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Biomedical subjects

P Rubin

Publications and source records attributed to P Rubin.

At least 235 records · Page 13Linked to original sources
PubMed1987

Correlation of radiotherapeutic parameters and treatment related morbidity--analysis of RTOG Study 77-06.

The current report is an updated and detailed analysis of treatment related morbidity in RTOG 77-06, a Phase III randomized study comparing prostatic irradiation versus pelvic irradiation followed by a prostatic boost, in patients with Stage A2 and B carcinoma of the prostate without evidence of nodal involvement. A total of 453 analyzable cases were accrued from 1978 to 1983, when the study was closed. All cases of treatment related morbidity were classified as to severity (using a clinical severity grading system). The data were then correlated with a number of radiotherapeutic parameters including treatment volumes (fields), doses, and techniques. Overall, pelvic irradiation, compared to prostate irradiation only, was not associated with a significantly increased incidence of treatment related morbidity. Within the range of pelvic doses used in this study a significant dose effect could not be detected. Total doses to the prostate of more than 7000 cGy were associated with an increased risk of rectal bleeding. Certain treatment techniques, (AP/PA irradiation of the pelvic lymphatics) were associated with an increased incidence of bowel complications.

Humans↗
PubMed1987

Simultaneous radiation therapy and cisplatin chemotherapy in advanced cancer of the head and neck. A pilot study at Tygerberg Hospital, Parowvallei, South Africa.

Fifty patients with advanced carcinoma of the head and neck were treated in a nonrandomized pilot study utilizing simultaneous cisplatin and radiotherapy. Treatment was delivered in two segments. The initial partial course (PC) consisted of 75-100 mg/m2 of cisplatin and concomitant radio-therapy to 20.00 Gy in 1 week, with 4-week split. Patients who tolerated therapy and experienced at least a partial response (PR) went on to complete the full course of therapy (FC), with the second phase consisting of 120 mg/m2 of cisplatin and 38.40 Gy of radiation. Total cisplatin delivered ranged between 195 and 220 mg/m2, and the total radiation dose was 58.40 Gy. Of 38 evaluable patients, 31 (82%) had at least a partial response (PR). However, at time of analysis 20 months after study, 27 (71%) patients were alive with disease or dead. Mean disease-free survival (DFS) for patients receiving FC therapy (10.05 months) was greater than that for patients who received only PC therapy (2.65 months), but the difference in overall survival (OS) was not statistically significant (11.95 FC versus 10.29 PC). Response rates and the minimal toxicity are within the range of other reported studies. Randomized studies should seek optimal time-dose schedule and establish advantages in terms of crude survival and disease-free survival.

Adolescent↗
PubMed1987

A major challenge in cancer therapy: metastasis.

Although metastasis remains a major cause of death, current therapeutic techniques used in the management of malignant disease are usually effective in achieving primary tumor control. There are many important issues to be considered in the management of pulmonary metastasis. Some of the more important issues, which will be discussed, include solitary v multiple metastases, when is cure possible, prognostic signs, and palliation.

Humans↗
PubMed1987

Hyperprolactinemia and hypothyroidism following cytotoxic therapy for central nervous system malignancies.

