Impact of radiotherapy on normal brain tissue: semi-automated quantification of decrease in perfusion.

PURPOSE: We attempted to ascertain the impact of Co-60 conventional external radiotherapy (cRT) on the perfusion of normal brain tissue in relation to the radiation doses delivered to the tumors in patients with primary brain tumors. MATERIALS AND METHODS: After surgery 18 patients (pts) were due to undergo cRT with a total dose of 5400- 6400 cGy. All the patients had a Tc-99m-HMPAO SPECT study prior to cRT (basal), 15th and 30th days of cRT as well as 1 (in 6 pts), 3 (in 9 pts), and 6 (in 3 pts) months after cRT. For quantitative evaluation, the entire set of transverse slices were divided into 4 regions as frontal, parietal, occipital and temporal regions by means of a computer software program. Semi-automated quantification was performed on a total of 1392 regions in 87 studies to determine left to right ratios. An interregional difference of at least 10% was considered abnormal. RESULTS: After elimination of tumor sites, 80 normal brain regions showed decreased perfusion after cRT. The percent decrease in perfusion was (mean 22.5+/-9.9) significantly higher in areas irradiated with doses > 3000 cGy (p < 0.05). CONCLUSION: cRT has adverse effects on the perfusion of normal brain tissue for doses > 500 cGy. Our findings justify treating patients with small and limited lesions with stereotactic radiotherapy in order to minimize the adverse effects of cRT on normal tissues.

Colonic anastomotic healing after preoperative chemo-radiotherapy in rat.

PURPOSE: To prevent micrometastasis at an earlier stage and to increase the lateral or circumferential tumor free margins, there is a rationale for neo-adjuvant chemo-radiotherapy in patients with colorectal cancer. In order to investigate the effects of such a protocol on colonic anastomotic healing, an experimental study resembling the clinical use of neo-adjuvant concomitant 5-FU+ irradiation treatment of colorectal cancer was conducted. MATERIALS AND METHODS: Seventy-one male Wistar rats were divided into three groups: a control group (I) underwent left colon resection and primary anastomosis (n = 20); a sham-treated group (II, n = 20); and a study group (III) which received fractionated irradiation to the whole pelvis to a total dose of 22 Gy, 5.5 Gy per fraction, in four consecutive days with linear accelerator and concomitant intra-peritoneal 5-FU (20 mg/kg/day) for five consecutive days. The last fraction of irradiation and the last injection were given four and three days before colonic resection and anastomosis, respectively. Within each group one-half of the animals were anesthetized on the third postoperative day and one-half on the seventh postoperative day. Abdominal wound healing, intraperitoneal adhesions, anastomotic complications, and anastomotic bursting pressure measurements were recorded. Following these measurements the anastomotic segment was resected for hydroxyproline content, myeloperoxidase activity, and histopathological evaluation. RESULTS: There were no differences in the abdominal wound healing, intraperitoneal adhesions, and anastomotic complications between groups. At three and seven days, the mean bursting pressures of the anastomoses were 36.5 mm Hg and 208 mm Hg in group I, 34.5 and 228 in group II, and 27 and 167 in group III, respectively (p < 0.01, group III vs both groups I and II on day seven). The burst occurred at the anastomosis in all animals tested on the third postoperative day, and one in group I (10%), none in group II, and four in group III (40%) on the seventh postoperative day. CONCLUSION: Preoperative pelvic fractionated irradiation and concomitant 5-FU delays anastomotic healing.

Histological evaluation of colonic anastomotic healing in the rat following preoperative 5-fluorouracil, fractionated irradiation, and combined treatment.

