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Biomedical subjects

R G Parker

Publications and source records attributed to R G Parker.

At least 19 recordsLinked to original sources

Biologically effective dose distribution based on the linear quadratic model and its clinical relevance.

PURPOSE: Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. METHODS AND MATERIALS: A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user's input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians' intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. RESULTS: Two sample cases serve to illustrate the application of our tool in clinical practice. (a) For an orthogonal wedged pair of x-ray beams treating a maxillary sinus tumor, the biological effect at the ipsilateral mandible can be quantified, thus illustrates the so-called "double-trouble" effects very well. (b) For a typical four-field, evenly weighted prostate treatment using 10 MV x-rays, physical dosimetry predicts a comparable dose at the femoral necks between an alternate two-fields/day and four-fields/day setups. However, our BED display reveals an approximate 21% higher BED for the two-fields/day scheme. This excessive dose to the femoral necks can be eliminated if the treatment is delivered with a 3:2 (anterio-posterior/posterio-anterior (AP/PA): bilaterally opposed (BLO)) dose weighting. With Co-60 beams, the increase of BED with alternate two-fields/day, 1:1 setup was even more pronounced (26%). CONCLUSION: We have demonstrated the feasibility of constructing a biologically oriented dose distribution for clinical practice of radiotherapy. The discordance between physical dose distributions and the biological counterparts based on the given treatment schemes was quantified. The computerized display of BED at nonprescription points greatly enhanced the versatility of this tool. Although the routine use of this implementation in clinical radiotherapy should be cautiously done, depending largely on the accuracy of the published biological parameters, it may, nevertheless, help the clinicians derive an optimal treatment plan with a particular fractionation scheme or use it as a quantitative tool for outcome analysis in clinical research.

Feasibility Studies

Fast-neutron therapy in advanced head and neck cancer: a collaborative international randomized trial.

PURPOSE: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. RESULTS: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). CONCLUSION: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity.

Adult

Reminiscence: a continuity theory framework.

The goal of this article is to provide theoretical underpinnings for reminiscence by reviewing and evaluating previous research, and integrating it within a theoretical framework. Using a continuity theory perspective (Atchley, 1989), propositions are generated which may facilitate reminiscence research across the life span. Three global functions of reminiscence are derived from continuity theory (private, social, and cognitive functions) and are used as a foundation for the creation of seven propositions.

Aged

Craniopharyngioma: treatment in the CT and MR imaging era.

PURPOSE: To determine optimal treatment in patients with craniopharyngiomas. MATERIALS AND METHODS: In 1977-1990, 49 patients (age range, 3-67 years; median age, 35 years; 25 female, 24 male) with craniopharyngiomas were examined. Follow-up was 5-17 years (median, 8 years). Fifteen patients were aged younger than 18 years. RESULTS: All patients underwent surgical resection. Complete resection was achieved in 19. Seven patients underwent additional surgery for recurrent disease. Rate of mortality due to surgical complications was 10% (n = 5). Eight patients had marked perioperative or long-term morbidity. Twenty-five patients judged to have undergone subtotal resection underwent postoperative radiation therapy (RT). RT doses were 4,600-6,287 cGy administered in fractions of 180-200-cGy/d. Actuarial 5-year progression-free survival in patients who underwent complete resection was 63% (12 of 19 patients) versus 96% (24 of 25 patients) in patients who underwent subtotal resection followed by RT (P = .04). No RT dose response was observed. Patient functional status has not been substantially affected by adjuvant RT. CONCLUSION: RT achieves excellent tumor control after subtotal resection of craniopharyngiomas.

Adolescent

Postirradiation sarcomas. A single-institution study and review of the literature.

