tbuckley/cabot-search huggingface dataset:
Prognostic impact of SOX9 in stage II colon cancer: Results from a large nationwide cohort.
Authors: Torben Hansen, Natacha D. Trabjerg, Sanne Kjaer-Frifeldt, Ann Christina Eriksen, Jan Lindebjerg, Lars Henrik Jensen, Anders Kristian Moeller Jakobsen, Flemming Brandt Sørensen
Journal: Journal of Clinical Oncology (2020)

183 Background: Up-regulation of the transcription factor SOX9 has been described in colon cancer, and it has been argued that differences in the expression levels dictates cell proliferation. The aim of the present study was to analyze the prognostic impact of SOX9 in patients with stage II colon cancer. Methods: Individual patient data and formalin fixed paraffin embedded tumor tissue were collected from a large unbiased, population-based cohort, representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The SOX9 expression was evaluated by immunohistochemistry on whole tumor sections. Patients were classified into three groups dependent on the SOX9 expression gradient in the tumor: luminal, peripheral, and uniform for comparison with the clinical data. The endpoint was disease free survival (DFS). Results: A total of 1,153 patients were included. We detected an expression-dependent relationship between SOX9 and prognosis. Patients with tumors exhibiting a luminal expression pattern (N = 267, increasing SOX9 expression towards the luminal compartment of the tumor) were characterized by a significantly better DFS compared to the uniform (N = 846) and peripheral (N = 40) patterns, p = 0.0070. The five-year DFS rates were 74%, 67%, and 56%, respectively. Multiple Cox regression analysis, confirmed an independent prognostic advantage of the luminal SOX9 expression pattern, as compared to the uniform pattern, hazard ratio (HR) 0.7211 (95% confidence interval (CI) 0.5561-0.9351), p = 0.0137, whereas the possible disadvantage of the periphery pattern could not be verified, p = 0.1405. Conclusions: The present results support a prognostic impact of SOX9 in stage II colon cancer. The consequence of an altered SOX9 expression seems to differ between intra-tumoral compartments, and we propose that a gradient-dependent evaluation should be applied to provide the most clinically relevant information about this transcription factor.
Test of InheRET, an online tool to facilitate NCCN Guideline compliant referrals for cancer genetic counseling.
Authors: Lynn McCain, Kara J. Milliron, Amanda Cook, Lee Schroeder, James Arthurs, Diane M Harper, Susan Ernst, Philip Zazove, Jasmine Diana Parvaz, David Keren, Sofia Merajver
Journal: Journal of Clinical Oncology (2019)

1530 Background: Identifying the ~60 million unaffected persons in the US at risk for inherited cancers has the potential to reduce their cancer risk by up to 95%. However, most of these individuals are not identified currently because of multifactorial deficits in the 3-generation pedigree collection in clinical settings. Methods: Here we evaluated the impact InheRET, an online family history gathering and risk assessment reporting tool, has on facilitating National Comprehensive Cancer Network (NCCN) Guideline-compliant referrals for cancer genetic counseling/genetic evaluation by decreasing and/or removing the barriers of 1) in-clinic 3-generation family history collection, and 2) interpretation of the family and personal history in light of current NCCN Guidelines. Patients enrolled from primary care and specialty clinics completed the family health history from a web-enabled devices using InheRET Inherited Risk Evaluation Tool. Results: Of 255 enrolled patients, 78.4% completed the history form and, of these, 86.5% completed the feedback survey. 39.2% of primary care and 79.9% of specialty cancer genetics patients were found to be at increased risk. Patients with ≤ HS education ranked InheRET at 4.7/5.0 for Understandability and 3.33/5.0 for Ease of Use. Following the addition of clarifying directions, they ranked InheRET at 5.0 and 4.0, respectively. Pts. &lt;60 ranked InheRET between 3.5 and 3.8 on Ease of Use, while those 60-69 and 70+ ranked it 3.0 and 2.7, respectively, potentially reflective of lower technical skills. Age did not impact Understandability. In the cancer genetics clinic, 86% of pts. completed the online survey, in ~ 1 week, compared to paper forms, which required reminders, and &gt;4 weeks to obtain. Conclusions: In this pilot, InheRET accelerated appropriate referrals and efficient utilization of genetic counseling services; improvements to navigation are being implemented prior to dissemination.
Modeling causal associations between frailty components and mortality in older patients with cancer: A structural equation approach.
Authors: Florence Canoui-Poitrine, Claudia Martinez-Tapia, Frédéric Pamoukdjian, Simone Mathoulin-Pélissier, Matthieu Frasca, Elena Paillaud, Michael Bringuier, Etienne Brain, Jean-Philippe David, Marie Laurent, Sylvie Bastuji-Garin, Etienne Audureau
Journal: Journal of Clinical Oncology (2019)

