tbuckley/cabot-search huggingface dataset:
P05.06 Hearing preservation after gamma knife radiosurgery for cerebellopontine angle meningiomas
Authors: K Abdel Karim, W A Reda, A M N El Shehaby, R Emad, S R Tawadros, A Nabeel
Journal: Neuro-Oncology (2018)

The presence of the hearing apparatus in the vicinity of cerebellopontine angle (CPA) meningiomas makes hearing function, theoretically, at risk during gamma knife treatment. The two most common tumors in the CPA are vestibular schwannomas followed by meningiomas. To assess the hearing function after gamma knife treatment of CPA meningiomas and assess factors affecting the hearing outcome. Additionally, we opted to compare these results with those after gamma knife treatment of vestibular schwannomas (VS), since most of information on hearing outcome after SRS (stereotactic radiosurgery) comes from reports on VS treatment. Hearing preservation, to the best of our knowledge, has never been separately addressed in studies involving gamma knife radiosurgery for CPA meningiomas. In this study, we included patients that underwent a single session of gamma knife radiosurgery between 2002 and 2014. The patients were divided into two groups. Group A included 66 patients with CPA meningiomas with serviceable hearing and tumor extension in to the region centred on internal auditory meatus. Group B included 144 patients with vestibular schwannomas with serviceable hearing. All the patients had serviceable hearing before treatment (Gardner-Robertson (GR) grade 1 and 2). The median prescription dose was 12 Gy (10–12 Gy) in both groups. The median follow up of Groups A and B was 42 months (6–149 months) and 49 months (6–149 months), respectively. At the last follow up, the tumor control rate was 97% and 94%, in Groups A and B, respectively. Hearing preservation was determined to be maintained serviceable hearing according GR hearing score. The hearing preservation rate was 98% and 66% and the 7-year serviceable hearing preservation rate was 75% and 56%, respectively among both groups. In Group A the median maximum cochlear dose in the patients with preserved and worsened hearing was 6 Gy and 5.5 Gy, respectively. No statistical significance was found. In group B factors affecting hearing preservation were hearing grade, tumor diameter, cochlear dose and follow up duration. The only determinant of hearing preservation between both groups was tumor type. Gamma knife radiosurgery for CPA meningiomas provides excellent hearing preservation in addition to high tumor control rate. Hearing outcome better with CPA meningiomas than VS. Cochlear dose critical threshold maybe higher than previously reported. Further prospective studies on determinants of hearing outcome after GKS including cochlear dose.
Innovative approach to determine overall survival (OS) benefit for orphan diseases using case match control analyses (CMCA): The PROPEL experience of pralatrexate in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL).
Authors: Owen A. O'Connor
Journal: Journal of Clinical Oncology (2017)

7521 Background: The challenges in conducting randomized studies in orphan diseases poses limitations on our ability to identify the most promising treatments. Randomized studies in this setting can take protracted periods of time to complete, can be very expensive while not offering the promise of significant commercial return, and could become irrelevant as the pace of scientific advancement continues. The majority of drugs approved in this setting are often approved on surrogate end-points like progression free survival (PFS) or complete response (CR) rates in single arm studies. CMCA are statistically stronger than single arm studies, and can be highly informative in this setting. Methods: We established an integrated international database of patients with R/R PTCL to clarify the OS advantage of pralatrexate using original data from the PROPEL study, an international, multicenter phase II study in patients with R/R PTCL. The propensity score was used to match cases and controls. Cases were matched based on histology, number of previous treatments received, age at diagnosis and sex. Results: With 1:1 ratio match, we identified 83 cases and 83 controls. In total, 83 patients out of 109 treated on the PROPEL study were successfully matched. OS was plotted for each of the two study populations. The survival curves for the control population were found to be nearly identical to that reported for this population from other datasets. The overall survival was 4.04 months (95% CI 2.83, 5.78), which is consistent with historical controls describing this population. The median OS in for the pralatrexate treated cohort in this analysis was 16.6 months (95% CI: 11.99-25.56). The OS was a highly statistically significant difference between these two populations, with a hazard ratio of 0.426 (95% CI: 0.296-0/61). This difference held up for each of the major histologic subsets, including PTCL-NO and angioimmunoblastic PTCL. Conclusions: This approach can be used to better understand how new drugs in orphan diseases perform in heterogeneous patient populations. Clinical trial information: NCT00364923.
