tbuckley/cabot-search huggingface dataset:
Limb salvage surgery in pediatric and AYA patients with osteosarcoma: The incidence of venous thrombosis (VT).
Authors: Sarah Jane McKillop, Quincy S. Chu, Karen E. Mulder, Mary E Bauman, Ashley Crosty
Journal: Journal of Clinical Oncology (2017)

e22505 Background: Pediatric, adolescent and young adult (AYA) patients with a diagnosis of osteosarcoma require surgical resection for local control in addition to adjuvant chemotherapy. Limb salvage surgery (LSS) has long been established as the standard of care. Pediatric and AYA patients with sarcoma are know to have an increased risk of VTE however thromboprophylaxis is not routinely used in the pediatric oncology patients. Here we review our experience over a 5 year period with patients up to 21 years diagnosed with osteosarcoma of the lower extremity treated with LSS, amputation or rotationplasty as local control and the development of VTE. Methods: A retrospective chart review was completed of patients up to 21 years of age treated for osteosarcoma of the lower extremity between January 2011 and December 2016 at our institutions. Those that underwent surgical resection of the tumor were included. Data regarding age, type of surgical procedure, the presence of a venous thrombosis, the time from diagnosis and surgery to detection of VTE and the use of anticoagulants was collected Results: 18 patients were identified: median age 14 year (6-21), 8 patients had LSS, 4 underwent rotationplasty and 6 had an amputation. Seven VTE were identified, 5 occurred in patients receiving LSS, 2 in a patient post rotationplasty and 0 in the amputation group. 6 of the 7 VTE occurred within the upper venous system, associated with the central venous line. Conclusions: In pediatric AYA patients being treated for lower limb osteosarcoma, the incidence of VTE was significantly increased for those undergoing LSS (63%) and rotationplasty (50%) compared to those receiving amputation (0%). While the population reviewed is small, based on these findings, prophylactic anticoagulation for patients with osteosarcoma, especially those patients undergoing LSS and rotationplasty should be considered beyond the immediate perioperative period. Larger prospective studies are needed to determine the risk of VTE and risks and benefits of prophylactic anticoagulation in this patient population.
Current utilization paradigm of PD-1/PD-L1 inhibitors in unapproved area: A multi-institutional cohort study in China.
Authors: Shaodong Hong, Zhihuang Hu, Jin Sheng, Xuanye Zhang, Sha Fu, Yuhong Wang, Wei Liang, Wenfeng Fang, Li Zhang
Journal: Journal of Clinical Oncology (2018)

e18503 Background: Currently, no PD-1/PD-L1 inhibitors have been approved by the Chinese FDA. Such care disparities definitely limit the therapeutic opportunities of Chinese cancer patients. We conducted this multi-institutional cohort study to investigate the current utilization paradigm of PD-1/PD-L1 inhibitors in China. Methods: Cancer patients from five academic hospitals in China who have received at least one dose of PD-1/PD-L1 inhibitors between 2015 and 2017 were included. Clinical and demographic characteristics, treatment pattern, monitoring of immune-related adverse events (irAEs) and overall survival (OS) were assessed. Results: 801 patients across 25 cancer types were eligible for the analysis, including 458 (57.2%) clinical trial participants (CTPs) and 343 (42.8%) patients who purchased the drugs from outside China mainland (self-purchasers). The agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, and four agents developed by domestic pharmaceutical companies. They were used as monotherapy (76.0%), or combined with chemotherapy (11.4%), CTLA-4 inhibitors (3.6%), targeted agents (3.4%), radiotherapy (1.6%), radiofrequency ablation (1.0%), cytokine-induce killer (0.7%), and others (2.2%). The performance status of self-purchasers was significantly worse than that of CTPs (ECOG PS 2-4: 28.3% vs. 0.7%; p < 0.001). 23.3% of the self-purchasers received only one single dose, mainly due to rapid progression or symptom deterioration (47.5%). Referred to indications by US FDA, off-label use was observed in 63.6% of self-purchasers, which was significantly associated with worse OS than on-label use (HR, 1.23; p = 0.045). Twenty-five self-purchasers (6.7%) received PD-1/PD-L1 inhibitors as near-end-of-life care, leading to a median post-treatment OS of 22 days. Among self-purchasers, only 107 patients (31.2%) were regularly monitored for irAEs. Conclusions: Though still not approved by the Chinese FDA, PD-1/PD-L1 inhibitors have been widely used in China within or outside clinical trials. This study implies that accelerated administrative approval as well as regulated and on-label prescription of PD-1/D-L1 inhibitors are highly needed in China.
Genetic testing and results in population-based breast cancer patients and ovarian cancer patients.
Authors: Allison W. Kurian, Kevin C. Ward, Nadia Howlader, Dennis Deapen, Ann S. Hamilton, Angela Mariotto, Daniel Miller, Steven J. Katz, Lynne Penberthy
Journal: Journal of Clinical Oncology (2018)