e23021 Background: The independent prognostic value of both oncological and geriatric parameters is well-established in older cancer patients. Yet little is known about the causal pathways between them and how they may interact to affect mortality. Using structural equation modeling (SEM), we aimed to assess the direct and indirect impact of geriatric impairments and oncological parameters on mortality in older patients with cancer. Methods: Patients ≥70 years recruited in the ELCAPA cohort for geriatric assessment (GA), between 2007 and 2016, were included. The six following geriatric domains were assessed: function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support. SEM analysis tested prespecified relationships between geriatric and oncological characteristics (i.e. stage, cancer site and anti-cancer treatment) and their influence on 6- and 12-months mortality following GA. Model fit was assessed through Root Mean Squared Error of Approximation (RMSEA) and Tucker-Lewis Index (TLI). Results: This analysis included 1434 patients (mean age, 80 years (±5.6); female, 48%; 48% metastasis; main localizations: colorectal (19%), upper digestive tract (17%), and breast (17%)). The 6- and 12-months mortality were 56% and 68%, respectively. Significant direct paths to increased mortality were identified for functional impairment (standardized coefficient (SC): 0.37; p &lt; 0.001 and 0.32; p &lt; 0.001), poor nutritional status (SC: 0.11; p = 0.005 and 0.14; p = 0.001) and poor social support (SC = 0.07; p = 0.08 and 0.09; p = 0.02), along with tumor site, metastatic status and anti-cancer treatment. SEM additionally revealed the indirect effects on mortality of comorbidities, cognitive impairment and depression mediated through functional and nutritional status. Model fit was excellent (RMSEA = 0.036, TLI = 0.941). Conclusions: SEM analysis showed the direct effects of functional and nutritional impairments on mortality and also revealed their central mediating role in the indirect impact of comorbidities, depression and cognitive impairment on mortality. Clinical trial information: NCT02884375.
Impact of smoking cessation in locally advanced head and neck cancers undergoing radiation.
Authors: Ruth Lauren Sacks, Yong Cui, Maher A. Karam-Hage
Journal: Journal of Clinical Oncology (2019)

6068 Background: Multiple studies have highlighted the negative outcomes associated with smoking during radiation (XRT) for locally advanced head and neck cancer. However, there has been little research investigating the potential benefit of smoking cessation prior to XRT and the effect on response rates, relapse, distant metastases, secondary malignancies, and overall survival. Methods: We reviewed 680 patients at the University of Texas MD Anderson Cancer Center from 2005-2012 with locally advanced head and neck cancer undergoing XRT. 127 were referred to the Tobacco Treatment Program (TTP) based on provider referrals, self-referrals, or screening. Of those referred and retrospectively reviewed, 89 were identified as current smokers and 41 of them participated in the TTP for smoking cessation. Among these 89 patients, 50 patients (18 participated in the TTP) quit smoking prior to XRT and 29 patients (19 participated in the TTP) continued to smoke, which are referred to as Quitters and Smokers, respectively. 10 patients (2 participated in the TTP) had incomplete data and were excluded from further analysis. Results: Quitters had 100% complete response (CR) on initial assessment following XRT. 7/50 (14%) developed relapsed disease with 4 local recurrences (LR) and 3 distant metastases (DM). 6/50 (12%) developed secondary malignancies. By contrast, Smokers had 96.5% CR on initial assessment following XRT. 8/29 (27.5%) developed relapsed disease with 6 LR and 2 DM. 6/29 (20.6%) developed secondary malignancies. The median follow ups for Quitters and Smokers were 57.5 and 54 months with overall survival rates of 82% and 79%, respectively. Conclusions: Current smokers that achieved smoking cessation prior to XRT demonstrated lower rates of relapse, DM, and secondary malignancies compared to those that continued to smoke. Thus, smoking cessation is an integral part of head and neck cancer treatment and needs to be further incorporated in cancer care to improve cancer treatment outcomes. As a future direction, a comparable group of patients who did not smoke from the same time range will be compared for response rates, LR, DM, secondary malignancies, and survival.
Chemotherapy rechallenge or reintroduction (CTr/r), regofenib (REG) and TAS-102 for metastatic pretreated colorectal cancer (mCRC) patients (pts): A propensity score analysis of treatment beyond second-line (PROSERpINA Study).
Authors: Maria Alessandra Calegari, Ina Valeria Zurlo, Michele Basso, Armando Orlandi, Maria Bensi, Floriana Camarda, Brunella Di Stefano, Raffaella Vivolo, Carmelo Pozzo, Isabella Sperduti, Emilio Bria, Lisa Salvatore, Giampaolo Tortora
Journal: Journal of Clinical Oncology (2019)

