tbuckley/cabot-search huggingface dataset:
Surgery in combination with peptide receptor radionuclide therapy is effective in metastatic neuroendocrine tumors and is definable by blood gene transcript analysis.
Authors: Andreja Frilling, Daniel Kaemmerer, Mark S. Kidd, Ashley K Clift, Justin Stebbing, Richard P. Baum, Leandro Castellano, Harpreet Singh Wasan, Irvin Mark Modlin
Journal: Journal of Clinical Oncology (2017)

e15697 Background: Neuroendocrine tumours (NET) of the pancreas (PNET) or small bowel (SBNET) frequently present with metastases at initial diagnosis, undermining the efficacy of surgical treatment. Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues, 90 Y-DOTATOC and 177 Lu-DOTATATE, has been shown to achieve prolonged progression-free survival (PFS) in a substantial number of non-surgical patients with advanced NET. Our aim was to prospectively determine the efficacy of a combination of radical loco-regional surgery and PRRT in patients with metastasised NET. Methods: A set of inclusion criteria was defined (e.g. G1/G2 NET, initial tumour diagnosis, treatment naïve patient, stage IV NET, positivity on 68Ga DOTA- PET/CT, eligibility for surgery and PRRT). Patients underwent PRRT within 3 months following surgery. Follow-up included biochemistry and imaging. In a sub-cohort, blood-based neuroendocrine gene transcript analysis of 51 genes (NETest) was used to define the effectiveness of treatment. Outcome measures included 5-year overall survival (OS) and PFS from initial diagnosis. Results: Twenty-five patients (5 PNET, 20 SBNET) met eligibility criteria and were included. There were 13 men (52%) and mean age was 57.1 years. All patients with SB NET underwent right hemicolectomy, terminal ileal resection and mesenteric lympadenectomy. In all PNET patients only limited pancreatic resection was required. The median number of PRRT cycles was 4 (range 2-6). Post-treatment mortality was 0%. Surgical morbidity was 12% (all Clavien-Dindo grade 1). Transient grade 1 toxicity occurred post-PRRT in 40%. NETest scores were increased in 8 patients (100%) pre-operatively and decreased in all following treatment. NETest decreases correlated with diminished tumour volume (R 2 =0.37, p=0.02). Median follow-up was 48 months (range 12-72months). Five-year OS was 90% and 5-year PFS was 84.3%. Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NET. The NETest accurately measures the effectiveness of treatment.
An analysis of thank-you notes to an oncologist.
Authors: Melanie J. Mackean, Anna Roberta Mackean, Fiona E Wilson, Richard Shillcock
Journal: Journal of Clinical Oncology (2016)

e21553 Background: Patient surveys and patient complaints have been extensively studied by healthcare services in order to gain feedback to improve patient care. However, analysis of a common form of patient and carer feedback—thank-you cards and letters—has been largely ignored. Examining the content of thank-you messages offers insight into the patient experience, what they viewed as important in the patient-doctor interaction, and into overall care. The authors present what they believe to be the first analysis of the messages and language of thanks to an oncologist. Methods: All notes of thanks, unprompted, to an oncologist over a 12 year period of work were redacted and examined for gender of author, gender and status of patient, words used and themes raised. Inductive content analysis was performed independently by two of the authors and verified by a third. Lexical analysis was performed using LIWC2007 and visualized using ‘word clouds.’ Results: A total of 269 thank-you messages were examined in detail. Four overarching themes were identified: (1) Patient-doctor relationship; (2) Cancer treatment itself; (3) The patient and bereavement; and (4) The future, with sub-themes for each. The theme concerning the professionalism and other attributes of the doctor predominated, followed by mentions of the patient, the nature and implications of death. Lexical analysis showed the 27,730 transcribed words accentuated emotional writing and positive emotion compared with normative controls. The word cloud produced a powerful image with ‘time’ and ‘care’ as the most prominent words. Conclusions: The thank-you messages represented a squaring of cognitive and emotional accounts with the doctor and the hospital. Thematic analysis suggested a need for closure following bereavement. The positive emotional language used sets a benchmark for language analysis using LIWC. This work can be used to inform those wishing to pursue a career in oncology and to present the professional role of the oncologist in a realistic and positive light to the general public and care providers. LIWC comparison Normative Control Writing Normative Emotional Writing Thank-you Corpus Social Processes 5.55% 9.09% 15.14% Affective Processes 2.57% 6.02% 9.32% Positive emotion 1.83% 3.28% 8.12%
Phase Ib trial of superoxide (SO) dismutase (SOD) mimetic GC4419 to reduce chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients (pts) with oral cavity or oropharyngeal carcinoma (OCC).