1578 Background: Genetic testing for cancer risk has expanded rapidly, with more genes tested. Little is known about test use or pathogenic variant (PV) prevalence among population-based cancer patients. Methods: Women aged ≥20 years, diagnosed with breast or ovarian cancer in 2013-14 and reported to SEER registries covering the entire populations of Georgia and California, were included. Registry data were linked to clinical genetic testing results, performed from 1/1/2012 through 4/30/2016, by 4 laboratories that did nearly all cancer genetic testing in these states. Results: There were 77,085 breast cancer and 6,001 ovarian cancer patients, with almost 30,000 patients of racial groups other than non-Hispanic (NH) White. One-quarter (24.1%) of breast and one-third (30.9%) of ovarian cancer patients had genetic test results. While test use was similar across racial groups for breast cancer, testing in ovarian cancer patients was lower in NH Blacks (21.6%, CI 18.2-25.4%, vs NH Whites: 33.8%, CI 32.3-35.4%). The most prevalent PVs in breast cancer patients were BRCA1 (3.2%), BRCA2 (3.1%), CHEK 2 (1.6%), PALB2 (1.0%), ATM (0.7%), NBN (0.3%) and TP53 (0.3%); and in ovarian cancer patients were BRCA1 (8.7%), BRCA2 (5.8%), CHEK2 (1.4%), BRIP1 (0.9%), MSH2 (0.8%), ATM (0.6%) and RAD51C (0.6%). Racial differences in PVs included BRCA1 (ovarian cancer: NH Whites, 7.2%, CI 5.9-8.8%; Hispanics, 16.1%, CI 11.8-21.2%) and CHEK2 (breast cancer: NH Whites, 2.3%, CI 1.8-2.8%; NH Blacks, 0.2%, CI 0-0.8%). Among those tested for all genes designated by the National Comprehensive Cancer Network as associated with their cancer type (breast: ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, TP53; ovarian: BRCA1, BRCA2, BRIP1, EPCAM, MLH1, MSH2, MSH6, PMS2, STK11, RAD51C, RAD51D), 7.7% of breast and 14.5% of ovarian cancer patients had a PV. Conclusions: Clinically tested, population-based breast cancer patients and ovarian cancer patients had 8-15% PV prevalence in guideline-designated cancer risk genes. CHEK2 and ATM PVs were relatively prevalent in ovarian cancer patients: this merits further study because CHEK2 and ATM are not known to be ovarian cancer risk genes. Racial testing disparities are targets for improvement.
P04.02 Adoptive transfer of lymphokine activated NK cells in combination with anti-PD-1 immune checkpoint inhibitor in therapy of glioblastoma
Authors: M Shevtsov, E Pitkin, B Nikolaev, L Yakovleva, Y Marchenko, I Guzhova, B Margulis, G Multhoff
Journal: Neuro-Oncology (2018)

