In vitro radiosensitivity and normal tissue damage.
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Humans↗
Biomedical subjects
S L Tucker
Publications and source records attributed to S L Tucker.
Salvage central lymphatic irradiation in follicular lymphomas following failure of chemotherapy: a feasibility study.
PURPOSE: Management of follicular lymphoma after chemotherapy failure has been controversial and has ranged from watchful waiting to high-dose chemotherapy. High-dose chemotherapy with bone marrow reconstitution may produce clinical and molecular complete responses at the risk of serious morbidity and mortality. It has been previously reported that central lymphatic irradiation (CLI) can achieve long-term relapse-free survival in patients with Stage I, II, or III follicular lymphoma. Therefore, we investigated the feasibility of treating patients in whom front-line chemotherapy failed with salvage CLI instead of instituting more intensive chemotherapy. METHODS AND MATERIALS: Salvage CLI with curative intent for patients with follicular lymphoma was started at The University of Texas M. D. Anderson Cancer Center in 1992. Eleven patients whose disease showed poor response to or relapsed after chemotherapy were managed with this approach. The median age of the patients was 61 years. Criteria for exclusion included bone marrow involvement or other evidence of Ann Arbor Stage IV disease at any time during the course of the disease. Overall survival and relapse-free survival were calculated from the first day of CLI. RESULTS: Ten patients were alive at a median follow-up of 25 months (range 9-73 months). The treatment was well tolerated in general. Two patients could not complete CLI: one 75-year-old patient owing to prolonged platelet count depression and deterioration in general medical condition, and a 66-year-old patient because of exacerbation of preexisting pancytopenia and worsening of heart disease. Everyone who completed CLI remains in remission at the time of this report, except for one patient who had a relapse in the right lacrimal gland at 32 months. This patient was treated with local radiation therapy and is free of disease. Eventual recovery of the blood counts was observed for the patients who completed CLI. CONCLUSION: These results demonstrate for the first time that with CLI, it is possible to achieve complete remission of acceptable quality in follicular lymphoma patients who experience a chemotherapy failure. The main toxicity is limited to transient depression in hematological profiles. The treatment is fairly well tolerated and seems to carry little risk compared with high-dose chemotherapy and bone marrow rescue. Salvage CLI may not necessarily compromise future treatment with chemotherapy, including autologous bone marrow or stem cell transplantation, because the patients' blood counts recover.
Aged↗
Numerical chromosomal changes in DNA hypodiploid solid tumors: restricted loss and gain of certain chromosomes.
BACKGROUND: DNA hypodiploidy is a unique and rare finding associated with aggressive behavior in solid tumors. Identifying the chromosomal changes underlying this feature may provide important information on the development and progression of these neoplasms. METHODS: Fluorescence in situ hybridization analysis using alpha-satellite probes for nine autosomes and the two sex chromosomes was performed on interphase cells from 27 solid tumors which had been shown to be DNA hypodiploid by flow cytometry. The chromosomal abnormalities were correlated with the DNA index and tumor subtypes. RESULTS: The data show mutually exclusive loss of certain chromosomes and compensatory gain of other chromosomes in different tumors. The net loss was slightly more than the net gain for the chromosomes tested. Polysomy of chromosome 7 and monosomy of chromosomes 17, X and loss Y were found in most tumors. Significant differential loss of chromosomes 6,10, and 12 among DNA hypodiploid breast, kidney and lung carcinomas was noted. CONCLUSIONS: Our study shows (i) gain of chromosome 7 and loss chromosome 17 in most DNA hypodiploid tumors, (ii) specific chromosomal loss was noted in breast and renal cell carcinomas, and (iii) that different mechanisms for DNA hypodiploid and hyperdiploid development may exist.
Adult↗
Pitfalls in estimating the influence of overall treatment time on local tumor control.
