[en] Purpose/Objective: The results of the Patterns of Care Study consensus panel on esophageal cancer will be presented with special attention to the treatment decision tree and best current management guidelines. As has been done in the previous refresher courses, this course will review a multitude of aspects of esophageal cancer with emphasis on clinically relevant issues including the following: (1) The etiology and epidermiology of esophageal cancer with emphasis on the rising incidence of adenocarcinoma. (2) Esophageal anatomy and lymph node drainage. (3) Tumor characteristics including pattern of spread and tumor biology. (4) Diagnostic studies. The use of espohagoscopy, esophagogram, CT scan, endoscopic ultrasound with particular emphasis on recent studies on the value of endoscopic ultrasound in determining depth of wall penetration and nodal involvement. (5) Staging. Both clinical and pathologic staging systems as well as CT staging systems will be reviewed. Important prognostic factors not included in staging system will also be discussed. (6) Treatment and Results. The primary management of esophageal cancer with either surgical approach or radiotherapeutic approach will be compared and contrasted. The use of concurrent chemotherapy and radiation will be a major review topic as will the results of randomized and nonrandomized studies utilizing concurrent radiation-chemotherapy versus radiation alone. (7) The role of radiation as adjuvant treatment. (8) Techniques of radiation which optimize the therapeutic ratio will be reviewed. (9) Palliation. A variety of noncurative treatments for palliating esophageal cancer including laser, PDT, and stent placement as well as the management of TE fistula will be discussed

[en] Purpose/Objective: This course will review a multitude of aspects of esophageal cancer with emphasis on clinically relevant issues including the following: (1) The etiology and epidemiology of esophageal cancer with emphasis on the rising incidence of adenocarcinoma. (2) Esophageal anatomy and lymph node drainage. (3) Tumor characteristics including pattern of spread and tumor biology. (4) Diagnostic studies. The use of esophagoscopy, esophagogram, CT scan, endoscopic ultrasound with particular emphasis on recent studies on the value of endoscopic ultrasound in determining depth of wall penetration and nodal involvement. (5) Staging. Both clinical and pathologic staging systems as well as CT staging systems will be reviewed. Important prognostic factors not included in staging system will also be discussed. (6) Treatment and Results. The primary management of esophageal cancer with either surgical approach or radiotherapeutic approach will be compared and contrasted. The use of concurrent chemotherapy and radiation will be a major review topic as will be the results of randomized and nonrandomized studies utilizing concurrent radiation-chemotherapy versus radiation alone. (7) The role of radiation as adjuvant treatment. (8) Techniques of radiation which optimize the therapeutic ratio will be reviewed. (9) Palliation. A variety of noncurative treatments for palliating esophageal cancer including laser, PDT, and stent placement as well as the management of TE fistula will be discussed

[en] Purpose: An innovative technique is used to harvest backscatter electrons for the treatment of superficial small lesions of skin, oral cavity, and rectum where a significant dose gradient and maximum surface dose is desired. Methods and Materials: Backscatter electrons are harvested out of the primary electron beams from the linear accelerators. The design consists of a short cylindrical cone that fits snugly over a long cylindrical electron cone. The short cylindrical cone has a thick circular plate of high atomic number medium (Pb) attached to the distal end, and a lateral slit of variable length and width. The width of the slit could be closed as desired by rotating the two cones and the length can be increased by lowering the short cylindrical cone. Primary electrons strike the Pb plate perpendicularly and produce backscatter electrons that pass through the lateral slit for treatment. Using film and a parallel plate ion chamber, backscattered electron dose characteristics are studied. Results: The depth dose characteristic of the backscatter electron is very similar to that of the 0.2 mm Al half-value layer x-ray beam that is commonly used for the intracavitary and superficial lesions. The backscatter electron energy is nearly constant and effectively ≤ 1 MeV from the clinical megavoltage beams. The backscatter electron dose rate of 0.32-0.8 Gy/min could be achieved from modern accelerators without any modification. The beam flatness is dependent on the slit size and the depth of treatment, but is satisfactory to treat small lesions. Conclusions: The measured data for backscatter electron energy, fluence, depth dose, flatness, dose rate, and absolute dose indicates that the harvested backscattered electrons are suitable for clinical use