Prognostic importance of p16 status for women with vulvar squamous cell carcinoma (SCC) treated with radiotherapy.
Authors: Larissa Janeen Lee, Brooke E. Howitt, Esther Oliva, Hongkai Zhang, Paul J. Catalano, Christopher Crum, Paula Bu, Nicole Cimbak, Rebecca Demaria, Rita Murphy, Neil S. Horowitz, Ursula A. Matulonis, Andrea Lyn Russo
Journal: Journal of Clinical Oncology (2017)

5599 Background: To evaluate the association between p16 status and in-field recurrence (IFR), progression-free (PFS) and overall (OS) survival in patients with vulvar SCC treated with radiation (RT) with or without surgical resection. Methods: In a multi-institutional retrospective cohort study, we identified 105 women with vulvar SCC who received RT between 1985-2011. Immunostaining for p16 was performed on archival tumor tissue using the Leica Bond III staining platform. Histopathology and p16 stains were reviewed by pathologists with expertise in gynecologic cancer; the intensity and extent of p16 staining in tumor cells were classified as negative (focal, weak, patchy) or positive (moderate or strong diffuse linear positive). Actuarial estimates of PFS, OS and IFR were calculated using the Kaplan-Meier method and compared by the logrank test. Multivariable analysis (MVA) was performed using the Cox proportional hazards model. Results: Patients with p16-positive disease were significantly younger at diagnosis (median 67 vs. 77 years) and were more likely to be current smokers (51% vs. 0%) and to have received concurrent chemotherapy (68% vs. 47%, all p&lt;0.05). FIGO stage distribution, RT intent and median RT doses were similar by p16 status. With a median follow-up of 61 months, 5-year PFS and OS rates were 35% and 40%, respectively. Women with p16-positive tumors had significantly better 5-year PFS and OS rates than those with p16-negative tumors (61% and 23%, p&lt;0.01 and 64% and 29%, p=0.01, respectively). The 5-year IFR rate was also lower for those with p16-positive disease (17% vs. 65%, p&lt;0.01). On univariate analysis, use of concurrent chemotherapy was not associated with PFS (p=0.5), OS (p=0.3) or IFR (p=0.8). On MVA adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.57, 95% CI 0.33-0.97) and lower IFR (HR 0.24, 95% CI 0.09-0.6). Conclusions: In a multi-institutional setting, women with p16-positive vulvar SCC treated with RT had a lower IFR rate and longer survival than those with p16-negative disease. The magnitude of prognostic importance of p16 status is similar to that seen in oropharyngeal, anal and cervical cancers treated with RT.
Exploration of baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICI) or cytotoxic chemotherapy (CCT).
