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Biomedical subjects

L J Peters

Publications and source records attributed to L J Peters.

At least 109 records · Page 6Linked to original sources
PubMed1992

Devices valuable in head and neck radiotherapy.

Normal tissue reactions limit the use of radiotherapy in the management of patients with head and neck neoplasms. Customized intraoral stents can help prevent unnecessary irradiation of various normal tissues thus reducing severity of reactions. Two basic types of devices, referred to as shielding and positional stents, are presented. The fabrication and the application of such devices are illustrated through five case reports. Recommendations on use of these tools and the possibility of combining these means with methods to improve dose distribution within the target volume containing air gaps are provided. Close collaboration between the attending radiotherapist and dentist is essential for designing appropriate devices for individual patients. However, when properly designed and used, these stents are effective in reducing treatment morbidity.

Adult↗
PubMed1992

Radiosensitivity measurement of keratinocytes and fibroblasts from radiotherapy patients.

Genetic diversity is believed to influence cellular radiosensitivity and individual variability in normal tissue reactions to radiotherapy. To measure normal cell radiosensitivity in vitro, we investigated a culture technique that yields keratinocyte and fibroblast cell cultures from small skin biopsy samples (average weight 32 mg). This technique uses 3T3 NIH cells as feeder cells, culture medium containing dialyzed fetal calf serum, low calcium, and various growth factors for keratinocyte growth. A calcium concentration of 4 x 10(-3) M and the use of lethally irradiated NIH 3T3 feeder cells were critical to the success of this method. Primary keratinocyte cultures were successfully obtained from nine biopsy specimens, and radiosensitivity measurements were obtained in six of the resulting strains. Keratinocytes were, in general, more radioresistant than fibroblasts derived from the same specimen. We conclude that radiosensitivity assessment of keratinocyte and fibroblast cultures derived from small punch biopsy specimens is feasible. Further studies can now be carried out to determine the degree of variability between individuals and the relationship between in vitro keratinocyte and fibroblast radiosensitivity and their value in predicting normal tissue responses to radiotherapy.

Cell Survival↗
PubMed1992

The relationship between apoptosis and atrophy in the irradiated lacrimal gland.

Atrophy is generally considered to be a true late effect of radiation. However, in serous glands, atrophy was thought to be a consequential late effect because serous cells die within hours of irradiation and the apparent effects of atrophy are observed contemporaneously with radiation treatment. Therefore, to determine the pathogenesis of atrophy in serous glands, it is necessary to differentiate between parenchymal loss as a result of direct radiation death of serous cells and parenchymal loss as a result of serous cell death that is secondary to fibrosis, vascular damage, or precursor cell death. The lacrimal glands of 62 rhesus monkeys have been irradiated to single doses of 2.5 to 20 Gy and examined at intervals of 4 hr to 112 days postirradiation. Serous cells (nuclei) and acini were counted in at least 30 high power fields per (dose, time) point. At each dose and time of sacrifice, the average number of nuclei per acinus and the average number of acini per high power field were calculated. Also at each dose and time, the distribution of the number of nuclei per acinus was examined to determine how the frequency of acinar sizes changed as a function of irradiation. The number of cells per acinus appears to rise initially, but this is likely a result of the degranulated cells being physically smaller, yielding an artificially higher count. Within 4 days after 12.5 Gy, the average number of nuclei per acinus approaches control values and remains within the range of controls for at least 112 days. The number of acini per high power field decreases steadily for 30 days after 12.5 Gy. From 30 to 112 days, there is some recovery of this number, but it remains well below control values. At 24 hr, the number of nuclei per acinus shows a distinct dose response up to 20 Gy. However, at 30 days there is no evidence of a dose response for this parameter. These results indicate that even though serous cells die in significant numbers within hours of irradiation, the atrophy of the lacrimal gland (and by extension, the parotid gland) is a result of the death of the serous stem cell or precursor. Consequently, protection of serous cells from radiation apoptosis will not diminish serous gland atrophy.

Animals↗
PubMed1992

Re-treatment of nasopharyngeal carcinoma in 53 patients.