There is a growing interest in neoadjuvant chemo- and radiotherapy as a treatment modality for colorectal cancer which could affect mechanical and biochemical parameters of anastomotic healing. This study investigated the effect of such protocols on colonic anastomotic healing by evaluating the histopathological parameters. One hundred and sixty male Wistar rats were divided into six groups: a control group (I, n = 20), a saline group (II, n = 30) which received 1 ml NaC1 intraperitoneally, a sham-irradiated group (III, n = 20), a 5-fluorouracil (5-FU) group (IV, n = 30), which received 5-FU (20 mg/kg) intraperitoneally for 5 consecutive days, an irradiated group (V, n = 40) which received fractionated irradiation to the whole pelvis to a total dose of 22 Gy, 5.5 Gy per fraction on 4 consecutive days, and a concomitant 5-FU + irradiation group (VI, n = 20) which received 5-FU as in group IV and irradiated as in group V. All groups underwent left colonic resection with primary anastomosis, and the last fraction of irradiation and the last injection were given 4 and 3 days before the operation, respectively. Within each group one half of the animals were killed on the third postoperative day and the other half on the seventh postoperative day. After the resection of the anastomotic segments, histopathological examination was evaluated. Apposition of the wound edges of the mucosa and the muscularis were not affected by the therapy. The level of granulocytes was high, inflammatory exudate and necrosis persisted, granulation tissue formation was delayed, and the levels of macrophages and fibroblasts were low. We conclude that colonic anastomotic healing can be affected by the administration of preoperative chemotherapy, irradiation, and chemoirradiation.

Thyroid dysfunction in children receiving neck irradiation for Hodgkin's disease.

Thyroid function was studied in 46 long-term survivors of pediatric Hodgkin's disease with a median follow-up time of 10.5 years. The mean age of the patients at the time of treatment was 8 years. Treatment consisted of radiotherapy alone in seven patients and combined radiation and chemotherapy in 39 patients. The radiotherapy dose to the thyroid gland was less than 2000 cGy in one, 2000-2500 cGy in 15, 2500-3000 cGy in 17, and greater than 3000 cGy in 13 patients. Evaluation consisted of clinical examination and thyroid function tests of total and free triiodothyronine, thyroxin, arid thyroid stimulating hormone levels. Twenty-one of 46 patients (45.6%) showed thyroid function abnormalities, however only nine of them had diffuse or nodular hyperplasia on physical examination. Risk factors of age, chemotherapy schema, total radiation dose, and dose per fraction did not significantly influence the incidence of thyroid dysfunction.

Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia.

A prospective double blind randomized trial comparing two different dose schedules of continuous steroid coverage during prophylactic cranial radiotherapy (CRT) in leukemic children was conducted to find out the optimum dose to be prescribed to reduce the incidence of Somnolence Syndrome (SS). Between April 1994 and February 1996, 32 patients with acute lymphoblastic leukemia received CRT of 18 Gy in 10 fractions. Patients were randomized to receive oral dexamethasone of 2 or 4 mg/m2 during radiotherapy. The diagnosis of SS was made clinically based on symptoms of somnolence. All patients were followed for a minimum of 8 months. The overall incidence of SS was 40%. The development of SS was steroid dose dependent. In low dose steroid arm the incidence of SS was 64.3% (9/14), compared to 17.6% (3/17) in high dose arm with statistically significant difference (P = 0.008). The median time to development of SS was 4 weeks. The most common symptom of SS was drowsiness followed by anorexia, headache, nausea, vomiting, decreased activity, irritability, fever and ataxia, respectively. The duration of symptoms ranged from 2 to 14 days. The development of SS was not related to the presence of acute reactions, age at the time of CRT and sex. In all cases the symptoms subsided completely and spontaneously. Our results suggest that steroid coverage at a dose of 4 mg/m2 during CRT reduces the incidence of SS. However, a multicentric prospective randomized trial is needed to determine the role and the optimal dose of steroid.

Choroid metastasis of undifferentiated nasopharyngeal carcinoma.

Choroid metastasis of primary nasopharyngeal carcinoma is an infrequent event. Here, we report a case of nasopharyngeal carcinoma with metastases to the choroid successfully treated by external beam radiotherapy.

Basal cell carcinomas developing in a case of medulloblastoma associated with Gorlin's syndrome.

We report a case of a 20-year-old male with Gorlin's syndrome (nevoid basal cell carcinoma syndrome), developing multiple basal cell carcinomas within irradiation fields 10 years after the treatment of medulloblastoma.

Effects of preoperative fractionated irradiation on left colonic anastomoses in the rat.

