Biomedical subjects

M Austin-Seymour

Publications and source records attributed to M Austin-Seymour.

32 records · Page 2Linked to original sources

PubMed1989

Fractionated proton radiation therapy of chordoma and low-grade chondrosarcoma of the base of the skull.

Sixty-eight patients with chordoma or low-grade chondrosarcoma at the base of the skull received fractionated high-dose postoperative radiation delivered with a 160-MeV proton beam. Protons have favorable physical characteristics which allow the delivery of high doses of radiation to these critically located tumors. The methods employed for these treatments are described. These patients have been followed for at least 17 months and for a median of 34 months. The median tumor dose was 69 CGE (cobalt Gy equivalent): CGE is the dose in proton Gy multiplied by 1.1, which is the relative biological effectiveness for protons compared to cobalt-60. The daily dose was 1.8 to 2.1 CGE. For this group the 5-year actuarial local control rate is 82% and disease-free survival rate is 76%. The incidence of treatment-related morbidity has been acceptable.

Adolescent↗

PubMed1988

Conservative treatment of uveal melanoma: probability of eye retention after proton treatment.

Enucleation was performed after proton treatment in 57 of 1006 (5.7%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986. Only 2% of 99 patients with small tumors and 4% of 566 patients with intermediate size tumors underwent enucleation after treatment; 10% of 341 patients with large tumors lost the treated eye. No eyes were removed after 52 months, with 89% of enucleations performed during the first 36 months after treatment. Eye retention rates at 60 months were 89.1 +/- 3.0% for the entire group, and 97 +/- 3.7%, 92.7 +/- 3.1%, and 78.3 +/- 7.0% in patients with small, intermediate, and large tumors, respectively. Significantly greater enucleation rates were observed in patients with large tumors than in those with intermediate tumors (p = less than .0001), in patients with tumor height greater than 8 mm relative to those with tumors less than or equal to 8 mm, p = (less than .0001), with tumor diameter greater than 16 mm compared to less than or equal to 16 mm, (p = less than .0001), and with tumor involvement of the ciliary body compared to involvement of the choroid only (p = less than .0001). Possible strategies to decrease the likelihood of enucleation in patients at apparently increased risk of losing the eye after conservative therapy, that is, those with large tumors involving the ciliary body, might include a lower total dose, a more protracted treatment course, or a lower radiation dose and adjuvant treatment with chemotherapy and/or immunotherapy, with hyperthermia, or with other radiation sensitizers.

Actuarial Analysis↗

PubMed1988

Endocrine function following high dose proton therapy for tumors of the upper clivus.

The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

Adolescent↗

PubMed1988

The role of MR and CT in evaluating clival chordomas and chondrosarcomas.

Sixteen chordomas and nine chondrosarcomas of the clivus were evaluated with CT and MR either before (22 cases) or after (three cases) treatment with proton beam irradiation. The ability of these imaging techniques to provide information necessary to direct patient treatment was studied. The tumor was detected and its gross margins were identified by both techniques in all instances. No reliable diagnostic features allowing differentiation between these two tumors were encountered. MR generally was superior in defining the exact position of the brainstem and optic chiasm relative to the tumor, and it frequently provided superior information about tumor extension into the nasopharynx and cavernous sinus. CT was always better than MR in demonstrating tumoral calcification and in defining the exact anatomy of bone destruction. MR was generally superior to CT in demonstrating the position of the cavernous internal carotid artery relative to the tumor and often provided superior visualization of the vertebral and basilar arteries. In cases in which bone-induced artifact obscured the interface between the neural axis and tumor in the CT image, or in which the tumor had suprasellar extension and was likely to compress the optic chiasm and tracts, MR was of great value in planning irradiation therapy. The high occurrence of clinically asymptomatic signal intensity alterations in the MR studies of previously treated patients appears to limit the differential diagnostic value of this information. Given its greater availability and lower cost, CT appears to be the technique of choice for routine follow-up of previously treated patients.

Adolescent↗

PubMed1987

Uveal melanomas near the optic disc or fovea. Visual results after proton beam irradiation.

Proximity to the disc and fovea is a risk factor for visual loss after proton beam irradiation of uveal melanomas. Of 562 eyes treated over a 10-year period with pretreatment visual acuity of 20/200 or better, 363 (64.6%) contained tumors within 2 disc diameters (DD) of the disc or fovea. Rates of visual loss after treatment to worse than 20/200 and causes of visual decline were evaluated using Kaplan-Meier analysis. Cumulative rates of visual loss among subjects with tumors near the disc or fovea were 33 and 47% 1 and 2 years after treatment compared to 17 and 28%, respectively, for subjects with tumors located farther from both structures. The leading cause of visual loss in the first year among eyes with tumors near the disc or fovea was retinal detachment. Controlling for other predictors of visual loss to worse than 20/200, location near the disc or fovea was independently related to visual loss primarily due to retinal detachment, cataract, and radiation retinopathy. Despite the unfavorable location of these tumors, over half of patients with 20/200 or better pretreatment visual acuity had useful vision 2 years after treatment.

