tbuckley/cabot-search huggingface dataset:
Addressing Financial Barriers to Patient Participation in Clinical Trials: ASCO Policy Statement
Authors: Karen M. Winkfield, Jonathan K. Phillips, Steven Joffe, Michael T. Halpern, Dana S. Wollins, Beverly Moy
Journal: Journal of Clinical Oncology (2018)

Research conducted through clinical trials is essential for evaluating new treatment modalities, establishing new standards of cancer care, and ultimately improving and prolonging the lives of patients with cancer. However, participation in trials has been low, and this is attributable to various factors including patient financial barriers. Such financial barriers include the rising cost of cancer care; a lack of transparency in coverage policy; and the perception of ethical, compliance, or institutional impediments to patient financial support. ASCO convened a roundtable discussion with a variety of stakeholders to define the scope of the problem, as well as to identify clinical practice and policy solutions applicable at the institutional and system-wide levels. This statement summarizes key discussions from the ASCO Roundtable, as well as findings from the literature, and provides ASCO's recommendations for overcoming financial barriers that may otherwise prevent participation in clinical trials. These recommendations broadly address the following key areas: (1) improving the policy environment for coverage of clinical trials; (2) facilitating transparency among providers, patients, and payers for trial-related out-of-pocket costs; (3) refuting the specter of inducement to enable targeted financial support for patients; and (4) improving the available data on costs of cancer clinical trials.
Clinical implications of the 2012 US Preventive Services Task Force (USPSTF) PSA screening recommendation in prostate cancer diagnoses and 5-year survival at a Minnesota safety net health care system.
Authors: Kevin Gale, Daniel Fellows Pease, Joseph Guinness, Andres Wiernik
Journal: Journal of Clinical Oncology (2017)

5051 Background: Prostate specific antigen (PSA) screening for prostate cancer has declined following the USPSTF 2012 recommendation. How screening rates and prostate cancer diagnoses have subsequently changed in a racially diverse patient population is not well defined. In this study, we aim to determine the impact of the USPSTF screening recommendation in the Hennepin Healthcare System (HHS) in the state of Minnesota. Methods: A single-institution retrospective analysis of data from our electronic health record, to identify the characteristics of PSA screening and new prostate cancer diagnoses for men ≥50 years between 2008 and 2015. Data before and after May 2012 were compared. P-values were calculated using binominal and generalized linear models. Results: Nearly 22,000 patients underwent PSA screening from 2008 to 2015. PSA screening rates decreased after May 2012 for the four largest demographics represented (p &lt; 0.001). Hispanics and Blacks were more likely to be screened when compared to Whites and Asians (p &lt; 0.05). 319 cases of prostate cancer were diagnosed from 2008 to 2015 with 87 cases (27.3%) diagnosed by PSA-screening. The number needed to screen to diagnose one patient with prostate cancer at HHS was 137.5, and 9.5% of patients (1146 patients) had a false positive PSA that led to further testing or a biopsy. $56,090 was spent in screening costs per diagnosis of early stage prostate cancer via screening. Patients diagnosed from screening were less likely to present with high Gleason scores (8-10) compared to non-screening diagnosis (8% vs 23.3%, p &lt; 0.01). The 5-year survival percentage (prostate cancer mortality) was improved for those patients diagnosed by PSA screening vs the non-screened group (100% vs 89.3%, p &lt; 0.05). Conclusions: PSA screening has declined at HHS since the USPSTF recommendation against prostate cancer screening. Implementation of PSA screening in our healthcare system is expensive and leads to a high number of false positives. Despite this, the 5-year survival from prostate cancer is significantly higher when patients are diagnosed by PSA screening.
Changing patterns of subsequent malignancies in the Childhood Cancer Survivor Study cohort.
