Biomedical subjects

Q T Le

Publications and source records attributed to Q T Le.

30 records · Page 2Linked to original sources

PubMed1999

Postoperative irradiation of minor salivary gland malignancies of the head and neck.

OBJECTIVES: (1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors. MATERIALS AND METHODS: Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months-28.9 years). RESULTS: The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81 % and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted. CONCLUSIONS: Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.

Adenocarcinoma↗

PubMed1999

Apoptosis-associated proteins and the development of oral squamous cell carcinoma.

Expression of apoptosis-associated proteins was evaluated in premalignant and malignant oral epithelial lesions, to test the hypothesis that protein regulation of apoptosis may be altered in the development of oral squamous cell carcinoma. Ninety archived paraffin-embedded specimens from 25 patients (two or more sequential biopsies each) and eight control specimens were evaluated in immunohistochemically stained sections for tumor suppressor protein p53, p53 binding protein mdm-2, and apoptosis regulatory proteins Bcl-2, Bcl-X, Bax, and Bak. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild dysplasia, or moderate dysplasia; the initial diagnosis for the remaining eight patients ranged from severe dysplasia to moderately differentiated squamous cell carcinoma. Thirty of 90 specimens showed positive p53 expression, nine of which were dysplasias. In patients with one or more lesions displaying p53 expression, there was increased intensity of staining with disease progression. Bak was expressed in 57/90 specimens, including 27 dysplasias of various grades. There was also a significantly increased intensity of Bak staining with disease progression, which did not appear to be dependent upon p53 status. Bcl-X was expressed in 73/90 specimens, with staining displayed earlier in premalignant lesions than either p53 or Bak. Ten of 90 specimens were positive for Bcl-2 (all were dysplasias or carcinomas), and only 2/90 specimens were positive for Bax. Eleven of 90 specimens were positive for mdm-2; six of which were also positive for p53. These data show that apoptosis-associated proteins are altered in variable patterns in both premalignant and malignant oral epithelial lesions. p53 and especially Bak and Bcl-X are expressed early; Bax is largely absent; and Bcl-2 and mdm-2 show sporadic expression in the development of oral premalignant and malignant disease.

Adult↗

PubMed1999

Cell cycle proteins and the development of oral squamous cell carcinoma.

Expression of cell cycle regulatory proteins was evaluated in premalignant and malignant oral epithelial lesions, to test the hypothesis that protein regulation of the cell cycle may be altered in the development of oral squamous cell carcinoma. Archived paraffin-embedded specimens (n = 90) from 25 patients with recurrent or persistent lesions were evaluated in immunohistochemically stained sections for cell cycle regulatory proteins p53, Rb, Cyclin D1, p27, and p21. The cell cycle was also evaluated by expression of nuclear protein Ki 67. Sections were graded semiquantitatively using a 0-3 + scale to indicate the percentage of positively stained cells. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild dysplasia, or moderate dysplasia; the initial diagnosis for the remaining eight patients ranged from severe dysplasia to moderately differentiated squamous cell carcinoma. Thirty-three of 90 specimens showed positive p53 expression, 11 of which were dysplasias. Eighty-nine of 90 specimens, from all stages of disease, showed positive Rb expression. Twenty-three of 90 specimens showed positive Cyclin D1 expression, typically in the later stages (carcinoma) of a patient's disease. Eighty-four of 90 specimens showed positive p21 expression; while 55 of 90 specimens were positive for p27. In control mucosa, p27 was highly expressed, while Rb and p21 proteins were expressed at relatively low levels; p53 and Cyclin D1 proteins were largely absent. Generally, staining of p53, Rb, p21, and Ki 67 increased with time in serial biopsies, while p27 showed decreased staining with disease progression. These data show that cell cycle regulatory proteins are altered in both premalignant and malignant disease, and that protein phenotypes are heterogeneous. P53 expression is seen early, and Cyclin D1 expression is seen late in the development of oral premalignant and malignant disease. Expression of p53, Rb, p21 and Ki67 increased, while p27 decreased, with disease progression.

Adult↗

PubMed1999

DNA damage measured by the comet assay in head and neck cancer patients treated with tirapazamine.

Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

Animals↗

PubMed1999

Optimization of importance factors in inverse planning.

Inverse treatment planning starts with a treatment objective and obtains the solution by optimizing an objective function. The clinical objectives are usually multifaceted and potentially incompatible with one another. A set of importance factors is often incorporated in the objective function to parametrize trade-off strategies and to prioritize the dose conformality in different anatomical structures. Whereas the general formalism remains the same, different sets of importance factors characterize plans of obviously different flavour and thus critically determine the final plan. Up to now, the determination of these parameters has been a 'guessing' game based on empirical knowledge because the final dose distribution depends on the parameters in a complex and implicit way. The influence of these parameters is not known until the plan optimization is completed. In order to compromise properly the conflicting requirements of the target and sensitive structures, the parameters are usually adjusted through a trial-and-error process. In this paper, a method to estimate these parameters computationally is proposed and an iterative computer algorithm is described to determine these parameters numerically. The treatment plan selection is done in two steps. First, a set of importance factors are chosen and the corresponding beam parameters (e.g. beam profiles) are optimized under the guidance of a quadratic objective function using an iterative algorithm reported earlier. The 'optimal' plan is then evaluated by an additional scoring function. The importance factors in the objective function are accordingly adjusted to improve the ranking of the plan. For every change in the importance factors, the beam parameters need to be re-optimized. This process continues in an iterative fashion until the scoring function is saturated. The algorithm was applied to two clinical cases and the results demonstrated that it has the potential to improve significantly the existing method of inverse planning. It was noticed that near the final solution the plan became insensitive to small variations of the importance factors.

Algorithms↗

PubMed1999

Estimation theory and model parameter selection for therapeutic treatment plan optimization.

Treatment optimization is usually formulated as an inverse problem, which starts with a prescribed dose distribution and obtains an optimized solution under the guidance of an objective function. The solution is a compromise between the conflicting requirements of the target and sensitive structures. In this paper, the treatment plan optimization is formulated as an estimation problem of a discrete and possibly nonconvex system. The concept of preference function is introduced. Instead of prescribing a dose to a structure (or a set of voxels), the approach prioritizes the doses with different preference levels and reduces the problem into selecting a solution with a suitable estimator. The preference function provides a foundation for statistical analysis of the system and allows us to apply various techniques developed in statistical analysis to plan optimization. It is shown that an optimization based on a quadratic objective function is a special case of the formalism. A general two-step method for using a computer to determine the values of the model parameters is proposed. The approach provides an efficient way to include prior knowledge into the optimization process. The method is illustrated using a simplified two-pixel system as well as two clinical cases. The generality of the approach, coupled with promising demonstrations, indicates that the method has broad implications for radiotherapy treatment plan optimization.

Algorithms↗

PubMed1998

Analysis of titanium dental implants after failure of osseointegration: combined histological, electron microscopy, and X-ray photoelectron spectroscopy approach.

A multitechnique approach has been used to characterize the surface of nonosseointegrated titanium implants and the surrounding biological tissues. Five pure titanium dental implants were used as reference, and 25 removed implants were studied. Surface and in-depth chemical compositions of the implants (from a total of 16 patients) were investigated by X-ray photoelectron spectroscopy (XPS). Histological slides of the surrounding tissues were examined by light microscopy, XPS, and electron microprobe analysis. None of the failed implants presented the regular surface composition and depth profile of the TiO2 overlayer; foreign elements (Ca, Na, P, Si, Cl, Zn, Pb, and Al) were observed on some implants. Fibrosis, lymphocytic and plasmocytic infiltrates, and granulomatous lesions were detected in the surrounding tissues. XPS and electron microprobe analysis indicated the presence of Zn, Fe, Sn, and Ti in the tissues. As a possible scenario for implant failure, we propose and discuss a oxidoreduction mechanism, leading to a partial dissolution or the complete dissociation of the protective titanium dioxide overlayer and to ion diffusion through the surrounding tissues.

Connective Tissue↗

PubMed1998

The etiology of bacterial pneumonia and meningitis in Vietnam.

