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  • 1
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    Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study
    Elsevier BV ; 2018
    In:  The Lancet Oncology Vol. 19, No. 7 ( 2018-07), p. 965-974
    Details
    In: The Lancet Oncology, Elsevier BV, Vol. 19, No. 7 ( 2018-07), p. 965-974
    Type of Medium: Online Resource
    ISSN: 1470-2045
    URL: Article
    DOI: 10.1016/S1470-2045(18)30201-8
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 2
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    Outcomes after totally minimally invasive versus hybrid and open Ivor Lewis oesophagectomy: results from the International Esodata Study Group
    Oxford University Press (OUP) ; 2022
    In:  British Journal of Surgery Vol. 109, No. 3 ( 2022-02-24), p. 283-290
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 109, No. 3 ( 2022-02-24), p. 283-290
    Abstract: Large studies comparing totally minimally invasive oesophagectomy (TMIE) with laparoscopically assisted (hybrid) oesophagectomy are lacking. Although randomized trials have compared TMIE invasive with open oesophagectomy, daily clinical practice does not always resemble the results reported in such trials. The aim of the present study was to compare complications after totally minimally invasive, hybrid and open Ivor Lewis oesophagectomy in patients with oesophageal cancer. Methods The study was performed using data from the International Esodata Study Group registered between February 2015 and December 2019. The primary outcome was pneumonia, and secondary outcomes included the incidence and severity of anastomotic leakage, (major) complications, duration of hospital stay, escalation of care, and 90-day mortality. Data were analysed using multivariable multilevel models. Results Some 8640 patients were included between 2015 and 2019. Patients undergoing TMIE had a lower incidence of pneumonia than those having hybrid (10.9 versus 16.3 per cent; odds ratio (OR) 0.56, 95 per cent c.i. 0.40 to 0.80) or open (10.9 versus 17.4 per cent; OR 0.60, 0.42 to 0.84) oesophagectomy, and had a shorter hospital stay (median 10 (i.q.r. 8–16) days versus 14 (11–19) days (P = 0.041) and 11 (9–16) days (P = 0.027) respectively). The rate of anastomotic leakage was higher after TMIE than hybrid (15.1 versus 10.7 per cent; OR 1.47, 1.01 to 2.13) or open (15.1 versus 7.3 per cent; OR 1.73, 1.26 to 2.38) procedures. Conclusion Compared with hybrid and open Ivor Lewis oesophagectomy, TMIE resulted in a lower pneumonia rate, a shorter duration of hospital stay, but higher anastomotic leakage rates. Therefore, no clear advantage was seen for either TMIE, hybrid or open Ivor Lewis oesophagectomy when performed in daily clinical practice.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1093/bjs/znab432
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
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    RA07.06: BASELINE FDG-PET/CT PARAMETERS AS PREDICTOR FOR RESIDUAL TUMOUR AFTER NEOADJUVANT CHEMORADIOTHERAPY IN OESOPHAGEAL CANCER PATIENTS
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 35-35
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 35-35
    Abstract: An optimal model for predicting pathologic response after neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer has not been defined yet. FDG-PET/CT is frequently used in response assessments. The aim of this side study of the preSANO trial (NL41732.078.13) was to investigate if the FDG-PET parameters SUVmax, total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were predictive for residual tumour in the resected specimen of oesophageal cancer patients treated with nCRT. Methods Patients underwent FDG-PET/CT at baseline according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.). All parameters were corrected for lean body mass. MTV was defined as the volume within a 41% of SULmax ( = SUV/lean body mass) isocontour threshold at tumour and lymph nodes. TLG was calculated as SULmean x MTV. Logarithmic transformation was performed because of non-normal distribution of TLG and MTV. Baseline PET parameters were compared to tumour regression grade in the resection specimen (TRG3–4 =  〉  10% residual tumour vs. TRG1 = complete response). Peroperatively irresectable tumours were recoded as TRG4. Analyses were performed using an independent-samples T-test. Results From a total of 207 patients who underwent FDG-PET/CT before nCRT, 197 were included for analysis (5 were non-FDG avid, 5 had incomplete data). Histological type of tumour: adenocarcinoma (AC) n = 154, squamous cell carcinoma (SCC) n = 42, and one adenosquamous carcinoma. Thirty-seven patients (19%) had TRG1 and 41 patients (21%) had TRG3–4. In complete responders (TRG1), SULmax, TLG and MTV (mean ± SD) were 9.6 ± 5.8, 85.3 ± 85.5 and 13.0 ± 9.9, respectively. In patients with TRG3–4, SULmax, TLG and MTV were 9.4 ± 5.4145.8 ± 164.6 and 21.9 ± 16.2, respectively. SULmax was not significantly different between both groups (P = 0.8), but log(TLG) and log(MTV) (P = 0.008 and P = 0.001) were. In adenocarcinomas, log(TLG) did not differ between groups (P = 0.1). Conclusion Initial FDG tumour mass, expressed as MTV, (rather than SULmax) is the most contributing factor in predicting residual disease after nCRT in both SCC and AC. The effect is stronger in SCC. Therefore, baseline FDG tumour mass should be included in a prediction model, besides other clinical and tumour parameters. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.RA07.06