Authors: Carryn M. Anderson, Bryan G. Allen, Wenqing Sun, Sanjiv S. Agarwala, Christopher M. Lee, Madhavi L. Venigalla, Larisa Greenberg, Douglas Adkins, Yuhchyau Chen, Weining Zhen, Diane R. Mould, Jon Holmlund, Jeffrey Mark Brill, Stephen T. Sonis, John Michael Buatti
Journal: Journal of Clinical Oncology (2016)

10120 Background: CRT-induced SO significantly contributes to OM initiation. GC4419 (MW=483) specifically mimics SOD’s dismutation of SO to H2 O2 , and reduced severe OM (SOM) in a hamster cheek pouch model. With cisplatin (CDDP) in CRT, about 70% of pts with OCC develop SOM (World Health Organization [WHO] Grade 3-4) at a median 40 Gy/4 wks to onset (Table). There are no approved OM drugs for these pts. Methods: Serial 3-6 pt cohorts; locally-advanced, non-metastatic OCC; definitive or post-op Rx; planned for intensity-modulated (IM)RT to approx. 70 Gy total (>50 Gy to > 2 oral sites), 2.0-2.2 Gy/fx M-F plus CDDP; plus escalating doses of GC4419, 60-minute IV infusion, M-F for 3-7 weeks, ending < 60 minutes before IMRT. WHO Grade OM was assessed twice weekly. GC4419 was measured in plasma by LC/MS. Circulating cytokines (Cy) mechanistically related to OM were assayed (multiplex assays). Results: 46 pts received GC4419 (duration/daily dose levels): 3 weeks/15-112 mg (N=20); 4-5+ weeks/112 mg (N=12); 6-7 weeks/30 or 90 mg (N=14). DLTs (Gr 3) @ 112 mg: gastroenteritis (3 wks); vomiting with hyponatremia (5+ wks). Gr 3 nausea/vomiting and Gr 1 peri-infusional facial tingling appeared dose-related. Other AEs represented known effects of IMRT/CDDP. Multiple parameters of SOM (N=43 evaluable) were improved compared with historical controls (Table). Cmax and AUC were dose-proportional with plasma t1/2 ~ 2 hours. Increases in inflammatory Cy levels appeared to distinguish pts with SOM through week 6, consistent with known OM pathogenesis. Conclusions: SOM was briefer, delayed, less severe, and less frequent than expected, with greatest benefit when GC4419 was dosed over the full IMRT period. GC4419-related toxicity was acceptable. A randomized, placebo-controlled Phase 2 trial is in progress with GC4419 doses of 30 and 90 mg/d. Clinical trial information: NCT01921426.SOM results. Parameter Historical Placebo Pts (N=188) GC4419 all evaluable (N=43) GC4419, 30 or 90 mg/d x 6-7 weeks (N=14) Median duration, days 22-26 7 2.5 % Gr. 4 23 19 0 Median days to onset 32-35 >50 >50 Incidence through 60 Gy, % 60 37 28 Incidence at any time, % 68 53 50 * Placebo arms, Le et.al and Henke et.al., JCO 2011.
Correlation between triodothyronine levels and cancer cell proliferation in high Ki-67 estrogen receptor-positive breast cancer patients.
