tbuckley/cabot-search huggingface dataset:
Uptake of adjuvant chemotherapy (AC) for colon cancer in older and younger patients (pts) in the Irish population.
Authors: Zia Rehman, Seamus Coyle, Jane Sze Yin Sui, Emmet Jordan, Chalen Lee, Sandra Deady, Harry Comber, Miriam O'Connor, Paula Calvert, Anne M. Horgan
Journal: Journal of Clinical Oncology (2013)

e14515 Background: The use of AC in older patients with colon cancer in clinical practice is uncertain. We examined uptake of AC and it’s impact on survival in older pts with stage II and III colon cancer in a national cohort. Methods: Using the National cancer Registry of Ireland, 3,486 pts with stage II and III colon cancer treated with curative resection from 2004-2009 were identified. Clinopathological features and AC use were compared between those ≥70 yrs and those &lt; 70 yrs. Data from a single institution were reviewed to determine drivers of treatment decisions. Results: 2,026 pts with stage II disease were identified, 60% ≥ 70 yrs. AC was utilized in 10% and 40% of ≥ 70 and &lt;70 yrs, respectively (p&lt;0.0001). A benefit for AC over observation was seen in older [HR 0.36; p &lt;0.0001] and younger pts [HR 0.43; p&lt;0.0004]. Of 46 stage II pts from a single institution there were no significant differences between ≥ 70yrs (n=26) and &lt;70yrs (n=23) in terms of ECOG PS, Charlson comorbidity scores (CCI), tumor grade, T3/T4 disease, R0/R1 resections, obstruction/perforation, lymphovascular invasion or nodal yield. However, only 12% ≥ 70yrs received AC compared to 57% of &lt;70yrs (p=0.0002). Of 1,460 pts with stage III disease, 51% were ≥ 70 yrs. 34% of older and 83% of younger pts received AC (p&lt;0.0001). A benefit from AC compared to observation was seen in pts ≥ 70yrs [HR 0.30; p &lt;0.0001] and &lt;70yrs [HR 0.22; p&lt;0.0001]. Of 65 stage III pts from the single institution there were no differences in CCI, ECOG PS, tumor grade, R0/R1 resections between &gt;70yrs (n=20) and &lt;70yrs (n=45). There was a difference in those receiving AC: 75% ≥ 70yrs compared to 96% &lt;70yrs (p=0.02). Conclusions: Adoption of AC is associated with a survival benefit in older pts (age ≥ 70 yrs), however, is still underutilized in clinical practice. Age impacts the decision to treat in our cohort.
Breast cancer stratification based on the expression ratio of the progesterone and estrogen receptors.
Authors: K. Bendrat, J. von Frese, K. Roeser, B. Padberg, S. Brockmoeller, A. Debus, T. Singer, K. Friedrichs, C. Lindner, A. Niendorf
Journal: Journal of Clinical Oncology (2011)

e11071 Background: The receptors for estrogen (ESR1) and progesterone (PGR) are widely used for risk stratification of breast cancer (BC). The corresponding proteins are routinely determined by immunohistochemistry (IHC) to categorize tumors into ESR1|PGR groups (+|+), (+|-) and (-|-) each with different therapy approaches. We expected a combined quantitative ESR1|PGR analysis could improve BC risk stratification. Methods: Events (E) were defined as death or recurring disease within 5 years, controls being alive without event for longer than 5 years. Fresh frozen samples of 217 invasive ductal carcinomas with known IHC receptor status (E=70, event rate=0.32) from patients receiving standard therapy were tested for ESR1 and PGR expression by qRT-PCR. Results: Grade, size, nodal status, ER and PR status (IHC) were significant clinical parameters. qRT-PCR results confirmed the established ESR1|PGR IHC-groups. Based on the sum S (ESR1+PGR) and the ratio Q (PGR/ESR1) of receptor expression BCs were stratified into three groups: high risk (n=49, E=32, OR=20.4, 95%CI=7.3-56.7, p<0.0001), medium risk (n=97, E=32, OR=5.3 CI=2.1-13.6; p=0.0005) and low risk (n=71, E=6, OR=1) characterized by high (ESR1+PGR) expression and a high expression ratio Q. The new method performed significantly different (p=0.017) from the Nottingham prognostic index (NPI) especially regarding the diagnostic “grey zone”: only 16 good clinical courses were placed into the intermediate risk group compared to 41 by the NPI (p=0.0041). The results were validated in the external chip data set GSE3494. Expression parameters S and Q were calculated (cut off values had to be adapted due to the different platform) and used to stratify 156 BCs (E=45, rate=0.29) into high risk (n=44, E=20, OR=14.2, CI=3-66.4, p<0.001), medium risk (n=76, E=23, OR=7.4 CI=1.6-33.3; p<0.01) and low risk (n=36, E=2, OR=1). Conclusions: Quantitative ESR1 and PGR analysis is a useful addition to receptor IHC by establishing a continuous numerical value. For ESR1|PGR positive BCs a high (PGR/ESR1) ratio is predictive of a favourable clinical outcome under standard clinical management.
Attitudes toward cancer and psycho-oncology services.
Authors: C. C. M. O'Sullivan, S. Collier, A. Buckmaster, A. M. O'Dwyer
Journal: Journal of Clinical Oncology (2011)

