tbuckley/cabot-search huggingface dataset:
Overall survival of elderly metastatic colorectal cancer patients treated in second and third line by tumor site.
Authors: Patricia Luhn, Edward Cha, Angela Fu-Chi Hsieh, Michael Taylor, William Grossman
Journal: Journal of Clinical Oncology (2017)

742 Background: The anatomical side of the colon where a tumor arises has been shown to be prognostic in patients treated with first-line therapy; patients with tumors that arise from the left side of the colon have significantly longer survival compared with patients whose tumors arise from the right side of the colon. However, there is little evidence of whether this factor is prognostic in later lines of treatment. The objective of this study was to determine the impact of tumor side on the survival of metastatic colorectal cancer patients who received second line (2L) or third line (3L) therapy. Methods: Metastatic (stage IV) colorectal cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database linked to Medicare claims diagnosed 2001-2005 who received 2L (n = 921) or 3L (n = 502) therapy were included in the study. Overall survival (OS) was determined from the start of the indicated line of therapy and was estimated using the Kaplan-Meier method; statistical differences were tested using the log-rank tests. Results: The distribution of tumor sites was similar for 2L and 3L treated patients (right: 36%; left: 58%; transverse: 6%; for 2L). The median follow up time from start of therapy was 11 months (mo) for 2L and 10 mo for 3L patients. Median OS for left-sided tumors receiving 2L+ therapy was 13.6 mo (95%CI: 11.9, 14.8) compared with 8.7 mo (95%CI: 7.5, 9.9) for right-sided tumors (log-rank p &lt; 0.001). Similar results were seen in patients receiving 3L+ therapy, although the difference was of lesser magnitude. The median OS for patients with left-sided tumors was 10.8 mo (95%CI: 9.6, 12.9) compared with 7.6 mo (95%CI: 5.7, 9.4) for right-sided tumors (log-rank p = 0.002). Conclusions: These results suggest that side of tumor origin remains a prognostic factor for colorectal cancer patients treated in later lines of therapy (2L+).
Effect of induction chemotherapy (IC) on survival in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with chemoradiotherapy: Single center experience.
Authors: Chan-Young Ock, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, J. Hun Hah, Tack-Kyun Kwon, Dong-Wan Kim, Hong-Gyun Wu, Myung-Whun Sung, Dae Seog Heo
Journal: Journal of Clinical Oncology (2014)

e17032 Background: Eventhough IC can lower distant metastasis rates in LA-HNSCC, survival benefit of IC has not yet been confirmed. We evaluated whether IC prior to concurrent chemoradiotherapy (CCRT) improves overall survival comparing with CCRT alone. Methods: Medical records were retrospectively reviewed for 224 patients who were diagnosed of LA-HNSCC from January 2005 to January 2013. We analyzed overall survival (OS) and progression-free survival (PFS) between the patients who received IC followed by CCRT (N=144) and CCRT alone (N=80). Results: Of total 224 patients, 195 were male. Median age was 61.0 years old. Sites of disease were as follows: oropharynx= 101; hypopharynx= 42; larynx= 23; oral cavity= 32; nasal cavity= 6; and others= 20. Among the IC group, 71 patients (49.3%) had received docetaxel plus cisplatin as IC regimen. Of all patients, 199 patients (88.9%) had CCRT with weekly cisplatin. The median follow-up duration was 48.5 months (range 13.8-100.6 months). Three year OS rate was significantly higher in IC followed by CCRT group compared to CCRT alone group (77.1% vs. 66.9%, hazard ratio [HR] 0.55; 95% CI 0.32 to 0.94, P=0.029). Three year PFS rate was 64.6% in IC followed by CCRT group and 54.0% in CCRT alone group (HR 0.645; 95% CI 0.41-1.02, P=0.059). Subgroup analysis showed male, old age (more than 60), high N stages (N2 or N3) had more clinical benefits when they treated with IC followed by CCRT, rather than CCRT alone. Patterns of treatment failure, either loco-regional or distant relapse-free survival were not significantly different between two groups. Conclusions: In this single center retrospective analysis, IC followed by CCRT had superior OS comparing with CCRT alone in LA HNSCC, especially with high N stages.
