S. Porciani

Post-irradiation hyperamylasemia as a biological dosimeter

Serum alpha-amylase was measured before and 24 h after either total body (31 patients) or localized irradiation including the salivary glands (40 patients) or the pancreatic area (22 patients). A significant increase in amylasemia was observed for doses to the parotid glands larger than 0.5 Gy. A sigmoid function of dose was fitted to the data and predicted a maximum amylasemia level for doses larger than 4 Gy and smaller than 10 Gy. The raw data from other published series were adequately described by the same model. However, the confidence limits of the parameters remained wide, because of a considerable interindividual variability. Post-irradiation hyperamylasemia appears to provide a good criterion for triage of accidentally irradiated patients: 24 h after a dose larger than 2 Gy to the parotid glands, 91% of the patients had an amylasemia level higher than 2.5-fold the upper normal value (sensitivity). Conversely, 96% had their serum amylasemia lower than 2.5-fold the upper normal value when dose was smaller than 2 Gy (specificity). However, a retrospective estimation of the absorbed dose (dosimetry) is not likely to be very precise because of the large interindividual variability.

Plasma Amylase Activity as a Biochemical Indicator of Radiation Injury to Salivary Glands

Irradiation of the salivary glands produces a rapid increase of salivary amylase in serum, released by the highly radiation sensitive serous cells of the glands. Serial assays of salivary amylase in serum were performed in patients treated by radiation to the upper neck region. The changes observed were compared with the amount of salivary gland mass irradiated and with the dose fractionation modality used. The irradiated volume included either the entire salivary gland mass or less than 50 per cent of the gland. Two fractionation modalities were used: a conventional fractionation of 2 Gy per day, 5 times a week, or a multiple daily fractionation of 2 Gy, 3 times a day in two series of 4 days with a 4-day interval. Both parameters (salivary gland mass irradiated and fractionation modality used) significantly influenced the shape of the amylase curve in the serum. Serum amylase may therefore be considered a reliable biologic indicator of early injury to the salivary glands.

Serum amylase and tissue polypeptide antigen as biochemical indicators of salivary gland injury during iodine-131 therapy

The study evaluated the possibility of using serum α-amylase and tissue polypeptide antigen (TPA) as biochemical markers of radiation injury in the salivary gland of patients with thyroid carcinoma treated with iodine-131. The results demonstrated that the two molecules increased 1 day after 1311 administration and returned to near control values on the 3rd day. The increase was greater and longer lasting in those patients treated with the higher 1311 administered activity. However, when the patients were divided into groups based on recovery time, which determined patients with different radionuclide elimination rates, the increase in the two molecules was greater and more lasting in those subjects with a longer period of hospitalization. A comparison with the values obtained from patients with tumours of the head and neck treated with external radiotherapy demonstrated that after the 1st day of treatment the salivary gland received an absorbed dose which, based on α-amylase levels, ranged between 0.24 and 1.89 Gy and, based on TPA levels, between 0.28 and 2.29 Gy.

Polyamine levels in healthy and tumor tissues of patients with colon adenocarcinoma

Tissue polyamine levels were determined in patients with colon adenocarcinoma to try to identify biochemical indicators able to characterize the growth and the metabolism of human solid tumors. Polyamine content was determined in the tumor and in the “healthy” mucosa sampled at different distances within the resection edges. For each patient the polyamine content in the tumor was compared with that in the mucosa. The results demonstrated that the spermidine concentration was higher in the tumor than in the healthy mucosa; the differences were statistically significant. However, spermine in the tumor increased to a lesser degree. No statistically significant differences were observed among these mucosae at different localizations, but the spermine concentration in the mucosa after the tumor showed values very close to those of the neoplasia.

Effects of Irradiation with Conventional and Multiple Daily Fractionation on Serum Amylase Activity

The behaviour of serum alpha-amylase activity was determined in patients with head and neck cancer treated by radiation therapy. The levels of serum alpha-amylase activity during conventional and multiple daily fractionation were compared. Starting from the second day of treatment an increase of serum alpha-amylase activity was observed. The increase and its duration depended on the total daily dose: after the first day of treatment a linear correlation between serum levels and total daily dose could be observed. The size of the amylase increase correlated to the proportion of salivary gland tissue included in the irradiated volume.