Variations in the overall treatment time of human tumors occur for a number of reasons: differences in standard treatment schedules among centers, occurrence of public holidays during treatment, machine maintenance or breakdown, and decisions made by physicians to change treatment for individual patients based on patient or tumor response. It is now widely accepted that tumor proliferation can occur during treatment, and many efforts have been made to quantify the effects of varying the treatment time. Some of the many problems associated with obtaining quantitative estimates of the time factor are discussed. The aim of this paper is to illustrate that estimates of the time factor for tumor repopulation should be regarded with skepticism and used with extreme caution.
Appointments and Schedules↗
Subdiaphragmatic stage I & II Hodgkin's disease: long-term follow-up and prognostic factors.
PURPOSE: To report long-term follow-up results and to analyze prognostic factors for overall and disease-free survival in patients with subdiaphragmatic Stage I & II Hodgkin's disease. METHODS AND MATERIALS: From September 1962 to April 1995, 109 patients presented at the M. D. Anderson Cancer Center with subdiaphragmatic Hodgkin's disease. The medical records of these patients were retrospectively reviewed; 22 patients who received no treatment at the M. D. Anderson Cancer Center or who had radiation therapy at other institutions were excluded. The remaining 87 patients formed the basis of this study. The median age of our group was 33 years with a male: female ratio of 3.3:1. The histological subtypes were nodular sclerosis in 21 (24.1%) patients, mixed cellularity in 31 (35.6%), lymphocyte predominance in 33 (37.9%), lymphocyte depletion in 1 (1.1%) and unclassified histology in 1 (1.1%). Of the patients, 32 (36.8%) underwent laparotomy for diagnosis or staging purpose, 74 (85.1%) had lymphangiography, and 35 (40.2%) had computerized tomography of the abdomen and pelvis. Among the patients, 22 (25%) had more than three sites of nodal involvement at presentation, 56 (64.4%) had pelvic or abdominal disease, and 14 (18.4%) had bulky disease that was defined as disease with the largest dimension > or = 7 cm. Stage distribution was IA in 33.3%, IIA in 39.1%, and IIB in 27.6%. Treatment was radiotherapy alone in 60 (69%) patients, chemotherapy and radiation in 23 (26.4%), and chemotherapy alone in 4 (4.6%). RESULTS: The 10- and 20-year actuarial overall survival rates for all patients were 74.6% and 55.3%, and the corresponding disease-free survival rates were 72.4% and 67.5%, respectively. On univariate analysis, age > 40 years, B symptoms, nodular sclerosis or mixed cellularity histology, and decreased albumin or hemoglobin levels were statistically significant adverse pretreatment factors for overall survival. B symptoms, decreased albumin level, more than 3 sites of disease at presentation, and Stage II were statistically significant negative pretreatment prognostic factors for disease-free survival. Only B symptoms and decreased albumin level predicted worse outcome in both overall and disease-free survivals. On multivariate analysis, age > 40 years, nodular sclerosis and mixed cellularity histology, and decreased hemoglobin levels were three independent risk factors for overall survival. An analysis of the pattern of failure revealed that the majority of the patients with central Stage II disease who did not receive mantle radiation failed in the supradiaphragmatic area. Late complications of radiation were infrequent. CONCLUSIONS: Long-term follow-up of this group of patients revealed similar overall and disease-free long-term survival, as would be expected from supradiaphragmatic Hodgkin's disease. For patients with central Stage II disease, it is anticipated that supradiaphragmatic radiation therapy would improve the disease-free survival.
Adolescent↗
The prognostic significance of the biomarkers p21WAF1/CIP1, p53, and bcl-2 in laryngeal squamous cell carcinoma.