Authors: Lucie Marie Turcotte, Yutaka Yasui, Qi Liu, Sue Hammond, Michael A. Arnold, Rebecca M Howell, Todd M. Gibson, Wendy M. Leisenring, Gregory T. Armstrong, Leslie L. Robison, Joseph Philip Neglia
Journal: Journal of Clinical Oncology (2016)

10503 Background: Limited data exist on whether historical changes in therapeutic exposure have altered subsequent neoplasm (SN) risk after surviving childhood cancer. Methods: Occurrence of SNs was evaluated in 23,603 5-year survivors diagnosed <21 years of age from 1970-99. Cumulative SN incidence and 95% confidence intervals (CI) at 15 years from diagnosis and standardized incidence ratios (SIRs - using SEER incidence rates) for subsequent malignant neoplasms (SMNs) were compared over treatment eras. Piecewise exponential models assessed changes in rates over treatment eras, adjusting for demographic and clinical characteristics. Results: With 365,757 person-years at risk, a total of 3310 SNs (including 1026 SMNs, 233 benign meningiomas, 1855 non-melanoma skin cancers [NMSCs], 196 other) among 1760 survivors were reported and validated. Exposure to therapeutic radiation decreased by treatment decade (77.3%, 57.5%, 42.0%), while use of alkylating agents (41.5%, 53.6%, 55.3%) and epipodophyllotoxins (2.1%, 13.6%, 31.5%) increased. Cumulative incidence of SMNs at 15 years was lower for survivors diagnosed in the 1990s (1.6%, 95% CI 1.4-1.9) vs. 1970s (2.3%, 95% CI 2.0-2.7, p=0.001). A similar decline was seen for NMSCs (0.1%, 95% CI 0.1-0.2 vs. 0.7%, 95% CI 0.6-1.0, p<0.001). SIRs for SMNs declined significantly for survivors with attained age ≥20 (Table). After adjusting for demographics and cancer diagnosis, incidence rates declined every 5-year era by 7% for SMNs (95% CI 3%-12%, p=0.001), 20% for NMSCs (95% CI 14% -25%, p<0.001), and 17% for meningiomas (95% CI 8%-27%, p=0.001). Inclusion of treatment exposures attenuated the treatment era-associated decline of SN rates, indicating the decline was at least partially attributable to changes in treatment exposure. Conclusions: Although survivors remain at increased risk for SNs, risk is reduced for survivors diagnosed in more recent eras. Models suggest historical reductions in treatment exposure have contributed to the decreased risk. SIRs for SMNs by attained age and treatment era of primary diagnosis. 1970-74 1975-79 1980-84 1985-89 1990-94 1995-99 P-trend 5-19 y 10.9 10.2 9.7 9.7 10.2 6.3 0.077 20-29 y 6.4 5.2 5.0 4.5 3.6 3.6 0.002 30-39 y 6.3 5.0 5.5 4.2 2.7 4.8 0.006
Chronic pain and accumulation of growth factors in perifocal tissues of melanoma and impact on malignancy and early metastasis.
Authors: I. M. Kotieva, Oleg I. Kit, Elena M. Frantsiyants, Irina V. Kaplieva, Lidia K. Trepitaki, Valeria A. Bandovkina, Ludmila Ya. Rozenko, Natalia D. Cheryarina, Yulia A. Pogorelova
Journal: Journal of Clinical Oncology (2018)

e21621 Background: Over 40% of adults live with chronic pain, and the number is growing; 50% of cancer patients have chronic pain. The purpose of the study was to determine levels of some growth factors in tumor (T), perifocal tissues (PT) and in intact skin (IS) of female mice with chronic neurogenic pain in the dynamics of the В16/F10 melanoma development. Methods: The study included 64 female C57BL/6 mice. B16/F10 melanoma was transplanted under the skin of the back to animals of the main group 2 weeks after the sciatic nerve ligation; the controls underwent the same procedure without the ligation. Levels of EGF, EGFR, IGF1, IGF2, FGF21 and TGF-β1 were determined by ELISA. Results: Chronic pain increased skin levels of IGF1 (by 24 times), IGF2 and EGF (by 3 times). Levels of all factors increased in PT of animals with chronic pain 1 week after the tumor transplantation: IGF1 – by 10 times, IGF2 – by 8 times, FGF21 – by 4 times, TGF-β1 and EGFR – by 2 times, and EGF – by 1.4 times. Levels of EGF and EGFR increased in T by 1.8 times, and IGF1 – by 1.4 times. Such changes maintained up to the end of the experiment (the death of mice in 3 weeks). Chronic pain effect on the В16/F10 melanoma development, compared to the control group, was characterized by an early tumor onset, bifocal tumor growth, an early 100% metastasis (including metastases to non-typical sites), and decreased survival of animals. Conclusions: Due to changed metabolic profile of the body, chronic pain contributes to the accumulation of growth factors, especially in perifocal tissues of melanoma, enhancing its malignancy and provoking early metastases.