[en] Purpose: CA 19-9 has been identified as a tumor marker for pancreatic carcinoma and has been shown to have some utility in predicting outcome in surgically treated patients. The purpose of this study was to evaluate its usefulness as a prognostic indicator in patients treated with radiotherapy. Materials and Methods: A retrospective review of all patients treated with radiotherapy of definitive intent (N=104) for carcinoma of the pancreas at Fox Chase Cancer Center from 1980-1994 was undertaken. Patients were categorized into four groups: planned preoperative radiation with resection (N=25), planned preoperative radiation without successful resection (N=35), postoperative radiation (N=21), and radiation without planned resection (N=23). For each group except those treated without planned resection, median dose for external beam radiotherapy was 50.4 Gy (range=21.6-63.0 Gy). Those in the fourth group were treated with a median dose of 55.8 Gy (range=36.0-60.4 Gy). Ninety-seven percent of patients in the first three groups were also treated with 5-FU based chemotherapy, as were 61% of those in the fourth group. Results: Mean/median survival for all groups was (14.6(10.0)) mos. (range=1-67 mos.). Univariate analysis showed significant differences in survival among the groups: preop with resection 22.2 mos., preop without resection 9.5 mos., postop 16.8 mos. and without planned resection 12.2 mos. (p=0.0005). Overall, patients who underwent resection had a mean survival of 19.7 mos., compared to 10.6 mos. in those who did not (p=0.0006). CA 19-9 level at diagnosis was found to be a significant prognostic indicator on univariate analysis, with a mean survival of 8.3 mos. in those having a level greater than the median of 680, compared to 20.2 mos. in those who did not (p=0.0003). Similarly, post-treatment nadir was significant, with a mean survival of 11.3 mos. in those with levels above the median of 162.5, versus 26.1 mos. in those below the median (p=0.001). On stepwise multivariate analysis, pre-treatment CA 19-9 level was found to be a significant predictor of survival (p=0.0014). Other potential indicators of outcome, including age, sex, KPS, prediagnosis weight loss, location of tumor, clinical TNM staging, size of lesion, vascular involvement on angiography, and sequence of radiation with respect to resection, were evaluated and were not found to be significant. Conclusion: CA 19-9 was demonstrated to be a useful prognostic indicator in patients treated with radiotherapy, while other more traditional indicators of outcome were of less utility

[en] Purpose: 1) to measure the basic structural characteristics of radiation oncology facilities for the entire country, providing census data for January 1, 1994; 2) to allow comparisons by facility type, equipment, or patient load; 3) to allow comparisons of the patterns of equipment and personnel to previous surveys; and 4) to make a preliminary assessment of the geographic distribution of facilities. Methods and Materials: A mail survey verified whether each potential facility delivered megavoltage radiation therapy and collected data on treatment machines, other equipment, personnel, new patients, and procedures performed. Responses were obtained from 99% of potential facilities. The census data was summarized for the entire country, by hospital-based, free-standing, or federal category, by single or multiple treatment machine group, and by new patient load category. Geographic analysis compared the center of radiation oncology facilities with the center of cities or towns having a population of more than 25,000 residents in 1990. Results: In the United States in 1994, 1542 facilities delivered megavoltage radiation therapy, with 2744 treatment machines, 2777 FTE radiation oncologists, 1349 FTE physicists, 1314 FTE dosimetrists, and 7167 FTE radiation therapists. They treated 560,262 new patients and reported that 60% were treated with curative intent. Eighty percent of the facilities had a dedicated treatment planning computer and 15% had a time-sharing treatment-planning computer, but 5% had no treatment-planning capability. Ninety-five percent of all facilities reported that patients were simulated at that facility. Fourteen percent of all facilities used hyperthermia, 8% intraoperative radiation therapy, 12% stereotactic radiosurgery, and 19% conformal therapy with 3D planning. Of all facilities 35% reported having a dedicated CT scanner and 12% reported having a CT simulator in the department. The distributions of these measures were reported for hospital-based, free-standing, and federal facilities, for single-treatment machine, and multiple-treatment machines facilities, and for three categories based on patient load. Only 18 cities with a population over 25,000 were more than 25 miles from a radiation oncology facility, of which only eight were more than 50 miles from a facility. Conclusion: The Facilities Surveys continue to provide a unique source of census data on radiation oncology in the United States, allowing comparisons by facility group and over time

