Radiotherapy For Malignant Tumors Research Articles

First experience with a new echographic contrast agent.

The intravenous injection of an ultrasound contrast agent can enhance signals from blood flow. Broad toxicological and pharmaceutical studies in animals confirmed the safety and efficacy of an ultrasound contrast agent made of microparticles of galactose with stabilised microbubbles in watery suspension (SH U 508 A). In this paper 10 patients with different malignant orbital and ocular tumours have been evaluated with an echo colour Doppler machine before and after the injection of SH U 508 A. An enhancement of the Doppler signals in the lesions in different degrees has been detected. This echographic contrast agent seems to be very important not only in the evaluation of vascular lesions, but also in evaluating the effectiveness of radiotherapy in malignant tumours and could spread the echographic indications in several other ophthalmic fields.

Postoperative radiation therapy for malignant tumors of minor salivary glands. Outcome and patterns of failure

In the treatment of major salivary gland cancers, the addition of adjuvant postoperative radiation therapy for patients with high risk features has been shown to reduce the incidence of local failure. This retrospective study was done to determine the effectiveness of this approach for minor salivary gland cancers, to document patterns of failure, and to define prognostic variables for treatment outcome. Between 1961 and 1990, 160 patients received postoperative radiation at the University of Texas M. D. Anderson Cancer Center (UTMDACC) after gross total removal of their tumors. These operations ranged from excisional biopsies to craniofacial resections with orbital exenterations depending on the original site and size of the tumor. The primary tumor site was in the oral cavity-oropharynx in 111 patients and in the nasal cavity or paranasal sinuses in 46 patients. The most prevalent histologic type was adenoid cystic carcinoma (71%). Microscopic positive margins were present in 64 (40%) patients. Half of the patients had pathologic evidence of perineural invasion. Radiation therapy techniques varied, depending on the site and extent of disease and the era of treatment. Doses ranged from 50 to 75 Gy (median, 60 Gy; mean 59.2 Gy). Follow-up for surviving patients ranged from 24 to 270 months (median, 110 months). Fifty-seven (36%) patients experienced disease relapse. Nineteen (12%) patients had a local recurrence: 6 within 5 years of treatment, 8 between 5 and 10 years, and 5 after 10 years. Regional failures occurred in 3 of 13 patients with initially node-positive disease but were uncommon (less than 5%) in patients with node-negative disease, regardless of elective neck treatments. Distant metastases developed in 43 patients, mostly (79%) within 5 years of treatment. Actuarial overall survival rates at 5, 10, and 15 years were 81%, 65%, and 43%, respectively. Complications occurred in 51 patients and were of three predominate types: hearing loss (26 patients), ocular injury (15 patients), and bone exposure/necrosis (12 patients). Improved techniques, including better immobilization, customized beam shaping, and treating multiple fields per day, have substantially reduced the risk of serious complications during the past decade. Postoperative radiation therapy is effective in preventing local recurrence in most patients with minor salivary gland tumors after gross total excision. When local failure occurs, it tends to be a late event. For most patients, the authors recommend a postoperative dose of 60 Gy in 30 fractions to the operative bed; if there is named nerve invasion, the path of the nerve is treated electively to its ganglion.

GUINEA-PIG SPINAL-CORD AS A MODEL FOR THE STUDY OF LATE RADIATION-INJURY AND REPAIR

The risk of normal tissue damage imposes severe limitations on the radiotherapy of malignant tumours. The aim of this study was to examine the morphology of late radiation injury with special reference to microvasculature in the irradiated guinea pig spinal cord. Gamma radiation from a cobalt-60 source was used to irradiate the lumbar region of guinea pigs. A total dose of up to 94.5 Gy was given using 4.5 Gy fractions. Twenty such guinea pigs which survived more than 2 years post-irradiation were deeply anaesthetized and Mercox resin was perfused through the thoracic aorta. Ten minutes following perfusion, irradiated segments of the spinal cords were removed and either fixed in formalin for histology and morphometry or corroded in KOH for microvascular cast preparation. The latter were observed under the scanning electron microscope. All irradiated specimens showed multifocal white matter vacuolation. None of these spaces communicated with blood vessels. No such vacuolation was observed in grey matter. Glial cell counts in the irradiated white matter were reduced. Microvascular morphometry revealed 3.30% of the area was occupied by vasculature in the non-irradiated white matter. The corresponding value for irradiated white matter was 2.38% (p=0.003). No difference in the vascular area was noted in the non-irradiated grey matter (9.75%) and irradiated grey matter (10.36%; p=0.36) Microvascular casts did not reveal telangiectasia. However, irradiated specimens showed focal avascular regions. This was consistent with the light microscopic observation of focal degeneration and necrosis of irradiated white matter. These results suggest that late radiation injury in guinea pigs results primarily from damage to glial elements and the microvasculature is secondarily affected.