Authors: Dickran Garo Kazandjian, Yutao Gong, Haykanush Kazandjian, Richard Pazdur, Gideon Michael Blumenthal
Journal: Journal of Clinical Oncology (2018)

3035 Background: Previous studies have suggested the importance of dNLR and LDH as prognostic markers and indicators of inflammation in cancer and other inflammatory diseases. More recently, the lung immune prognostic index (LIPI), the combination of dNLR and LDH, was found to be associated with progression free survival (PFS) and overall survival (OS) in pts with NSCLC treated with ICI but not CCT suggesting its potential use as a predictive marker. We performed an exploratory retrospective analysis of LIPI on pooled clinical trial data from studies evaluating ICI in 2nd line mNSCLC submitted to the FDA. Methods: We identified 5 randomized, second line trials (N = 3399) evaluating ICI versus docetaxel submitted to FDA between 2014-2017 for mNSCLC. Only pts with available dNLR/LDH data were included (71.8%). LIPI scores were calculated based on dNLR and LDH values per Mezquita et al. (JAMA Oncol. 2018). Univariate and multivariate COX proportional PFS and OS hazard ratios (HR) were generated for dNLR, LDH, and other major covariates including age, smoking status, histology, and ECOG. Median PFS and OS estimates based on the LIPI score (0,1, or 2) were generated using the Kaplan–Meier method. Results: In the final analysis, 1368 ICI and 1072 CCT were evaluable for low (0), intermediate (1), and high (0) LIPI (TABLE). Conclusions: This exploratory retrospective analysis indicates that LIPI may be a prognostic biomarker for both ICI and CCT for 2nd line mNSCLC. LIPI (n) ICI CCT 0 (620) 1 (583) 2 (165) 0 (380) 1 (508) 2 (184) OS HR (95%CI) 1.71 (1.47,2.00) 2.91 (2.36, 3.59) 1.45 (1.23, 1.71) 2.05 (1.67, 2.53) months (95%CI) 15.6 (13.5, 17.6) 8.9 (7.9, 9.7) 4.53 (3.1, 6.2) 10.5 (9.2, 11.8) 7.89 (7.0, 8.7) 5.29 (4.3, 6.3) PFS HR (95%CI) 1.34 (1.17, 1.54) 1.7 (1.38, 2.1) 1.37 (1.18, 1.60) 1.79 (1.46, 2.20) months (95%CI) 5.7 (4.6, 6.2) 3.5 (2.7, 4.2) 2.1 (1.7, 2.3) 5.4 (4.7, 6.1) 3.7 (3.2, 4.1) 2.4 (2.1, 3.4)
Abstract 18583: Use of a Metronome to Improve Quality of In-Hospital Cardiopulmonary Resuscitation
Authors: Jeff Bolstridge, Heather M Delaney, Renée I Matos
Journal: Circulation (2016)

Introduction: Survival is known to be poor for both out-of-hospital and in-hospital cardiac arrest (IHCA). High-quality cardiopulmonary resuscitation (CPR) is the primary component in influencing r...
Family quality of life (FQOL) of patients with cancer and caregivers.
Authors: Jamie Goldman, Mary S. Dietrich, Nancy L. Wells, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2017)

e21568 Background: There are no validated tools assessing FQOL in the cancer population. We developed a 32-item cancer specific tool (CFQOL) comprised of general and cancer specific subscales directed towards the patient and caregiver. Domains included family interactions, roles, communication, and emotional support. Methods: 150 patient-caregiver dyads in a general oncology population completed the CFQOL, SF36, FACT, BC-FQOL, and FACE IV tools. Exploratory factor analysis was used to identify the underlying structure. We compared the CFQOL with validated measures using Spearman's Rho. Results: Characteristics: Patients - median age 59, 57% male, 96% Caucasian, and 65% in treatment. Caregivers - median age 56, 67% spouses/partners and 86% primary caregiver. The analysis revealed a single underlying structure for both the general and cancer-specific domains (Cronbach's α 0.96 and 0.94 respectively). Median scores for patients on both measures were 4.5 out of 5 (IQR: 4-5); caretaker scores were lower (median: 4.2, IQR: 3.5-4.2, p &lt; .05). As expected, convergent validity was supported with those tools focusing on similar themes to those in the CFQOL, and items involving physical aspects demonstrated divergent validity but were not statistically significant (table 1). Conclusions: The CFQOL is a brief, valid tool for assessing multiple constructs relevant to FQOL in the cancer patient population. Patterns of correlations were similar for general and cancer subscales questioning the need for both sub-scales. Further validation and exploration of sensitivity to change is indicated. [Table: see text]
SAT0125 The impact of selected comorbidities on treatment outcome in patients with rheumatoid arthritis: an exploratory cohort study.