BACKGROUND: With improvement in survival after cancer treatment, it is becoming increasingly important to examine treatment-related morbidity and mortality. Sarcomas can develop in the irradiated field after radiation therapy (RT). The authors undertook a study to estimate the risk, and compared the risk of postirradiation sarcoma (PIS) with other treatment modalities used against cancer. METHODS: Since 1987 the authors have reviewed the records of 1089 patients with head and neck, gynecologic, gastrointestinal, and extremity sarcomas. Of these 1089 patients, 37 had a prior history of RT. RESULTS: Conditions for which these patients received RT included: Hodgkin's disease (2 patients), retinoblastoma (3), non-Hodgkin's lymphoma (2), acne (1), astrocytoma (1), multiple recurrent mixed parotid tumor (1), laryngeal cancer (1), papillary adenocarcinoma of the thyroid (1), bony fibrous dysplasia (1), lymphangioma (1), squamous cell carcinoma of the nasopharynx (1), Ewing's sarcoma (1), choriocarcinoma (1), menorrhagia (4), cervical cancer (6), ovarian cancer (2), breast cancer (7), and hypoplasia (1). RT doses ranged from 3000 to 12,440 cGy. Latency time from RT to the development of PIS averaged 12 years. More than 15,000 patients have received RT for various conditions at our institution since 1955. CONCLUSIONS: From our data and a review of the literature, we estimate the risk of PIS with long-term follow-up to be 0.03-0.8%. From a review of the literature that compared mortality risks of chemotherapy, general surgery, and anesthesia, the risk of PIS appears no worse. Thus, given the large number of patients who can be cured or receive palliative treatment with RT, concern regarding PIS should not be a major factor influencing treatment decisions in patients with cancer.

Adolescent

Primary central nervous system lymphoma. Results at the University of California at Los Angeles and review of the literature.

The authors report 24 patients with primary central nervous system lymphoma (PCNSL) treated from 1977 to 1992. There were 13 females and 11 males. Median age was 57 (range: 17-84). Patients were symptomatic for a median of 3 months. Headache was the most common complaint. Median Karnofsky performance score was 70. There were 19 patients with solitary PCNSL, and 5 had multiple deposits. Disease was confined to the supratentorium in 23 patients. Cerebrospinal fluid cytology was positive in 5 of 22 patients examined. All patients received whole-brain irradiation with or without supplemental tumor boost. Tumor doses ranged from 10 to 60 Gy. Intrathecal chemotherapy was administered to 16 patients and 7 received systemic agents. After follow-up ranging from 1 to 66 months, median survival and progression-free survival were each 8 months. One- and 3-year actuarial survival rates were 50% and 36%, respectively. One- and 3-year actuarial progression-free rates were 41% and 15%, respectively. Relapse occurred in 18 patients, and in 17 there was a component of local progression. Lesions recurred in the spinal meninges in 1 patients and in the vitreous in 1. Patients with Karnofsky performance status > or = 70 demonstrated median progression-free survival of 27 months, compared to 4 months for patients < 70 (p = .024). No other significant patient or treatment-related prognostic factors were identified. Clinical dementia occurred in 2 of 11 patients surviving at least 1 year. Review of the literature indicates PCNSL demonstrates relative radioresistance. The most immediate improvement in prognosis for patients with PCNSL can be achieved by properly sequencing systemic and intrathecal chemotherapy with radiation therapy.

Actuarial Analysis

Postirradiation sarcoma of the head and neck.

BACKGROUND: With improvement in survival after cancer treatment, it is becoming increasingly important to study treatment-related morbidity and mortality. Sarcoma can develop in the irradiated field after radiation therapy. The authors performed a study to estimate the risk, and compared the risk of sarcoma after radiation therapy with that of other treatment modalities used against cancer. METHODS: Between 1955 and 1988, 229 patients with sarcoma of the head and neck were seen at the University of California, Los Angeles (UCLA), Medical Center. Of these, 13 (6%) had a previous history of radiation therapy to the head and neck. RESULTS: Radiation doses were known in 10 of 13 patients and ranged from 30 to 124.4 Gy. The latency time from radiation therapy to the development of postirradiation sarcoma (PIS) ranged from 3 months to 50 years, with a median of 12 years. More than 2000 patients have received radiation therapy to the head and neck for various conditions at the UCLA Medical Center since 1955. CONCLUSIONS: The authors conclude that most head and neck sarcomas are not radiation related and that the risk of PIS after head and neck irradiation for other diseases is low. From a review of the literature comparing mortality risks of chemotherapy, general surgery, and anesthesia, the risk of PIS appears no worse. Given the large number of patients who can be cured or receive palliation with radiation therapy, concern about PIS should not be a major factor influencing treatment decisions in patients with cancer.

