Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

PURPOSE: This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. MATERIALS AND METHODS: The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. RESULTS: The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). CONCLUSIONS: The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

[Current indications for thyroidectomy]. / Le indicazioni chirurgiche alla tiroidectomia.

Thyroid surgery, one of the most common interventions in endocrine surgery, is practiced by many specialists who perform this procedure exclusively. It accounts for the bulk of work even in reference centers that treat rare endocrine tumors (e.g. adrenal and gastrointestinal tract cancer). Better results are obtained by experienced and skilled operators. Surgeons who correctly perform thyroid surgery can achieve excellent outcomes even in other areas of endocrine surgery. So it is surprising that not more is being done to teach the procedure, which has always been considered something of an art, perhaps because surgical treatment of rare endocrine tumors is more stimulating to teach than routine surgical procedures. Nonetheless, teaching correct surgical technique is essential for reducing and avoiding postoperative complications caused by inadequate experience and knowledge. Numerous studies have reported that the incidence of complications is high and that the rate is growing: 5% involve permanent injury to the recurrent laryngeal nerve after intervention for a benign tumor, despite repeated reports that the incidence could be reduced to near zero or at least to 1%. Alarmingly high is the 20% incidence of persistent hypoparathyroidism after total thyroidectomy. Here, too, accurate technique could reduce this rate to 1%. An important point is that permanent laryngeal nerve injury and persistent hypoparathyroidism are both sources of considerable discomfort for patients. One of the chief objectives of modern endocrine surgery is, therefore, to reduce the complications rate to acceptable levels by establishing adequate, uniform teaching protocols and universal guidelines that would help improve the practice of surgery.

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

BACKGROUND: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. METHODS: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). RESULTS: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain alpha(LF) index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. CONCLUSION: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes: in vivo and in vitro studies.

Intracellular free calcium concentrations (Ca++i) were studied in polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice, when hypothyroid (visit 1) and after restoration of euthyroidism by L-T4 TSH-suppressive therapy (visit 2). PMNs from patients at visit 1 had significantly lower resting (Ca++)i levels compared to both visit 2 and controls. Values at visit 2 did not differ from those of the controls. Stimulus-induced (Ca++)i rise was also significantly blunted at visit 1 and normalized at visit 2, possibly through a differential contribution of distinct intracellular Ca++ stores, as suggested by the response pattern to the chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy subjects with high TSH concentrations impaired intracellular Ca++ store function. Both resting (Ca++)i levels and fMLP-induced (Ca++)i rise increased in the presence either of low-concentration TSH or of T4, but effects of TSH and T4 were not additive. T3, rT3, and TRIAC had no effect. In conclusion, this study provides evidence for a direct relationship between thyroid status and (Ca++)i homeostasis in human PMNs, mainly related to direct actions of TSH and T4 on these cells.

[Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results]. / Terapia radiometabolica dell'ipertiroidismo con approccio dosimetrico semplificato. Risultati clinici.

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.

EBVD and alternating MOPP/EBVD with or without localized field radiotherapy in advanced or unfavorably presenting Hodgkin's disease.

PATIENTS AND METHODS: Ninety-five patients with previously untreated, advanced or unfavorably presenting Hodgkin's disease were recruited in ten centers. Twenty-five patients with stage II-A-bulky disease received four courses of EBVD (epirubicin, bleomycin, vinblastine, dacarbazine) plus involved field radiotherapy (Group 1); 24 patients in stage I-B, II-B and III-A received 6 courses of EBVD (11 of them also received radiotherapy on bulky localizations (Group 2); 46 patients in stage III-AS > or = 3 nodes, III-B and IV received MOPP/EBVD 4 + 4 courses (Group 3). RESULTS: Eighty patients (84%) achieved CR, eight patients (8%) a PR, five patients did not respond and two progressed during therapy. CRs were achieved by 23/25 patients (92%) in Group 1, 21/24 (87%) in Group 2 and 36/46 (78%) in Group 3. The mean duration of follow-up was 33.3 months (range 5-69). There were three deaths from directly treatment-related causes. Twelve patients suffered chronic toxicity, including six who suffered lung toxicity and two who developed secondary myelodysplasia. CONCLUSIONS: The results achieved in this co-operative study are similar to those reported by most single-Institution trials and those with adriamycin-containing regimens. Long-term toxicity deserves careful consideration.

Role of postoperative radiation therapy in the management of early stage primary gastric non-Hodgkin's lymphomas: a retrospective analysis.