BACKGROUND: The clinical course of laryngeal squamous cell carcinoma (LSCC) varies considerably among patients. New biologic markers are needed to facilitate the stratification of individual patients within the conventional clinicopathologic stages of LSCC. METHODS: Eighty-three LSCCs from an equal number of patients who received at least 10 years of follow-up were investigated for p53, p21WAF1/CIP1, and bcl-2 protein expression by immunohistochemical techniques. The results were correlated with various clinicopathologic parameters, DNA content, and patient outcome by univariate and multivariate statistical analyses. RESULTS: Stage IV disease, large tumor size (>3 cm), positive lymph node status, extranodal extension, and p53 overexpression (in > 75% of cells) correlated significantly with prognosis in univariate analysis. There was no correlation between patient outcome and age, gender, race, histologic differentiation, or expression of bcl-2 or p21WAF1/CIP1. In multivariate analysis, lymph node status and p53 overexpression were the only factors significantly associated with survival. CONCLUSIONS: High p53 expression and positive lymph node status were independent predictors of the outcomes of patients with LSCC. These factors may assist in prognostication and better classification of patients for treatment.
Adult↗
Factors influencing the development of lung fibrosis after chemoradiation for small cell carcinoma of the lung: evidence for inherent interindividual variation.
PURPOSE: Clinical observations often reveal individual differences in the severity of lung fibrosis after definitive radiation therapy for lung cancer. Recent experimental studies suggest that the risk of developing lung fibrosis may be genetically controlled. The present study was undertaken to examine the magnitude of individual variation in the incidence and severity of lung fibrosis in a well-defined patient population treated by concurrent chemoradiation for limited small-cell lung carcinomas (LSCLC). MATERIALS AND METHODS: Between 1989 and 1994, 56 patients with LSCLC were enrolled in one of two controlled prospective studies of concurrent chemotherapy and concomitant conventional (45 Gy in 25 fractions q.d. over 5 weeks) or accelerated (45 Gy in 30 fractions b.i.d. over 3 weeks) radiotherapy. Chemotherapy consisted of cisplatin and etoposide (PE) or PE plus ifosfamide and mesna (PIE). Of the 56, a group of 25 patients who had serial computerized tomography (CT) examinations of the chest and were deemed to have unequivocal radiographic complete responses were selected for this study. The severity of lung fibrosis was recorded for each patient from the CT images using an arbitrary scale (0 to 3) at 1 year after treatment. Radiographic fibrosis scores were recorded on 1-3 CT slices in 3 different dose-areas (20-30 Gy; 30-40 Gy; and >40 Gy) that were defined using the corresponding CT slices from the patient's CT treatment plan. Of these patients, 23 (92%) had at least 2 slices scored; 11 patients had all 3 slices scored. RESULTS: Among the clinical and treatment parameters investigated (including type of chemotherapy), only total dose and fractionation schedule were identified as significant and independent determinants of lung fibrosis. Radiographic fibrosis scores were higher in high-dose areas and among patients treated with the accelerated schedule. Using a fit of the proportional odds (PO) model based on the total dose and fractionation schedule, fibrosis score residuals were calculated for each patient. The residual for each score is defined as the difference between the observed and expected score based on the dose and treatment schedule received. Average residuals varied significantly among patients (p = 0.005, Kruskal-Willis test). Using a modified version of the PO model, the coefficient of variation in patient heterogeneity was estimated to be 10.1% (95% confidence interval: 6.2-14.9%). Inclusion of the heterogeneity factor, in addition to total dose and fractionation schedule, improved the fit of the PO model to an extremely high level of significance (p < 10(-7)). CONCLUSIONS: Our data indicate that the risk and severity of lung fibrosis analyzed radiographically on CT images increases with total dose and with the use of an accelerated radiation schedule, for patients treated with chemoradiation for small-cell lung cancer. There was also demonstrable patient-to-patient heterogeneity, suggesting that the risk of lung fibrosis is strongly affected by inherent factors that vary among individuals.
Adult↗
Individualization of radiotherapy dose prescriptions by means of an in vitro radiosensitivity assay.
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Humans↗
Stage I Hodgkin disease: radiation therapy and chemotherapy at the University of Texas M. D. Anderson Cancer Center, 1996-1997.
