Biomedical subjects

S L Tucker

Publications and source records attributed to S L Tucker.

At least 19 recordsLinked to original sources

PubMed2003

Nucleotide excision repair proteins and their importance for radiation-enhanced transfection.

PURPOSE: Irradiated cells transfect more efficiently than unirradiated cells because of a radiation-induced increase in plasmid integration. However, the molecular mechanism is unclear. Because of recent observations that nucleotide excision repair (NER) proteins can be involved in certain types of recombination in yeast, it was hypothesized that NER proteins might play a role in this radiation-enhanced integration. MATERIALS AND METHODS: Hamster and human cells with inactivating mutations in NER genes were irradiated at doses from 0 to 6 Gy and then immediately transfected with a linearized selectable marker plasmid. Transfection-enhancement ratios (TERs) were calculated as the ratio of the number of drug-resistant colonies in unirradiated cells to the number of transfectants in irradiated cells, corrected for cytotoxicity from radiation. RESULTS: Transfection into unirradiated rodent cells was unaffected by NER mutation status. Transfection into unirradiated human cells, however, was increased by NER mutation. The TERs were 5 and 100 for CHO and primary human fibroblasts, respectively, after exposure of the cells to 6 Gy. Mutations in ERCC1, XPA, XPB, XPC, XPF, XPG and CSB dramatically reduced TER. Mutations in ERCC1, XPC, XPF, XPG and CSB suppressed transfection so that the TER was significantly below 1. CONCLUSIONS: The mechanism of radiation-enhanced plasmid integration was distinct from that of plasmid integration in unirradiated cells, and NER gene products were critical for enhanced integration to occur.

Animals↗

PubMed2001

Long-term results with radiotherapy for Stage I-II follicular lymphomas.

PURPOSE: To analyze the long-term results with radiotherapy (RT) for early-stage, low-grade follicular lymphomas. METHODS AND MATERIALS: From 1960 to 1988, 80 patients with Stage I (n = 33) or II (n = 47), World Health Organization Grade 1 (n = 50) or 2 (n = 30) follicular lymphoma were treated with RT. The lymph nodes or spleen were involved in 97% of cases. The maximal tumor sizes ranged from 0.5 to 11.0 cm (median 2.0). The RT fields encompassed only the involved Ann Arbor nodal region (involved-field RT) in 9% of the patients. The fields also included 1-3 adjacent, grossly uninvolved nodal regions (regional RT) in 54% of patients but were smaller than mantle or whole abdominopelvic fields. Mantle or whole abdominopelvic fields encompassing up to 6 grossly uninvolved regions (extended-field RT) were used in the remaining 37% of patients. The total RT doses ranged from 26.2 to 50.0 Gy given in daily 1.0-3.0-Gy fractions. RESULTS: The follow-up of the surviving patients ranged from 3.5 to 28.7 years (median 19.0). No recurrences were found >17.0 years after RT, with 13 patients free of disease at their last follow-up visit 17.6-25.0 years after treatment. In 58% of cases, death was not from follicular lymphoma. The 15-year local control rate was 100% for 44 lymphomas <3.0 cm treated with only 27.8-30.8 Gy (median 30.0 in 20 fractions). Progression-free survival was affected by the maximal tumor size at the start of RT (15-year rate 49% vs. 29% for lymphomas <3.0 cm vs. > or =3.0 cm, respectively, p = 0.04) and Ann Arbor stage (15-year rate 66% vs. 26% for Stages I and II, respectively, p = 0.006). Ann Arbor stage also affected the cause-specific survival (15-year rate 87% vs. 54% for Stages I and II, respectively, p = 0.01). No significant difference was found in overall survival between those treated with extended-field RT and those treated with involved-field RT or regional RT (15-year rate 49% and 40%, respectively, p = 0.51). The 15-year incidence rate of Grade 3 or greater late complications according to the Subjective, Objective, Management, and Analytical scale in patients treated with 26.2-30.8 Gy vs. 30.9-50.0 Gy was 0% and 6%, respectively. CONCLUSIONS: RT can cure approximately one half of Stage I and one quarter of Stage II, World Health Organization Grade 1 or 2 follicular lymphomas. Follicular lymphomas <3.0 cm can be controlled locally with doses of 27.8-30.8 Gy, and there is a trend toward a higher incidence of late complications with doses of >30.8 Gy. Doses of 25-30 Gy delivered in 15-20 fractions should be examined prospectively in patients with follicular lymphomas of <3.0 cm.

