Phase I study of intraperitoneal irinotecan with systemic capecitabine and oxaliplatin for patients with gastric peritoneal metastases.

Background: Peritoneal metastases of gastric cancer are associated with a poor prognosis (median overall survival (OS) ∼9 months). Catheter-based intraperitoneal (CBIP) chemotherapy is a locoregional approach to deliver chemotherapy leading to higher intraperitoneal (IP) concentrations of cytotoxic drugs compared to intravenous administration.

Method: This multicenter, open-label 3 + 3 + 3 dose-escalation phase I trial evaluated 3-weekly IP irinotecan with oral capecitabine and intravenous oxaliplatin (CAPOX).

Emerging treatment modalities for gastric cancer with peritoneal metastases: A systematic review.

Introduction: Gastric cancer remains associated with a high mortality, since patients often present with advanced-stage disease such as peritoneal metastases. Treatment options in this setting are limited and mainly consist of palliative systemic therapy.

Objectives: This systematic review aims to summarize emerging therapeutic strategies for patients with peritoneally metastasized gastric cancer in relation to response, toxicity and survival.

Real-world study on fluoropyrimidine-related toxicity outcomes in cancer patients with select DPYD variant alleles that received DPYD genotype-guided dosing.

DPYD gene variations are associated with severe fluoropyrimidine toxicity, and an initial 50% dose reduction is widely recommended for heterozygous carriers of relevant DPYD variants, including DPYD*2A, DPYD*13, c.2846A>T, and c.1236G>A.

Hospital variation in treatment for synchronous metastatic esophageal and gastric cancer: A nationwide population-based study in the Netherlands.

Care for metastatic esophageal (EC) or gastric cancer (GC) includes a large variety of treatment modalities. Data on treatment variation across centers are unknown. This study investigated treatment variation across hospitals and its effect on overall survival (OS) in the Netherlands by conducting a nationwide retrospective cohort study with population-based data from the Netherlands Cancer Registry.

Dose-individualisation of fluoropyrimidines based on pre-treatment serum uracil levels: the Alpe2U study.

Background: DPYD-guided dosing enhances safety of fluoropyrimidine-based chemotherapy. However, approximately 23 % of patients still experience severe toxicity unexplained by the four commonly tested DPYD-variant alleles. Elevated pre-treatment uracil levels have been proposed as a surrogate marker for reduced DPD activity and an independent predictor of toxicity.

Treatment Adherence to Adjuvant Chemotherapy According to the New Standard 3-month CAPOX Regimen in High-risk Stage II and Stage III Colon Cancer: A Population-based Evaluation in The Netherlands.

Background: A 3-month adjuvant treatment regimen with capecitabine and oxaliplatin (CAPOX) for high-risk stage II (T4N0) and stage III (node-positive) colon cancer was implemented in the Netherlands in 2017. The IDEA trial showed a clinically irrelevant difference in long-term outcomes in combination with a substantial decrease in toxicity in comparison with a 6-month regimen. A significantly increased dose intensity was observed in the 3-month arm, which might be essential to achieve optimal long-term outcomes.

Longitudinal health-related quality of life in patients with pancreatic cancer stratified by treatment: a nationwide cohort study.

Background: Pancreatic adenocarcinoma (PAC) has a poor prognosis and substantially impairs health-related quality of life (HRQoL). Large studies on longitudinal HRQoL in patients with PAC, taking patient treatment into account, are lacking. This study aimed to investigate HRQoL over time in patients with PAC undergoing various treatments.

Patient-reported outcomes during first-line palliative systemic therapy alternated with pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: a single-arm phase II trial (CRC-PIPAC-II).

Background: The CRC-PIPAC-II study prospectively assessed bidirectional therapy (BT) consisting of first-line palliative systemic therapy and electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC-OX) in patients with unresectable colorectal peritoneal metastases (CPM). This study describes the exploration of patient-reported outcomes (PROs).