3556 Background: The optimal treatment for mCRC beyond 2nd line is still questioned. Recently, REG and TAS-102 showed to improve survival compared to BSC. While in real-world practice CTr/r is often considered in this setting, supporting evidences are limited. In absence of studies comparing all these strategies, we aimed to compare the prognostic performance of CTr/r, REG and TAS-102 in mCRC treated beyond 2nd line. Methods: mCRC pts progressing after at least 2 lines of CT, treated with CTr/r, REG or TAS-102 between Jan-10 and Jan-19 were considered eligible. The primary endpoint was OS; secondary endpoints were PFS and RR. Cox’s proportional hazard models for survivals were estimated. A propensity score (PS) adjustment for baseline characteristics was further accomplished for survival analysis. Results: The clinical data of 341 pts (CTr/r 133, REG 150, TAS-102 58) were retrospectively collected. At multivariate analysis type of treatment, ECOG PS, number of metastatic sites and treatment line independently correlated with OS ( p &lt; .001, p .001, p &lt; .001 and p .029, respectively). The mOS was 18.5 (95% CI, 14.3–22.7), 6 (95% CI, 5.6–9.5) and 7.6 months (95%CI, 5.6–9.5), for CTr/r, REG and TAS-102 group, respectively (log-rank p &lt; .0001). mOS was significantly longer for pts receiving CTr/r than for those treated with REG/TAS-102 (15.8 vs 7.1 months; adjusted HR 1.96, 95% CI 1.44-2.66; p &lt; .0001) at the PS analysis, adjusted for ECOG PS, number of metastatic sites and treatment line; 2-yrs OS was 34% and 11.6% for CTr/r and REG/TAS-102, respectively. PFS was significantly longer for pts receiving CTr/r than for those treated with REG/TAS-102 (5.5 vs 3.9 months; HR 1.45, 95% CI 1.11-1.91; p .006) at the PS analysis. Accordingly, RR was higher in pts receiving CTr/r compared to REG/TAS-102 (29.0 vs 1.5%; Chi-square p &lt; .00001). Conclusions: Our analysis, although underpowered, generates the hypothesis of a superiority of CTr/r in comparison to REG or TAS-102, in both efficacy and activity. Given the retrospective nature of our analysis, and the potential role of selection bias in treatment assignment, a prospective validation is mandatory.
Clinical benefit of bevacizumab in Mexican ovarian cancer patients according to the intention of treatment by the oncologist.
Authors: Dolores Gallardo-Rincon, Antonio Bahena-Gonzalez, Edgar Montes-Servín, Elizabeth Montes-Servín, David Michel-Tello, Alfredo Toledo-Leyva, Gabriela Alamilla, Raquel Espinosa-Romero, Ernesto Gonzalez-Ibarra, Flavia Morales-Vasquez, Claudia Cano Blanco, Jaime A Coronel-Martinez, Lucely Del Carmen Cetina-Perez
Journal: Journal of Clinical Oncology (2019)