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 4
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    PS02.064: ACCURACY OF F-18-FDG-PET/CT IN MONITORING TUMOUR RESPONSE AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH OESOPHAGEAL CANCER
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 138-139
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 138-139
    Abstract: Neoadjuvant chemoradiotherapy (nCRT) induces a pathologically complete response in approximately 30% of patients with oesophageal cancer. To explore the possibility of safe postponement of surgery, accurate clinical response evaluations are needed to exclude residual disease. The present study aims to assess the value of F-18-FDG-PET/CT for the detection of residual tumour ( 〉  10% tumour cells = TRG3–4 vs. no vital cells = TRG1) or metastases after nCRT. Methods FDG-PET/CT at baseline and 12 weeks after nCRT was performed according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.) and the protocol of the preSANO study. Qualitative analysis included sensitive reading of presence of residual tumour and/or metastases. A lesion was considered FDG-positive, when any uptake in the lesion itself was above the adjacent oesophageal background uptake. Quantitatively, SUV/lean body mass (SUL) measurements at tumour, lymph nodes, oesophagus, liver and bloodpool were recorded and compared with pathology (resection specimen: gold standard). Results Some 129 of 207 patients with FDG-avid tumours at baseline proceeded to FDG-PET/CT at around 12 weeks after nCRT just before surgery. Forty-one of 129 patients had TRG3–4, of whom 6 were missed on FDG-PET/CT (15% false negative) with SULmax 2.07 ± 0.25, SUL-ratio tumour/oesophagus (SULR) 1.35 ± 0.14. Sensitivity for TRG2–3-4 vs. TRG1 was 57/71 (80%). SULmax and SULR of FDG-positives were 3.76 ± 1.33 and 1.82 ± 0.69 respectively, compared to SULmax 2.21 ± 0.42 and SULR 1.31 ± 0.22 in FDG-negatives. Distant metastases were detected in 18 of 190 (10%) patients. Of all patients with postponed surgery, 12 had ≥ 1 additional FDG-PET/CT during follow-up (25–49.7 weeks after nCRT). Eventually, 4 patients underwent surgery. Three of 4 had increased FDG-signal and TRG3–4; 1 patient had decreased FDG-signal and no tumour left (TRG1). Conclusion FDG-PET/CT at around 12 weeks after nCRT misses TRG3–4 tumours in 15% and detects residual TRG2–3-4 in 80%. Furthermore, PET-CT detects distant metastases in 10% of patients after nCRT. These data indicate that serial FDG-PET may become valuable in an active surveillance approach. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.PS02.064
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 5
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    FA01.02: THE EFFECT OF POSTOPERATIVE COMPLICATIONS AFTER MIE ON LONG-TERM SURVIVAL: A RETROSPECTIVE, MULTI-CENTER COHORT STUDY
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 1-1
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 1-1
    Abstract: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated. Methods Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses. Results A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29–2.32, P  〈  0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32–2.63, P  〈  0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38–5.35, p 0.004). For all other complications, no significant influence on long-term survival was found. Conclusion The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.FA01.02
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 6
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    PS02.083: CIRCULATING CELL FREE TUMOR DNA FOR DISEASE MONITORING AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER: PROOF-OF-PRINCIPLE
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 144-144
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 144-144
    Abstract: An active surveillance approach has been proposed for patients with a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (SANO trial). To justify renouncing surgical resection, patients with residual disease after nCRT should be accurately identified. However, substantial residual disease (TRG3–4) cannot be detected in 10% of patients with current diagnostic tests (preSANO trial). Circulating cell free tumor DNA (ctDNA) potentially improves detection of residual malignancy after nCRT and could be used for disease monitoring. The objective of this study was to investigate the feasibility of using ctDNA as biomarker for disease status after nCRT in esophageal cancer. Methods Twelve typical patients from the preSANO trial with variable pathological responses to nCRT were included. Blood was drawn and processed pretreatment. The feasibility of detecting TP53 mutations in baseline tumor biopsies was investigated