PURPOSE: To summarize 30 years of experience in treatment of and prognosis for stage I Hodgkin disease. MATERIALS AND METHODS: The authors reviewed retrospectively the cases of 196 patients seen and followed up at one institution from 1967 to 1997. All patients were treated with radiation therapy, and 46 also received combination chemotherapy as part of their initial treatment. Radiation therapy techniques included involved or regional-field irradiation in 83 patients, extended field irradiation (mantle or inverted Y) in 74, and subtotal nodal irradiation in 39 (median radiation doses for subclinical and clinical disease were 30 and 40 Gy, respectively, at 1.5-2.0 Gy per fraction). Of 46 patients treated with combination and radiation therapy, 26 received subtotal nodal irradiation; in the remaining 20, chemotherapy was combined with more limited-field radiation therapy. Follow-up ranged from 3 to 356 months (median, 144 months). RESULTS: The actuarial overall survival, disease-specific survival, and freedom from progression at 10 and 20 years were 82% and 66%, 94% and 91%, and 77% and 70%, respectively. In multivariate analysis, age adversely influenced overall survival, and female sex favorably affected freedom from progression. Mixed cellularity histology and mantle field technique adversely influenced disease-specific survival. Laparotomy significantly influenced disease-specific survival but not overall survival. CONCLUSION: Radiation therapy results in an excellent outcome in patients with favorable stage I Hodgkin disease. Pathologic staging is no longer necessary.
Adolescent↗
Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma.
BACKGROUND: Interleukin-6 has important lymphoid bioregulatory effects, and serum levels of interleukin-6 are often elevated in patients with lymphoma. OBJECTIVE: To determine the relation between serum levels of interleukin-6 before treatment and outcome in patients with diffuse large-cell lymphoma. DESIGN: Retrospective cohort analysis with multivariate analysis. SETTING: Tertiary referral center. PARTICIPANTS: 118 untreated patients with diffuse large-cell lymphoma who were enrolled in frontline chemotherapy protocols and 45 healthy controls. MEASUREMENTS: Serum levels of interleukin-6 were measured by using a sensitive enzyme-linked immunosorbent assay. Levels below the upper limit of the range for controls were considered normal. Outcomes were complete response, failure-free survival, and overall survival. RESULTS: Serum levels of interleukin-6 were higher in patients with lymphoma (median, 4.6 pg/ml [range, undetectable to 224 pg/mL]) than in controls (median, undetectable [range, undetectable to 4.3 pg/mL]) (P = 0.009). The complete response rate was 95% for persons with normal interleukin-6 levels and 55% for persons with high interleukin-6 levels (P = 0.001). Patients with high interleukin-6 levels had inferior failure-free and overall survival rates (P < 0.001 for both comparisons). The actuarial 4-year failure-free and overall survival rates were 72% and 85%, respectively, for persons with normal interleukin-6 levels and 37% and 46%, respectively, for persons with high interleukin-6 levels. In multivariate analysis, interleukin-6 was selected as the most significant predictor of complete response and failure-free survival. Failure-free and overall survival of patients stratified according to International Prognostic Index score could be further stratified by interleukin-6 level (P < or = 0.03 for all comparisons). CONCLUSION: In patients with diffuse large-cell lymphoma, serum interleukin-6 levels are an independent prognostic factor for complete response and failure-free survival.
Antineoplastic Combined Chemotherapy Protocols↗
Spatial heterogeneity of the volume effect for radiation pneumonitis in mouse lung.