Topical problems in dosimetric planning of radiation therapy of malignant tumors

Topical problems in dosimetric planning of radiation therapy of malignant tumors

Radiation retino- and opticopathy. A prospective study.

This is a report of a prospective study of irradiation pathology of retina and optic nerve following radiotherapy for malignant tumors in the region of the nose, pharynx, nasopharynx, and sinuses. The eyes, optic nerves or supplying blood vessels were situated in or near the radiation field. In 16.7% of the cases after an average of 2 1/4 years interval pathology of retina and optic nerve did occur.

Critical analysis of methods of reconstruction of exenterated orbits

Reconstructive procedures were used on 14 patients who had undergone orbital exenteration and radiotherapy for malignant tumours. All patients were tumour free after a follow-up of between 5 and 18 years. Reconstruction was carried out in 3 stages. In the first operation the orbit was filled, in the second the orbital rims and eyelids were shaped, and in the third a cavity for a static eye prosthesis was created. Critical assessment of results showed that the first stage alone produced a marked improvement in appearance and occluded existing fistulae. The subsequent procedures improved aesthetic results further. Difficulties were encountered from retraction of the tissues and insufficient tissue mobility.

Postoperative radiation therapy for major salivary gland malignancies

Between 1966 and 1982 there have been 46 patients treated with surgery plus post-operative radiation therapy for malignant tumors of salivary gland origin. The indication(s) for radiotherapy included positive margins (42%), advanced local tumor (37%), positive nodes (33%), or high grade histology (48%). Overall actuarial local control at 5 years was 73%, being 100% for T1, 83% for T2, 80% for T3, and 43% for T4. Actuarial survival at 5 years was 80% for T1, 83% for T2, 60% for T3, and 48% for T4. Patients with positive nodes (N+) did worse than those with negative nodes (No), with locoregional control and survival at 5 years being 58% vs. 83%, (P = 0.025) and 38% vs. 80% (P = less than .01), respectively. We found no need for contralateral neck treatment even for those with positive nodes. Also, to date, none of eight patients with adenoid cystic histology has failed locally, as opposed to three of eight failures in patients treated with surgery alone. We believe that post-operative irradiation provides excellent locoregional control for appropriate patients with malignant tumors of major salivary glands.

Intracardiac extension of malignant uterine tumors: Echocardiographic detection and successful surgical resection

The echocardiographic findings of two unusual cases of malignant uterine tumors that invaded the heart are reported. A woman previously operated on for invasive cervical carcinoma had multiple embolic phenomena and evidence of obstruction to mitral flow. An echocardiogram showed a mass in the left atrium that reached the mitral valve ring. The tumor was implanted in a pulmonary vein and was removed with no complications. Cell type indicated metastatic carcinoma of the cervix. In the second case the patient had a large abdominal mass and precordial manifestations of obstruction and regurgitation of the tricuspid valve. An echocardiogram showed that a mass emanating from the inferior vena cava filled the right atrium and part of the right ventricle. The trajectory of the tumor was followed to its origin in an ovarian vein by tomography. The entire tumor was removed and identified as endometrial stromal sarcoma. An increase in operations with or without radiation therapy for malignant tumors has augmented the frequency of metastatic invasion of the heart; intracavitary extension tends to results from embolization or propagation along great veins. This is the first report of a uterine carcinoma reaching the heart by way of the pulmonary veins and of invasion of the heart by endometrial stromal sarcoma, both with successful excision.

顎骨の放射線骨障害に関する臨床的研究

Radiotherapy is indispensable as one of the treatments for malignant tumor in maxillomandibular and oral surgical field and the best way for preservation of functions, but it causes osteoradionecrosis in some cases.The incidence of osteoradionecrosis in maxillomandibular and oral surgical field is higher than in other bone sites because the mandible is included in the irradiation field in addition to the presence of teeth and various anatomical factors.In the present study osteoradionecrosis which had developed after radiotherapy for malignant tumor was studied clinically and therapeutically and the following results were obtained.1. The subjects were 28 patients with squamous cell carcinoma and 2 patients with adonoid cystic carcinoma aged 38 to 72. The ratio of male: female was 3.3: 1. The time of manifestation was 1 month-14 years after irradiation. The main symptoms were pain and exposed bone mainly in the region of mandibular molar tooth.2. Osteoradionecrosis was observed in 10 cases supposed to be induced by tooth extraction but also in 5 edentulous cases.3. When the osteoradionecrosis cases were classified into limited area type and wide range type on the basis of clinical findings. X-ray of the jaws showed the presence of bone resorption and induration together in many wide range type cases.4. Scintigram of bone showed widespread accumulation of radiation even in clinically limited area type, and the picture of some loss of bone and the intensity of the accumulation were considered to be extremely useful as an index in making therapeutical plans and decisions on the prognosis of tumor of the jaws.5. As the method of treatment, sequestrectomy was performed in 14 of 19 cases of the limited area type and 4 of 11 cases of the wide range type and excision of the jaws in 4 cases.6. Hyperbaric oxygen therapy was carried out in 3 cases and had good effect.

