Health outcomes and budget impact projection of anti-PD-(L)1s in cancer care in Portugal.

Introduction: PD-[L]1 inhibitors revolutionized cancer treatment but challenge the affordability of health systems. This policy-focused model aimed to estimate the health and budget impact of anti-PD-(L)1s in Portugal and inform current discussions. Materials and methods: The Health Impact Projection (HIP) model estimates clinical (life years, progression-free survival [PFS] years, and quality-adjusted life years [QALY] gained and adverse events [AEs] incurred) and economic (direct and indirect costs) outcomes in a world where cancer patients are initiating treatment with standard-of-care (SOC) versus SOC plus anti-PD-(L)1s over a 3-year time horizon. Indications included adjuvant and metastatic melanoma, non-small cell lung cancer (first and second line), metastatic triple-negative breast cancer, head and neck cancer, urothelial carcinoma, and renal cell carcinoma. Model inputs were based on publicly available literature data and expert opinion. Results: The model estimated that, over 3 years, 7,773 patients would be treated with anti-PD-(L)1s, realizing a gain of 4,787 life years, 6,901 PFS years, and 4,214 QALYs and avoiding 399 AEs. The introduction of anti-PD-(L)1s had a projected average annual impact of ≈ €108 million and a share of 20% of total cancer medicines expenditure and 0.6% of total healthcare expenditure in 2021. Although higher disease management costs are expected for patients living longer with anti-PD-(L)1s and drug acquisition costs are considerable, that is partially offset by a reduction in end-of-life costs (€611,092/year) and costs associated with patient productivity lost to cancer (€9,128,142/year). Discussion: This model highlights the significant survival and QoL benefit of anti-PD-(L)1s for cancer patients in Portugal, with a relatively low increased cost in total healthcare expenditure.

A Potential Link Between Prolonged Cork Exposure and Intestinal-Type Sinonasal Adenocarcinoma - Special Findings of a Retrospective Cohort Analysis.

INTRODUCTION: intestinal-type sinonasal adenocarcinoma (ITAC) is a rare epithelium tumor of the nasal cavities and paranasal sinuses. Exposure to wood and leather dusts is a strong etiological factor related to its development. Prolonged cork exposure has rarely been associated. MATERIALS AND METHODS: thirty-seven-year (1981-2018) retrospective cohort analysis of all consecutive patients with sinonasal cancer (SNC) followed at our institution. Medical records were reviewed to determine patient demographics, occupational/environmental exposure, location and extent of the tumor, stage, histopathology findings, treatment strategies, and oncologic outcomes. Survival analysis was done using Kaplan-Meier method. RESULTS: we evaluated 379 patients with SNC, including 39 (10.3%) ITAC. Patient median age was 73 years (range 49-87), 56% male and 69% with identified professional occupational exposure (54% for cork; 69.2% considering only those for which an agent has been identified). Seventy-two percent had locally advanced disease (stage III or IVA-B). The initial treatment was surgery in 77%, and 54% received adjuvant radiotherapy. The median time to progression, progression-free survival, and overall-survival was 2.36 years (95% CI 1.54-8.70), 1.96 years (95% CI 1.43-3.74), and 3.51 years (95% CI 2.33-10.02), respectively. CONCLUSION: ITAC is an uncommon malignancy that grows silently, which contributes to delayed diagnosis, advanced stage and low survival rates. In our cohort, we observed a high prevalence of cork occupational exposure. This finding may lead to the implementation of protection measures and suggest a potential link to be further studied.

Improved long-term results of intensity-modulated radiotherapy for a non-endemic European nasopharyngeal carcinoma cohort: single-center retrospective study.

PURPOSE: Report our matured outcomes of European nasopharyngeal carcinoma (NPC) treatment from a non-endemic region in the IMRT era. METHODS: We reviewed 109 consecutive patients with biopsy proven NPC treated between 2009 and 2013. All received IMRT as per RTOG 0615. Toxicity was scored accordingly to CTCAE 4.03. Platinum-based chemotherapy was delivered following the Intergroup 0099. RESULTS: Median age of 53 years; 97% Caucasian; 74% male; 72% WHO grade III; 43% T1; 14% T2; 18% T3, 25% T4; 17% N0; 17% N1; 39% N2; 27% N3. Compliance to adjuvant chemotherapy was 88%. With a median follow up of 56 months, the 4-year local control was 90.2% (88.6% for T1; 100% for T2; 85% for T3; and 91.7% for T4), the 4-year distant metastases-free survival was 86% and an overall survival rate was 77%. Local control and survival were better in G3 (p < 0.001 and p = 0.032, respectively). Xerostomia was the most frequent late toxicity in 55% (n = 60). Hypothyroidism requiring hormonal reposition occurred in 15.5% (n = 17). From the 36 deaths, 20 were due to distant metastases, 3 grade 5 toxicity, 2 from local progression, 5 non-cancer deaths and unknown cause in the remaining 6. On multivariable analysis, age (p = 0.017), local recurrence and distant metastases were associated with death (p < 0.001, both). CONCLUSION: Our matured data from the IMRT era showed a major improvement from our 3D cohort series reaching excellent local and regional control, even in T4. Local recurrences, despite few, and distant metastases were correlated with the risk of death.

Clinical experience in invasive fungal infections: multiple fungal infection as the first presentation of HIV.

Fungal infections constitute an important cause of morbidity and mortality in HIV-infected patients. The authors describe the case of a 40-year-old healthy male patient with a 2-month history of fever, shivers, asthenia and anorexia, who had lost weight during the past 6 months. Laboratory investigations revealed a positive HIV screening. Computed tomography scans of the chest and abdomen showed thoracic and lumbo-aortic adenopathies. Cryptococcus neoformans was isolated from cultures of blood, bone marrow, cerebrospinal fluid and from material obtained by transbronchial biopsy. Moreover, Cryptococcus spp. were seen in the lymph node biopsy. Pneumocystis jirovecii was isolated from bronchoalveolar lavage, whereas Aspergillus fumigatus and Aspergillus flavus were detected in material from a transbronchial biopsy. The patient initially received treatment with sulfamethoxazole plus trimethoprim and amphotericin B, which resulted in a substantial clinical improvement. After the diagnosis of invasive aspergillosis, amphotericin B was replaced by voriconazole as antifungal therapy and antiretroviral therapy was added. The simultaneous occurrence of three different infectious diseases-disseminated cryptococcosis, invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonitis-in a HIV-infected patient is extremely rare and there is no doubt that both early diagnosis and treatment are crucial for the patient's chances of survival.