009 FIGO staging system for EC.
Is ultrasonography useful to detect lymph-node invasion in melanoma patients? Results of a meta-analysis using techniques adapted to the evaluation of diagnostic tests
Authors: P. Saiag, M.-L. Bafounta, A. Beauchet, S. Chagnon
Journal: Journal of Clinical Oncology (2005)

7538 Background: Attempts to diagnose early nodal spread in melanoma patients are warranted to initiate earlier therapeutic lymphadenectomy, although the efficacy of this strategy on patient survival has not been proven in controlled clinical trials. The usefulness of lymph node ultrasonography (US) to improve nodal invasion detection during follow up of melanoma patients is debated. Our aim was to assess, using for the first time in this field meta-analysis techniques for diagnostic tests, the respective value of US and palpation examinations to detect nodal invasion in AJCC stage I-III melanoma patients. Methods: Five computerized databases were screened to December 2003. Original studies exploring the scope of our study were selected when they compared palpation and US and provided calculated or calculable sensitivity and specificity values. Guidelines for meta-analyses evaluating diagnostic tests were used. Results: We selected 12 studies representing 6,642 patients, with at least 16225 paired palpation and US examinations which were performed by trained physicians in 5 and 7 studies, respectively. Despite limitations of selected studies (variable independence between evaluations or false-negatives definitions, verification bias, with histology performed in suspected cases only in most studies), their sufficient quality allowed to perform meta-analysis. US had a higher discriminatory power than palpation, with respective estimated odds ratios of 1755 [95% CI 726 to 4238] and 21 [4 to 111](p=0.0001), respective estimated positive-likelihood ratios of 41.9 [29 to 75] and 4.55 [2 to 18], and respective estimated negative-likelihood ratios of 0.024 [0.01 to 0.03] and 0.22 [0.06 to 0.31]. Conclusions: US is more accurate than palpation to detect lymph node invasion during the follow up of melanoma patients melanoma. It should probably be implanted in routine patient follow-up programs. No significant financial relationships to disclose.
Embolization versus embolization and systemic therapy in patients with hepatocellular carcinoma and metastatic disease: A retrospective analysis.
Authors: Sunnie Kim, Karen T. Brown, Yuman Fong, Stephen Barnett Solomon, Joanne F. Chou, Marinela Capanu, James J. Harding, Eileen Mary O'Reilly, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2014)

363 Background: Transarterial chemoembolization (TACE) provides a survival benefit in a subset of patients with unresectable hepatocellular carcinoma (HCC). Even though data are lacking, patients with metastatic HCC (mHCC) are sometimes treated with transarterial therapies to address the hepatic disease. Sorafenib is a standard treatment for patients with mHCC. Methods: A retrospective analysis was conducted on patients diagnosed with HCC who had undergone hepatic arterial embolization (HAE) between 2006 and until 2013. Overall survival (OS) was calculated from date of HAE to date of death and estimated by Kaplan Meier Methods. Patients alive at their last follow up date were censored. Results: Of 243 patients who had undergone HAE at MSKCC during the study period, 36 patients had mHCC on initial diagnosis. Of these, 22 received HAE only, while 14 received HAE plus systemic therapy at some time during their whole treatment course. Conclusions: Patients with mHCC who underwent HAE alone had a poor OS. These data suggest that there maybe a survival benefit in patients with mHCC treated with transarterial therapies add to systemic therapy that is given at some time during their whole treatment course. These results contrast with recent data on the use of combined modality in locally advanced disease. Further studies of combined modality therapy in the setting of mHCC may be warranted. [Table: see text]