Adolescent

Minor salivary gland tumors of the head and neck: treatment strategies and prognosis.

Between 1961 and 1985, 117 patients with malignant tumors of the minor salivary glands of the upper aerodigestive tract were treated with curative intent at the University of California, Los Angeles (UCLA). The length of follow-up ranged from 24-225 months, with a median of 38 months. The most common site of origin was the oral cavity (65 cases), and the most common histology was adenoid cystic carcinoma (69 cases). Tumor size, histology, and site were important prognostic factors. For oral cavity lesions, small tumors were well controlled with resection alone (25 of 26) or local excision, followed by irradiation (7 of 7). For advanced tumors arising from the paranasal sinuses and pharynx, the control rates were 43% (15 of 35) and 29% (5 of 17), respectively. Ninety-three percent (27 of 29) of patients with mucoepidermoid carcinoma had no evidence of disease at last follow-up versus 55% (38 of 69) of patients with adenoid cystic carcinoma and 56% (10 of 18) of those with adenocarcinoma. It appears that resection with good margin is adequate treatment for small lesions. Large, poorly differentiated tumors require a combined approach: surgery and radiation therapy.

Adolescent

Chondrosarcoma of the head and neck. The UCLA experience, 1955-1988.

Chondrosarcoma of the head and neck is a rare tumor. In an attempt to clarify optimal treatment of these lesions, we reviewed the records and pathologic material of 18 consecutive cases of head and neck chondrosarcoma seen at our institution between 1955 and 1988. Follow-up ranged from 3 to 168 months with a median of 72. Absolute 5-year survival was 68% (11/16), with 9/16 (56%) patients surviving disease-free. Grade was the most important prognostic factor. Only one of 7 (14%) patients known to have high grade histology was rendered disease-free, as opposed to 9/10 (90%) with low-grade lesions. Tumor size and completeness of surgical resection were also important prognostic factors. Four of 10 patients managed initially with surgery alone achieved local control with greater than 5-year survival. All four had low-grade lesions. Five patients received surgery and radiation as primary treatment, and three are disease-free with greater than 5-year follow-up. Two of these were irradiated because of positive margins. One patient received radiation alone and has persistent disease. Two patients received combined chemotherapy and surgery because of high-grade lesions, and one is free of disease with greater than 5-year follow-up. Patients with incomplete resections should receive further surgery or postoperative radiation therapy. High-grade lesions should be treated aggressively.

Adolescent

Sarcomas of the head and neck. Prognostic factors and treatment strategies.

The authors reviewed 164 cases of head and neck sarcoma from adult patients seen at the University of California, Los Angeles (UCLA), between 1955 and 1988. The median follow-up was 70 months. Multivariate analysis demonstrated that tumor grade, size, and surgical margin status were the most important independent prognostic factors. Thirty-one percent (27 of 85) of patients with high-grade lesions were free of disease versus 81% (44 of 55) with low-grade lesions at last follow-up. Sixty-seven percent (50 of 76) of patients with lesions smaller than 5 cm were free of disease versus 38% (33 of 88) with lesions larger than 5 cm. In 16 patients, low-grade lesions, measuring less than 5 cm and with negative margins histologically, were controlled with surgery alone. For the 94 patients whose primary tumors were treated at UCLA, local control was achieved in 52% (26 of 50) of patients treated with surgery alone and 90% (20 of 22) with combined therapy (surgery and radiation therapy [RT] with or without chemotherapy). Seventy-five percent (6 of 8) of patients with positive surgical margins treated with postoperative RT achieved local control versus 26% (5 of 19) of patients receiving no additional treatment. In conclusion, surgery alone appears to be adequate treatment for small, low-grade tumors and negative surgical margins. Patients with incomplete resection or high-grade tumors should receive aggressive treatment--surgery and RT.

Adult

Conservation therapy for invasive lobular carcinoma of the breast.

