Treatment outcomes and prognostic factors after chemoradiotherapy for anal cancer.

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare malignancy with rising incidence, associated with human papilloma virus (HPV). Chemoradiotherapy (CRT) is the preferred treatment. The purpose was to investigate treatment failure, survival and prognostic factors after CRT. MATERIAL AND METHODS: In this prospective observational study from a large regional centre, 141 patients were included from 2013 to 2017, and 132 were eligible for analysis. The main inclusion criteria were SCCA, planned radiotherapy, and performance status (ECOG) ≤2. Patient characteristics, disease stage, treatment, and treatment response were prospectively registered. Disease-free survival (DFS), overall survival (OS), and locoregional treatment failure after CRT were analysed. Hazard ratios (HRs) were estimated with Cox`s proportional hazards model. RESULTS: Median follow-up was 54 (range 6-71) months. Eighteen patients (14%) had treatment failures after CRT; of these 10 (8%) had residual tumour, and 8 (6%) relapse as first failure. The first treatment failure was locoregional (11 patients), distant (5 patients), and both (2 patients). Salvage abdomino-perineal resection was performed in 10 patients, 2 had resections of metastases, and 3 both. DFS was 85% at 3 years and 78% at 5 years. OS was 93% at 3 years and 86% at 5 years. In analyses adjusted for age and gender, HPV negative tumours (HR 2.5, p = 0.024), N3 disease (HR 2.6, p = 0.024), and tumour size ≥4 cm (HR 2.4, p = 0.038) were negative prognostic factors for DFS. CONCLUSION: State-of-the-art chemoradiotherapy for SCCA resulted in excellent outcomes, and improved survival compared with previous national data, with <15% treatment failures and a 3-year DFS of >80%.

High dose methotrexate chemotherapy: pharmacokinetics, folate and toxicity in osteosarcoma patients.

AIMS: To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy. METHODS: MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma patients (288 cycles) and AUC (area under the blood concentration-time curve) was calculated. Pretreatment concentrations of folate in serum (S) and erythrocytes (ER) were determined. Hepatic, renal and haematological toxicities, assessed by routine laboratory parameters, as well as mucositis were graded according to National Cancer Institute Common Terminology Criteria for adverse events (CTCAE v.3.0). Dermatitis and pleuritis were reported as occurred or not. RESULTS: S- and ER-folate pretreatment concentrations increased significantly with increasing number of HD MTX cycles (P < 0.001). ER-folate pretreatment concentrations were higher among males (median 610 nmol l⁻¹, 95% CI 550, 680) compared with females (median 465 nmol l⁻¹, 95% CI 430, 520, P < 0.001), but showed no correlation with MTX or 7-OH-MTX pharmacokinetics. We found correlations between alanine aminotransferase peak concentration (ALAT(max) ) and clearance of MTX (P < 0.001), gender (P < 0.001), age (P < 0.001) and 7-OH-MTX concentrations (P < 0.001), the latter being the main factor influencing ALAT(max) . CONCLUSION: Our results suggest that 7-OH-MTX is involved in the development of HD MTX hepatic toxicity and that young female patients are most affected.

Extraosseous uptake with DPD (Teceos(®)).

OBJECTIVE: During a short period of 10 days, four patients presented with intense extraosseous uptake of a technetium-labelled bone-seeking agent, three in the heart and one in the liver at our hospital. During the next 6 weeks, identical heart uptake was found in another two patients. Two patients were re-examined, with identical uptake on the second occasion. A search for a possible cause was initiated. METHODS: Bone scintigraphy with Teceos(®) was performed after labelling the kit as described in the Summary of Product Characteristics [IBA, http://www.iba-molecular.com/sites/default/files/spcT1901E.pdf (in french, 29/3/2011)]. On two occasions, the kit used was retrospectively analysed, without any apparent abnormality. Two patients were re-examined 1 month later, with identical cardiac and liver uptake on repeat examination. Contact with referring physicians and blood test screening did not show any consistent reason for these extraosseous uptakes. Additionally, five cases at other hospitals in Norway have been brought to our attention. RESULTS: In at least ten patients, intense cardiac uptake has been recorded, all in relatively old patients, and one young patient had massive liver uptake. No abnormalities in labelling or composition of 3,3-diphospho-1,2-propanedicarboxylic acid were found. DISCUSSION: Liver and cardiac uptakes of bone-seeking agents have been described in amyloidosis, and for the heart, after myocardial infarction. We have ruled out any possible contamination by interfering radiopharmaceuticals and cannot find any reason for these findings. Eleven patients with amyloidosis seem one of several hypotheses that is highly improbable.