PURPOSE: In a previous study to determine the effect of partial volume irradiation on damage and morbidity from pneumonitis in mouse lung, a critical determinant of the volume effect was the spatial location of the irradiated subvolume within the lung. The goals of the present study were to (a) define the dose-volume effect curves for radiation pneumonitis in mouse lung, (b) define the threshold volume, and (c) further investigate the spatial heterogeneity of the radiosensitivity of mouse lung. METHODS AND MATERIALS: Eight fractional volumes ranging from 94% to 17% of the lungs of C3Hf/Kam mice were irradiated with single doses ranging from 12 to 22 Gy, depending on the volume irradiated. The fractional volumes irradiated were determined from computed tomographic scans of mouse lung. To determine the effect of location of irradiated subvolume, equivalent volumes in the base and the apex were irradiated by shielding the prescribed adjacent volume in the apex or base respectively. Dose-response curves of breathing rate at 22 weeks and lethality at 28 weeks were constructed for each subvolume irradiated in the apex or base and fitted by logit analysis, and ED50s and LD50s with 95% confidence limits obtained, respectively. Lungs from dead mice or mice sacrificed when moribund were examined for histologic signs of pneumonitis. RESULTS: Irradiation of any of the eight subvolumes in the base yielded a consistently lower isoeffect dose for both assays of radiation pneumonitis than if the same irradiated subvolume was located in the apex. Plots of isoeffect dose for breathing rate as a function of subvolume irradiated in the base or apex showed that these curves were not linear but exhibited a plateau between irradiated volumes of 70% and 80% in both the apex and base. A similar curve was obtained for lethality and volume irradiated in the base. A threshold volume, i.e., irradiation of that volume that should produce no changes in breathing rate or mortality, was dependent on the location of the irradiated subvolume. CONCLUSION: The response of mouse lung to partial volume irradiation is heterogeneous and is critically dependent on the specific location of the irradiated subvolume in the lung, i.e., a given subvolume in the base is consistently more sensitive than the same subvolume in the apex using either breathing rate or lethality as assays of radiation pneumonitis. We suggest that this heterogeneity is due to the anatomy of the tracheobronchial tree, i.e., to the distribution of non-gas exchange-conducting airways in the irradiated volume. These data have implications for the modeling of dose-volume effects in the lung and the prediction of normal tissue complication probabilities for radiation pneumonitis in humans.
Animals↗
Estimation of the spatial distribution of target cells for radiation pneumonitis in mouse lung.
PURPOSE: Recent studies of Liao et al. and Travis et al. have demonstrated that irradiation of cross-sectional partial volumes contiguous to the base of mouse lung produces a higher incidence of pneumonitis than irradiation of equally sized subvolumes contiguous to the apex. One interpretation of this finding is that the critical target cells for pneumonitis are not distributed uniformly throughout the lung. The purpose of the present study was to test this interpretation by obtaining an estimate of the spatial distribution of the critical target cells for pneumonitis in mouse lung, based on the partial-volume data. METHODS AND MATERIALS: A mathematical model was derived describing the probability of radiation pneumonitis as a function of dose, volume of lung irradiated, and location in the lung of the irradiated subvolume. The model includes a nonparametric description of the spatial target-cell distribution in lung, to be estimated from data. The model was fitted to the lethality data of Liao et al. and Travis et al. to obtain estimates of the proportion of target cells contained in each of various subvolumes of the lung. RESULTS: The results indicate that the critical target cells in mouse lung are concentrated in the base and, to a somewhat lesser extent, in the apex of the lung, with fewer cells in the middle region. The estimated spatial distribution of target cells in mouse lung agrees well with the distribution of alveoli, whose concentration in the midlung is limited by the presence of the major conducting airways. CONCLUSION: Heterogeneity in the spatial distribution of critical target cells in normal tissue implies that the complication probability (NTCP) depends on the location in the organ of the irradiated subvolume, as well as on radiation dose and subvolume size. Calculations using an NTCP model for mouse lung indicate that irradiation of equal subvolumes of lung with the same dose can lead to complication probabilities covering the full range from 0 to 100%, depending only on the location in the lung of the irradiated subvolume.
Animals↗
Induction chemotherapy followed by radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma: results of a matched cohort study.