Disease-Free Survival↗

PubMed2001

Comparison of two total body irradiation fractionation regimens with respect to acute and late pulmonary toxicity.

BACKGROUND: Total body irradiation (TBI) is commonly used with autologous bone marrow transplantation (BMT) for treatment of hematologic malignancies. Pulmonary complications of TBI can cause long-term morbidity and mortality. The authors have compared the pulmonary toxicity and efficacy of two different TBI fractionation regimens in otherwise identical autologous BMT protocols. METHODS: Between 1990 and 1997 patients younger than 60 years of age with low-grade lymphoma at high risk of treatment failure were enrolled on one of two sequential protocols for autologous BMT differing only in their TBI regimens. The preoperative chemotherapy regimens were identical and consisted of intravenous etoposide (1500 mg/m(2)) for 1 day, intravenous cyclophosphamide (60 mg/kg) for 2 days, and mesna (10 mg/kg). The TBI used in protocol A consisted of twice-daily fractions of 1.7 grays (Gy) for 3 days to a total of 10.2 Gy through lateral fields, with no lung shielding. In protocol B, the TBI consisted of 3 Gy once daily for 4 days to a total of 12 Gy through anteroposterior fields, with lung shielding (5 half-value layers) during the third dose. Fifty-eight patients were treated on protocol A and 24 on protocol B. The groups were equivalent with regard to age, performance status (PS) and gender. Lung function was assessed objectively by pulmonary function tests (PFTs) before and at intervals after TBI. The pulmonary function parameters assessed included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)), diffusing capacity for carbon monoxide (DL(CO)), and total lung capacity (TLC). Each patient's post-TBI PFTs were normalized to the corresponding pre-TBI values and analyzed using a random effects model. Clinical pulmonary function status was scored according to Radiation Therapy Oncology Group criteria for acute and late lung toxicity. All clinical pulmonary toxicities such as pneumonitis, pneumonia, and diffuse alveolar hemorrhage, whether specifically related to TBI or not, were scored. Toxicity was classified as either acute (i.e., occurring within 90 days of TBI) or late (i.e., occurring more than 90 days after TBI). The endpoints of analysis were overall survival (OS), freedom from progression, and chronic pulmonary toxicity. Survival, progression, and complication free survival were computed using the method of Kaplan and Meier. RESULTS: Three-year actuarial OS rates were 66% and 67% for protocols A and B, respectively. Patients 50 years of age or older had a hazard ratio of death 3.5 times higher than younger patients. Freedom from progression was significantly different for the 2 TBI regimens (P < 0.001; log-rank test): 31% at 3 years in the protocol A group compared with 82% in protocol B group. Patients on protocol A had a rate of progression 4.7 times higher than patients on protocol B. The TBI protocols did not differ significantly in their effects on FVC, FEV(1), FEF(25-75), DL(CO), and TLC. Patients 45 years of age or older had lower average posttransplant values of FEV(1), FVC, and DL(CO) than younger patients. There was no significant difference in acute or late toxicity rates between patients on the two protocols. Seven of the 57 patients in the twice-daily TBI (protocol A) group had acute pulmonary events (Grade 3 or greater), compared with 6 of the 24 patients in the once-daily (protocol B) group (P = 0.19). The 3-year freedom from late complications rate was 80% in the protocol A group and 70% in the protocol B group (P = 0.45). Patients with a PS of 1 had a hazard ratio of late complications 3.2 times greater than patients with a PS of 0 (P < 0.001). CONCLUSIONS: It is possible to intensify TBI from a total dose of 10.2 Gy delivered in 6 twice-daily fractions to 12 Gy delivered in 4 once-daily fractions without significantly increasing the risk of pulmonary toxicity. The increased dose may contribute to a decrease in the recurrence rate in these patients. (c) 2001 American Cancer Society.

Adult↗

PubMed2001

Hematologic recovery after central lymphatic irradiation for patients with stage I-III follicular lymphoma.