Fifty-three patients with locally recurrent or persistent nasopharyngeal carcinoma were re-treated with megavoltage radiation therapy at The University of Texas M. D. Anderson Cancer Center from 1954 through 1989. The time from initial treatment to re-treatment ranged from 2 to 189 months (median 33 months). Documented local disease was confined to the nasopharynx in 27 patients (Group 1), while in the other 26 patients there was local spread beyond the nasopharynx (Group 2). At the time of re-treatment, nodal disease was present in 27 of the 53 cases. Forty-two patients were re-treated with external beam therapy alone and 11 with a component of brachytherapy. Re-treatment doses specified at the nasopharyngeal vault ranged from 27.5 to 99 Gy (median 57 Gy), and total cumulative dose ranged from 80 to 160 Gy (median 112 Gy). Overall 5-year actuarial local control (LC), disease-free survival (DFS), and survival rates were 35%, 18%, and 21%, respectively. Patients with Group 1 disease did better than those with Group 2 disease in terms of 5-year survival, 32% versus 9% (p = 0.01) and 5-year DFS, 23% versus 12% (p = 0.002). Nodal status at the time of re-treatment did not predict for LC or survival. The 5-year survival of patients with lymphoepitheliomas was 28% compared with 13% for patients with squamous cell carcinomas (p = 0.04). Eight patients developed severe complications from re-treatment, of which five involving the brain (two), spinal cord (one), and lower cranial nerves (two) were fatal. The incidence of severe complications was related to the total cumulative dose of external beam irradiation: 4% for patients receiving doses less than or equal to 100 Gy compared with 39% for those patients who received doses greater than 100 Gy (p = 0.066). Beginning in 1977, a combination of external beam therapy (20 to 30 Gy) and intracavitary cesium (40 to 50 Gy surface dose) was used in selected cases: 9 of the 53 patients were re-treated with this combination. Of these, 7 achieved LC with a follow-up of 7 to 102 months and none sustained a severe complication. Five-year actuarial LC, DFS, and survival in this group were 67%, 44% and 60% respectively.

Adolescent↗
PubMed1992

The role of radiotherapy in the primary management of cutaneous melanoma.

The historical role of radiotherapy in the management of cutaneous melanoma has largely been for palliation. Fractionation schedules using infrequent large doses have proved convenient and effective. Response rates range from 50% to 85% with the likelihood of complete response strongly dependent on tumor volume. These observations, along with radiobiological data showing a wide range of cellular radiosensitivity within the same histotype, suggest that radiotherapy would be most reliably effective against microscopic or subclinical disease. A few investigators have evaluated the role of radiotherapy combined with surgery as a curative approach in early-stage, high-risk disease. Patterns of failure after surgery alone indicate a substantial risk of local and regional recurrence that can be reduced by radiotherapy. Strategies for integrating radiotherapy into primary management are reviewed and additional studies are suggested.

Clinical Trials as Topic↗
PubMed1992

Neutron RBE for primate spinal cord treated with clinical regimens.

The RBEs of high-energy neutrons given in 9 or 12 fractions for cervical spinal cord injury in rhesus monkeys was determined using photons at 2.2 Gy per fraction as the reference radiation. Because the dose-response functions were not parallel, the RBE was not constant but rather increased with dose or, equivalently, with the probability of myelopathy. This required the development of a novel method of determining the RBE versus level of response. The RBE is presented as a function of probability of myelopathy from 0.1 to 99%. At a 50% incidence of myelopathy, the RBE (+/- 1 SE) was 5.22 +/- 0.15. A difference in the histopathology of lesions induced by photon and neutron treatments was observed.

Animals↗
PubMed1991

Radiation apoptosis of serous acinar cells of salivary and lacrimal glands.

Xerostomia and xerophthalmia are common and potentially serious local side effects of radiotherapy for head and neck cancer. Clinical observations supported by experimental findings show that radiation, even in low doses, causes acute diminutions of saliva and tears by rapidly killing the serous cells of the salivary and lacrimal glands, respectively. Serous acini of salivary and lacrimal glands have similar developmental, morphologic, and functional characteristics. Serous acinar cells are functionally mature, secretory epithelial cells that normally do not divide and are long lived. Irradiation of the salivary and lacrimal glands of rhesus monkeys resulted in selective death of serous acinar cells within 24 hours. The paradigm for acute radiation seroadenosis is intermitotic or interphase cell death caused by apoptosis.

Animals↗
PubMed1991

Cyclophosphamide 24 hours before or after total body irradiation: effects on lung and bone marrow.

