scholarly journals Are clinical trial eligibility criteria an accurate reflection of a real-world population of advanced non-small-cell lung cancer patients?

2018 ◽  
Vol 25 (4) ◽  
Author(s):  
K. Al-Baimani ◽  
H. Jonker ◽  
T. Zhang ◽  
G.D. Goss ◽  
S.A. Laurie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Ecog Ps

Background Advanced non-small-cell lung cancer (nsclc) represents a major health issue globally. Systemic treatment decisions are informed by clinical trials, which, over years, have improved the survival of patients with advanced nsclc. The applicability of clinical trial results to the broad lung cancer population is unclear because strict eligibility criteria in trials generally select for optimal patients.Methods We performed a retrospective chart review of all consecutive patients with advanced nsclc seen in outpatient consultation at our academic institution between September 2009 and September 2012, collecting data about patient demographics and cancer characteristics, treatment, and survival from hospital and pharmacy records. Two sets of arbitrary trial eligibility criteria were applied to the cohort. Scenario A stipulated Eastern Cooperative Oncology Group performance status (ecog ps) 0–1, no brain metastasis, creatinine less than 120 μmol/L, and no second malignancy. Less-strict scenario B stipulated ecog ps 0–2 and creatinine less than 120 μmol/L. We then used the two scenarios to analyze treatment and survival of patients by trial eligibility status.Results The 528 included patients had a median age of 67 years, with 55% being men and 58% having adenocarcinoma. Of those 528 patients, 291 received at least 1 line of palliative systemic therapy. Using the scenario A eligibility criteria, 73% were trial-ineligible. However, 46% of “ineligible” patients actually received therapy and experienced survival similar to that of the “eligible” treated patients (10.2 months vs. 11.6 months, p = 0.10). Using the scenario B criteria, only 35% were ineligible, but again, the survival of treated patients was similar in the ineligible and eligible groups (10.1 months vs. 10.9 months, p = 0.57).Conclusions Current trial eligibility criteria are often strict and limit the enrolment of patients in clinical trials. Our results suggest that, depending on the chosen drug, its toxicities and tolerability, eligibility criteria could be carefully reviewed and relaxed.

A phase II study of nedaplatin (CDGP) and docetaxel (TXT) in patients with advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7660-7660 ◽  
Author(s):  
S. Fujino ◽  
Y. Asada ◽  
Y. Nakano ◽  
Y. Suzumura ◽  
S. Inoue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Ecog Ps

7660 Background: Nedaplatin (CDGP) is a cisplatin derivative developed in Japan. In non-small cell lung cancer (NSCLC), its response as monotherapy has been reported to be 20.5%, while when used in combination with vindesine, its efficacy is similar to cisplatin (CDDP). With respect to adverse effects, it causes less nausea/vomiting and nephrotoxicity compared to CDDP. By these data, we conducted a phase II study of combination treatment with CDGP and docetaxel (TXT) in advanced NSCLC. Methods: Forty six patients (Male/Female 39/7, median age 65 years (40–79), IIIB/IV 20/26) were enrolled from March 2004 to March 2006. Eligibility criteria included signed informed consent, age over 20 and under 80, measurable disease, ECOG PS 0–1, adequate bone marrow reserve, no previous chemotherapy or radiotherapy, and life-expectancy of at least 12 weeks. Treatment consisted of 80 mg/m2 CDGP and 60 mg/m2 TXT on day one with about 1,000 ml of hydration every 3–4 weeks. Results: One hundred and forty four cycles were given to 46 pts (mean cycles 3.1) and the mean dosages actually administered were 75.5±6.1 mg/m2 for CGDP and 57.7±4.6 mg/m2 for TXT. An over all response rate was 52.2% (squamous cell carcinoma 66.7%, adenocarcinoma 44.0%), median survival time was 12 months and 1-year survival rate was 50%. NCI-CTC grades 3–4 leukopenia, neutropenia, nausea/vomiting and appetite loss occurred in 44 (29.2%), 50 (34.7%), 5 (3.5%), 6 (4.2%) cycles, respectively. There was no grade 3–4 anemia, thrombocytopenia and neuropathy. Conclusions: This combination of chemotherapy was well tolerated, and its activity and survival for advanced NSCLC were acceptable. The update data will be presented at the meeting. No significant financial relationships to disclose.

