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Biomedical subjects

M Rotman

Publications and source records attributed to M Rotman.

At least 55 records · Page 3Linked to original sources
PubMed1987

Radiotherapy with or without misonidazole for patients with stage IIIB or stage IVA squamous cell carcinoma of the uterine cervix: preliminary report of a Radiation Therapy Oncology Group randomized trial.

Between August 1980 and November 1984, 119 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (4600 cGy pelvis plus 1000 cGy parametrial boost) followed by intracavitary or external boost to the primary with or without misonidazole (MISO) (400 mg/m2 daily 2 to 4 hours prior to radiation therapy). Patients in the two treatment groups were evenly distributed with respect to stratification variables including stage, Karnofsky Performance score, and positivity of para-aortic nodes. Eighty-nine percent of patients had Stage IIIB disease and 88% had a Karnofsky score of 80 or better. Seventy-five percent of patients treated with radiation therapy alone and 79% of patients treated with radiation therapy plus MISO received a boost via intracavitary application. Life threatening (Grade 4) complications occurred in 5 patients receiving radiation therapy alone and one patient receiving radiation therapy plus MISO. MISO toxicity (Grade 3) was limited to severe nausea and vomiting in two patients. With 119 evaluable patients and a median follow-up of 33 months, 64% of patients receiving radiation therapy alone are alive at 18 months compared with 54% for patients assigned to radiation therapy plus MISO. The median survival for patients treated with radiation therapy alone and radiation therapy plus MISO was 1.9 years and 1.6 respectively. At this point in the study the difference in survival is inconsistent with the hypothesis of an improvement associated with MISO. There have been 23 deaths among the 49 patients treated with radiation therapy plus MISO who have been followed for at least 18 months compared with 17 deaths in 48 patients treated with radiation therapy alone. The chance of observing this number of deaths with radiation therapy plus MISO if the addition of MISO improves survival by 10 to 20% is 0.003 and less than 0.001, respectively. The addition of MISO to radiation failed to improve survival for these patients. The results cannot be explained by an uncharacteristically high survival on the radiation therapy alone arm or by an imbalance in the distribution of prognostic factors. Local-regional control remains a problem in the management of patients with advanced cervical carcinoma. More effective and less toxic radiosensitizing agents are needed.

Adolescent↗
PubMed1987

Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck.

As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to "standard" 5 treatments per week among "control" patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for "control" patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial. Other nitroimidazole analogs (e.g. SR-2508) are now being investigated.

Aged↗
PubMed1986

Depletion of cellular ATP inhibits Na+/H+ antiport in cultured human cells. Modulation of the regulatory effect of intracellular protons on the antiporter activity.

The metabolic energy dependency of Na+/H+ exchange activity was investigated in cultured human A431 carcinoma cells and foreskin fibroblasts. Following the activation of Na+/H+ exchange which results from loading cells with Na+ or Li+, depletion of cellular ATP by incubation with metabolic inhibitors causes an inhibition of Na+/H+ exchange activity. This inhibition is reversible and correlates with the extent of the reduction in the ATP pool. On the other hand, reduction of the intracellular pH (pHi) to approximately 6.0-6.2 results in a similar effective activation of Na+/H+ exchange in both control and ATP-depleted cells. Na+/H+ exchange activity in ATP-depleted cells that either have or have not been loaded with Na+ shows a steep dependency on pHi, being essentially abolished above pHi of 6.4-6.5, whereas control cells show a considerable activity also at more alkaline pHi values. Thus, Na+/H+ exchange activity in ATP-depleted cells shows an increased dependency on intracellular protons. These findings suggest that although metabolic energy is not required as a driving force for Na+/H+ antiport, depletion of metabolic energy substrates inhibits the antiporter activity due to a modulation of an intracellular proton-dependent regulatory mechanism.

Adenosine Triphosphate↗
PubMed1986

Complications of combined radical hysterectomy and pelvic radiation.

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 48 women treated by radical hysterectomy (RH) and pelvic node dissection (PND) and in 25 women who received 5000-5400 rad of external pelvic radiation (RT) after RH-PND. No major complications developed in the surgery-only group, but the 5-year minor GI complication rate was 4% and the 5-year minor UT complication rate was 10%. In 9 patients receiving RT at 200 rad/day, one major GI complication (13%) and one major UT complication (14%) developed. In 16 patients receiving RT at 180 rad/day only minor GI complications (7%) and minor UT complications (13%) developed. The conclusion is that after RH-PND, adjunctive RT delivered at 180 rad/day through four ports results in acceptable, minimal complications.