Methods: In this phase II trial, 20 patients with isolated CPM were treated with up to three cycles of BT, each cycle consisting of two to three courses of systemic therapy, followed by ePIPAC-OX (92 mg/m).

Tumor immune microenvironmental characteristics in Human Epidermal Growth Factor-2 (HER2) positive esophageal adenocarcinoma: A comparative analysis and biomarker study.

Background: HER2 targeting in esophageal adenocarcinoma (EAC) has shown potential, but often fails to show durable response. Given the contributions of the tumor immune microenvironment (TIME) to therapeutic responses, we aimed to chart the TIME characteristics of HER2 positive tumors.

Methods: 84 biopsies were taken from the TRAP cohort (neoadjuvant chemoradiotherapy (nCRT) according to CROSS with trastuzumab and pertuzumab; n = 40; HER2n = 40) and a control cohort with nCRT only (n = 44; HER2- n = 40, HER2n = 4) before treatment.

Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study.

Background: Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting.

First-line palliative systemic therapy alternated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: A single-arm phase II trial (CRC-PIPAC-II).

Background: Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy.

Methods: This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m) with intravenous leucovorin (20 mg/m) and 5-fluorouracil (400 mg/m).

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4).

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD).

Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer.

Intraperitoneal irinotecan with concomitant FOLFOX and bevacizumab for patients with unresectable colorectal peritoneal metastases: protocol of the multicentre, open-label, phase II, INTERACT-II trial.

Introduction: The peritoneum is the second most affected organ for the dissemination of colorectal cancer (CRC). Patients with colorectal peritoneal metastases (CPM) face a poor prognosis, despite the majority of patients being treated with palliative systemic therapy. The efficacy of palliative systemic therapy is limited due to the plasma-peritoneum barrier.

Trajectories of emotional functioning and experienced care of relatives in the last year of life of patients with advanced cancer: A longitudinal analysis of the eQuiPe study.

Objective: Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory.

Survival of Patients With Cancer With Variant Alleles and Dose-Individualized Fluoropyrimidine Therapy-A Matched-Pair Analysis.

Purpose: -guided fluoropyrimidine dosing improves patient safety in carriers of variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between variant carriers treated with a reduced dose and wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis.

Gender differences in tumor characteristics, treatment and survival of colorectal cancer: A population-based study.

Background: The importance of sex and gender as modifiers of health and disease is increasingly recognized. The aim of this study was to analyze gender differences in incidence, tumor characteristics, treatment and relative survival (RS) in colorectal cancer (CRC).

Methods: Observational population-based study including patients diagnosed with CRC in the Netherlands between 2010 and 2020.

Phase I study of intraperitoneal irinotecan combined with palliative systemic chemotherapy in patients with colorectal peritoneal metastases.

Background: Patients with colorectal peritoneal metastases who are not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) owing to extensive peritoneal disease have a poor prognosis. It was hypothesized that these patients may benefit from the addition of intraperitoneal irinotecan to standard palliative systemic chemotherapy.

Methods: This was a classical 3 + 3 phase I dose-escalation trial in patients with colorectal peritoneal metastases who were not eligible for CRS-HIPEC.

Locally recurrent rectal cancer: Oncological outcomes for patients with a pathological complete response after neoadjuvant therapy.

Background: For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR appears to be associated with improved outcomes. The aim of this retrospective cohort study was to compare the oncological outcomes of patients with locally recurrent rectal cancer with and without a pCR.

Fecal levels of SCFA and BCFA during capecitabine in patients with metastatic or unresectable colorectal cancer.

Background: Gut bacteria-derived short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) are considered to have beneficial metabolic, anti-inflammatory as well as anti-carcinogenic effects. Previous preclinical studies indicated bidirectional interactions between gut bacteria and the chemotherapeutic capecitabine or its metabolite 5-FU. This study investigated the effect of three cycles of capecitabine on fecal SCFA and BCFA levels and their associations with tumor response, nutritional status, physical performance, chemotherapy-induced toxicity, systemic inflammation and bacterial abundances in patients with colorectal cancer (CRC).

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe.

Background: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease).