Artificial intelligence (AI)–powered pathologic response (PathR) assessment of resection specimens after neoadjuvant atezolizumab in patients with non-small cell lung cancer: Results from the LCMC3 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 106-106
Author(s):  
Sanja Dacic ◽  
William D. Travis ◽  
Jennifer Margaret Giltnane ◽  
John Abel ◽  
Filip Kos ◽  
...  
Keyword(s):  
Assessment Tool ◽  
Regression Line ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Strongly Correlated ◽  
Tumor Bed ◽  
Viable Tumor ◽  
Line Slope ◽  
Phase Ii And Iii

106 Background: PathR is an efficacy endpoint in Phase II and III neoadjuvant trials and is proposed as a surrogate for disease-free survival (DFS) and overall survival. Machine learning (ML)–based, automated approaches standardize quantification of areas of tumor bed and residual viable tumor. Here we show that automation may provide a scalable alternative to or complementary tool for manual assessment. Methods: We determined inter-reader variability for PathR among pathologists in the LCMC3 (NCT02927301) study and developed an AI-powered digital PathR assessment tool in line with manual consensus recommendations. Study cases were reviewed for PathR by a local site pathologist and 3 central expert pathologists (n = 127). When determined manually, major PathR (MPR) was defined as ≤10% viable tumor averaged per case. ML models were trained and validated by the PathAI research platform using digitized H&E-stained tumor sections. The digital PathR model predicted percent viable tumor for each case as the sum of the cancer epithelium area from each slide divided by the sum of tumor bed area for each slide. DFS (clinical cutoff: Oct 23, 2020) was reported for patients with manual and digital PathR assessment (n = 135). For digital MPR, we used a prevalence-matched cutoff that maintained the same proportion of patients as manual MPR. Results: Inter-reader agreement among 1 local and 3 central pathologists for manual PathR was good (n = 127; ICC = 0.87; 95% CI: 0.84-0.90). Agreement was 91% (κ = 0.82) on manual MPR and 98% (κ = 0.88) on pathologic complete response (pCR). 6 patients had unanimous pCR. Digital and manual PathR were strongly correlated (n = 135, Pearson r = 0.78) and digital PathR demonstrated an outstanding predictability for manual MPR (AUROC = 0.975). The range was 0%-60% for digital PathR and 0%-100% for manual PathR with a regression line slope < 1.0 (m = 0.303) indicating systematic differences between the methods, consistent with digital PathR using a high-resolution segmentation of cancer epithelium from stroma across each slide. Longer DFS was observed for MPR yes vs no with both digital and manual assessment (Table). Conclusions: This analysis showed good inter-reader agreement for manual and strong correlation of AI-powered digital and manual PathR. Comparable DFS rates for manual MPR and digital MPR are encouraging in the preliminary data. These data support further studies of digital PathR as a standardized and scalable tool to determine PathR. Clinical trial information: NCT02927301. [Table: see text]

624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Free Survival

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

scholarly journals Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeon Hee Park ◽  
Samir Lal ◽  
Jeong Eon Lee ◽  
Yoon-La Choi ◽  
Ji Wen ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Pathologic Complete Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Transcriptome Profiling ◽  
Complete Response ◽  
Strongly Correlated ◽  
Breast Cancers ◽  
Breast Cancer Cohort ◽  
Tumor Biopsies ◽  
Infiltrating Lymphocytes

AbstractTo elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.

Early analysis of toxicity and surgery in patients treated with cetuximab single agent followed by 5-fu, cetuximab and pelvic radiotherapy as neo-adjuvant treatment for operable, locally advanced rectal cancer (rc)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14531-14531
Author(s):  
F. Bertolini ◽  
S. Zironi ◽  
N. Malavasi ◽  
C. Dealis ◽  
F. Bertoni ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Surgical Complication ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Tumor Biomarkers ◽  
Ki 67 ◽  
Tumor Biopsy

