(18)F-FDG PET/CT versus bone scintigraphy in the follow-up of gastric cancer.

A 53-year-old patient underwent a positron emission tomography/computed tomography with 2-fluoro-2-deoxy-d-glucose ((18)F-FDG PET/CT) in the suspicious of gastric tumor recurrence (mediastinal and abdominal lymph nodes). PET/CT identified only an area of (18)F-FDGuptake in the twelfth thoracic vertebrae. Unexpectedly, a bone scintigraphy revealed many "hot" spots changing the diagnosis (single metastasis versus plurimetastatic disease) and impacting on patient's management.

Bronchoscopically-guided conformal radiation therapy for radiographically occult lung carcinoma.

Radiographically occult lung carcinoma has a very good prognosis after complete surgical resection. In medically inoperable patients three-dimensional conformal radiation therapy cannot be performed, as computed tomography scan images fail to localize the disease. Presented here is an original technique of marking radiographically occult tumors by fiberoptic bronchoscopy, applied on four patients. No short-term complications were recorded. All the patients are alive, with no evidence of disease, after a mean follow-up of 15 months.

Radiotherapy and concurrent continuous infusion of cisplatin with adjuvant surgery in nonresectable Stage III lung carcinoma: short- and long-term results of a Phase II study.

PURPOSE: Cisplatin-enhanced radiotherapy plus adjuvant surgery was evaluated in nonresectable non-small cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Doses of 50 Gy (administered in standard fractionation in 5 weeks) were delivered with concurrent cisplatin in continuous infusion (daily dose: 4 mg/m2), to 32 Stage IIIa and 45 Stage IIIb patients enrolled in a Phase II study. Patients without progression underwent surgery. RESULTS: Esophagitis (64%), nausea/vomiting (34%), and pulmonary toxicity (14%) were the main side effects. Grade 3 toxicity occurred in 4 instances. A clinical locoregional major response was achieved by 55 patients (there were 10 complete responses). Forty patients underwent surgery, 7 with a nonradical procedure. Seven patients died due to surgery-related complications, which were significantly impacted by right pneumonectomy (71% vs. 6% of the other procedures, p < 0.0001). Eighteen of the 40 surgical patients were assessed to be without viable tumor and 11 with microresidual carcinoma. There were 13 disease-free, 5-year survivors. CONCLUSIONS: Toxicity was low but activity high with the chemoradiotherapy. Adjuvant surgery increased the rate of complete responses, but right pneumonectomy had an unacceptable mortality. The role of surgery needs further refinement. Integration of the chemoradiotherapy schedule with cisplatin-based induction chemotherapy is advisable.

Accuracy evaluation of fusion of CT, MR, and spect images using commercially available software packages (SRS PLATO and IFS).

PURPOSE: A problem for clinicians is to mentally integrate information from multiple diagnostic sources, such as computed tomography (CT), magnetic resonance (MR), and single photon emission computed tomography (SPECT), whose images give anatomic and metabolic information. METHODS AND MATERIALS: To combine this different imaging procedure information, and to overlay correspondent slices, we used commercially available software packages (SRS PLATO and IFS). The algorithms utilize a fiducial-based coordinate system (or frame) with 3 N-shaped markers, which allows coordinate transformation of a clinical examination data set (9 spots for each transaxial section) to a stereotactic coordinate system. The N-shaped markers were filled with fluids visible in each modality (gadolinium for MR, calcium chloride for CT, and 99mTc for SPECT). The frame is relocatable, in the different acquisition modalities, by means of a head holder to which a face mask is fixed so as to immobilize the patient. Position errors due to the algorithms were obtained by evaluating the stereotactic coordinates of five sources detectable in each modality. RESULTS: SPECT and MR position errors due to the algorithms were evaluated with respect to CT: deltax was < or = 0.9 mm for MR and < or = 1.4 mm for SPECT, deltay was < or = 1 mm and < or = 3 mm for MR and SPECT, respectively. Maximal differences in distance between estimated and actual fiducial centers (geometric mismatch) were in the order of the pixel size (0.8 mm for CT, 1.4 mm for MR, and 1.8 mm for SPECT). In an attempt to distinguish necrosis from residual disease, the image fusion protocol was studied in 35 primary or metastatic brain tumor patients. CONCLUSIONS: The image fusion technique has a good degree of accuracy as well as the potential to improve the specificity of tissue identification and the precision of the subsequent treatment planning.

