A hypofractionated radiotherapy schedule with 57.75Gy in 21 fractions for T1-2N0 prostate carcinoma: Analysis of late toxicity and efficacy.

PURPOSE: The primary endpoint was to assess the late toxicity of a hypofractionated radiotherapy schedule in relation to radiation parameters concerning the rectum and bladder. The second endpoint was to assess a composite of biochemical and clinical failure. METHODS: Sixty-four prospectively selected patients diagnosed with localized low risk prostate cancer, Gleason score (GS) <7, PSA <10, and T1-2N0, were treated with external 3- dimensional conformal radiotherapy (3D-CRT). Patients received 57.75 Gy in 21 daily fractions of 2.75 Gy/fraction. RESULTS: Late gastrointestinal (GI) toxicity was as follows: grade 0: 47 (73.4 %) patients, grade 1: 12 (19.2 %), grade 2: 4 (6.3%), and grade 3: 1 (1.6%). There was a significant correlation between D50, V70 and EORTC/RTOG late rectal toxicity score (p<0.001 and p=0.006, respectively). Grade 1 and 2 late bladder toxicity was seen in 4.7 and 1.6% of the patients, respectively. With a median follow up of 18 months no biochemical relapse was observed. CONCLUSION: The present study supports the use of hypofractionated radiation therapy which showed a high therapeutic ratio with acceptable toxicity and no biochemical relapse during follow-up.

Transformation of physical DVHs to radiobiologically equivalent ones in hypofractionated radiotherapy analyzing dosimetric and clinical parameters: a practical approach for routine clinical practice in radiation oncology.

PURPOSE: The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. METHODS AND MATERIALS: To achieve this transformation, we used both the linear-quadratic model (LQ model) and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. RESULTS: Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and D50 (P < 0.001) and V60 (P = 0.001) dosimetric parameters, calculated for α/ß = 10 Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and V(≥60) dosimetric parameter, calculated for both α/ß = 2.3 Gy (P < 0.001) and α/ß = 10 Gy (P < 0.001). The new tool seems reliable and user-friendly. CONCLUSIONS: Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions.

Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article.

Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) which have a combined incidence of 5-8/100,000 population, represent the most common primary central nervous system tumors. The treatment outcomes even with aggressive approach including surgery, radiation therapy and chemotherapy are dismal with median reported survival is less than 1 year. Temozolomide is a new drug which has shown promise in treating malignant gliomas and other difficult-to-treat tumors. This drug is a per os (p.o) imidazotetrazine second-generation alkylating agent which represents the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation. The efficacy of temozolomide was tested in vitro studies and has demonstrated schedule-dependent antitumor activity against highly resistant malignancies, including high-grade glioma (HGG). In addition, in clinical studies, temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative minimal myelosuppression that is rapidly reversible, and activity against a variety of solid tumors in both children and adults. Moreover, preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O(6)-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma. At the present time temozolomide is approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy. Temozolomide's characteristics which make it a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types are its predictable bioavailability and minimal toxicity. An overview of the mechanism of action of temozolomide and a summary of results from more important randomized controlled clinical trials in high grade gliomas are presented here.