Cataract↗

PubMed1987

Long-term results of proton beam irradiated uveal melanomas.

The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis.

Eye Diseases↗

PubMed1987

[Fractionated proton radiotherapy].

Investigations in proton beam therapy of cancer patients have been initiated at the Cyclotron Laboratory, Harvard University, Cambridge, USA, since 1974 using a proton beam with the energy of 160 MeV for fractionated irradiation of uveal melanoma (899 cases), chordoma and chondrosarcoma of the base of the skull (96), sarcoma of the soft tissues and bones (79), prostatic cancer, head and neck tumors, etc. (altogether 1331 patients had been irradiated by June, 1986). To stop a beam in the target computer-assisted three-dimensional design and heterogeneity calculations were performed; computed compensatory boles were produced. Proton beam therapy is used alone or in combination with proton beam irradiation, routine radiotherapy. Areas of particular interest are ocular melanoma, chordoma and chondrosarcoma of the base of the skull, paraspinal sarcomas. Investigations in the field of proton beam therapy of malignant meningioma, metastases to the paraaortic lymph nodes hold promise.

Humans↗

PubMed1986

Prognostic factors for metastasis following proton beam irradiation of uveal melanomas.

Prognostic indicators for the development of metastasis following proton beam irradiation of uveal melanomas were evaluated for 510 patients treated from 1975 to 1984. Thirty-three patients developed metastasis (6.5%) from 3 to 51 months following treatment. The primary site of metastasis was the liver in 28 cases (85%). Both demographic and clinical factors were considered. The three leading predictors of survival without metastasis after proton beam irradiation in order of importance were: (1) largest diameter of the tumor; (2) location of the anterior margin of the tumor; and (3) age at treatment. Worse prognosis was associated with largest tumor diameter greater than 15.0 mm, tumor involvement of the ciliary body and age at treatment older than 59 years.

Adult↗

PubMed1986

Visual outcome after proton beam irradiation of uveal melanoma.

Prognostic factors for visual loss following proton irradiation of uveal melanoma were evaluated for 440 eyes treated from 1975 to 1984, with visual acuity 20/200 or better before treatment. Analysis involved Kaplan-Meier survival curves and Cox proportional hazards analysis with visual outcome defined as worse than 20/200. Prognostic factors were tumor height: rate ratio (ratio of rate of visual loss for one category of the variable relative to the rate of visual loss for a reference category of that variable) of 5.26 (95% confidence interval, 2.66-10.39) for tumors greater than 5 mm compared to tumors 3.0 mm or less in height; distance of tumor from the optic disc and fovea: rate ratio 2.59 (1.63-4.11) for tumors 2DD or less from both the optic disc and fovea compared to those greater than 2 DD from these structures. Also predictive of visual loss were tumor location close to disc only, or close to fovea only, macular detachment, worse pretreatment vision, and higher radiation doses delivered to both the disc and fovea, and lens. Regression analysis using a visual acuity scale gave similar results.

Adolescent↗

PubMed1985

192Ir pharyngoepiglottic fold interstitial implants. The key to successful treatment of base tongue carcinoma by radiation therapy.

Twenty-eight patients with squamous carcinomas of the base tongue were seen and evaluated in a conjoint Head and Neck Tumor Board at Stanford between 1976 and 1982. Fourteen patients were treated by combined external beam and interstitial irradiation, 11 of whom had Stage III and IV carcinomas (American Joint Committee). An initial dose of 5000 to 5500 rad was first delivered by external beam irradiation in 5 to 5.5 weeks, followed approximately 3 weeks later by an iridium 192 (192Ir) interstitial implant boost by the trocar and loop technique. The key to successful treatment of these neoplasms was found to be the use of a lateral percutaneous cervical technique, which placed horizontal loops through the oropharyngeal wall above and below the hyoid bone; the superior loop included the pharyngoepiglottic fold and the tonsilloglossal groove. Standard multiple loop implants (submentally inserted) of the base tongue from the vallecula anteriorly to the circumvallate papillae were also used routinely. This approach has been successful, since 10 of the 14 patients (71%) remain without evidence of disease (mean follow-up, 32 months). There have been only two local recurrences, both on the pharyngoepiglottic fold in patients who did not receive the now standard pharyngoepiglottic fold/lateral pharyngeal wall implants. No patients have relapsed after 18 months. The other 14 patients were treated prospectively during the same period by combining initial resection, radical neck dissection, and postoperative irradiation. In this group, there were more locoregional failures compared to the group treated with radiation therapy alone (5 tongue recurrences and 7 neck relapses); in addition, more severe complications were noted in these 14 patients who received surgery and postoperative irradiation. The authors believe that combined external beam and interstitial irradiation is effective treatment for base tongue carcinomas, especially when the high-dose distribution includes the adjacent tonsilloglossal groove, pharyngoepiglottic fold, and oropharyngeal wall to and below the level of the hyoid bone, in addition to treating an adequate base tongue volume.