[en] Purpose: CA 19-9 has been identified as a tumor marker for pancreatic carcinoma and has been shown to have some utility in predicting outcome in surgically treated patients. The purpose of this study was to evaluate its usefulness as a prognostic indicator in patients treated with radiotherapy. Materials and Methods: A retrospective review of all patients treated with radiotherapy of definitive intent (n = 104) for carcinoma of the pancreas at Fox Chase Cancer Center from 1980-1994 was undertaken. Patients were categorized into four groups: Planned preoperative radiation with resection (n = 25); planned preoperative radiation without successful resection (n 35); postoperative radiation (n = 21); and radiation without planned resection (n = 23). For each group, except those treated without planned resection, median dose for external beam radiotherapy was 50.4 Gy (range 21.6-63.0 Gy). Those in the remaining fourth group were treated with a median dose of 55.8 Gy (range = 36.0-60.4 Gy). 97% of patients in the first three groups were also treated with 5-FU-based chemotherapy, as were 61% of those in the fourth group. Pretreatment and follow-up CA 19-9 levels were available for 69 patients. Results: Median survival time for all groups was 10 months (range 1-67 months). Univariate analysis showed significant differences in survival among the groups: Preop with resection 22 months; preop without resection 10 months, postop 17 months; and without planned resection 12 months (p 0.0005). Overall, patients who underwent resection had a median survival time of 19 months, compared to 11 months in those who did not (p 0.0006). CA 19-9 level at diagnosis was found to be a significant prognostic indicator on univariate analysis, with a median survival time of 8 months in those having a level greater than the median of 680 U/ml, compared to 20 months in those who did not (p = 0.0003). Similarly, the posttreatment nadir was significant, with a median survival time of 11 months in those with levels above the median of 162.5 U/ml, vs. 26 months in those with levels below 162.5 U/ml (p = 0.001). The median survival time for patients whose CA 19-9 levels decreased in response to treatment by more than 75% was 23 months (range 6-34 months) vs. 8 months (range = 3-21) in those with 75% or less response (p = 0.003). On stepwise multivariate analysis, pretreatment CA 19-9 level was found to be a significant predictor of survival (p = 0.005). Other potential indicators of outcome, including age, gender, KPS, prediagnosis weight loss, location of tumor, clinical TNM staging, size of lesion, vascular involvement on angiography, and sequence of radiation with respect to resection, were evaluated and were not found to be significant. Conclusion: CA 19-9 was demonstrated to be a useful prognostic indicator in patients treated with radiotherapy; other, more traditional, indicators of outcome were of less utility

[en] Purpose: Transforming growth factor alpha (TGFA) stimulates the growth and proliferation of cells, and its overexpression has been correlated with patient survival in a variety of tumors, including squamous carcinoma of the esophagus. This study was performed to investigate the influence of TGFA in patients with esophageal adenocarcinoma (EA) receiving high-dose radiation and chemotherapy (HDRCT). Methods and Materials: Thirty-one patients with localized esophageal adenocarcinoma were enrolled in a Phase II study involving high dose radiation and concurrent 5-fluorouracil (5-FU)/mitomycin-C with or without esophagectomy. Twenty-seven pretreatment (tumor not available in 4) and 11 posttreatment (insufficient tumor in 20) specimens were immunostained using the avidin-biotin-peroxidase technique. Results: Fifteen of 27 (56%) pretreatment and 4 out of 11 (36%) postchemoradiation specimens had intense TGFA staining. Eight patients with intense and seven with little or no staining on pretreatment biopsy underwent esophagectomy. Median survival for the eight patients was 28 months, and for the seven patients 19 months (p = 0.4). Transforming growth factor alpha staining of posttreatment specimens that contained residual tumor also did not correlate with overall (p = 0.36) or disease-free (p = 0.17) survival. Among the 10 patients with both pre and posttreatment TGFA specimens, decreasing or negative TGFA expression was associated with a better median disease-free survival (32 vs. 13 months, p = 0.04) than persistently positive or increasing TGFA expression. Conclusion: There is frequent overexpression of TGFA in EA. Although pretreatment TGFA expression was not associated with survival, patients with tumors that persistently expressed or that increased TGFA expression had a worse prognosis. Posttreatment TGFA expression may serve as a prognostic marker in patients with EA treated with HDRCT

