While the problem of vaccine hesitancy is not new, it has become more pronounced with the new COVID-19 vaccines and represents an obstacle to resolving the crisis. Even people who would usually trust ...vaccines and experts now prefer to wait for more information. A cross-sectional online survey was conducted in Slovenia in December 2020 to find out the attitudes of the population regarding COVID-19 vaccination and the factors that affect these attitudes. Based on 12,042 fully completed questionnaires, we find that higher intention to get vaccinated is associated with men, older respondents, physicians and medical students, respondents who got the influenza vaccination, those who knew someone who had gotten hospitalised or died from COVID-19 and those who have more trust in experts, institutions and vaccines. Nurses and technicians were less likely to get vaccinated. In answers to an open question, sceptics were split into those doubting the quality due to the rapid development of the vaccine and those that reported personal experiences with side effects of prior vaccinations. Although the Slovenian population is diverse in its attitudes towards vaccination, the results are comparable to those found in other countries. However, there are potential limitations to the generalizability of the findings that should be addressed in future studies.
Background
In every report on incurable disease, clear presentation of toxicity and of quality of life (QoL) is of essential importance. This postulate was assessed on a series of publications on ...systemic treatment for advanced lung cancer.
Materials and methods
The analysis covered papers on original phase II–IV clinical trials published between 2013 and 2015 and included in the PubMed database.
Results
Selected for analysis were 349 publications on 333 trials with a total of 78.977 patients. Only 33 trials (10%) dealt with small cell lung cancer. Most trials (56.5%) included only information on frequency and grade of specific toxic phenomena and did not provide data on the frequency of
any
serious toxicity. The ratio between the frequency of any grade ≥ 3 toxicity and response rate was often unfavorable, especially for second-line treatment of non-small cell lung cancer (3.0) and second-line treatment of small cell lung cancer (5.3). Assessment of QoL was mentioned in 68 (20.4%) trials, of which only 46 publications provided adequate data.
Conclusions
A substantial proportion of publications on trials for advanced lung cancer do not offer adequate information for decisions in clinical practice. Presentation of toxicity should include information on the frequency of
any
serious toxicity. Quality of life should be monitored and reported in every trial of an incurable disease. Simple instruments for the assessment of QoL are strongly recommended, so as to alleviate burden to patients and to staff, avoid bias due to poor compliance and enable clear analysis and presentation.
There is a lack of data on the efficacy and safety of concurrent chemoradiotherapy in elderly, limited-stage, patients with SCLC.
We compared outcomes of patients 70 years of age or older versus ...younger patients within the Concurrent Once-daily Versus twice-daily RadioTherapy (CONVERT) trial. Patients were randomized to receive 45 Gy/30 twice-daily fractions/19 days or 66 Gy/33 once-daily fractions/45 days concurrently with platinum-based chemotherapy. Overall survival and progression-free survival were evaluated using Kaplan-Meier methodology and Cox proportional hazards regression.
Of 547 patients randomized between April 2008 and November 2013, 57 did not receive protocol treatment and were excluded. Of the 490 patients included, 67 (14%) were 70 years of age or older (median age: 73 years; range: 70–82). Fewer older patients received the optimal number of radiotherapy fractions (73% versus 85%; p = 0.03); however, chemotherapy compliance was similar in both groups (p = 0.24). Neutropenia grade 3/4 occurred more frequently in the elderly (84% versus 70%; p = 0.02) but rates of neutropenic sepsis (4% versus 7%; p = 0.07) and death (3% versus 1.4%; p = 0.67) were similar in both groups. With a median follow-up of 46 months; median survival in the elderly versus younger groups was 29 (95% confidence interval CI: 21–39) versus 30 months (95% CI: 26–35), respectively; (hazard ratio: 1.15, 95% CI: 0.84–1.59; p = 0.38). Median time to progression in the elderly versus younger groups was 18 months (95% CI: 13–31) versus 16 months (95% CI: 14–19), respectively (hazard ratio: 1.04, 95% CI: 0.76–1.41; p = 0.81).
Concurrent chemoradiotherapy with modern radiotherapy techniques should be a treatment option for fit, older patients.
In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and ...performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.
Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent
hybridization).
Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups.
Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.
Disparities in cancer care are a reality of the modern world. Unfortunately, current clinical research is in the hands of for-profit pharmaceutical companies and of researchers from the developed ...world. Problems specific to cancer care in developing countries and among deprivileged populations are ignored. Independent clinical research can offer new valuable knowledge and identify affordable and cost-effective treatments. As such, research not depending on commercial sponsors should become one of the important avenues to alleviate the problem of cancer disparities.
Abstract Introduction The sensitivity and specificity of immunohistochemistry (IHC) was compared to standard PCR-based method for detecting common activating epidermal growth factor receptor (EGFR) ...mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR TKIs treatment outcome and estimated cost-effectiveness for the upfront IHC testing. Methods The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested using automated immunostainer. 60/79 EGFR mutation-positive cases were treated with EGFR TKIs for advanced disease and included in treatment outcome analysis. Decision tree was used for the cost-effectiveness analysis. Results The overall sensitivity and specificity of IHC-based method compared to the PCR-based one were 84.8% (95% CI 75.6–91.6) and 100% (95% CI 85.4–100), respectively. The median PFS and OS of patients with IHC positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs 14.0 months; OS: 34.4 vs 34.4 months). The PCR and IHC cost ratio needs to be about eight-to-one and four-to-one in Caucasian and Asian population, respectively, to economically justify upfront use of IHC. Conclusion The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability.
Background. Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).
Patients and ...methods. Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.
Results. Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2-3 (11 patients - 21%) and brain metastases (15 patients - 28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.
Conclusions. While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations
When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs ...should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment.
Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson's correlation coefficient and the coefficient of determination, separately for first-line and second-line setting.
The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with non-squamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months.
Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.
Background. The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study ...compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid.
Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).
Results. From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively.
Conclusions. Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance
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