Biomedical subjects

K K Ang

Publications and source records attributed to K K Ang.

At least 91 records · Page 5Linked to original sources

PubMed1994

Modulation of fibrinolysis by ionizing radiation.

Radiation-induced damage to the central nervous system is believed to be targeted to glial or endothelial cells or both, although the pathophysiology of this process is still poorly understood. A series of experiments were, therefore, conducted, including irradiation to primary rat astrocytes (in vitro) and rat spinal cords (in vivo). The levels of plasminogen activators (uPA and tPA) and their inhibitors (PNI and PAI-1) were determined by fibrin zymography, ELISA, amidolytic activity assay, complex formation, and Western blot analysis. Fibrin zymography revealed the presence of M(r) 48,000 (uPA) and M(r) 68,000 (tPA) lytic bands that were increased in irradiated samples. Three- to four-fold higher levels of tPA and 8- to 10-fold higher levels of uPA were detected in irradiated samples. Western blot analysis confirmed the presence of a 51-kDa band (PAI-1) in irradiated samples. PAI-1 is undetectable in nonirradiated spinal cord. Serum-free medium and cell and spinal cord extracts of nonirradiated samples showed a 43-kDa band (PNI), the intensity of which is decreased in irradiated samples. Four- to five-fold decreased levels of PNI were detected in irradiated serum-free media and cell extracts, but no levels of PNI were detected in irradiated spinal cord extracts. This study provides additional information regarding the proposed roles of plasminogen activators and their inhibitors in the development of CNS damage after irradiation.

Animals↗

PubMed1994

Radiation-induced injury to the visual pathway.

Radiation-induced injury to the visual pathway was reviewed in a cohort of patients treated for various cancers of the nasal cavity and paranasal sinuses between 1969 and 1985. The study subjects consisted of 219 patients, 137 men and 82 women, in whom detailed records were available on the extent of orbital shielding, treatment plan for estimating doses delivered to various optic structures, and visual acuity follow-up information. There was a wide range in doses administered to various optic structures because patients with different primary lesion types were included and the radiotherapy techniques used varied during this era. The endpoint of the study was visual acuity < 20/100. The Cox proportional hazard model was used to assess the influence of various factors on the latent time to visual impairment and to fit the LQ model to the failure-time data. Actuarial curves showing the proportion of patients with visual impairment as a function of dose and time were generated. Corneal injury occurred in 24 of the 49 patients treated with the 3-field technique without any orbital shielding; variables affecting the incidence of cornea injury were total radiation dose and chemotherapy. Symptomatic retinopathy was diagnosed in 7 of 77 patients who received irradiation to a relatively large retinal surface, but no variables were found to correlate with this complication. Eight patients developed ipsilateral blindness due to optic neuropathy and 11 patients had bilateral visual impairment secondary to chiasm injury. The total radiation dose was identified as the predominant determinant. None of patients receiving a dose of < 50 Gy developed optic neuropathy or chiasm injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Blindness↗

PubMed1994

Plasminogen activator inhibitor-1 in the pathogenesis of delayed radiation damage in rat spinal cord in vivo.

The pathophysiology of radiation-induced damage to the central nervous system (CNS) is poorly understood. Preliminary data suggest that fibrinolytic inhibitors are involved in the development of necrosis. In this study, cervical spinal cord irradiation was studied in 90 rats by measuring plasminogen activator inhibitor (PAI)-1 on Days 2, 7, 30, 60, 90, 120, 130, or 145 after irradiation. Paralysis due to radiation necrosis developed in all animals kept alive for 140 to 150 days. Assay of PAI-1 was by Western blot, enzyme-linked immunosorbent assay (ELISA), and complex formation with 125I-labeled urokinase. No PAI-1 was detected in normal spinal cord tissue or in irradiated spinal cord up to Day 90. However, PAI-1 was detected at Day 120 and was marked by elevated ELISA levels at the time of paralysis. Western blot showed detectable PAI-1 (51 kD) at Day 120 and very significant levels at the time of paralysis. Complex formation with 125I-labeled urokinase was also detected at Day 120 with similar results. Immunohistochemical studies showed that PAI-1 was highly concentrated within and immediately adjacent to zones of necrosis at 145 days and was absent in normal tissue. This study adds considerable weight to the proposal that PAI-1 is closely associated with the pathogenesis of CNS radiation necrosis.

