The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study

Background: The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses. Methods: Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgr

Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19):an investigator-initiated, randomised, open-label, phase 2 trial

Background Almost all patients with malignant mesothelioma eventually have disease progression after first-line therapy. Previous studies have investigated maintenance therapy, but none has shown a great effect. We aimed to assess the efficacy and safety of switch-maintenance gemcitabine in patients with malignant mesothelioma without disease progression after first-line chemotherapy. Methods We did a randomised, open-label, phase 2 trial in 18 hospitals in the Netherlands (NVALT19). We recruited patients aged older than 18 years with unresectable malignant mesothelioma with no evidence of disease progression after at least four cycles of first-line chemotherapy (with platinum and pemetrexed), who had a WHO performance status of 0-2, adequate organ function, and measurable or evaluable disease. Exclusion criteria were active uncontrolled infection or severe cardiac dysfunction, serious disabling conditions, symptomatic CNS metastases, radiotherapy within 2 weeks before enrolment, and concomitant use of any other drugs under investigation. Patients were randomly assigned (1:1), using the minimisation method, to maintenance intravenous gemcitabine (1250 mg/m(2) on days 1 and 8, in cycles of 21 days) plus supportive care, or to best supportive care alone, until disease progression, unacceptable toxicity, serious intercurrent illness, patient request for discontinuation, or need for any other anticancer agent, except for palliative radiotherapy. A CT scan of the thorax or abdomen (or both) and pulmonary function tests were done at baseline and repeated every 6 weeks. The primary outcome was progression-free survival in the intention-to-treat population. Safety was analysed in all participants who received one or more doses of the study drug or had at least one visit for supportive care. Recruitment is now closed; treatment and follow-up are ongoing. This study is registered with the Netherlands Trial Registry, NTR4132/NL3847. Findings Between March 20, 2014, and Feb 27, 2019, 130 patients were enrolled and randomly assigned to gemcitabine plus supportive care (65 patients [50%]) or supportive care alone (65 patients [50%]). No patients were lost to follow-up; median follow-up was 36.5 months (95% CI 34.2 to not reached), and one patient in the supportive care group withdrew consent. Progression-free survival was significantly longer in the gemcitabine group (median 6.2 months [95% CI 4.6-8.7]) than in the supportive care group (3.2 months [2.8-4.1]; hazard ratio [HR] 0.48 [95% CI 0.33-0.71]; p=0.0002). The benefit was confirmed by masked independent central review (HR 0.49 [0.33-0.72]; p=0.0002). Grade 3-4 adverse events occurred in 33 ( 52%) of 64 patients in the gemcitabine group and in ten (16%) of 62 patients in the supportive care group. The most frequent adverse events were anaemia, neutropenia, fatigue or asthenia, pain, and infection in the gemcitabine group, and pain, infection, and cough or dyspnoea in the supportive care group. One patient (2%) in the gemcitabine group died, due to a treatment-related infection. Interpretation Switch-maintenance gemcitabine, after first-line chemotherapy, significantly prolonged progression-free survival compared with best supportive care alone, among patients with malignant mesothelioma. This study confirms the activity of gemcitabine in treating malignant mesothelioma

Cost-effectiveness of prophylactic cranial irradiation in stage III non-small cell lung cancer

INTRODUCTION In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective. METHODS A cohort partitioned survival model was developed based on individual patient data from three randomized phase III trials (N = 670). Quality-adjusted life years (QALYs) and costs were estimated over a lifetime time horizon. A willingness-to-pay (WTP) threshold of €80,000 per QALY was adopted. Sensitivity and scenario analyses were performed to address parameter uncertainty and to explore what parameters had the greatest impact on the cost-effectiveness results. RESULTS PCI was more effective and costly (0.443 QALYs, €10,123) than no PCI, resulting in an incremental cost-effectiveness ratio (ICER) of €22,843 per QALY gained. The probability of PCI being cost-effective at a WTP threshold of €80,000 per QALY was 93%. The probability of PCI gaining three and six additional months of life were 76% and 56%. The scenario analysis adding durvalumab increased the ICER to €35,159 per QALY gained. Using alternative survival distributions had little impact on the ICER. Assuming fewer PCI fractions and excluding indirect costs decreased the ICER to €18,263 and €5554 per QALY gained. CONCLUSION PCI is cost-effective compared to no PCI in stage III NSCLC, and could therefore, from a cost-effectiveness perspective, be considered in routine care

Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer:the NVALT-8 study

Background: Retrospective studies suggest that low molecular weight heparin may delay the development of metastasis in patients with resected NSCLC. Methods: Multicentre phase 3 study with patients with completely resected NSCLC who were randomised after surgery to receive chemotherapy with or without nadroparin. The main exclusion criteria were R1/2 and wedge/segmental resection. FDG-PET was required. The primary endpoint was recurrence-free survival (RFS). Results: Among 235 registered patients, 202 were randomised (nadroparin: n = 100; control n = 102). Slow accrual enabled a decrease in the number of patients needed from 600 to 202, providing 80% power to compare RFS with 94 events (α = 0.05; 2-sided). There were no differences in bleeding events between the two groups. The median RFS was 65.2 months (95% CI, 36—NA) in the nadroparin arm and 37.7 months (95% CI, 22.7—NA) in the control arm (HR 0.77 (95% CI, 0.53–1.13, P = 0.19). FDG-PET SUVmax ≥10 predicted a greater likelihood of recurrence in the first year (HR 0.48, 95% CI 0.22–0.9, P = 0.05). Conclusions: Adjuvant nadroparin did not improve RFS in patients with resected NSCLC. In this study, a high SUVmax predicted a greater likelihood of recurrence in the first year. Clinical trial registration: Netherlands Trial registry: NTR1250/1217

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)

Background: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. Methods: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3–4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. Discussion: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. Trial registration: clinicaltrials.gov NCT03348150; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing

The accuracy of methods for determining the internal length of a nasogastric tube in adult patients : a systematic review

Background Blind insertion of nasogastric (NG) tubes is performed for several reasons: nutrition and medication administration, gastric aspiration/decompression, and other, diagnostic reasons. Accidental intraesophageal and intestinal placement is common, and increases the risk of serious complications. Therefore, accurate determination of the internal length of the NG tube before placement is considered a prerequisite for achieving correct gastric positioning. Objectives We aimed to identify, assess, and summarize the evidence on the accuracy of methods for determining the internal length of an NG tube in adults. Methods Cochrane Library, Excerpta Medica database (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science were searched up to 31 January, 2022. Studies were eligible when reporting data on the accuracy of methods for determining internal NG tube length in adults. Study selection, risk-of-bias assessment, and data extraction were performed independently by 2 investigators. Risk-of-bias was assessed using the Cochrane Risk-of-Bias Tool and the Joanna Briggs Institute Critical Appraisal Checklist for Cross Sectional Studies. A narrative synthesis of the results was then conducted. Results Twelve articles were included in this review. All studies were observational, cross-sectional in nature, except for 1 randomized controlled trial. Ten methods for determining the internal length of an NG tube were described. Correctly positioned NG tubes ranged from 13% to 99%. Results showed that the tip of the nose-earlobe-xiphoid distance (NEX) + 10 cm (mean: 59.9-60.7 cm) and (NEX x 0.38696) + 30.37 + 6 cm (mean: 56.6-56.7 cm) could potentially result in accuracy as high as 97.4% and 99.0%, respectively. Conclusions Current data do not provide conclusive evidence of 100% accuracy in finding a correctly placed NG tube when using a method for determining the internal length. Blind placement, using any of the documented methods, cannot be considered safe without additional verification of tube tip positioning. Furthermore, using any of these 10 methods does not reduce the risk of pulmonary intubation

An outpatient nursing nutritional intervention to prehabilitate undernourished patients planned for surgery : A multicentre, cluster-randomised pilot study

Background & aims: To improve the nutritional status of surgical patients before hospital admission, an Outpatient Nursing Nutritional Intervention (ONNI) was developed. The ONNI comprehends five components: determining causes of undernutrition, performing a nutritional care plan including tailored and general advice, self-monitoring of nutritional intake and eating patterns, counselling and encouragement, and conducting a follow-up telephone call to discuss improvements in nutritional behaviour. Here, we evaluate the feasibility and effectiveness of the ONNI. Methods: In a multi-centred, cluster-randomised pilot study, nurses from outpatient clinics were randomly allocated to usual care (UC) or the ONNI. Patients planned for elective surgery were included if they were at increased risk for undernutrition based on the Malnutrition Universal Screening Tool (MUST) and hospital admission was not planned within seven days. Feasibility outcomes included participation rate, extent of intervention delivery, and patient satisfaction. Nutritional intake was monitored for two days before admission. Body weight, BMI and MUST scores at hospital admission were compared to measurements from the outpatient clinic visit. Data were analysed on an intention-to-treat basis by researchers who were blinded for patients and caregivers. Results: Forty-eight patients enrolled the feasibility phase. Participation rate was 72%. Nurses delivered all intervention components adequately in the end of the implementation period. Finally, 152 patients (IG: n = 66, 43%) participated in the study. A significant difference in mean energy intake (870 kcal/d, 95%CI:630-1109 p < 0.000) and mean protein intake (34.1 g/d, 95%CI: 25.0–43.2; p < 0.000) was observed in favour of the IG. Nutritional energy requirements were achieved in 74% (n = 46) of the IG and in 17% (n = 13) of the UC group (p < 0.000), and protein requirements were achieved in 52% (n = 32) of the IG, compared to 8% (n = 6) of the UC group (p < 0.000). Body weight, BMI and MUST scores did not change in either group. Conclusions: The ONNI is a feasible and effective intervention tool for nurses at outpatient clinics. Patients in the IG had more nutritional intake and fulfilled nutritional requirements significantly more often than patients receiving UC. Further research is required to determine the optimal pre-operative timing of nutritional support and to measure its effect on other patients groups. Clinical trial registration: The study protocol was registered at the ClinicalTrial.gov website with the following identifier: NCT02440165.</p

