The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants of the GLA gene. Heterozygous female patients may show much more variability in clinical manifestations, ranging from asymptomatic to full-blown disease. Because of this heterogeneous clinical picture in women, the diagnosis of FD has typically been delayed for more than a decade, and the optimal time to initiate treatment remains controversial. Case Presentation. Here, we present two unrelated female patients diagnosed with FD harbouring the same pathogenic GLA variant. We discuss the implications of initiating specific therapy at different stages of the disease, with and without organ involvement (early versus late therapeutic intervention). Conclusions: These clinical cases suggest that initiating specific treatment at an earlier age in women with FD may prevent organ involvement and associated clinical events.

Influence of the persistence of tobacco and alcohol use in the appearance of second neoplasm in patients with a head and neck cancer. A case-control study.

OBJECTIVE: To evaluate the influence of persistent tobacco and alcohol use on the risk of a second metachronous neoplasm in the aerodigestive tract in head and neck squamous cell carcinoma (HNSCC) patients. METHODS: A matched case-control study was carried out in 514 patients with HNSCC. Case patients developed a second metachronous neoplasm in the aerodigestive tract after treatment of an index HNSCC. A patient free of second neoplasm was individually matched to every case patient by location of the index tumor, tumor stage, sex, previous tobacco and alcohol consumption, age, general health status, and treatment. Data about persistence in tobacco and alcohol consumption after treatment of the index tumor was collected retrospectively. A validation study was carried out to confirm the adequacy of this retrospective information. RESULTS: Persistent tobacco smoking and alcohol drinking after treatment of a HNSCC contributed to the risk of appearance of second neoplasm. The odds ratio of a second neoplasm for patients who continued to smoke was 2.9 (95% CI OR 1.8-4.1), and for patients who continued to use alcohol it was 5.2 (95% CI OR 3.3-7.9). There was a strong association between persistence of tobacco and alcohol use after treatment of the HNSCC index tumor. According to the attributable risk estimation, persistent tobacco and alcohol consumption would be responsible for one-third of the second neoplasms in the patients with a HNSCC index tumor. CONCLUSIONS: Persistence of tobacco and alcohol use after treatment of a HNSCC had a significant influence on the appearance of a second neoplasm in the aerodigestive tract. Cessation of tobacco and alcohol use should be a major goal after treatment of a HNSCC.

Metachronous second primary tumours in the aerodigestive tract in patients with early stage head and neck squamous cell carcinomas.

Early-stage head and neck carcinomas can usually be controlled with the appropriate treatment. In these patients, the long-term prognosis mainly depends on second metachronous malignancies, frequently in the aerodigestive tract. Our study aims to identify risk factors for the appearance of second tumours in this group of patients with early head and neck cancer. Of 949 patients included in the study, 189 (20%) developed a metachronous second primary malignancy, most frequently in the aerodigestive tract. Independent risk factors associated with second tumours were heavy alcohol use and the location of the index tumour in the oropharynx. Compared to non-drinkers, heavy drinkers (>80 g/day) presented a 1.8-times higher risk of a second tumour (CI 95%: 1.01-3.50). Patients with oropharyngeal tumours had a 2.15-higher risk than patients with oral cavity tumours (CI 95%: 1.03-4.47). Recursive partitioning analysis was used to characterise two risk groups for second tumours. The low-risk group included patients over 75 years and patients with low levels of carcinogen use. It comprised 171 patients (18%) with a 5.3% frequency of second tumours. The high-risk group accounted for 80% of the patients (n = 778), and the rate of second neoplasms was 16.3%. Classification of the patients according to the mentioned variables allows us to focus follow-up and prevention efforts on high-risk patients.

Comparison of the Radiation Therapy Oncology Group recursive partitioning classification and Union Internationale Contre le Cancer TNM classification for patients with head and neck carcinoma.

BACKGROUND: Prognostic models need to be tested in external validation studies to assess generalizability. Recursive partitioning analysis (RPA), a prognostic system based on the creation of a classification tree, has been proposed as a classification method in patients with head and neck carcinoma. The aim of this study was to compare the RPA and Union Internationale Contre le Cancer (UICC) TNM classification systems in patients with head and neck carcinoma treated consecutively in a single center. METHODS: A total of 2166 patients with carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx was classified according to both the RPA and the TNM classification systems, and the results were compared. The endpoints considered were observed survival and survival free of locoregional tumor. The two methods of classification were evaluated objectively by use of measures of intrastage homogeneity (hazard consistency), interstage heterogeneity (hazard discrimination), predictive power (outcome prediction), and patient distribution between stages (balance). RESULTS: When the endpoint considered was observed survival, there were no clinically relevant differences between the two classifications. However, when the endpoint was locoregional control, the RPA system was sensitive to the type of treatment used, and it was not generalizable. CONCLUSIONS: To evaluate generalizability, new classification proposals need external validation studies that objectively measure the quality of the model. The performance of the RPA system was not reproducible in our cohort of patients when the endpoint evaluated was locoregional control.