Animals↗

PubMed1994

Prevention and management of radiation myelopathy.

The dramatic nature of radiation-induced spinal cord injury causes clinicians to avoid doses that could lead to this complication, sometimes even to the point of possibly compromising tumor control. As a consequence, clinical data on radiation myelopathy are limited. So far, experimental investigations have been devoted to establishing the dose-response, time-dose-fractionation relationships, and volume effects for CNS injury in various animal models. Concepts and parameters gained from such laboratory studies have been useful for the development of new radiotherapy strategies in terms of dose fraction schedules and dose adjustments as a function of radiation volumes. Further advances in therapeutic strategies, however, must come from elucidation of the pathogenesis of radiation-induced CNS injury. Results of recent studies warrant revision of the current concept that such injuries result simply from reproductive killing of glial "stem cells" and endothelial cells. Emerging evidence indicates that various cell types contribute to determining the progression of radiation lesions.

Animals↗

PubMed1994

Elevated levels of plasminogen activators in the pathogenesis of delayed radiation damage in rat cervical spinal cord in vivo.

The pathophysiology of the cellular basis of radiation-induced demyelination and white-matter necrosis of the central nervous system (CNS) is poorly understood. Preliminary data suggest that tissue damage is partly mediated through changes in the proteolytic enzymes. In this study, we irradiated rat cervical spinal cords with single doses of 24 Gy of 18 MV photons or 20 MeV electrons and measured the levels of plasminogen activators at days 2, 7, 30, 60, 90, 120, 130 and 145 after irradiation, using appropriate controls at each time. Fibrin zymography revealed fibrinolytic bands representing molecular weights of 68,000 and 48,000 in controls and irradiated samples; these bands increased significantly at days 120, 130 and 145 after irradiation. Inhibition of these enzymatic bands with specific antibodies against tissue-type plasminogen activator (tPA) and amiloride, an inhibitor for urokinase plasminogen activator (uPA), confirmed that these bands were tPA and uPA. Enzymatic levels quantified by densitometry showed a twofold elevation in the levels of tPA and more than a tenfold increase in uPA after 120 days' irradiation. Activity of uPA was increased threefold by day 2 and increased steadily with time compared to nonirradiated control samples. Enzyme-linked immunosorbent assay (ELISA) also showed a threefold increase in the tPA content in the extracts of irradiated rat cervical spinal cords at days 120, 130 and 145. This study adds additional information to the proposed role of plasminogen activators in the pathogenic pathways of radiation damage in the CNS.

Animals↗

PubMed1993

Prospective comparison of in vitro normal cell radiosensitivity and normal tissue reactions in radiotherapy patients.

PURPOSE: This pilot study was undertaken to assess the relationship between in vitro radiosensitivity of different normal cell types and the type and severity of normal tissue reactions in individual patients after radiotherapy. METHODS AND MATERIALS: Twenty-one patients with head and neck cancer were studied prospectively; four with head and neck and two with breast cancer were studied retrospectively. The retrospective cases were chosen because they exhibited unusual (severe or minimal) normal tissue reactions after radiotherapy. Small skin biopsies and blood samples were obtained and used to generate in vitro fibroblast and lymphocyte cultures, respectively. Clonogenic assays were used to measure in vitro fibroblast and lymphocyte radiosensitivity after high- and low-dose rate irradiation. Head and neck patients were treated by conventional, hyperfractionated, or concomitant boost regimens, which have been found to yield an equal probability of late normal tissue reactions. The highest dose received by each normal tissue in the target volume was estimated using computed tomography treatment plans. The median patient follow-up time was 19 months (range: 13-25). RESULTS: The distributions of in vitro radiosensitivity parameters and the grade of tissue reaction scores in the patients showed a broad range between individuals. When in vitro parameters were compared to the acute and late tissue reactions, the radiosensitivity of fibroblasts, measured as surviving fraction at 2 Gy after high-dose rate irradiation, showed a highly significant correlation with the maximum grade of late effects (p < 0.0001 for the whole group and p = 0.0013 for the group of patients studied prospectively). No significant correlation was found between fibroblast radiosensitivity and maximum grade of acute effects or between lymphocyte radiosensitivity and either acute or late effects. CONCLUSION: We conclude that individuals vary in normal cell radiosensitivity, and that in vitro measurements of fibroblast radiosensitivity may predict the magnitude of late normal tissue reactions after radiotherapy. These preliminary results, however, need to be validated in a larger group of patients.