Authors: Alexandros Tzovaras, Iordanis Mourouzis, Nikos Tsapralis, Grecory Tsoukalas, Nikolaos Tsoukalas, Sofia Stamatopoulou, Georgios Oikonomopoulos, Ioannis Misitzis, Christos Pantos, Alexandros Ardavanis
Journal: Journal of Clinical Oncology (2012)

e11073 Background: Although thyroid hormone is a critical regulator of cell growth, differentiation and survival during development, the relationship between thyroid hormone status and breast cancer has not been adequately explored. Recent findings suggest that T3 administration reduces cancer cell proliferation depending on the type of tumor cell line with aggressive tumors to be more sensitive to thyroid hormone treatment. Thus, the present study investigated the potential relationship between thyroid hormone levels and strong prognostic factors (such as tumor size, nodal status, and Ki67) in estrogen receptor positive (ER+) breast cancer patients. Methods: 86 ER(+) breast cancer patients were studied. Levels of TSH (μΙU/ml), FT3 (pg/ml) and FT4 (ng/ml) were measured in all patients before surgery. After surgical excision of the tumor, samples were taken for histopathological analysis to determine tumor size, an index of cell proliferation Ki67 and HER2 receptor expression. HER2 receptor when amplified, it results in an aggressive subtype of breast cancer. In addition, activation of Akt and ERK signaling was examined in tumor samples by western blotting analysis. Akt signaling activation is linked to cell differentiation, while ERK signaling activation induces cell proliferation and dedifferentiation. Results: See table. HER2(+) breast cancers were found to have 2.0 fold increase in levels of phospho-p44/total p44 ERK and 3.0 fold decrease in levels of phospho-Akt/total Akt as compared to HER2(-) breast cancers. In HER(-) breast cancers no correlation was found between TSH, FT3 or FT4 and tumor size, Ki67 and nodal status. However, in HER(+) breast cancers a strong negative correlation was found only between FT3 levels and Ki67, r = -0.60 and p = 0.004. Conclusions: Levels of FT3 show a negative strong correlation with cell proliferation of HER2(+) aggressive breast cancers. This finding may have important therapeutic implications. [Table: see text]
Pharmacogenetics of treatment response in patients with high-risk neuroblastoma: A Children’s Oncology Group study.
Authors: Navin R. Pinto, Mary J Emond, Charles Spiekerman, Arlene Naranjo, Karen W Makar, Julie R. Park, Jeannine S. McCune
Journal: Journal of Clinical Oncology (2016)

10560 Background: While outcomes for patients with high-risk neuroblastoma have improved over time, largely through intensification of therapy, biologic factors predictive of high-risk treatment failure remain elusive. Furthermore, the role of germline genetic variation in treatment failure has not been extensively investigated. Methods: Single nucleotide polymorphism (SNP) genotyping was performed on selected genes in the pharmacokinetic pathway of cyclophosphamide (CY) for children with high-risk neuroblastoma enrolled on the Children’s Oncology Group high-risk neuroblastoma protocol, ANBL0532. Response after two cycles of topotecan/CY (ranging from complete response to progressive disease) was used as a continuous outcome and with dominant model scoring of the SNP genotype as the independent variable for the association studies, adjusting for age at diagnosis, race (as determined by 30 genotyped SNPs serving as ancestry informative markers), stage, MYCN status and histology. Results: Of the 652 patients enrolled on ANBL0532, 303 participated in the pharmacogenetics aim. We tested 110 SNPs (in 37 genes) that were either tagging or had associations of interest previously reported. ABBC1 and ABCC4 had SNPs with nominal p-values < 0.01. After correction for multiple testing, two intronic SNPs in ABBC1, rs4148353 and rs17287570, were significantly associated with response to two cycles of topotecan/CY, p < 0.04 and p < 0.10, respectively. For both SNPs, the presence of one or more alternative alleles was associated with inferior outcome (coefficient estimate -0.56 and - 0.46, respectively). Conclusions: ABCC1, is a key regulator of chemotherapeutic cellular efflux, including CY. Genetic variants in ABCC1 which may alter the function of transporter impact outcome in children with high-risk neuroblastoma. Pediatric validation is underway in patients with rhabdomyosarcoma also treated with cyclophosphamide-containing regimens. Clinical trial information: NCT00567567.
