Radiotherapy of bladder cancer: relevance of bladder volume changes in planning boost treatment

PURPOSE: This study aims to evaluate tumor motion with controlled changes of the bladder volume, and to assess the reproducibility of bladder (and tumor) position using a urinary catheter balloon as an immobilization device. METHODS AND MATERIALS: First, three patients with tumor growths in three different bladder regions (trigone, left lateral wall, anterior wall) were evaluated. Three-dimensional CT-based reconstructed images were used to measure the displacement of the tumors when 100 cc were removed from a bladder originally filled with 170 cc of contrast. The 3D calculated boost beam arrangements and field sizes for the three tumors in the partially emptied bladders were used to simulate treatment of the same tumors in the maximally filled bladders. Dose-volume histograms were obtained. Second, verification of an ellipsoid model for bladder volume changes was undertaken in 41 patients. Third, in eight additional patients a urinary catheter balloon filled with 80-cc sterile saline solution was used in an attempt to reproduce the shape and spatial coordinates of the bladder during the boost treatment. A pair of orthogonal films with the 80-cc balloon filled with contrast material were taken at simulation and repeated twice at weekly intervals during radiotherapy. The reproducibility was quantified by sequentially calculating the common surface of the bladder images in each orthogonal view. RESULTS: Target motion, especially in the craniocaudal axis, appeared to be more relevant for tumors arising in the bladder walls (15 mm) than in the trigone (5 mm). Underdosage (<95% of the prescribed dose to the target volume) was observed in 20, 20, and 50% (with 1 cm margins around the tumor) and in 10, 10, and 15% (with 1.5 cm margins around the tumor) of the tumors arising in the trigone, left lateral wall, and anterior wall, respectively. The ellipsoidal model was validated with a strong correlation coefficient allowing to establish a predictive model for bladder wall displacements as a function of bladder volume. In the balloon reproducibility study, mean reproducibility factors of 0.84 (+/-0.06) and 0.82 (+/-0.07) were obtained for both anteroposterior and lateral views, respectively. CONCLUSIONS: Changes in bladder volume and shape related to bladder filling can result in clinically significant displacements of the target volume. A minimum of 2-cm margins around the target may compensate for extreme bladder volume changes during boost treatment. An ellipsoidal model for the bladder is consistent with these observations. Although an 80-cc urinary catheter balloon helped to immobilize the bladder, reproducibility was less than perfect.     

Radiotherapy in the treatment of breast carcinoma

In the treatment of breast cancer a radiation therapy is indicated under the following conditions: 1. Postoperative irradiation only of the regional lymph-nodes also in stage I (T1, N0). 2. Postoperative irradiation of the regional lymph-nodes and the thorax wall in cases with great primary tumours (T2), in cases with involved axillary lymph-nodes and, of course, in all cases with "grave signs". 3. Preoperative irradiation only in those cases when it seems possible that an inoperable tumour would become operable. 4. As the sole local treatment only in cases with very large inoperable tumours or in special cases (e.g. very high risc or refusal of the operation). 5. As local treatment of a local recidive or of isolated metastases. 6. As supporting local therapy (e.g. threatening fracturation of our fracturated bone metastases; brain metastases) in cases of generalized metastatic disease treated by hormonal or cytostatic therapy.     

Radiotherapy in the treatment of brain metastasis from small cell lung carcinoma: study on appropriately controlled dose

Fifty-two brain metastatic lesions occurring in 20 patients with small cell lung carcinoma (SCLC) were irradiated, and then the relationship between tumor size, dose and control was clinically and histopathologically studied. Lesions of 8 mm in diameter and those of 10 mm in diameter were determined to be controllable by irradiation at about 38 Gy and 42 Gy, respectively. According to size-dependent curative minimum doses, the lesions could be divided by the 10 Gy/ 5fr/wk method into controlled and non-controlled groups with the curve expressed as dose (Gy) = 15.27 log10 [tumor volume (mm3)] +0.6. Based on these results, tumors of 2 mm and 3 mm in diameter were estimated to be controllable at 14 and 20 Gy, respectively. Thus prophylactic cranial irradiation (PCI) in the treatment of SCLC was thought to be not always necessary if early treatment of small metastatic lesions, detected by Gd-DTPA-enhanced MRI could be achieved. The optimal interval between follow-up examinations was thought to be 1 month during the first two years after the diagnosis of SCLC, and then 3 months after that. In addition, the omission of PCI can save many patients who do not actually require PCI from suffering its adverse effects.     