Brachytherapy↗

PubMed1985

Precision, high dose radiotherapy. II. Helium ion treatment of tumors adjacent to critical central nervous system structures.

In this paper we present a technique for treating relatively small, low grade tumors located very close to critical, radiation sensitive central nervous system structures such as the spinal cord and the brain stem. A beam of helium ions is used to irradiate the tumor. The nearby normal tissues are protected by exploiting the superb dose localization properties of this beam, particularly its well defined and controllable range in tissue, the increased dose deposited near the end of this range (i.e., the Bragg peak), the sharp decrease in dose beyond the Bragg peak, and the sharp penumbra of the beam. To execute this type of treatment, extreme care must be taken in localization of the tumor and normal tissues, as well as in treatment planning and dosimetry, patient immobilization, and verification of treatment delivery. To illustrate the technique, we present a group of 19 patients treated for chordomas, meningiomas and low grade chondrosarcomas in the base of the skull or spinal column. We have been able to deliver high, uniform doses to the target volumes (doses equivalent to 60 to 80 Gy of cobalt-60) while keeping the doses to the nearby critical tissues below the threshold for radiation damage. Follow-up on this group of patients is short, averaging 22 months (2 to 75 months). Currently, 15 patients have local control of their tumor. Two major complications, a spinal cord transection and optic tract damage, are discussed in detail. Our treatment policies have been modified to minimize the risk of these complications in the future, and we are continuing to use this method to treat such patients. We are enthusiastic about this technique, since we believe there is no other potentially curative treatment for these patients.

Aged↗

PubMed1985

Proton therapy at Harvard.

Fractionated precision high-dose proton radiotherapy has been carried out at the Harvard Cyclotron Laboratory (HCL) since 1973, in a collaborative effort with the Radiation Medicine Department of Massachusetts General Hospital (MGH) and the Retina Service of the Massachusetts Eye and Ear Infirmary (MEEI). This paper will discuss proton treatment in general, treatment planning procedures, and results to date in major patient categories. 846 patients have been treated with fractionated proton therapy at the Harvard Cyclotron, with normal tissue and tumor responses consistent with an RBE of 1.1 for the proton beam. Proton beam therapy is the treatment of choice for patients with uveal melanomas, and chordomas and chondrosarcomas involving the skull base and cervical spine. Improved dose distribution possible with protons have allowed greater doses than are given conventionally to be delivered to patients with prostatic carcinoma, head and neck malignancies, ano-rectal cancers, and retroperitoneal tumors. Doses employed have been usually 10 to 20% greater than normally would be delivered in our department to such tumors. Generally, local control rates have been good.

Animals↗

PubMed1985

Progress in low-LET heavy particle therapy: intracranial and paracranial tumors and uveal melanomas.

The Harvard Cyclotron Laboratory in collaboration with the Department of Radiation Medicine of the Massachusetts General Hospital and the Retina Service of the Massachusetts Eye and Ear Infirmary provides low-LET heavy particle therapy with 160 MeV protons. The improved dose distribution of protons results from their physical characteristics. A total of 965 patients have been treated as of December 31, 1984. Dose is expressed in units of cobalt gray equivalent (CGE) which is the dose in Gy multiplied by the RBE (1.1) for modulated protons relative to 60Co radiation. Sixty-seven patients with chordomas or low-grade chondrosarcomas of the base of skull or cervical spine have received proton treatment. Forty-three of these patients have been followed for at least 8 months with a median follow-up of 27 months. The median dose is 69 CGE. The 3-year actuarial local control rate is 89%. Seven patients with gliomas, eight with craniopharyngiomas, and six with meningiomas have also received proton radiation treatments. A total of 615 patients with uveal melanomas have received a median dose of 70 CGE in five fractions. Tumor regression has been seen in 94% with 66% having vision of 20/100 or better.

Actuarial Analysis↗

PubMed1983

Helium charged-particle radiotherapy of locally advanced carcinoma of the esophagus, stomach, and biliary tract.

Sixty-five patients with squamous carcinoma of the esophagus (32 patients), carcinoma of the stomach (18 patients) and carcinoma of the biliary tract (15 patients) received from 6000 to 7000 equivalent rad (60-70 Gray-equivalents) of helium radiotherapy at 2.0 GyE per fraction, four fractions per day, using multiportal, spread-out Bragg peak therapy. All patients had locally advanced disease without evidence of distant metastases. Partial compensation for tissue inhomogeneities was accomplished. Although palliation of symptoms and regression of tumor was commonly seen, local failure occurred in most patients (77%). The median survival was 8 months. It does not appear that an increase in tumor dose relative to normal tissues can be achieved that would be high enough to increase locoregional control rates over historical control rates with low-LET irradiation. Further studies will be carried out with heavier particles such as neon or silicon in hopes of achieving greater biological effect on these difficult-to-control tumors.

Adenocarcinoma↗