Biopsy↗

PubMed1993

Decreased levels of glia-derived nexin/protease nexin I in irradiated rat spinal cord in vivo.

The pathophysiology of the cellular basis of radiation induced demyelination and white matter necrosis of the Central Nervous System (CNS) is poorly understood. There have been no previous studies that have shown the effect of irradiation on glia-derived nexin. In this study, rats were given cervical spinal cord irradiation, and glial derived nexin or protease nexin I (GDN/PNI) was measured on days 2, 7, 30, 60, 120, 130, and 145 after irradiation. The level of GDN/PNI significantly decreased after irradiation compared to levels in control spinal cord, and there was no detectable levels of GDN/PNI by the time paralysis developed. This study adds considerable weight to the proposal that GDN/PNI has an important role in the pathogenesis of CNS radiation damage.

Amyloid beta-Protein Precursor↗

PubMed1993

Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial.

PURPOSE: This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors. METHODS AND MATERIALS: Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving > 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk. RESULTS: The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of < or = 54 Gy had a significantly higher primary failure rate than those receiving > or = 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at > or = 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, > or = 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status > or = 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received > or = 63 Gy. CONCLUSION: With daily fractions of 1.7 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio.

Adult↗

PubMed1993

The tolerance of primate spinal cord to re-irradiation.

PURPOSE: This study was designed to assess the tolerance of the cervical spinal cord of rhesus monkeys to re-irradiation. This information is essential for treatment recommendations in previously irradiated patients. METHODS AND MATERIALS: Control animals received a single course of treatment to total doses of 70.4 Gy, 77.0 Gy, or 83.6 Gy in daily fractions of 2.2 Gy. Twelve asymptomatic animals that received 70.4 Gy were re-irradiated two years later to cumulative doses of 83.6, 92.4, or 101.2 Gy. Another group of 15 animals received 44 Gy and two years later were re-irradiated to cumulative doses of 83.6, 92.4, 101.2, or 110 Gy. The clinical endpoint was myeloparesis. A complete necropsy was performed in all animals when myeloparesis manifested or at the end of observation period. RESULTS: Only two of the 12 asymptomatic animals of the 70.4 Gy dose-response study group and two of the 15 animals that had received 44 Gy initially developed myelopathy within two years of re-irradiation. The ED50 value of the single-course irradiation was 76.1 +/- 1.9 Gy, while the extrapolated ED50 for retreatment after 44 Gy was > or = 110 Gy. The lesions of the two symptomatic animals that received 70.4 Gy initially were mixtures of white matter and vascular lesions similar to those observed after single course irradiation. However, both symptomatic animals given 44 Gy initially had hemorrhagic infarcts in the white matter. CONCLUSION: The results of this study indicate that substantial recovery of occult injuries induced by the initial 44 Gy had occurred within two years. The difference between the types of lesions observed after a single course and re-irradiation suggests that vascular injury may recover less efficiently or at slower rate than white matter damage. The dependence of the extent of recovery on the initial dose and the time course of such recovery in primates are being investigated.

Animals↗

PubMed1993

Squamous cell carcinoma of the maxillary sinus.