BACKGROUND: The authors previously reported that central lymphatic irradiation (CLI) can induce molecular remission in patients with Stage I-III follicular lymphoma, as measured by polymerase chain reaction analysis for t(14;18) (q32;q21). Hematologic toxicity has been considered a major consequence of CLI. This study was undertaken to analyze the patterns of hematologic recovery after CLI. METHODS: Thirty-three patients with Stage I-III follicular lymphoma were treated with CLI between January 1993 and February 1998. CLI consisted of irradiation to mantle, upper two-thirds of abdomen, and pelvic fields. Each field was treated to 30.0-30.6 grays (Gy) at 1.5-1.8 Gy per fraction, with a boost to 36.0-39.6 Gy at the same rate to the sites of macroscopic disease. A break of approximately 4 weeks was given after treatment of each field. Twenty-four patients who were followed for a minimum of 1 year from the end of CLI form the basis of this analysis. Fourteen patients were male. Three patients had Stage I disease, 6 patients had Stage II disease, and 15 patients had Stage III disease. The International Prognostic Index (IPI) for malignant lymphoma was 0 for 5 patients, 1 for 13 patients, and 2 for 6 patients. The Eastern Cooperative Oncology Group performance status was 0 for 21 patients and 1 for 3 patients. The median values for their pretreatment characteristics were as follows: age, 60 years (range, 34-73 years); height, 173 cm (range, 155-193 cm); weight, 79 kg (range, 57-107 kg); body surface area (BSA), 1.95 m(2) (range, 1.61-2.31 m(2)); bone marrow cellularity, 27%(range, 2-75%), platelet count, 233,000/mm(3) (range, 139,000-339,000/mm(3)), white blood cell (WBC) counts, 6400/mm(3) (range, 4200-10,900/mm(3)); and hemoglobin, 14.5 mg/dL (range, 11.8 -16.6 mg/dL). The median duration of CLI was 159 days (range, 137-345 days). Ten patients had cardiovascular disease. The number of sites receiving a boost dose of > or = 36.0 Gy was 0 sites in 1 patient, 1 site in 6 patients, 2 sites in 11 patients, 3 sites in 5 patients, and 4 sites in 1 patient. The platelet, hemoglobin, and WBC counts were followed every 3 months after completion of CLI. These counts were normalized to the pretreatment counts for statistical analyses. Univariate and multivariate analyses were performed to investigate the correlations between patient factors and hematologic status at 1 year posttreatment. Pearson correlation analysis was used for the continuous factors (patient age, height, weight, BSA, bone marrow cellularity, and duration of CLI), and the Mann-Whitney test was used for categoric factors (IPI, gender, performance status, stage, number of sites receiving > or = 36.0 Gy, and presence or absence of cardiovascular disease). RESULTS: There was continued recovery, essentially approaching the pretreatment levels, over 3 years for platelet, WBC, and hemoglobin counts. Factors that were associated significantly with normalized platelet counts at 1 year by univariate analyses were age (P = 0.015) and cardiovascular disease (P = 0.041). Age was the only significant factor by multivariate analyses, with older patients having lower platelet counts at 1 year posttreatment. No factors were found that were associated significantly with 1-year normalized WBC or hemoglobin levels by either univariate or multivariate analyses. CONCLUSIONS: All three of the hematologic components (platelets, WBC, and hemoglobin) essentially recover after patients undergo CLI over a 3-year period. Older age was the only significant adverse factor that affected the platelet recovery, as detected by multivariate analysis. (c) 2001 American Cancer Society.

Adult↗

PubMed2001

Extent and kinetics of recovery of occult spinal cord injury.