e19568 Background: There is a considerable body of literature suggesting that perceived stigma is a major obstacle in seeking appropriate psychological/psychiatric care. To date, there has been little research into patients’ attitudes towards attending psycho-oncology services. This study aimed to investigate patients’ levels of emotional distress and attitudes towards being referred to a psycho-oncology service. Methods: We invited all eligible patients (N=322) attending the Haematology/Oncology Day ward of a large teaching hospital during a two week period to participate in the study. Over 93% of patients (N=300) agreed to complete 2 self-report standardised questionnaires and an attitudinal questionnaire. We considered patients aged 18 or over, with a cancer diagnosis and an ECOG performance status of 3 or less. Results: A significant level of distress was noted in our patient cohort.57.9% of patients reported feeling either extremely or very distressed with respect to their cancer diagnosis. The five issues related to cancer and its treatment which patients found most concerning were fatigue (62.7%), work (43.0%), fear of recurrence (42.8%), anxiety (38.3%) and finances (32.8%). Stigma was noted with respect to patient’s willingness to engage with psycho-oncology services. 18.7% and 19.3% of patients said that they would be very uncomfortable attending a psychologist or a psychiatrist as opposed to only 3.7% of those referred to a dietician. Patients were reluctant to take medications that were perceived to have mood altering properties. 29.4% of patients reported that they would be very uncomfortable if their doctor prescribed them antidepressants as opposed to only 3.7% of those prescribed anti-emetics. Conclusions: This study aimed to investigate possible attitudinal barriers to receiving appropriate psycho-oncology interventions in cancer patients. Significant levels of stigma and distress exist in our patient cohort, comparable to levels observed in similar studies. Future endeavours should focus on education of patients and physicians alike, in order to ensure that all patients requiring psycho-oncology services receive them.
Eight weekly infusions of rituximab (R) for relapsed patients (pts) with indolent B-cell lymphoma mostly pretreated with R: A Japanese multicenter phase II study.
Authors: T. Igarashi, K. Murayama, K. Itoh, M. Kurosawa, H. Nagai, T. Watanabe, K. Tobinai
Journal: Journal of Clinical Oncology (2010)

e18510 Background: To evaluate the efficacy and safety of R × 8 dosing monotherapy in pts with relapsed or refractory indolent B-cell NHL with pharmacokinetic (PK) assessment. Methods: In a multi-center phase II study from Nov. 2004 to July 2008, pts received weekly R (375 mg/m2) for 8 consecutive weeks. Median follow-up was 503 days. 51 pts (25M: 26F) (median age 59, 32-79) out of 52 pts enrolled were evaluated. 12 pts had extranodal diseases (7 BM+). Central pathology review revealed: follicular (46), marginal zone (5). Median prior chemotherapy regimens was 1 (1-7). 38 pts were pretreated with R. FLIPI: low (26), intermediate (16), and high (9). 45 eligible pts were evaluated on a protocol-compatible (PC) basis, whereas 51 pts on an ITT basis for response and PFS. Results: Overall response rate (ORR) of all (51) and eligible (45) pts were 61% including 41% CR and 69% including 47% CR, respectively. All of mild to moderate infusion-related toxicities were reversible. Grade 3/4 non-hematological adverse events occurred in 5 pts. Median PFS for evaluable pts were 476 days (95% CI, 322 -) by PC analysis, and 464 days (95%CI, 308 -) by ITT analysis. Advanced stage was an unfavorable factor affecting ORR (Odds ratio = 0.151, P=0.0474). In PC analysis, PFS was significantly associated with FLIPI (low vs. intermediate + high), with hazards ratio of 2.607. FLIPI at re-staging retained a predictive power for PFS (log-rank test, P=0.0037). In 33 pts pretreated with R, ORR was 64% with 39% CR. Median PFS of the R pretreated pts was a little shorter than that of pts without R (421 days vs. 532 days; log-rank test, P=0.3722). There were no correlations between PK parameters and ORR (15 pts). However, PFS of pts showing higher R serum levels(> 450 μ g/mL of C max level) was longer than that of lower R levels (log-rank test, P= 0.0176). Conclusions: Therapy of eight weekly infusions of R is effective in relapsed or refractory pts with indolent B-NHL regardless of prior R treatment. FLIPI can predict the benefit of this 8 weekly monotherapy. Median PFS with 8 weekly infusions appears to be longer (476 days vs. 245 days) than that with 4 weekly infusions of our previous study (Ann Oncol. 2002;13:928). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Seminar Presentation by Zenyaku Kogyou Co., Ltd.
Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC
Authors: J.J. Knox, C.H. Barrios, T.M. Kim, T. Cosgriff, V. Srimuninnimit, K. Pittman, R. Sabbatini, S.Y. Rha, T.W. Flaig, R.D. Page, J.T. Beck, F. Cheung, S. Yadav, P. Patel, L. Geoffrois, J. Niolat, N. Berkowitz, M. Marker, D. Chen, R.J. Motzer
Journal: Annals of Oncology (2017)

BackgroundRECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points.Patients and methodsPatients received either first-line everolimus followed by second-line sunitinib at progression (n = 238) or first-line sunitinib followed by second-line everolimus (n = 233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored.ResultsAt final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1–26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0–29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9–1.6]. Median OS was 22.4 months (95% CI 18.6–33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8–33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1; 95% CI 0.9–1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences.ConclusionsResults of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals.Clinical Trials numberClinicalTrials.gov identifier, NCT00903175
Modulation of candidate therapy targets in regionally advanced prostate cancer by androgen ablation and docetaxel.
Authors: V. Tzelepi, E. Efstathiou, P. Troncoso, C. A. Pettaway, A. Hoang, C. Logothetis, L. C. Pagliaro
Journal: Journal of Clinical Oncology (2010)

4663 Background: The purpose of our study was to determine the modulation of candidate therapy resistance signaling pathways following 1-year androgen ablation (AA) and docetaxel (DOC) relative to no treatment in regionally advanced prostate cancer. The study complements findings following short term therapy (Efstathiou et al, JCO 25(18S):5066, 2007). Methods: Tissue microarrays were constructed from prostatectomy specimens of 29 patients who received AA and three cycles of DOC and 47 untreated patients (CTR). We analyzed expression of (1) epithelial markers: proliferation (ki67), apoptosis (bcl2), neuroendocrine differentiation (chromogranin, synaptophysin) (2) stromal-epithelial interaction markers: angiogenesis (VEGF), Hedgehog (Hh) pathway (Shh, Gli1, Patched 1), androgen synthesis (Cyp17A, SRD5a1) and androgen signaling [androgen receptor (AR), phosphorylated AR (pAR)] by immunohistochemistry. Percentages of positive epithelial and stromal cells were recorded seperately. Results: Significant modulation of stromal-epithelial interaction pathways was observed. Enhancement of Hh signaling following treatment was evidenced by nuclear transcription factor Gli1 (mean, epithelial: AA/DOC:93.7, CTR:15.3, p<0.001, stromal: AA/DOC:65.2, CTR:3.2, p<0.001) and epithelial Patched 1 (AA/DOC:61.9, CTR:34.3, p<0.001). Increased expression of androgen synthetic enzymes included Cyp17A (epithelial: AA/DOC:93.7, CTR:73.6, p=0.004, stromal: AA/DOC:78.6, CTR:34.7, p<0.001) and SRD5a1 (epithelial: AA/DOC:94.4, CTR:26.2, p<0.001 and stromal: AA/DOC:81.7, CTR:16.2, p<0.001). Epithelial pAR expression was enhanced in treated (31.1) compared to untreated tumors (5.1, p<0.001). Conclusions: These observations support the hypothesis that Hh signaling and transition from endocrine to intracrine androgen signaling are implicated in resistance to standard therapy and provide support for the development of combinatorial microenvironment targeting strategies. Moreover, temporal heterogeneity is suggested by the absence of AR amplification following three months of AA (Efstathiou et al, JCO 25(18S):5066, 2007) that must be accounted for in therapy development. No significant financial relationships to disclose.
The effect of cetuximab and panitumumab on primary progressive cancer to chemotherapy.
Authors: A. Shaker, V. Ranpura, S. Wu
Journal: Journal of Clinical Oncology (2011)