Eighty-five patients with squamous cell cancer of the maxillary sinus received all of their treatment at The University of Texas M.D. Anderson Cancer Center between the years 1971 and 1986. Their records were evaluated according to stage, disease at presentation, symptoms and signs at presentation, treatment, and outcome. There were no differences in locoregional control or survival between groups treated with surgery alone vs surgery plus radiotherapy. Careful analysis of the data indicates that there was almost certainly some selection bias for the patients undergoing combination therapy, as most of this group had historically adverse prognostic factors identified. Those patients who underwent radiotherapy alone or chemotherapy presented with either metastatic or locally advanced disease and were treated with palliative intent; therefore, comparison between this group and standard therapy groups was impossible in this retrospective review. Although it is tempting to speculate that combination therapy improved locoregional control and survival in patients with more advanced disease, none of the data presented in this review reach statistical significance. Furthermore, there is no difference in survival in this population compared with a study at this institution 20 years ago. Squamous cell cancer of the maxillary sinus continues to be a challenging neoplasm. Radiotherapy may improve locoregional control and survival in a group of patients with more advanced disease and may have its greatest utility in earlier-stage disease. A multi-institutional prospective trial is needed to find ways to improve outcome in this patient population.

Adolescent↗

PubMed1993

Analysis of interleukin-2-activated killer cells of rhesus monkeys: striking resemblance to the human system.

We have found numerous and exquisite homologies between the interleukin-2 (IL-2)-activated killing systems of rhesus monkeys and humans. Lymphocytes with high oncolytic and proliferative activity were generated from peripheral blood, spleen, and bone marrow of monkeys after culture with IL-2. The distribution of lymphocyte subsets in IL-2 cultures closely paralleled that seen in humans, including a decrease in CD4+ and increase in CD8+, CD38+, and CD25+ lymphocytes and an increase in density of CD2 molecules. We also describe three distinct subsets of monkey lymphocytes, CD16+,56-, CD16+,56+"dim", and CD16-,56+"bright", and show that the CD56+"bright" subset is substantially increased (to as high as 79%) after IL-2 activation. Furthermore, as in humans, the cells with oncolytic activity were characterized as CD56+, CD16+/-, and CD8+. This strong homology with humans indicates that the rhesus monkey may be a valuable preclinical model for evaluation of therapeutically relevant biological response modifiers.

Animals↗

PubMed1993

Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies.

Fifteen different murine tumours were evaluated with respect to the degree of apoptosis development that occurs in the tumour tissue in the first few hours following irradiation in vivo. Animals were killed at 3 or 6 h following irradiation with 0, 2.5, 10 or 25 Gy. Apoptosis was scored as percent aberrant nuclei by microscopic examination of histological sections made from the tumour specimens. Results showed that three of four mammary adenocarcinomas, one ovarian adenocarcinoma, and one lymphoma displayed at least 10% apoptotic cells after 25 Gy, whereas five sarcomas, three squamous cell carcinomas, and a hepatocarcinoma did not. The time courses and dose responses were similar in those tumours that responded. These data were compared with the known response of these same tumours when analysed using conventional assays. The tumours that did respond by significant apoptosis had longer specific growth delays and lower TCD50 (dose to cure 50% of animals) doses, thus suggesting that an acute apoptotic response following irradiation may be a feature of certain tumours that respond well to irradiation. Additionally, this analysis revealed heterogeneity in the apoptotic response both within an individual tumour specimen and among different tumour types. These observations of intra and intertumour heterogeneity are consistent with the idea that the propensity for apoptosis in tumours is genetically regulated.

Adenocarcinoma↗

PubMed1993

Radiotherapy for head and neck neoplasms.

This review presents several relatively new areas of interest in radiotherapy for head and neck neoplasms. In the clinical arena, improving radiotherapy outcome by altering radiation schedules has undergone rigorous testing in patients with squamous cell carcinomas. The initial results show that such an approach increases the local control rate in subsets of patients by 10% to 15%. Randomized multi-institutional studies, sponsored by large cooperative groups, are ongoing to assess the relative merits of various altered fractionation strategies. In the field of laboratory investigations, attempts have been made to develop tests reliable in predicting the radiation response of tumors and normal tissues. If successful, it would be possible to design the optimal radiation regimen for individual patients based on the results of these tests, thereby improving the therapeutic ratio. Technologic innovations have enhanced the flexibility to conform radiation to the target volume so that higher doses can be delivered to the tumor without exceeding the tolerance of the surrounding normal tissues. Large-scale clinical studies evaluating the value of conformal therapy are being developed. Finally, long-term results of radiotherapy in the management of chemodectomas have been reported in recent years. These data have clearly defined the role of radiotherapy in the treatment of skull-base paragangliomas.