Implementation of clinical next-generation sequencing (NGS) of non-small cell lung cancer (NSCLC) to identify EGFR amplification as a potentially targetable oncogenic alteration.
Authors: Geoffrey R. Oxnard, Christine A. Lydon, Neal Ian Lindeman, Priyanka R. Shivdasani, Gary Y. Chin, Frank C. Kuo, Bruce E. Johnson, Pasi A. Janne, Lynette M. Sholl
Journal: Journal of Clinical Oncology (2014)

8090 Background: Tumor genotyping has become fundamental in the care of NSCLC. Targeted NGS can simultaneously test for oncogenic mutations, rearrangements, and amplifications using one platform and specimen. Using an institute-wide prospective trial, we aimed to evaluate feasibility of NGS and clinical impact for patients (pts). Methods: Testing commenced in our CLIA-certified lab in 7/13. NSCLC pts were identified for whom NGS was ordered as a supplement to routine genotyping. All pts provided informed consent. A minimum of 50ng DNA was analyzed by massively parallel sequencing on an Illumina HiSeq 2500, using hybrid capture to target exonic and/or intronic sequences in 305 cancer genes. Coverage was normalized to a panel of normals and expressed as a log2ratio, with high amplification defined as log2ratio >2. Results: As of 12/2013, NGS was ordered on 191 NSCLC pts: 45 (24%) were screened out due to insufficient tissue, and results from another 33 are pending at time of submission. Testing was completed on 113 with a turnaround time (TAT) as short as 12 days: 86% non-squamous NSCLC, 14% squamous NSCLC, 19% never-smokers, 54% female. Using this single assay, key targetable alterations were identified in 77% of non-squamous and 50% of squamous cases (Table). Three cases showed high EGFR amplification; one of these, a 61 yo never-smoker, initiated second-line erlotinib 150mg daily and had a response sustained for 23 weeks, interrupted by CNS progression. One ALK FISH positive case showed no rearrangement by NGS and a KRASQ61L mutation, potentially indicating false positive FISH. Conclusions: Clinical NGS of NSCLC can efficiently identify targetable mutations, rearrangements, and amplifications, with acceptable specimen requirements and TAT. This assay has now been adopted for routine clinical genotyping. EGFR amplification may represent a rare targetable oncogenic alteration with sensitivity to erlotinib. Nonsquamous Squamous N = 97 % N = 16 % Point mutations EGFR 10 10 BRAF 6 6 1 6 PIK3CA 6 6 4 25 KRAS 30 31 1 6 Insertions/deletions EGFR 8 8 HER2 1 1 Rearrangements ALK 4 4 ROS1 RET 1 1 High amplification EGFR 3 3 HER2 MET 4 4 PIK3CA 1 1 2 13 FGFR1 1 1
Quality of Survivorship in a Rare Disease: Clinicofunctional Outcome and Physical Activity in an Observational Cohort Study of 618 Long-Term Survivors of Ewing Sarcoma
Authors: Andreas Ranft, Corinna Seidel, Christiane Hoffmann, Michael Paulussen, Ann-Christin Warby, Henk van den Berg, Ruth Ladenstein, Claudia Rossig, Uta Dirksen, Dieter Rosenbaum, Herbert Juergens
Journal: Journal of Clinical Oncology (2017)

Purpose Significantly improved survival rates in patients with Ewing sarcoma have raised interest in accessing the quality of long-term survivorship. In this study, subjective and objective measurement tools, preclassified as physical or mental scores, were used to assess clinicofunctional outcome and physical activity after intensive bone tumor treatment. Methods Long-term outcome of 618 survivors from consecutive Ewing sarcoma trials was assessed by the Toronto Extremity Salvage Score, Short-Form Health Survey (SF-36), Brief