PURPOSE: To obtain clinically useful quantitative data on the extent and kinetics of recovery of occult radiation injury in primate spinal cord, after a commonly administered elective radiation dose of 44 Gy, given in about 2 Gy per fraction. METHODS AND MATERIALS: A group of 56 rhesus monkeys was assigned to receive two radiation courses to the cervical and upper thoracic spinal cord, given in 2.2 Gy per fraction. The dose of the initial course was 44 Gy in all monkeys. Reirradiation dose was 57.2 Gy, given after 1-year (n = 16) or 2-year (n = 20) intervals, or 66 Gy, given after 2-year (n = 4) or 3-year (n = 14) intervals. Two animals developed intramedullary tumors before reirradiation and, therefore, did not receive a second course. The study endpoint was myeloparesis, manifesting predominantly as lower extremity weakness and decrease in balance, occurring within 2.5 years after reirradiation, complemented by histologic examination of the spinal cord. The data obtained were analyzed along with data from a previous study addressing single-course tolerance, and data from a preliminary study of reirradiation tolerance. RESULTS: Only 4 of 45 monkeys completing the required observation period (2-2.5 years after reirradiation, 3-5.5 years total) developed myeloparesis. The data revealed a substantial recovery of occult injury induced by 44 Gy within the first year, and suggested additional recovery between 1 and 3 years. Fitting the data with a model, assuming that all (single course and reirradiation) dose-response curves were parallel, yielded recovery estimates of 33.6 Gy (76%), 37.6 Gy (85%), and 44.6 Gy (101%) of the initial dose, after 1, 2, and 3 years, respectively, at the 5% incidence (D(5)) level. The most conservative estimate, using a model in which it was assumed that there was no recovery between 1 and 3 years following initial irradiation and that the combined reirradiation curve was not necessarily parallel to the single-course curve, still showed an overall recovery equivalent to 26.8 Gy (61%). The spinal cords of symptomatic monkeys consistently revealed a mixture of white matter necrosis and vascular injury, but the majority of spinal cords of asymptomatic animals did not exhibit overt lesions detectable by light microscopy. CONCLUSION: Combined analysis with the data of the previous studies yielded firm evidence that the spinal cord has a large capacity to recover from occult radiation injury induced by a commonly prescribed elective dose. This finding strengthens the rationale for selective use of radiotherapy to treat second primary tumors arising in previously irradiated tissues or late recurrences. However, some caution should be exercised in applying quantitative experimental data, because the length of follow-up in these experiments was limited to 2-2.5 years after reirradiation, whereas human myelopathy cases occasionally occur after longer latency. Because there is a large variation in long-term recovery among tissues, the tolerance of other tissues at risk should also be taken into account in prescribing therapy.

Animals↗

PubMed2001

Radiation therapy after a partial response to CHOP chemotherapy for aggressive lymphomas.

PURPOSE: To analyze the results with involved-field radiotherapy after aggressive lymphomas had decreased in size by 50-99% in response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. METHODS AND MATERIALS: From 1988 through 1996, 294 previously untreated patients with Working Formulation intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these patients achieved, based on international working group guidelines, a partial (50-75%) response (n = 25), or unconfirmed complete (76-99%) response (n = 19) to a median of 6 cycles of chemotherapy. These patients were treated with salvage involved-field radiotherapy (n = 32) or chemotherapy (n = 12), e.g., MINE-ESHAP, without autologous stem-cell rescue (ASCR). RESULTS: Median follow-up was 43 months. Partial responders experienced similar outcomes to unconfirmed complete responders. Local control (4-year rates: 86% vs. 53%, p = 0.009) and progression-free survival (4-year rates: 67% vs. 8%, p < 0.0001), but not overall survival (4-year rates: 70% vs. 50%, p = 0.067) were significantly better in those who received salvage radiotherapy, which was well tolerated. CONCLUSION: Progression-free and overall survival in aggressive lymphoma patients who underwent salvage radiotherapy were similar to results reported for high-dose chemotherapy with ASCR. The role of salvage radiotherapy in partial and unconfirmed complete responders to CHOP chemotherapy justifies examination in a large, cooperative group trial.

Adolescent↗

PubMed2001

DNA image analysis combined with routine cytology improves diagnostic sensitivity of common bile duct brushing.

BACKGROUND: Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS: Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of > or = 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical fol- low-up. RESULTS: Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, BD in 9 cases, and A in 16 cases. BD and A patterns were significantly associated with malignancy (P < 0.001). A DH > or = 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH > or = 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > or = 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS: Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted.

Adult↗

PubMed2001

BCR rearrangement-negative chronic myelogenous leukemia revisited.

PURPOSE: To document the characteristics of patients with major breakpoint cluster region (M-bcr) rearrangement-negative chronic myelogenous leukemia (CML). PATIENTS AND METHODS: The hematopathologist, who was blinded to patients' molecular status, reviewed the referral bone marrows and peripheral-blood smears from 26 patients with Philadelphia (Ph) translocation-negative CML who lacked Bcr rearrangement (and other evidence of a Bcr-Abl anomaly) and 14 patients (controls) with chronic-phase Ph-positive CML. Clinical data was ascertained by chart review. RESULTS: Among the 26 M-bcr rearrangement-negative CML patients, three pathologic subtypes emerged: (1) patients indistinguishable from classic CML (n = 9), (2) patients with atypical CML (n = 8), and (3) patients with chronic neutrophilic leukemia (n = 9). Among the 14 patients with Ph-positive CML who were included in the blinded review, 13 were classified as classic CML, and one was classified as atypical CML. The only statistically significant difference between M-bcr rearrangement-negative subgroups was in the proportion of patients having karyotypic abnormalities, an observation common only in patients with atypical CML (P = 0.008). However, the small number of patients in each subgroup limited our ability to differentiate between them. Interferon alfa induced complete hematologic remission in five of 14 patients; four of these remissions lasted more than 5 years. Only one of 26 patients developed blast crisis. The median survival of the 26 patients was 37 months. CONCLUSION: Patients with M-bcr rearrangement-negative CML fall into three morphologic subgroups. Disease evolution does not generally involve blastic transformation. Instead, patients show progressive organomegaly, leukocytosis, anemia, and thrombocytosis. Some patients in each subgroup can respond to interferon alfa.

