tbuckley/cabot-search huggingface dataset:
Prognostic factors in nonfunctional well-differentiated gastroenteropancreatic neuroendocrine tumors: Single Institute Experience.
Authors: Mutlu Dogan, Oznur Bal, Fahriye Tugba Kos, Nurullah Zengin
Journal: Journal of Clinical Oncology (2018)

e16176 Background: Grade 1 & 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are well-differentiated (WD). Methods: We evaluated 115 nonfunctional WD GEP-NETs retrospectively. Results: Median age was 54 years (18-80) with female predominance (62.6%) . Pancreatic (34%) and gastric (25.2%) were most common sites. Most (78.3%) had operable disease. 57% had lymph node dissection (LND). 56.7% had grade 1 disease, one third had lower mitotic rate ( < 2 / 10HPM) and/or ki-67 index ( < 3%). 24.3% had necrosis, 35% had lymphovascular invasion (LVI), 19% had perineural invasion (PNI), 13% had positive margin. Median tumor size was 2.5 mm (0.2-23). Median values were as 7000/mm3 (3300-18200) for WBC, 4200/mm3 (1500-30000) for neutrophil, 2190/mm3 (400-5300) for lymphocyte, 259000/mm3±6.8 months (table 1). Leucocytosis & necrosis were poor prognostic factors (p = 0.03, p < 0.0001). Conclusions: Most patients with WD GEP-NETs are female in the fifth decade. Leukocytosis and necrosis are poor prognostic factors. Table 1 Mean OS (mo) p Age year < 54 134.3 ± 5.3 0.57 ≥54 169.3 ± 9.5 Sex female 141.3 ±6.3 0.47 male 172.6 ±12.5 Localization pancreas 163.4 ± 12.8 0.69 others 121.5 ± 5.6 ECOG PS < 2 135.8 ± 3.5 0.11 ≥2 149.0 ±22.9 Stage early 145,5 ± 4.8 0.07 advanced 104.7±10.0 Surgery - 77.9 ± 4.0 0.73 + 175.5 ±6.0 Grade I 174.7±8.0 0.49 II 137.9±10.8 Mitoz < 2 ±8.0 0.62 > 2-20 ± 6.2 Kİ-67 < 3% 148.9 ±5.0 0.17 3-20% 92.8 ± 14.5 Necrosis - ±6.2 < 0.0001 + ± 12.6 LND - 181.0 ± 4.9 0.22 + 136.1± 12.2 LVI - 170.7 ±14.1 0.89 + 134.4±5.2 PNI - ± 13.1 0.42 + ±6.8 Positive margin - ±18.1 0.53 + ±18.1 Hemoglobin (g/dL) < 12.4 176.7 ± 8.8 0.18 ≥12.4 129.2 ± 6.2 Leukocyte (/mm3) < 7000 ±8 0.03 ≥7000 ± 3.1 Neutrophil (/mm3) < 4200 182.1 ±3.9 0.15 ≥4200 126.4±7.2 Lymphocyte (/mm3) < 2190 132.2 ± 7.0 0.90 ≥2190 170.6 ±8.7 Platelet (/mm3) < 259000 145.3 ±6.0 0.55 ≥259000 169.8±9.3 Median LDH (U/L) < 225 180.7±5.2 0.58 ≥225 145.2 ±6.1
<i>EGFR</i> mutant cfDNA and CTC detection as biomarkers in patients diagnosed with advanced non-small cell lung cancer.