BACKGROUND: Prospective randomized and retrospective studies on adjunctive chemotherapy in patients with advanced locoregional nasopharyngeal carcinoma have yielded conflicting results and the role of chemotherapy in this disease had not been clearly defined. The authors report the results of a single institution, matched cohort study comparing a group of 61 patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy followed by radiation therapy with a matched group treated with radiotherapy alone. METHODS: Between 1985 and 1992, 61 patients with advanced locoregional nasopharyngeal carcinoma received induction chemotherapy (cisplatin, 100 mg/m2 on Day 1 and 5-fluorouracil [5-FU], 1000 mg/m2, on Days 1-5) for 3 cycles followed by definitive radiation therapy (CT/RT group). This group was matched with a group of 61 patients from a population of 378 patients who received radiation therapy alone (RT group). Matching characteristics were T classification, N classification, histology, and level of cervical lymph node metastases. These characteristics were found to be significant determinants of distant metastasis (DM) and/or survival in a multivariate analysis that was performed in the entire radiotherapy group. Radiation therapy consisted of 66-72 gray in 6.5 to 7 weeks in both groups. Fifty-nine patients (97%) in both groups had Stage IV disease. Fifteen patients (25%) in both groups had lower cervical lymph node metastases. The tumor histologic types also had similar distribution in both groups. Median follow-up time among surviving patients of the CT/RT group was 4.9 years (range, 1.3-9.8 years). RESULTS: The 5-year cumulative incidence of DM was 19 +/- 5% for the CT/RT group and 34 +/- 6% for the RT alone group (P = 0.019; log rank test). This reduction in distant failure was more prominent in patients with intermediate (N2-N3 disease; upper or midcervical lymph nodes), or high risk (N2-N3 disease; lower cervical lymph nodes) of DM. This reduction in DM translated into improvement in disease free survival (DFS) and overall survival (OS). The 5-year actuarial DFS rates were 64 +/- 6% for the CT/RT group compared with 42 +/- 7% for the RT group (P = 0.015). The 5-year actuarial OS rates were 69 +/- 6% (CT/RT group) and 48 +/- 7% (RT group), respectively (P = 0.012). The incidence of locoregional failure was slightly lower in the CT/RT group, but this difference did not reach statistical significance. There was no significant difference in the incidence and severity of acute mucositis between the two groups during radiotherapy. The 5-year cumulative incidence of Grade 3 or higher late complications was also similar in both groups (5 +/- 3% in the CT/RT group and 8 +/- 3% in the RT group; P = 0.721). CONCLUSIONS: This matched cohort study provides additional evidence that induction cisplatin-5-FU chemotherapy prior to definitive radiation improves freedom from distant metastasis, DFS, and OS for patients with locoregional Stage IV nasopharyngeal carcinoma without increasing treatment-related morbidity.
Adolescent↗
Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local and regional control.
PURPOSE: This retrospective study was conducted to review the results of treatment and to identify prognostic factors for local and regional control in a population of 378 patients with nasopharyngeal carcinomas treated in a single institution by radiation therapy alone. METHODS AND MATERIAL: All patients were treated at The University of Texas M. D. Anderson Cancer Center between 1954 and 1992 following a consistent treatment philosophy but with evolving technique. There were 286 males and 92 females with a median age of 52 years (range: 16-86 years). The majority of the patients were Caucasian (282 patients, 75%). Thirty-two patients (8%) had one or more cranial nerve deficits. Three-fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3 164 patients). Histologically, 193 tumors (51%) were squamous cell carcinomas, 154 (41%) lymphoepitheliomas, and 31 (8%) unclassified carcinomas. Average total dose varied with T-stage and ranged from 60.2 to 72.0 Gy. Median follow-up time was 10 years. RESULTS: For the entire population the 5-, 10-, and 20-year actuarial survival rates were 48, 34, and 18%, respectively, with 184 patients (49%) dying of nasopharyngeal cancer. Actuarial control rates at 5, 10, and 20 years were 71, 66, and 66% for the primary site and 84, 83, and 83% for the neck. A total of 100 patients (26%) had local failures and 51 patients (13%) had regional failures with a median time to recurrence of 8.2 months and 13 months, respectively. Advanced T-stage, squamous histology, and presence of cranial nerve deficits were poor prognostic factors for local control in both univariate and multivariate analyses. N-stage and tumor histology were significant factors for neck control. Treatment year, total dose within the ranges used, and duration of treatment did not have any significant effect on local or regional control. The actuarial incidence of Grade 3-5 late complications was 16, 19, and 29% at 5, 10, and 20 years, respectively. Twelve patients (3%) died of treatment-related complications; all but one fatal complication occurred before 1971 and the other in 1976. CONCLUSIONS: This study shows very good long-term local and regional control rates for nasopharyngeal carcinomas after definitive radiotherapy and establishes a benchmark for newer treatment strategies. Improvements in treatment technique over the years have dramatically reduced the frequency of severe late complications. Patients with advanced stage tumors and differentiated squamous histology have a relatively poor prognosis when treated with conventional radiotherapy and are candidates for dose escalation or combined modality studies.