Adult↗

PubMed2001

Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy.

PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control for breast cancer patients treated with breast-conservation therapy. PATIENTS AND METHODS: The data from 484 breast cancer patients who were treated with breast-conserving surgery and radiation were analyzed. Only patients with lymph node-negative disease were studied to provide comparative groups with a similar stage of disease and a similar competing risk for distant metastases. Actuarial local control rates of the 277 patients treated with systemic therapy (128, chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with the rates for the 207 patients who received no systemic treatment. Only 10% of the patients had positive (2%), close (3%), or unknown margin status (5%). RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v 89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that did not receive systemic treatment (P =.004, log-rank test). There was no statistical difference in local control between patients treated with chemotherapy and patients treated with tamoxifen alone (P =.219). Systemic treatment, margin status, young patient age, estrogen and progesterone receptor status, and primary tumor size were analyzed in a Cox regression analysis. The use of systemic treatment was the most powerful predictor of local control: patients who did not receive systemic treatment had a relative risk of local recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P =.004). CONCLUSION: In this retrospective analysis, systemic therapy appears to contribute to long-term local control in patients with lymph node-negative breast cancer treated with breast-conservation therapy.

Adult↗

PubMed2001

The significance of molecular response of follicular lymphoma to central lymphatic irradiation as measured by polymerase chain reaction for t(14;18)(q32;q21).

BACKGROUND: More than 80% of the patients with follicular lymphoma have a characteristic chromosomal translocation, t(14;18)(q32;q21), at the major breakpoint region (MBR) or minor cluster region (MCR) involving the bcl-2 oncogene. This study was undertaken to assess the significance of the molecular response rate measured by the polymerase chain reaction (PCR) evidence of translocation among patients with Stage I to III follicular lymphoma treated with central lymphatic irradiation (CLI). METHODS AND MATERIALS: Thirty-three patients with Stage I-III follicular lymphoma were treated with CLI on a prospective protocol. Bone marrow and peripheral blood samples were obtained before CLI for PCR analysis of t(14;18)(q32; q21). PCR-positive patients were followed by PCR analysis at regular intervals during and after CLI, and the results were correlated with clinical outcome. The following pretreatment factors were also investigated for their relationship to relapse and molecular response: gender, age, lactate dehydrogenase (LDH) and beta-2 microglobulin (beta2M) levels, Ann Arbor stage, and International Prognostic Index (IPI) for malignant lymphoma. RESULTS: The subjects were 19 men and 14 women, with a median age of 52 years (range 30-69), who started CLI between January 1993 and February 1998. Median follow-up was 44 months (range 12-67), and all but 2 patients were still alive at the last follow-up. Four patients were Stage IA, 8 were Stage IIA, 19 were Stage IIIA, and 2 were Stage IIIB. Two patients had abnormal LDH levels (> 618 U/dL) and 7 patients had abnormal beta2M levels (> 2 mg/dL). Nine patients had IPI = 0, 16 had IPI = 1, and 8 had IPI = 2. All patients achieved complete response (CR). Twelve patients have relapsed to date. The median overall time to relapse was 54 months. The actuarial proportion of patients free from relapse at 3 years was 87% (95% confidence interval [CI] 69-95%). A total of 287 PCR results were available, 64 from bone marrow and 223 from peripheral blood. Pretreatment PCR data were available for 27 patients, of whom 21 were positive and 3 were unambiguously negative (in blood and bone marrow for both MBR and MCR). For the 19 PCR positive patients for whom we had post-treatment results, there was a clear and steady decreasing trend toward loss of PCR positivity (49% positive for bone marrow and 32% positive for peripheral blood at 3 years). There was a clear trend for increasing PCR positivity with increasing IPI: 10% for IPI = 0, 31% for IPI = 1, and 63% for IPI = 2 at 3 years for blood. The same trend was also observed for bone marrow. The IPI was the only statistically significant predictor for relapse with a relapse-free survival of 91% at 3 years for IPI < 2 and 75% for IPI = 2 (p = 0.024, log-rank test). CONCLUSION: Molecular response to CLI occurs gradually over years. High IPI is a negative predictor for molecular response and relapse-free survival.

