Patient with severe COVID-19 treated with corticosteroids. / Pasient med alvorlig covid-19 behandlet med steroider.

BACKGROUND: Treatment with corticosteroids for COVID-19 and ARDS (acute respiratory distress syndrome) is controversial and has generally not been recommended. CASE PRESENTATION: A woman in her sixties was admitted to hospital after ten days of flu-like symptoms. She was confirmed as Sars-CoV-2-positive and experienced a steady decrease in oxygen saturation (SaO2), despite being given increasing amounts of supplemental oxygen. On day three she was intubated and placed on a ventilator. She had a three-phased trajectory where ventilation was extremely challenging, prone positioning and permissive hypercapnia were necessary, and inflammation markers increased. There was no improvement in the third phase, and on day 19 on the ventilator, we decided to give her corticosteroids. Two days later she could be weaned from the ventilator. INTERPRETATION: In our patient with severe ARDS from COVID-19, we saw rapid improvement after she was given corticosteroids, and her case is a contribution to the discussion regarding use of corticosteroids for the most severely ill COVID-19 patients.

Initial Experience after Transition to Immune Checkpoint Inhibitors in Patients with Non-small Cell Lung Cancer Treated in a Rural Healthcare Region.

Objective The aim of this study was to investigate the patterns of palliative care, terminal care, and hospital deaths in deceased patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). Methods This study involves a retrospective analysis of a group of 32 patients treated with first- or second-line ICI regimens. The group was compared with a matched contemporary cohort of patients who received systemic treatment that did not include an ICI. The 1:1 matching was based on sex, age, stage of cancer (IV versus lower), and initial treatment after diagnosis (locoregional versus systemic). Results The median overall survival from diagnosis was 9.8 months [95% confidence interval (CI): 7.4-12.2 months] in the non-ICI patients and 11.6 months (95% CI: 5.9-17.3 months) in the ICI group (p: 0.09). Death resulting from toxicity was recorded in two patients (non-ICI) and one patient (ICI), respectively (p: 0.8). Hospital death was more common after ICI (19 versus 11 patients, p: 0.08). During the last three months of life, non-ICI patients spent a median of 11 days (range: 0-28) in the hospital, compared with 20 days (range: 0-45) for ICI patients (p: 0.005). More ICI patients (21 versus 14) received systemic therapy during the last three months of life (p: 0.13). However, treatment rates during the last four weeks were comparable (eight non-ICI and six ICI patients, respectively; p: 0.8). Conclusion We did not identify any concerns regarding the fatal toxicity of ICI treatment. Due to several different baseline parameters, there are reasons to believe that hospitalization and hospital death in the ICI group were mainly related to unevenly distributed disease characteristics and not to ICI administration itself. Since real-world data from rural patient cohorts might differ from those obtained in clinical trials, it is necessary to conduct additional and larger studies about ICI-associated patterns of terminal care.

A Four-Tiered Prognostic Score for Patients Receiving Palliative Thoracic Radiotherapy for Lung Cancer.

Palliative radiotherapy improves lung cancer related symptoms. Prognosis should be taken into account when deciding about fractionation. In this study, prognostic factors derived from multivariate analysis were used to assign a point sum reflecting 6-month survival. Four prognostic groups were compared. Performance status, lactate dehydrogenase, C-reactive protein, liver/adrenal gland metastases, and extrathoracic disease status significantly predicted survival and formed the basis of the score. The four groups had a median survival of 0.8, 1.6, 3.3, and 10.5 months (6-month survival 0, 10, 30, 70%; 12-month survival 0, 0, 12, 40%; p = 0.0001), respectively. In the unfavorable group best supportive care might be preferable.

Pembrolizumab as second-line therapy in non-small cell lung cancer in northern Norway: budget impact and expected gain-a model-based analysis.