[en] Purpose: Doses at the interface between tissue and low-density inhomogeneities with the interface positioned perpendicular to the beam direction have been well studied. When the inhomogeneity lies parallel to the beam direction (i.e., a lateral interface), the resulting dose distribution is not as well known. Lateral lung--soft-tissue interfaces are common in many fields used to treat malignancies in the thorax region including tangential breast fields and anteroposterior fields for lung and esophageal cancer. The purpose of this study was to evaluate the dose distribution along lateral interfaces and to determine the implications for treatment. Methods and Materials: A polystyrene and cork slab phantom was irradiated from the side to simulate treatment fields with lateral lung--soft-tissue interfaces. The beam was positioned with the isocenter in polystyrene and the field edge in cork. Cork slabs (0.6-2.5 cm) were used to simulate different thicknesses of lung between the field edge and the target volume. Measurements were made using a parallel plate ionization chamber. With the chamber position held constant, polystyrene slabs were added between the cork and the chamber to study the dose distribution in the interface region. Interface doses were studied as a function of the amount of cork in the field, field size, beam energy (6-18 MV), and depth. Results: Doses in the interface region were lower by as much as 10% compared to doses in a homogeneous phantom. For a given cork width and field size, the magnitude of the underdose increased by several percent as the x-ray energy increased from 6 to 18 MV. The underdose at the interface was 5% for 6 MV and 8% for 18 MV X-rays with a 1-cm cork width. For a 2.5-cm cork width, underdoses of 2.5% and 3% at distances up to 2.5 and 4 mm lateral to the interface were observed for 6- and 18-MV X-rays, respectively. However, doses right at the interface were 1% greater for 6 MV and 3% less for 18 MV than doses in a homogeneous phantom. For a given cork width, the interface doses were not significantly dependent on field width but decreased by an additional 2-3% as the length decreased to 4 cm. Additional decreases were also observed when the measurement depth decreased to 3 cm. With a 1-cm width of cork in the field, a lateral distance of 3-4 mm from the interface was necessary to ensure doses of at least 98% of the homogenous dose with 6-MV X-rays. A lateral distance of 6-7 mm was necessary for 10- and 18-MV X rays. Conclusion: Underdosing will occur in the soft tissues adjacent to low-density inhomogeneities. The magnitude depends primarily on the width of the inhomogeneity seen in the treatment field, but also on field size, depth, and beam energy. For treatment fields with a lateral lung interface, a segment of tissue approximately 3-4 mm thick for 6 MV and 6-7 mm thick for higher-energy beams may be underdosed. Lung widths of ≥1.75 cm as observed on film will generally guarantee doses of at least 96% of those calculated with no inhomogeneity corrections. High-energy beams are often used to treat sites in the thorax or breast to improve dose homogeneity throughout the treatment volume. Potential underdosing due to the presence of lung should be considered and may require a decrease in beam energy or an increase in the margin between the target volume and the field edge to ensure adequate treatment

[en] Late gastrointestinal complications of radiation therapy have been recognized but not extensively studied. In this paper, the late effects of radiation on three gastrointestinal sites, the esophagus, the stomach, and the bowel, are described. Esophageal dysmotility and benign stricture following esophageal irradiation are predominantly a result of damage to the esophageal wall, although mucosal ulcerations also may persist following high-dose radiation. The major late morbidity following gastric irradiation is gastric ulceration caused by mucosal destruction. Late radiation injury to the bowel, which may result in bleeding, frequency, fistula formation, and, particularly in small bowel, obstruction, is caused by damage to the entire thickness of the bowel wall, and predisposing factors have been identified. For each site a description of the pathogenesis, clinical findings, and present management is offered. Simple and reproducible endpoint scales for late toxicity measurement were developed and are presented for each of the three gastrointestinal organs. Factors important in analyzing late complications and future considerations in evaluation and management of radiation-related gastrointestinal injury are discussed

[en] Purpose: There is no consensus in the literature regarding the role of lymphangiography in promoting hypothyroidism in individuals with Hodgkin's disease irradiated with a mantle field. We sought to analyze the onset and rate of developing clinical or chemical hypothyroidism as well as possible factors related to its development in patients who received irradiation to the thyroid gland during treatment of Hodgkin's disease. Methods and Materials: One hundred and forty-two patients with Hodgkin's disease were treated at the Fox Chase Cancer Center between June 1967 and October 1993. All patients were treated with curative intent with radiation therapy using a mantle field. After exclusion of patients without available thyroid function tests, < 200 days of follow-up, or no radiation to the thyroid, 104 patients were eligible for analysis. Follow-up ranged from 7-170 months (median: 43 months). Sixty-seven patients had a lymph angiogram. Seventy-three patients were treated with radiation alone and 31 with radiation plus chemotherapy. Results: The actuarial 2-, and 5-year rates of biochemical hypothyroidism for all 104 patients were 18 and 37%, respectively. Forty patients developed hypothyroidism: 9 (23%) at ≤ 1 year, 18 (45%) at ≤ 2 years, and 33 (83%) at ≤ 5 years. The actuarial 2-, and 5-year rates of biochemical hypothyroidism for patients who underwent a lymph angiogram were 23 and 42%, respectively, compared to 9 and 28%, respectively, for patients who received mantle irradiation without a lymph angiogram (p = 0.05). The effects of lymph angiogram, total thyroid dose, stage, chemotherapy, dose per fraction, energy, and age were evaluated for all patients by Cox proportional hazards regression analysis. The use of a lymph angiogram (p = 0.05) was the only variable that significantly influenced hypothyroidism. Conclusions: This paper demonstrates in a multivariate analysis accounting for other potentially important variables the significant effect of lymphangiography and subsequent radiation therapy on the development of hypothyroidism. This information must be balanced with the fact that lymph angiograms remain a useful aid in assessing lymph node involvement, staging patients, and planning treatment fields