Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients.

PURPOSE: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. METHODS: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). RESULTS: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. CONCLUSIONS: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.

Prospective evaluation of the SeptiFAST multiplex real-time PCR assay for surveillance and diagnosis of infections in haematological patients after allogeneic stem cell transplantation compared to routine microbiological assays and an in-house real-time PCR method.

We prospectively evaluated a multiplex real-time PCR assay (SeptiFast, SF) in a cohort of patients undergoing allo-BMT in comparison to an in-house PCR method (IH-PCR). Overall 847 blood samples (mean 8 samples/patient) from 104 patients with haematological malignancies were analysed. The majority of patients had acute leukaemia (62%) with a mean age of 52 years (54% female). Pathogens could be detected in 91 of 847 (11%) samples by SF compared to 38 of 205 (18.5%) samples by BC, and 57 of 847 (6.7%) samples by IH-PCR. Coagulase-negative staphylococci (n=41 in SF, n=29 in BC) were the most frequently detected bacteria followed by Escherichia coli (n=9 in SF, n=6 in BC). Candida albicans (n=17 in SF, n=0 in BC, n=24 in IH-PCR) was the most frequently detected fungal pathogen. SF gave positive results in 5% of samples during surveillance vs in 26% of samples during fever episodes. Overall, the majority of blood samples gave negative results in both PCR methods resulting in 93% overall agreement resulting in a negative predictive value of 0.96 (95% CI: 0.95-0.97), and a positive predictive value of 0.10 (95% CI: -0.01 to 0.21). SeptiFast appeared to be superior over BC and the IH-PCR method.

Influence of Tumor Site on Survival in Young Patients with Head and Neck Squamous Cell Carcinoma.

The number of patients under the age of 45 diagnosed with head and neck squamous cell carcinomas (HNSCC) is increasing, probably due to the incidence of oropharyngeal cancers. Comparisons of HNSCC in young and old patients regarding tumor site and survival in sample sizes of relevance are rarely published. The aim of the study was to analyze the differences in survival between age groups dependent on tumor site and the influence of oropharyngeal cancers on the rising rates of HNSCC in the young. The records of 4466 patients diagnosed with HNSCC were reviewed retrospectively. Patients younger than 45 years were divided further into four subgroups for specific age differences in the young. The influences of patient and clinicopathological characteristics on survival were assessed using Kaplan-Meier analyses. Among the patient cohort, 4.8% were younger than 45 years. Overall survival (OS) in these patients was better, with a 5-year OS of 66.1% (vs. 46.4%), while relapse-free survival (RFS) was better in the older patient population, with a 5-year RFS of 74.9% (vs. 68.1%). Decreased RFS in the young was found for advanced tumor stages and tumor sited at the larynx. Hypopharynx and advanced stages were independent risk factors for OS under 45 years. Overall, 44.4% of all HNSCC in patients under 30 years were nasopharyngeal cancers, and incidence decreased with age. The incidence of oropharyngeal cancers increased significantly with age. Better OS in the young may be explained by lower tumor and disease stages, whereas oropharyngeal tumors and HPV were not found to cause rising rates of HNSCC. Laryngeal malignancies in young patients might be related to an increased malignant potential and should, consequently, be treated as such.

Doxorubicin induces drug efflux pumps in Candida albicans.

Candida albicans is one of the most important opportunistic fungal pathogens. It can cause serious fungal diseases in immunocompromised patients, including those with cancer. Treatment failures due to the emergence of drug-resistant C. albicans strains have become a serious clinical problem. Resistance incidents were often mediated by fungal efflux pumps which are closely related to the human ABC transporter P-glycoprotein (P-gp). P-gp is often overexpressed in cancer cells and confers resistance to many cytotoxic drugs. We examined whether cytotoxic drugs commonly used for cancer treatment (doxorubicin and cyclophosphamide) could alter the expression of genes responsible for the development of fluconazole resistance in Candida cells in the way they can influence homologous genes in cancer cell lines. ABC transporters (CDR1 and CDR2) and other resistance genes (MDR1 and ERG11) were tested by real-time PCR for their expression in C. albicans cells at the mRNA level after induction by antineoplastic drugs. The results were confirmed by a lacZ gene reporter system and verified at the protein level using GFP and immunoblotting. We showed that doxorubicin is a potent inducer of CDR1/CDR2 expression in C. albicans at both the mRNA and protein level and thus causes an increase in fluconazole MIC values. However, cyclophosphamide, which is not a substrate of human P-gp, did not induce ABC transporter expression in C. albicans. Neither doxorubicin nor cyclophosphamide could influence the expression of the other resistance genes (MDR1 and ERG11). The induction of CDR1/CDR2 by doxorubicin in C. albicans and the resulting alteration of antifungal susceptibility might be of clinical relevance for the antifungal treatment of Candida infections occurring after anticancer chemotherapy with doxorubicin.

