Personalized medicine in colorectal cancer diagnosis and treatment: a systematic review of health economic evaluations.

BACKGROUND: Due to its epidemiological relevance, several studies have been performed to assess the cost-effectiveness of diagnostic tests and treatments in colorectal cancer (CRC) patients. OBJECTIVE: We reviewed economic evaluations on diagnosis of inherited CRC-syndromes and genetic tests for the detection of mutations associated with response to therapeutics. METHODS: A systematic literature review was performed by searching the main literature databases for relevant papers on the field, published in the last 5 years. RESULTS: 20 studies were included in the final analysis: 14 investigating the cost-effectiveness of hereditary-CRC screening; 5 evaluating the cost-effectiveness of KRAS mutation assessment before treatment; and 1 study analysing the cost-effectiveness of genetic tests for early-stage CRC patients prognosis. Overall, we found that: (a) screening strategies among CRC patients were more effective than no screening; (b) all the evaluated interventions were cost-saving for certain willingness-to-pay (WTP) threshold; and (c) all new CRC patients diagnosed at age 70 or below should be screened. Regarding patients treatment, we found that KRAS testing is economically sustainable only if anticipated in patients with non-metastatic CRC (mCRC), while becoming unsustainable, due to an incremental cost-effectiveness ratio (ICER) beyond the levels of WTP-threshold, in all others evaluated scenarios. CONCLUSIONS: The poor evidence in the field, combined to the number of assumptions done to perform the models, lead us to a high level of uncertainty on the cost-effectiveness of genetic evaluations in CRC, suggesting that major research is required in order to assess the best combination among detection tests, type of genetic test screening and targeted-therapy.

Health decentralization at a dead-end: towards new recovery plans for Italian hospitals.

The recent introduction by the central government of recovery plans (RPs) for Italian hospitals provides useful insights into the recentralization tendencies that are being experienced within the country's decentralized, regional health system. The measure also contributes evidence to the debate on whether there is a long-term structural shift in national health strategy towards more centralized stewardship. The hospital RPs aim to improve the clinical, financial and managerial performance of public-hospitals, teaching-hospitals and research-hospitals through monitoring trends in individual hospitals' expenditure and tackling improvements in clinical care. As such they represent the central governments recognition of the weaknesses of the decentralization process in the health sector. The opponents of the reform argue that financial stability will be restored mainly through across-the-board reductions in hospital expenditure, personnel layoffs and closing of wards, with considerable negative effects on the most vulnerable groups of patients. While hospital RPs are comprehensive and complex, unresolved issues remain as to whether hospitals have the necessary managerial skills for the development of effective and achievable plans. Without also devising an overall plan to tackle the long-standing managerial weaknesses of public hospitals, the objectives of the hospital RPs will be undermined and the decentralization process in the health system will gradually reach a dead-end.

Efficiency and optimal size of hospitals: Results of a systematic search.

BACKGROUND: National Health Systems managers have been subject in recent years to considerable pressure to increase concentration and allow mergers. This pressure has been justified by a belief that larger hospitals lead to lower average costs and better clinical outcomes through the exploitation of economies of scale. In this context, the opportunity to measure scale efficiency is crucial to address the question of optimal productive size and to manage a fair allocation of resources. METHODS AND FINDINGS: This paper analyses the stance of existing research on scale efficiency and optimal size of the hospital sector. We performed a systematic search of 45 past years (1969-2014) of research published in peer-reviewed scientific journals recorded by the Social Sciences Citation Index concerning this topic. We classified articles by the journal's category, research topic, hospital setting, method and primary data analysis technique. Results showed that most of the studies were focussed on the analysis of technical and scale efficiency or on input / output ratio using Data Envelopment Analysis. We also find increasing interest concerning the effect of possible changes in hospital size on quality of care. CONCLUSIONS: Studies analysed in this review showed that economies of scale are present for merging hospitals. Results supported the current policy of expanding larger hospitals and restructuring/closing smaller hospitals. In terms of beds, studies reported consistent evidence of economies of scale for hospitals with 200-300 beds. Diseconomies of scale can be expected to occur below 200 beds and above 600 beds.

Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial.

The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 µg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC.

Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients.

Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred and twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients.