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Biomedical subjects

P Rubin

Publications and source records attributed to P Rubin.

At least 217 records · Page 12Linked to original sources

Craniopharyngiomas: fluctuation in cyst size following surgery and radiation therapy.

Patients with craniopharyngiomas who demonstrate cyst enlargement after surgery and radiation are often presumed to be treatment failures. Therapeutic approaches in various centers include repetitive cyst aspirations, surgical reexcision, and installation of cytotoxic agents such as methotrexate, 32P, or 198Au. Each intervention has associated severe or even lethal side effects. Not all patients with craniopharyngioma who have cystic enlargement after primary therapy require an intervention, as demonstrated by 4 patients recently managed in the University of Rochester Medical Center. Since 1978, when computed tomography was routinely in use, we have managed 11 patients with craniopharyngiomas who were treated with surgery followed by radiation therapy. Three of these patients demonstrated post-irradiation enlargement of the residual cystic component followed by a decrease in size without surgical intervention. An additional patient showed cystic growth followed by stabilization of size. It is noteworthy that the cyst enlarged within the first 5 months after radiation therapy in the 3 patients who subsequently demonstrated a diminution in the size of their cysts. This suggests that the mechanism for cyst formation remained intact and subsequently abated because of a radiation-induced lesion. We conclude that after treatment with surgery and radiation therapy, the cystic component of craniopharyngiomas may increase and, without intervention, subsequently decrease in size. Thus, in the asymptomatic patient who demonstrates cystic growth soon after primary therapy, close observation alone may be warranted.

Adolescent↗

Absence of prognostic significance, peritoneal dissemination and treatment advantage in endometrial cancer patients with positive peritoneal cytology.

Peritoneal cytology has been shown to be one of the prognostic factors in endometrial cancer. A series of 134 patients was seen between January 1977 and March 1985 with clinical Stage I (or treated as a clinical Stage I) endometrial adenocarcinoma at the University of Rochester Cancer Center. The majority of patients underwent extrafascial hysterectomy with the majority of washings obtained at the time of surgery. Fourteen percent (19/134) of the patients were found to have positive cytology. Eleven patients with positive cytology (11/19) were treated with local-regional pelvic treatment; the other eight patients received whole abdominal therapy. The recurrence rates were less with the local treatment than with the whole abdominal treatment groups (9.1% vs. 25%) in those patients having positive cytology. There was no statistical difference in recurrence rates between the pathologic Stage I patients with positive cytology (10%) versus those patients having negative cytology (5%), nor was there statistical difference in survival between pathologic Stage I positive or negative cytology patients. It is suggestive from this non-randomized study that positive cytology in endometrial cancer is not an independent prognostic factor and that whole abdominal irradiation did not influence outcome.

Adenocarcinoma↗

Tolerance of pelvic normal tissues to hyperfractionated radiation therapy: results of Protocol 83-08 of the Radiation Therapy Oncology Group.

A prospective, centrally randomized Phase I/II trial of hyperfractionation in definitive radiation therapy for locally advanced squamous and transitional cell carcinoma of the bladder was conducted by the Radiation Therapy Oncology Group (RTOG) from April 1983 through June 1986. Patients with T3-4 and T2 N+ (AJC) histologically-confirmed cancer of the bladder received twice daily radiation therapy with 1.2 Gy per fraction and a minimum of 4 hr between fractions. All patients received a whole pelvic total dose of 50.4 Gy: Total doses to reduced volumes were 60.0 Gy, 64.8 Gy, or 69.6 Gy. Of 54 patients entered, 50 were eligible. An unbalanced treatment assignment was used: Nine patients received 60.0 Gy, 15 patients received 64.8 Gy and 26 received 69.6 Gy. Performance status (Karnofsky) was 90-100 in 72% of patients and 92% had transitional carcinoma. Eighty percent of tumors were T3 or T4. Observation of at least 18 months was available for 26 patients. Grade 3 acute reactions (within 90 days) were reported in eight patients (one at 60.0 Gy, three at 64.8 Gy and four at 69.6 Gy). Five patients experienced a total of seven major late effects--four Grade 3 and three Grade 4. The cumulative probability of Grade 3 and 4 late complications of treatment for the 46 patients at risk for late complications was 5% +/- 3% at 6 months, 7% +/- 4% at 12 months, and 10% +/- 5% at 18 and 24 months. The cumulative probability of Grade 3 or 4 late complications for patients who received a total dose of 69.6 Gy was 5% +/- 4% at 6 and 12 months and 11% +/- 8% at 18 and 24 months. Only one patient who experienced major late effects was also reported to have major acute reactions. Comparisons of survival of patients treated in the current study with those who received 60 Gy in 30 fractions in 6 weeks in RTOG Protocol 71-04, did not suggest any deleterious effects from hyperfractionated radiation therapy to the pelvis. The normal pelvic tissues tolerated hyperfractionated radiation therapy sufficiently well to justify exploring it, alone and with brachytherapy, in other pelvic tumors.