Clinical Trials as Topic↗

PubMed1993

Development of apoptosis in irradiated murine tumors as a function of time and dose.

In a previous paper (Radiat. Res. 127, 308-316, 1991), we reported that a moderately radiosensitive, transplantable murine ovarian carcinoma (OCaI) displayed apoptosis after irradiation whereas a radioresistant hepatocellular carcinoma (HCaI) did not. These initial observations have been followed up in this detailed analysis of the development of apoptosis in these two tumors as a function of time and dose. Histological sections of OCaI and HCaI carcinomas were scored at various times between 0.5 and 24 h after single doses of 2.5 or 25 Gy gamma radiation for the incidence of apoptosis. The percentage of nuclei undergoing apoptosis in untreated tumors was 5% in OCaI and 0.6% in HCaI. The peak in the number of apoptotic bodies occurred in the OCaI tumors 3-5 h after either dose. After 2.5 Gy, the peak incidence was about 20% and after 25 Gy it was about 30%. Irrespective of dose, HCaI tumors had an incidence of apoptosis of less than 3%. Based on the results of this time course, 4 h after irradiation was chosen for the determination of the dose response, over doses ranging from 2.5 to 25 Gy. The dose response for the OCaI tumors reached a plateau at 25-30% apoptotic nuclei after doses of about 7.5 Gy and above. Autoradiographic analysis of histological sections from mice injected with [3H]thymidine showed that some apoptotic bodies in the OCaI tumors arose from cycling cells. These results confirm that the apoptotic mode of cell death may represent an important response in some irradiated tumors.

Animals↗

PubMed1992

Intrinsic radiosensitivity of normal human fibroblasts and lymphocytes after high- and low-dose-rate irradiation.

The existence of heritable radiosensitivity syndromes and clinical observations in radiotherapy patients suggests that human cellular radiosensitivity differs among individuals. We report here an in vitro study of radiosensitivity in 30 fibroblast and 29 lymphocyte cultures obtained from cancer patients and controls. In 25 cases, both fibroblasts and lymphocytes were obtained from the same donors. Fibroblasts were cultured from skin biopsy samples, and peripheral T-cell lymphocytes were cultured from blood. Clonogenic survival assays were performed by using high- and low-dose-rate irradiation; lymphocytes were in G0 phase and fibroblasts in confluent plateau phase. Various end points were calculated and compared (i.e., surviving fraction at 2 Gy, initial slope of the survival curve, and doses resulting in 10 and 1% survival, respectively). Depending on the end point, the coefficient of variation of the survival parameters ranged from 31 to 68% for lymphocytes and 21 to 41% for fibroblasts following high-dose-rate irradiation. Similar ranges were obtained after low-dose-rate irradiation. Variance analysis performed on replicate assays in cultures derived from the same patient showed that variation due to technical or sampling errors was significantly lower than variation between individuals (P = 0.00034 and 0.014 for fibroblasts and lymphocytes, respectively). No correlation was observed between the radiosensitivity of lymphocyte and fibroblast cultures derived from the same donors. We conclude that there is significant variation in normal cell radiosensitivity among individuals. On the other hand, comparisons of lymphocyte and fibroblast radiosensitivities suggest that tissue-specific characteristics, such as differentiation status, may variably modulate radiosensitivity.

Breast Neoplasms↗

PubMed1992

Is the experience with CHART compatible with experimental data? A new model of repair kinetics and computer simulations.