Authors: Silvia Calabuig-Fariñas, Eloisa Jantus-Lewintre, Clara Mayo-de las Casas, Nuria Jordana-Ariza, Ariadna Balada, Ana Blasco, Miguel Angel Molina-Vila, Rafael Rosell, Carlos Camps
Journal: Journal of Clinical Oncology (2016)

e23039 Background: One of the most promising developments in translational cancer has been the emergence of liquid biopsy as a non-invasive biomarker. CTCs and cfDNA offer valuable prognostic and predictive information, and allow the monitoring of the treatment. The aim of this study was to correlate the EGFR mutational status in both CTCs as cfDNA at diagnosis and during follow-up with the outcome in NSCLC patients. Methods: Blood samples were collected from 16 advanced NSCLC patients, and repeated sampling was performed during follow-up and at progression. CTCs were isolated by size using a filtration-based device (ScreenCell), characterized and enumerated by H&E; whereas cfDNA was obtained from plasma. CTC and cfDNA genotyping was performed by PNA-Taqman assay for EGFR 19del, L858R and T790M detection. Results: 16 patients with advanced NSCLC were enrolled in the study, 11 harbored the exon 19 deletion and 5 the L858R mutation in exon 21. Median age of the cohort was 65 years, 81% were female, 81% never-smokers, 94% were ADC. The follow-up ranged from 3 to 48 months. All patients were treated with EGFR-TKIs. 12 and 37 blood samples were collected at baseline and during follow-up, respectively. CTCs were observed by H&E with a range 1-30/3 ml. Our results confirm that detected mutations can provide early information about outcome. Early undetectable blood mutations after EGFR-TKI might predict a large clinical response, whereas in TKI-responders patients, EGFR mutation remained undetectable, its reappearance preceded disease progression. In one case, where the mutation persisted during treatment, a rapid progression and exitus was observed. These results suggest that periodic monitoring of EGFR-mutational status in cfDNA or CTCs could provide information regarding response or resistance to treatment. Conclusions: CTC and cfDNA are promising biomarkers for the management of patients with advanced NSCLC: could lead to accurate diagnosis, early progression disease detection, close monitoring and personalized therapies. Although there is a need to validate these results in a larger patient cohort and to standardize the methodology. This work was supported by Astra Zeneca (ISSIRES 0110) and López-Trigo Grant
Impact of fertility preservation by ovarian stimulation on breast cancer outcomes.
Authors: Ying Wang, Shaina Lee, Pierre Camateros, Kirstin Ann Perdrizet, Daniel Yokom, Ellen Warner, Jeffrey Roberts, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2017)

e21588 Background: Chemotherapy and hormone therapy results in potential ovarian toxicity and delay in child-bearing among women of reproductive age with breast cancer. Whether short term ovarian stimulation is safe is not well studied. We examined the effects of short-term ovarian stimulation on patients’ breast cancer recurrence rates. Methods: Women diagnosed with localized breast cancer between 2005 and 2011 at any one of five cancer centres and referred to a reproductive endocrinologist in British Columbia, Canada, were identified from a central database. Clinical, pathological, treatment, and outcome characteristics were compared for patients who did and did not undergo ovarian stimulation prior to systemic cancer treatment. Results: Seventy-seven patients were included: median age was 33, all were ECOG 0/1, 31 (40%) had lymph node involvement, 62 (81%) had estrogen receptor (ER) positive disease, and 18 (23%) had HER2 positive disease. Thirty-four (44%) women underwent ovarian stimulation: they were more likely to receive chemotherapy than patients who declined ovarian stimulation (p = 0.001). Age, number of existing children, radiation, and hormonal treatments were not significantly associated with decision to undergo ovarian stimulation (p &gt; 0.05). After a median follow-up of 3.7 years, 7 (21%) patients who pursued ovarian stimulation and 9 (21%) patients who did not experienced disease recurrence. There was no association between ovarian stimulation and rate of local or distant breast cancer recurrence (p = 0.658). Conclusions: We did not find a harmful effect of short term ovarian stimulation on breast cancer recurrence rates. Limitations include short follow-up, a small sample size, and few relapses. Patients who received chemotherapy were more likely to pursue ovarian stimulation, suggesting that patients were well informed about the negative impact on fertility of chemotherapy and of the importance of fertility preservation prior to potentially gonado-toxic treatments.