Endocrinologic dysfunction including hyperprolactinemia and hypothyroidism are recognized complications of irradiation to the hypothalamic-pituitary axis or thyroid gland in the course of treating CNS malignancies. However, the frequency of these adverse effects in both short- and long-term survivors may be underestimated. Sixty-five patients treated in the University of Rochester Cancer Center since 1968 with radiation with or without BCNU chemotherapy for CNS tumors not involving the hypothalamic-pituitary axis were evaluated for thyroid, prolactin, and gonadal disturbances regardless of clinical symptomatology. Prolactin values were elevated in 19 of 47 patients (40%). For males and females treated with greater than 55 Gy, abnormal values were present in nine of 11 (82%) and seven of 14 (50%), respectively. For males and females treated with less than or equal to 55 Gy, two of nine (22%) and one of 13 (8%), respectively, were abnormal (P = .0001). Six of six patients who also received BCNU chemotherapy were hyperprolactinemic, as compared with six of ten (60%) who did not receive BCNU. Seven of eight females with elevated prolactin levels had menstruation abnormalities, and five of seven adult males noted a decrease in libido. Mild abnormalities in testosterone concentration were found in three of nine men evaluated, all of whom had normal gonadotropins. Of 47 patients who did not receive irradiation to the spinal axis (and thus the thyroid gland), ten (21%) had a decreased thyroxin (T4) value. Only one of these patients had an elevated thyroid-stimulating hormone (TSH) value. Of 32 patients who received greater than 55 Gy, ten (31%) had a low T4, compared with zero of 15 who received less than or equal to 55 Gy (P = .0001). Four of eight patients (50%) who also received BCNU had low T4 values, as compared with three of 14 (21%) who did not receive BCNU. Of 15 patients who were treated with 4 to 10 MV photon irradiation to the spinal axis, five patients (33%) had elevated TSH values. The mean spinal axis dose in these patients was 33 Gy. Two euthyroid children in this group manifested the early onset of puberty. The complex of endocrinologic abnormalities observed in several patients receiving only cranial irradiation, that is elevated prolactin, decreased thyroid, and gonadal hormone secretion in the presence of otherwise normal pituitary hormone levels, suggests a radiation-induced insult to the hypothalamic regulation of pituitary function.

Adolescent↗
PubMed1987

The differential protection by WR2721 of skin versus growing cartilage following irradiation in weanling rats.

The potential for radioprotection of growing cartilage by the thiophosphate WR2721 was evaluated in weanling rats using single fractions of irradiation. Protection of acute skin toxicity was monitored simultaneously. Single doses of 600, 1200, 1800, or 2400 cGy were administered to the left tibia of CrL:CD(SD)BR female rats in groups of 12. Identically treated groups were injected with 310 mg/kg WR2721 (2/3 the determined LD50/30) in a concentration of 26 mg/ml intraperitoneally 15 min prior to irradiation. Rats untreated or given WR2721 without radiation served as control groups. Radiographs of the irradiated and unirradiated tibiae for each animal were obtained weekly to the date of sacrifice at 80 days following the initial treatment. Skin toxicity was assessed weekly starting on the second week using Moulder's scale (J.E. Moulder, J.J. Fischer, and A. Casey, Radiology 115, 465-470 (1975]. No significant difference in bone growth as measured by tibial lengths for the WR2721-treated or untreated animals was observed. Skin toxicity including moist desquamation occurred in irradiated limbs and was substantially less in rats treated with WR2721. As opposed to previous work with cysteamine, WR2721 as administered had no significant radioprotective effect on tibial growth in weanling rats but substantially reduced the accompanying skin toxicity.

Amifostine↗
PubMed1987

Chorionic gonadotropin decreases intraocular pressure and aqueous humor flow in rabbit eyes.

The effect of human chorionic gonadotropin (hCG) on the rabbit eye was studied. Intravitreal injections of hCG in albino rabbits provoked a reduction of intraocular pressure (IOP). Intravenous administration of hCG in single doses of 5,000-10,000 units in male pigmented rabbits caused a significant reduction in IOP from 1.5-5 hr after injection. When two successive intravenous doses of 5,000 units of hCG were given at 0 and 3 hr to pigmented rabbits, a significant reduction of net aqueous flow occurred, as measured by scanning fluorophotometry. These results indicate that the decrease in aqueous flow rate in the rabbit eye after administration of hCG can account for the reduction in IOP.

Animals↗
PubMed1986

Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report.