Earlier literature suggests a high incidence of multicentricity and bilaterality, with an overall poor prognosis, in patients with invasive lobular carcinoma of the breast. Consequently, there is considerable disagreement regarding appropriate local management of this disease. To determine the influence of invasive lobular histologic findings on local tumor control, disease-free survival, and overall survival, the authors reviewed 60 patients with Stage I and II invasive lobular breast carcinoma treated with local tumor excision and radiation therapy between 1981 and 1987 (mean follow-up, 5.5 years; range, 2.5 to 10 years). The 5-year actuarial risk of locoregional recurrence was 5%, with two of three failures occurring in the regional lymphatics. The mean time to locoregional failure was 28 months. The 5-year actuarial disease-free survival (84%) and overall survival (91%) were comparable to those seen in several large series of similarly treated patients with invasive ductal carcinoma. Contralateral breast cancer occurred at a rate of approximately 0.6% per year. This study and a review of the literature suggest that breast conservation, with local resection and radiation therapy, is appropriate therapy for invasive lobular breast cancer.

Adult

Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced hemiparkinsonism on the kinematics of a two-dimensional,multijoint arm movement in the rhesus monkey.

The effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the kinematics of two-dimensional arm movements in the primate were studied. Two rhesus monkeys were trained to move a manipulandum at various distances and directions in horizontal space from a centrally located target box. Several kinematic parameters including reaction time, and time and amplitude of peak tangential velocity were analysed. Following an extensive control evaluation period, the animals were unilaterally injected with MPTP into the internal carotid artery. The animals were restudied for up to 289 days following induction of hemiparkinsonism. Larger-amplitude movements (greater than 3.5 cm) were more severely affected than smaller amplitude movements. Both animals exhibited marked changes in the arm movements including increased time-to-peak velocity and decreased peak velocity. The degree of the kinematic changes was spatially dependent, with the decrease in velocity as well as the time-to-peak velocity being more pronounced for the larger, outward movements. Reaction time increased but showed no spatial dependency. Kinematic deficits persisted over the entire time-period studied. Also, the kinematic changes were reduced by levo-3,4 dihydroxyphenylalanine in a dose-dependent manner. Tyrosine hydroxylase immunohistochemistry documented extensive cell loss in the substantia nigra. These results show that both the timing as well as the amplitude of the velocity profiles are disrupted by MPTP consistent with the known akinesia and bradykinesia of parkinsonism. Although abnormalities were present for all directions and distances, a spatial dependency to the deficits was detected. The observation of more pronounced changes for larger, outward movements suggests a role for the basal ganglia in production of larger-amplitude movements directed away from the body.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Sustained release of nerve growth factor from biodegradable polymer microspheres.

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.

Adrenal Medulla

Continual intracavitary administration of amphotericin B as an adjunct in the treatment of aspergillus brain abscess: case report and review of the literature.

Aspergillus brain abscess is often a fatal disease, regardless of the mode of therapy. Most often seen in the compromised host, it is notoriously refractory to systemic antifungal agents and intrathecal antimycotics. Even with radical surgical debridement, only 13 patients, including the present case, have survived longer than 3 months after being treated for aspergillus brain abscess or granuloma. Studies have shown poor penetration of amphotericin B into the brain and cerebrospinal fluid. One way to achieve therapeutic levels of the agent near the abscess is through the direct introduction of the agent into the abscess site via an indwelling catheter. In the present case, a woman with an aspergillus abscess of the left temporal lobe was treated by a combination of systemic agents, radical debridement, and local therapy, resulting in a cure with a follow-up of 6 years. This is the first reported instance of the use of long-term, local antifungal therapy delivered to the area of the abscess cavity, using a closed reservoir system, and this patient is only the second renal transplant patient reported to have survived aspergillus brain abscess. This form of treatment produced no untoward long-term side effects or neurological sequelae. Local irrigation with antifungal agents should be considered in conjunction with systemic antifungal drugs and drainage and/or debridement in cases of fungal intracerebral aspergilloma. This technique may also prove useful with other fungal brain lesions.

Adult