Response to checkpoint inhibition in lung cancer with molecular driver alterations.
Authors: Amanda Tufman, Kathrin Kahnert, Diego Kauffmann-Guerrero, Benjamin-Alexander Bollmann, Simone Reu, Zulfiya Syunyaeva, Christian Schneider, Farkhad Manapov, Thomas Wehler, Rudolf M. Huber, Heiko Golpon
Journal: Journal of Clinical Oncology (2018)

e21071 Background: Checkpoint inhibitors are widely used in NSCLC. While there is evidence that EGFR mutation driven tumours respond poorly to checkpoint inhibition, little is known about the sensitivity of other molecular driver cohorts. We present a multicenter cohort of NSCLC patients with molecular drivers treated with checkpoint inhibitors. Methods: Patients were identified from clinical databanks at two academic centers. Clinical data and molecular pathology results (sequential analysis for individual drivers and panel testing using the Oncomine Focus Panel from Life-Technologies). Molecular subgroups and controls were analysed for treatment response and time to treatment failure (TTF). Results: We identified 82 patients with advanced NSCLC treated with a checkpoint inhibitor. 38 driver alterations were found in 32 patients including mutations in KRAS, PiK3Ca, EGFR (activating and rare mutations), KIT, ERBB2, ERBB4 and MET, amplifications in MET, ERBB2 FGFR1 and MYC, and rearrangement in ALK and RET. Controls had a mean TTF of 24.9 weeks. This was similar to TTF in patients with KRAS (24.7 weeks) or PiK3Ca (25.3 weeks) mutation. TTF was shorter in those with EGFR mutation, MET amplification or MET mutation. Tumours with alterations in ALK, RET, KIT, ERBB2 or ERBB4 did not benefit from checkpoint inhibition. Conclusions: NSCLC with KRAS mutation or PiK3Ca mutation seems to respond well to checkpoint inhibition, whereas tumours with RET fusion or MET, ERBB2, KIT or EGFR mutation seem to respond poorly. Further larger cohorts must be studied to determine the best treatment sequences for patients with genetic driver alterations. Molecular Driver Response Rate under checkpoint inhibition (%) Disease Control Rate under checkpoint inhibition Time to treatment failure (mean; weeks) KRAS Mutation 21 % 57 % 24.7 PiK3Ca Mutation 33 % 33 % 25.5 Common activating EGFR Mutation 33 % 33 % 12.5 Rare or Complex EGFR Mutation 0 % 0 % 8.7 MET Mutation 33 % 66 % 19.5 MET Amplification 0% 0% 4.1 Individual patients with ALK Translocation, RET Fusion, KIT Mutation, ERBB4 Mutation, ERBB2 Mutation or ERBB2 Amplification 0% 0% 9.0 Individual patients with MYC Amplification or FGFR1 Amplification 100% 100% 43.0 No Known Driver Alteration 52 % 56 % 25.3
Efficacy of trastuzumab for HER-2 positive breast cancer in a real-life setting: A decade of experience under national treatment coverage regulations.