Impact of Smoking on the Survival of Patients With High-risk HPV-positive HNSCC: A Meta-analysis.

BACKGROUND/AIM: High risk Human papillomavirus (hr-HPV) and smoking are independant risk factors for head and neck squamous cell carcinomas (HNSCC). While hr-HPV+ HNSCC has a better prognosis than smoking-associated HNSCC no systematic data are yet available about the combined risk. PATIENTS AND METHODS: We performed a meta-analysis to assess the overall survival of HNSCC patients relative to the hr-HPV and smoking status. A literature review up to November 2019 was conducted in PubMed and Cochrane Library using the search terms 'HPV, Smoking and HNSCC'. RESULTS: Nine out of 748 articles were included, 1,436 out of 2,080 patients were hr-HPV+ The prevalence of hr-HPV+ smokers was 36%. The meta-analysis showed a significantly better 5-year overall survival for HPV+ non-smokers compared to smokers with risk ratio of 1.94 (95% confidence intervaI=1.46-2.58). CONCLUSION: Smoking is a negative prognostic factor for overall survival in patients with hr-HPV+ HNSCC and should thus be an important part of staging and treatment.

Fever range whole body hyperthermia for re-irradiation of head and neck squamous cell carcinomas: Final results of a prospective study.

OBJECTIVES: Fever-range whole body hyperthermia (FRWBH) has been shown to improve tumor oxygenation in vivo. A prospective pilot study addressed the question if addition of FRWBH to re-irradiation is feasible in recurrent head and neck squamous cell carcinomas (HNSCC) with unfavorable prognostic features. MATERIALS AND METHODS: The study completed accrual with the recruitment of ten patients between April 2018 and March 2020. Re-irradiation was administered using volumetric arc hyperfractionated radiotherapy with bi-daily 1.2 Gray (Gy) single fractions and a total dose of 66 Gy to all macroscopic tumor lesions. Concomitant chemotherapy consisted mostly of cisplatin (7 patients). FRWBH was scheduled weekly during re-irradiation. The study was registered in the clinicaltrials.gov database (NCT03547388). RESULTS: Only five patients received all cycles of FRWBH. Poor patient compliance, active infections during treatment and study restrictions due to the Covid-19 pandemic were the main reasons for omitting FRWBH. No increase of acute toxicity was observed by FRWBH. Exploratory evaluation of outcome data suggests that FRWBH treatment according to protocol does not seem to have a detrimental effect on tumor control or survival and might even increase treatment efficacy. CONCLUSION: FRWBH is difficult to apply concomitant to re-irradiation in HNSCC. No excess toxicity was observed in patients receiving FRWBH and exploratory analyses suggest potential anti-tumor activity and decreased patient-reported depression scores after FRWBH.

Prognostic Factors Predict Oncological Outcome in Older Patients With Head and Neck Cancer Undergoing Chemoradiation Treatment.