using a next generation sequencing (NGS) panel. Subsequently, baseline blood samples of patients in whom specific TP53 mutations could be identified in baseline tumor biopsies or the surgical resection specimen were analyzed for ctDNA using cell free DNA NGS kits with single molecule barcoding (Oncomine Thermo Fisher). Results Baseline biopsy samples were available in 8 out of 12 patients. In 7 of these 8 patients (88%) specific TP53 mutations could be identified in their baseline biopsies. In 11 out of 12 patients (92%) specific TP53 mutations could be identified in baseline biopsies or the resection specimen. Eight of these 11 mutations were potentially detectable by the Oncomine panel. The panel detected TP53 mutational ctDNA in 4 of these 8 samples (50%). Conclusion Specific and clonal TP53 mutations can be identified in pretreatment biopsy samples and in surgical resection specimens of patients with esophageal cancer. These mutations can be matched to ctDNA identified in blood samples. Hence, ctDNA analyses in blood samples can potentially be used for disease monitoring during active surveillance and for disease monitoring in follow-up after surgical resection. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.PS02.083
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 7
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    793 PATIENTS’ PREFERENCES FOR ACTIVE SURVEILLANCE OR STANDARD ESOPHAGECTOMY AFTER NEOADJUVANT CHEMORADIOTHERAPY: A DISCRETE CHOICE EXPERIMENT IN PATIENTS AFTER STANDARD ESOPHAGECTOMY
    Oxford University Press (OUP) ; 2021
    In:  Diseases of the Esophagus Vol. 34, No. Supplement_1 ( 2021-09-17)
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 34, No. Supplement_1 ( 2021-09-17)
    Abstract: Active surveillance after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal cancer is currently topic of investigation. In a discrete choice experiment, patients’ preferences can be quantified by asking patients to state their preference over hypothetical treatment alternatives. The aim of the present study was to assess patients’ preferences for either active surveillance or standard esophagectomy in patients who underwent neoadjuvant chemoradiotherapy followed by surgery without signs of recurrence. Methods A discrete choice experiment was performed in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by standard esophagectomy at least one year earlier. Patients completed a questionnaire consisting of eighteen choice sets considering active surveillance or standard esophagectomy. Treatment alternatives were characterized by attributes with varying attribute levels hypothesized to influence treatment choice: five-year survival, short-term and long-term health related quality of life (HRQOL), annual number of diagnostics required and the risk that esophagectomy is still necessary later in time. The importance of attributes and willingness to trade-off 5-year survival for other attributes were assessed using panel latent class model. Results A total of 107 patients were consecutively included, of whom 100 (93%) responded between August 2018 and October 2020. Regardless of the attribute levels, 28 patients preferred active surveillance and 28 patients preferred standard esophagectomy. When considering both treatments, five-year survival and long-term HRQOL were considered most important attributes. Patients were willing to trade-off 5.4% five-year overall survival to obtain a better long-term HRQOL. Conclusion At least one year after neoadjuvant chemoradiotherapy and esophagectomy, over a quarter of patients would choose not to undergo standard esophagectomy again, regardless of the attribute levels. Patients were willing to trade-off five-year survival chance in order to achieve an HRQOL which was much better than their own situation. When considering both treatments, five-year survival and long-term HRQOL were the most important determinants in the choice for treatment.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doab052.793
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 8
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    FA03.04: ACTIVE SURVEILLANCE VS SURGERY IN CLINICALLY COMPLETE RESPONDERS AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER: A PROPENSITY-MATCHED STUDY
    Oxford University Press (OUP) ; 2018
    In:  Diseases of the Esophagus Vol. 31, No. Supplement_1 ( 2018-09-01), p. 7-7
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 31, No. Supplement_1 ( 2018-09-01), p. 7-7