BACKGROUND: To date no studies on the incidence of Haemophilus influenzae type b (Hib) disease, Hib carrier rates in infants and children or the proportion of bacterial meningitis cases caused by Hib in Vietnam have been performed. The availability of safe and highly effective Hib vaccines makes such information important. METHODS: The bacterial etiology of a sample of infants and children with pneumonia and meningitis seen at Pediatric Hospital No. 1 in Ho Chi Minh City was studied by culture and latex agglutination of blood, cerebrospinal fluid, urine and pleural fluid. The carriage rate of pneumococci and Hib was studied in a sample of outpatient children. RESULTS: Hib caused 53% of 34 culture-proven bacterial meningitis cases and pneumococci caused 18%. Of 31 meningitis cases diagnosed by latex agglutination, 39% were caused by Hib and 55% by pneumococci. Ninety percent of cases of Hib meningitis occurred in children <1 year of age. Fifty percent of meningitis cases were associated with acute respiratory infection. In 213 bacteremic pneumonia cases 92.5% of blood cultures grew Streptococcus pneumoniae and only 1% grew Hib. The carrier rate of Hib in outpatients <5 years of age with upper respiratory tract infection increased from 2% to 7.6% between 1993 and 1996. CONCLUSION: Hib is the most frequent cause of meningitis in infants and children admitted to hospitals in South Vietnam. Ninety percent of Hib meningitis cases occur in patients < 1 year of age. Bacteremic Hib pneumonia in Vietnam is rare. The results suggest that Hib is the major cause of meningitis in Vietnam but do not permit conclusions regarding its true incidence. The carrier rate of Hib in children <5 years of age in Vietnam has increased to approximately 7% since 1993.

Carrier State↗

PubMed1997

Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma.

PURPOSE: To evaluate the influence of fraction size, overall time, total dose, and other prognostic factors on local control of T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1956 and 1995, 398 consecutive patients with early glottic carcinoma (315 T1 and 83 T2) were treated with once-a-day definitive radiotherapy at the University of California, San Francisco, and associated institutions. Treatment was delivered 5 days per week. Minimum tumor dose ranged from 46.6 to 77.6 Gy (median: 63 Gy). The fraction size was < 1.8 Gy in 146; 1.8-1.99 Gy in 128; 2.0-2.24 Gy in 62, and > or = 2.25 Gy in 62 patients. Overall time ranged from 34 to 75 days (median: 50 days). The majority of patients treated with a fraction size of 2.25 Gy completed therapy within 43 days. Median follow-up of all alive patients was 116 months (range 3-436 months). RESULTS: Five-year local control was 85% for T1 and 70% for T2 glottic carcinomas (p = 0.0004). For T1 lesions, within the dose and time range evaluated, there was no apparent relationship between fraction size, overall time, total dose, and local control on multivariate analysis. Treatment era was the only significant prognostic factor (p = 0.02), and anterior commissure (AC) involvement was of borderline significance (p = 0.056). Five-year local control was 77% for patients treated between 1956-1970, 89% for between 1971-1980, and 91% for between 1981-1995; 80% for patients with AC involvement and 88% for those without. For T2 lesions, prognostic factors for local control on multivariate analysis were: overall time (p = 0.003), fraction size (p = 0.003), total dose (p = 0.01), impaired vocal cord mobility (p = 0.02), and subglottic extension (p = 0.04). Five-year local control was 100% for T2 lesions treated with overall time < or = 43 days vs. 84% for overall time > 43 days; 100% for fraction size > or = 2.25 Gy vs. 44% for fraction size < 1.8 Gy; 78% for total dose > 65 Gy vs. 60% for total dose < or = 65 Gy; 79% for normal cord mobility vs. 45% for impaired cord mobility, and 58% for lesions with subglottic extension vs. 77% for those without. The severe complication rate for the entire group was low: 1.8%. CONCLUSIONS: Total dose, fraction size, and overall time were significant factors for local control of T2 but not T1 glottic carcinomas. Anterior commissure involvement was associated with decreased local control for T1 but not T2 lesions. For T1 lesions, local control improved over the treatment era. For T2 lesions, local control decreased with impaired cord mobility and subglottic extension.

Adult↗

PubMed1997

Prognostic factors in adult soft-tissue sarcomas of the head and neck.