Improvements in access to cancer clinical trials facilitated by comprehensive genomic profiling in non-small cell lung cancer.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 59-59
Author(s):  
Woojung Lee ◽  
Scott Spencer ◽  
Josh John Carlson ◽  
Tam Dinh ◽  
Victoria Dayer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Comprehensive Genomic Profiling

59 Background: The use of comprehensive genomic profiling (CGP) in cancer patients could lead to additional enrollment in clinical trials that study novel genetic biomarkers, potentially reducing treatment costs for payers and improving health outcomes for patients. Our objective was to estimate the number of additional clinical trials in which patients with non-small cell lung cancer (NSCLC) could potentially enroll due to the use of CGP vs. a comparator panel of 50 genes or less. Methods: Clinical trials in NSCLC that started between 2015 - 2020 were identified from the Aggregate Analysis of ClinicalTrials.gov (AACT) database. Trials with unknown status or study sites outside the United States only were excluded. We abstracted information on required genetic alterations based on the study eligibility criteria. We calculated the incremental number of trials available to patients due to results generated by CGP (FoundationOne CDx, 324 genes) vs. a commercially available comparator panel that was 50 genes or less (Oncomine Dx Target Test, 23 genes) by phase and calendar year. The additional trials were characterized by disease severity, type of therapy, and setting. Results: Enrollment eligibility was dependent on genetic variant status in 35% (250/709) of all identified NSCLC trials. There were 29 (248 vs. 219) additional clinical trials available to patients through the use of CGP, 12% of all gene-specific trials for NSCLC. We identified 45 uses of genetic markers in the 29 additional clinical trials. The most frequent genetic marker in the incremental trials was microsatellite instability, accounting for 44% of all identified markers (20/45). The incremental number of trials available to patients due to the use of CGP did not vary significantly over time but varied by phase – most of the additional clinical trials were in phase 1 or 2 (28/29, 97%). Most of the incremental trials were in metastatic disease (22/29, 76%) and were conducted in academic or advanced community settings (18/29, 62%). The most frequently studied type of intervention in these studies was targeted monotherapy (8/29, 28%), followed by immuno-monotherapy (7/29, 24%). Conclusions: Clinical trials in NSCLC initiated over the past 5 years have consistently included CGP-specific genes or markers in eligibility criteria. Patients with NSCLC have the potential to benefit from the use of CGP as compared to smaller gene panels through improved access to clinical trials.[Table: see text]

Phenotyping clinical trial treatment regimens in cancer: An integrative ontology, artificial intelligence and knowledge engineering approach.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14054-e14054
Author(s):  
Yun Mai ◽  
Kyeryoung Lee ◽  
Zongzhi Liu ◽  
Zhiqiang Li ◽  
Scott Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Regimens

e14054 Background: Matching clinical attributes (i.e. indications, lab tests, treatment regimens) of clinical trial eligibility criteria with real world patient data is extremely challenging. Attribute phenotyping is one of the key components of Trial2Patient, a customized system developed by Sema4 to find patients for clinical trials. Transforming treatment regimens to a standard ontology and encoding drugs with standard nomenclatures will facilitate the semantic retrieval of treatments mentioned in clinical trial criteria. This will also enable the interoperation between different data sources that is often required for fast-learning and scalable healthcare information system. Methods: Free text containing treatment regimen/medication terms were extracted and preprocessed from three sources: 1) clinical trials listed in a commercial database citeline.com, 2) clinical trials listed in clinicaltrials.gov, and 3) National Comprehensive Cancer Network (NCCN) Guidelines. The regimen terms such as neoadjuvant therapy for non-small cell lung cancer, checkpoint inhibitor, EGFR inhibitor, androgen deprivation therapy (ADT), among many others, were profiled by AI methods (i.e. pattern reorganization and rule-based) and knowledge engineering via Sema4’s in-house knowledge base (CAV), Pharmaprojects in citline.com and NCCN Guidelines. The drugs related to each regimen were identified and mapped to RxCUI via RxNorm ontology. Results: We identified 76 regimen terms for non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and prostate cancer (e.g. PD-L1 ≥1% nonsquamous NSCLC, bone antiresorptive therapy for M1 castration resistant prostate cancer), and 14,476 drug-category pair (e.g. pembrolizumab is a PD-1 inhibitor, pembrolizumab is used as the third line and beyond systemic therapy for M1 CRPC). All drugs identified were mapped to RxCUI for real world patient matching. Conclusions: This approach systematically extracted and normalized regimens and medications mentioned in clinical trials in NSCLC, SCLC and prostate cancer to standard codes. These standardized data can be used in mapping treatment histories of a patient to the eligibility criteria for clinical studies or for identifying studies relevant to a patient. The outcome of profiling cancer treatment regimens through standard ontology RxNorm may be particularly valuable in cancer studies based on real-world evidence.