PURPOSE: Radiotherapy is frequently used as a (neo)adjuvant to surgery in colorectal cancer patients, and because such therapy could influence the integrity of the anastomosis, we decided to investigate the effect of preoperative irradiation on colonic anastomosis. METHODS: Seventy-two male Wistar rats, weighing 200 to 348 g, were divided into three groups: a control group (I) underwent left colon resection and primary anastomosis (n = 20); a sham irradiated group (II, n = 20); a study group (III) that received fractionated irradiation to the whole pelvis (anterior-posterior pelvic field), for a total dose of 22 Gy, 5.5 Gy per fraction, on four consecutive days with linear accelerator (n = 32). Four days after irradiation, both Groups II and III underwent the same operation as performed in Group I. Within each group, one-half of the animals were anesthetized on the third postoperative day and one-half on the seventh postoperative day. Abdominal wound-healing, anastomotic complications, and anastomotic bursting pressure measurements were recorded. Following these measurements, the anastomotic segment was resected for hydroxyproline content and myeloperoxidase activity. RESULTS: Irradiated animals had more pronounced weight loss during therapy. There were no differences with abdominal wound-healing, intraperitoneal adhesions, and anastomotic complications between groups. At days 3 and 7, mean bursting pressures of the anastomosis were determined at 36.5 and 208 mmHg in Group I, 34.5 and 228 mmHg in Group II, and 25 and 150 mmHg in Group III, respectively (P < 0.01 Group III vs. both Groups I and II on days 3 and 7). The burst occurred at the anastomosis in all animals tested on the third postoperative day and one in Group I (10 percent), none in Group II, and six in Group III (37.5 percent) on the seventh postoperative day. In addition, hydroxyproline content and myeloperoxidase activity was significantly lower in Group III. CONCLUSION: Although preoperative fractionated irradiation significantly decreased the anastomotic bursting pressure and more burst occurred in the anastomotic line on postoperative day 7, the clinical outcome was similar among the groups.

Monitoring response to therapy with thallium-201 and technetium-99m-sestamibi SPECT in nasopharyngeal carcinoma.

UNLABELLED: This study prospectively assessed the value of 201Tl and 99mTc-sestamibi (MIBI) SPECT in monitoring disease regression/progression as compared with MRI findings in patients with nasopharyngeal carcinoma (NPC) having radiotherapy with or without chemotherapy. METHODS: Eighteen patients (age range 15-78 yr, mean 45 yr) had consecutive SPECT imaging using a dual-head gamma camera after the injection of 111 MBq 201Tl and 555 MBq MIBI before therapy and at 3 mo and 6 mo after completion of therapy. A total of 106 SPECT studies was correlated with contemporaneous MRI studies. Tumor-to-background ratios were obtained on coronal slices. Visually detectable lesions in the region of the nasopharynx and cervical lymph nodes were considered positive for residual disease. The gold standard for the presence of disease was the combination of repeat MRI scans, endoscopic examination and clinical evaluation performed 12-15 mo after completion of therapy. RESULTS: MIBI-SPECT proved superior to both 201Tl SPECT and MRI after 3 or 6 mo follow-up in predicting complete response. Accuracy rates in the detection of residual disease in the nasopharynx are 39%, 72% and 89% for MRI, 201Tl and MIBI, respectively, for the 3-mo evaluation; 71%, 71% and 94% for MRI, 201Tl and MIBI, respectively, for the 6-mo evaluation. CONCLUSION: MIBI SPECT could be used as a screening test in predicting response to therapy in patients with NPC.

Kaposi's sarcoma: the efficacy of a single fraction of 800 cGy.

BACKGROUND: Although Kaposi's sarcoma is the most common neoplasm in association with AIDS, classic Kaposi's sarcoma is rare. The best treatment modality is still unclear. METHODS: Between December 1993 and December 1995, 42 fields in 12 patients with Kaposi's sarcoma were treated at our department. Only 3 patients had a history of renal transplantation and immunosuppressive treatment. A single dose of 800 cGy with 4-6 MeV electron beams was delivered to all patients. RESULTS: Complete response rates at the 1st, 6th and 12th months after treatment were 45.2, 62 and 89.7%, respectively. Side effects included various degrees of hyperpigmentation and mild edema and fibrosis in 1 patient. CONCLUSION: Our results suggest that a single application of 800 cGy is as effective as a more protracted course of radiotherapy with a comparable complication rate.