    Abstract: Nearly one third of esophageal cancer patients show a pathologically complete response in their resection specimens after neoadjuvant chemoradiotherapy (nCRT) according to CROSS regimen. This raises questions whether all patients benefit from surgery or if active surveillance can be applied to patients with a clinically complete response (cCR) after nCRT. This retrospective-multicenter propensity matched study compared outcomes of patients with a cCR after nCRT undergoing active surveillance or standard surgery. Methods Patients that refused surgery after nCRT between 2012–2017 from 4 hospitals were included. For the standard surgery group, patients from the preSANO trial were enrolled. A cCR was defined as endoscopies with multiple (bite-on-bite) biopsies, EUS-FNA and PET-CT showing no residual disease 6 and 12 weeks after completion of nCRT. Optimal propensity-score matching generated a matched cohort (1:2) matched for age, comorbidities, cT, cN, histology of the tumor and biopsy type. For comparison of severity of complications according to Clavien-Dindo (CD) classification, a separate optimal propensity-score matching cohort was generated (1:2) for all patients in the active surveillance group that underwent surgery. Primary outcome was overall survival, secondary outcomes were rate of radically resected tumors, distant dissemination rate and rate of postoperative complications according to the CD-classification. Results 75 patients were identified of whom 50 patients underwent standard surgery and 25 patients underwent active surveillance. 13 of 25 patients in the active surveillance group underwent surgery for locoregional recurrent disease. Median follow-up was 23.7 months for the standard surgery group and 18.8 months for the active surveillance group. There was no statistically significant difference between the groups in overall survival (HR = 0.48, 95%C.I. 0.10–2.2, P = 0.96). In both groups, all tumors were radically resected. There were no statistically significant differences in distant dissemination rate between the active surveillance and standard surgery group (16.0% versus 22.0%, P = 0.76) or in severity of complications (CD ≥ 3;46.2% versus 23.1%, P = 0.16). Conclusion There was no statistically significant difference in overall survival, distant dissemination rate and severity of complications between patients undergoing standard surgery or active surveillance after nCRT. However, since sample sizes were small, especially for the severity of complications, these results should be interpreted with caution. Disclosure All authors have declared no conflicts of interest.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doy089.FA03.04
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 9
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    Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy: dysphagia is uncommon
    Oxford University Press (OUP) ; 2023
    In:  British Journal of Surgery Vol. 110, No. 10 ( 2023-09-06), p. 1381-1386
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 110, No. 10 ( 2023-09-06), p. 1381-1386
    Abstract: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. Methods Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer (‘SANO’) trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0–100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. Results In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3–4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0–0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. Conclusion Dysphagia and clinically relevant stenosis are uncommon during active surveillance.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1093/bjs/znad211
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 10
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    681 PATTERN OF RECURRENCE IN PATIENTS WITH A PATHOLOGICALLY COMPLETE RESPONSE AFTER NEOADJUVANT CHEMORADIOTHERAPY AND SURGERY FOR OESOPHAGEAL CANCER
    Oxford University Press (OUP) ; 2021
    In:  Diseases of the Esophagus Vol. 34, No. Supplement_1 ( 2021-09-17)
    Details
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 34, No. Supplement_1 ( 2021-09-17)
    Abstract: Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20 and 50% of patients having a pathological complete response (pCR). Disease, however, still recurs in 20–30% of these patients. The aim of this study was to assess the pattern of recurrence in patients with pCR after nCRT and surgery. Methods All patients with pCR after neoadjuvant chemoradiotherapy and surgery included in the phase II and III ChemoRadiotherapy for Oesophageal followed by Surgery Study (CROSS) trials (April 2001—March 2009) and after the CROSS trials (September 2009—October 2017) were identified. The site of recurrence was compared to the applied radiation and surgical fields. Outcomes were median time to recurrence, overall and progression-free survivals. Results A total of 141 patients with a median follow-up of 100 (interquartile range [IQR] 64–134) months were included. Some 29 of 141 patients (21%) developed recurrence. Of these, four (14%) had isolated locoregional recurrence, 15 (52%) distant recurrence only and ten (34%) had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five were within the radiation field, seven outside the radiation field and two at the border. Median (IQR) time to recurrence was 24 (10–62) months. The 5-year overall survival was 74% and recurrence-free survival 70%. Conclusion Despite good overall survival, recurrence still occurred in 21% of patients. Most recurrences were distant, outside the radiation and surgical fields.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    URL: Article
    DOI: 10.1093/dote/doab052.681
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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