Adult↗

PubMed2001

Dose-response analysis for radiotherapy delivered to patients with intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to CHOP-based induction chemotherapy.

PURPOSE: To test the hypothesis that prechemotherapy tumor size affects the dose of radiation that should be delivered to intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-based induction chemotherapy. METHODS AND MATERIALS: From September 1988 through December 1996, 294 patients with newly diagnosed, Stage I-IV, intermediate-grade or large-cell immunoblastic lymphomas were enrolled on 2 prospective protocols at the M. D. Anderson Cancer Center. Treatment consisted of CHOP-based chemotherapy with or without involved field radiotherapy. One hundred seventy-two patients, with 178 nodal sites and 87 nonbony, extranodal sites of disease achieved a complete response to 2-6 cycles of chemotherapy and underwent involved field radiotherapy. Total radiation doses ranged from 30.0 to 50.4 Gy (mean +/- standard deviation: 39.7 +/- 2.5 Gy) over 22-49 days using a daily fraction size of 1.3-2.3 Gy. Because various fraction sizes were delivered, the linear-quadratic model was used to convert total radiation doses to biologically equivalent doses given at 1.8 Gy per fraction (D1.8). An alpha/beta ratio of 10 Gy was used for the lymphomas, resulting in D1.8 ranging from 29.1 to 50.8 Gy. Regression tree analysis was performed on nodal sites of disease to determine which of the following factors were predictive of local control: age, tumor size, D1.8, total radiation dose, and duration of radiotherapy. Based on the results of the regression tree analysis, Kaplan-Meier analysis was used to determine the probability of local control per site as a function of tumor size and D1.8. Regression tree analysis was also performed on patients with nonbony disease who received D1.8 = 29.1-39.1 Gy to determine if small lymphomas could be locally controlled with relatively low doses of radiation. The log-rank test was used to compare local control curves. RESULTS: The median length of follow-up among survivors was 63 months. Regression tree analysis of nodal sites identified 3 distinct groups: (a) lymphomas < or = 10 cm and D1.8 = 29.1-39.1 Gy; (b) lymphomas < or = 10 cm and D1.8 = 39.2-50.8 Gy; and (c) lymphomas > 10 cm. For nonbony lymphomas that measured < 3.5 cm, low doses of radiation resulted in excellent local control (5-year rates: 96% vs. 97% for D1.8 = 29.1-39.1 Gy vs. D1.8 = 39.2-50.8 Gy; p = 0.610). For 3.5-10.0 cm lymphomas, higher doses of radiation resulted in better local control (5-year rates: 40% versus 98% for D1.8 = 29.1-39.1 Gy versus D1.8 = 39.2-50.8 Gy, p < 0.0001). A narrow dose range (D1.8 = 39.2-40.7 Gy) was delivered to the 8 lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, resulting in a 5-year local control rate of only 70%. There was no difference in local control for nodal versus nonbony, extranodal sites of disease. CONCLUSION: D1.8 ranging from 29.1 to 39.1 Gy yielded excellent local control for nonbony lymphomas measuring < 3.5 cm that had completely responded to a median of 3 cycles of CHOP-based chemotherapy. D1.8 ranging from 39.2 to 50.8 Gy yielded excellent local control for nonbony lymphomas measuring 3.5-10.0 cm that completely responded to either 3 or 6 cycles of chemotherapy. For nonbony lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, D1.8 ranging from 39.2 to 40.7 Gy yielded suboptimal local control, suggesting that higher doses of radiation are indicated.

Adolescent↗

PubMed2001

Genetic heterogeneity in saliva from patients with oral squamous carcinomas: implications in molecular diagnosis and screening.

