Adjuvant chemotherapy has not improved disease-free survival among patients with resected esophageal or gastroesophageal junction cancer. In this trial, after neoadjuvant chemoradiotherapy and ...resection, patients with residual disease were randomly assigned to receive nivolumab or placebo. Nivolumab doubled the median disease-free survival from 11.0 to 22.4 months.
Introduction
The peritoneum is a predilection site for gastric cancer metastases. Current standard treatment for gastric cancer patients with synchronous peritoneal metastases is palliative systemic ...therapy. However, its efficacy is largely unknown. The aim of this study was to investigate the incidence, treatment and survival patterns of gastric cancer patients with synchronous peritoneal metastases in the Netherlands.
Methods
All newly diagnosed gastric adenocarcinoma patients with synchronous peritoneal metastases between 1999 and 2017 were selected from the Netherlands Cancer Registry (NCR). Incidence, treatment and survival patterns were analyzed.
Results
In total, 3,773 patients were identified from the NCR. The incidence of synchronous peritoneal metastases in gastric cancer patients increased from 18% in 2008 to 27% in 2017. The use of systemic therapy increased from 15% in 1999–2002 to 43% in 2013–2017 (
p
< 0.001). The median survival of the entire cohort did not significantly increase over time. Median survival of patients treated with systemic therapy increased from 7.4 months in 1999–2002 to 9.4 months in 2013–2017 (
p
= 0.005). In contrast, median survival of patients
not
treated with systemic therapy decreased from 3.3 months in 1999–2002 to 2.1 months in 2013–2017 (
p
< 0.001). Some clinical and pathological data such as the extent of the peritoneal metastases were not available.
Conclusion
Synchronous peritoneal metastases are increasingly diagnosed in gastric cancer patients. In recent years, more patients were treated with systemic treatment and survival of these patients increased. However, as survival of the entire group did not improve over time, the effect of systemic therapy remains unknown.
Floxuridine’s high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of ...floxuridine.
Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed.
265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL IQR: 0.472–0.747 for cycle 1 day 7, 0.579 ng/mL IQR: 0.470–0.693 for cycle 1 day 15, 0.646 ng/mL IQR: 0.463–0.8546 for cycle 2 day 7, and 0.534 ng/mL IQR: 0.4257–0.7075 for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation.
The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %−37.8 %) over a period of 15 days (n = 18).
Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time.
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•An assay was developed measuring serum floxuridine concentrations down to 0.25 ng/mL•Negligible serum floxuridine concentrations were measured during the HAIP cycles•Floxuridine concentration in the pump may gradually decline•No floxuridine-attributed extrahepatic toxicity were detected
Purpose
Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional ...(3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases.
Methods
This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing
18
F‑fluorodeoxyglucose uptake for their degree of suspicion.
Results
The mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6–15.5) versus 13.0 (10.4–15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland–Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (−3.60–3.75), −0.26 (−2.34–1.82), 4.66 (−29.61–38.92) cm
3
and −0.95 (−19.9–18.0) cm
3
for tumour SUVmax, lymph node SUVmax, MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6 (4.3–8.8) and 6.8 (4.5–9.1) for 3D and motion-compensated, respectively.
Conclusion
SUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection.
Chemoradiotherapy and surgery are the basis of the potentially curative treatment for esophageal cancer. Approximately 1 in 5 patients, however, do not benefit from this intensive treatment due to ...early treatment failure. The aim of this study was to evaluate levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 at diagnosis, in relation to survival and early treatment failure (disease recurrence or death within 1 year after surgery).
Patients with esophageal adenocarcinoma scheduled for chemoradiotherapy followed by surgery between 1998 and 2014 were selected from a retrospectively collected database if both CEA and CA19-9 levels were measured before the start of treatment.
Pretreatment CEA and CA19-9 levels were known in 102 patients. Median overall survival differed (P<0.001) between patients with normal levels of both CEA and CA19-9 (n=59; 51 mo), patients with elevated CEA only (n=13; 43 mo), patients with elevated CA19-9 only (n=19; 24 mo), and those with elevated levels of both CEA and CA19-9 (n=11; 11 mo). Elevation of both CEA and CA19-9 was associated with early treatment failure (odds ratio: 10.4; 95% confidence interval: 2.4-45.5, P=0.002). Median time to tumor recurrence was 34 months in patients with normal CEA and CA19-9 levels, and 7 months in those with elevated levels of both (P=0.003).
Pretreatment elevated CEA and CA19-9 levels were significantly associated with early treatment failure and decreased overall survival in this esophageal adenocarcinoma patient cohort treated with curative intent. Until prospective validation, CEA and CA19-9 might play a role in identifying high-risk patients before the start of intensive locoregional therapy.
Background:
Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions.
Aim:
A structured reflection could improve patients’ quality of life and ...spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being.
Design:
The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time.
Participants:
Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group.
Results:
A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life (β = 0.52, adj. R2 = 0.26) and satisfaction with life (β = 0.61, adj. R2 = 0.37).
Conclusion:
Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace.
Purpose
Chemotherapy-resistance remains a major obstacle to effective anti-cancer treatment. We previously showed that platinum analogs cause the release of two fatty acids. These platinum-induced ...fatty acids (PIFAs) induced complete chemoresistance in mice, whereas co-administration of a COX-1 inhibitor, indomethacin, prevented PIFA release and significantly enhanced chemosensitivity. To assess the safety of combining indomethacin with platinum-based chemotherapy, and to explore its efficacy and associated PIFA levels, a multi-center phase I trial was conducted.