Preparative regimens for bone marrow transplantation (BMT) use a sequence of drugs, such as cyclophosphamide, in combination with radiation. However, the optimum sequencing of the two agents that will maximize tumor cell kill and minimize normal tissue damage is unknown and controversial. The studies presented here were done in order to determine the effect of cyclophosphamide on bone marrow and lung damage in mice when given 24 h before or after total body irradiation (TBI). A range of single doses of TBI was given before or after a single sublethal dose of 180 mg/kg of cyclophosphamide. The bone marrow of all mice intended for lung damage assessment was reconstituted with 5 x 10(6) syngeneic bone marrow cells. Lung damage was assessed by breathing rate and lethality; bone marrow damage by lethality at 30 days. LD50 values for pneumonitis were obtained between 30 and 84 days after cyclophosphamide and radiation and between 80 and 180 days after radiation alone. Dose modifying factors were obtained as the ratio of LD50s for mice given only TBI compared to those for mice given cyclophosphamide and TBI. Cyclophosphamide enhanced radiation pneumonitis when given before or after TBI, giving DMFs of 1.4 and 1.2 (1.1-1.4, 95% c.l.) respectively. The effect of cyclophosphamide on radiation pneumonitis was drug dose-dependent. The LD50 for death from bone marrow damage was reduced when cyclophosphamide was given either before or after TBI but the effect was greater, i.e. the LD50 was lower when cyclophosphamide was given after TBI. These data show that cyclophosphamide given 24 h after TBI causes less lung damage but more bone marrow damage in this mouse model.

Animals↗
PubMed1991

Maxillary sinus carcinomas: natural history and results of postoperative radiotherapy.

Between 1969 and 1985, 73 patients with maxillary sinus cancers underwent surgical excision and postoperative radiotherapy. The clinical stage distribution by the AJC system was 3T1, 16T2, 32T3, and 22T4. Six patients had palpable lymphadenopathy at diagnosis. Surgery for the primary tumor consisted of partial or radical maxillectomy, and if disease stage indicated it, ipsilateral orbital exenteration. This was followed by radiation treatment delivered through a wedge-pair or three-field technique. All but three patients received 50-60 Gy in 2 Gy fractions to an isodose line defining the target volume. Elective neck irradiation was not routinely given. Clinically involved nodes were treated with definitive radiotherapy (five patients) or combined treatment (one patient). Forty-five patients had no evidence of disease at the last follow-up. The 5-year relapse-free survival for the whole group was 51% The overall local control rate was 78%. Patients with larger tumors, particularly if they also had histological signs of nerve invasion, had a higher recurrence rate than others. The overall nodal recurrence rate without elective neck treatment was 38% for squamous and undifferentiated carcinoma, and only 5% for adenoid cystic carcinomas. Therefore, our current recommendation is to deliver elective nodal irradiation routinely to patients with squamous or undifferentiated carcinoma, except for those who have T1 lesions. Treatment complications were vision impairment, brain and bone necrosis, trismus, hearing loss, and pituitary insufficiency. The incidence of major side effects was determined by disease extent and treatment technique. Many technical refinements were introduced in order to limit the dose to normal tissues in an attempt to reduce the complication rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1991

Professional liability in radiotherapy: experience of the Fletcher Society.

We have conducted a study to ascertain the pattern and background of lawsuits related to the practice of radiotherapy among physician-members of the Gilbert H. Fletcher Society. Eighty-four percent of the members of the society replied to the questionnaire; one-third have sustained a lawsuit with an actuarial probability of 30% at 10 years, 50% at 20 years, and 65% at 30 years. Lawsuits occurred across the spectrum of practice type, location, experience, disease site, and technique. Two-thirds of the suits were dropped or successfully defended. Regardless of the outcome, the experience of being sued was found to have influenced 33% of those sued to practice more conservatively. Recommendations of the membership directed towards minimizing the risk of being sued, while maintaining an aggressive treatment philosophy, are presented. Based on this study, we believe that formal medicolegal education should be included in the curriculum of radiotherapy residents' training program.

Humans↗
PubMed1991

Radiation therapy following resection of non-small cell bronchogenic carcinoma.