Symptom Inventory (BSI), and Rosenberg Self-Esteem Scale questionnaires and by the accelerometric StepWatch 3 Activity Monitor. Prospective measurements were correlated retrospectively with standardized primary trial data. Results were compared with 316 nonrandom healthy peers by using effect sizes ( d). Median observation time was 12.9 years from primary diagnosis (range, 3.7 to 31.2 years). Results Absolute subjective scores were moderate to good for survivors. Compared with control subjects, unfavorable outcome was shown on physical Toronto Extremity Salvage Score, SF-36 Physical Component Summary, and BSI-Somatization scales (| d| ≥ 0.50; P < .01), in contrast to SF-36 Mental Component Summary, BSI-Anxiety, BSI-Depression, and Rosenberg Self-Esteem Scale mental scales (| d| ≤ 0.31). Survivors were less active than control subjects, as demonstrated by a step count difference of 1,742 steps per day ( d = -0.43; P < .01); however, on average, the recommended level for an active lifestyle was achieved (≥ 10,000 steps). Location of pelvic tumor was the major inferior disease-specific prognostic factor in physical scores ( P < .01), whereas nondisease-specific inferior factors in questionnaires were older age and female sex ( P < .01). Conclusion Survivors of Ewing sarcoma apparently returned to a normal life with minor limitations. Observed reductions in physical scores should be a focus in future research to optimize treatment strategies to reduce a negative impact on the quality of survivorship.
A phase II trial of neoadjuvant chemotherapy with GSL (GEM+TS-1+LV) for marginally resectable pancreatic cancer.
Authors: Yoshihiro Sakamoto, Hiroyuki Isayama, Kei Saito, Junichi Arita, Yousuke Nakai, Kiyoshi Hasegawa, Takeyuki Watadani, Taku Aoki, Kazuhiko Koike, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2017)

TPS516 Background: The impact of neoadjuvant chemotherapy (NAC) for borderline resectable pancreatic cancer is under debate. In this context, a phase II trial of neoadjuvant chemotherapy for marginally resectable pancreatic cancer is undergoing since Jan 2014 (UMIN000012480). In this trial, we employed GSL regimen (Gemcitabine 1000mg/m2, TS-1 80mg/m2, LV 50mg) which have reported favorable results (33% of response rate, 93% of disease control rate and 16.6 months of overall survival) for unresectable pancreatic cancer (Cancer Chemother Pharmacol 2014; 74:911). Methods: The subjects were marginally resectable, pathologically proven pancreatic cancer, which consists of borderline resectable because of arterial attachment (BR-A) and locally advanced or unresectable (LA, UR) with short-segment ( = / &lt; 3cm) arterial abutment based on NCCN guideline 2015. At least two surgeons, two medical oncologists, and one radiologist joined a consensus meeting to decide the indication of NAC and evaluated the efficacy of NAC every month. Patients with CR, PR or SD for 2-6 months underwent curative surgery combined with dissection of the nerve plexus around major arteries. The primary endpoint was R0 resectional rate, and the secondary endpoints were resectional rate, response rate, adverse effect, surgical morbidity, mortality, operative time and hospital stay period. Twenty-four patients are going to be enrolled, and 23 patients have undergone enrollment of NAC at the time of submission of the present abstract. Clinical trial information: 000012480.
Expression of amphiregulin (AREG) and response to first-line panitumumab (pmab) + FOLFIRI in metastatic colorectal cancer (mCRC).
