Cost effectiveness of linear accelerators.

Cost analysis of radiation therapy and cost benefit analysis of Co60 versus linear accelerator therapy are useful exercises for radiation therapy departments. Such analysis will show that the costs of radiation therapy are significant. However, the cost benefit is most likely to be seen where survival is increased and morbidity is decreased. In centers where there is a high population of patients treated for palliation, the cost benefit is unlikely to be realized.

Hypofractionated radiation therapy in the modern era.

Choice of the appropriate fractionation schedule in a modern radiation therapy department requires clear understanding of the radiobiologic principles that govern the tumor or normal tissue responses to radiation therapy as well as the goals and expected outcomes for the individual patient. Although the majority of patients will be most appropriately treated with conventional fractionated radiation therapy (dose per fraction less than 225 cGy), there may still be a role hypofractionated treatment for selected patients. Currently it is not feasible to taylor the fractionation regiment to the patient's individual and specific tumor cell survival characteristics. Thus, in malignant melanoma, despite the demonstration of "wide shoulders" on the cell survival curve, it has not been demonstrated clinically that large doses per fraction are clearly advantageous. Many patients may be well palliated with hypofractionated regimens. However, this requires the physicians to carefully select their patients and where resources allow, many patients will be better palliated with higher total doses and lower doses per fraction. This is especially true if they survive for longer than one year. Lastly, new technology that allows for the delivery of highly conformal radiation therapy needs further study relative to the optimal fractionation in its application.

Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC)

PURPOSE: To identify a clinically relevant and available parameter upon which to identify non-small cell lung cancer (NSCLC) patients at risk for pneumonitis when treated with three-dimensional (3D) radiation therapy. METHODS AND MATERIALS: Between January 1991 and October 1995, 99 patients were treated definitively for inoperable NSCLC. Patients were selected for good performance status (96%) and absence of weight loss (82%). All patients had full 3D treatment planning (including total lung dose-volume histograms [DVHs]) prior to treatment delivery. The total lung DVH parameters were compared with the incidence and grade of pneumonitis after treatment. RESULTS: Univariate analysis revealed the percent of the total lung volume exceeding 20 Gy (V20), the effective volume (Veff) and the total lung volume mean dose, and location of the tumor primary (upper versus lower lobes) to be statistically significant relative to the development of > or = Grade 2 pneumonitis. Multivariate analysis revealed the V20 to be the single independent predictor of pneumonitis. CONCLUSIONS: The V20 from the total lung DVH is a useful parameter easily obtained from most 3D treatment planning systems. The V20 may be useful in comparing competing treatment plans to evaluate the risk of pneumonitis for our individual patient treatment and may also be a useful parameter upon which to stratify patients or prospective dose escalation trials.

Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group.

CONTEXT: Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy. OBJECTIVE: To report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma. DESIGN: Randomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991. SETTING: Multi-institution participation, ranging from tertiary academic referral centers to general community practices. PATIENTS: Patients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. Interventions Combined modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n = 62): 64 Gy in 32 fractions over 6.4 weeks. MAIN OUTCOME MEASURES: Overall survival, patterns of failure, and toxic effects. RESULTS: Combined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group). CONCLUSION: Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.

Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients.