BACKGROUND: Pembrolizumab is a new drug approved in several countries for second-line therapy in non-small cell lung cancer (NSCLC) being programmed cell death ligand (PD-L1) positive. This drug has a high cost, and the cost-effectiveness ratio has been debated. PATIENTS AND METHODS: The budget impact to the Northern Norwegian Regional Health Authority trust of implementing pembrolizumab in second-line therapy in patients with PD-L1-positive NSCLC was calculated. A model was developed employing data from the Cancer Registry of Norway, the KEYNOTE-010 study, the price list from The Hospital Pharmacy of North Norway, the cost of analysing PD-L1 expression and the cost of travelling. Today's cost of second-line therapy was compared with the new standard employing pembrolizumab. The sale price of pembrolizumab in Norway was not published due to price confidentiality. Norwegian krone (NKr) was converted into Euros (€) at a rate of 1€=Nkr 8.8138. (Bank of Norway, 21 February 2017). RESULTS: 105 new patients were identified available for pembrolizumab per year. The annual cost of pembrolizumab was €5.2 million, hospital pharmacy administration costs €0.1 million, PD-L1 testing €0.3 million, oncologist/pulmonologist/nurses €0.2 million, radiology €0.06 million and transportation €0.4 million. Savings due to avoided present second-line therapy was calculated €0.4 million. Consequently, the cost of implementing pembrolizumab was €5.5 million and the annual budget impact was €5.0 million. A mean gain of at least 9 months per patient treated was necessary to make pembrolizumab cost-effective. CONCLUSIONS: The net budget impact of pembrolizumab was €5.0 million. The expenditure could not be indicated cost-effective. Price confidentiality is a growing problem in health economics and it has become a 'menu without prices' setting.

Palliative Thoracic Radiotherapy for Lung Cancer: What Is the Impact of Total Radiation Dose on Survival?

BACKGROUND: Effective symptom palliation can be achieved with low-dose palliative thoracic radiotherapy. In several studies, median survival was not improved with higher doses of radiation. More controversy exists regarding the impact of higher doses on 1- and 2-year survival rates. Therefore, a comparison of survival outcomes after radiotherapy with different biologically equivalent doses (equivalent dose in 2-Gy fractions, EQD2) was performed. METHODS: This was a retrospective single-institution study of 232 patients with small or non-small cell lung cancer. Most commonly 2 fractions of 8.5 Gy were prescribed (34%), followed by 10 fractions of 3 Gy or equivalent regimens (30%, EQD2 circa 33 Gy). The highest EQD2 consisted of 45 Gy. Intention-to-treat analyses were performed. RESULTS: Survival was significantly shorter with regimens of intended EQD2 < 33 Gy, e.g., 2 fractions of 8.5 Gy (median 2.5 months compared to 5.0 and 7.5 months with EQD2 of circa 33 and 45 Gy, respectively). The 2-year survival rates were 0%, 7% and 11%, respectively. In 128 prognostically favorable patients, median survival was comparable for the three different dose levels (6 - 8.3 months). The 2-year survival rates were 0%, 10%, and 13%, respectively (not statistically significant). CONCLUSION: Although most of the observed survival differences diminished after exclusion of poor prognosis patients with reduced performance status and/or progressive extrathoracic disease, a slight increase in 2-year survival rates with higher EQD2 cannot be excluded. Because of relatively small improvements, a confirmatory randomized trial in this subgroup would have to include a large number of patients.

External Validation of a Prognostic Score for Patients Receiving Palliative Thoracic Radiotherapy for Lung Cancer.

BACKGROUND: Palliative thoracic radiotherapy is a common treatment for patients with incurable lung cancer. A recent study suggested that a prognostic score based on performance status and N and M stage predicts survival and might support decision-making (eg, when deciding about fractionation). Our aim was to perform a validation study in an independent, larger dataset. PATIENTS AND METHODS: This was a retrospective single-institution study of 232 patients with small- or non-small-cell lung cancer, with methodology comparable with that of the original study. Three subgroups were created, based on the point sum resulting from assessment of performance status and N and M stage (10-11, 12-14, 15-17 points). RESULTS: Performance status and N and M stage were significantly associated with overall survival after palliative radiotherapy in uni- and multivariate analyses. An unfavorable prognosis (10-11 points) was predicted in 56 patients (24%). Their median survival was 1.2 months. The intermediate group consisted of 137 patients (59%) with a median survival of 5.3 months. A favorable prognosis (15-17 points) was predicted in 39 patients (17%), whose median survival was 8.2 months. The difference between the intermediate and favorable subgroups did not reach statistical significance (P = .1, as compared with P = .0001 for the remaining 2 comparisons). CONCLUSION: In the original study, the median survival of patients in the 3 different prognostic strata was 2, 6, and 38 months. Except for the favorable subgroup, the validation study confirmed these results. Given the large, clinically highly relevant discrepancy (8 vs. 38 months), additional studies are needed in order to inform therapeutic decisions in patients with favorable point sum of 15 to 17.