Adolescent↗
Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer.
BACKGROUND: The value of these prognostic factors was compared with that of other clinicopathologic factors such as tumor grade, tumor stage, mucin production, vascular invasion, perineural invasion, and lymphatic invasion. OBJECTIVE: To determine whether the development of distant recurrence in patients with node-negative colon cancer could be predicted using vessel count and vascular endothelial growth factor (VEGF) expression. DESIGN: Paraffin-embedded colon cancers were immunostained for factor VIII, VEGF, basic fibroblast growth factor, and proliferating cell nuclear antigen; slides were reviewed for differentiation, mucin production, and the presence of vascular, lymphatic, and/or perineural invasion. SETTING: A large academic cancer referral center where 27 patients with node-negative colon cancer were operated on during 1988 and 1989. MAIN OUTCOME MEASURE: The development of and interval to recurrence. RESULTS: Eight patients developed liver, lung, or lymph node metastases at a median of 24 months. The median follow-up for patients without cancer recurrence was 60 months. The mean tumor vessel count for those patients who remained disease-free was significantly fewer than for those patients who suffered a recurrence (20 vs 33, respectively). By univariate analysis, 3 factors- perineural invasion, vessel count, and VEGF expression- were correlated with time to recurrence. By multivariate analysis, only vessel count was significantly related to differences in time to recurrence. Expression of VEGF correlated with vessel count. CONCLUSION: Vessel count and expression of VEGF may be useful for predicting distant recurrence in patients with node-negative colon cancer.
Adult↗
Chromosomal and DNA ploidy characterization of salivary gland neoplasms by combined FISH and flow cytometry.
Concurrent DNA ploidy by flow cytometry and interphase FISH analysis of chromosomes 6 through 12, 17, 18, X, and Y were prospectively performed on 22 salivary gland neoplasms (four benign and 18 malignant) to investigate the diagnostic and biological implications of their alterations in these neoplasms. Our results show that benign neoplasms lack DNA aneuploidy and numerical chromosomal abnormalities. Low-grade malignant neoplasms, except for two lesions, manifested small chromosomal gains and losses and were generally DNA diploid or near-diploid aneuploid, whereas all high-grade tumors showed marked polysomy and were DNA aneuploid. Marked intratumoral and intertumoral chromosomal heterogeneity also were noted in and between individual tumors. Although polysomy was the main finding in DNA aneuploid lesions, monosomy was more noted in DNA diploid neoplasms and was restricted to chromosomes 8, 11, and 17. Significant correlation between the DNA index, chromosomal aneusomy, histological grade, and tumor stage was noted. Our study indicates that (1) benign salivary gland neoplasms lack gross DNA content and numerical chromosomal abnormalities, (2) clonal chromosomal alterations are manifested in most DNA diploid and all DNA aneuploid malignant tumors, (3) chromosomal gain is the most common alteration; chromosomal loss is less frequent and restricted to certain chromosomes, and (4) DNA aneuploidy and chromosomal aneusomy characterize tumors with aggressive features.