Authors: Claus-Henning Kohne, Ralf D. Hofheinz, Laurent Mineur, Henry Letocha, Richard Greil, Josef Thaler, Brian Twomey, Kelly Smith Oliner, Michael Boedigheimer, Jan-Henrik Terwey, Meinolf Karthaus
Journal: Journal of Clinical Oncology (2015)

3536 Background: Biomarker analyses have shown that patients (pts) with RASwild-type (WT) mCRC can achieve overall survival (OS) benefits with first-line pmab plus chemotherapy. Other biomarkers may exist that could optimize pt selection. Epidermal growth factor receptor (EGFR) ligand (eg AREG) levels have been correlated with OS during anti-EGFR therapy. Here we investigate the relationship between AREG expression and treatment outcome in a single-arm first-line mCRC study of pmab + FOLFIRI. Methods: Qualified reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure AREG RNA expression in archival formalin-fixed, paraffin embedded tumor samples from mCRC pts in two pmab trials (STEPP and 314). The STEPP analysis was used to establish a cut-off point in AREG expression that identified the best responders. This cut-off was applied prospectively to samples previously analyzed for RAS in the 314 trial. Using the RAS MT subgroup as a non-responding comparator, Cox proportional hazards (PH) models were used to evaluate AREG expression levels as a continuous covariate. Decision curves were used to estimate the progression-free survival (PFS) hazard ratio (HR) with increasing levels of baseline AREG expression. Results: In the 314 trial 100 pts had evaluable AREG levels. Among 50 RAS WT pts, high AREG expression was associated with objective response (OR) (Table). The high AREG group had better PFS HRs (RAS WT/RASMT: 0.30 [95% confidence intervals {CI} 0.12–0.75] compared with the low AREG group (PFS HR 0.49 [95% CI 0.21–1.1]). There was a significant biomarker-by-AREG expression interaction in the Cox PH model (p = 0.03). Conclusions: Treatment decision curves based on the PH model suggest that most RAS WT patients express AREG at levels where treatment benefit is predicted. Future analysis of samples from a RAS WT population may provide further insights. Clinical trial information: NCT00508404. RAS WT RAS MT High AREG (N=31) Low AREG (N=19) High AREG (N=14) Low AREG (N=36) Objective responses n 21 7 4 16 Rate (95% CI), % 67 (51–82) 38 (18–58) 31 (10–53) 45 (29–60)
Feasibility of circulating tumour cell (CTC) enumeration and molecular profiling (MP) as a biomarker in advanced endometrial cancer (aEC).
Authors: Charlotte Rose Lemech, Leah Ensell, Jennifer Paterson, Gemma Eminowicz, Helen Lowe, Natalie Griffin, Rupali Arora, Hendrik-Tobias Arkenau, Martin Widschwendter, Nicola MacDonald, Adeola Olaitan, Tim Mould, Tim Meyer, John Anthony Hartley, Anita Mitra, Jonathan A. Ledermann, Mary McCormack, Rebecca Sophie Kristeleit
Journal: Journal of Clinical Oncology (2014)

5600 Background: CTCs are prognostic and predictive markers in many solid tumours. There are no validated biomarkers to assess treatment (tx) response or molecular therapies in aEC. We conducted a feasibility study to determine whether CTCs were detectable and suitable for MP in aEC. Methods: As of January 2014, 30 patients (pt) with aEC had baseline (B) and up to 3 follow-up (FU) blood samples at intervals of 2-3 months (m) up to 6m. CTCs were evaluated using the Veridex CellSearch platform, with stathmin (S) antibody in the 4thchannel. EpCAM, S and phospho-S6 immunohistochemistry (IHC) was performed on pt FFPE tumour tissue. Results: 17/30 (57%) pt had detectable CTCs [1 CTC (n=6), 2 (5), 4 (2), 7 (1), 8 (1), 22 (1), 172 (1)]. 11/17 CTCs were S positive (+), 1 S negative (-) and 5 non-evaluable (NE). Of the 17 CTC+ pt: 11 were sampled at B and during first-line C for mEC; 6 were CTC+ at B but FU was not available (5 died, 1 refused). Of the 11 CTC+ pts sampled during tx: 7pt were B CTC+ and had decreased CTC during C, 6 of which correlated with CT response and 1 of the 6 had increased CTC on 3rdFU correlating with CT progression (PD); 4pt were B CTC- and became CTC+ during tx, 2 at PD and 2 are in FU. 18 available FFPE blocks had EpCAM+ staining on IHC, consistent with aEC epithelial origin. Conclusions: To our knowledge, this is the first published data confirming CTC enumeration and molecular analysis is feasible in aEC. 57% of pt were CTC+ which was associated with increased stage and tumour burden. Of the 11 pt sampled at B and during tx, 8 (72%) had CTC counts that correlated with CT response. FU is ongoing. CTC may be useful as a biomarker of response as well as molecular profiling in aEC. Pt clinicopathological (CP) profiles. CTC + n=17 (%) CTC - n=13 (%) Median age (y) 66 66 Met sites <2/≥2 3/14 (18/82) 4/9 (31/69) Mean Ca125 (range) 242 (6-2362) 115 (4-787) FIGO stage III/IV; IV at diagnosis 1/16 (6/94); 8 4/9 (31/69); 1 Type 2 EC 11 (65) 8 (62) Grade 3 14 (82) 10 (76) Myometrial invasion >50% 9* (64) 6^ (60) LVSI 8* (57) 4^ (40) Cervical invasion 5* (36) 2^ (20) Surgery alone 4~ 2° Adjuvant chemotherapy (C) or radiation (R) or both 0,1,4~ 3,5,2° C for metastatic (m) EC 15 7 *from 14 (3 biopsy only) ^from 10 (1 biopsy only, 2 NE). ~from 9. °from 12.