A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small cell lung cancer with wild type EGFR (OLCSG1202).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20614-e20614
Author(s):  
Akihiro Bessho ◽  
Nobuaki Ochi ◽  
Shoichi Kuyama ◽  
Nobukazu Fujimoto ◽  
Takahiro Umeno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Thymidine Phosphorylase ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Phase Iii ◽  
Wild Type ◽  
Small Cell Lung

e20614 Background: S-1 is an oral fluoropyrimidine anticancer agent that combines tegafur, gimeracil, and oteracil potassium. Two phase III trials in advanced non-small cell lung cancer (NSCLC) showed the non-inferiority of combination of S-1 with carboplatin or cisplatin compared with standard platinum doublet chemotherapy. Although the S-1/platinum is one of the first line combinations for advanced NSCLC, efficacy and safety of the regimen in the elderly remain unknown. Methods: Patients were required to be previously untreated advanced NSCLC with wild-type EGFR, aged 70 or more, PS of 0-2. They received oral S-1 (40 mg/m2, twice daily) for 2 weeks and carboplatin (AUC 5 on day 1) every 4 weeks as an induction treatment. After 4 cycles of the induction, S-1 alone (40 mg/m2, twice daily for 2 weeks) was administrated every 4 weeks as a maintenance therapy until PD. Primary endpoint was overall response rate (ORR), which was expected more than 20%, and secondary endpoints included disease control rate (DCR), PFS, OS, and toxicity profile. The association between clinical outcomes and gene expressions including thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, VEGF and ERCC1 in tumors was evaluated. Results: Thirty-three patients were enrolled between March 2013 and June 2015. Median age was 78 years old (range: 70 – 89), and 51.5% had a PS of 0. ORR was 30.3% (95% CI: 14.6 – 46.0%) and DCR was 57.6% (95% CI: 40.7 – 74.4%). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%) and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. Median PFS and OS times were 134 days (95% CI: 79 – 173) and 479 days (95% CI: 250 – 571), respectively. Low thymidine phosphorylase expression was associated with DCR (P < 0.01). Conclusions: Carboplatin plus S-1 showed preferable efficacy and tolerable toxicity for elderly with NSCLC. (Clinical trial number: UMIN000009345) Clinical trial information: 9345.

Updates in Local-Regionally Advanced Non–Small Cell Lung Cancer

2019 ◽  
pp. 553-562 ◽  
Author(s):  
Anne S. Tsao ◽  
Shruti Jolly ◽  
Jay M. Lee
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Early Stage ◽  
Standard Of Care ◽  
Small Cell ◽  
Small Cell Lung