Meta-analysis of skip metastasis after sentinel lymph node mapping in gastrointestinal cancers and its biological relevance: An international study.
Authors: Sukamal Saha, Mohamed Elgamal, Suresh Mukkamala, Thushy Siva, Patrick Knight, Avian Chang, Swetha Pentapati, Sunil Kaushal, Mustafa Alnounou, Sreenivas Mannam, Dilip Desai, Kiran Devisetty, David Wiese, Madan L. Arora, Sandeep Singh Grewal, Trevor Singh
Journal: Journal of Clinical Oncology (2018)

e15698 Background: Skip metastases (Mets) may appear later in breast cancer (BrCa) and melanoma (M) patients (pts) after sentinel lymph node mapping (SLNM) causing understaging and undertreatment. However, in gastrointestinal (GI) cancers (Ca), regional lymphadenectomy is done during SLNM. Hence, the impact of skip mets may differ. A meta-analysis was designed from literature research of esophageal (E), gastric (G), colon (C)and rectal (R) Ca pts undergoing SLNM to find the biological impact of skip mets. Methods: By using pubmed, studies from 2001-2016 focusing on SLNM of E,G,C and R Ca were queried and 79 publications were tabulated with all parameters including skip mets. Results: Of the 7796 pts, there were 707 pts for E, 2588 G, 4011 C and 490 R Ca. Total success rate was 92.4% ( E 93.5%, G 96.9%, C 90.4%, and R 83.4%). The average number of total lymph nodes (LNs)/SLNs was E-31.7/3.4, G-33.3/4.7, C-17.6/3.0, and R-11.4/2.3. Overall, 34.4% pts had LN mets, with highest incidence observed in E (44.9%), followed by C (42.2%), R (38.6%), and G (18.7%) . Skip mets were seen in (19.3%) LN +ve pts; the highest in R (24.3%) and the lowest in G (11.8%). Overall sensitivity, accuracy and negative predictive value were 80.7, 92.8, and 89.7% respectively (Table 1). All pts with +ve LNs, either true +ve SLNs or skip mets in non-SLNs, were staged as Stage III disease and treated with chemo therapy. Conclusions: In spite of higher skip mets rate in GI Ca compared to Br or M, all pts with skip mets in non-SLNs or true positive SLNs were staged as stage III & treated with chemotherapy. Hence, no pts with skip mets were understaged or undertreated. Accordingly, skip mets in GI Ca have no biological relevance. Table 1: SLNM in GI Ca GI Ca No. of pts No, of successful SLNM SLNM success % Average No. of LN Average No. of SLNs No. of pts with +ve LN +ve LNs % No. of pts with +ve SLN Skip mets Skip mets % Sensitivity % Accuracy % Negative predictive value E 707 661 93.5 31.7 3.4 318 44.9 252 66 20.7 79.2 90.0 83.8 G 2588 2508 96.9 33.3 4.7 484 18.7 427 57 11.8 88.2 97.7 97.3 C 4011 3626 90.4 17.6 3 1691 42.2 1343 348 20.6 79.4 90.4 84.7 R 490 409 83.4 11.4 2.3 189 38.6 149 48 24.3 75.3 86.9 78.2 Total 7796 7204 92.4 23.5 3.35 2682 34.4 2171 519 19.3 80.7 92.8 89.7
Pembrolizumab-based therapy in previously treated high grade extrapulmonary neuroendocrine carcinomas.