This is the final analysis of Protocol #78-10 which explored increasing single-doses of half-body irradiation (HBI) in patients with multiple (symptomatic) osseous metastases. When given as palliation, HBI was found to relieve pain in 73% of the patients. In 20% of the patients the pain relief was complete; over two thirds of all patients achieved better than 50% pain relief. The HBI pain relief was dramatic with nearly 50% of all responding patients doing so within 48 hours and 80% within one week from HBI treatment. Furthermore, the pain relief was long-lasting and continued without need of retreatment for at least 50% of the remaining patient's life. These results compare favorably with those obtained by the Radiation Therapy Oncology Group (RTOG) using several conventional daily fractionated schemes on similar patients in a prior study (RTOG #74-02). HBI achieves pain relief sooner and with less evidence of pain recurrence in the irradiated area than conventionally treated patients. The most effective and safest of the HBI doses tested were 600 rad for the upper HBI and 800 rad for the lower or mid-HBI. Increasing doses beyond these levels did not increase pain relief, duration of relief, or achieved a faster response; however, the increase in dose was associated with a definite increase in toxicity. Single-dose HBI was well tolerated with no fatalities seen among 168 treated patients. A comprehensive premedication program has proven to decrease the acute radiation syndrome to very acceptable levels. There were excellent responses found in practically all tumors treated, but especially breast and prostate among which over 80% of all patients experienced pain relief, 30% in a complete fashion. Single-dose HBI emerges as one of the safest, fastest, and more effective palliative tools for intractable cancer pain in modern radiation oncology.

Bone Neoplasms↗
PubMed1986

Predictive biochemical assays for late radiation effects.

Surfactant precursors or other products of Type II pneumocytes have the potential to be the first biochemical marker for late radiation effects. This is particularly clinically important in the combined modality era because of the frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation or chemotherapy. Accordingly, correlative studies have been pursued with the Type II pneumocyte as a beginning point to understand the complex pathophysiology of radiation pneumonitis and fibrosis. From our ultrastructural and biochemical studies, it is evident that Type II pneumocytes are an early target of radiation and the release of surfactant into the alveolus shortly after exposure persists for days and weeks. Through the use of lavaging techniques, alveolar surfactant has been elevated after pulmonary irradiation. In three murine strains and in the rabbit, there is a strong correlation with surfactant release at 7 and/or 28 days in vivo with later lethality in months. In vitro studies using cultures of type II pneumocytes also demonstrate dose response and tolerance factors that are comparable to the in vivo small and large animal diagnostic models. New markers are being developed to serve as a predictive index for later lethal pneumonopathies. With the development of these techniques, the search for early biochemical markers in man have been undertaken. Through the use of biochemical, histological, and ultrastructural techniques, a causal relationship between radiation effects on type II pneumocytes, pulmonary cells, endothelial cells of blood vessels, and their roles in the production of pneumonitis and fibrosis will evolve.

Animals↗
PubMed1986

Hodgkin's disease: is there a price for successful treatment? A 25-year experience.

Three hundred-twenty patients with Hodgkin's disease (HD) were studied retrospectively to assess the impact of treatment on survival and the development of second malignant neoplasms (SMN). All stages of HD were considered. Treatment groups included XRT only, XRT + multiagent chemotherapy (MAC), XRT + single agent chemotherapy (SAC), and chemotherapy only (Chemo). MAC was subdivided into MOPP and non-MOPP regimens. Twenty-one patients developed 23 SMN, only two of which were acute leukemias. Survival was greatest for XRT only because of a large proportion of early stage HD in this group. SMN were seen in all treatment groups except Chemo only. The XRT + MAC group had a significantly elevated observed-to-expected ratio for SMN, but it was difficult to attribute this to either MOPP or non-MOPP due to very small numbers of patients. The actuarial risk of SMN for both MOPP and non-MOPP rises dramatically between 10 and 15 years, however, extrapolation cannot be done, again because of very small numbers. We conclude that there is an increased risk of SMN in patients treated aggressively for HD, but that the exact cause of SMN is difficult to determine.

Antineoplastic Agents↗
PubMed1986

Protection by WR-2721 of human bone marrow function following irradiation.