Aged↗

Myelin basic protein and magnetic resonance imaging for diagnosing radiation myelopathy.

The identification of radiation myelopathy using biochemical assays and imaging techniques has not previously been accomplished but has clear clinical application. Measurement of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) and visualization of the spinal cord using magnetic resonance imaging (MRI) gives a potentially accurate diagnosis of radiation myelopathy. Female New Zealand white rabbits were irradiated to the thoracic spinal cord with single doses of 15-45 Gy. Animals receiving higher doses (greater than or equal to 22 Gy) generally demonstrated an early paresis (4-8 weeks) that temporarily improved, and then progressed to complete paralysis by 14-18 weeks. MBP levels in the CSF became strikingly elevated to 100-1000 times the normal value. Subsequent, experiments in which rabbits were serially assessed for MBP levels demonstrated a transient elevation, which corresponded to the transient paresis, followed by dramatic elevations concurrent with the onset of paralysis. Magnetic resonance imaging (MRI) of the irradiated spinal cord showed a geographically distinct region of abnormality that corresponded to the radiation field. Histopathology demonstrated demyelination, focal astrocytosis, erythrodiapedesis, and perineuronal edema in the irradiated sections. It appears that MBP levels in the CSF reflect not only radiation-induced myelopathy but also transient demyelination, and that MRI may have the potential to indicate the region of damage.

Animals↗

Final report on phase I trial of WR-2721 before protracted fractionated radiation therapy.

This is the final report of the Phase I Protocol for the initial clinical study of Multiple Dose WR-2721 with radiotherapy (RTOG 80-02). The essential object of the study was to determine the highest dose of WR-2721 that could be given daily for the greatest number of weeks 15 to 30 minutes before conventional radiation treatment schedules. Eighty-four patients were entered into various dose levels. The major and dose-limiting toxicities were emesis, hypotension and malaise. The latter symptom was characterized by increasing weakness, fatigability, and ill-feeling. The maximum tolerated dose (MTD) established by this study is 340 mg/m2 given 4 days a week (excepting Wednesday) for 5 weeks. The drug is delivered intravenously in 7 minutes. There were no long-term blood chemistry changes. There were no deaths due to the administration of the radioprotector.

Adolescent↗

Treatment of breast cancer among elderly women with segmental mastectomy or segmental mastectomy plus postoperative radiotherapy.

Elderly women with cancer are often treated non-aggressively. Between January 1972 and March 1984, 128 women greater than 60 years were treated for Stage I or II breast cancer with segmental mastectomy (SGM) plus/minus postoperative radiation at one of our four area hospitals. Whereas 82% of similar patients less than 60 years were referred for postop radiation, only 39.8% of patients greater than 60 were so referred. Referral rates progressively diminished with increasing patient age above 60. Thus, we reviewed the outcome of 77 elderly women treated with SGM and 51 treated with SGM+RT. Treatment groups were similar with regard to prognostic clinical and histologic parameters. Mean follow-up is 51.4 months. Among SGM patients, 45.5% of patients between 60-70 years, 37.9% of those greater than 70, and 20% of those greater than 80 years experienced loco/regional failure prior to death. Conversely, only two local failures occurred among all elderly women treated with SGM+RT. Distant failure was approximately 11% and was unaffected by treatment. Complications of SGM+RT were modest. These data suggest that SGM+RT can be safely and effectively applied to the elderly. Moreover, the data suggests that postop radiation may be more beneficial when extended to elderly patients post segmental mastectomy than among younger women. Referring surgeons should focus upon their patients' physiologic and not chronologic age as a basis for treatment allocation decisions.

Age Factors↗

Adverse effects of brain irradiation correlated with MR and CT imaging.