e14066 Background: The addition of antibodies against epidermal growth factor receptor including cetuximab and panitumumab to chemotherapeutic agents have clinical activity for many advanced cancers, which can be divided into primary and secondary progressive diseases according to sensitivity to chemotherapy. The effect of these antibodies on primary progression to chemotherapy is not clear. We performed a systemic review and meta-analysis of published randomized controlled trials (RCT) to determine their effect on the risk of primary progressive disease (PPD). Methods: Databases including PubMed and abstracts presented at the ASCO conferences and the European Society of Medical Oncology until December, 2010 were searched to identify relevant studies. Eligible studies included phase II and III RCTs in which the combination of cetuximab or panitumumab with chemotherapy was compared with chemotherapy alone. PPD was defined as progressive disease as the best response according to RECIST criteria. Summary incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a fixed-effects or random-effects model. Results: A total of 5,786 patients from 10 trials were included in the analysis. Overall, the addition of cetuximab or panitumumab to chemotherapy significantly increased response rate (RR 1.46, 95% CI: 1.16-1.86; p=0.002) and decreased the rate of stable disease (RR 0.88, 95% CI: 0.79-0.98; p=0.022), but did not significantly decrease the risk of PPD (incidence 21.6% vs 23.1%, RR: 0.89; 95% CI: 0.77-1.04, p=0.13). The effect on PPD did not significantly vary among tumor types (p=0.14) and differ between cetuximab and panitumumab (p=0.75). For colorectal cancer, there was a trend favoring a reduced risk of PPD in K-Ras wild type (RR 0.71, 95% CI: 0.47-1.09, p=0.12), but not in mutant K-Ras (RR 0.97, 95% CI: 0.51-1.86, p=0.93). Notably, cetuximab and panitumumab significantly reduced the risk of PPD associated with irinotecan-based chemotherapy (RR 0.71, 95% CI: 0.63-0.80, p=0.017) but not with oxaliplatin-based chemotherapy (RR 1.09, 95% CI: 0.89-1.35). Conclusions: Cetuximab or panitumumab may be effective in primary progressive cancers to a specific chemotherapeutic regimen.
Impact of age on sexual preservation after prostate brachytherapy: A prospective evaluation in men without erectile dysfunction.
Authors: Tristan Brahmi, Ariane Lapierre, Hamza Samlali, Imad Eddine Selmaji, Corina Udrescu, Alain Ruffion, Olivier Chapet
Journal: Journal of Clinical Oncology (2016)

105 Background: Sexual preservation is an important issue in the treatment of localized prostate cancer. In this study, we evaluate the long-term incidence of erectile dysfunction (ED) after prostate brachytherapy (PBT), in men without ED. Methods: Between 2006 and 2012, prospective data of patients treated with brachytherapy for a low or intermediate-risk prostate cancer (d’Amico classification), were collected. Erectile function (EF) was assessed with IIEF5 score (5-Item Version of the International Index of Erectile Dysfunction) at six weeks and then every year during the follow-up. No ED was defined by an IIEF5 score ≥ 22/25 and a mild ED by a score between 17 and 21. Results: Up to this point, 70 patients, with an initial IIEF5 ≥22, were analyzed with a mean follow-up of 46.5 months. At 6 weeks and 1, 2, 3 and 4 years after brachytherapy, mean IIEF5 scores in all 70 patients were 24.6, 21.3, 19.7, 19.1 and 17.3, respectively. In ≤ 65 years old group, the scores were 24.7, 20.9, 21.3, 21.1, 19.7 and 20, respectively. In &gt; 65 years old group, the scores were 24.6, 21.8, 21.3, 18.1, 18.2 and 14.9, respectively. The evaluation of ED according to age groups is represented in the table. Conclusions: At 4 years of follow-up after brachytherapy, patients 65 years old and younger have an EF preservation rate &gt;80% with 50% of them having no ED. For patients older than 65 years, the rate of EF preservation decreased at 50% after 4 years of follow up with only few of them having no ED. This difference between the 2 groups of age is probably more related to an age effect than a brachytherapy toxicity. At the time of the meeting, more data and results will be available. [Table: see text]
Outcomes for a multi-institutional cohort of patients treated with intra-operative radiation therapy for advanced or recurrent renal cell carcinoma.
Authors: Jonathan J. Paly, Christopher Leigh Hallemeier, Peter J. Biggs, Andrzej Niemierko, Falk Roeder, Rafael Martinez-Monge, Jared Myers Whitson, Felipe A. Calvo, Gerd Fastner, William Wong, Rodney J. Ellis, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2013)