SURGICAL MANAGEMENT OF RADIATION ENTEROCOLITIS

Radiotherapy for malignant tumors is effective and established. However, there are many complications in radiotherapy. A typical complication is radiation enterocolitis. It is difficult to treat severe histological damage to the irradiated tissues. This paper reports our experience with 26 patients with radiation enterocolitis for whom surgical treatment was given during a period of 16 years in our surgical department. The most frequent original disease requiring irradiation was cancer of the cervix uteri (15 cases) which was followed by cancer of the urinary bladder (7 cases). All of these patients had received external 60Co irradiation. The ileum was the most frequent site of the lesion, followed by the rectum, sigmoid and descending colon. The period between the end of irradiation and the onset of enterocolitis ranged from 2 months to 10 years, with an average of 28 months. The main symptoms were intestinal obstruction in the ileum, and melena and fistula in the rectum and sigmoid colon. Intestinal resection was performed in 10 patients, a bypass operation in 4, and colostomy in 12. As to types of intestinal suture in these cases, Gambee's single layer method was thought useful from our experience. Colostomy as surgical managment of melena and fistula did not yield satisfactory results.

Radiotherapy Treatment Design Using Mathematical Programming Models

The design of treatment for external beam radiation therapy of malignant tumors is a complex decision-making process. This paper introduces and develops mathematical programming models that can aid this process. After briefly discussing the necessary background material, we state our linear and mixed-integer programming models, along with some variations that can be usefully implemented in some situations. We then compare our design for a case of lung cancer with a standardized approach, and the advantages of our models become evident. We close with several comments about the potential utility of this class of models in treating other types of cancers.

Late Effects on Skeleton after Radiation Therapy for Malignant Tumors in Children

Late Effects on Skeleton after Radiation Therapy for Malignant Tumors in Children

The role of post-operative radiation therapy in the treatment of malignant tumors of the parotid gland.

Twenty-nine patients treated with postoperative radiotherapy for malignant tumors of the parotid gland were reviewed at the Joint Center for Radiation Therapy. Most patients were treated between 5,000 and 6,500 rad. All were treated because of microscopic residual disease, extra capsular extension, or tumor close to the facial nerve. The overall results showed one in-field failure, two marginal recurrences, and eight patients failed distantly. Poor prognostic factors included high-grade, extracapsular extension, and nodal involvement. We conclude that patients with malignant tumors of the parotid should be treated with postoperative radiation therapy if any of the bad prognostic signs are present. This may enable the surgeon to spare the facial nerve and obtain local control results equal to or better than more radical surgical procedures.

Facial Bone Scintigraphy

The uptake of 99Tcm-DP in normal facial bones was not changed by irradiation of malignant tumors. The intensity of the pathologic uptake into regions with active parodontitis in a few patients increased during irradiation. The uptake of 99Tcm-DP in bone with neoplastic growth varied during the period of treatment, probably depending on the tumor reaction to irradiation.

Postirradiation neoplasia: A symposium

Summary It is impossible to prove that radiation given for benign conditions in infancy and childhood is an etiologic factor in the subsequent development of carcinoma in the head and neck area. Nevertheless, the suggestive evidence is quite impressive and the information from many sources correlates well. There are some conflicting reports but, in general, it can be said that very high doses of radiation are less likely to be carcinogenic than lesser amounts. Very small doses of radiation are probably not carcinogenic either. In general, the younger the patient at the time of exposure to radiation, the greater is the risk of subsequent development of carcinoma. The breast seems to be an exception, however, as it is more sensitive to radiation carcinogenesis between the ages of 10 and 35. Chronic low doses of radiation seem to be more carcinogenic in humans. The latent interval between irradiation and the appearance of carcinoma in most sites averages about 30 years; leukemia tends to occur 5–8 years after irradiation. The atomic bomb data are confusing. Up to 30% of the Hiroshima bomb radiation consisted of neutrons, whereas the neutron radiation of the Nagasaki bomb was very low. The higher incidence of breast cancer associated with the former type of irradiation may be related to the higher carcinogenicity of neutrons. On the other hand, the lower normal incidence of breast carcinoma in Japanese women may be a modifying factor of RBE of radiation in tumor induction. Irradiation for malignant tumors in all parts of the body, although an exceedingly valuable addition to the cancer therapy armamentarium, probably predisposes to the later development of irradiation carcinoma in the long-term survivors. This becomes increasingly important as more children and young adults with malignant tumors are clinically cured of their original malignant tumor with multimodal therapy including irradiation. The risk of carcinogenesis in radiation-treated patients never disappears. These patients should be followed carefully for life.