PURPOSE: To determine the relation between the incidence of radiation pneumonitis and the three-dimensional dose distribution in the lung. METHODS AND MATERIALS: In five institutions, the incidence of radiation pneumonitis was evaluated in 540 patients. The patients were divided into two groups: a Lung group, consisting of 399 patients with lung cancer and 1 esophagus cancer patient and a Lymph./Breast group with 78 patients treated for malignant lymphoma, 59 for breast cancer, and 3 for other tumor types. The dose per fraction varied between 1.0 and 2.7 Gy and the prescribed total dose between 20 and 92 Gy. Three-dimensional dose calculations were performed with tissue density inhomogeneity correction. The physical dose distribution was converted into the biologically equivalent dose distribution given in fractions of 2 Gy, the normalized total dose (NTD) distribution, by using the linear quadratic model with an alpha/beta ratio of 2.5 and 3.0 Gy. Dose-volume histograms (DVHs) were calculated considering both lungs as one organ and from these DVHs the mean (biological) lung dose, NTDmean, was obtained. Radiation pneumonitis was scored as a complication when the pneumonitis grade was grade 2 (steroids needed for medical treatment) or higher. For statistical analysis the conventional normal tissue complication probability (NTCP) model of Lyman (with n=1) was applied along with an institutional-dependent offset parameter to account for systematic differences in scoring patients at different institutions. RESULTS: The mean lung dose, NTDmean, ranged from 0 to 34 Gy and 73 of the 540 patients experienced pneumonitis, grade 2 or higher. In all centers, an increasing pneumonitis rate was observed with increasing NTDmean. The data were fitted to the Lyman model with NTD50=31.8 Gy and m=0.43, assuming that for all patients the same parameter values could be used. However, in the low dose range at an NTDmean between 4 and 16 Gy, the observed pneumonitis incidence in the Lung group (10%) was significantly (p=0.02) higher than in the Lymph./Breast group (1.4%). Moreover, between the Lung groups of different institutions, also significant (p=0.04) differences were present: for centers 2, 3, and 4, the pneumonitis incidence was about 13%, whereas for center 5 only 3%. Explicitly accounting for these differences by adding center-dependent offset values for the Lung group, improved the data fit significantly (p < 10(-5)) with NTD50=30.5+/-1.4 Gy and m=0.30+/-0.02 (+/-1 SE) for all patients, and an offset of 0-11% for the Lung group, depending on the center. CONCLUSIONS: The mean lung dose, NTDmean, is relatively easy to calculate, and is a useful predictor of the risk of radiation pneumonitis. The observed dose-effect relation between the NTDmean and the incidence of radiation pneumonitis, based on a large clinical data set, might be of value in dose-escalating studies for lung cancer. The validity of the obtained dose-effect relation will have to be tested in future studies, regarding the influence of confounding factors and dose distributions different from the ones in this study.

Prevalence and correlates of obesity in preschool children.

Obesity, a common nutritional disorder in childhood, is a complex problem that is poorly understood. The purpose of this study was to identify the prevalence of obesity in preschool children, and to examine the relationships between obesity and gender, race, socioeconomic status, and health problems. Data were collected from 309 charts of children enrolled in a Head Start program. Ninety-nine (32%) of the children were obese. Obese children had significantly higher blood pressure readings than those who were not obese. This study represents a beginning effort to learn more about the prevalence of, and factors associated with, obesity in preschoolers.

Medication compliance and the older hemodialysis patient.

OBJECTIVE: The purpose of this study was to identify relationships between demographic factors, psychosocial characteristics, and medication compliance rates in older patients receiving hemodialysis and to determine the effectiveness of a teaching program on medication-taking behavior. DESIGN: A descriptive correlational study design was used. SAMPLE/SETTING: A total of 26 patients, age 65 and over, undergoing hemodialysis at an inner city outpatient dialysis clinic met sample criteria. METHODS: The instrument included a demographic data form, the Iowa Self-Assessment Inventory (ISAI) to measure psychosocial variables, and a form to collect data to calculate medication compliance rates. RESULTS: All participants were African-American. Mean age was 70. Sample attrition was high. Scores were below the norm for most ISAI psychosocial factors, medication compliance rates were low, and the teaching intervention did not affect compliance rates. CONCLUSION: Medication compliance in this older dialysis patient population was problematic, and further research in this area is essential.

Lead poisoning and associated risk factors among preschoolers enrolled in a Head Start program.

Despite the fact that lead poisoning is one of the most common pediatric health problems in the United States today, little is known about the prevalence and correlates of this disease among nonurban preschool children living in the southern United States. The purpose of this study was to measure the prevalence of abnormal lead levels and to explore the relationships between lead levels and gender, weight, hemoglobin, and ethnicity. Using a chart review protocol, data were collected from 81 charts of children enrolled in a Head Start program in Florida. The prevalence rate of elevated lead levels was 18.5%, a rate higher than that found in most previous research. No relationship was found between lead levels and gender, weight, hemoglobin, and ethnicity. The results highlight the importance of local screening efforts. Controversies in screening are discussed in this article in some detail with the aim of assisting health care providers make decisions about whether universal screening for lead levels in children is appropriate and whether use of the Centers for Disease Control questionnaire has sufficient value. Further study is needed regarding prevalence rates in different geographic areas in the United States, and factors associated with elevated lead levels.