Changes in lung volume and volume of emphysema after unilateral lung reduction surgery: analysis with CT lung densitometry

PURPOSE: To evaluate changes in volume of the lungs and volume of emphysema after unilateral lung reduction surgery (ULRS) by using computed tomographic (CT) lung densitometry. MATERIALS AND METHODS: Twenty-eight patients underwent CT before and 3 months after ULRS. With use of a density mask software program and a three-dimensional graphics workstation, CT scans were analyzed to define the volume of the lungs and the volume of emphysema. Pre- and postoperative mean CT numbers were determined. RESULTS: After ULRS, the surgically reduced lung volume decreased 22%, and the intact opposite lung volume increased 4%. Emphysema in the surgically reduced lung decreased 14% and was unchanged in the intact opposite lung. Mean CT numbers in the surgically reduced lung increased 26 HU but were unchanged in the intact opposite lung. CONCLUSION: The effects of ULRS on each lung can be evaluated by using CT lung densitometry and a three-dimensional graphics workstation. ULRS reduces emphysema and lung volume in the surgically reduced lung without statistically significant worsening of contralateral emphysema at 3 months.     

Surgical treatment of severe emphysema: lung transplantation or volume reduction?

In recent years, lung transplantation (LT) and volume reduction surgery (LVRS) have been proposed for selected patients with end-stage pulmonary emphysema. Retrospectively, we analyzed the perioperative time course of 30 patients with emphysema who underwent either LVRS (n = 17) or LT (n = 13). In the LVRS group, patients were significantly older, presented less severe functional disability and all but one could be extubated at the end of surgery. In contrast, patients undergoing LT required postoperative mechanical ventilation (19 +/- 11 hrs) and had a prolonged hospital stay (37 [25-60] days vs 19 [11-42] days in LVRS patients) due to reperfusion lung edema, infection, hemorrhage and acute rejection. Six months postoperatively, forced expiratory volume in 1 second was improved and was significantly larger after LT compared with LVRS (+200% vs +63%). Our preliminary results suggest that, although LT produces greater functional improvement, LVRS is associated with lower surgical risk and is an alternative therapy in selected patients with severe emphysema.     

Radiotherapy in the treatment of dermatologic malignancies

A large set of monoclonal antibodies (MAbs) directed against the fusion glycoprotein complex F1F2 of bovine respiratory syncytial virus (BRSV) and several polyclonal sera from infected or vaccinated animals were tested in Pepscan to locate linear epitopes on the F-protein. The polyclonal sera mapped to antigenic sites that correspond exactly to known antigenic sites on the F protein of human RSV. Only the neutralizing MAb 3 could be mapped with Pepscan. MAb 3 reacted with three successive overlapping linear peptides that shared the amino acid sequence 173STNKAVVSLS182. The sequence of this novel neutralization site is conserved in all known BRSV- and human RSV-strains and is located on the N-terminus of F1, adjacent to the hydrophobic, putative fusion-related region. This region is probably part of a central coiled-coil stem that is structurally conserved in paramyxovirus fusion and orthomyxovirus hemagglutinin glycoproteins. This linear conserved epitope may be a potential candidate for a peptide-based vaccine which can induce neutralizing antibodies against all groups and subgroups of RSV. Furthermore, the proposed structural features of the neutralization site may aid in the design of a peptide-based vaccine.     

Dexamethasone treatment during hemorrhagic shock: changes in extracellular fluid volume and cell membrane transport

Changes in extracellular fluid volume and cell membrane transport during hemorrhagic shock and the effects of dexamethasone treatment on these changes were measured. It is well known that prolonged hemorrhagic shock leads to irreversible changes and a progressive decrease in blood pressure despite reinfusion for lost blood. Pharmacologic doses of glucocorticoids provide some protection against these changes. Therefore, one purpose in the present study was to identify possible sites of glucocorticoid action whicy may prevent the irreversible changes from occurring. The extracellular fluid volume in normal control, nontreated dogs in shock, and dexamethasone-treated dogs in shock were measured by a dilution technique, using [35S] sodium sulfate. Cell membrane cation transport capabilities were measured in liver slices, diaphragm slices, and red blood cells taken from normal control, nontreated rats in shock, and dexamethasone-treated rats in shock. The accumulation of radioactivity by the tissues incubated with 22Na served as an indicator of cell membrane ion transport capabilities. The results indicate that in animals subjected to prolonged hemorrhagic shock, there is a fluid shift from the extracellular space into intracellular spaces, reducing blood volume. Cell membranes are damaged and transport mechanisms are altered; therefore, the cells are unable to extrude ions along with water. Dexamethasone treatment was shown to prevent extracellular fluid volumes from decreasing below that amount due to the plasma lost during hemorrhage. Also, it prevented some cell membrane damage and maintained membrane transport mechanisms near normal. In addition, at the onset of dexamethasone injection, blood pressure increased, and urine output was restored.     