Authors: Natalia Camejo, Cecilia Castillo, Rafael Alonso, Emiliano Rivero, Camila Mezquita, Agustin Rosich, Fiamma Dellacasa, Luciana Silveira, Jonathan Nuñez, Lucia Beatriz Delgado
Journal: Journal of Clinical Oncology (2018)

e18789 Background: In clinical trials, trastuzumab (TTZ) has shown an overall survival benefit (OS) in patients with HER-2 positive breast cancer (BC), both in the adjuvant and in the metastatic setting. Herein, we assessed the efficacy of TTZ in patients treated in routine practice but according to national treatment coverage protocols with similar patient selection criteria and follow-up, to those included in clinical trials that demostrated improved survival. These coverage protocols have been develloped by the National Fund of Resources (FNR) of Uruguay, which funds these indications since more than a decade. Methods: All patients with early and advanced BC treated with TTZ in our country between January 1th 2006 and December 31th 2016 according to coverage protocols stated by the FNR were evaluated. Data source was the database of the FNR. OS, analyzed by Cox proportional-hazards regression was the primary outcome. Results: The FNR reported data on 1944 women treated with TTZ during the aboved mentioned decade, of whom 1085 (55,8 %) were postmenopausal. The median age was 52,8 years and 1240 (61.5%) were HER-2 and hormone receptors positive. TTZ was administered as adjuvant therapy for 1209 (62%) patients of whom 275 (23 %)/ 673 (56 %)/ 222 (18 %) had disease stages I/II/III at diagnosis, respectively. In addition, 223 (11.5%) patients received TTZ combined with chemotherapy as first-line treatment for the advanced disease. Five years OS in the adjuvant setting was 87% (95% CI 85–89%). For patients that received TTZ as first line treatment for advanced BC median survival was 31.3 months (95% CI 10.1– 52.5 months). Conclusions: Our survival results are not inferior to those reported in clinical trials, both in the adjuvant (HERA trial OS at 4 years: 89.3%; B-31/N9831 OS at 6 years: 89.8%; BCIRG006 OS at 5 years: 91%) and the advanced (median survival of 25 months reported at Slamon D; N Engl J Med. 2001) settings. These results support the feasibility and importance of treating patients in routine practice stated by coverage protocols that are based in patient selection criteria and methods published in positive clinical trials.
Abstract 17251: Notch Signaling by Delta-Like 4 In Macrophages Contributes to Lesion Formation after Vascular Injury
Authors: Daiju Fukuda, Hideo Yagita, Masanori Aikawa
Journal: Circulation (2012)

Purpose: Monocytes/macrophages play causal roles in the neointimal hyperplasia after vascular injury through the promotion of inflammation, which associates with restenosis, a major limitation of the coronary angioplasty. The Notch pathway regulates embryonic development and contributes to physiological and pathological processes in adult tissues. We recently showed that Notch signaling triggered by Delta-like 4 (Dll4), one of the Notch ligand, promotes inflammatory responses in macrophages, leading to the development of cardiometabolic disorders. The role of Dll4 in the neointimal hyperplasia, however, remains unknown. This study tested the hypothesis that Dll4-mediated Notch signaling contributes to the lesion formation after vascular injury. Methods and Results: We induced wire-mediated vascular injury to C57BL/6 mice. Vascular injury promotes the expression of Dll4 (N=5, P<0.05), but not Jagged 1, another major Notch ligand. Immunohistochemistry in the lesions co-localized Dll4 expression and Notch ac...
Dependency of radiotherapy and combinatorial radio-immunotherapy responses on the systemic t cell immune response.