14531 Background: Pre-operative chemo-radiotherapy in locally advanced RC has been used to improve local control and to facilitate sphincter-sparing surgery for distal tumors. Cetuximab, an anti EGFR monoclonal antibody, has proved efficacy in advanced colorectal cancer. Methods: Study design provided: 1) tumor biopsy to confirm diagnosis and to measure tumor biomarkers (EGFR, TS, p53, MAP kinase, Ki 67, p21, bcl-2; immunological cell profile at the tumor level: CD45RO, CD68, CD56 CD4+/CD25+, CD31, HLA-A, -B and -C), 2) Cetuximab single agent (400 mg/sqm loading dose, then 250 mg/sqm weekly) for 3 doses, 3) a second biopsy to evaluate tumor biomarkers, 4) Cetuximab 250 mg/sqm weekly plus 5FU (225 mg/sqm in continuous infusion) concomitantly with RT (50 Gy), 5) surgery. Tumor biomarkers are measured again on tumor specimen in non pCR patients (pts). 66 pts with resectable uT3/uT4 N0/+ RC will enter the study. Primary aim is: toxicity and activity (pathologic complete response). Secondary aim is: evaluation of biological parameters, rates of sphincter sparing surgery and disease free survival. Results: Up to now 29 pts are valuable for toxicity (M/F= 22/5; median age: 61; range: 35–74). Ultrasound staging at diagnosis is: uT3N0: 7; uT3N1: 20; uT4N1: 2. Four pts (14%) withdrew neo-adjuvant treatment after 1 administration of Cetuximab: 2 for hypersensitivity reactions (1 G3; 1 G4), 1 for progression and 1 for purulent arthritis. Twenty-two pts (75%) presented acne-like rash; treatment with Cetuximab was interrupted or reduced in 4 pts (14%): in 2 for acne-like rash grade 3 (NCI-CTC) and in 2 pts for refuse. Grade 1–2 gastro-intestinal toxicity (unrelated to Cetuximab) was observed in 13 pts (proctitis: 4; diarrhoea: 9); in 1 case: diarrhoea G4. Twenty pts are valuable for surgery: 18 pts (90%) underwent conservative surgery. Two pts (10%) experienced post-surgical complications: 1 anastomotic fistula and 1 colonic necrosis. Conclusions: Pre-operative treatment with 5FU, Cetuximab and pelvic RT is well tolerated and does not increase surgical complication rate. An update on efficacy data and biological markers evaluation will be presented at the meeting. No significant financial relationships to disclose.

Impact of pathologic complete response to preoperative docetaxel-based chemotherapy on disease-free survival in esophagogastric adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 123-123
Author(s):  
Sylvie Lorenzen ◽  
Nils Homann ◽  
Salah-Eddin Al-Batran ◽  
Florian Lordick ◽  
Tibor Schuster ◽  
...  
Keyword(s):  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Clinicopathological Parameters ◽  
Tumor Type ◽  
Disease Specific Survival ◽  
Free Survival ◽  
The Impact ◽  
Disease Free ◽  
Disease Specific

123 Background: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after treatment with preoperative docetaxel/platin /fluoropyrimidine based chemotherapy. Methods: This analysis of a prospective database identified patients who received at least one cycle of preoperative docetaxel/platin/fluoropyrimidine-based chemotherapy for at least T3/4 and N+ disease. An association of pretreatment clinicopathologic factors and pCR was investigated. Overall survival, disease-free survival and disease-specific survival were analyzed according to the achievement of a pCR. Results: A total of 120 patients received preoperative docetaxel-based chemotherapy and underwent subsequent resection of the primary tumor. 15 pts (13%) had distant metastases (M1) at initial diagnosis. 18 patients achieved a pCR in the primary (15%). Median follow-up was 41.1months. The median DFS and OS for the whole population was 24.1 and 48.6 months, respectively. DFS was significantly prolonged in pCR compared to non-pCR patients (HR 2.65, 95% CI 1.1- to 6.2; 3-year DFS probability: 71.8%±10.7 and 37.7%±5.1, respectively, P-value log-rank test=0.018). For patients with a pCR the median DFS was not reached and for those without pCR the median DFS was 22.1 months. Patients with a pCR showed an almost 50% decreased risk of death compared to non-pCR patients (HR 0.53; 95%CI 0.23 to 1.23; P=0.131). Disease-specific survival (DSS) was significantly longer in pCR vs. non-pCR patients (HR 0.188, 95%CI 0.046-to 0.77; P= 0.021). Two clinicopathological parameters were identified as predictors of pCR: tumor localization in the EGJ (p=0.019) and intestinal tumor type according to Laurén’s classification (p=0.042). Conclusions: The analysis confirms that pCR to neoadjuvant chemotherapy is a predictor of favourable patient outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ and intestinal histology represent factors significantly associated with the achievement of pCR.