Protection by WR-2721 of bone marrow (BM) from depression following hemibody irradiation (HBI) was assessed in patients receiving palliative therapy for widespread symptomatic metastasis on a Phase I/II Radiation Therapy Oncology Group (RTOG) protocol. Twenty-five patients are currently evaluable for the assessment of hematologic toxicity. HBI (600 or 700 cGy) was delivered starting 15-30 min after WR-2721 (600-900 mg/m2) intravenous infusion. Twenty patients from previous RTOG HBI studies were comparable in terms of radiation dose, hematologic data, and previous cytotoxic therapy. The WBC and platelet count nadirs at any time within 6 wk following HBI were used for data analysis, and toxicity was rated according to RTOG criteria. For the patients treated with WR-2721, moderate, severe, or life-threatening toxicity were seen in 16%, 12%, and 0% of the patients, respectively, compared to 30%, 15%, and 10% of patients in the group not treated with WR-2721. For the subpopulation of patients treated with the higher irradiation dose (700 cGy), differences in toxicity appeared to be greater. Conversely, for the sub-population of patients treated only to the upper hemibody, the difference in toxicity was less apparent. The percentage change from the median pre-treatment white blood cell (WBC) and platelet counts (PC) was not different between the WR-2721 treated and non-treated group; however, the median WBC count for the WR-2721 group returned to the pre-treatment value by the fourth week following HBI, whereas, it remained at 61% of the pre-HBI value for the control group. Within the group of patients treated with WR-2721, 5 of 17 (29%) receiving 600 mg/m2 demonstrated a greater than 75% decline in either WBC or platelets, compared to 0/8 patients treated with 750-900 mg/m2. These preliminary data support a protective effect by WR-2721 on radiation-induced bone marrow depression in humans, which may become more apparent with the use of higher radiation and WR-2721 doses.

Amifostine↗
PubMed1986

Long term effects of radiation and combined modalities on mouse lung.

The lung appears to be the major dose-limiting organ in radiation of the thorax. Early responses (less than 1 week) involve the type II pneumocyte and increased surfactant biosynthesis and secretion. Later changes, which appear to be related to the surfactant response, lead to classical radiation pneumonitis, which is often fatal. Animals which survive radiation pneumonitis develop progressive fibrosis, a late-appearing response, which reduces compliance and available air space, and is usually fatal. This study centers on the fine structural changes in the lungs of LAF1 mice, 63 weeks following various radiation exposures (5-13 Gy). Doses which are subthreshold in evoking surfactant and pneumonitic responses precipitate fibrosis and atelectasis by 63 weeks, and involve type II pneumocyte sloughing and degeneration. Of the two major deterrents to lung irradiation (pneumonitis and fibrosis), these results suggest that fibrosis always follows pneumonitis, but pneumonitis is not a necessary preliminary step to fibrosis. Bleomycin elicits several morphological alterations characteristic of radiation, and, when combined with the latter, appears to exacerbate radiation effects.

Animals↗
PubMed1985

Hodgkin's disease stages IA and IIA. A long-term follow-up study on the gains achieved by modern therapy.

One hundred forty-nine supradiaphragmatic Stage IA and IIA Hodgkin's disease (HD) patients treated according to one of two different policies, were analyzed to quantitate the therapeutic gains achieved in recent years. Forty-nine patients were managed according to the pre-1969 policy consisting of mantle radiotherapy (XRT) only without laparotomy staging and without subdiaphragmatic treatment. These cases constitute the old series (OS). Ninety-eight patients after 1969 received staging laparotomy-splenectomy and were treated with total or subtotal nodal irradiation, and in a small number also multiagent chemotherapy (MAC). These patients constitute the new series (NS). All prelaparotomy IA and IIA cases are included in the NS even if they became Stage III at laparotomy. Salvage therapy for relapsing disease differed between the OS and NS. The majority of OS relapsing patients received salvage XRT, while the majority of relapsing NS patients received MAC. The NS and OS patient groups are comparable by pretreatment parameters. There is a large and statistically significant improvement in disease-free survival (DFS) and survival (S) in the NS over the OS. At 13 years the NS group had a DFS of 65% compared to 38% in the OS, and S in the NS was 82% compared to 37% in the OS. The improvement in DFS is almost totally due to the addition of prophylactic periaortic XRT in the NS patients. A striking reversal of relapse patterns for the OS and NS was observed. Periaortic nodal relapse occurred in 37% of the OS patients and accounted for 64% of all relapses, while in the NS this failure pattern occurred in only 2% of all cases. Supradiaphragmatic relapse accounted for 74% of all relapses in the NS. Improved salvage of relapsed patients in the NS further added to the overall gain in survival. Whereas no relapsed patient in the OS achieved long-term survival (14% at 10 years, 0 at 25 years), one-half of NS relapses were salvaged by MAC (54% survival at 10 years from relapse). These data clearly document the striking therapeutic gains in Stage IA and IIA supradiaphragmatic HD resulting from the use of prophylactic periaortic XRT and MAC salvage for relapsing patients.

