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Biomedical subjects

M A Varia

Publications and source records attributed to M A Varia.

9 recordsLinked to original sources

Invasive carcinoma of the uterine cervix in women age 25 or less.

The incidence of cervix cancer in young women appears to be increasing. However, the influence of young age on prognosis remains unknown. There is almost no information on the prognosis of very young women, age 25 years or less, with invasive cervical carcinoma. From April 1969 to June 1987, 40/2195 (1.8%) patients, age 25 years or less, with invasive carcinoma of the uterine cervix were diagnosed, staged, and treated at our institution. Median age was 24.7 years (range 20.7 to 25.9 years). Distribution by FIGO stage was: Stage IA 7 (18%), Stage IB 23 (58%), Stage II 4 (10%), Stage III 4 (10%), and Stage IVA 2 (4%). Thirty-four (85%) patients had squamous cell carcinoma and six (15%) had adenocarcinoma. Treatment consisted of radical hysterectomy for all Stage IA patients, radical hysterectomy with or without bilateral pelvic node dissection for the 12 early Stage IB patients, and radiation with or without surgery for the remaining 11 Stage IB patients and all Stage II-IVA patients. Median follow-up was 122 months (range 13.2-190.6 months). Five-year disease-free survival rates were: Stage IA 100%; Stage IB 54.8%; and Stage II-IVA 13.7%. Five-year disease-free survival for the Stage IB patients with squamous cell carcinoma age 25 years or less was 64.7%, compared with 83% for women of all ages with Stage IB squamous histology treated at our institution. Seven of 23 Stage IB patients suffered regional recurrence only, one a local recurrence only, one a distant recurrence only, and one a combined recurrence. Seventy-five percent of these patients presented with Stage I disease; however, one-third died from their disease. The major site of failure was in the pelvis only. This, coupled with the low risk of long-term serious complications, suggests that more aggressive pelvic therapy may result in improved disease-free survival.

Adenocarcinoma

A controlled study of efficacy of interstitial or external irradiation in a virus-induced brain-tumor model in rats.

In a controlled study of interstitial radiotherapy in the avian sarcoma virus (ASV)-induced glioma model in rats, prolongation of survival was demonstrated (p = 0.08 in Experiment 1 and p = 0.03 in Experiment 2) following mean dosages of 7582 to 9902 cGy 125I, when compared to nontreatment or to control studies with implantation of nonradioactive seeds. More significant (p = 0.02) prolongation of survival was demonstrated following external beam whole-head radiotherapy with nine fractions of 333 cGy, three times weekly over 3 weeks (total dose 3000 cGy). Survival was more prolonged when whole-head radiotherapy was begun 35 days following virus inoculation rather than at 71 days, probably reflecting a greater efficacy with smaller tumor targets.

Animals

Analysis of results of radiation therapy for stage IB carcinoma of the cervix.

From April of 1969 through December of 1980, 197 patients with Stage IB, invasive, epidermoid carcinoma of the cervix received radical radiation therapy. The treatment consisted of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 5000 to 5500 rad to the pelvic lymph nodes. The 2-, 5-, and 10-year, disease-free survival rates were 87%, 83%, and 81%, respectively. Thirty-six patients developed recurrent and/or metastatic disease. The sites that failed to remain disease-free were: locoregional in five patients (3%), locoregional with distant metastases in 15 patients (8%), and distant metastases only in 14 patients (7%). In addition, there were two patients (1%) who are considered to have died of disease but the site or sites of recurrence could not be determined. Thirty-nine patients developed complications. The complications were mild and self-limiting--Grade I--in 24 patients (12%) and of moderate severity--Grade II--in eight patients (4%). Seven patients (4%) developed severe--Grade III--complications. A correlation was found between the dose to Point A, the bladder, and the rectum and the complications. The mean dose to Point A for patients without and with complications were 7453 rad (SE +/- 91) and 7737 (SE +/- 124), respectively, with a P value of .05. The mean dose to the bladder for patients without and with urinary complications was 5590 rad (SE +/- 103) and 6335 rad (SE +/- 411), respectively, with a P value of 0.14. The mean dose to the rectum for patients without and with intestinal complications was 5837 rad (SE +/- 103) and 6810 rad (SE +/- 236), respectively, with a P value of 0.001. No correlation was found between the dose to Point A and locoregional recurrences.

Brachytherapy

Effect of methylprednisolone on radiotherapy of F344 rats with avian sarcoma virus induced gliomas.

We have examined the impact of methylprednisolone acetate (MPA) on survival of F344 rats that were bearing avian sarcoma virus (ASV)-induced gliomas and that were treated optimally with radiotherapy. Toxicity of MPA (dose range of 0.2-5.0 mg/kg X 7 over 3 weeks) was first established in non-tumor bearing rats as assessed by their relative failure to gain weight. Doses of 2.0 or 5.0 mg/kg X 7 caused animals to be 21.8 or 43.9%, respectively, underweight compared with vehicle controls. In rats bearing ASV-induced gliomas, treatment with 3,000 cGY (nine fractions over a 3-week period) alone or with 0.2 or 1.0 mg MPA/kg (X 6 during the 3-week radiotherapy course) produced a significantly prolonged survival compared with that of untreated, tumor bearing rats. However, MPA did not enhance survival when given concurrently with radiotherapy; indeed, at the higher of these two doses, median survival of tumor-bearers was slightly less than with radiotherapy alone. This trend towards interference with the beneficial effects of radiotherapy was more pronounced with the highest dose of MPA studied, 5.0 mg/kg body weight X 6. These animals had a median survival time that was significantly less than that of tumor-bearers receiving radiotherapy alone, but not significantly different from untreated rats with gliomas. The possible significance of these observations is discussed.