Next-generation sequencing ordering trends in the cancer trajectory.
Authors: Joseph Ma, Chelsea Hagmann, Alexandra Dullea, Winnie S Wang, Warren Yau, Carolyn Revta, Janet M Armstrong, Eric Roeland
Journal: Journal of Clinical Oncology (2017)

10104 Background: Next-generation sequencing (NGS) molecular tumor profiling is increasingly being ordered for advanced cancer patients to evaluate non-traditional therapeutic options. The timing of when NGS is ordered relative to date of diagnosis, palliative care (PC) consultation, and death remains unknown. The primary objective of this study was to examine NGS ordering patterns among cancer patients. Methods: This was a single center, retrospective data analysis in cancer patients at our institution between January 2011 and February 2016. Cancer patients ≥16 yrs of age were identified from a tumor registry and matched to an existing NGS tumor profiling database. Additional data were collected from an electronic medical record and compiled into a single database. Differences in the date of when NGS was ordered compared to date of diagnosis, PC consultation, and/or date of death were determined. A Mann-Whitney rank sum test examined differences in patients where NGS was ordered relative to the date of PC consultation. Logistic regression examined variables possibly associated with PC consultation. Results: Analysis included 1596 (807 women) cancer patients. Mean±SD age was 55.5±15.2 years, 30.8% (n = 492) of patients had metastatic disease, with breast and lung the most common cancers. The difference between date of cancer diagnosis and date of NGS order was 1053.6±1568.5 days (n = 1546). The difference between date of NGS order and date of death was 221.2.4±186.6 days. Two-hundred and fifty-one patients (15.7%) received a PC consultation, of which 82 patients had a NGS order before the PC consultation and 169 patients had a NGS order after the PC consultation. The mean difference in number of days between a NGS order before versus after a PC consultation was 147.3±216.8 vs. 179.8±169.7 days (p &lt; 0.005). Four-hundred and sixty-six (29%) patients have died with 121 receiving a PC consultation. Metastatic disease, but not age and sex, was associated with PC completion (OR 1.7; 95%CI 1.27-2.21). Conclusions: NGS was frequently ordered near the time of death. PC consultations were completed in a minority of patients. NGS ordering in advanced cancer patients may serve as a trigger for PC consultation.
Reduction in time between cervical cancer diagnosis and treatment.
Authors: Carla Rameri Alexandre Silva De Azevedo, Jurema Telles O Lima, Gustavo Fernandes Godoy Almeida, Mirella Rebello Bezerra, Flavia Orange
Journal: Journal of Clinical Oncology (2018)

e17514 Background: Cervical cancer is still the third most incident cancer among Brazilian women. early diagnosis and access to oncological therapy are challenging. For 135 patients treated in 2016/2017, the mean time between cervical cancer diagnosis and treatment was 107 days. Brazilian Health Regulations suggest 60 days as a limit. Methods: Between July and August 2017 an intervention study based on ASCO’s Quality Training Program methodology and mentoring. It’s involved Baseline Data analysis,Process Map, Cause & Effect Diagram, Measures and Prioritized List of Changes (Priority/Pay –Off Matrix). The selected intervention was the navigation of the patient guided by a nurse. Results: after two months of intervention in a group of 135 patients the median time interval between diagnosis and oncologic therapy of 20% was reduced. With a relative increase of 24% in the compliance recommended by the health system. Conclusions: This patient navigation process reduced in 21 days (24%) the time between cervical cancer confirmation and treatment in a short period of time and without the need for extension of medical team or acquisition of equipment. this way can be a path to reduce inquiry in oncological care, particularly in low-medium economic development countries.