The landscape for therapy in local-regionally advanced non–small cell lung cancer (NSCLC) has shifted dramatically in the last year as a result of the PACIFIC trial, which demonstrated a significant survival benefit with the addition of 1 year of durvalumab after concurrent chemoradiation. This is a new standard of care for unresectable local-regionally advanced NSCLC and is the first trial to show that immunotherapy can increase survival in earlier-stage NSCLC. Several clinical trials are underway or in development to explore the role of adding immunotherapy to concurrent chemoradiation, followed by a year of immunotherapy or to even replace chemotherapy in this treatment paradigm. In resectable disease, adjuvant chemotherapy is still the standard of care for stage IB (tumors ≥ 4 cm) through stage III disease. However, new studies are investigating the role of adding immunotherapy to neoadjuvant chemotherapy or as adjuvant therapy for 1 year after resection. Molecular profiling for early-stage disease is not currently the standard of care, but several national clinical trials are studying the benefit of adding adjuvant-targeted therapies. This article will detail the current standard practices in early-stage and local-regionally advanced NSCLC and describe the evolving strategies that are under investigation that may further refine our current practice.

scholarly journals Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients—Mechanism of Action and Future Concepts

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2836
Author(s):  
Kamila Wojas-Krawczyk ◽  
Paweł Krawczyk ◽  
Michał Gil ◽  
Maciej Strzemski
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Limited Effectiveness

Due to the limited effectiveness of immunotherapy used as first-line monotherapy in patients with non-small-cell lung cancer (NSCLC), the concepts of combining classical immunotherapy based on immune checkpoint antibodies with other treatment methods have been developed. Pembrolizumab and atezolizumab were registered in combination with chemotherapy for the treatment of metastatic NSCLC, while durvalumab found its application in consolidation therapy after successful chemoradiotherapy in patients with locally advanced NSCLC. Exceptionally attractive, due to their relatively low toxicity and high effectiveness, are treatment approaches in which a combination of two different immunotherapy methods is applied. This method is based on observations from clinical trials in which nivolumab and ipilimumab were used as first-line therapy for advanced NSCLC. It turned out that the dual blockade of immune checkpoints activated T lymphocytes in different compartments of the immune response, at the same time affecting the downregulation of immune suppressor cells (regulatory T cells). These experiments not only resulted in the registration of combination therapy with nivolumab and ipilimumab, but also initiated other clinical trials using immune checkpoint inhibitors (ICIs) in combination with other ICIs or activators of costimulatory molecules found on immune cells. There are also studies in which ICIs are associated with molecules that modify the tumour environment. This paper describes the mechanism of the synergistic effect of a combination of different immunotherapy methods in NSCLC patients.

scholarly journals Influence of Performance Status on the Effectiveness of Pembrolizumab Monotherapy in First-Line for Advanced Non-Small-Cell Lung Cancer: Results in a Real-World Population

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 890
Author(s):  
Rocío Jiménez Jiménez Galán ◽  
Elena Prado-Mel ◽  
María Antonia Pérez-Moreno ◽  
Estefanía Caballano-Infantes ◽  
Sandra Flores Moreno
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Ecog Ps

The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0–1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0–1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0–1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.

Real-world outcomes of toripalimab (JS001) in advanced non-small cell lung cancer: A multicenter retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21193-e21193
Author(s):  
Zhihua Ruan ◽  
Bo Zhu ◽  
Yi Na Wang ◽  
Baogang Liu ◽  
Mengxia Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Antiangiogenic Agent ◽  
Small Cell Lung