Animals

An integrated system for interstitial 192Ir implants.

An efficient system for preparing, afterloading, and removing interstitial 192Ir strands has been developed. Use of the system reduces the risk of personnel exposure and eliminates some patient discomfort. The system is "integrated" in that all aspects of the implantation process are considered, from source preparation to source removal. Strand preparation is facilitated by an "assembly line" process using shielded equipment. Components include a handling block for measuring and cutting active strands, a mirror, and a transport container. Afterloading and removal techniques use quick release devices and several forms of afterloading tubing and catheters, each terminated by a Luer lock adapter. Both blind-end and through-and-through implants are possible. Each 192Ir strand, threaded through an injection cap that mates with the Luer lock adapter, is quickly inserted into its tubing or catheter and locked into place. No crimping is required and no additional positioning of the sources is needed. Strand removal is easily accomplished by unlocking and removing the injection cap. The strands receive no mechanical damage and can be reused after appropriate cleaning. More than 100 cases have been performed without incident. Applications include head/neck, breast, and template and non-template vaginal wall treatments.

Brachytherapy

A spreadsheet program for brachytherapy planning.

A computer program (brachy-spread) which allows spreadsheet-like interactive adjustment of the loading of any brachytherapy application has been implemented. Sources are collected into objects, each assigned an activity and duration of implant. Activities and times may be adjusted by moving a cursor to the datum to be edited and entering a new value from the keyboard. Alternatively, the desired total dose to a given calculation point may be edited resulting in a recalculation of the time for all objects. For each of a set of calculation points, dose rates, total doses, and the percent contribution of each object to the point are displayed and instantly updated as the times and activities are adjusted. The program design includes rapidly updated display of isodose curves in previously selected arbitrary planes. A strategy for providing rapid dose display involving precalculation of fractional dose tables is used. The program has significantly reduced the time required to determine the appropriate loading of GYN applications and of implants which involve a combination of line sources and seeds.

Algorithms

Carcinoma of the cervix, stage III. Results of radiation therapy.

From April 1969 through December 1980, 203 patients with Stage III epidermoid carcinoma of the cervix were treated with radiation therapy with curative intent. The disease-free survival at 2, 5, and 10 years was 50%, 33%, and 27%, respectively. The survival was better for patients with Stage IIIB disease than for those with Stage IIIA disease. Eighty-eight patients were treated with external beam therapy only, and 115 received external beam and brachytherapy. The disease-free survival was better for the combination therapy group initially, but this difference was not sustained beyond 5 years. One hundred eight patients experienced recurrence within the irradiated field, for a locoregional recurrence rate of 53%. Twenty-seven patients had complications (13%). The complications were mild in 13 patients, moderate in 4 patients, and severe in 10 patients. A study was made of the relationship of the dose to Point A and the occurrence of complications. Similar analyses were made of the bladder and rectal doses and the subsequent occurrence of urinary and intestinal complications. In these analyses, the mean dose to Point A and the critical organs was higher for the groups of patients with complications than for those patients without complications. This relationship was also observed when the patients were stratified for treatment with either external beam plus brachytherapy or external beam therapy alone.

Brachytherapy

1000 cGy single dose palliation for advanced carcinoma of the cervix or endometrium.

Between January 1980 and the present, 42 patients with symptomatic, incurable gynecologic malignancies were treated at the University of North Carolina with 1000 cGy in a single fraction to the pelvis, repeated once or twice at monthly intervals as necessary. Of patients with adequate follow-up, total cessation of bleeding was seen in 18 of 30 (60%), complete pain relief in 2/9 (22%), and complete tumor eradication in 7/28 (25%). These palliative benefits were permanent in approximately half of the patients. Five serious treatment complications have been documented, four occurred more than 10 months after treatment. We conclude that 1000 cGy single-fraction whole pelvis treatment can be an effective means of palliating advanced gynecologic cancer provided the patient has a life expectancy of less than 1 year. Patients with a longer life expectancy are at risk for both recurrence of symptoms and for treatment related complications.

Adult

Analysis of results of radiation therapy for Stage II carcinoma of the cervix.

From April 1969 through December 1980, 251 patients with invasive, epidermoid carcinoma of the cervix received radical radiation therapy consisting of a combination of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 6000 to 6500 rad to the pelvic lymph nodes. The disease-free survival at 2, 5, and 10 years for patients with Stage IIA disease was 90%, 76%, and 76%, respectively, whereas for patients with Stage IIB disease it was 77%, 62%, and 59%, respectively. The survival for the entire group at 2, 5, and 10 years was 80%, 65%, and 62%, respectively. Sixty-eight patients had a recurrence within the irradiated volume, for a locoregional recurrence rate of 27% (68/251). In 49 patients complications developed for an overall complication rate of 19.5% (49/251). An analysis of the complications and their degree of severity revealed a correlation with the dose of intracavitary plus external beam therapy given to Point A and to the rectum. The mean dose to Point A for patients with and without complications were 7877 rad (standard error [SE] +/- 95) and 7593 rad (SE +/- 67), respectively. The mean rectal dose for patients with and without intestinal complications were 6767 rad (SE +/- 157) and 6426 rad (SE +/- 78), respectively. The dose difference between patients with and without complications was statistically significant for Point A (P = to 0.0163) but not for the rectal dose (P = to 0.0887). There was no correlation between the bladder dose and urinary complications. Other treatment methods as well as patient and tumor parameters, are being currently analyzed to identify which factors, singly or in combination, may contribute to the development of treatment failures or complications.

Adult