Proinflammatory and regulatory cytokine levels in AIDS cachexia.

The serum concentrations of inflammatory (Interleukin-1 beta, Tumor necrosis alpha, Interleukin-6) and regulatory cytokines (Interleukin twelve) have been studied in ten AIDS cachectic patients and compared to a control group. A cytokine imbalance, and peculiarly a significant increase in proinflammatory cytokines (Interleukin-1, Interleukin-6, Tumor necrosis Factor alpha) and a decrease in regulatory cytokines such as Interleukin-12 were found. A significant correlation resulted between weight loss and Interleukin-1 beta and 6. A negative correlation between Interleukin-1 and 12 was noted, indicating that this last cytokine has an important regulatory role also in advanced state of the disease.

Increased survival in brain metastatic patients treated with stereotactic radiotherapy, omega three fatty acids and bioflavonoids.

Stereotactic radiotherapy represents a method to effectively treat brain metastases with high precision and with high doses. Few acute toxicities are associated with stereotactic radiotherapy, however delayed reactions may occur and after six months, 20% of patients can develop radionecrosis. To avoid this adverse effect, in patients with metastases localized in critical brain areas, a supplementation of Omega three fatty acids and bioflavonoids has been used. At the end of 1997, we initiated a series of retrospective studies to test the efficacy of stereotactic radiotherapy on 405 patients, and the prognostic importance on survival of various variables among which this type of supplementation. From the comparison of various survival curves with the Cox multivariate analysis, it emerged that the patients using this supplementation had a decreased risk ratio and an improvement in survival time. A decreased number of radionecrosis was noted. We suggest their use as radioprotectors.

Design and characterization of a dynamic multileaf collimator.

The characteristics of a prototype computer-assisted dynamic multileaf collimator (DMLC), specifically designed for small-field conformal radiotherapy, were evaluated at the Istituto Nazionale Tumori of Milan. The collimating device consists of two opposing banks of 16 pairs of 8 cm thick, 3.6 mm wide tungsten leaves and allows shaping of a radiation field up to a size of 10 x 10 cm2 at the isocentre. The screening thickness of each leaf is 6.25 mm at the accelerator gantry isocentre. The leaves have a trapezoidal cross section and move along an arched path, thus providing a 'double focused' collimation system. The DMLC was installed on the head of a Varian Clinac 2100C linear accelerator. Mechanical and dosimetric evaluations were performed to test the stability of the mechanical isocentre and to determine leaf leakage, penumbra width, accuracy of leaf positions and uniformity of leaf speed. Displacement of the mechanical isocentre was less than 1 mm at all gantry angles. Standard radiographic films exposed to 6 MV x-ray radiation were used for dosimetric evaluations. Leakage between leaves was less than 2.5%, and leakage through abutted leaves was less than 5.5%. The penumbra width between 20% and 80% isodose at different positions of leaf banks was 2.7 mm in the direction of the leaf motion and 3.1 mm along the side of the leaf with a standard deviation of 0.2 mm in both directions. Accuracy in the positioning of the leaf was 0.3 mm, whereas the maximum repositioning error was less than 0.2 mm. Finally, during movement of the leaves at the maximum speed of 0.5 mm s(-1), the standard deviation of the leaf positioning error was 0.2 mm, proving an accurate uniformity of leaf speed.

Tumor microcirculation and its significance in therapy: possible role of omega-3 fatty acids as rheological modifiers.