Forty-one patients treated for primary malignancies of the brain at the University of Rochester Cancer Center since 1970 were assessed for adverse effects of irradiation clinically, and by computerized tomography (CT) and magnetic resonance (MR) imaging. At diagnosis, patients ranged in age from 1-65 years (median 19 years) and the most common tumor (in 30) was astrocytoma. Radiation doses ranged from 45 to 81.3 Gy (median 56.8 Gy). White matter changes visible on MR were graded on a scale of 1-4, with grades 1-2 known to occur in some normal patients. Areas of increased signal intensity not associated with the tumor or surgery were visible in all patients (gr 1 = 37%, gr 2 = 32%, gr 3 = 17%, gr 4 = 15%) whereas only 35% had regions of abnormality (hypodensity) on CT. Sulci enlargement and ventricular abnormalities (asymmetry or dilatation) were present in approximately 50% of patients by each technique. Higher grade MR lesions were associated with radiation to large volumes and high doses. For the 36 patients treated with 1.5-2.0 Gy daily fractions, the mean radiation dose by grade was as follows: gr 1 = 55.1 Gy, gr 2 = 58.8 Gy, gr 3 = 60.0 Gy, gr 4 = 63.5 Gy. All 5 patients treated on a hyperfractionated schedule had gr 1-2 changes despite receiving greater than 70 Gy. Fifty percent of patients treated to the whole brain (+/- boost) had gr 3-4 changes, compared with 14% treated with local fields (peak dose regions similar in both groups). Among the children (less than or equal to 13 years), 20% had gr 3-4 changes compared with 56% of adults (excluding hyperfractionated patients). This finding may be due entirely or in part to the lower radiation doses used for children (mean 54.4 Gy vs. 63.7 Gy in adults). Clinical abnormalities attributable to irradiation included an impairment in mental functioning in 7 adults, and learning disabilities in 5 children. Five of these adults (71%) had gr 3-4 changes on MR as compared to gr 3-4 changes in 29% of the remaining adult group. Five patients developed seizure disorders. We conclude that adverse effects of brain irradiation are more sensitively imaged by MR than CT and that these abnormalities are associated with larger treatment volumes and either (or both) higher doses or older age. Conversely, some patients treated with high radiation doses have unremarkable changes on MR, and others have severe white matter changes which are not clinically expressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Astrocytoma↗

The prognosis and therapy of chronic lymphocytic leukemia under age 50 years.

Twelve percent of patients with CLL studied by the Eastern Cooperative Oncology Group (ECOG) were under age 50 years. Except for clinical stage (more unfavorable presentations), and sex distribution (all but one being male), presenting clinical and laboratory features were identical to the whole population. The response rates and response duration were similar as well. Despite the more advanced stage these patients appear to have a survival advantage over their older counterparts.

Adult↗

Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group.

This report details the patterns of tumor recurrence in two prospective randomized studies involving 551 patients with histologically proven unresectable or medically inoperable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Patients were treated according to two protocols, depending on the stage of the tumor: (1) Patients with T1, 2, 3-NO, 1, 2 tumors were randomized to four different regimens: 4000 cGy split course (2000 cGy in five fractions, per 1 week, 2 weeks rest and additional 2000 cGy in five fractions, per 1 week) or 4000, 5000, or 6000 cGy continuous courses, five fractions per week. (2) Patients with T4, any N or N3, any T stage tumors were randomized to be treated with 3000 cGy tumor dose (TD), ten fractions in 2 weeks, 4000 cGy split course (described above), or 4000 cGy continuous course. In the patients with less advanced tumors (Study 1) the intrathoracic failure rate within the irradiated volume was 48% with 4000 cGy continuous, 38% with 4000 cGy split course or 5000 cGy continuous, and 27% for patients receiving 6000 cGy continuous course. The failure rate in the nonirradiated lung ranged from 25% to 30% in the various groups. Patients with adenocarcinoma or large cell undifferentiated carcinoma had better intrathoracic tumor control (35%) than those with squamous cell carcinoma (20%). The incidence of distant metastases was 75% to 80% in all histologic groups. Distant metastases appeared sooner after therapy in the patients with adenocarcinoma or large cell undifferentiated carcinoma. The initial failure rate in the brain was 7% in patients with squamous cell carcinoma, 19% with adenocarcinoma, and 13% in patients with large cell carcinoma. The ultimate incidence of brain metastases was 16% in squamous cell carcinoma, and 30% for adenocarcinoma or large cell undifferentiated carcinoma. Higher doses of irradiation will be necessary in order to improve the intrathoracic tumor control. Clinical trials by the Radiation Therapy Oncology Group, some of them involving multiple daily fractionation, are in progress. Furthermore, because of the high incidence of distant metastases, effective systemic cytotoxic agents are critically needed to improve survival of lung cancer patients. The high frequency of brain metastases suggests that, as in small cell carcinoma of the lung, elective irradiation of the brain may be necessary, if not to improve survival to enhance the quality of life of patients with adenocarcinoma and large cell carcinoma.

Adenocarcinoma↗

Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10.00 Gy vs 20.00 Gy schedules.

Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As of February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. Our historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients.

Adult↗