OER of Fission Neutrons for Induction of Heteroallelic Reversion in Diploid Yeast

A sensitive strain of diploid yeast, Saccharomyces cerevisiae BZ 34, was used to study the OER of fission neutrons with the induction of arginine prototrophs as the end point. A Standard Neutron Irradiation Facility (SNIF) which significantly cuts down thermal neutron and ..gamma.. contamination was used for fast neutron irradiation in a swimming pool reactor. For irradiation under hypoxic conditions, a high cell titer, viz 10/sup 8//ml, in a glass-stoppered vial was used which would use up the dissolved oxygen and hence achieve hypoxia. Gamma rays from a /sup 60/Co ..gamma.. cell were used to determine OER for purposes of comparison. The values of OER for fast neutron and ..gamma.. radiation were found to be 1.17 +- 0.19 and 2.42 +- 0.12, respectively. Computations were made with the LET distributions relevant for pile neutrons on the basis of charged particle data and it was found that the computed value of OER 1.68 is larger than the observed value 1.17 +- 0.19. This observation may have application in radiotherapy of malignant tumors.

Neurologic complications after irradiation of malignant tumors of the testis.

Of 156 consecutive patients with malignant tumor of the testis 99 were alive two years after treatment. Of these, 12 had radiation-induced neurologic complications which, in 5 instances, consisted of persisting, wholly or partially disabling paresis in the lower limbs. Five had mild, transient symptoms and had persisting symptoms which were not incapacitating. In all those with disabling symptoms the irradiation dose had been higher than 1 600 reu, corresponding to 54.5 Gy over 6 weeks with daily fractions 5 days a week.

Enhanced Lymphocyte-mediated Killing of Tumour Cells after Tumour Irradiationin Vivo

The effect of local X-irradiation of a syngeneic carcinoma of fibrosarcoma growing in the leg of W/Fu rats on the ability of host spleen lymphocytes to kill syngeneic and allogeneic tumour cells in vitro was examined. Lymphocytotoxicity was found to be enhanced one day after local X-irradiation (4000 R) when compared with unirradiated tumour-bearing rats (p = 0.05 to 0.01). This enhancing effect of local irradiation was not observed when the lymphocytes were tested 1 week or later after X-irradiation, nor when normal legs of non-tumour bearing rats were irradiated. Mechanisms which might possibly explain these results are a reduction in release of tumour-specific antigen which can act as an inhibitor of cell-mediated cytotoxicity, or depletion of suppressor cells in the lymphocyte population. These findings may be relavant to clinical studies of cellular immunity in patients undergoing radiotherapy of malignant tumours.

Irradiation-Induced Tumours of the Head and Neck

Though irradiation-induced tumours are uncommon they represent a well defined entity. At this Hospital, 14 "irradiation-induced" head and neck tumours were encountered in 11 patients over a 10-year period. The irradiation had been given for tuberculous lymph-adenitis in 6 of the patients, for lupus vulgaris in one, and thyrotoxicosis in another; the other 3 patients had received radiotherapy for malignant tumours. The interval between the treatment and the diagnosis of the tumour disease ranged from 9 to 48 years (mean 32). The induced tumours included 10 squamous cell carcinomas of the hypopharynx (4 tumours), the buccal mucosa (3), the skin (2), and the larynx (1), one poorly differented carcinoma of the parotid gland, 2 thyroid carcinomas and 1 fibrosarcoma of the stenocleidomastoid muscle. Three of the patients had multiple tumours. In view of the risk of cancer--albeit a small one--associated with radiological diagnosis and radiotherapy, these should be performed only on strict indications, especially in young patients.

Tolerance dose of the spinal cord on radiation myelopathy.

Radiation myelopathy has developed in 9 cases among irradiated patients as a side effect following radiotherapy for malignant tumors. The dose to the spinal cord was 5, 000-10, 000 rads, the over all treatment time 42-71 days. Several causative factors of the radiation myelopathy were picked up.The degree of radiation influences in the spinal cord seem to be time-dose dependent, as reported by Boden and Pallis. A recommended tolerance dose to spinal cord was over 4, 000 rads and over 5, 000 rads according to Tsuya's and Friedman's reports respectively and an NSD* of 1, 300 rets and 1, 500 rets was recommended by Maier and Phillips respectively. From the data presented it is apparent that degree of occurrence of radiation myelopathy depends greatly on fractionation and irradiation dose. When the patients are treated in more than 21 fractions at a daily dose of 200 rads and the dose to the spinal cord irradiated is more than 5, 000 rads, it can be considered to be the critial level for radiation myelopathy.