Polyamine Content as A Marker of Radiation Injury in the Rat Spleen

The modifications of the polyamines putrescine (put), spermidine (spd) and spermine (spm) in rat spleen after 3 Gy whole-body irradiation were studied. Rats were irradiated at four different times of the day (00.00, 06.00, 12.00 and 18.00) and sacrificed between 12 h and 62 days after irradiation. Control animals, sacrificed at the same times of the day, showed higher levels of the spd/spm ratio during the hours of light. After irradiation the polyamine content was rapidly and significantly reduced over a period of 20 days. The modification of the amount of spm lasted for a longer period of time. Normal values of polyamine content were reached at later times when the mitotic activity was restored. The results show a close correlation between polyamine concentration and [3H]thymidine uptake.

Prognostic Significance of Tissue Polypeptide Antigen (TPA) in Head and Neck Carcinomas

The serum tissue polypeptide antigen (TPA) was determined before and at the end of radiotherapy in a group of patients with head and neck epidermoid carcinoma. The baseline values were significantly higher than those in healthy control subjects. They did not depend on the site of the neoplasia but increased with clinical stage. A cut-off value of 85 U/l discriminated two groups of patients according to survival: patients whose values were lower than the cut-off had a disease-free 6-year survival rate of 61%, compared to only 22% in patients with higher TPA levels. Until the second year of follow-up, patients with complete response had baseline values significantly lower than relapsed patients. However, at 5 years the pretreatment values were similar for patients being disease-free, patients with recurrence and patients deceased within the 2-5 year period.

URINARY POLYAMINES IN PATIENTS WITH ADVANCED CERVICAL CANCER OR PELVIC CANCER RECURRENCE DURING AND AFTER RADIOTHERAPY

The urinary excretion of polyamines was evaluated before, during and after radiotherapy in 16 patients with advanced squamous cell carcinoma of the uterine cervix (stage IIb or IIIb) and in 7 cases with pelvic recurrence after surgery for various types of carcinoma. The concentration of spermidine was significantly higher in the patients with primary tumors than in those with recurrent tumors. After the first radiation fractions putrescine increased in the patients with primary tumors whereas it decreased in patients with recurrent tumors. The values tended to return to baseline levels with time following treatment initiation. Polyamine increased markedly during treatment in patients who remained disease-free for at least 5 years but not in the patients with progressive disease or relapse. The results suggest a different polyamine metabolism and a different response to radiotherapy of recurrent tumors compared to primary tumors. The increase of urinary polyamines, but not the baseline values, seemed to be correlated to the response after radiotherapy.

Polyamines in the Small Intestine of Rats after Whole-body Irradiation

The behaviour of polyamines (putrescine, spermidine and spermine) in the small intestine was studied in rats exposed to a single whole-body dose of 3 Gy administered at four different times of the day. Polyamine content decreased a few hours after irradiation but quickly returned to normal values. Putrescine levels reached the lowest values and returned to the control levels later than spermidine and spermine. A temporary increase in spermidine and spermine content was observed from 5 to 20 days. The postirradiation behaviour of the animals exposed at different times of the day showed no important differences. Polyamine modifications were studied in relation to [3H]thymidine uptake and other morphological and biochemical parameters. The results indicate that polyamine content can be used to monitor the damage and recovery phases of radiation injury in the small intestine.

Marker determination for response monitoring: radiotherapy and disappearance curves.

This paper reports the results of studies on the possible role of biochemical markers in monitoring the effects of ionizing radiations and in the follow-up of cancer patients submitted to radiotherapy. Three different case series were analyzed: patients with head and neck cancer, prostate carcinoma and residual thyroid tumors or uptaking metastases (131-Iodine therapy). Serum TPA and amylase were serially determined in patients with head and neck or thyroid cancer to measure the radiation damage to the salivary glands. In the former group a statistically significant correlation between the increase of both molecules and the total dose administered after the first day of treatment (2, 3, 4 or 6 Gy) was observed. In patients treated for thyroid cancer the damage to the salivary glands was revealed by an increase in TPA and amylase serum levels, dependent on the dose of 131-Iodine administered. Moreover, an association was demonstrated between pretreatment values of TPA in patients with head and neck tumors and prognosis: patients with values below the cutoff have significantly higher survival rates than those with higher values. In patients with prostate carcinoma PSA was confirmed to have better diagnostic and prognostic value than PAP. Patients with metastases show an inversion or lack of negative trend in PSA levels observed in the disease-free patients. This precedes the clinical diagnosis of metastases by 1 to 15 months.