Adoptive immunotherapy based on transfusions of ex vivo activated natural killer (NK) cells could increase the survival of neuro-oncological patients. 14-mer peptide TKDNNLLGRFELSG (TKD) residing in the amino acid sequence of aa450-463 of the C-terminal domain of Hsp70 and low dose IL-2 have been shown to stimulate the cytolytic and migratory capacities of CD94+ NK cells. Combination therapy with anti-PD-1 antibodies and adoptive transfer of activated immune cells could further improve the anti-glioma immunotherapy. Autologous lymphocytes were ex vivo stimulated with IL-2 (100 IU/ml) / TKD (2 μg/ml) peptide. Therapeutic efficacy was assessed in the orthotopic GL261 glioma model in C57/Bl6 mice. Activated cells were systemically administered on the 5th, 7th, 9th and 11th days following tumor cells inoculation. Anti-PD-1 antibodies were intraperitonealy injected (500 μg after tumor implantation with repeat injections every 3 days (250 μg) for a total of 4 injections) as single-agent therapy or in combinatorial regimen with adoptive transfer of stimulated cells. Tumor progression was assessed emlpoying magnetic resonance imaging (MRI) with subsequent volumometry. Immunohistochemistry of the tumor sections was performed to assess the lymphocytes infiltration. Purity and cell surface density of different NK cells markers determined before and after stimulation demonstrated the increase in percentage of NKp30+, NKp44+ and CD69+ NK cells following IL-2/TKD activation. Combination therapy of anti-PD-1 antibodies and activated cells significantly delayed tumor progression in glioma-bearing animals (MRI volumometry) as compared to the monotherapy regimens of anti-PD-1 or stimulated NK cells alone (P<0.001). Adoptive immunotherapy with anti-PD-1 antibodies (as shown by immunohistochemistry) increased tumor infiltration with activated CD8+ T cells, natural killer (NK1.1) cells and decreased suppressive PD1+ immune cells. This was accompanied with an increase of granzyme B and IFNγ production in the peripheral blood. Activation of innate and adaptive immune responses resulted in prolonged animals survival in combination therapy group. The obtained results support the combinatorial strategy of immune checkpoint inhibitor anti-PD-1 and adoptive cells immunotherapy in treatment of glioblastoma. The study was supported by Alexander von Humboldt Fellowship, DFG grant SFB824/2, Germany and grant of the Russian Science Foundation 14-50-00068 and by the Federal Agency of Scientific Organizations, Russia, State Grant of the Ministry of Health of the Russian Federation №32.
The role of race and economic characteristics in the presentation and survival of patients with non-small cell lung cancer.
Authors: Kerri McKie, Jianying Zhang, Geoffrey Graeber, Debra Maddox, John Charles Flickinger, Malcolm M. DeCamp, John M. Varlotto, James Liebmann, William Vincent Walsh, Lisa Huang, Nengliang Yao, Karl Uy, Cameron Stock
Journal: Journal of Clinical Oncology (2016)

8552 Background: Little is understood regarding the inter-relation between economic and racial/ethnic differences in presentation and survival of lung cancer patients. Our investigation will investigate these differences in the white-hispanic(H), white-non-hispanic(W), Black( B), Asian(A ), and the remaining population( R). Methods: A retrospective review of the SEER database was conducted through the years 2004-2012. Population differences were assessed via chi-square testing. Univariate and Multivariate analysis( MVA) were used to detect overall survival(OS) differences in the total population and for those patients with early-stage(T1-T2 < 4cm N0) surgically-resectable tumors(ESR). Results: During the years of our study, independent of race, the percentage of Stage I progressively decreased(54.15% to 43.5%, p < 0.0001) while Stage 4 progressively increased(13.1%-21.1%, p < 0.0001). As compared to the other populations, B were more likely to present with younger age, male sex, no insurance/unknown insurance, stage IV, and a median household income less than $50,000. W and A populations were more likely to have Stage I disease, have surgery recommended and performed as compared to the B, H, and R populations. In the entire population, factors significantly associated with OS in the MVA were female sex, younger age, being insured, Asian race, median household income > 50,000 as well as early stage, performance of surgery, and well-differentiated tumors. Factors significantly associated with OS in the MVA in the ESR tumors were Asian race, younger age, marriage, median household income > $50,000, and well-differentiated tumors. Conclusions: While accounting for histologic and economic variables, A had a higher OS in the entire lung cancer population and with ESR tumors. Median household income was associated with OS in the entire population and in the ESR tumors.
An explorative study of the psychological profile of women who access an oncofertility unit.
Authors: Valentina E. Di Mattei, Letizia Carnelli, Giorgia Mangili, Paola M.V. Rancoita, Martina Bernardi, Martina Mazzetti, Paola Taranto, Alice Bergamini, Enrico Papaleo, Massimo Candiani
Journal: Journal of Clinical Oncology (2017)