Physical activity as a predictor of outcomes in hematopoietic stem cell transplantation (HSCT) recipients.
Authors: Asmita Mishra, Binglin Yue, Jongphil Kim, Claudio Anasetti, Joseph A. Pidala, Marcie Lynn Riches, Heather S.L. Jim
Journal: Journal of Clinical Oncology (2015)

7027 Background: Prior analyses in cancer patients demonstrated lower mortality associated with greater physical activity. The association of recreational physical activity and mortality in patients receiving HSCT remains unclear. The aim of this retrospective study is to analyze the relationship between pre-HSCT self-reported physical activity by the IPAQ short form and post-HSCT outcomes. Methods: Data were collected from the Moffitt Cancer Center Health Research Informatics and transplant databases. Between 01/01/2011 and 11/19/2013, 238 consecutive and unique patients received either an autologous (auto) (n = 152) or allogeneic (allo) (n = 86) HSCT. IPAQ scoring algorithm was used to ascertain metabolic equivalent of task-hours (MET-hrs) per week. Based on MET-hrs/wk aggregate score, patients were subsequently divided into three activity categories: low (n = 61), moderate (n = 70), and vigorous (n = 107). Results: Median follow-up for survivors was 7.1 months (range 2.9-11.1 months). There was no significant difference in age, gender, KPS, CIBMTR disease risk, HCT-CI, conditioning intensity, number of prior chemotherapy regimens, and pulmonary function among the three categories (p = NS). For alloHSCT, six month overall survival differed significantly between the three groups [Low: 73% (95% CI: 50 – 87%); Moderate: 81% (59 – 91%); Vigorous: 91% (76 – 97%) P =0.0033] (Fig. 1). In univariate analysis, vigorous activity was associated with decreased risk non-relapse mortality compared to low activity (HR: 0.07 (95% CI: 0.01-0.56) P =0.0127). After adjusting for disease risk and KPS, alloHSCT recipients reporting vigorous activity had a lower mortality than those who reported low physical activity in multivariate analysis (HR: 0.189 (95% CI:0.063-0.567) P =0.0029). Self-reported physical activity is not associated with mortality, relapse-free survival, or non-relapse mortality in autoHSCT recipients (p = NS). Conclusions: Vigorous activity for patients undergoing HSCT is an independent predictor of survival after alloHSCT. Further studies are warranted to evaluate impact of physical activity on HSCT outcomes. An ongoing prospective single center trial assessing this is nearly complete.
PERCIST criteria to predict survival at 3 months following intra-arterial resin-based yttrium-90 (Y-90) radioembolization therapy of unresectable intrahepatic cholangiocarcinoma refractory to standard chemotherapy: A proof of concept study.