Authors: A. Emamifar, I. M. Jensen Hansen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with Rheumatoid Arthritis (RA) may present with various comorbidities resulting in worse treatment response.[1-2] <h3>Objectives</h3> To investigate the impact of selected comorbid diseases on RA outcome with the aim of Disease Activity Score in 28 joints-C-Reactive Protein (DAS28-CRP). <h3>Methods</h3> All our RA patients were included in this study. Patients' demographics, serology results and DAS28-CRP at the time of diagnosis and after 4 months of treatment initiation were collected. Patients' electronic hospital records were evaluated for a positive history of thyroid diseases, Diabetes Mellitus (DM), primary hyperparathyroidism, vitamin B12 deficiency and presence of other diagnosed autoimmune diseases. <h3>Results</h3> 1035 RA patients were included. 63.4% were female, mean of age 67.1 years, mean of disease duration 9.6 years, 58.6% rheumatoid factor positive and 51.3% anti-cyclic citrullinated peptide positive. The observed prevalence of thyroid diseases was 11.8%, DM 10.4%, primary hyperparathyroidism 2.8%, vitamin B12 deficiency 5.8%, and other diagnosed autoimmune diseases 1.6%. There were significant associations between presence of thyroid diseases and female gender (p&lt;0.001); DM and greater age (p&lt;0.001); primary hyperparathyroidism and longer disease duration (p=0.002); other diagnosed autoimmune diseases and antinuclear antibody positivity (p&lt;0.001). RA patients with thyroid diseases (p=0.001) and other comorbid autoimmune diseases (p&lt;0.001) had significantly poorer initial response to the RA treatment compared to patients with isolated RA. Univariate analyses revealed that age, presence of thyroid diseases, presence of other diagnosed autoimmune diseases and DAS28-CRP at the time of diagnosis were significantly associated with ∆DAS28-CRP. Additionally, multivariate analysis demonstrated that ∆DAS28-CRP deterioration was significantly correlated to the presence of thyroid diseases (unstandardized regression coefficient (standard error);-0.188(0.088),p=0.030) and presence of other diagnosed autoimmune diseases (-0.537(0.208),p=0.010). (table1) <h3>Conclusions</h3> RA patients are at increased risk of specific comorbidities with possible impact on the treatment outcome. The authors, therefore, recommend to do periodical assessment of comorbidities to diagnose concurrent comorbid diseases as early as possible. <h3>References:</h3> [1] Emamifar A, et al. Thyroid disorders in patients with newly diagnosed rheumatoid arthritis is associated with poor initial treatment response evaluated by disease activity score in 28 joints-C-reactive protein (DAS28-CRP): An observational cohort study. Medicine (Baltimore) 2017;96:e8357. [2] Emamifar A, et al. Patients with newly diagnosed Rheumatoid Arthritis are at increased risk of Diabetes Mellitus: An Observational Cohort study. Acta Reumatol Port 2017 [Epub ahead of print]. <h3>Disclosure of Interest:</h3> None declared
Association between progression-free survival (PFS) rate (PFSR) and overall survival (OS) in LUME-Meso, a study of nintedanib (N) vs. placebo (P) in combination with first-line pemetrexed/cisplatin (PEM/CIS) in patients (pts) with malignant pleural mesothelioma (MPM).