e17097 Background: Ovarian cancer (OC) is the first cause of gynecological cancer, and the fifth cause of women cancer-death in US. In Mexico, more than 4,500 new cases of ovarian cancer are diagnosed yearly and it represents the second cause of gynecological cancer mortality. Bevacizumab (BVZ) is an antiangiogenic antibody that has been approved for first-line and recurrence therapy in OC patients. The aim of the study was to evaluate the clinical benefit of BVZ in different lines of treatment in Mexican OC patients. Methods: A total of 94 OC patients treated with BVZ were recruited at the Ovarian Cancer Program of the Instituto Nacional de Cancerología, from February 2012 to September 2018. Clinicopathological characteristics and toxicity was correlated with line of treatment. PFS curves were estimated by the Kaplan–Meier method, while comparisons among groups were analyzed with log-rank or Breslow tests. Results: Most of the patients were stage IIIC (69.1%) with HGSP histology (73.4%). 24 patients (25.5%) received BVZ as first-line treatment before debulking surgery (50% for suboptimal and 45.8% for optimal cytoreduction). 48 patients (51.1%) received BVZ for second-line (72.9% after a platinum-resistant and 27.1% after a platinum-sensitive recurrence) and 22 patients (23.4%) for three or more lines of treatment. Venous thromboembolic events (VTE) were more frequent in multi-treated patients ( P= 0.030). The median PFS was 23.7, 11.7 and 5.8 months for first, second and third or more lines, respectively. Patients with optimal debulking surgery had a better PFS compared with suboptimal and BVZ in first-line patients (24.8 vs 20.9; P= 0.050). Patients with BVZ in second-line who are a platinum-sensitive recurrence had better PFS compared to those with a platinum-resistant disease (15.1 vs 7.6; P= 0.040). Conclusions: OC patients had clinical benefit from treatment with BVZ when used as first-line and first recurrence treatments. The use of BVZ for third or later line treatment has a questionable benefit and is associated with a higher rate of VTE. Also, we highlight that 77% of the patients had the greatest-benefit while 33% had limited-benefit.
Ado-trastuzumab emtansine in patients with <i>HER2</i> amplified salivary gland cancers (SGCs): Results from a phase II basket trial.
Authors: Bob T. Li, Ronglai Shen, Michael Offin, Darren J. Buonocore, Mackenzie L. Myers, Aishwarya Venkatesh, Pedram Razavi, Michelle S. Ginsberg, Gary A. Ulaner, David B. Solit, David Michael Hyman, Charles M. Rudin, Erika Gedvilaite, Dana Tsui, Maria E. Arcila, Mark G. Kris, Gregory Weitsman, Tony Ng, Maurizio Scaltriti, Alan Loh Ho
Journal: Journal of Clinical Oncology (2019)

6001 Background: SGCs are rare tumors with no approved therapy for metastatic disease. HER2 amplification occurs in 8% among all SGC histologies, and 25-33% of the aggressive salivary duct carcinoma (SDC) histologic subtype. We hypothesized that ado-trastuzumab emtansine, a HER2 targeted antibody drug conjugate, may be clinically active in these patients. Methods: A cohort of patients with HER2 amplified SGCs were enrolled into a multi-histology basket trial of ado-trastuzumab emtansine, treated at 3.6mg/kg IV every 3 weeks. The primary endpoint was overall response rate (ORR) by RECIST v1.1 or PERCIST. A Simon two-stage optimal design was applied with type I error rate under 2.7%, power of 89%, H0 10%, H1 40%; H0 will be rejected if 6 or more responses are observed in 24 patients. Other endpoints include duration of response (DOR), progression-free survival (PFS), and toxicity. HER2 amplification was identified by next generation sequencing (NGS), and tumors were subsequently tested by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Fluorescence lifetime imaging microscopy - Förster resonance energy transfer (FLIM-FRET) assessed the propensity for HER2-HER3 heterodimerization, which leads to receptor internalization. Results: 10 patients with HER2 amplified SGCs were treated. The median age was 65 (range 36-90 years), 90% were male. The median lines of prior systemic therapy was 2 (range 0-3). ORR was 90% (9/10, 95% CI 56-100%) including 5 complete responses after prior trastuzumab, pertuzumab and anti-androgen therapy. After a median follow up period of 12 months (range 4-20 months), median DOR (range 2-19+) and median PFS (95% CI 4–22+ months) were not reached. Toxicities included grade 1 or 2 infusion reaction, thrombocytopenia and transaminitis; there were no treatment related deaths. HER2 amplification by NGS (fold change 2.8 to 22.8) correlated with HER2/CEP17≥2 by FISH (8/8 tested) or IHC3+ (10/10 tested). FLIM-FRET tested positive in 3/3. Conclusions: Ado-trastuzumab emtansine is highly efficacious in patients with HER2 amplified SGCs as identified by NGS. This study has met its primary endpoint, and cohort expansion is warranted to confirm these results. Clinical trial information: NCT02675829.
A pan-cancer analysis of microsatellite instability as a predictor of Lynch syndrome in Chinese population.
Authors: Pinzhu Huang, Yanhong Deng, Jianwei Zhang, Meijin Huang, Jun Huang, Jinglin Liang, Mengli Huang, Jing Zhao, Chan Gao, Wenzhuan Xie, Shangli Cai
Journal: Journal of Clinical Oncology (2019)