Adult↗
Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival.
PURPOSE: This retrospective study was conducted to identify the prognostic factors for distant metastasis and survival in a population of 378 patients with nasopharyngeal carcinomas treated by radiation therapy alone. MATERIALS AND METHODS: All patients were treated at the University of Texas M.D. Anderson Cancer Center between 1954 and 1992, following a consistent dose and volume prescription policy. There were 286 males and 92 females. The median age was 52 years (range: 16-86 years). The majority of the patients were white Caucasians (282 patients,75%). Tumors were classified as squamous cell carcinomas (193; 51%), lymphoepitheliomas (154; 41%), or unclassified carcinomas (31, 8%). Three fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3 164 patients). The treatment techniques included opposed lateral fields with or without an anteroposterior or an anterior oblique pairs for dose supplementation to the primary site. Average total doses per T-stage ranged between 60.2 and 72.0 Gy. Median follow-up time was 10 years (range 0.3 to 28.6 years). RESULTS: A total of 103 patients (27%) developed distant metastases at a median time of 8 months (range: 1-90 months). Actuarial rates for distant metastasis were 30%, 32%, 32% at 5, 10, and 20 years, respectively. Actuarial rates for disease specific survival at the same time points were 53%, 45%, and 39% with 184 patients (49%) dying of their nasopharyngeal cancer. Advanced T-stage, N-stage, and non-lymphoepithelioma histology were independent adverse prognostic factors for disease specific survival. Advanced N-stage and low neck disease were independent adverse prognostic factors for distant metastasis with a very high rate of distant metastases for those patients who presented with both adverse factors (relative risk 7.86). On average, patients with distant metastasis lived 5 months after they were diagnosed with metastatic disease (range: 0-172 months), although four patients (4%) survived more than 5 years after diagnosis. CONCLUSIONS: This study demonstrates good long term survival rates after definitive radiotherapy for patients with nasopharyngeal carcinomas. Patients with advanced and lower neck disease have the highest risk of developing distant failures. Such patients can be considered the reference risk group to test the value of adjunctive chemotherapy.
Adolescent↗
Quantifying the position and steepness of radiation dose-response curves.
Radiation dose-response curves are of fundamental importance both in practical radiotherapy and as the basis of more theoretical considerations concerning the potential benefit to be gained from modified dose-fractionation schedules or of the effects of dosimetric and biological variability. The steepness of the dose-response curve is a key parameter and quantitative measures of steepness derived from clinical data are strongly needed. Unfortunately, there are many ambiguities associated with quantifying the steepness of radiation dose-response curves and these are identified and discussed in the present paper. The following problems are reviewed. (1) In the literature, various descriptors of 'steepness' are reported. We focus on the normalized dose-response gradient, gamma, and the dose-response slope, theta. The mathematical properties and the relationship between these are discussed. (2) Steepness estimates depend on the mathematical model used to describe the dose response relationship. Three standard formulations are considered: the Poisson, the logistic and the probit dose-response model. The magnitude of the model dependence is influenced by the range of the empirical dose-response data available, and is most pronounced for data concentrated around very low or very high response levels. (3) Reparametrizations of the standard models in terms of position and steepness are given, and it is pointed out that some previously published formulas are only approximations. (4) The method of analysis can influence the steepness estimate. An analysis of a specific data set shows that the use of the least-squares method rather than the preferred maximum likelihood method may influence both the steepness estimate and its confidence interval. (5) Dose-response data generated with a fixed number of fractions rather than a fixed dose per fraction will produce steeper dose-response curves. The approximation involved in describing such a set of dose-response data by a position and a single steepness parameter is discussed. (6) The importance of specifying the statistical uncertainty of the steepness estimate is stressed. All of these problems are illustrated by a practical example, in which dose-response data from the literature are re-analysed.
Dose-Response Relationship, Radiation↗