PURPOSE: Older patients with head and neck cancer (HNC) represent a challenging group, as frailty and comorbidities need to be considered. This study aimed to evaluate the efficacy and side effects of curative and palliative (chemo) radiation ([C]RT) with regard to basic geriatric screening in older patients. METHODS: This study included HNC patients aged ≥70 years who were treated with curative or palliative (C)RT. Clinicopathological data including Charlson Comorbidity Index (CCI), Karnofsky performance status (KPS), and treatment data were analyzed as predictors of overall survival (OS). RESULTS: A total of 271 patients (median age, 74 years) were enrolled. The majority had UICC stage III/IV (90%) and underwent curative treatment (85.2%). A total of 144 (53.1%) patients received definitive and 87 (32.1%) had adjuvant (C)RT. Overall, 40 patients (14.8%) received palliative (C)RT. Median follow-up duration (curative setting) was 87 months, and the 2- and 5-year OS rates were 57.8 and 35.9%, respectively. Median OS was significantly different for age ≤75 vs. >75 years, CCI <6 vs. ≥6, KPS ≥70 vs. <70%, Tx/T1/T2 vs. T3/T4, and adjuvant vs. definitive (C)RT, respectively. Age 70-75 years (p = 0.004), fewer comorbidities when CCI < 6 (p = 0.014), good KPS ≥ 70% (p = 0.001), and adjuvant (C)RT (p = 0.008) independently predicted longer survival. Palliative RT resulted in a median OS of 4 months. CONCLUSION: Older age, lower KPS, higher CCI, and definitive (C)RT are indicators of worse survival in older patients with HNC treated curatively. Without a comprehensive geriatric assessment in patients aged >75 years, the KPS and CCI can be useful tools to account for "fitness, vulnerability or frailty" to help in treatment decision-making.

CNS aspergillosis: recognition, diagnosis and management.

Early diagnosis of CNS aspergillosis requires a high degree of clinical suspicion, because there are no typical clinical symptoms or CSF findings. Clinical features are usually dramatic and tend to progress rapidly. Changes in mental status, hemiparesis and seizures are most common, but other nonspecific neurological features may occur and should always be an indication for neuroradiological examination in high-risk patients, in order to allow early initiation of antifungal therapy. Low density lesions with little or no mass effect and minimal or no contrast enhancement on CT scans that are usually more numerous on MRI and show intermediate signal intensity within high-signal areas on T2-weighted images, may suggest CNS aspergillosis. Cerebral lesions in CNS aspergillosis are often located not only in the cerebral hemispheres but also in the basal ganglia, thalami, corpus callosum and perforator artery territories. There is frequently a lack of contrast enhancement or perifocal oedema, due to the immunosuppressed status of the patient. A definite diagnosis requires brain tissue for histopathological analysis. However, neurosurgery is often not feasible, so that any of the neuroradiological findings mentioned above should raise the suspicion of CNS aspergillosis in immunocompromised patients and lead to early initiation of antifungal therapy. In the past, amphotericin B-based therapy was the treatment of choice for CNS aspergillosis, but this treatment produced negligible effects. Recently, voriconazole has been reported to be more effective than amphotericin B in the treatment of invasive aspergillosis. Response rates of about 35% have been achieved with voriconazole in patients with CNS aspergillosis. Combination therapy with antifungal agents, such as voriconazole plus caspofungin or liposomal amphotericin B, is being investigated in vitro and in animal models, and optimistic results have been observed. A combined medical and neurosurgical treatment should be considered in all patients with this disease.

Development of a new real-time TaqMan PCR assay for quantitative analyses of Candida albicans resistance genes expression.

Candida albicans is an important opportunistic pathogen that can cause serious fungal diseases in immunocompromised patients including cancer patients, transplant patients, and patients receiving immunosuppressive therapy in general, those with human immunodeficiency virus infections and undergoing major surgery. Its emergence spectrum varies from mucosal to systemic infections and the first line treatment is still based on fluconazole, a triazole derivate with a potent antifungal activity against most of C. albicans strains. Nevertheless the emergence of fluconazole-resistant C. albicans strains can lead to treatment failures and thus become a clinical problem in the management of such infections. For that reason we consider it important to study mechanisms inducing azole resistance and the possibilities to influence this process. In this work we give a short report on a real-time PCR (TaqMan) assay, which can be used for quantitative analyses of gene expression levels of MDR1, CDR1 and ERG11, genes supposed to contribute to development of the resistance mechanisms. We show some results achieved with that assay in fluconazole susceptible and resistant strains that confirm results seen earlier in experiments using Northern blot hybridisation and prove that the comparative DeltaCt method is valid for our system.

Voriconazole: review of a broad spectrum triazole antifungal agent.

Voriconazole is a second-generation triazole antifungal agent, structurally derived from fluconazole with an extended spectrum of activity against a wide variety of yeasts and moulds. Developed for the treatment of life-threatening fungal infections, it appears to be an effective therapy option for invasive aspergillosis, fluconazole-resistant candidiasis and refractory or less-common invasive fungal infections. It is available for both oral and intravenous administration and is characterised by an acceptable safety and tolerability spectrum.