Authors: Claire Hooker, Jennifer A. Chan, Rahul Raj Aggarwal, Pelin Cinar, Tom Hope, Kanti Kolli, Li Zhang, Susan Calabrese, Jennifer Ann Grabowsky, Jenna Zhang, Lawrence Fong, Nitya Prabhakar Raj, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2018)

TPS4147 Background: The efficacy of immune checkpoint inhibitors (CPI) has not been established in extrapulmonary high grade neuroendocrine carcinomas (EP-HGNECs), a disease for which additional treatment options are needed. Pembrolizumab (PEM) has demonstrated safety and preliminary efficacy in small cell lung cancer. This phase 2 study aims to evaluate the efficacy and safety of PEM-based therapy in biomarker unselected EP-HGNECs. Methods Design: Open label, adaptive Simon’s 2-stage study of PEM alone (Part A) and PEM plus chemotherapy (weekly irinotecan (IRI) or paclitaxel (P); dealers’ choice) (Part B). If more than 2 responses out of 14 pts by week 18 (stage 1 part A), then 21 additional patients (pts) will enroll in stage 2 (Part A), which corresponds to H0 10% vs. H1 26% at type I error of 0.05 with power 80%. If there is insufficient activity, the study will proceed to Part B, with a safety lead-in of 6-12 pts for IRI/PEM (up to two dose levels, 1 and -1), then 16 additional patients will be accrued for a total of 22 patients treated with PEM plus chemotherapy based on one-side binomial test of H0 10% vs. H1 31% at type I error of 0.05 with power 80%. Total N needed to attain 80% power will be either 35 (Part A) or 36-42 (Part A then B) with overall type I error of 0.1. Key eligibility: EP-HGNEC of all sites (excluding Merkel cell carcinoma) with progression during or after first line systemic therapy, no prior CPI, bilirubin and creatinine ≤1.5x ULN, ECOG PS 0-1, agreeable to baseline tumor biopsy. Treatment: PEM 200 mg IV Q21days for up to 35 treatments. Primary endpoint (EP): Overall radiographic response rate by RECIST1.1. Secondary EP: Safety, duration of response, overall survival, progression-free survival. Exploratory EP: irRECIST v RECIST1.1, baseline PBMC and tumor immune cell profiles, T cell receptor (TCR) repertoires change from baseline to post treatment time points, tumor mutation profile, Ki67 index, PD-L1 expression. Current enrollment: 5 of planned 14 patients in stage I of Part A (6/2017-present). Clinical trial information: NCT03136055.
Implications of the Eighth Edition of the TNM Proposal: Invasive Versus Total Tumor Size for the T Descriptor in Pathologic Stage I-IIA Lung Adenocarcinoma
Authors: Koji Kameda, Takashi Eguchi, Shaohua Lu, Yang Qu, Kay See Tan, Kyuichi Kadota, Prasad S. Adusumilli, William D. Travis
Journal: Journal of Thoracic Oncology (2018)
Patient-derived cell models for cancer precision medicine.
Authors: Xuefeng Liu, Ewa Krawczyk, Nancy Palechor-Ceron, Aleksandra Dakic, Sujata Choudhury, Vera Simic, Richard Schlegel
Journal: Journal of Clinical Oncology (2016)

e23188 Background: Recently, we described the conditional reprogramming (CR) which allows to rapidly establish primary cultures from normal and tumor specimens. The Combination of CR and Organoids ( (Matrigel, air-liquid interface (ALI)) cultures represents next generation human cancer models and functional diagnostics for cancer precision medicine as described in August in the NCI precision medicine initiative and three nature review articles (Nat Rev Cancer. 2015 Dec; Nat Rev Genet. 2015 Jul; Nat Rev Clin Oncol. 2014 Nov.). The technique is relatively simple and has been reproduced in more than 50 laboratories (including an original and independent article in Science from Massachusetts General Hospital) (Science. 2014, 346(6216):1480-6.). Importantly, the CR technology can generate 2×106cells in a week from small biopsies, and can generate cultures from cryopreserved tissue and from fewer than four viable cells. We therefore initiated studies to examine whether CR cultures reflected the biology and genotype of the original tumor and whether cultures might be used to predict clinical responses. Methods: Surgical specimens from patients with prostate and lung cancer were collected. CR and Organoids cultures were used. Results: We first worked out standard protocols for clinical sampling, storage, shipping, freezing and the preparation of conditioned medium. CR methods were then used to generate matched cultures from both tumor cells and adjacent normal cells from patients with prostate cancer or lung cancer. CR cultures were established efficiently from these tumors ( > 95% for prostate and lung cancer CRCs). The data with Organoids cultures demonstrated that CR cells re-expressed cell specific markers and were well-differentiated. We also characterized them for their growth properties, induction of tumors in immunodeficient mice, karyotype, and their exome and transcriptome profile. Conclusions: The combination of CR (2D) and Organoids (3D) culture conditions provides optimal conditions for establishing patient-derived cells and for study of translational cancer biology. These cell-based approaches should be useful for defining the functional heterogeneity of the respective primary tumors and for evaluating appropriate therapies.
