ChemoTherapy aNd chemoradioTherapy for adenocarcinoma of the OESophagus and esophagogastric junction with oligometastases: Protocol of the TNT-OES-1 trial

Zijden, Charlène J. van der; Eyck, Ben M; Gaast, Ate van der; Doorn, Leni van; Nuyttens, J.; Lanschot, J. Jan B. van; Wijnhoven, Bas P. L.; Mostert, Bianca; Lagarde, Sjoerd M.

doi:10.1016/j.conctc.2022.100934

Cited by 6 publications

(5 citation statements)

References 32 publications

(56 reference statements)

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“…A total of 290 of 325 (89%) patients underwent surgery at a median of 9 weeks (interquartile range [IQR] 7-12) after completion of nCRT. In 35 patients, surgery was not performed because of active surveillance at own request (5), distant metastases (20), died before surgery (5), physically unfit for surgery (4), and refused surgery (1). Resection was performed in 284 of 290 (98%) patients; 4 patients had distant metastases detected perioperatively and 2 had unresectable tumour (T4b).…”

Section: Patientsmentioning

confidence: 99%

“…Ten‐year overall survival (OS) of adenocarcinoma patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery according to the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS [ 2 ]) regimen is 36% [ 3 ]. Better understanding of the association between histopathologic features and therapy response may guide different therapeutic strategies, such as primary surgery and/or alternative (neo)adjuvant regimens [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

Valkema

Vos

Post

et al. 2023

The Journal of Pathology CR

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Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet‐ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well‐formed glands), which is a possible confounder. We studied the pre‐ and post‐treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well‐formed glands, extracellular mucin, SRCs, and PCCs were scored in pre‐treatment biopsies and post‐treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3–4 (i.e. >10% residual tumour), overall survival, and disease‐free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre‐treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre‐treatment histopathological factors were unrelated to tumour regression grade. Pre‐treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19–2.53). Patients with post‐treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10–2.99). In conclusion, pre‐treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre‐treatment and any SRCs post‐treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts.

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Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

Valkema

Vos

Post

et al. 2023

The Journal of Pathology CR

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“…Understanding of these presurgical treatments is crucial for the anesthesiologist to accurately risk-stratify patients and reduce perioperative morbidity. effect is present such as neutropenia, a dose reduction or postponing the next cycle is considered [8].…”

Section: Key Pointsmentioning

confidence: 99%

“…Some of the common adverse effects include pancytopenia and risk of infection, gastrointestinal adverse effects and weight loss, fatigue, skin changes and hair loss. If an adverse effect is present such as neutropenia, a dose reduction or postponing the next cycle is considered [8].…”

Section: Esophageal Cancermentioning

confidence: 99%

Presurgical radiation and chemotherapy in preparation for thoracic tumor resection

Tavakoli

Turner

Diaz-Gutierrez

2022

Current Opinion in Anaesthesiology

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Purpose of reviewThis article aims at describing the role of neoadjuvant chemotherapy, radiation therapy as well the novel immunotherapy and targeted therapy in thoracic oncology with focus on anesthetic considerations of such treatments for the surgical patient. Recent findingsIn recent years, immune check point inhibitors have changed the landscape of thoracic oncology treatment. In this review, we summarize the key studies that have been fundamental in this change. SummaryRather than a comprehensive review, the purpose of this work is to provide the reader with an overview of the most common neoadjuvant regimens used in current practice, with the corresponding most prevalent adverse effects as it pertains for patients with esophageal and lung cancer, malignant pleural mesothelioma and mediastinal tumors. Considerations relevant to the anesthesiologist, including specific toxicities related to each treatment type, and the impact of each treatment type on perioperative outcomes and complications will be discussed.

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“…New combinations of (neo)adjuvant therapies are explored to improve treatment efficacy in patients with stage IV esophageal cancer. Ongoing research focuses for example on the tolerability of a sequential combination of chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) [6] and chemoradiotherapy (nCRT according to CROSS) [7], to downstage oligometastatic esophageal cancer and optimize locoregional disease control [8,9].…”

Section: Introductionmentioning

confidence: 99%

The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction

et al. 2022

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Therapies that target specific tumor drivers or immune checkpoints are increasingly explored for esophageal cancer patients. This review addresses developments in therapies with targeted anti-human epidermal growth factor receptor 2 (HER2) agents and immune checkpoint inhibitors in patients with stage IV esophageal cancer. First-line palliative treatment with the anti-HER2 agent trastuzumab in combination with chemotherapy has been approved for use in patients with HER2 positive gastro-esophageal adenocarcinoma. Neoadjuvant chemoradiotherapy plus perioperative trastuzumab however has not demonstrated a survival benefit in advanced esophageal cancer patients eligible for surgery. Potentially better responses are expected with dual agent anti-HER2 therapy instead of monotherapy. In the metastatic setting, the antibody–drug conjugate trastuzumab deruxtecan is effective after progression on trastuzumab. Nivolumab and pembrolizumab, antibodies blocking the programmed cell death 1 (PD-1) receptor on T cells, have recently gained approval for clinical use in esophageal cancer patients for specific indications. Synergistic effects might be achieved with combinations of immune checkpoint inhibitors that target PD-1 on T cells or PD ligand 1 (PD-L1) on tumor cells and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) receptor on T cells. Multiple clinical trials investigating combinations of targeted and immunotherapies, with or without (neo)adjuvant chemo(radio)therapy, for curative and palliative treatment, are underway, and are expected to deliver a long-awaited improvement in the prognosis of esophageal cancer patients.

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ChemoTherapy aNd chemoradioTherapy for adenocarcinoma of the OESophagus and esophagogastric junction with oligometastases: Protocol of the TNT-OES-1 trial

Cited by 6 publications

References 32 publications

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

Presurgical radiation and chemotherapy in preparation for thoracic tumor resection

The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction

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