Radiotherapy in the treatment of solitary plasmacytoma

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.     

Effects of immersion in water and changes in intrathoracic blood volume on lung function in man

1. In healthy, normal subjects simultaneous peripheral venous occlusion of all four limbs caused a small but significant increase in vital capacity (VC) and single-breath carbon monoxide transfer factor (DLCO) without significantly changing total lung capacity (TLC), residual volume (RV), pulmonary gas flow or pulmonary compliance. 2. Immersion in water to the neck resulted in a small but significant fall in VC, FEV 1.0/FVC and TLC, and a rise in DLCO, but flow/volume curves and 'closing volume' were unchanged. Peripheral venous occlusion during immersion only significantly increased VC and DLCO; pulmonary compliance and flow/volume curves did not alter significantly. 3. It is concluded that peripheral venous occlusion produces these effects by altering intrathoracic blood volume. Water immersion reduces TLC, mainly from the hydrostatic pressure, and VC is reduced from both the hydrostatic pressure and the increase in intrathoracic blood volume consequent on immersion. The increase in DLCO is due, almost entirely, to the increase in intrathoracic blood volume.     

Effect of set-up error on the dose across the junction of matching cranial-spinal fields in the treatment of medulloblastoma

PURPOSE: The effect of systematic and stochastic setup error on the dose delivered to the gap region for the three field radiation treatment of medulloblastoma is studied. The consequences of such setup error is discussed. METHODS AND MATERIALS: The treatment of medulloblastoma is typically a 3 field technique, in which two lateral cranial fields are matched with a spine field. The x-ray dose delivered to the region between the matched fields depends upon the gap size. The choice of the gap width between the cranial and spinal fields is controversial. It is currently a compromise between minimizing the risk of dose hot spots to the spine, and the associated clinical complications, as well as the magnitude of cold spots (underdosing) across the gap, with the associated risk of disease recurrence. In this paper, we examine the effect of gap width with a moving junction, referred to as "field feathering", on the dose across the field junction for a 6MV photon beam. In addition, we have studied 129 portal films and 40 simulation films to assess the accuracy and precision of patient setup during treatment with a plan involving feathered fields. Selected landmarks observable on both portal and simulation films were identified and the variation in the distances to the field edges measured. The distribution of patient setup error was convoluted with the beam profiles for a 6MV linac. These convoluted field edges were used obtain dose profiles across the gap region as a function of gap separation. The consequences for therapy are discussed. In addition, analysis of patient setup error on an alternative treatment involving beam modifiers to broaden the beam penumbra is discussed. RESULTS: The magnitude of the spatial stochastic and systematic setup error was determined to be approximately three and two millimeters respectively. The dosimetric consequences of patient setup error lead to over and under dosing in the spinal gap region for the three field technique. The degree of under or over dose depends on the nature and magnitude of the patient setup error. CONCLUSIONS: The effect of patient setup error can lead to significant dosimetric errors in the dose to the gap region depending on the magnitude of the setup errors. The effective over and under dose can be compensated by the use beams modifiers such as a beam spoiler or vibrating jaws.     

Homogeneous dose distribution in the moving-strip technic

The moving-strip technique employing a 60Co beam, is used in radiotherapy for whole abdominal irradiation in ovarian tumours and lymphomas. With this technique the spread of received dose from single strip, around an average value, is very high. Our paper suggest a computerized method for a more homogeneous dose distribution in central strips and a lower dose in out-side tissues.     

Radiotherapy, local control and survival in lung cancer

Better local control in locally advanced IIIA-B non small cell lung cancer, not considered for surgery, can be achieved through therapy intensification with non conventional fractionation of radiation dose, concomitant boost to the tumor volume, conformal therapy and combined modality therapy. All these procedures tend to produce an improved response, which, if stable in time, may also improve local control and survival. The reported experiences define a positive and encouraging trend on which new guidelines for a more suitable definition of standard therapies for the disease can be modulated.     