Impact of early palliative interventions on the outcomes of care for patients with non-small cell lung cancer.

PURPOSE: The aim of this study is to address the question "does early palliative care in addition to standard oncology care or late additional palliative care improve patterns of terminal care in patients who died from non-small cell lung cancer (NSCLC)?" METHODS: We performed retrospective single-institution study of 286 patients. Palliative care was provided by a dedicated multidisciplinary palliative care team (PCT). An arbitrarily defined cutoff of 3 months before death was chosen to distinguish between early and late additional palliative care. Referral was at the discretion of the treating physicians who provided standard anticancer treatments. RESULTS: Patients who received early (8 %) or late (27 %) additional palliative care were significantly younger than those who did not receive additional palliative care. The likelihood of active anticancer treatment in the last month of life was lowest in the early additional palliative care group, p = 0.03. Patients who received early or late additional palliative care were significantly less likely to lack a documented resuscitation preference, p = 0.0001. Patients who received early additional palliative care were significantly less likely to become hospitalized in the last 3 months of life, p = 0.003. Place of death was also numerically different, with hospital death occurring in 33 % of patients who received early additional palliative care, as compared to 48 % in the late and 50 % in the no PCT group, p = 0.35. Anticancer treatment intensity was not reduced if the PCT contributed to the overall management. CONCLUSION: Early additional palliative care resulted in relevant improvements. The optimal timing of this intervention should be examined prospectively.

Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy (TRT) is recommended for limited disease small cell lung cancer (LD SCLC). Twice daily TRT is well documented, but not universally implemented - probably mainly due to inconvenience and concerns about toxicity. A schedule of three-week hypofractionated TRT is a commonly used alternative. This is the first randomized trial comparing twice daily and hypofractionated TRT in LD SCLC. MATERIAL AND METHODS: Patients received four courses of cisplatin/etoposide (PE) and were randomized to TRT of 42 Gy in 15 fractions (once daily, OD) or 45 Gy in 30 fractions (twice daily, BID) between the second and third PE course. Good responders received prophylactic cranial irradiation of 30 Gy in 15 fractions. RESULTS: 157 patients were enrolled between May 2005 and January 2011 (OD: n = 84, BID: n = 73). Median age was 63 years, 52% were men, 84% had performance status 0-1, 72% had stage III disease and 11% non-malignant pleural effusion. The treatment arms were well balanced. The response rates were similar (OD: 92%, BID: 88%; p = 0.41), but more BID patients achieved a complete response (OD: 13%, BID: 33%; p = 0.003). There was no difference in one-year progression-free survival (PFS) (OD: 45%, BID: 49%; p = 0.61) or median PFS (OD: 10.2 months, BID: 11.4 months; p = 0.93). The median overall survival in the BID arm was 6.3 months longer (OD: 18.8 months, BID: 25.1 months; p = 0.61). There were no differences in grade 3-4 esophagitis (OD: 31%, BID: 33%, p = 0.80) or pneumonitis (OD: 2%, BID: 3%, p = 1.0). Patients on the BID arm reported slightly more dysphagia at the end of the TRT. CONCLUSION: There was no difference in severe toxicity between the two TRT schedules. The twice daily schedule resulted in significantly more complete responses and a numerically longer median overall survival, but no firm conclusions about efficacy could be drawn from this phase II trial.

