Low-dose hyperradiosensitivity: is there a place for future investigation in clinical settings?

BACKGROUND AND PURPOSE: In vitro radiation doses of below 0.5 Gy have been shown to be more effective than higher doses per unit dose in killing clonogenic cells of many epithelial tumor cell lines. This phenomenon is known as low-dose hyperradiosensitivity. Preclinical studies have now suggested that there is synergism between chemotherapy and low-dose fractionated radiotherapy (LD-FRT). To test the clinical efficacy of this approach, we prospectively evaluated concurrent palliative chemotherapy and LD-FRT in patients with various types of epithelial tumors. METHODS AND MATERIALS: Patients suffering from relapses or metastases of epithelial tumors were scheduled to receive concurrent LD-FRT (two fractions of 0.4 Gy per day) and chemotherapy. Radiologic assessments were performed after three cycles of chemotherapy plus LD-FRT. RESULTS: Between June 2006 and October 2007, 12 patients with lung cancer, 7 patients with head-and-neck tumors, 2 patients with breast cancer, and 1 patient with esophageal carcinoma, for a total patient population of 22, underwent concomitant LD-FRT and chemotherapy. All patients but 3 (86%) had received previous treatments for their cancer. The median total dose of LD-FRT delivered was 800 cGy (range, 320-1280 cGy). The overall response rate was 45% (42% in previously treated patients). Grade 3-4 hematologic toxicities (Radiation Therapy Oncology Group ratings) were observed in 2 patients. At a median follow-up of 6.5 months, however, no local toxicity was observed. CONCLUSION: In our experience, concurrent LD-FRT and chemotherapy was well tolerated. Because the response rate seems promising, prospective Phase II studies of the strategy are now under way.

Dose and volume as predictive factors of pulmonary toxicity.

Dose and volume and their correlation with the development of pulmonary toxicity are among the most widely studied and validated factors in radiotherapy. Most common treatment planning systems allow prompt assessment of Vdose and Mean Lung Dose (MLD). The former represents the percentage of normal lung parenchyma receiving a dose equal to or higher than the established threshold dose; the latter corresponds to the mean dose delivered to the normal lung parenchyma. Most important studies reported on the subject and threhold values recommended for Vdose and MLD are analyzed. The monitoring system of late toxicity used by the authors is presented.

Dose and volume impact on radiation-induced xerostomia.

Radiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glands. Methods of measuring the salivary output are essentially represented by 99mTc-pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or unstimulated saliva. There are subjective and objective criteria of classification and grading of the secretion of saliva. Radiation-induced xerostomia, namely the residual salivary gland function is evidently associated with the mean dose absorbed. The salivary output tends to decrease after the end of radiotherapy. The partial dose-volume is substantially correlated with the mean dose to the whole gland. As for ipsilateral irradiation for head and neck cancer, conformal RT or IMRT allow to spare the contralateral parotid gland without increasing the risk of contralateral nodal recurrences. The monitoring system of late toxicity used by the authors is presented.

Biological optimization of the dose in elderly patients.

The incidence of tumors in elderly people is constantly growing. Because of the advanced-age associated physiological alterations, in the treatment of the elderly the evaluation of correlated morbidities cannot be overlooked. Most likely, the presently available technologies pave a new way to radiotheray in the possibility of personalized treatments and biological optimization of the dose (e.g. with special techniques as IMRT, stereotaxy) to provide treatment plans suitable for the patient clinicopathological conditions while keeping in mind the evaluation of quality life.

Clinical target volume definition in the elderly patient.

Elderly age is one of the main risk factors to be associated with the onset of different tumors. The tumor in the elderly almost always appears at a late, advanced stage for the lack of an accurate attention to symptoms-signs, as well as for the absence of involvement in mass screening campaigns. In the choice of a radiotherapy treatment in the elderly, the healthy tissues adjacent to the tumor may show a different ability for repair; this should be kept in mind in the definition of the target volume together with the possible presence of comorbidities specific to the elderly age.

Biological factors and therapeutic modulation in radiotherapy of head and neck cancer.

The most recent clinical studies are increasingly concerned about the molecular factors in terms of prognosis, predictivity of response to treatments and development of novel, targeted therapeutic strategies. An integrated diagnostic and prognostic approach is envisaged where molecular biology with the study of biological markers "integrates" TNM to enhance the control of primary disease, resulting in a prolonged disease-free overall survival, earlier and effective control of locoregional progression and better quality of life (organ and function preservation). The prognostic or predictive role of the response to treatment for some markers (p53, EGFR, cyclin D1, telomerase activity) is defined in part in head and neck tumors. More statistically relevant data are necessary to establish which of these factors can permit a better selection of candidates for more aggressive or molecular targeted therapies or for a closer follow-up, thus contributing to the change of the natural history of these tumors.