e21557 Background: Advances in cancer treatment have resulted in an increase in survival rates. Thus, quality of life after disease is being addressed more often; loss of fertility is a crucial aspect, especially in young women. This study aims to investigate the psychological profile of women who access the Oncofertility Unit at the San Raffaele Hospital before gonadotoxic treatment. Psychological consultation is undertaken prior to the medical evaluation as an integrative part of fertility preservation counselling. Our hypothesis is that women who access the Unit present psychologically adaptive characteristics, which facilitate a better adjustment to diagnosis and disease; this involves the decision to cryopreserve their oocytes to avoid possible future infertility. Methods: Seventy-six women were counselled between January 2014-2017; 96% of these (N = 73) decided to undergo cryopreservation. Only these women returned the administered questionnaires and took part in the study. A self-report measure and three validated questionnaires were used: the Beck Depression Inventory (BDI-II), the State Trait Anxiety Inventory Form-Y (STAI-Y), and the Temperament and Character Inventory – Revised (TCI-R). Results: The age range of the sample was 19-42 years (mean = 30.49; SD = 5.42); 21% (N = 15) of patients were older than 35 years. Seventeen women (23%) were single and 12% (N = 9) had children prior to the cancer diagnosis. Regarding the BDI, 89% (N = 65) of patients obtained minimal depression scores [0-13]. On the STAI-Y trait subscale, 70% (N = 51) of patients’ scores fell within the low anxiety range [20-40]; state anxiety scores were higher, but only 18% (N = 13) of women reported high levels [60-80]. The TCI-R highlighted that 95% (N = 69) of patients had medium or high levels of Persistence (perseverance despite fatigue Conclusions: Women who access the Unit report low levels of psychological distress (depression and anxiety) and show adaptive personality traits. This supports our hypothesis. The main study limitation of the study is the lack of data regarding women who decided not to undergo cryopreservation.
Sofosbuvir-based therapy in patients with chronic hepatitis C virus infection and malignancies: A prospective study of 143 patients.
Authors: Harrys A. Torres, Minas P. Economides, Andreas Kyvernitakis, Parag Mahale, Jeff Hosry, Aung Naing, Francesco Turturro, Ahmed Omar Kaseb, Issam I. Raad, Bruno Palma Granwehr
Journal: Journal of Clinical Oncology (2017)

e18152 Background: Data on the management of chronic hepatitis C virus (HCV) infection in cancer patients (pts) are sparse with many of them excluded from cancer clinical trials (CCT). We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in such pts. Methods: Consecutiveptstreated with SOFBT at MD Anderson (1/2014-2/2017) were included in a prospective observational study. Efficacy (sustained virological response 12 weeks [SVR12] after SOFBT) was assessed based on intention to treat (ITT) analysis. A posthoc per-protocol analysis (PPA) was performed on pts with 12 weeks of follow-up post SOFBT. Adverse events (AEs) and drug-drug interactions (DDIs) were evaluated. Results: Of the 143 pts studied, the majority were men (102; 89%), white (89; 62%) and had genotype 1 (103; 72%). The most common cancers were non-Hodgkin lymphoma (NHL), hepatocellular carcinoma (HCC) (24; 17%, each) and breast cancer (11; 8%). Of the 31 infected pts excluded from CCTs, 27 (87%) were granted access after SVR. The overall SVR12 were 90% ITT (129/143) and 91% PPA (118/130). SVR12 ITT were 80% (8/10) for SOF+peg-interferon+ ribavirin, 86% (24/28) for SOF+ ribavirin, 95% (20/21) for SOF+simeprevir, 90% (64/71) for SOF/ledipasvir, 100% (8/8) for SOF+daclatasvir and 100% (5/5) for SOF/velpatasvir. The most common AEs were grade 1 (50; 35%), predominantly anemia (22%). DDIs or grade 4 AEs did not occur. Two pts died during the study period, both from reasons unrelated to SOFBT. In 3 pts with HCV-associated NHL, SOFBT was used alone without chemotherapy. Two of them had splenic marginal zone NHL and achieved complete remission (CR); the remaining pt had follicular lymphoma with stable cancer (SC) after SOFBT. No cases of de novo HCC occurred within 6 months of SOFBT. In the same period, 10% (4/40) of pts with SC had progression (acute leukemia, breast cancer, HCC and NHL in 1 each) and 5% (4/75) of pts with CR developed relapse (acute leukemia in 3, NHL in 1). More pts who failed SOFBT had cirrhosis (77% vs 27%, P = .001) and poorer adherence (≥ 2 missed appointments) (43% vs 4%, P = .001) than those with SVR. Conclusions: SOFBT is effective and safe in cancer pts; it improves access to CCT and may induce CR in selected NHL pts.
Phase Ib trial of nivolumab combined with metformin for refractory/recurrent solid tumors.
Authors: Toshio Kubo, Katsuyuki Hotta, Takashi Ninomiya, Hironari Kato, Shigeru Horiguchi, Atsushi Takamoto, Toshiyuki Kozuki, Naoyuki Nogami, Hiroshi Ishii, Tomohiro Nishina, Daijiro Harada, Shinichi Toyooka, Hiroyuki Okada, Toshiyoshi Fujiwara, Heiichiro Udono, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2018)