442 Background: For patients with advanced or locally recurrent (LR) renal cell carcinoma (RCC), the role of intra-operative radiation therapy (IORT) remains controversial. We analyzed outcomes in a multi-institutional cohort of patients with RCC who received IORT. Methods: Between 1985 and 2010, 98 patients were treated with IORT for advanced or LR RCC at 9 institutions. We collected demographic, clinical, treatment, and outcomes data for all patients. Overall (OS), disease specific (DSS), and disease-free survival (DFS) was estimated using the Kaplan-Meier method. A multivariate Cox hazards regression was used to test significance. Results: IORT was delivered at nephrectomy for advanced disease (28%) or during resection of LR RCC in the renal fossa (72%). 69% of patients were male and mean age at RCC diagnosis was 57. At initial nephrectomy, primary T-stage was 17% T1, 12% T2, 55% T3, and 16% T4. Prior to IORT, 87% had visibly complete surgical resection of tumor. Mean IORT dose delivered was 14.7Gy (range 9-20Gy). Average post-op hospitalization was 10.7 days. Median follow-up after IORT was 1.6 years. OS at 1 and 5 years after IORT was 69% and 37% for advanced patients and 94% and 55% for LR patients, respectively. DFS at 1 and 5 years was 72% and 39% for advanced patients and 96% and 52% for LR patients, respectively. DSS at 1 and 5 years was 72% and 41% for advanced patients and 96% and 60% for LR patients, respectively. For the entire cohort, higher IORT dose (HR 1.3, p &lt; 0.001), positive initial node status (HR 2.9-3.6, p &lt; 0.01), and presence of sarcomatoid features (HR 3.7-6.9, p &lt; 0.05) had a significant association with decreased OS, DFS and DSS. Patients who received adjuvant systemic therapy after IORT showed decreased DSS (HR 2.4, p = 0.03). When analyzing LR tumors alone, positive margin (HR 2.6, p = 0.01) was associated with decreased OS. Conclusions: We report on the largest known cohort of patients with RCC managed with IORT and we have identified factors associated with survival. Outcomes in our cohort with LR RCC treated with local resection and IORT compare favorably to similar groups treated with resection alone suggesting improved DSS may be possible with IORT.
Development of a guidance for including patient-reported outcomes (PROs) in post-approval clinical trials of oncology drugs for comparative effectiveness research (CER).
Authors: E. M. Basch, A. P. Abernethy, C. D. Mullins, M. R. Tiglao, S. R. Tunis
Journal: Journal of Clinical Oncology (2011)

6000 Background: Although an FDA guidance is available to direct the development and inclusion of PROs in preapproval clinical research towards drug approval and labeling, no such guidance exists in the post-market CER context. Because the clinical setting and stakeholders in CER differ from the preapproval space, different methodological and practical considerations are necessary. The aim of this project is to develop specific recommendations for capturing the patient perspective in post-market oncology trials and other studies that fall into the general category termed CER. Methods: A semi-structured questionnaire pertaining to the use of PROs in CER was developed based on a review of scientific literature and consultation with PRO study methodologists. In-depth interviews were conducted using these questions with 15 individuals from the clinical research, clinical practice, regulatory, payer, and patient communities. Based on interview responses, a list of potential guidance topics was developed. The Center for Medical Technology Policy convened a multidisciplinary working group of leading medical researchers in PROs, ePRO consultants, and patient advocates to discuss these topics and develop an outline of best practice recommendations for integrating PROs in CER. Results: A series of recommendations focused on establishing standards for the use of PROs in CER were developed. These recommendations address selection of appropriate measures; inclusion of a “core minimum item set” across all oncology CER trials; and inclusion of items which assess symptoms, global QOL, perceived value of care, and treatment compliance. The recommendations also provide guidance for how to implement PROs in real-world studies and minimize missing data. Conclusions: The patient perspective is an essential component of CER. PRO methods used in CER differ from the preapproval context. For improved consistency across trials, a guidance is being developed which identifies a standard core item set to be considered for use across all oncology CER studies.
Persistent kallikrein 5 activation induces atopic dermatitis-like skin architecture independent of PAR2 activity
Authors: Yanan Zhu, Joanne Underwood, Derek Macmillan, Leila Shariff, Ryan O'Shaughnessy, John I. Harper, Chris Pickard, Peter S. Friedmann, Eugene Healy, Wei-Li Di
Journal: Journal of Allergy and Clinical Immunology (2017)