Authors: Nick Pavlakis, Federica Grosso, Nicola L. Steele, Anna K. Nowak, Silvia Novello, Sanjay Popat, Laurent Greillier, Martin Reck, Tom John, Paul Taylor, Natasha B. Leighl, Giovanni Luca Ceresoli, Jens Benn Sørensen, David Planchard, Brett Gordon Maxwell Hughes, Julien Mazieres, Mark A. Socinski, Ute von Wangenheim, Jose Barrueco, Giorgio V. Scagliotti
Journal: Journal of Clinical Oncology (2018)

8568 Background: We evaluated the relationship between PFSR and OS in the Phase II part of LUME-Meso, a double-blind, placebo-controlled study that showed improved PFS (primary endpoint; hazard ratio [HR] = 0.56; 95% confidence interval [CI]: 0.34–0.91; p = 0.017), for N vs P; for OS HR = 0.77; 95% CI 0.46–1.29. Methods: Pts with unresectable MPM (ECOG PS 0–1), stratified by histology (epithelioid/biphasic), were randomized 1:1 to receive ≤6 cycles PEM (500 mg/m2)/CIS (75 mg/m2) on Day 1 + N or P (200 mg bid on Days 2–21), followed by N or P monotherapy maintenance. PFSR was defined as the proportion of pts who did not meet criteria for progressive disease (PD) at the specified time point (a ‘landmark analysis’). PFSR was assessed at 6 (PFSR6) and 8 (PFSR8) months. The association with OS was then evaluated based on the progression status at the landmark. Pts who died prior to the landmark were excluded from analysis. Results: 87 pts were randomized (N: 44; P: 43). The PFSR6 analysis included 71 pts (28 with PD and 43 without PD); subsequently there were 52 deaths. The PFSR8 analysis included 63 pts (32 with PD and 31 without PD); subsequently there were 45 deaths. There were more pts treated with N vs P who had not progressed at 6 (63% vs 37%) and 8 (71% vs 29%) months. Both PFSR6 and PFSR8 predicted OS (HR for PFSR6: 0.19; 95% CI: 0.11–0.35; HR for PFSR8: 0.18; 95% CI: 0.09–0.37). In the PFSR6 analysis, median OS was 22.8 months (95% CI: 15.6–28.4) in pts without PD prior to the landmark vs 6.1 months (95% CI: 3.3–7.0) in pts with PD prior to the landmark. In the PFSR8 analysis, median OS was 23.9 months (95% CI: 15.6–28.4) in pts without PD prior to the landmark vs 5.0 months (95% CI: 3.9–11.6) in pts with PD prior to the landmark. PFSR also predicted OS in pts with epithelioid histology at 6 months (n = 63; HR = 0.19; 95% CI: 0.10–0.36) and at 8 months (n = 57; HR = 0.20; 95% CI: 0.09–0.40). Conclusions: In our study in pts with MPM, landmark PFSR at 6 and 8 months predicts OS. These data are consistent with previously published findings. Phase III of LUME-Meso is ongoing (NCT01907100). Clinical trial information: NCT01907100.
Analysis of tumor samples from SOLO2: Concordance of <i>BRCA</i> mutation (<i>BRCA</i>m) detection in tumor vs. blood and frequency of <i>BRCA</i>-specific loss of heterozygosity (LOH) and loss of function somatic mutations.
Authors: Darren R. Hodgson, Simon Patrick Dearden, Jessica S Brown, Tsveta Milenkova, Jerry S Lanchbury, Michael Perry, Alexander Gutin, Victor Abkevich, Kirsten Timms, Elizabeth Harrington, J Carl Barrett, Zhongwu Lai, Brian Andrew Dougherty, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2018)

12017 Background: The PARP inhibitor olaparib is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer (PSR OC) in the USA based on pivotal studies (Study 19, SOLO2) that demonstrated a progression-free survival benefit of olaparib (Ledermann et al 2012, 2016; Pujade-Lauraine et al 2017). Patients (Pts) with BRCAm benefit most from olaparib, but questions remain on the functional equivalence of germline (g) and somatic BRCAm and the frequency and impact of BRCA-gene-specific LOH (Dougherty et al 2017; Maxwell et al 2017). Methods: Blood and tumor samples from 241 pts with gBRCAm in a Phase III trial of olaparib maintenance monotherapy (300 mg bid tablets; SOLO2; NCT01874353) were analyzed. A concordance analysis of gBRCAm and tumor BRCAm (tBRCAm) status was conducted; gene-specific LOH for BRCA1 and BRCA2 and assessment of homologous recombination deficiency (HRD) using Myriad HRD score (Tumor BRACAnalysis CDxTM test) was also determined. Results: tBRCAm testing was evaluable in 241/289 gBRCAm pts. There was 98% and 100% concordance between pts’ BRCA1m and BRCA2m status, respectively, in tBRCAm vs gBRCAm. 13/241 (5.4%) of gBRCAm were due to large rearrangements (exonic insertions or deletions), of which 4 involving BRCA1 were not detected in the tumor. A further deleterious somatic mutation in BRCA1 was identified in 1/241 pts with gBRCAm tumors. This was a large rearrangement in BRCA1, causing an exon 1–22 deletion that likely constituted the second ‘hit’ in this tumor. Of 210 evaluable LOH samples, 144/144 (100%) gBRCA1m and 65/66 (99%) gBRCA2m tumors had gene-specific LOH. The pt without BRCA2 LOH had an HRD score of 53, was progression-free for 911 days and remained on olaparib at data cut-off. Conclusions: Very high concordance between tBRCA and gBRCA testing is demonstrated, supporting wider implementation of tBRCA testing in addition to availability of gBRCA testing to determine BRCAm status in OC. Deleterious somatic BRCAm almost never arises in gBRCAm tumors, in keeping with BRCA loss being a driver of tumorigenesis in OC. In PSR gBRCAm pts, gene-specific LOH in tumors is almost universal. Clinical trial information: NCT01874353.
Liquid biopsy to predict benefit from rechallenge with cetuximab (cet) + irinotecan (iri) in RAS/BRAF wild-type metastatic colorectal cancer patients (pts) with acquired resistance to first-line cet+iri: Final results and translational analyses of the CRICKET study by GONO.
Authors: Daniele Rossini, Chiara Cremolini, Elena Conca, Marzia Del Re, Adele Busico, Filippo Pietrantonio, Francesca Bergamo, Romano Danesi, Mariaelena Casagrande, Emiliano Tamburini, Emanuela Dell'Aquila, Antonia Strippoli, Gianluca Masi, Giuseppe Tonini, Francesca Negri, Domenico C. Corsi, Paola Ermacora, Rossana Intini, Alfredo Falcone, Daniele Santini
Journal: Journal of Clinical Oncology (2018)

12007 Background: CRICKET (NCT02296203) was designed to investigate the activity of the rechallenge with cet and iri as 3rd-line treatment in RAS/BRAF wild-type mCRC pts with acquired resistance to 1st-line cet- and iri-based therapy. The role of liquid biopsies as a tool to identify pts more likely to benefit from this strategy was investigated. Methods: Eligibility criteria included RAS/BRAF wild-type status on tissue samples; prior 1st-line iri-based, cet-containing regimen with at least RECIST partial response (PR), 1st-line PFS ≥6 months, and progression within 4 weeks after the last cet; prior 2nd-line oxaliplatin- and bevacizumab-based treatment. Pts received 3rd-line cet + iri until PD. The primary endpoint was response rate (RR) according to RECIST v1.1. With p0 = 5%, and p1 = 20%, 1-sided-α and β errors of 0.05 and 0.20, 27 pts were required. The null hypothesis can be rejected if responses are observed in ≥ 4 pts. Liquid biopsies were collected at the rechallenge baseline. ctDNA was analyzed with ddPCR for specific RAS/BRAF mutations (mut), and then by ultra-deep NGS with Ion Torrent S5 XL. Results: Between Jan 2015 and Jun 2017, 28 pts were enrolled in 9 centres. The primary endpoint was met. Six PRs (two unconfirmed) and 9 disease stabilizations (RR: 21%,95%CI: 10-40%, disease control rate: 54%,95%CI: 36-70%) were reported. RAS mut were found in liquid biopsies collected at the rechallenge baseline in 12 (48%) out of 25 evaluable pts (6 KRAS G12D, 5 KRAS G12V with 1 harboring also Q61H and 1 NRAS Q61L). No RAS mut were detected in samples from pts who achieved a confirmed PR. Pts with RAS wt ctDNA, had significantly longer PFS than those with RAS mut ctDNA (mPFS: 3.9 vs 1.9 mos; HR: 0.48 [95%CI 0.20-0.98], p = 0.048). No BRAF or PIK3CA mut were found. Conclusions: This is the first prospective demonstration of the activity of rechallenge with cet + iri in some mCRC pts initially sensitive and then resistant to first-line iri- and cet-based therapy, with no RAS/BRAF mut in pre-treatment liquid biopsies. Partially funded by Merck Serono SpA. Clinical trial information: NCT02296203.