Authors: Kevin Lee Min Chua, Xiaotian Lin, Eugenia Yeo, Waseem Ahamed Shihabuddeen, Pek Lim Chu, Kar Peng Low, Dennis Poon, Enya Ong, Joseph Wee, Michael Fehlings, Alessandra Nardin, Khee Chee Soo, Melvin Chua
Journal: Journal of Clinical Oncology (2018)

12056 Background: Combinatorial immune checkpoint blockade (ICB) with radiotherapy (RT) potentiates anti-tumour response via modulation of the immune microenvironment. However, detailed host-specific mechanisms underpinning dramatic clinical responses of RT-ICB are poorly understood. Here, we performed deep characterization of the systemic immune response in circulating T cells following treatment with RT and RT-ICB. Methods: We recruited a cohort of 29 patients with biopsy-proven metastatic cancers (10 prostate, 10 EBV+ nasopharynx, 9 others) who underwent RT (N = 13) or RT-ICB (N = 16; anti-PD1/-PDL1/-CTLA4), under a prospective observational study protocol. All patients received ablative RT (8-50 Gy in 1-5 fractions). Patient blood samples were longitudinally collected at following timepoints: baseline, 2 d, 7 d, and 14 d post-RT/RT-ICB. Circulating T cells were profiled by a customized CyTOF panel of 41 T cell surface markers, and analyzed using the t-SNE method (ACCENSE v3.0). Results: Median follow-up was 3.6 mo (0.5–8 mo). At time of reporting, 26 of 29 patients had evaluable lesions; response of any kind was observed in 9 of 12 cases in the RT cohort and 12 of 14 cases in the RT-ICB cohort. However, we observed increased complete response rates at 1 mo in the RT-ICB than RT group (50% vs 8%). Additionally, we observed abscopal responses in 2 of 14 RT-ICB cases. We detected significant shifts in the CD8+ and CD4+ T cells that peaked 7 d post-RT (P < 0.001). Interestingly, the majority of responses (67%) involved the expansion of a distinct immunophenotype of elevated TbetDimCD28high effector memory CD8+ and CD4+ T cells post-RT. These responses were reproduced in the RT-ICB cohort; in particular, CD28highCD27high CD4+ T cells were increased in the exceptional responders (P = 0.027). Lastly, for a patient with abscopal response, this was associated with a 25% reduction of TH2 CD4+ T cells. Conclusions: Here, we characterized the systemic immune repertoire of circulating CD8+ and CD4+ T cells in response to RT, either alone or in combination with immunotherapy. Our data suggests that expansion of a distinct CD28highCD27high CD4+ T cell population may account for the dramatic responses to RT-immunotherapy.
Targeting the paracrine hormone-dependent guanylate cyclase/cGMP/phosphodiesterases signaling pathway for colorectal cancer prevention
Authors: N.S. Yarla, H. Gali, G. Pathuri, S. Smriti, M. Farooqui, J. Panneerselvam, G. Kumar, V. Madka, C.V. Rao
Journal: Seminars in Cancer Biology (2018)
Pre-operative tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study.