A novel candidate tumor suppressor and a potential prognostic biomarker, hVPS52, in gastric cancer.
Authors: Jian Zhang, Xi-Chun Hu
Journal: Journal of Clinical Oncology (2016)

e15537 Background: The hVPS52 is a subunit of human GARP (Golgi associated retrograde protein) complex involved in retrograde transport from the early and late endosome to the late Golgi. Few transport proteins have been identified to play a role in anti-tumor effects. We sought to investigate the expression levels, mechanisms, and prognosis value of hVPS52 in primary gastric cancer. Methods: The protein expression of hVPS52 was investigated in various cancer cell lines including gastric, breast, lung, colon and liver cancers. The replication-deficient adenovirus expressing hVPS52 (Ad-hVPS52) and the control adenovirus (Ad-Vec) were constructed. Sixty-six paired cancerous and matched adjacent noncancerous gastric mucosa tissues with patient clinicopathological information were gathered in FUSCC for analysis. Results: Western blot and IHC staining data showed that hVPS52 expression was significantly decreased not only in gastric cancer cells (MGC80-3, BGC823), but also in gastric cancer tissue samples (positive rates in cancerous vs. noncancerous samples: 22.7% vs. 72.7%, p＜0.001). The result also showed that the low hVPS52 expression was significantly correlated with later clinical stage (expression rate, stage III-IV vs. I-II: 8.8% vs. 37.5%, p = 0.018). Kaplan–Meier survival curves revealed that the reduced expression of hVPS52 was associated with a poor prognosis in gastric cancer patients (3-year OS, 50.6% vs. 86.2%, p = 0.013). The loss of heterozygosity of hVPS52 was found in 44.4% of cancerous tissues. Cell viability assay and crystal violet staining assay established the anti-tumor effect of hVPS52 overexpression via Ad-hVPS52. The marked apoptosis was observed when gastric cancer cells were infected by Ad-hVPS52 based on the TUNEL assay and flow cytometry. Cathepsin D/Bax/Cyto C/Caspase9/Caspase3 was identified as the main pathway to trigger the specific apoptosis. In vivo xenografted tumor model showed that hVPS52 overexpression significantly inhibited the growth of tumor. Conclusions: Our study suggests that hVPS52 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric cancer, which provides a new anti-tumor strategy warranting further investigation.
Predictive model for response to first-line treatment for metastatic non-small cell lung cancer.