e21193 Background: In the past 3 years, immunotherapy has revolutionized the treatment paradigm of advanced non–small cell lung cancer (NSCLC). Checkpoint inhibitors showed promising results in the treatment of patients with advanced NSCLC with improved outcomes in clinical trials, but results from clinical trials can be difficult to generalize to real-world patient populations. Herein, we disclose the data of efficacy profile of toripalimab, a novel humanized IgG-4 mAb against programmed cell death protein 1 (PD-1), for NSCLC in a real-world setting in China. Methods: This retrospective study leveraged electronic health record (EHR) data collected during routine patient care in 8 cancer centers in China. The cohort included patients with mNSCLC who had received toripalimab for metastatic disease (n = 166) with > 1 EHR-documented visit from January, 2019, to June, 2020. Patients (age ≥ 18yrs) with pathologically or histologically diagnosed advanced NSCLC receiving toripalimab treatment were enrolled in this retrospective, multicenter, real-world study. The endpoints included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and duration of response (DOR). Results: Between January 2019 and June 2020, 166 patients from 8 centers were eligible. The median age was 60.6 years, 134(81.7%) male, 123(76.4%) diagnosed as stage IV lung cancer, 69(42.9%) squamous histology, 25 (21.9%) underwent prior surgery and 94 (57%) received prior chemotherapy. Toripalimab was administered as first, second, and further lines of therapy in 45(28.1%), 60(37.5%) and 55(34.4%) patients, respectively. Among them, 28(17.5%) patients received toripalimab as monotherapy. 22(13.8%) received in combination with antiangiogenic agent and 132(82.5%) in combination with chemotherapy. The 164 patients were eligible for efficacy evaluation. The ORR and DCR were 21.3% and 81.7% for all the evaluable patients. The median PFS was 15.0 months (95% CI 10.2 – NA). The median PFS of adenocarcinoma and squamous cell carcinoma were 15.4 months(95% CI 10.2-NA) and 13.4 months(95% CI 10.6-NA), respectively. The PFS in first line and further-line treatment were 15.4 months(95% CI 12.6-15.4) and 13.4 months(95% CI 7.0-NA). Stratified analysis revealed that the PFS of toripalimab monotherapy and combination treatment were 15.0 months(95% CI 12.6-15.0) and 15.4 months(95% CI 8-NA). The PFS were comparable between the patients received with or without anti-angiogenesis agents (11.5m vs 15.4m). Conclusions: Toripalimab monotherapy or in combination with chemotherapy and/or antiangiogenic agent in real world were effective in advanced NSCLC patients.

scholarly journals Survival Analysis of Advanced Non–Small Cell Lung Cancer Patients Treated by Using Wheel Balance Cancer Therapy

2016 ◽  
Vol 15 (4) ◽  
pp. 467-477 ◽  
Author(s):  
Jongmin Kim ◽  
Chong-Kwan Cho ◽  
Hwa-Seung Yoo
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Conventional Treatment ◽  
Advanced Nsclc ◽  
Group Performance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ecog Ps

Objective. To investigate the clinical effect and the overall survival (OS) rate of patients with advanced non–small cell lung cancer (NSCLC) who have undergone Wheel Balance Cancer Therapy (WBCT). Methods. The cases of 33 patients with advanced NSCLC who were treated with WBCT at the East West Cancer Center (EWCC) between October 4, 2004, and October 3, 2013, without undergoing concurrent conventional treatment were analyzed. The Kaplan-Meier method was used to estimate the OS of the cases, and the median OS was calculated according to age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), conventional-treatment history, WBCT treatment duration, and histological tumor type. Results. The median OS of all patients was 31.1 (95% confidence interval [CI] = 3.5-58.7) months; the OS rates were 63.6% and 24.2% at years 1 and 2, respectively. The median OS rates of patients under and over 65 years were 45.2 (95% CI = 13.5-76.9) and 19.5 (95% CI = 7.1-31.8) months, respectively ( P = .189). The median OS rates of patients who received WBCT for >14 days but <28 days and those who received WBCT for ≥28 days were 16.2 (95% CI = 13.3-19.2) and 45.2 (95% CI = 14.4-76.0) months, respectively ( P = .437). The median OS rates of patients who had undergone prior conventional treatment and those who had not were 45.2 (95% CI = 9.1-81.3) and 3.9 (95% CI = unable to calculate) months, respectively ( P = .000). The median OS rates of patients with squamous cell carcinoma (SCC) and non-SCC lung cancer were 5.6 (95% CI = unable to calculate) and 45.2 (95% CI = 9.1-81.3) months, respectively ( P = .262). The median OS rate of patients with ECOG PS ≥3 was 14.3 (95% CI = 8.8-19.8) months; that of patients ECOG PS <3 could not be calculated. However, the mean OS rates of patients with ECOG PS <3 and with ECOG PS ≥3 were 85.7 (95% CI = 58.4-113.0) and 12.7 (95% CI = 8.5-16.9) months, respectively ( P = .000). No severe adverse events were encountered. Conclusions. Our study indicates that WBCT might be effective to prolong the length of survival for patients with advanced NSCLC who have previously undergone conventional treatment and have an ECOG PS <3.

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