Despite the great efforts to find new drugs or devices to suppress cancer cells, attempts to modify microcirculation and therefore the state of tumor cells and their surrounding normal tissues have not been given the attention they deserve. Solid tumors are composed of highly heterogeneous populations of malignant, stromal and inflammatory cells in a continuously adapting extracellular matrix. All of the above components interact and regulate each other to produce distinct microenvironments within the tumor mass. Abnormal microcirculation plays a particular role in the maintenance of this anomalous condition and favors the formation of metastasis, but on the other hand provides the therapist with an important site for intervention. In this brief overview we attempt to outline three aspects: (a) how the anomalous tumor blood flow provokes the nonuniform distribution of oxygen and nutrients within the tumor mass, thus determining different responses to the various cancer therapies; (b) how hemorheology is the clinical parameter most easily modified and (c) how omega-3 essential fatty acids are natural drugs that could be used in this sense beyond their antitumoral properties.

Clinical role of technetium-99m sestamibi single-photon emission tomography in evaluating pretreated patients with brain tumours.

One of the main problems regarding the follow-up of patients with brain tumours treated with radiotherapy is the distinction between radiation necrosis and tumour relapse. In many cases computed tomography (CT) scan is unable to distinguish between the two. We assessed the usefulness of brain single-photon emission tomography (SPET) with technetium-99m-sestamibi in cases where CT scan was not conclusive. The absence of tracer uptake in normal brain, the sharp uptake in neoplastic tissue, and the favourable physical properties of technetium make the scintigraphic method particularly accurate. We therefore propose the association of CT scan with 99mTc-sestamibi brain SPET in the follow-up of patients in whom a distinction between radiation necrosis and active disease is needed for an adequate therapeutic decision.

Iatrogenic pneumocephalus in a man with undifferentiated nasopharyngeal carcinoma. A case report.

A case of pneumocephalus in a 45-year-old male with undifferentiated rhinopharyngeal carcinoma is described. The patient was initially subjected to radiotherapy and then to transmaxillary resection and a second course of stereotactic radiotherapy for recurrent disease. Lastly, the patient was treated with chemotherapy because of local-regional disease progression. After two cycles of cisplatin, adriablastine and bleomycin, the patient suddenly entered in coma. Cerebral CT scan evidenced the presence of air in the frontal and lateral cornua, in the subarachnoid space of the base cisternae extending to the 7th cervical vertebra. After 8 months of a clinical stationary condition, the patient died. The various treatments used are critically reviewed, and modern therapeutic approaches for the neoplasm and the toxicity involved are discussed. We conclude that in nasopharyngeal carcinoma, for patients who relapse after radiotherapy, successive local-regional therapies (surgery, re-irradiation) should be carefully evaluated to avoid demolishing treatments, which are burdened with severe side effects that might influence the quality of life with only slight improvement of overall survival. Furthermore, the presence of persistant aqueous rhinorrhea in these patients should be carefully evaluated, because it could be an early symptom of a cerebrospinal fluid leak.

[Stereotactic radiotherapy with linear accelerators. Dosage considerations on collimators and photon beam energy]. / La radioterapia stereotassica con acceleratori lineari. Considerazioni dosimetriche sui collimatori e sull'energia di fasci di fotoni.

The small X-ray beam profiles produced by linear accelerators and used in stereotactic radiosurgery were studied. Circular focusing and not-focusing beams outlined by additional collimators (diameter ranging 10 to 30 mm) and square field outlined by the jaws (field size 10 to 30 mm) were measured. 6 and 18-MV X-ray beams from a dual energy accelerator and 6 and 15-MV X-ray beams produced by 2 single-energy accelerators were used. Measurements were carried out with Kodak X Omat V films in a perspex phantom in the same conditions for all the fields. To study the profile characteristics we introduced the V80/V20 = (R80/R20)3 ratio where R80 and R20 are respectively the mean distance of the 80% and 20% isodose lines from the beams axis. Measurement results show that 6-MV X-ray beams have a higher V80/V20 ratio than the ones obtained with the other energies. There is no significant difference between the beams produced with focused collimators and those produced with not-focused collimators. Square fields outlined by the jaws have a V80/V20 ratio greatly dependent on the accelerator used. This ratio is generally worse than the ones obtained with beams outlined by additional collimators.