Nontargeted Effect after Radiotherapy in a Patient with Non-Small Cell Lung Cancer and Bullous Pemphigoid.

Purpose. To describe tumor shrinkage of nonirradiated lung metastases in a patient with non-small cell lung cancer. Case Report. The patient had a concurrent autoimmune condition, bullous pemphigoid, which was clinically exacerbated during radiotherapy of mediastinal and axillary lymph node metastases. He also developed a series of infections during and after irradiation, and we hypothesize that the immunological events during this phase might have influenced the size of the nonirradiated metastases. Conclusion. Ionizing radiation generates inflammatory signals and, in principle, could provide both tumor-specific antigens from dying cells and maturation stimuli that are necessary for dendritic cells' activation of tumor-specific T cells. Even if the detailed mechanisms causing nontargeted immune modulatory effects in individual patients are poorly understood, clinical development of radioimmunotherapy is underway.

Oligometastatic non-small cell lung cancer: a significant entity outside of specialized cancer centers?

OBJECTIVE: To report the incidence, patterns of care, and outcomes of oligometastatic non-small cell lung cancer (NSCLC) in a rural practice setting in Norway. MATERIALS AND METHODS: A retrospective analysis was conducted of all patients with stage IV NSCLC at the initial diagnosis who received active treatment in the central part of Nordland, a rural county in northern Norway, during the period of 2006-2012. We analyzed overall survival and prognostic factors. RESULTS: The initial study population included 113 patients with stage IV disease who received active therapy; of these, 23 (20%) had oligometastatic spread (a maximum of 3 metastases to 1 organ). The median age was 71 years. Of the 23 patients, 16 (70%) did not receive radical or at least moderately aggressive local treatment for their thoracic disease. Of the remaining 7 patients, 4 (17.4%) did not receive systemic therapy. The median actuarial survival was 5.6 months in patients with more advanced metastases and 11.7 months in those with oligometastases (p = 0.03). Significant differences were also seen between the 2 oligometastatic patient groups with and without more intense thoracic treatment (median 19.7 vs. 7.6 months, p = 0.004). Further significant predictors of survival in patients with oligometastases were nodal stage (p = 0.028) and weight loss (p = 0.045). Trends were seen for T stage (p = 0.058) and performance status (p = 0.07). CONCLUSION: Oligometastatic NSCLC was diagnosed in a relevant proportion of patients; therefore, warranting prospective studies are recommended. Such studies are also needed to confirm the treatment-dependent survival differences observed in our patient population.

Active anticancer treatment during the final month of life in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death and consumption of healthcare resources worldwide. Significant costs are generated shortly before death, partly because of continued oncological treatment during the terminal stage of disease. We analyzed factors predicting for the likelihood of active anticancer therapy during the final month of life. Patients who died from NSCLC (any stage and treatment) during the years 2006-2013 within a defined geographical region of northern Norway were included (n=266). Out of these, 28.6% received oncological treatment during the final month of life. Hospital death occurred in 70% of patients who received active treatment during their last month of life, compared to 41% of other patients (p=0.0001). Multivariate analysis showed that lack of documented resuscitation preference (p=0.001) and the presence of superior vena cava compression (p=0.039) were the most important predictors of active therapy during the last month of life. Trends were observed with regard to use of steroids for symptom palliation (p=0.067) and advanced T stage (p=0.071). Given that patients with documented resuscitation preference before their last month of life (typically a do not resuscitate order) were unlikely to receive active treatment during the final month (2% versus 35% in patients without documented preference), early discussion of prognosis, options for symptom control and resuscitation preference are crucial components in strategies for improving terminal care.