P01.013 Long-term analyses of the NOA-08 randomized phase III trial of temozolomide versus radiotherapy for elderly patients with malignant astrocytomas
Authors: A Wick, T Kessler, M Platten, C Meisner, M Bamberg, U Herrlinger, J Felsberg, A Weyerbrock, C Seidel, J P Steinbach, M Sabel, J Vesper, J Debus, F Sahm, J Meixensberger, R Ketter, R Mayer-Steinacker, A von Deimling, G Reifenberger, M Weller, W Wick
Journal: Neuro-Oncology (2018)

While the NOA-08 trial and the NORDIC Elderly trial suggested an O6-methylguanine DNA-methyl transferase (MGMT) status-tailored use of radiotherapy (RT) and temozolomide (TMZ), recent data from the NCIC CE.6/EORTC 26062 showed that hypofractionated RT plus TMZ was superior to RT for unselected elderly patients with an impact of MGMT for the effect of TMZ. This is the long-term update of the NOA-08 trial (German Cancer Trials Registry ID 386 and NCT01502241) that compared efficacy and safety of RT alone to TMZ alone in elderly patients with anaplastic astrocytoma (AA) or glioblastoma (GB), both isocitrate dehydrogenase wildtype, using overall survival (OS) as primary endpoint and event-free survival (EFS) as well as efficacy according to MGMT status as major secondary endpoints. NOA-08 had randomized patients (N=412; 39 AA, 373 GB) > 65 years with a Karnofsky performance score ≥ 60 in electronically generated blocks of variable length without stratification to receive standard RT to 60 Gy in 30 x 2 Gy fractions or TMZ dosed according to tolerance in a one week on/one week off schedule with tolerability dependent dosing. The trial finished enrolment Nov 2 2009 and demonstrated non-inferiority of TMZ compared with RT (p=0·033). In the long-term analysis with a data cut-off Apr 1 2018 median OS was 8·2 [7·0–10·0] months for TMZ treatment versus 9·4 [8·1–10·4] months for RT; hazard ratio (HR)=0·93 (95% CI: 0·76-1·15)] of TMZ versus RT did not differ between both arms. Also, median EFS [3·4 [3·2–4·1] months versus 4·6 [4·2–5·0] months did not differ with a HR=1·02 (0·83-1·25)]. MGMT promoter methylation tested in tumor tissue (82/221 patients, 37·1%) was associated with prolonged OS [13·6 [10·1–16·5] versus 8·0 [6·9-9·9] months; HR=0·53 (0·40-0·70), p<0·0001]. Patients with MGMT promoter methylation had longer OS and EFS when treated with TMZ (18·4 [13·9–24·4] months and 8·5 [6·9–13·3] months) versus RT (9·6 [6·4–13·7] months and 4·8 [4·3–6·2] months, HR 0·44 [0.27–0.70], p<0·001 for OS and 0·46 [0.29–0.73], p=0·001 for EFS). Patients without MGMT promoter methylation had shorter EFS and a shorter OS with the usual testing not significant when treated with TMZ (6·7 [5·6–8·2] months and 3·0 [2·6-3·3] months) versus with RT (10·2 [8·0–12·0] months and 4·6 [3·7-6·4] months), HR 1·33 [0·95-1·87], p=0·099 for OS and 1·86 [1·32-2·62], p<0·001 for EFS). Also in the long-term analyses, NOA-08 confirms the non-inferiority of TMZ compared with RT in the treatment of elderly patients with WHO grade III or IV astrocytic gliomas. To improve OS and EFS, MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ and offers unexpectedly favorable long-term outcome with initial TMZ monotherapy.
Predictors of erlotinib utilization and the impact of erlotinib use on overall survival in advanced, non-small cell lung cancer.