Neoadjuvant trastuzumab (H), pertuzumab (P), and chemotherapy versus trastuzumab emtansine (T-DM1) and P in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC): Final outcome results from the phase III KRISTINE study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Miguel Martin ◽  
Kyung Hae Jung ◽  
Chiun-Sheng Huang ◽  
Nadia Harbeck ◽  
...  
Keyword(s):  
Randomized Study ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Her2 Positive ◽  
Free Survival ◽  
Post Surgery ◽  
Grade 3

500 Background: KRISTINE compared neoadjuvant chemotherapy plus dual HER2- blockade (HP) with T-DM1 plus P (T-DM1+P), a targeted regimen that omits standard chemotherapy. T-DM1+P resulted in a lower pathologic complete response (pCR) rate, but a more favorable safety profile. Here we present the final outcomes from KRISTINE. Methods: KRISTINE (NCT02131064) was a randomized study of T-DM1+P versus docetaxel, carboplatin, and H plus P (TCHP). Patients with HER2-positive stage II–III BC received 6 cycles of neoadjuvant T-DM1+P or TCHP q3w. Patients receiving T-DM1+P continued adjuvant T-DM1+P; patients receiving TCHP received adjuvant HP, for 12 cycles in each arm. Patients in the T-DM1+P arm without pCR were encouraged to receive standard adjuvant chemotherapy before adjuvant T-DM1+P. Secondary endpoints, analyzed with descriptive statistics, included event-free survival (EFS; all events pre- and post-surgery), invasive disease-free survival (IDFS; invasive events post-surgery), overall survival and safety. Results: At median follow-up of 37 months, EFS favored TCHP (HR = 2.61 [95% CI: 1.36–4.98]), due to more locoregional progression events in the T-DM1+P arm before surgery (6.7% vs 0; Table). pCR was associated with reduced risk of an IDFS event (HR = 0.24 [95% CI: 0.09– 0.60]) regardless of treatment arm. There were 5 deaths (2.3%) in the TCHP arm and 6 (2.7%) in the T-DM1+P arm. There were more grade ≥3 AEs with TCHP but a higher rate of AEs leading to treatment discontinuation with T-DM1+P. Conclusions: EFS numerically favors TCHP due to locoregional progression events with T-DM1+P prior to surgery. T-DM1+P was associated with fewer grade ≥3 AEs but increased treatment discontinuation. Clinical trial information: NCT02131064. [Table: see text]

Survival and recurrence of breast cancer patients with pathologic complete response after neoadjuvant chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12121-e12121
Author(s):  
Young Joo Lee ◽  
Sei-Hyun Ahn ◽  
Byung Ho Sohn ◽  
jong Won Lee ◽  
Il Yong Chung ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Good Prognosis ◽  
Her2 Status ◽  
Nodal Disease ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free

e12121 Background: Patients with Pathologic complete response after neoadjuvant chemotherapy is known to have a good prognosis. However, there is a difference depending on how the complete remission is defined. Methods: We analyzed basic characteristics and outcomes of 295 patients who had pathologic complete response defined as ypT0 and ypTis after neoadjuvant chemotherapy for breast cancer at Asan Medical Center in Seoul, Korea. Results: Median follow up period was 66.5 month(6~128 month). Overall survival was 94% at 5-year and 10-year. No difference was shown in preoperative age, grade, HR/HER2 status, Ki-67 level. Clinical stage III showed worst outcome(85.8%). Survival rate between ypT0N0 (98.8%) and ypTis (89.1%, p=0.00) and between ypT0/TisN residual (85.7%, p=0.00) was shown, but no statistical difference between ypTis and ypT0/Tis with residual nodes(p=0.539). Disease free survival also showed no statistical significance between age, HR/Her2 status. But patients with low Ki-67 level(0~20%)(68.2%) at diagnosis had worse DFS compared to high Ki-67 level(>20%)(87.5%)(P=0.013). No difference between intrinsic subtypes was shown. Patients with residual nodal disease had worse DFS(66.1%) than ypN0(89.1%)(p=0.00). DFS of ypT0N0 was 92.7% and ypTisN0(75.5%), ypT0/Tis with residual metastatic nodes(71.4%). There was no significant difference in type of chemotherapy regimen. Conclusions: Overall survival and disease free survival was different in ypT0N0 with ypTis and residual nodal disease. Good prognosis of pathologic complete response should be limited to cases in which the cancer has completely disappeared.