A population-based study of the pattern of terminal care and hospital death in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death and utilization of health care resources worldwide. Significant costs are generated in the months before death, with hospitalization being a major cost driver. Moreover, hospital death causes physical and emotional distress. We analyzed factors predicting the likelihood of hospital death from NSCLC. Patients who died from NSCLC (any stage and treatment) during the recent 5-year interval up to 31.12.2010, within a defined geographical region of northern Norway, were included (n=112). Only 15% of all patients did not require any hospitalization during their last 3 months. A minority of patients (24%) died at home, 53% in hospital and 23% in nursing homes. The likelihood of hospital death was independent of initial management and time between diagnosis and death. Even 45% of patients treated with best supportive care died in hospital. Multivariate analysis showed that initial tumor stage of T4 (RR 1.64), systemic therapy during the last 3 months of life (RR 2.60) and any active therapy during the last 4 weeks (RR 1.63) significantly increased the likelihood of hospital death, while early discussion of resuscitation preferences reduced it (RR 0.21). These four parameters suggest that early focus on symptom palliation and resuscitation preferences are crucial components of strategies improving terminal care. Patients with T4 tumors might experience unsatisfactory symptom control and should be offered a part in prospective studies addressing these issues.

"Fighting the system": families caring for ventilator-dependent children and adults with complex health care needs at home.

BACKGROUND: An increasing number of individuals with complex health care needs now receive life-long and life-prolonging ventilatory support at home. Family members often take on the role of primary caregivers. The aim of this study was to explore the experiences of families giving advanced care to family members dependent on home mechanical ventilation. METHODS: Using qualitative research methods, a Grounded Theory influenced approach was used to explore the families' experiences. A total of 15 family members with 11 ventilator-dependent individuals (three children and eight adults) were recruited for 10 in-depth interviews. RESULTS: The core category, "fighting the system," became the central theme as family members were asked to describe their experiences. In addition, we identified three subcategories, "lack of competence and continuity", "being indispensable" and "worth fighting for". This study revealed no major differences in the families' experiences that were dependent on whether the ventilator-dependent individual was a child or an adult. CONCLUSIONS: These findings show that there is a large gap between family members' expectations and what the community health care services are able to provide, even when almost unlimited resources are available. A number of measures are needed to reduce the burden on these family members and to make hospital care at home possible. In the future, the gap between what the health care can potentially provide and what they can provide in real life will rapidly increase. New proposals to limit the extremely costly provision of home mechanical ventilation in Norway will trigger new ethical dilemmas that should be studied further.

Why does the provision of home mechanical ventilation vary so widely?

There is wide variation in the provision of home mechanical ventilation (HMV) throughout Europe, but the provision of home mechanical ventilation can also vary within countries. In 2008, the overall prevalence of HMV in Norway was 19.9/100,000, and there were huge regional differences in treatment prevalence. The aim of this study is to find explanations for these differences. We gathered multidisciplinary respondents involved in HMV treatment from five hospitals in five different counties to six focus group conversations to explore respondents' views of their experiences systematically. We based the analysis on grounded theory. We found that uneven distribution of ''enthusiasm'' between hospitals seems to be an important factor in the geographical distribution of HMV. Furthermore, we found that the three subcategories, ''high competence,'' ''spreading competence,'' and ''multidisciplinary collaboration,'' are developed and used systematically in counties with ''enthusiasm.'' This culture is the main category, which might explain the differences, and is described as ''wise enthusiasm.'' The last subcategory is ''individual attitudes'' about HMV among decision-making physicians. The most important factor is most likely the uneven distribution of highly skilled enthusiasm between hospitals. Individual attitudes about HMV among the decision makers may also explain why the provision of HMV varies so widely. Data describing regional differences in the prevalence of HMV within countries is lacking. Further research is needed to identify these differences to ensure equality of provision of HMV.

Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer.

PURPOSE To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m(2) plus carboplatin area under the curve (AUC) = 5 (Calvert's formula) on day 1 or gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006. Patients who completed the baseline questionnaire were analyzed for HRQoL (n = 427), and those who received > or = one cycle of chemotherapy were analyzed for toxicity (n = 423). Compliance of HRQoL questionnaires was 87%. There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms (pemetrexed/carboplatin, 7.3 months; gemcitabine/carboplatin, 7.0 months; P = .63). The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin, including leukopenia (46% v 23%, respectively; P < .001), neutropenia (51% v 40%, respectively; P = .024), and thrombocytopenia (56% v 24%, respectively; P < .001). More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets, whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms. CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care.