Authors: Jennifer L. Ersek, James Thomas Symanowski, Edward S. Kim, Swann Arp Adams, James R. Hébert, Jan Marie Eberth
Journal: Journal of Clinical Oncology (2018)

e18741 Background: Epidermal growth factor receptor (EGFR)-directed therapies are approved for selected patients with non-small cell lung cancer (NSCLC); however, little information on predictors of utilization and efficacy in the population-based setting has been reported. We aimed to identify predictors of early erlotinib prescribing and evaluate the impact of erlotinib on survival in patients diagnosed with stage IIIB/IV NSCLC residing in South Carolina (SC). Methods: SC Central Cancer Registry cases diagnosed between January 1, 2002 and December 31, 2012 were linked to SC State Employee Health Plan (SCSEHP) and Medicaid administrative claims data. Logistic regression (LR) was used to identify predictors of erlotinib utilization. Kaplan-Meier methods were used to estimate survival distributions and log-rank tests compared the survival distributions between erlotinib groups. Cox proportional hazards (PH) modeling was used to assess the impact of patient demographic, disease, and treatment characteristics on survival, while adjusting for other prognostic covariates. Multivariable LR models were used to estimate propensity scores, which were then used as covariates in adjusted Cox PH models. Results: A total of 1,623 patients were eligible. Independent predictive factors for having at least one erlotinib claim, included younger age at diagnosis (p = .004), female sex (p = .048), SCSEHP (p < .001), out-of-state providers (p < .001), adenocarcinoma histology (p < .001), and having molecular testing (p = .018). Overall survival (OS) was longer for patients who received erlotinib (median OS = 14 versus 7 months, p < 0.001). After adjustment for significant prognostic factors, patients who received erlotinib had a 35% reduced risk of death compared to patients with no erlotinib (HR = 0.65, 95% CI: 0.56-0.75, p < .001). Conclusions: Several factors were associated with erlotinib utilization and disparities in access may exist. Erlotinib utilization was associated with a reduced risk of death in patients with NSCLC in SC.
Real-world characteristics, treatment patterns and outcomes of RET+ NSCLC compared to other rare driver mutations.
Authors: William Bruce Wong, Ning Wu, Ravindra Gupta
Journal: Journal of Clinical Oncology (2018)

e18706 Background: RET rearrangements are a potential clinically actionable driver mutation in NSCLC, however it’s rarity has led to limited studies, particularly in real-world settings. This study aims to describe prevalence, patient characteristics, current treatment patterns and outcomes in RET+ NSCLC in real-world settings in the U.S. Methods: This was a retrospective study of NSCLC patients treated in the Flatiron Health network from January 2011 - December 2016, who underwent FoundationOne tumor sequencing. Patients with RET rearrangements were identified via next-generation sequencing on the FoundationOne panel. Patient characteristics and treatment patterns were analyzed using descriptive statistics and patient timelines. Overall survival (OS) was determined using the Kaplan-Meier method and compared using log-rank test. ALK and ROS1 patients were included for comparison of demographics and OS only. Results: Of 2,139 patients in the database, a total of 111 patients were identified with a RET abnormality, of which 21 were identified to have a RET rearrangement, a positivity rate of 1% (21/2,139). In comparison, 69 patients were identified to be ALK+ (3.2%, 69/2139) and 29 patients had a ROS1+ (1.4%, 29/2139). Similar to ALK+ NSCLC patients, RET+ patients tended to be younger (Median Age: RET+: 59 years, ALK+: 59 years), have no history of smoking (RET+: 62%, ALK+: 51%) and had tumors of predominantly non-squamous histology (RET+: 100%, ALK+: 99%). The median time from advanced diagnosis to RET+ test result was 73 days (IQR: 32-718), with 43% of patients initiating or changing treatment within 30 days of the test result. 19% of RET+ patients had no record of treatment and 76% of patients were treated with chemotherapy, with the most common regimen being bevacizumab, carboplatin and pemetrexed. Among treated patients, 12-month OS was 62% and was similar to ROS1+ patients treated with chemotherapy in the first line (12-month OS, 60%; p = 0.89). Conclusions: The real-world patient characteristics and survival from this study appear consistent with other limited data on RET+ NSCLC. RET rearrangements continue to represent a rare but high unmet need disease, with limited targeted treatment options.