A new incomplete repair model is introduced that differs from previous models of this type by not assuming that repair is complete during long intervals, e.g. "overnight" intervals of 12-24 h. The model was used to assess the risk of myelopathy resulting from continuous hyperfractionated accelerated radiotherapy treatment (CHART) in light of recent experimental data on the rat spinal cord. Model calculations employing biexponential repair kinetics showed that CHART treatments might result in a higher myelopathy risk than an equal dose given in conventional 2-Gy fractions if the parameters obtained from the animal data hold. The probability of observing what has been reported for CHART was determined in computer simulations for different variance scenarios. The chance to observe four myelopathies in the 74 cervical cord patients was estimated to range between 25 and 62%, while the probability to see 0 in 68 thoracic cord patients ranged from 48 to 27%. These numbers were derived from reasonable assumptions about the repair kinetics (e.g. 60% of damage repaired with a half-time of 8 h) so that the over-all probability to observe 4/74 and 0/68 was maximized, and depending on the scenario fell in the range 12-17%. Finally, from these simulations a myelopathy risk of approximately 0.3-1.2% is predicted for the currently employed maximal CHART dose to the spinal cord, i.e. 42 Gy. We conclude that the CHART experience is not compatible with the new experimental data (p < 5%). Incomplete repair is unlikely to be the sole reason for the unexpected toxicity of CHART (p < or = 17%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Impact of spinal cord repair kinetics on the practice of altered fractionation schedules.

The kinetics of repair of sublethal lesions in the spinal cord was assessed in detail using a rodent model. Experiments were designed to obtain the fractionation sensitivity, alpha/beta, and to quantify the kinetics of repair after a clinically relevant fraction size. Pairs of 2-Gy fractions at intervals ranging from 0 to 24 h were given from Monday through Friday, to cumulative doses of 40-84 Gy. In addition, two groups of animals received 1.5 or 1.2 Gy twice a day at 8-h intervals, 5 days a week, to total doses of 66-90 Gy and 67.2-98.4 Gy, respectively. All irradiations were followed by a top-up dose of 16 Gy. Analysis of the experimental data revealed that a bi-exponential repair model fit the experimental data significantly better than did the mono-exponential model (p = 0.002). The repair half times obtained were 0.7 (0.2-1.3) h and 3.8 (2.6-4.9) h, respectively. The proportion of injury repaired by the longer half time was estimated to be 0.62 (0.37-0.86). The data showed that delivering 2 fractions per day at 6- or 8-h intervals instead of one per day led to a 16.5% (11.8-21.1%) and 13.5% (9.1-17.8%) reduction in the tolerance, respectively. Finally, the results indicated that when incomplete repair between fractions was accounted for, the linear-quadratic (LQ) model was valid in describing fractionation response down to 1.2 Gy per fraction.

Animals↗

PubMed1992

Carcinomas of the nasal cavity.

Between 1969 and 1985, 45 patients with carcinomas of the nasal cavity proper received curative treatment. Thirty patients had squamous cell carcinoma, one had undifferentiated carcinoma, 9 had adenocarcinoma, and 5 had adenoid cystic carcinoma. Eighteen patients were treated with definitive radiotherapy (interstitial brachytherapy in 5 and external beam therapy in 13 patients), and 27 received surgery and radiotherapy. The median length of follow-up was 11 years (range: 2.8-16.8 years). Thirty-six patients had no evidence of disease at the last follow-up visit. All 14 patients with carcinoma of the nasal septum had the disease controlled. Nine of 31 patients with lesions of the lateral wall and floor died of the disease, 5 of uncontrolled local disease, 2 of distant metastases, and 2 of both. The disease-specific survival rates at 5 and 10 years were 83 and 80%, respectively, and the corresponding overall survival rates were 75 and 60%, respectively. Blindness occurred in 4 patients, 2 due to orbital exenteration and 2 to radiation injury to the cornea and optic pathway. Other infrequent side effects were bone necrosis, dental decay, nasal stenosis, and septal perforation. This study indicated that the prognosis of patients with nasal cavity carcinoma was better than that of patients with maxillary sinus cancer treated during the same era. In addition, the study showed that carcinomas of the nasal septum were smaller than those of lateral wall and floor at diagnosis, so that excellent control could be achieved by definitive radiotherapy; when accessible, interstitial brachytherapy might be the treatment of choice in such patients.

Adenocarcinoma↗