Methods
The study was comprised of two arms: oxaliplatin plus capecitabine (CAPOX, arm I) and cisplatin plus gemcitabine, capecitabine or 5FU (arm II) in patients for whom these regimens were indicated as standard care. Indomethacin was escalated from 25 to 75 mg TID, using a standard 3 × 3 design per arm, and was administered orally 8 days around chemo-infusion from cycle two onwards. PIFA levels were measured before and after treatment initiation, with and without indomethacin.
Results
Thirteen patients were enrolled, of which ten were evaluable for safety analyses. In arm I, no dose-limiting toxicities were observed, and all indomethacin dose levels were well-tolerated. Partial responses were observed in three patients (30%). Indomethacin lowered plasma levels of 12-
S
-hydroxy-5,8,10-heptadecatrienoic acid (12-
S
-HHT), whereas 4,7,10,13-hexadecatetraenoic acid (16:4(n-3)) levels were not affected. Only one patient was included in arm II; renal toxicity led to closure of this cohort.
Conclusions
Combined indomethacin and CAPOX treatment is safe and reduces the concentrations of 12-
S
-HHT, which may be associated with improved chemosensitivity. The recommended phase II dose is 75 mg indomethacin TID given 8 days surrounding standard dosed CAPOX.
(1) Background: Perioperative chemotherapy is the current standard treatment for patients with resectable gastric cancer. Based on studies in patients with metastatic gastric cancer, oxaliplatin has ...replaced cisplatin in the curative setting as well. However, evidence to prefer oxaliplatin over cisplatin in the curative setting is limited. (2) Methods: We compared patient-related and tumor-related outcomes for cisplatin versus oxaliplatin in patients with resectable gastric cancer treated with perioperative chemotherapy in the CRITICS trial. (3) Results: Preoperatively, 632 patients received cisplatin and 149 patients received oxaliplatin. Preoperative severe toxicity was encountered in 422 (67%) patients who received cisplatin versus 89 (60%) patients who received oxaliplatin (p = 0.105). Severe neuropathy was observed in 5 (1%) versus 6 (4%; p = 0.009) patients, respectively. Postoperative severe toxicity occurred in 109 (60%) versus 26 (51%) (p = 0.266) patients; severe neuropathy in 2 (1%) versus 2 (4%; p = 0.209) for patients who received cisplatin or oxaliplatin, respectively. Diarrhea impacted the quality of life more frequently in patients who received oxaliplatin compared to cisplatin. Complete or near-complete pathological response was achieved in 94 (21%) versus 16 (15%; p = 0.126) patients who received cisplatin or oxaliplatin, respectively. Overall survival was not significantly different in both groups (p = 0.300). (4) Conclusions: Both cisplatin and oxaliplatin are legitimate options as part of systemic treatment in patients with resectable gastric cancer.
Background
The occurrence of a venous thromboembolism (VTE) is common in patients with cancer. Gastric cancer has been associated with one of the highest risks for VTE. Chemotherapy, especially ...cisplatin has been associated with a high VTE risk. In this study, risk factors for VTE occurrence and their potential impact on subsequent therapeutic interventions were investigated in patients who underwent preoperative chemotherapy, in the CRITICS gastric cancer trial.
Patients and methods
Patients with resectable gastric cancer were preoperatively treated with three cycles of 3‐weekly epirubicin, cisplatin or oxaliplatin, and capecitabine (ECC/EOC). VTE was defined as any thrombus in the venous system, excluding superficial and/or device related VTEs. Potential risk factors were analyzed in a multivariable regression model with age, gender, Body Mass Index (BMI), tumor localization, Lauren classification, type of chemotherapy (ECC/EOC), (cardiovascular) comorbidity, and previous VTE as independent risk factors. The impact of VTE on completion rate of preoperative chemotherapy, surgical resection rate, postoperative complications, and start of postoperative therapy were investigated.
Results
Of 781 patients, 78 (10%) of 781 patients developed a VTE during preoperative chemotherapy. On multivariable analysis, BMI ≥ 30 kg/m2 and previous VTE were associated with VTE occurrence (reference BMI < 25 kg/m2; OR 2.190; 95% CI 1.152‐4.164; P = .017/previous VTE; OR 3.617; 95% CI 1.201‐10.890; P = .022). Treatment with cisplatin was, compared to oxaliplatin, not significantly associated with VTE occurrence (OR 1.535; 95% CI 0.761‐3.094; P = .231). VTE occurrence did not affect completion of preoperative chemotherapy, surgical resection rate, postoperative complications, or start of postoperative therapy.
Conclusion
High BMI and previous VTE were independent risk factors for VTE occurrence during preoperative chemotherapy in patients with resectable gastric cancer. VTE occurrence in the preoperative setting did not affect receipt of further treatment.
High BMI and previous VTE were independent risk factors for VTE occurrence during preoperative chemotherapy in patients with resectable gastric cancer. Comparable proportions of patients proceeded to surgery and started postoperative therapy, suggesting that VTE occurrence during preoperative treatment did not affect receipt of further treatment.
PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of ...neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8
PD-1
T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.
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