1574 Background: Microsatellite instability (MSI) and mismatch repair deficiency (dMMR) are primarily tested in colorectal (CRC) and endometrial cancer (EC) to aid Lynch Syndrome (LS) diagnosis. A pan-cancer study presented at 2018 ASCO, however, revealed that up to 50% of LS patients had tumors not typically associated with LS, suggesting that patients with an MSI-high (MSI-H) phenotype should proceed to germline testing regardless of tumor type or family history. We thus set out to examine this potentially practice changing notion in Chinese population. Methods: MSI status and germline mutations in MLH1, MSH2, MSH6 and PMS2 genes were determined using a targeted next generation sequencing panel covering 100 MSI loci as well as MMR genes. Tumor mutation burden (TMB) levels were calculated for LS patients with MSI-H and MSS tumors, and intergroup differences were assessed using Mann Whitney U test or Fisher’s exact test. Results: Of 6,288 advanced tumors spanning &gt; 27 cancers, 0.8% (48/6,288) were EC, 21.6% (1,362/6,288) were CRC, and 77.6% (4,878/6,288) were other malignancies. 3.6% (224/6,288) of the samples were found to be MSI-H and 3.5% (217/6,288) harbored MMR mutations (somatic and germline). Germline mutations indicative of LS were identified in 0.1% (8/6,064) of the MSS group and 17% (38/224) of the MSI-H group (p &lt; 0.001). In contrast with the 2018 ASCO report, up to 63.8% of the 224 MSI-H tumors were CRC/EC, and only 8.9% (3/38) of the LS patients had MSI-H non-CRC/EC tumors (1 ovarian clear cell, 1 small bowel, and 1 gastric cancer). LS patients with non-CRC/EC tumors were more likely to be MSS compared to those with CRC/EC (70.0% vs 2.7%, p &lt; 0.001). Alterations in MLH1/ MSH2 were present in 78.3% (36/46) of the LS patients, and they demonstrated significantly better correlation with a MSI-H phenotype than MSH6/PMS2 alterations (94.4% vs. 40.0%, p = 0.0005). Additionally, in line with previous reports showing co-ocurrence of MSI-H and high TMB in gastrointestinal cancers, the LS patients with MSS tumors had a significantly lower median TMB compared with the MSI-H population (4.6 muts/Mb vs. 91.8 muts/Mb, p &lt; 0.001). Conclusions: Our study showed that in Chinese population, CRC/EC still predominated among LS-associated cancers, while non-CRC/EC LS patients were more likely to present with an MSS phenotype. The value of MSI-H/dMMR as a predictor of LS across different tumor types warrant further investigation.
Change in body composition and survival in patients with pancreatic cancer.
Authors: Mridula Krishnan, Lei Yu, Aneesha Dasgupta, Nicholas J Mullen, Ferdinand Osayande, Lyudmyla Derby Berim, Morshed Alam, Fang Yu, Jennifer Oliveto, Kelsey Klute, Pankaj K. Singh
Journal: Journal of Clinical Oncology (2019)

e15716 Background: The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise and continues to have a poor overall survival despite aggressive available treatment strategies. Sarcopenia is prevalent in PDAC patients and is likely caused by both disease and treatment. We hypothesized that ongoing muscle loss during treatment with chemotherapy would be associated with shorter progression-free survival (PFS) and overall survival (OS). Methods: We measured skeletal muscle index at L3 vertebra on baseline follow-up scans in patients with PDAC treated with chemotherapy at our institution. Patients were categorized by percent SMI lost over an 8-week period (&lt;10%, 10-20%, ≥20% loss). We compared PFS and OS between the groups. Results: We included 162 patients with stage I-IV pancreatic cancer. Baseline characteristics are listed in the Table. SMI loss was associated with shortened PFS and OS (p=0.009, p=0.032 respectively) via log-rank test for trend. Even after adjusting for confounders (age, gender, resection status, stage, baseline sarcopenia, treatment and therapy), the relative risk of death (2.0; 95% CI=1.10-3.64, p=0.023), and progression (1.83; 95% CI =1.08-3.10, p =0.024) were higher in those who lost ≥20% SMI. There was no significant association between BMI change or fat change with the survival outcomes. Conclusions: The loss of skeletal muscle during the first 8 weeks of chemotherapy is associated with shortened survival outcomes and is independent of stage and resection status in patients receiving chemotherapy for PDAC. Future studies should seek to understand mechanisms of muscle loss by both tumor and chemotherapy to improve survival in patients with PDAC. Baseline characteristics. [Table: see text]