Impact of innovation in oncology: more questions than answers.

Oncology is going through the fastest innovation period in the history of medicine and a growing number of patients improve or experience increased chances of survival. The declining death rate, starting from 1991, resulted in 2.9 million deaths avoided in the United States so far. A growing prevalence of patients is observed in all Western countries. New cancer drug approvals between 2000 and 2016, linked to other diagnostic, surgical, and health care improvements, were significantly associated with death reduction for the most common cancers. Alongside many positive aspects, other effects of innovations in oncology also deserve attention, especially challenges associated with the substantial increase of knowledge volume, the sharp growth of prevalence, and a concomitant or consequent increase in clinical, social, and organizational complexity. We analyse some of the consequences of oncology innovation on healthcare systems and professionals and present some suggestions on how these could be addressed by healthcare systems.

Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker.

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40-5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16-5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00-7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

Assessment of the Mutational Status of NSCLC Using Hypermetabolic Circulating Tumor Cells.

Molecular characterization is currently a key step in NSCLC therapy selection. Circulating tumor cells (CTC) are excellent candidates for downstream analysis, but technology is still lagging behind. In this work, we show that the mutational status of NSCLC can be assessed on hypermetabolic CTC, detected by their increased glucose uptake. We validated the method in 30 Stage IV NSCLC patients: peripheral blood samples were incubated with a fluorescent glucose analog (2-NBDG) and analyzed by flow cytometry. Cells with the highest glucose uptake were sorted out. EGFR and KRAS mutations were detected by ddPCR. In sorted cells, mutated DNA was found in 85% of patients, finding an exact match with primary tumor in 70% of cases. Interestingly, in two patients multiple KRAS mutations were detected. Two patients displayed different mutations with respect to the primary tumor, and in two out of the four patients with a wild type primary tumor, new mutations were highlighted: EGFR p.746_750del and KRAS p.G12V. Hypermetabolic CTC can be enriched without the need of dedicated equipment and their mutational status can successfully be assessed by ddPCR. Finally, the finding of new mutations supports the possibility of probing tumor heterogeneity.

Economic burden of patients affected by non-small cell lung cancer (NSCLC): the LIFE study.

PURPOSE: Non-small cell lung cancer (NSCLC) is a condition with significant clinical burden for patients and relevant economic impact. Limited evidence exists on the management costs of NSCLC patients, especially in the late phases of the disease. The main objective of this analysis was to evaluate the economic impact of clinical management of NSCLC patients in the Italian population. METHODS: This evaluation was an economic analysis of the observational and multicentre study LIFE, which described the therapeutic approach in routine clinical practice for NSCLC patients, progressing after first-line treatment. This study evaluated resource consumption in different Italian hospitals, including specialist visits, hospitalizations, accesses to first aid, pharmacological treatment, laboratory tests and palliative care. The National Healthcare Service perspective was adopted. RESULTS: In this study, N = 191 patients enrolled in the LIFE study were included. Patients were aged 64.2 years and were predominantly males (66%). In the different line of treatments, monthly costs of patients ranged between €1471 (first line) and €1788 (third line). The overall healthcare cost over the average period of observation (16.4 months) was €25,859 per patient. Overall, oncology therapy was the cost driver, although the composition of medical costs changed across the different lines of treatment, with costs for concomitant medication and palliative care being predominant in late phase of the disease. CONCLUSIONS: The economic burden of NSCLC is extremely high during the overall period of treatment, and a significant level of care is required in each stage of the disease.

Risk of unplanned visits for colorectal cancer outpatients receiving chemotherapy: a case-crossover study.

AIM: This study was conducted to evaluate the impact of chemotherapy on the risk of unplanned visit in a cohort of colorectal cancer outpatients. Chief complaints for unplanned visits and risk factors for hospital admission were also analyzed. PATIENTS AND METHODS: Clinical data of 229 consecutive colorectal cancer patients who were unexpectedly presented to our acute oncology clinic between 2006 and 2009 were reviewed. A case-crossover statistical analysis was applied to study the association between exposure to chemotherapy (trigger event) and the occurrence of unplanned visit (acute outcome) in three time windows (7, 15, and 21 days from the closest previous chemotherapy treatment). Cox model was used to assess the risk factors for hospitalization. RESULTS: There were 469 unplanned visits registered. Most of the patients had Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (80 %) and advanced cancer stage (78 %). The majority of unplanned visits (72 %) occurred within 30 days since last chemotherapy. The most frequent presenting complaints were pain, fatigue, and anorexia. The two time windows associated with higher risk of visit were 15 and 21 days from last treatment, both for early (odds ratio [OR] 3.8, CI 1.4-10.2 and OR 3.8, CI 1.4-10.2) and advanced disease stage (OR 1.71, CI 1-2.9 and OR 3, CI 1.5-5.9). Of the unplanned visits, 10 % resulted in hospital admission. Presenting with multiple symptoms and with deteriorated PS were both predictors for hospitalization. CONCLUSION: Chemotherapy exposition triggers the need for unplanned visits over the second and third week after treatment. The prompt and effective management of unexpected events may be cost- and time-saving and reduce pressure on oncology services.

Drug waste minimization as an effective strategy of cost-containment in oncology.

BACKGROUND: Sustainability of cancer care is a crucial issue for health care systems worldwide, even more during a time of economic recession. Low-cost measures are highly desirable to contain and reduce expenditures without impairing the quality of care. In this paper we aim to demonstrate the efficacy of drug waste minimization in reducing drug-related costs and its importance as a structural measure in health care management. METHODS: We first recorded intravenous cancer drugs prescription and amount of drug waste at the Oncology Department of Udine, Italy. Than we developed and applied a protocol for drug waste minimization based on per-pathology/per-drug scheduling of chemotherapies and pre-planned rounding of dosages. RESULTS: Before the protocol, drug wastage accounted for 8,3% of the Department annual drug expenditure. Over 70% of these costs were attributable to six drugs (cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab) that we named 'hot drugs'. Since the protocol introduction, we observed a 45% reduction in the drug waste expenditure. This benefit was confirmed in the following years and drug waste minimazion was able to limit the impact of new pricely drugs on the Department expenditures. CONCLUSIONS: Facing current budgetary constraints, the application of a drug waste minimization model is effective in drug cost containment and may produce durable benefits.

Drug waste minimisation and cost-containment in Medical Oncology: two-year results of a feasibility study.

BACKGROUND: Cost-containment strategies are required to face the challenge of rising drug expenditures in Oncology. Drug wastage leads to economic loss, but little is known about the size of the problem in this field. METHODS: Starting January 2005 we introduced a day-to-day monitoring of drug wastage and an accurate assessment of its costs. An internal protocol for waste minimisation was developed, consisting of four corrective measures: 1. A rational, per pathology distribution of chemotherapy sessions over the week. 2. The use of multi-dose vials. 3. A reasonable rounding of drug dosages. 4. The selection of the most convenient vial size, depending on drug unit pricing. RESULTS: Baseline analysis focused on 29 drugs over one year. Considering their unit price and waste amount, a major impact on expense was found to be attributable to six drugs: cetuximab, docetaxel, gemcitabine, oxaliplatin, pemetrexed and trastuzumab. The economic loss due to their waste equaled 4.8% of the annual drug expenditure. After the study protocol was started, the expense due to unused drugs showed a meaningful 45% reduction throughout 2006. CONCLUSION: Our experience confirms the economic relevance of waste minimisation and may represent a feasible model in addressing this issue.A centralised unit of drug processing, the availability of a computerised physician order entry system and an active involvement of the staff play a key role in allowing waste reduction and a consequent, substantial cost-saving.