A volumetric study of measurements and calculations of lung density corrections for 6 and 18 MV photons.

PURPOSE: For treatment of lung cancer, dose heterogeneity corrections and subsequent prescription alteration remain controversial. Previous dosimetry studies based on slab geometry with a single beam geometry do not represent the clinical situation. A circumscribed tumor within lung poses a more complex problem. Energy choice also remains controversial. METHODS AND MATERIALS: An anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm diameters by 5.0 cm length) with muscle-equivalent cylinders. The phantom was scanned on a CT simulator. Gross, clinical, and planning target volumes (GTV, CTV, PTV1 including tumor and regional nodes, PTV2 including tumor only) were designated slice-by-slice. Three-dimensional planning was performed with large fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2, for 6 and 18 MV photons. Homogeneous, Ratio-Tissue-Air-Ratio (RTAR), and convolution-adapted RTAR (CARTAR) calculation algorithms were tested. Film was placed between phantom slices at the "tumor" levels. The phantom was irradiated with monitor units corresponding to homogeneous calculations, based on a homogeneous prescription. Measured and calculated doses were compared by isodoses and dose volume histograms. Ionization chambers and TLDs were also used for some test cases. RESULTS: The measured minimum dose covering PTV2 was within 5% of the homogeneous prescription dose of 70 Gy for 6 MV photons, while a lower dose (89% of prescription dose) was measured for 18 MV. The algorithms overpredicted the minimum dose to PTV2 by 6-18%. If the monitor units had been reduced according to simplistic heterogeneous calculations, the small PTV2 would have only been covered by 58 Gy for 18 MV irradiation. Based on this, a clinician may opt to actually increase the prescribed dose, thereby offsetting decreased monitor units. None of the algorithms predicted the diffuse penumbra associated with 18 MV photons in lung. CONCLUSION: Before adjusting dose prescriptions based on heterogeneity corrections, realistic phantom studies must be performed. The accuracy and effect of the corrections must then be assessed. The deficient coverage of PTV2 by the 18 MV beam compares unfavorably with the slight increase (5%) in hot spots associated with 6 MV. Our studies support strong caution before reducing dose prescriptions based on simple algorithms.

Radiation therapy for intrathoracic recurrence of non-small cell lung cancer.

Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's Hospital between 1975 and 1988 presented with local recurrence after definitive surgery. No patient received radiation therapy after surgery as part of initial treatment and none had evidence of distant metastases at the time of local recurrence. The median time to first recurrence was 14 months. At recurrence, patients presented with disease in the bronchial stump (eight patients), ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five), or some combination thereof (23). Sixty-five percent of patients had histologic evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15 patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR) response--tumor response to radiation therapy. Among these patients, local control was achieved in 70% of patients with marginal recurrences (i.e., stump, parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival after radiation therapy for all patients was 8.5 months. The best indicators for long-term survival were the interval from initial surgery to first recurrence and tumor response to radiation therapy.

Results of a trial with topotecan dose escalation and concurrent thoracic radiation therapy for locally advanced, inoperable nonsmall cell lung cancer.

PURPOSE: To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA). METHODS AND MATERIALS: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose levels of 0.75 mg/m2 and 1.0 mg/m2 were tested. RESULTS: Six patients were accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose level, zero of six patients had > or = Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients had > or = Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced > or = Grade 4 hematologic toxicity. At the 1.0 mg/m2 dose level one of three patients had > or = Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease. CONCLUSIONS: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.

Prospective clinical evaluation of an electronic portal imaging device.