Authors: Juan C. Camacho, Nima Kokabi, David M. Schuster, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2013)

e15141 Background: To investigate the prognostic value of PET Response Criteria in Solid Tumors (PERCIST) on predicting survival in patients with unresectable intrahepatic cholangiocarcinoma (ICC) after resin-basedYttrium-90 (Y-90) radioembolization. Methods: IRB approved prospective correlative study in ICC patients refractory to standard chemotherapy who had 18F-FDG PET-CT before and after Y-90 therapy. Measurable tumor was defined as a lesion ≥ 1 cm in diameter and maximum standardized uptake ((max) SUV) ≥ 2.5. (Max) SUV was measured in targeted and non-targeted lesions after local therapy (overall response). PERCIST criteria defined complete response (CR) as no FDG uptake within target lesion, and partial response (PR) as reduction of 30% in FDG (max) SUV peak in measurable lesions. Objective response included PR/CR. PET imaging was acquired pre-treatment, 1-3-and-6 months following Y90. Survival analyses were carried out with Kaplan–Meier and Log-Rank proportional models using SPSS software v20 (IBM, Armonk, NY) with significance set at &lt;0.05. Results: 9 consecutive patients were enrolled (56% men, mean age 58). Median overall survival from Y90 was 21.7 months. Average max SUV pretreatment was 10.02 and after Y90, 6.03. At 1-month after Y90, target PERCIST criteria showed CR= 1 (11.1%), PR=1 (11.1%), SD=7 (33.3%) and PD=0 (0.0%). Following 3-month after Y90, target response was CR= 2 (22.2%), PR=3 (33.3%), SD=3 (33.3%) and PD=1 (11.1%). No correlation between survival and either target or overall PERCIST criteria response on 1-month follow-up scan was seen(p=0.260). Statistically significant prolonged overall survival was observed for patients with objective targeted response based on PERCIST criteria at 3-month scan (P=0.022). In addition, objective overall PERCIST response at 3-month showed significant correlation with overall survival (p= 0.011). Conclusions: In patients with unresectable ICC refractory to standard chemotherapy, PERCIST criteria at 3-months following Y-90 therapy predict overall survival.
Comprehensive genomic sequencing of appendiceal cancer tumors to identify different genomic alterations by subtype, novel treatment opportunities, and improved outcomes.
Authors: Celina Ang, Aatur D. Singhi, Alexa Betzig Schrock, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller, Siraj Mahamed Ali, Sherri Z. Millis
Journal: Journal of Clinical Oncology (2017)

599 Background: Appendiceal cancers are rare and consist of mucinous (M), adenocarcinoma (A), goblet cell carcinoma (GCC), pseudomyxoma peritonei (PMP), and several even rarer histologies. Current treatment involves surgical resection or debulking; no standard exists for adjuvant chemotherapy or metastatic disease treatment. Systemic treatment is often based on chemotherapy regimens used in colorectal cancer. Methods: Tissue from 518 appendiceal cancer patients was assayed by hybrid-capture based comprehensive genomic profiling (CGP) in the course of clinical care to evaluate genomic alterations (GA: base substitutions, indels, amplifications, copy number alterations, fusions/rearrangements) and targeted therapy opportunities; 315 genes frequently altered in cancer were assayed. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb sequenced DNA and reported as mutations/Mb. Results: Profiling across all appendiceal cancer histological subtypes identified different patterns in GAs across subtypes (table), most notably in GNAS, KRAS, and TP53. No PMP exhibited microsatellite instability (MSI-H) or high TMB ( &gt; 20 mutations/Mb); MSI-H cases included 3 M, 4 A, 1 GCC; 3-7% 12% A and 6% m had high TMB. Case reports of patients with tumors harboring GNAS alterations showed response to MEK inhibitors. Conclusions: Genomic profiles of tumors from patients with appendiceal cancers reveal differing profiles from colorectal cancers (CRC) and considerable heterogeneity between subtypes, suggesting an individualized approach to treatment. Therapeutic options include clinical trials targeting pathways involving KRAS, BRAF, GNAS, PIK3CA, FBXW7, SMAD4, APC, and ATM. Recent case reports indicate that GNAS is a clinical target for MEK inhibitors. Overall, given the poor prognosis of advanced stage appendiceal carcinoma patients, CGP may identify novel, unanticipated therapeutic targets in a significant subset of patients, including immunotherapy for high TMB patients. [Table: see text]