Adult↗
PubMed1986

Response of colo-rectal hepatic metastases to concomitant radiotherapy and intravenous infusion 5 fluorouracil.

Twenty-three patients with colo-rectal hepatic metastases were retrospectively reviewed after completing treatment with split course liver irradiation and continually infused concomitant intravenous 5-fluorouracil. Although no patient attained a complete response, an objective partial response was documented in 15 (Responders). The Responders had a median survival of 45 weeks whereas Non-responders had a median survival of 17 weeks. Patients with metastatic disease solely in the liver or those with a Karnofsky performance score (k.p.s) of over sixty, had a median survival of 49 weeks. Patients with multiple organ metastatic involvement had a median survival of 25 weeks and those with a Karnofsky with less than 60 had a median survival of 27 weeks. (p values of 0.006 and 0.03, respectively.) The overall survival of the group completing treatment was 30 weeks, and 19 patients (83%) achieved subjective palliation. The patients tolerated therapy well. There was minimal hematological toxicity; 3 patients developed a leucocyte count of less than 2000 and 1 developed a platelet count of 30,000. The palliation and prolongation of survival attained with minimal complications suggest that adjuvant liver irradiation with concomitant infusion 5-fluorouracil radiosensitization may be an option to offer patients identified to be at high risk of developing subclinical liver disease.

Adult↗
PubMed1986

Effect of misonidazole dose on survival in patients with stage IIIB-IVA squamous cell carcinoma of the uterine cervix: an RTOG randomized trial.

Between August 1980 and November 1984, 120 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (RT) (46 Gy pelvis + 10 Gy parametrial boost) followed by intracavitary or external boost to the primary +/- misonidazole (MISO) (400 mg/M2 2-4 hours prior to RT daily, maximum 12 gm/M2). The median at 24-28 hr misonidazole plasma level was 20 micrograms/ml 2-6 hr and 3.5 micrograms/ml. Approximately 60% of the patients on RT + MISO received 100% of expected total Misonidazole dose; peripheral neurologic toxicity was reported for nine patients receiving misonidazole (8 with mild and 1 with moderate paresthesia or pain). Time-dependent regression analyses found that actual cumulative misonidazole dose was not related to duration of survival from start of treatment (p = 0.5). MISO dose expressed as a percent of expected dose was marginally related to increased survival measured from 14 weeks on on study (p = 0.1). No improvement in survival was observed with the addition of misonidazole to RT (64% of the patients on RT alone were alive at 18 months versus 54% of those on RT + MISO).

Carcinoma, Squamous Cell↗
PubMed1986

Adjuvant chemotherapy with adriamycin, cytoxan, and cis-platinum in high-grade carcinoma of the prostate treated with definitive radiotherapy (RTOG pilot 81-12).

In a phase I-II trial, a regimen of Adriamycin, Cytoxan, and cis-Platinum has been tested as an adjuvant to definitive radiotherapy in patients with high-grade (Gleason score 8-10) locally advanced carcinoma of the prostate limited to the pelvis. The patients had no evidence of distant disease, were in good general condition, and had satisfactory cardiac, hepatic, and renal function. Radiation therapy consisted of 4,320-4,500 rad in 23-25 fractions to the pelvis followed by a boost to the prostate to a total of 6,480-7,020 rad in 36-39 treatments. Chemotherapy was scheduled to start 4 weeks after completion of radiotherapy and consisted of 300 mg/m2 of Cyclophosphamide, 30 mg/m2 of Adriamycin, and 50 mg/m2 of cis-Platinum cycles given at 4-week intervals. The primary aim of the study was evaluation of toxicity of the combined regimen. Nine patients were evaluable. No adverse effects of chemotherapy on the incidence and severity of radiation-related toxicity in the pelvis have been observed. Myelosuppression has been significant and has prevented delivery of full doses of chemotherapy. Although planned, no dose escalation was possible. Further reduction of dosage was necessitated in 67% of the patients. Delays in the delivery of chemotherapy were necessary in four patients; the delays ranged from 1 to 14 weeks. Although the regimen had been reported to produce a high rate of response in disseminated disease and has not been associated with an increased incidence of radiation-chemotherapy toxicity in the irradiated pelvis, it does not appear suitable for further testing in an adjuvant setup in patients treated with definitive radiotherapy.

Aged↗
PubMed1986

Comparison of 32P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation.

We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium 32P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with 32P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with 32P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with 32P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while 32P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or 32P treatment.

Bone Neoplasms↗
PubMed1985

Metastatic melanoma in brain. Rapid treatment or large dose fractions.