TPS3119 Background: Although immune-checkpoint inhibitors (ICIs) have shown significant survival benefits in several cancers, optimal outcomes have been limited to subsets of patients. We obtained complete regression of an engrafted solid tumor with metformin in a murine syngeneic model. This effect could not be obtained in T cell-deficient SCID mice. These findings suggested that metformin induced immune-mediated reactions. The combination of anti-PD-1 antibody (nivolumab) and metformin resulted in significant tumor regression. This combination also increased the number of tumor-infiltrating CD8 T cells producing IL-2, TNF-α, and IFN-γ, suggesting that this combination induced clinically synergistic antitumor effects. Based on these results, we initiated the following study. Objectives: To investigate the safety, efficacy, and pharmacokinetics of combined treatment with metformin and nivolumab. Methods: This was an open-label, phase Ib trial consisting of two parts (part 1 and 2). The recommended dose of metformin combined with nivolumab was determined in part 1, and the safety and efficacy at the optimal dose were examined in part 2. The inclusion criteria were as follows: histologically or cytologically diagnosed refractory/recurrent solid tumors in part 1, and non-small cell lung cancer or pancreatic cancer that was refractory to standard primary treatment in part 2; use of naïve ICIs; a performance status of 0 or 1; > 20 years of age; and adequate organ functions. The primary endpoints were safety, maximum tolerated dose (MTD), and dose limiting toxicity (DLT) in part 1, and pharmacokinetics and adverse event profiles in parts 1 and 2. The secondary endpoints were efficacy, tumor shrinkage, and progression-free survival. Nivolumab (3 mg/kg) was administered intravenously every 2 weeks. In part 1, metformin was started at 750 mg/day, and increased by 750 mg/day up to 2,250 mg/day. The MTD and recommended dose were determined by the 3+3 cohort method. The DLT evaluation period was 4 weeks from the start of administration. A total of 9–18 patients were enrolled in part 1, and 30 patients in part 2. Enrollment began in 2017 and will be complete by 2019. The UMIN registration number is 000028405. Clinical trial information: 000028405.
Lobectomy Is Associated with Better Outcomes than Sublobar Resection in Spread through Air Spaces (STAS)-Positive T1 Lung Adenocarcinoma: A Propensity Score–Matched Analysis
Authors: Takashi Eguchi, Koji Kameda, Shaohua Lu, Matthew J. Bott, Kay See Tan, Joseph Montecalvo, Jason C. Chang, Natasha Rekhtman, David R. Jones, William D. Travis, Prasad S. Adusumilli
Journal: Journal of Thoracic Oncology (2018)
ColotypeR: A tool to classify colon cancers by consensus molecular subtype and subtype-specific risk of recurrence.
Authors: Steven Allen Buechler, Sunil S. Badve, Yesim Gokmen-Polar, Emily Herring, Katelyn Ludwig, Amanda Hummon
Journal: Journal of Clinical Oncology (2018)

632 Background: Colon cancer is highly heterogeneous in prognosis and response to treatment. The consensus molecular subtypes (CMS1-4, and mixed) partition colon cancers into distinct groups. CMS4 tumors, a mesenchymal subtype, have the worst prognosis and poor response to standard chemotherapies. There is a critical need for accurate molecular subtyping, and subtype-specific management. Methods: Affymetrix microarrays colon cancer datasets (N = 813; GSE39582, GSE14333) were partitioned into training (AT; N = 370) and validation sets (AV; N = 443) balanced for clinical traits. A novel multistate gene methodology was used to predict CMS, and prognosticate subtype-specific relapse-free survival (RFS) in the training set. Accuracy of CMS prediction and prognostic significance was validated in the AV and TCGA colon cancer (COAD; N = 458) sets. Results: In the training set, a 20-gene panel (ColotypeR-CMS) predicts CMS subtype. Mean accuracy for CMS1-4 prediction was 0.87 in AV and 0.81 in COAD. In AV, 5-year RFS is 0.52 (95%CI 0.43 – 0.63) in the predicted CMS4, and 0.70 (95%CI 0.65 – 0.77) in the non-CMS4 samples. The risk of relapse for non-CMS4 samples was refined by a genomic score (ColotypeR-Risk) computed using expression of 25 genes in the training set. ColotypeR-Risk was prognostic of RFS (p = 0.0004) among the AV non-CMS4 samples, and also prognostic (p = 0.0001) among the stage II non-CMS4 AV samples not treated with chemotherapy. The prognostic significance of ColotypeR-Risk among non-CMS4 samples is independent of tumor location (right or left) and CMS subtype (CMS1-3 or mixed). ColotypeR-Risk was also prognostic of RFS in non-CMS4 samples in COAD (p = 0.005). Conclusions: ColotypeR identifies the consensus molecular subtypes (CMS1, CMS2, CMS3, CMS4, or mixed), and assesses subtype-specific risk of recurrence of colon cancer. ColotypeR identifies prognostic risk and molecular features that could help guide the management of colon cancer patients.