Factors influencing the delivery of nutritional care by nurses for hospitalised medical patients with malnutrition; a qualitative study

Objectives: To describe an insight into nursing nutritional care delivery in the hospital from the perspectives of observed nursing care and an exploration of multidisciplinary attitudes and experiences with patient participation in nutritional care. Background: The prevalence of malnutrition in hospitalised patients continues to be high. Nurses' essential role in the identification and treatment of malnutrition is an important aspect of the fundamentals of care. Nurses have a key role in providing optimal nutritional care in the hospital. A systematic nursing approach, combined with an active role for patients, is required to effectively counteract malnutrition. Design: A multicentre qualitative study using ethnographic observations and focus groups. Methods: Direct observation of nutritional care was conducted on two nursing wards; nurses and inpatients were observed; and data were thematically analysed based on the fundamentals of care framework. Subsequently, six focus groups were held on three nursing wards with nurses, dietitians and nutrition assistants (n = 34). Data were analysed using open, axial and selective coding. The COREQ guidelines were used for reporting the study. Results: During 54 days, representing 183 h, 39 nurses were observed in two medical wards. Three activities in nutritional care delivery were identified from observing nurses and patients: (1) screening and assessment/at-risk determination, (2) nutritional care plans and (3) monitoring and evaluating outcomes and transition-of-care planning. In addition, the focus groups identified barriers, facilitators, needs and expectations for optimal nursing nutritional care delivery. Conclusions: This study provides an understanding of the difficulties in the delivery of nursing nutritional care. Patient participation in the nutritional care process is rare. Evidence-based strategies are required to improve the knowledge and skills of nurses and patients to participate in (mal)nutrition care. Relevance: The findings of this study are used for the development of a nursing nutrition intervention to optimise patient participation in (mal)nutrition care. Patient or public contribution: During the study, patients were not involved with the observations of care and/or with the interviews; the researchers observed the nutritional care delivery at medical wards acting as passive participants. Nurses, nutrition assistants and dietitians were after the focus groups asked for feedback on the transcripts of the interviews

An outpatient nursing nutritional intervention to prehabilitate undernourished patients planned for surgery : A multicentre, cluster-randomised pilot study

Background & aims: To improve the nutritional status of surgical patients before hospital admission, an Outpatient Nursing Nutritional Intervention (ONNI) was developed. The ONNI comprehends five components: determining causes of undernutrition, performing a nutritional care plan including tailored and general advice, self-monitoring of nutritional intake and eating patterns, counselling and encouragement, and conducting a follow-up telephone call to discuss improvements in nutritional behaviour. Here, we evaluate the feasibility and effectiveness of the ONNI. Methods: In a multi-centred, cluster-randomised pilot study, nurses from outpatient clinics were randomly allocated to usual care (UC) or the ONNI. Patients planned for elective surgery were included if they were at increased risk for undernutrition based on the Malnutrition Universal Screening Tool (MUST) and hospital admission was not planned within seven days. Feasibility outcomes included participation rate, extent of intervention delivery, and patient satisfaction. Nutritional intake was monitored for two days before admission. Body weight, BMI and MUST scores at hospital admission were compared to measurements from the outpatient clinic visit. Data were analysed on an intention-to-treat basis by researchers who were blinded for patients and caregivers. Results: Forty-eight patients enrolled the feasibility phase. Participation rate was 72%. Nurses delivered all intervention components adequately in the end of the implementation period. Finally, 152 patients (IG: n = 66, 43%) participated in the study. A significant difference in mean energy intake (870 kcal/d, 95%CI:630-1109 p < 0.000) and mean protein intake (34.1 g/d, 95%CI: 25.0–43.2; p < 0.000) was observed in favour of the IG. Nutritional energy requirements were achieved in 74% (n = 46) of the IG and in 17% (n = 13) of the UC group (p < 0.000), and protein requirements were achieved in 52% (n = 32) of the IG, compared to 8% (n = 6) of the UC group (p < 0.000). Body weight, BMI and MUST scores did not change in either group. Conclusions: The ONNI is a feasible and effective intervention tool for nurses at outpatient clinics. Patients in the IG had more nutritional intake and fulfilled nutritional requirements significantly more often than patients receiving UC. Further research is required to determine the optimal pre-operative timing of nutritional support and to measure its effect on other patients groups. Clinical trial registration: The study protocol was registered at the ClinicalTrial.gov website with the following identifier: NCT02440165.</p