Preoperative treatment for marginally resectable metastatic melanoma: A single center experience in China.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22096-e22096
Author(s):  
Yu Xu ◽  
Xuxia Shen ◽  
Wei Sun ◽  
Yunyi Kong ◽  
Yong Chen ◽  
...  
Keyword(s):  
Positive Impact ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Complete Response ◽  
Braf V600e ◽  
Preoperative Treatment ◽  
Single Center Experience ◽  
A Prospective Study ◽  
The Impact

e22096 Background: Large randomized trials have proved that targeted therapy (TT) and immunotherapy (IT) can improve RFS for resectable Stage III melanoma. However, there is still a risk around 15%~25% of relapse within 1 year, especially worse for Stage IIID disease. Several neoadjuvant trials have shown a potentiality of long-term relapse-free after a pathologic complete response, especially for immunotherapy. We conducted a prospective study to investigate the impact of preoperative treatment on the anti-tumor efficacy and disease-free survival for Chinese melanoma. Methods: Stage IIID patients with matted nodes were recruited. For BRAF V600E-muted patients, Vemurafenib (V) was given for one months ahead of the surgery. For BRAF-wide-type patients, anti-PD1 antibody, Pembrolizumab(P) or Toripalimab (T) was given one dose per 3 weeks until response or intention-to-progression was observed. Pathologic assessment followed the principles for neoadjuvant therapy established by INMC. Results: Totally seven patients have been recruited. Detail information was listed in Table. Clinical ORR was 71%, however with no pCR observed. One patient in Vemurafenib group occurred brain mets within 1 month after surgery. All four patients in anti-PD1 group were relapse-free so far after median follow-up of 11 months. Conclusions: Preoperative BRAF targeted and anti-PD1 immunotherapy might guarantee a positive impact on anti-tumor response and local disease control for marginally resectable melanoma. However, the pathological criteria for neoadjuvant treatment might not be suitable to evaluate the matted or bulky specimen after preoperative treatment. [Table: see text]

Phase III study of perioperative pembrolizumab (pembro) plus neoadjuvant chemotherapy (chemo) versus placebo plus neoadjuvant chemo in cisplatin-eligible patients (pts) with muscle-invasive bladder cancer (MIBC): KEYNOTE-866.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS599-TPS599 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Gary D. Steinberg ◽  
Jens Bedke ◽  
Hiroyuki Nishiyama ◽  
Xiao Fang ◽  
...  
Keyword(s):  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Disease Stage ◽  
End Points ◽  
Free Survival ◽  
Investigation Methods ◽  
Muscle Invasive ◽  
Pathway Inhibition

TPS599 Background: MIBC prognosis is poor, despite standard neoadjuvant cisplatin-based chemo. PD-1/PD-L1 pathway inhibition is an effective first-line option for cisplatin-ineligible pts and a second-line option for platinum-based chemo pretreated pts. Neoadjuvant chemo + pembro, a PD-1 inhibitor, recently showed encouraging pathologic complete response rates, in cisplatin-eligible patients with MIBC (NCT02365766), warranting further investigation. Methods: KEYNOTE-866 (NCT03924856) is a randomized phase 3 study to assess efficacy and safety of chemo+perioperative pembro versus chemo+perioperative placebo for pts with MIBC. An estimated 790 patients will be randomly assigned 1:1 to neoadjuvant pembro+chemo (4 cycles) followed by adjuvant pembro after radical cystectomy+pelvic lymph node dissection (RC+PLND, 13 cycles) or neoadjuvant placebo+chemo (4 cycles) followed by adjuvant placebo after RC+PLND (13 cycles). Pts will receive neoadjuvant and adjuvant pembro 200 mg IV Q3W; neoadjuvant chemo will be gemcitabine 1000 mg/m2+cisplatin 70 mg/m2 IV Q3W. Pts will be stratified by tumor PD-L1 status (combined positive score [CPS] ≥10 vs CPS <10), disease stage (T2 vs T3/4), and region of treatment (Unites States vs Europe vs most of world). Adults (≥18 y) with histologically confirmed MIBC (T2-T4aN0M0) who are cisplatin-eligible, are clinically nonmetastatic (N0M0), and have an ECOG PS 0 or 1 will be enrolled. Pts are required to provide tumor tissue for histology and PD-L1 analysis. Pts will not be permitted to have previously received systemic antineoplastic treatment for MIBC or radiotherapy to the bladder. Imaging by CT/MRI will be performed Q12W for up to 96 wk after cystectomy, at discontinuation, and during follow-up starting at 3 y (Q24W). Primary end points are pathologic complete response and event-free survival in all pts and pts with PD-L1 CPS ≥10. Secondary end points are OS, disease-free survival, and pathologic downstaging rate in all pts and pts with PD-L1 CPS ≥10, and safety. Accrual began June 13, 2019. Clinical trial information: NCT03924856.

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