[Advantages of a system of positioning and localization made of thermo-conformable materials for irradiation of cervicofacial and encephalic lesions treated with stereotactic fractionated radiation]. / Vantaggi offerti da un sistema di posizionamento e localizzazione di materiale termoconformabile per l'irradiazione di lesioni cervico facciali ed encefaliche trattate con tecnica stereotassica in frazionamento.

In this work we first analyzed the reliability of materials supplied by the main firms, which must be considered when defining the lesion and planning target volume. The coordinates of specific target landmarks, i.e., bone, calcium deposition or catheters, on baseline CT scans were compared with those measured on control scans. Since the PLATO-SRS system yields 3 coordinates for each target, the final error is calculated by the evaluation of the shift of the different coordinates. The mean error reported for the first material (ORFIT) was 5 mm (13/23 patients). This margin of error is too high and was considered unacceptable; a second material was then tested. The latter, which is not recyclable and softens at higher temperatures, exhibited a mean error of 2.5 mm (10/23 patients), which allows daily repositioning of greater reliability. Treatment was repeated in 4/20 arcs in all, which number depended mainly on fraction size. Correct lesion location and patient positioning were allowed by laser landmarks on the mask made directly on the treatment couch. The laser too was checked before each treatment session, i.e., preferentially at the end of an ordinary working day.

Adjuvant therapy with essential fatty acids (EFAs) for primary liver tumors: some hypotheses.

Hepatocarcinoma is responsible for approximately 1 million deaths annually. It is usually discovered at an advanced stage and, if inoperable, has a poor prognosis. New therapies combining chemotherapy, hyperthermia, radiotherapy and immunomodulators have been recently attempted with various levels of success. Once the tumor is detected at an early stage, some possibilities of cure seem to emerge either by intratumoral percutaneous injection (PEI) of alcohol or by chemoembolization and interstitial hyperthermia. When the tumor volume is more than 5 cm, these therapies are less successful and radiotherapy can be used. All the techniques described have some limits; PEI, for instance, does not achieve a complete eradication of lesions > 3 cm and a non-homogenous alcohol distribution within the tumor leads to areas of necrosis. Radiotherapy, even if effective, is limited by dose-related radiation hepatitis. Another important limiting factor is the incomplete response to therapy and tumor recurrence. Essential fatty acids, especially gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) are discussed here for their ability to control primary tumor proliferation and increase response to chemotherapy, radiotherapy and hyperthermic treatment, thanks to their effects on cellular membranes (increased lipoperoxidation and modification of tumor stroma).

Omega-3 fatty acids can improve radioresponse modifying tumor interstitial pressure, blood rheology and membrane peroxidability.

Several studies provide evidence that hypoxic cells present in animal and human solid tumors, may be critical for the successful treatment of cancer. In particular hypoxic cells are resistant to ionizing radiation, photodynamic treatment and the large majority of chemotherapeutic drugs. Hypoxia is generally due to the inadequacy of vascular beds supporting the tumor and to an abnormal microcirculation. Three parameters, tumor interstitial fluid, hemorheological factors and lipoperoxidation, are considered and tentatively associated as playing a role in hypoxic cell treatment. Omega three fatty acids modify these factors and are discussed for their possible ability to enhance tumor cells susceptibility to radiotherapy.

Surgery after radiochemotherapy for stage III lung cancer: postoperative complications and late results.

Fifty-seven stage III lung cancer patients underwent radiochemotherapy and subsequent surgery. Forty radical (R-), six non-radical, and eleven exploratory operations were performed. Pneumonia (five cases), pulmonary insufficiency (one case), bronchial fistula (one case) were the major non-fatal complications. Four deaths due to adult respiratory distress syndrome (ARDS) or pulmonary embolism occurred. Sixty percent of the 10 patients who had no viable tumor at operation survived 3 years, as well as 41% of those who achieved a complete remission by resection and 11% of those with residual disease (R+) after operation. However, the 1- and 2-year survival rates were similar. The main pattern of failure in R- and R+ patients was extra- and intra-RT-field progression, respectively. A slightly higher rate of postoperative complications, with respect to current practice, was observed. However, data lead to argument on the improvement of locoregional control and long-term survival following radical surgery.