PURPOSE: To determine whether the clinical implementation of an electronic portal imaging device can improve the precision of daily external beam radiotherapy. METHODS AND MATERIALS: In 1991, an electronic portal imaging device was installed on a dual energy linear accelerator in our clinic. After training the radiotherapy technologists in the acquisition and evaluation of portal images, we performed a randomized study to determine whether online observation, interruption, and intervention would result in more precise daily setup. The patients were randomized to one of two groups: those whose treatments were actively monitored by the radiotherapy technologists and those that were imaged but not monitored. The treating technologists were instructed to correct the following treatment errors: (a) field placement error (FPE) > 1 cm; (b) incorrect block; (c) incorrect collimator setting; (d) absent customized block. Time of treatment delivery was recorded by our patient tracking and billing computers and compared to a matched set of patients not participating in the study. After the patients radiation therapy course was completed, an offline analysis of the patient setup error was planned. RESULTS: Thirty-two patients were treated to 34 anatomical sites in this study. In 893 treatment sessions, 1,873 fields were treated (1,089 fields monitored and 794 fields unmonitored). Ninety percent of the treated fields had at least one image stored for offline analysis. Eighty-seven percent of these images were analyzed offline. Of the 1,011 fields imaged in the monitored arm, only 14 (1.4%) had an intervention recorded by the technologist. Despite infrequent online intervention, offline analysis demonstrated that the incidence of FPE > 10 mm in the monitored and unmonitored groups was 56 out of 881 (6.1%) and 95 out of 595 (11.2%), respectively; p < 0.01. A significant reduction in the incidence of FPE > 10 mm was confined to the pelvic fields. The time to treat patients in this study was 10.78 min (monitored) and 10.10 min (unmonitored). Features that were identified that prevented the technologists from recognizing more errors online include poor image quality inherent to the portal imaging device used in this study, artifacts on the portal images related to table supports, and small field size lacking sufficient anatomical detail to detect FPEs. Furthermore, tools to objectively evaluate a portal image for the presence of field placement error were lacking. These include magnification factor corrections between the simulation of portal image, online measurement tools, image enhancement tools, and image registration algorithms. CONCLUSION: The use of an electronic portal imaging device in our clinic has been implemented without a significant increase in patient treatment time. Online intervention and correction of patient positioning occurred rarely, despite FPEs of > 10 mm being present in more than 10% of the treated fields. A significant reduction in FPEs exceeding 10 mm was made in the group of patients receiving pelvic radiotherapy. It is likely that this improvement was made secondarily to a decrease in systematic error and not because of online interventions. More significant improvements in portal image quality and the availability of online image registration tools are required before substantial improvements can be made in patient positioning with online portal imaging.

Prospective phase I/II studies of definitive irradiation and chemotherapy for advanced gynecologic malignancies.

PURPOSE: This is a prospective study to evaluate toxicity and efficacy of concurrent irradiation and three cycles of chemotherapy bolus cisplatin and infusion 5-fluorouracil (5FU) in patients with advanced gynecologic malignancies. MATERIALS AND METHODS: Patients received cisplatin, 50 mg/m2 I.V. rapid infusion, and 5-day continuous infusion of 5FU (750 mg/m2 per day (schedule A); or cisplatin 75 mg/m2 i.v. rapid infusion, and 4-day continuous infusion of 5FU 1,000 mg/m2 per day (schedule B). Schedule A was given to 25 patients in the first 36 months of the study and was changed to schedule B in an additional 42 patients. All patients received irradiation, which usually consisted of 20 Gy whole pelvis, 30-40 Gy split field, and two intracavitary insertions for a total of 80-90 Gy to point A. Primary cervical cancer occurred in 40 patients with 3 having stage IB bulky, 2 with stage IIA, 5 with stage IIB, 2 with stage IIIA, 23 with stage IIIB, 4 with stage IV, and 1 with stage IVB. Recurrent cervical carcinoma after radical hysterectomy occurred in 18 patients. The remainder of the patients consisted of two each with stages III and IV endometrial carcinoma, two with stage III vaginal carcinoma, two with stage III vulvar carcinoma, and one with recurrent vulvar carcinoma. Patients were treated from 1985 through 1992. RESULTS: The 5-year overall survivals for patients with stages IB (bulky)-IIB cervical cancer was 70%, 25% for stages IIIA-IVA, and 39% for patients with recurrent cervical carcinoma. All four patients with endometrial carcinoma have recurred and died. Two patients with vulvar carcinoma are alive and free of disease, and one is dead of intercurrent disease. One patient with stage III vaginal carcinoma is alive and free of disease, while the other recurred and died. No significant differences were observed in the toxicity of the two chemotherapy schedules. There were 9/39 (23%) grade 4 and one fatal complication in those with primary cervical carcinoma. The overall fistulae rate was 11% (4/39) with three patients developing rectovaginal fistulae and one having vesicovaginal fistula. CONCLUSION: Concurrent chemotherapy and irradiation for advanced gynecologic malignancies as administered in this study is highly toxic and fails to demonstrate an obvious survival improvement.