We performed microsatellite analysis at chromosomal regions frequently altered in head and neck squamous carcinoma on matched saliva and tumor samples from 37 patients who had oral squamous carcinoma. The results were correlated with the cytologic findings and traditional clinicopathologic factors to assess the diagnostic and biological potential of these markers. Our data showed that 18 (49%) of the saliva samples and 32 (86%) of the tumors had loss of heterozygosity (LOH) in at least one of the 25 markers studied. In saliva, the combination of markers D3S1234, D9S156, and D17S799 identified 13 (72.2%) of the 18 patients with LOH in saliva (P < 0.001). For tumors, markers D3S1234, D8S254, and D9S171 together identified 27 (84.3%) of the 32 tumors with LOH at any of the loci tested (P < 0.001). Eleven (55%) of the 20 saliva samples with cytologic atypia and seven (35%) of the 17 specimens without atypia had LOH. Significant correlation between LOH in tumor at certain markers and smoking and alcohol use was found. Our results indicate that: 1) epithelial cells in saliva from patients with head and neck squamous tumorigenesis provide suitable material for genetic analysis; 2) combined application of certain markers improves the detection of genetic alteration in these patients; 3) clonal heterogeneity between saliva and matching tumor supports genetic instability of the mucosal field in some of these patients; and 4) LOH at certain chromosomal loci appears to be associated with smoking and alcohol consumption.

Alcohol Drinking↗

PubMed2001

Surface attachment and pre-penetration stage development by plant pathogenic fungi.

Fungal pathogens cause many of the most serious crop diseases. One of the principal reasons for the success of this group is their ability to locate and perceive appropriate host surfaces and then to elaborate specialized infection structures. Here we review the processes implicated in surface attachment, germ tube elongation, and development of appressoria. The involvement of surface-acting proteins such as fungal hydrophobins and integrins in these processes is evaluated, along with a description of studies that have revealed the existence of conserved signaling pathways that regulate appressorium formation. Finally, we anticipate the prospect of genome-level analysis of fungal pathogens and the key research questions that will need to be addressed.

Fungal Proteins↗

PubMed2001

Correlation between lung fibrosis and radiation therapy dose after concurrent radiation therapy and chemotherapy for limited small cell lung cancer.

PURPOSE: To evaluate the relationship between physician-identified radiographic fibrosis, lung tissue physical density change, and radiation dose after concurrent radiation therapy and chemotherapy for limited small cell lung cancer. MATERIALS AND METHODS: Fibrosis volumes of different severity levels were delineated on computed tomography (CT) images obtained at 1-year follow-up of 21 patients with complete response to concurrent radiation therapy and chemotherapy for limited small cell lung carcinoma. Delivered treatments were reconstructed with a three-dimensional treatment planning system and geometrically registered to the follow-up CT images. Tissue physical density change and radiation dose were computed for each voxel within each fibrosis volume and within normal lung. Patient responses were grouped per radiation and chemotherapy protocol. RESULTS: A significant correlation was noted between fibrosis grade and tissue physical density change and fibrosis grade. For doses less than 30 Gy, the probability of observing fibrosis was less than 2% with conventional fractionation and less than 4% with accelerated fractionation. Physical lung density change also showed a threshold of 30-35 Gy. For doses of 30-55 Gy and cisplatin and etoposide (PE) chemotherapy, fibrosis probability was 2.0 times greater for accelerated fractionation compared with conventional fractionation (P < .005) and was correlated to increasing dose for both fractionation schedules. CONCLUSION: Lung tissue physical density changes correlated well with fibrosis incidence, and both increased with increasing dose greater than a threshold of 30-35 Gy. With concurrent PE chemotherapy, fibrosis probability was twice as great with accelerated fractionation as with once-daily fractionation.

Absorptiometry, Photon↗

PubMed2001

Four methodologies to improve healthcare demand forecasting.

Forecasting demand for health services is an important step in managerial decision making for all healthcare organizations. This task, which often is assumed by financial managers, first requires the compilation and examination of historical information. Although many quantitative forecasting methods exist, four common methods of forecasting are percent adjustment, 12-month moving average, trendline, and seasonalized forecast. These four methods are all based upon the organization's recent historical demand. Healthcare financial managers who want to project demand for healthcare services in their facility should understand the advantages and disadvantages of each method and then select the method that will best meet the organization's needs.

Decision Making, Organizational↗

PubMed2000

Impact of involved field radiotherapy after CHOP-based chemotherapy on stage III-IV, intermediate grade and large-cell immunoblastic lymphomas.

