Individualization of the subcutaneous amifostine dose during hypofractionated / accelerated radiotherapy.

BACKGROUND: Individualization of the daily dose of amifostine may prove of value in achieving maximum cytoprotection during radiotherapy. PATIENTS AND METHODS: Using an algorithm based on: i) the gradual increase of the amifostine dose, ii) an amifostine tolerance-recording scale and iii) the intermittent administration of dexamethasone, the individualization of the subcutaneous amifostine dose was prospectively attempted in a large cohort of 132 cancer patients, treated with 12-15 consecutive fractions of 3.4-3.5 Gy (hypofractionated accelerated radiotherapy with cytoprotection, HypoARC). RESULTS: Using the above algorithm, a daily dose of 1000 mg of amifostine was successfully delivered in 62% of patients. An additional 20% of patients tolerated well a mean daily dose of 750-975 mg. Nausea and fatigue were minimal, while fever/rash enforced amifostine interruption in 7% of cases. CONCLUSION: Individualization of the amifostine dose allowed an up to two-fold increased daily-dose administration of amifostine and can be tested as a support to aggressive radio-chemotherapy schemes aiming at improving the cure rates of cancer patients, while avoiding excess toxicity.

Nasopharyngeal carcinoma: the impact of CT-scan and of MRI on staging, radiotherapy treatment planning, and outcome of the disease.

The present study is a critical review of the role of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis and therapy of nasopharyngeal cancer. It is estimated that following CT-scan/MRI, T,N staging of the disease changes in about half of cases, which results in important adjustments of the radiotherapy treatment planning, both in terms of radiation field dimensions and of dose specifications. The development of novel technology with CT-scan-simulated 3-D conformal or intensity-modulated radiotherapy (IMRT) planning is gradually becoming the standard therapy for nasopharyngeal carcinoma (NPC). CT-scan/MRI is also of value in detecting massive parapharyngeal involvement, low-neck lymphadenopathy or fixation of nodes onto adjacent structures, which are important features indicating the necessity to integrate chemotherapy or surgical neck dissection in the overall treatment policy. CT-positron emission tomography (PET) scan is recently under evaluation for the identification of the most active tumor regions, which will allow a biological radiotherapy planning (RTP) using IMRT techniques.

Conformal hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC) for high risk prostatic carcinoma: rationale, technique and early experience.

Recent radiobiological analysis of the radiotherapy results for prostate cancer revealed that prostate carcinoma behaves as a late responding tissue, sharing an alpha/beta ratio lower than 2Gy. These findings suggest that hypofractionation may be more effective. Reduction of the overall treatment time could further increase response by abrogating the effect of rapid tumor repopulation. In the present study we report a conformal technique applied (to pelvis and prostate) for the treatment of high-risk prostate cancer, using hypofractionated and accelerated radiotherapy (3.4Gy x 15 consecutive fractions) supported with high-dose daily amifostine (1000mg subcutaneously) to protect normal tissues against early and late effects. The biological dose delivered to the prostate cancer by this HypoARC (hypofractionated accelerated radiotherapy with cytoprotection) technique is estimated to be 71.4Gy (alpha/beta= 1.5 Gy). The time-adjusted biological dose is estimated to 77-94 Gy. Amifostine tolerance was excellent. All seven patients recruited up to now have accomplished their treatment with grade 0-1 cystitis or diarrhoea (5/7 grade 0). The study is ongoing to assess efficacy and late effects of HypoARC.