Authors: Ahmed Ashour Badawy, Sejong Bae, Abbas Omar, Waleed O. Arafat, Gehan Abd Elatti Khedr, Stefan C. Grant
Journal: Journal of Clinical Oncology (2016)

e20657 Background: Advanced non-small cell lung cancer (NSCLC) is a worldwide problem. Despite widespread availability of multiple chemotherapies for stage IV NSCLC, response rates are generally low. We sought to develop a model that would identify simple predictive indicators to help identify patients most likely to derive benefit from treatment, of particular interest in countries with limited laboratory and imaging facilities and drug availability. Methods: A retrospective analysis of patients with stage IV NSCLC receiving systemic treatment at the University of Alabama at Birmingham (UAB Comprehensive Cancer Center) from 2002 to 2012 was performed. Fifty pretreatment risk factors including age, race, gender, presenting symptoms, and laboratory values, were evaluated by chi square testing, using SPSS software. Results: 409 patients received more than 10 different regimens as first line treatment in metastatic non-small-cell lung cancer as summarized in table. 76.4% of patients had performance status of 0-1 and 21.6 of patients has performance status 2. The following factors are statistically associated with poor response to first line treatment: smoking (p = 0.049), pleural metastases or effusion (p = 0.004), abdominal metastases (p = 0.033), hypoalbuminemia (p = 0.043) and hyponatremia (p = 0.002). Conclusions: Smoking, pleural metastases or effusion, abdominal metastases, hypoalbuminemia and hyponatremia are factors that can help identify patients who are less likely to respond to treatment. A mathematical model incorporating these factors is under development. This may help in the selection of patients for systemic therapy and may also improve stratification in clinical trials. Regimens Percentages Tyrosine kinase inhibitor 10.3 paclitaxel+ Carboplatin+ bevacizumab 6.8 paclitaxel+ carboplatin 25.9 Docetaxel + platinum 5.8 Carboplatin+ Gemcitabine 8.6 Carboplatin+ pemetrexed+ bevacizumab 7.8 pemetrexed single agent 6.6 Cisplatin+ Gemcitabine 2.4 Cisplatin+ pemetrexed+ bevacizumab 2.5 Gemcitabine + Navelibine 1.5 Other 21.8
The contribution of pre-existing cardiovascular (CV) risk factors to the risk of stroke or heart attack among non-Hodgkin lymphoma (NHL) survivors.
Authors: Talya Salz, Emily Craig Zabor, Peter de Nully Brown, Susanne Oksbjerg Dalton, Nirupa Jaya Raghunathan, Matthew J. Matasar, Richard Steingart, Henrik Hjalgrim, Peter Svenssen Munksgaard, Lena Specht, Andrew J. Vickers, Kevin C. Oeffinger, Christoffer Johansen
Journal: Journal of Clinical Oncology (2017)

10082 Background: Increased risk of myocardial infarction (MI) and cerebrovascular accident (CVA) among NHL survivors is commonly attributed to NHL treatment. The extent to which pre-existing CV risk factors also contribute to increased risk is unknown. We investigated this association among an entire national population of NHL survivors who have a full range of important CV risk factors. Methods: Using Danish population-based registries, we identified all adults diagnosed with primary aggressive NHL from 2000-2010 and followed them for MI and CVA from 9 months after diagnosis through 2012. MI and CVA diagnoses were ascertained from the nationwide Hospital Discharge Register and Cause of Death Register. CV risk factors (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at NHL diagnosis were ascertained algorithmically using the National Prescription Register and the Hospital Discharge Register. Cumulative anthracycline dose was coded continuously. Receipt of radiation was coded dichotomously for both chest and neck. Controlling for age, sex, treatment, and CV diseases, we used Cox multivariate regression to test the association between pre-existing CV risk factors and subsequent CVA or MI. Results: Among 2604 patients with NHL, median age was 62, and median follow-up time was 2.4 years. Overall, 131 patients were diagnosed with MI or CVA. Before NHL diagnosis, 40% of patients had at ≥1 CV risk factor, 13% had vascular disease, and 6% had intrinsic heart disease. 90% of the patients were treated with anthracyclines, 9% had received chest radiation, and 15% had received neck radiation. Patients with ≥1 CV risk factor had an increased risk of MI or CVA compared to patients with none (HR = 1.5 [95% CI = 1.1-2.2). Prevalent vascular disease, prevalent intrinsic heart disease, and NHL treatment were not associated with MI or CVA (p’s &gt; 0.05). Conclusions: In a large, well-characterized, and nationally representative cohort of NHL survivors, prevalent CV risk factors were associated with later CVA and MI. To prevent MI and CVA among survivors, decisions about post-treatment monitoring should take into account prevalent CV risk.