Between 1970 and 1982, 102 patients received postoperative radiotherapy after attempted curative resection of bronchogenic carcinoma at The University of Texas M. D. Anderson Cancer Center. Surviving patients had a minimum follow-up of 3 years. Eight patients had pathological Stage I disease, 29 Stage II, and 65 Stage III. The 5-year actuarial survivals for patients with stages I, II, and III disease were 83%, 55%, and 38%, respectively (p = .04). Corresponding values for patients with N0, N1, and N2 disease were 74%, 56%, and 28% (p = .01). No significant differences in survival were seen based on T stage or tumor histology. Nine patients had gross residual disease following surgery, and 19 had microscopic residual disease. The 5-year actuarial survival was 78% for 12 patients without nodal disease who had known gross (4 patients) or microscopic (8 patients) residual tumor following attempted curative resection. The pathologic status of the hilar and mediastinal lymph nodes was the most significant factor affecting the frequency of metastatic relapse, with 19% of patients with N0, 33% of those with N1, and 69% of those with N2 disease developing distant disease. The low overall rate of recurrence intrathoracically (16%) confirms that postoperative radiotherapy is effective in preventing local relapse even in patients with proven nodal involvement. The impact of adjuvant radiation therapy on survival cannot be determined from these data, and further data are needed, preferably from well designed prospective studies.

Adenocarcinoma↗
PubMed1991

Twice-daily, split-course abdominopelvic radiation therapy after chemotherapy and positive second-look laparotomy for epithelial ovarian carcinoma.

Between July 1983 and December 1988, 34 patients with ovarian carcinoma received whole abdominal irradiation in an attempt to eliminate residual disease following second-look laparotomy. Three additional patients who had initial complete responses to chemotherapy were treated for a recurrence of their disease. All patients had been treated with chemotherapy that included cisplatin and cyclophosphamide. Three patients had also received doxorubicin with some or all chemotherapy cycles. Thirty Gray of abdominopelvic radiation therapy (APRT) was delivered using a twice-daily, split-course schedule. Eleven patients also had a boost of 9-20 Gy to sites of residual disease. Treatment was well tolerated. Only one patient did not complete therapy and two patients had 1-week prolongations of treatment because of hematologic toxicity. Thirty-two percent of patients had grade 2 neoplasms and 61% had grade 3 disease. Three patients with grade 1 tumors continue to have no evidence of disease 20-50 months after irradiation. Patients with grade 2 and 3 neoplasms who had microscopic residual disease prior to APRT had relapse-free survival rates at 3-years of 10% and 14%, respectively. Twelve patients with gross residual disease had rapid recurrences (median time to relapse, 4.9 months) and all have died of their disease. Although 14 patients (38%) have experienced small bowel obstructions, all of these had known recurrent abdominal disease at the time. Twenty patients (54%) had undergone more than two abdominal surgeries prior to APRT, and several were noted to have extensive adhesions at second-look laparotomy. None of the five patients currently believed to be free of disease has experienced a small bowel obstruction. Radiation is only one of several factors that contributed to bowel obstructions. Although APRT may be able to eliminate residual disease in a small proportion of patients with microscopic residual disease after chemotherapy, the aggressive biology of tumors that respond incompletely to chemotherapy and the compromises in radiation dose and schedule that must be made in these heavily treated patients probably contribute to the disappointing results of this treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck.

BACKGROUND: Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors. Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis. METHODS: We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity. After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months. RESULTS: There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers. However, the isotretinoin group had significantly fewer second primary tumors. After a median follow-up of 32 months, only 2 patients (4 percent) in the isotretinoin group had second primary tumors, as compared with 12 (24 percent) in the placebo group (P = 0.005). Multiple second primary tumors occurred in four patients, all of whom were in the placebo group. Of the 14 second cancers, 13 (93 percent) occurred in the head and neck, esophagus, or lung. CONCLUSIONS: Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor.

Adult↗
PubMed1990

Regional radiotherapy as adjuvant treatment for head and neck malignant melanoma. Preliminary results.

From 1983 through 1988, 83 patients with high-risk cutaneous malignant melanoma (primary lesion thicker than 1.5 mm or palpable lymphadenopathy) of the head and neck region were enrolled in a study designed to assess the efficacy of a few large doses of radiation (24 to 30 Gy in 4 to 5 fractions). The actuarial 2-year locoregional control rates for the three groups were 95%, 90%, and 83%, respectively. Corresponding survival rates were 80%, 71%, and 69%. The majority of failures were due to distant metastases. Locoregional control rates were better than those reported earlier with surgery alone for comparable patients. The treatment morbidity was minimal.

Adolescent↗