BACKGROUND: Clinical approaches to early primary gastric non-Hodgkin's lymphomas have not yet been clearly defined, and the role of postoperative radiotherapy remains a matter of discussion. METHODS: Twenty-seven patients with early primary gastric non-Hodgkin's lymphoma were observed from December 1978 to December 1990 at our Institution. They were staged according to Musshoff and Schmidt-Volmer (19) as I E (n = 16), II E 1 (n = 7) and II E 2 (n = 4). All of them underwent local combined treatment, consisting of surgery and postoperative radiotherapy; chemotherapy was also administered to 10 patients, mainly with the CHOP regimen, for 4-6 cycles before radiotherapy. Irradiation was delivered using 10 MV photons from a linear accelerator. Large abdominal fields were employed in 21 cases with daily fractions of 1.5-2 Gy up to a median total dose of 30 Gy (range: 27-36 Gy). Six patients were irradiated only on the surgical bed up to 40.5 Gy (range: 39-40.5 Gy). RESULTS: The 5-year overall and disease-free survivals were respectively 92.4% and 89.8%. The main known prognostic indicators, stage of disease, type of surgery as well as age and sex, were not found to be statistically significant in our series. No clear difference emerged between patients sequentially treated with the combination surgery-chemotherapy-radiotherapy and those who did not receive adjuvant chemotherapy. Two patients recurred at distant sites, but no local failure was seen during the follow-up. CONCLUSIONS: Although no firm conclusion can be drawn, our experience, in agreement with recent published reports, points out that the use of postoperative radiotherapy is associated not only to favorable results in terms of local control and survival, but also, and moreover, to a negligible incidence of side effects and sequelae. However, in the absence of multi-institutional prospective randomized studies, whose activation is nowadays strongly warranted, the exact role of adjuvant therapies remains a matter of discussion, and the optimal treatment of early primary gastric non-Hodgkin's lymphoma still depends on individual experience and the physician's philosophy.

[Dosimetric study of the applications of intracavitary radiotherapy using a remote-loading device with mobile sources]. / Studio dosimetrico nelle applicazioni di radioterapia endocavitaria mediante apparecchiature remote-loading con sorgenti mobili.

This paper deals with the dosimetric aspects of remote-controlled afterloading irradiation devices used in brachytherapy. An afterloading device (Gammamed III) is available at Varese Regional Hospital, for intracavitary radiation therapy (low-dose rate). In the Gammamed afterloading method the radioactive sources contained in an applicator are introduced into the patient's body. This device is based on the principle of stepwise movement of three 137Cs radioactive sources (1.48; 2.96; 1.48 GBq). The results are here presented of a dosimetric study on the correspondence between algorithm for calculating isodose distributions in intracavitary treatment and experimental measurements in a phantom. Doses around the moving source were measured using thermoluminescent LiF-100 dosimeters (1 x 1 x 6 mm). Measurements were taken in a polystyrene phantom. Isodose distributions were estimated by reading the optical density of radiographic films. Doses were found to range around the calculated values within +/- 4% (with thermoluminescent dosimeters) and within +/- 8% (with films). The close agreement between the experimental and the calculated doses confirmed the acceptability of the dose distribution calculation model for the moving sources, and the Gammamed reliability.

The impact of whole-abdomen radiotherapy on survival in advanced ovarian cancer patients with minimal residual disease after chemotherapy.

Between March 1982 and March 1987, 26 patients with minimal residual epithelial ovarian cancer after cisplatin-based chemotherapy were treated with whole-abdomen irradiation [moving-strip technique (MST)] with or without pelvic boost. Prior to radiation residual disease was macroscopic (less than or equal to 0.5 cm) in 8 cases and microscopic (positive random biopsies) in 18 cases (8 diffuse, 10 localized). Eighty percent of patients completed the planned therapy, 34% with interruptions secondary to hematologic or gastrointestinal toxicity. With a median follow-up time from completion of radiotherapy of 24 months, 34.6% of patients remain alive. The 3-year survival rates (from the second-look procedure) are 50% for the patients with microscopic tumor and 25% for those with macroscopic residual disease. Progression-free intervals are statistically different in the two groups: 16.9 months for microscopic residuals and 6.16 months for macroscopic tumors (P = 0.037). All but two of the recurrences were in the irradiated field (pelvis and/or abdomen); one was distant (pleural) and one only retroperitoneal. Small bowel injury was the most limiting complication: 3.8% was registered as fatal acute enteritis and 19% as late obstruction or malabsorption syndrome, necessitating surgical intervention in 10% of treated cases.

[A new method of planning and performing abdominal irradiation using the moving strip technic]. / Nuovo metodo di studio e di esecuzione dell'irradiazione addominale con "moving strip technique".

We make use of an individualized moving strip technique (MST) for ovarian cancer radiotherapy. On the pelvis, strip fields have smaller width than in usual MST proposed by Dembo and Delclos, and different heights. Femoral heads are spared without needing lead shields. Thus our technique can be useful for patients previously treated by heavy chemotherapy. Dosimetric checks by computer, TLD, and film dosimetry, show a fair dose homogeneity inside target volume.