Actuarial Analysis↗
PubMed1985

Laparotomy-staged IA versus IIA Hodgkin's disease. A comparative study with evaluation of prognostic factors for stage IIA disease.

Ninety-one laparotomy-staged (LAP) IA and IIA Hodgkin's disease (HD) patients were analyzed to evaluate the prognostic significance of stage, mediastinal status, extranodal disease and histology. Forty IA patients were treated with radiotherapy (XRT) only; of 51 IIA patients, 44 received XRT only and 7 had additional chemotherapy. Disease-free survival (DFS) at 5 and 10 years was 81% and 70%, respectively, with overall survival (S) of 93% and 86%, respectively. Disease-free survival for IA patients (93% at 5 and 10 years) was significantly superior to IIA (73% at 5 years, 52% at 10 years). Survival differences were not statistically significant. For IIA patients receiving XRT only, large mediastinal disease was an adverse factor for DFS. Small mediastinal disease in IIA was significantly better than no mediastinal disease. For the whole group of LAP IA and IIA treated by XRT only, three prognostic groups were identified: (1) Stage IA and Stage IIA with mediastinal disease, but less than 7.5 cm in width was highly favorable with less than 10% relapse; (2) Stage IIA nonmediastinal had an intermediate prognosis with relapse in about 33%; (3) Stage IIA large mediastinal (greater than or equal to 7.5 cm) had an unfavorable DFS with relapse in about 55%. The third group contained a highly unfavorable subset with mediastinal masses greater than 10 cm, all of whom relapsed. Salvage therapy was successful in 60% of relapsing patients. In the context of relatively effective salvage therapy, the role of adjuvant chemotherapy in adverse prognostic groups is discussed and it is concluded that the only clearly justifiable use for adjuvant chemotherapy is in patients with massive (greater than 10 cm) mediastinal adenopathy.

Adult↗
PubMed1985

Systemic hemibody irradiation for overt and occult metastases.

Hemibody irradiation was initially employed as a palliative technique to treat diffuse metastatic disease in one session as opposed to multiple fields over an extended period. It provides a radiation treatment for disseminated cancer and therefore has been termed "systemic" therapy. Since it is possible to treat both halves of the body sequentially, it allows radiation treatment to the whole body in larger doses than could be accomplished with total-body irradiation. Because of the success in terms of dramatic rapid pain relief and the objective response on metastatic disease, it has been explored in the treatment of occult disease and as consolidation therapy in patients with tumors that have responded to chemotherapy. When hemibody irradiation is combined with chemotherapy, responses have been shown in metastases for several primaries, particularly small cell carcinoma, which is perhaps the most encouraging, and supports further research in the treatment of micrometastatic disease for this tumor type. As the technique moves from its current research phase into more general clinical use, radiation oncologists should become more familiar with the treatment, and the hospitalization originally required may be able to be avoided. An intensive premedication program has been developed to facilitate this. Innovative approaches using radiosensitizers, radioprotectors, hyperthermia, and hyperfractionation are ideas that are starting to be tested and will be further explored in the near future.

Amifostine↗
PubMed1985

Nephrogenic adenoma.

Nephrogenic adenoma is an uncommon, benign, apparently metaplastic response of urothelium to chronic infection or irritation. Endoscopically, these lesions easily can be mistaken for malignant tumors, and their scarcity only heightens the possibility of this error. A case report of nephrogenic adenoma accompanied by endoscopic photographs is presented to improve awareness and avoid inappropriate therapy.

Adenoma↗