PURPOSE: To analyze the impact of involved field radiotherapy on local control, freedom from progression, and overall survival in patients with clinical Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based induction chemotherapy. METHODS AND MATERIALS: From July 1989 through October 1996, 32 patients with clinical Stage III and 27 patients with clinical Stage IV, intermediate grade, or large-cell immunoblastic lymphomas were prospectively enrolled on two protocols at The University of Texas M. D. Anderson Cancer Center. None had previously undergone treatment for lymphoma. The median patient age was 54 years (range: 26-85 years). There were a total of 172 involved sites of disease at presentation. All 59 patients received CHOP-based chemotherapy. At least six cycles of chemotherapy were delivered to 92% of the patients. Involved field radiotherapy (39.6-40.0 Gy in 20-22 fractions in 74% of cases) was administered to 28/59 (47%) patients beginning 3-4 weeks after chemotherapy. Sites were irradiated at the discretion of the treating physician. Irradiated and nonirradiated groups were compared in terms of maximum pre-chemotherapy tumor size and University of Texas M. D. Anderson Cancer Center tumor score. Kaplan-Meier estimates of local control per patient, freedom from progression, and overall survival for the irradiated and nonirradiated groups were calculated in terms of the stage of disease and treatment delivered. The resulting curves were compared using the log-rank test. The Cox proportional hazards model was used to assess the prognostic significance of tumor size, tumor score, treatment delivered, and stage. RESULTS: The median length of follow-up for all patients was 53 months (range: 4-96 months). The median tumor size at the start of chemotherapy in irradiated patients was 4.5 cm (range: 0-15 cm) versus 3 cm (range: 0-7 cm) in nonirradiated patients (p = 0.004). The irradiated and nonirradiated groups were not significantly different in terms of tumor scores. Radiotherapy improved (p = 0.001) local control (5-year rates: 89% versus 52%) for Stages III and IV combined. This benefit was due to the dramatic improvement (p = 0.0009) in local control for patients with lymphomas measuring > or =4 cm at the start of chemotherapy (5-year rates: 89% for irradiated patients versus 33% for nonirradiated patients). Radiotherapy also improved (p = 0.003) freedom from progression (5-year rates: 85% for irradiated patients versus 51% for nonirradiated patients) for Stages III and IV combined. On multivariate analysis, radiotherapy was the most significant factor affecting local control and freedom from progression. Overall survival was not significantly different (p = 0. 620) between irradiated and nonirradiated patients (5-year rates: 87% versus 81%, respectively). When Stages III and IV were analyzed separately, radiotherapy improved local control and freedom from progression but not overall survival. Radiotherapy was tolerated reasonably well, with the main toxicity being moderate myelosuppression. Eleven out of 12 (92%) patients with recurrent disease at the time of their last follow-up visit were treated initially with chemotherapy alone. CONCLUSION: Involved field radiotherapy improved local control and freedom from progression in patients with > or = 4 cm Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to CHOP-based induction chemotherapy. Involved field radiotherapy was tolerated reasonably well.

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PubMed2000

Stereotactic radiosurgery for brain metastases: results and prognostic factors.

This study was conducted to determine prognostic factors for tumor response and patient survival after stereotactic radiosurgery (SRS) for brain metastasis. Eighty-four patients with brain metastasis underwent SRS at a single institution. After fixation of the head with a stereotactic frame, computed tomography treatment planning was performed. The metastatic lesion was treated with multiple arcs to a median dose of 19 Gy. Forty-seven patients (56%) had a solitary brain lesion. Fifty-nine patients (70%) had evidence of extracranial disease at the time of SRS. The median survival duration from SRS was 7 months. Sixty-three percent of the patients had an objective radiographic response to SRS, which in turn was associated with superior central nervous system control. Age, collimator size, number of arcs, tumor location, and histology did not influence objective response rates. Patients who had a solitary lesion or who received treatment within 2 weeks after diagnosis were more likely to have an objective response than were those who did not (P < 0.05). Progressive brain disease accounted for 37% of the deaths. Nineteen patients (23%) had an in-field relapse. Four severe complications were attributed to SRS. This study confirms the role of SRS as an acceptable treatment option for patients with solitary or limited brain metastases. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 157-162 (2000).

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PubMed2000

Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant.

PURPOSE: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. METHODS AND MATERIALS: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. RESULTS: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p = 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. CONCLUSIONS: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment.

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