Preoperative concomitant cisplatin/VP16 and radiotherapy in stage III non-small cell lung cancer.

PURPOSE: To evaluate the therapeutic effectiveness of a combined chemoradiotherapy program, followed by surgery in selected cases, in Stage III non-small cell lung cancer. METHODS AND MATERIALS: Between August 1988 and February 1990, 43 patients Staged IIIa-b (UICC 1987, 58% IIIb) have been treated with concomitant chemotherapy (cisplatin 15 mg/m2 and VP16 75 mg/m2, 5 days a week on week 1 and 5) and radiotherapy (40 Gy split course, 2 Gy/day on week 1, 2, 5, and 6), followed by attempted curative thoracotomy or more cycles of full dose chemotherapy with the same two drugs. RESULTS: Planned chemoradiotherapy has been given to 91% of patients; 13/43 patients have been operated, with 12 complete resections and three (7%) pathological complete responses. Toxicity was significant, with two postoperative deaths and two fatal radiation pneumonitis. Crude progression-free survival rate is 21% at 30 months, with nine patients (21%) alive and free from progression at follow-up times ranging from 31 to 49 months. Subset survival analysis showed a possibly greater therapeutic effect for non-squamous histology as compared to squamous carcinoma. CONCLUSION: These results are encouraging in a cohort of patients with quite advanced disease (58% Stage IIIb).

Non-resectable Stage IIIa-b lung carcinoma: a phase II study on continuous infusion of cisplatin and concurrent radiotherapy (plus adjuvant surgery).

Thirty-eight patients with non-resectable non-small-cell Stage IIIa-b lung cancer were treated in a Phase II study with radiotherapy (50 Gy in a 25-fraction split-course) plus con-current continuous infusion of cisplatin given at a daily dose of 6 mg/m2, with the aim of investigating its radiopotentiation properties. Treatments were given on an outpatient basis by means of a central venous catheter and a portable pump. Adjuvant surgery was undertaken when feasible. Toxicity was mild to moderate. The probability of a partial or complete locoregional response at 4 weeks after treatment completion was 83% (confidence limits at 95%: 13). Eighteen patients were resected. Overall 1-, 2- and 3-year progression-free survival probabilities were 42, 24 and 21%. These figures were 63, 37 and 24% in observed survival curves. Patients with squamous-cell tumors had observed survival rates of 82, 50 and 28% at 1, 2 and 3 years, compared to 42, 19 and 19% in patients with non-squamous histology. The high response and survival rates obtained at a low price according to toxicity require further investigation.

On extravisceral soft tissue sarcomas. Effectiveness of radiation treatment and problems of radiotherapy and radiosurgical treatment.

A series of 355 extravisceral soft tissue sarcomas is presented with reference to the effectiveness of radiation treatment for each histological type and the problems of radiotherapy and surgical treatment. Liposarcoma was the most radiosensitive soft tissue sarcoma. By utilizing all types of treatment and especially radiosurgery with postoperative radiotherapy, the percentage of disease-free patients after a minimum of 3 years from treatment varied from 27% to 52.9% for the different types of sarcoma. Nevertheless, in most cases the effectiveness of radiotherapy was unpredictable. It was found that doses varying from 52-60 Gy, with 2 Gy for each of 26-30 applications within 6-8 weeks, were sufficient for radical treatments. In relation to unpredictability of radiotherapy results, it was concluded that preoperative was more advisable than postoperative treatment owing to the possibility to prove the effectiveness of radiotherapy. Postoperative treatment is useless in nonradiosensitive cases and might negatively affect surgical modalities.