A subgroup of 59 patients selected on the basis of favorable prognostic factors from a larger group of 194 patients treated for intracranial metastases of melanoma was analyzed with a view to assessing the relative efficacy of different accelerated fractionation regimens. The most effective modification of the previously standard therapy was a shortening of the overall treatment time, although this was also associated with the use of larger doses per fraction. Patients who had brain metastases only at the time of treatment showed a longer survival time than those with coexistent metastases in other organs and survived longer if treated with 10 fractions within 1 week rather than 20 fractions in 2 weeks. The same was found in patients who underwent complete resection of intracranial tumor before irradiation. A complete surgical resection also increased the probability of eliminating intracranial disease, but overall the median survival increased by less than 2 months. It is concluded that a short overall treatment time is more important than large fraction sizes in attempts to improve the treatment of metastatic intracranial melanomas with favorable prognosis.

Brain Neoplasms↗
PubMed1985

Intracranial metastases from melanoma. Clinical features and treatment by accelerated fractionation.

One hundred ninety-four patients with intracranial metastatic melanoma were treated at the M. D. Anderson Hospital between January 1972 and September 1977, using seven different accelerated irradiation regimens. The total tumor dose varied from 3000 to 4800 rad, and the overall treatment time from 1 to 2 weeks. In these patients, whose disease had progressed to brain metastases, freedom from such metastases had decreased logarithmically with time from initial presentation. This suggests a random distribution of progression rates with a mean time of 2.5 years between diagnosis and development of intracranial metastases. Overall, there was no significant improvement in the results from accelerated fractionation in the treatment of intracranial metastases. The result of treatment did not depend on the site of the primary, the number of intracranial metastases, the total dose, or the dose per fraction. There were, however, two subgroups not mutually exclusive, that benefited significantly from the accelerated fractionation: patients having had a complete resection of brain metastases, and those having no detectable extracranial metastases at the time of their treatment for intracranial metastases.

Adolescent↗
PubMed1985

Complications of combined surgery and radiation therapy for carcinoma of the endometrium.

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 133 women with carcinoma of the endometrium who were treated by both radiotherapy and hysterectomy. Major complications developed in 8% of patients who received external pelvic radiation but in none with intracavitary radiation. GI complications were more frequent and more severe in patients receiving external pelvic radiation than in those who received only intracavitary radiotherapy, irrespective of the sequence of treatment. UT complications were more frequent with prehysterectomy external radiotherapy (N = 39) than with posthysterectomy external radiotherapy (N = 21).

Brachytherapy↗
PubMed1977

Supportive therapy in radiation oncology.

Measures for supportive care of the radiation therapy patient are presented. These include emotional support prior to and during the course of therapy facilitated by a written interview that allows the radiation oncologist to be a supportive communicator of realistic information. A discussion is made of the support of body tissues affected by combination radiation and chemotherapy. These tissues usually include skin, oral, esophageal and intestinal mucosa, and teeth. Means of maintaining nutritional support following weight loss of patients during therapy are described.

Adult↗
PubMed1977

Radiation therapy of choroidal melanoma.

During the past 8 years, 32 patients with melanoma of the choroid have been treated with cobalt-60 ophthalmic applicators. Excluding three patients lost to follow-up, 24 patients who have now been observed for at least 3 years after treatment form the subject of this study. Each application but two delivered 8,500 to 10,000 rads to the tumour apex. A second application was performed in large tumours showing a poor response to the initial plaque treatment. The factors affecting results include age of the patient, tumour size, total dose delivered, and dose rate. Three out of seventeen patients with tumour diameters greater than 12 mm died of their disease with pulmonary and/or liver metastasis. Three eyes required enucleation and no residual tumour was found in two specimens. Three patients, average age 76 years, died from causes other than melanoma. An 83 per cent relative survival, excluding the three patients lost to follow-up, compares favourably with enucleation. The low incidence of metastasis after radiotherapy suggests augmentation and/or continuation of the host's immune response. Low energy radiation using Iodine-125, with its unusual protective characteristics is ideal for treatment of choroidal melanoma.

Aged↗
PubMed1975

Renal metastases simulating Kaposi sarcoma. Radionuclide scanning, an aid in diagnosis and treatment planning.

A case of renal cutaneous metastases simulated Kaposi sarcoma and the condition was misdiagnosed as Kaposi sarcoma. A new technique was employed using the isotope technetium 99m as the compound sodium pertechnetate Tc 99m for the diagnosis and evaluation of the extent of Kaposi sarcoma. The failure to demonstrate a positive isotope scan in our case was a clue to the incorrect diagnosis of Kaposi sarcoma.

Aged↗