Oesophageal Chemoradiotherapy in the UK—Current Practice and Future Directions

Gwynne, S.; Falk, Stephen; Gollins, Simon; Wills, L.; Bateman, Andrew; Cummins, Sebastian; Grabsch, Heike; Hawkins, M.; Maggs, R.; Mukherjee, Somnath; Radhakrishna, Ganesh; Roy, Rajarshi; Sharma, Ricky A.; Spezi, Emiliano; Crosby, T.

doi:10.1016/j.clon.2013.01.006

Cited by 25 publications

(26 citation statements)

References 59 publications

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“…The South East Wales MDT treatment algorithms for oesophageal and gastric cancer have been described previously 12,13 . Definitive chemoradiotherapy was offered to patients with localized squamous cell carcinoma and to patients with adenocarcinoma deemed unsuitable for surgery because of disease extent and/or medical co-morbidity 16,17 . Particular emphasis was placed on the incidence of morbidity of grade III or higher.…”

Section: -Day Mortalitymentioning

confidence: 99%

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Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery

et al. 2020

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Background: Surgeon-level operative mortality is widely seen as a measure of quality after gastric and oesophageal resection. This study aimed to evaluate this alongside a compound-level outcome analysis.Methods: Consecutive patients who underwent treatment including surgery delivered by a multidisciplinary team, which included seven specialist surgeons, were studied. The primary outcome was death within 30 days of surgery; secondary outcomes were anastomotic leak, Clavien-Dindo morbidity score, lymph node harvest, circumferential resection margin (CRM) status, disease-free (DFS), and overall (OS) survival.Results: The median number of annual resections per surgeon was 10 (range 5-25), compared with 14 (5-25) for joint consultant teams (P = 0⋅855). The median annual surgeon-level mortality rate was 0 (0-9) per cent versus an overall network annual operative mortality rate of 1⋅8 (0-3⋅7) per cent. Joint consultant team procedures were associated with fewer operative deaths (0⋅5 per cent versus 3⋅4 per cent at surgeon level; P = 0⋅027). The median surgeon anastomotic leak rate was 12⋅4 (range 9-20) per cent (P = 0⋅625 versus the whole surgical range), overall morbidity 46⋅5 (31-60) per cent (P = 0⋅066), lymph node harvest 16 (9-29) (P < 0⋅001), CRM positivity 32⋅0 (16-46) per cent (P = 0⋅003), 5-year DFS rate 44⋅8 (29-60) per cent and OS rate 46⋅5 (35-53) per cent. No designated metrics were independently associated with DFS or OS in multivariable analysis. Conclusion:Annual surgeon-level metrics demonstrated wide variations (fivefold), but these performance metrics were not associated with survival.

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Section: -Day Mortalitymentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20] to 24 (17-29)) (P < 0⋅001). 11-23) (surgeon range 11 (i.q.r.…”

Section: Unit Versus Individual Surgeon Dataunclassified

Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery

et al. 2020

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“…Whilst higher pCR rates are achieved with CRT than with induction chemotherapy alone [5, 6], unfortunately, approximately 70% of patients receiving neoadjuvant treatment show moderate or no response [7]. Consequently, this sub-group of patients are unnecessarily subjected to CRT-associated adverse events, including an increased risk of surgical complications [8, 9], as well as a delay to surgery, which can ultimately worsen prognosis and increase clinical expense [10]. Presently, standard clinicopathological factors do not predict treatment response and there are currently no predictive markers used routinely in the clinic.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype

et al. 2016

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Resistance to neoadjuvant chemoradiation therapy (CRT) remains a critical barrier to the effective treatment of esophageal adenocarcinoma (EAC). Cancer stem-like cells (CSCs) are a distinct subpopulation of cells implicated in the resistance of tumors to anti-cancer therapy. However, their role in the resistance of EAC to CRT is largely unknown. In this study, using a novel in vitro isogenic model of radioresistant EAC, we demonstrate that radioresistant EAC cells have enhanced tumorigenicity in vivo, increased expression of CSC-associated markers and enhanced holoclone forming ability. Further investigation identified a subpopulation of cells that are characterised by high aldehyde dehydrogenase (ALDH) activity, enhanced radioresistance and decreased expression of miR-17-5p. In vitro, miR-17-5p was demonstrated to significantly sensitise radioresistant cells to X-ray radiation and promoted the repression of genes with miR-17-5p binding sites, such as C6orf120. In vivo, miR-17-5p was significantly decreased, whilst C6orf120 was significantly increased, in pre-treatment EAC tumour samples from patients who demonstrated a poor response to neoadjuvant CRT. This study sheds novel insights into the role of CSCs in the resistance of EAC to CRT and highlights miR-17-5p as a potential biomarker of CRT sensitivity and novel therapeutic target in treatment resistant EAC.

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“…The role of radiation therapy dose escalation in improving outcomes for definitive CRT has been recently identified as one of the priorities for research in esophageal cancer in the United Kingdom (10). Nevertheless, the optimal combination of radiation therapy and chemotherapy doses needs to be carefully established in order to improve locoregional control.…”

Section: Introductionmentioning

confidence: 99%

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

Warren¹,

Carrington²,

Hurt³

et al. 2014

International Journal of Radiation Oncology*Biology*Physics

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PurposeThis study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity.Methods and MaterialsTwenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm3. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA62.5) was compared to a standard dose plan of 50 Gy/25 fractions (RA50). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared.ResultsClinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA50) to 56.3% (RA62.5), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA50) versus 5.6% (RA62.5) P<.001 and median lung NTCP 6.5% (RA50) versus 7.5% (RA62.5) P<.001.ConclusionsDose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

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Oesophageal Chemoradiotherapy in the UK—Current Practice and Future Directions

Cited by 25 publications

References 59 publications

Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery

Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery

MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

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