Authors: Guy Kantor, Eberhard Stoeckle, Martine Delannes, Marc-Andre Mahe, Antoine Italiano, Michèle Kind, Christine Dupouy, Antoine Giraud, Mikael Antoine, Maud Toulmonde, Augustin Mervoyer, Gwennael Ferron, Carine A. Bellera, Paul Sargos
Journal: Journal of Clinical Oncology (2017)

e22501 Background: To evaluate efficacy and feasibility of radiotherapy (RT: high-level dose 54 Gy, with 30 fractions over / 6 weeks) followed by surgery, for retroperitoneal liposarcomas. Methods: Helical tomotherapy was used for pre-operative RT. Clinical Target Volume (CTV) and main organs at risk were systematically delineated with the surgeon. Surgery was planned 4 to 8 weeks after RT. Inclusion criteria were operable, biopsy-proven, retroperitoneal liposarcomas. Toxicity was graded according to CTCAE V3.0. Overall survival (OS) was estimated using Kaplan-Meier method. Due to competing risks, we estimated the cumulative incidence of loco-regional relapse; 95% confidence intervals are reported [95%CI]. Results: Patients:From 04/2009 to 09/2013, 48 patients were included. Mean age: 62 years (y) (36 to 82). All but 1 patient were OMS ≤ 2. Histological types were 20 well differentiated (WDLS) and 28 dedifferentiated liposarcomas. Mean CTV was 2954 cc. Treatment:1 patient did not have surgery. Dosimetric constraints were respected. Monobloc exerese was systematically achieved. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1; 2%). Oncological outcomes:Median follow-up was 4.7 y. Cumulative incidence of loco-regional relapse at 3 and 5 y was 17% [8%; 29%] and 31% [16%; 47%] respectively. Estimates were 5% and 35% for dedifferentiated liposarcoma and 26% and 26% for well differentiated liposarcoma. OS at 3 and 5 y was 81% [66%; 89%]) and 78% ([63%; 88%] respectively. Toxicity: 2 months after surgery, 10 grade 3 toxicities and 1 grade 4 toxicity were reported for 6 patients; 3 patients died within 6 months after surgery, 2 of which were related to treatment. After 1 y, no further severe toxicity was observed; 5 cases of second cancers were reported: 1 myeloid leukeamia, 2 pancreatic, 2 breast carcinomas. Conclusions: This trial highlights the feasibility of preoperative 54 Gy RT. Although efficacy data (local control and OS) are encouraging, high incidence rates of acute toxicities and second cancers should be considered. Preoperative RT for WDLS remains questionable. Results from ongoing EORTC phase III Strass trial may provide further level of evidence for this approach. Clinical trial information: NCT01841047.
Treatment strategies in patients with hepatocellular carcinoma in a real-life cohort.
Authors: Martha Kirstein, Nora Schweitzer, Katerina Lappas, Theresa Winter, Michael Manns, Arndt Vogel
Journal: Journal of Clinical Oncology (2016)

e15630 Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Several local and sytemic therapies are available for patients with HCC depending on the stage of the disease. According to the stage migration concept based on the Barcelona Clinic Liver Cancer (BCLC) classification, patients are supposed to shift upon progression to the next treatment option for a more advanced BCLC stage. However, treatment sequencing might be more heterogenous in clinical practice. Methods: In this study, we retrospectively analyzed 1924 patients with HCC treated from 2000 to 2015 in real-life clinical practice at Hannover Medical School. sease stages with improvement of mOS. Results: Median overall survival (mOS) was 15 months in the total population. HCC was most often diagnosed at intermediate and advanced stage. Median/mean diameter of the largest lesion was 53/63.2(4-270)mm and 734(39.6%) patients were diagnosed with multinodular ( > 3) HCC. 451 patients (23.4%) received only best supportive care (BSC). Transarterial chemoembolization (TACE) was the most common initial treatment (n = 495, 33.6%), followed by resection (n = 391, 26.5%), systemic therapies (n = 266, 18%) and radiofrequency ablation (RFA, n = 260, 17.6%). 43.6% of the patients received the treatment proposed by BCLC. Subsequent treatment stage migration occurred only in 39% of all patients with any subsequent therapy. 24 (7.7%) of the initially resected patients subsequently underwent LT, 62 patients initially treated with RFA received a resection (1.2%) or LT (22.7%), 184 patients treated with TACE underwent LT (8.3%), resection (2%) or RFA (26.9%) and 7% of the initially systemically treated patients received more than BSC. Subsequent use of treatments suggested for earlier disease stages according to BCLC resulted in a better outcome for RFA and TACE (27 and 20 months vs. 23 and 16 months). Resection was primarily performed in large HCC ( ≥ 5cm). Most patients that underwent LT, received bridging therapies before LT (71.5%). Conclusions: Patients in this real-live cohort were not strictly treated according to the BCLC algorithm. RFA and TACE treated patients frequently received subsequent treatments proposed for earlier disease stages with improvement of mOS.