PURPOSE: The main objectives of this study were (a) to review the treatment results of primary head and neck soft-tissue sarcoma at our institution, (b) to identify important prognostic factors in local control and survival, and (c) to assess the efficacy of salvage therapy. METHODS AND MATERIALS: Sixty-five patients were treated at the University of California, San Francisco, between 1961 and 1993. Seventeen patients (27%) had low-grade, 10 (15%) had intermediate-grade, and 38 (58%) had high-grade sarcomas. Tumors were > 5 cm in 35 patients. Local management consisted of surgery alone in 14 patients (22%), surgery and radiotherapy in 40 (61%), and radiotherapy alone in 11 (17%) patients. The median follow-up was 64 months. RESULTS: The 5-year actuarial local control rate of the entire group was 66%. Tumor size and grade were important predictors for local control on multivariate analysis. The actuarial local control rate at 5 years was 92% for T1 vs. 40% for T2 primaries (p = 0.004), and 80% for Grade 1-2 vs. 48% for Grade 3 tumors (p = 0.01). None of the patients treated with radiotherapy alone with a dose of 50-65 Gy were controlled locally. Combined radiotherapy and surgery appeared to yield superior local control compared to surgery alone (77% vs. 59%); however, the difference was not statistically significant. The 5-year actuarial overall and cause-specific survivals were 56% and 60%, respectively. Unfavorable prognostic factors for cause-specific survival on multivariate analysis were age > 55 (p = 0.009), high tumor grade (p = 0.0002), inadequate surgery (p = 0.008), and positive surgical margins (p = 0.0009). In patients who underwent salvage therapy for treatment failure, the 5-year actuarial survival after salvage treatment was 26%. CONCLUSION: Tumor size and grade were important predictors for local control. Age, grade, adequacy of surgery, and status of surgical margins were significant prognostic factors for survival. There was a trend of improved local control with combined surgery and radiotherapy compared to either modality alone for high-risk patients. Radiotherapy alone with doses < or = 65 Gy was insufficient for control of gross disease. Aggressive salvage therapy was worthwhile in patients whose disease was uncontrolled after the initial treatment.

Adolescent↗

PubMed1994

Pattern of recurrence of medulloblastoma after low-dose craniospinal radiotherapy.

PURPOSE: We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation. METHODS AND MATERIALS: Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (< or = 30 Gy) or high-dose craniospinal fields and low-dose (< or = 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy. RESULTS: Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors. CONCLUSIONS: Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

Adolescent↗

PubMedDate not supplied

Adult medulloblastoma: an analysis of survival and prognostic factors.

PURPOSE: This analysis aimed to review the experience in the management of adult medulloblastoma at the University of California, San Francisco, and to identify important prognostic factors for survival and posterior fossa control. PATIENTS AND METHODS: We performed a retrospective review of 34 adult patients, age > or = 15, with cerebellar medulloblastoma treated with radiotherapy at the University of California, San Francisco from 1970 to 1994. All patients underwent a surgical procedure (complete resection in 17, subtotal resection in 10, and biopsy alone in seven), followed by craniospinal irradiation. Most patients treated after 1979 also received chemotherapy. Twenty were classified as poor-risk due to either incomplete resection or evidence of disease outside of the posterior fossa at diagnosis. RESULTS: The 5-year posterior fossa control and overall survival rates were 61% and 58%, respectively. The majority of relapses occurred in the posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring older patients), gender (favoring female patients), and extent of disease at diagnosis (favoring localized disease) were important prognostic factors for posterior fossa control. There was a trend toward improved posterior fossa control with higher radiation dose to the posterior fossa in patients with a complete resection. Gender and extent of disease at presentation were significant prognostic factors for survival. The 5-year survival rates were 92% for female patients versus 40% for male patients, and 67% for patients with localized disease versus 25% for those with disseminated disease. The prognosis following recurrence was poor; all died of the disease. DISCUSSION: Survival for adult medulloblastoma was comparable to its pediatric counterpart. In patients with localized disease at presentation, gender (favoring female patients) and age (favoring older patients) were important prognostic factors for posterior fossa control and survival. In patients with disseminated disease at presentation, the prognosis is poor, and innovative therapy is needed to improve survival.

Adolescent↗