Double-phase Tc-99m-SestaMIBI SPECT imaging in a case of glomus jugulare tumor.

We performed a double-phase Tc-99m-SestaMIBI SPECT study on a patient who presented with a mass located at the skull base. The results were compared with double-phase T1-201 SPECT study. Early phase (30 min) SPECT images of both radiopharmaceuticals demonstrated increased radiotracer uptake in the region of the tumor. However, late images (180 min) revealed rapid wash-out of Tc-99m-SestaMIBI from the tumor, suggestive of a benign vascular tumor, while T1-201 images showed slower wash-out. Tc-99m-SestaMIBI SPECT findings were also confirmed by carotid angiography and biopsy, while a contemporaneous MRI scan was inconclusive in differentiating benign from malignant tumor. Initial and one-year follow-up whole body CT scans were negative for any metastatic sites, supporting the diagnosis of benign glomus jugulare tumor.

Pre- and post-therapy thallium-201 and technetium-99m-sestamibi SPECT in nasopharyngeal carcinoma.

UNLABELLED: We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for evaluating the extent of primary disease and differentiating residual/recurrent disease from post-therapy changes in patients with nasopharyngeal carcinoma (NPC). METHODS: Fifty patients (20 initial presentation, 30 post-therapy evaluation) underwent 201Tl and MIBI imaging. The findings were correlated with CT/MRI results. Tumor-to-background ratios were obtained. Biopsy confirmation (14 patients) and/or 6-12 mo clinical follow-up data (16 patients) were available in the post-therapy group. RESULTS: All primary disease sites were accurately detected by both imaging studies in the pretherapy group. However, MIBI-SPECT was superior to 201Tl SPECT (p = 0.0057) in detecting regional metastases (sensitivities of 95% versus 68%). In the post-therapy group, MIBI and 201Tl imaging were true-positive in 14 of 16 patients with proven residual/recurrent. In 17 patients who had no evidence of residual/recurrent tumor. CT/MRI was false-positive in 13 when MIBI and 201Tl imaging were true-negative in 10 and false positive in 3. MIBI, 201Tl and CT/MRI had sensitivities of 87.5%, 87.5%, 100%, specificities of 82.4%, 76.5%, 23.5% and accuracies of 85%, 82%, 61%, respectively. Tumor-to-background ratios were < or = 1.5 in all false-positive cases except one. CONCLUSION: MIBI-SPECT proves more accurate than 201Tl SPECT in detecting regional metastases at initial presentation. MIBI and 201Tl imaging have higher specificity and accuracy than CT/MRI and MIBI-SPECT is slightly more specific than 201Tl SPECT in differentiating residual/ recurrent disease from post-therapy changes in patients with NPC.

Influence of immediate post-therapy bone scintigraphy in the assessment of response to therapy in a case of nasopharyngeal carcinoma.

A patient with undifferentiated stage IV (T3N3M0) nasopharyngeal carcinoma (WHO type III) underwent pre- and one-month post-therapy bone scintigraphy as part of an ongoing trial combining scintigraphic and radiographic modalities. The patient had advanced disease in the nasopharynx and bulky cervical lymph nodes at presentation. Initial bone scintigraphy performed 10 days prior to therapy was negative for bone metastases. Immediately after concomitant chemoradiotherapy, bone scintigraphy revealed distant metastases, whereas clinical assessment of disease disclosed complete response to therapy in the nasopharynx and cervical lymph nodes. The scintigraphic findings were also confirmed by a subsequent MRI scan of the corresponding regions.

Familial glioma in two siblings.

We report two siblings who had intracranial gliomas, one with glioblastoma multiforme and the other with mixed oligo-astrocytoma. The genetic influences in the development of glioma are discussed.