Oxygen and 99mTc-MAA shunt estimations in patients with pulmonary arteriovenous malformations: effects of changes in posture and lung volume

BACKGROUND: Patients with arteriovenous malformations are routinely monitored with arterial oxygen saturation (SaO2) estimations (breathing air) from which an oxygen shunt fraction can be calculated. This simple estimation has been compared with an anatomically defined estimate of the right to left shunt using a radioisotopic method. The fall in SaO2 which occurs in patients with pulmonary arteriovenous malformations in the erect posture and at high lung volumes was used to test the ability of SaO2 alone to follow changes in right to left shunt. METHODS: Radiolabelled albumin macroaggregates (99mTc-MAA) or microspheres (MS) were injected intravenously and kidneys and lungs were imaged. The shunt fraction (QS/QTTc) in the supine position at functional residual capacity (baseline) was obtained by quantifying right kidney radioactivity. On standing or while breath holding at total lung capacity, shunt fraction was calculated from baseline QS/QTTc and from lung counts and the injected dose. Arterial oxygen saturation (SaO2) was recorded by a pulse oximeter for calculation of the oxygen shunt (QS/QTO2) (breathing air). RESULTS: In the postural study (n = 8) SaO2 decreased from a mean (SD) value of 89 (5)% supine to 80 (6)% erect, corresponding to QS/QTO2 28 (8)% and 44 (8)% respectively. QS/QTTc increased from 28.7 (10.3)% to 39 (14.3)%. In the lung volume study (n = 8) QS/QTTc increased from 16.6 (11.5)% at functional residual capacity to 23.3 (11.9)% at total lung capacity while QS/QTO2 increased from 19.5 (7.5)% to 25.9 (10.6)% respectively. When all measurements were compared for QS/QTTc% and QS/QTO2% (n = 32) the difference in the mean values was 2.5% (absolute) and the limits of agreement between the two methods were +38% to -18% (relative). In neither the postural nor the volume study did delta (QS/QTO2) reliably predict delta (QS/QTTc)%. CONCLUSIONS: In pulmonary arteriovenous malformations the simple physiological shunt calculated from SaO2 breathing air agreed well with the anatomical right to left shunt measured with 99mTc-MAA, but predicted poorly the changes in anatomical shunt induced by postural or lung volume changes.     

Radiotherapy of choroidal metastases: breast cancer as primary site

Forty-two cases of metastatic breast cancer to the choroid treated by radiation therapy were reviewed. Fifteen patients (36%) had bilateral and 27 patients (64%) had unilateral choroidal involvement. In 12 patients (29%) the choroid was the first site of dissemination. The median survival period after choroidal metastases was 10 months. Most patients were treated with Co60 in doses of 2500 rads tumor dose (TD) in ten fractions, 2500 rads, (TD) in five fractions and 3000 rads (TD) in ten fractions. An early group of patients had orthovoltage therapy. Good visual responses were obtained with each of the above treatment programs. Radiation treatment in the range of 2500-3000 rads TD in a short course is recommended for palliation of metastatic breast cancer to the choroid.     

Metered dose inhalers III: Metaproterenol sulphate; particle size distribution and dose uniformity

Three American products and one Canadian product were examined for content uniformity and particle size distribution. The results showed that not all products performed equally well. Some of the products exhibited high sprays early in the canister lifetime and all products demonstrated loss of prime. The particle size distributions were determined using the Andersen cascade impactor (USP Induction Port) and the fine particle fraction was determined using the twin impinger. The results showed that three of the four products had similar particle size distribution profiles. Both the Andersen cascade impactor and the twin impinger yielded the same trends in the amount of drug substance delivered to the fine particle fraction.     

High dose chemotherapy in metastatic carcinoma of the breast

PURPOSE: To verify tolerance and clinical efficacy of high-dose chemotherapy (HDCT) in metastatic breast cancer (MBC). PATIENTS AND METHODS: We submitted to HDCT with autologous peripheral blood cells transplant 66 patients, with MBC responding to induction chemotherapy. The condizioning regimen was ICE: iphosphamide 3.3 g/m2 dd. -8/-6, carboplatin 450 mg/m2 plus etoposide 400 mg/m2 dd. -5/-3 (21 patients = 78%); CTM: cyclophosphamide 100 mg/kg dd. -4/-3, tyothepa 500 mg:m2 d.-5, mytoxantrone 40 mg/m2 d. -6 (6 patients, 22%). RESULTS: Median number of aphereses was 2 (range 1-5), median amount of CD34+ cells/kg bw of 10 x 10E6 (range 3.5-38.2). Median recovery time was 10th day for PMN (range 8-37) while for platelets it was 9th day (range 8-37): total hospital stay was of 24 days (range 22-48). After induction therapy we had PR in 13/27 metastatic patients (48%) and CR in 14/27 (52%). After conditioning treatment we had PR in 12/27 (44%) and CR in 15/27 (56%). Median time to progression was 19 months (range 7-38) and median survival 52 months (range 7-59+), with 30% surviving beyond 4 years. CONCLUSIONS: Feasibility of HDCT in advanced breast cancer seems verified. The promising results need to be confirmed.