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T Goffman

Publications and source records attributed to T Goffman.

13 recordsLinked to original sources
PubMed1994

Treatment of locally advanced cancer of the head and neck with 5'-iododeoxyuridine and hyperfractionated radiation therapy: measurement of cell labeling and thymidine replacement.

BACKGROUND: The halogenated pyrimidines 5'-iododeoxyuridine (IdUrd) and 5'-bromodeoxyuridine (BrdUrd) are under active study as radiation sensitizers for a variety of malignancies. Head and neck neoplasms may also be suitable for halogenated pyrimidine-mediated sensitization; previous regimens using intra-arterial BrdUrd delivery, however, were poorly tolerated. PURPOSE: A pilot study was undertaken with the use of intravenous IdUrd with hyperfractionated radiotherapy to assess tolerance. In addition, serial tumor biopsy specimens were obtained to determine the kinetics of IdUrd labeling and incorporation. METHODS: Twelve patients with squamous cell carcinomas of the head and neck (one patient had stage II cancer, one had stage III, and 10 had stage IV) were treated with hyperfractionated radiation therapy at a dose of 1.2 or 1.5 Gy twice a day, to a total dose in the range of 70-76 Gy. IdUrd (1000 mg/m2 per day) was infused for a maximum of 14 days at the beginning and then again during the middle of the radiotherapy. A tumor biopsy specimen was obtained from 11 patients following initiation of treatment with IdUrd. Eight patients consented to serial biopsy to allow the study of IdUrd-labeling indices and thymidine replacement over time. Incorporation of IdUrd into tumor DNA was determined by high-performance liquid chromatography, and cell labeling was determined with the use of an anti-BrdUrd/IdUrd monoclonal antibody in conjunction with flow cytometry. Patients continue to be followed to assess local control. RESULTS: A plot of corrected IdUrd replacement as a function of infusion time suggests the possibility of a plateau after 5-7 days of infusion at 7.5%-8%. The average rate of replacement from days 1 to 5 was 1.3% per day and was determined by linear regression analysis. Acute toxic effects, especially mucositis, were severe enough to require delays in the radiation therapy. Eleven of 12 patients treated had complete clinical remissions. Seven of these patients remain clinically free of local disease at the time of death or most recent follow-up. CONCLUSIONS: The level of IdUrd incorporation and cell labeling should be adequate to produce sensitization. However, the treatment as prescribed in this study (two 14-day infusions of IdUrd during radical radiotherapy with only one planned split) was not completed in a single patient because of either dose-limiting hematologic toxicity or severe mucositis necessitating treatment break. Since this particular regimen is not tolerable, future protocols will have shorter exposures to IdUrd. IMPLICATIONS: Previous regimens using halogenated pyrimidine radiosensitizers have generally used protracted drug delivery schedules. In this study, a high level of IdUrd labeling was measured after 5-7 days of drug infusion. The halogenated pyrimidines deserve further study with the use of repetitive short courses to reduce toxicity and possibly improve efficacy.

Adult↗
PubMed1992

Topical application of nitroxide protects radiation-induced alopecia in guinea pigs.

We have recently found that treatment of Chinese hamster V79 cells with the stable nitroxide radical TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) afforded significant protection against superoxide, hydrogen peroxide, and X-ray mediated cytotoxicity. Radiation-induced alopecia is a common radiotherapeutic problem. Topical application of TEMPOL was evaluated for possible protective effects against radiation-induced alopecia using guinea pig skin as a model. For single acute X-ray doses up to 30 Gy, TEMPOL, when topically applied 15 min prior to irradiation provided a marked increase in the rate and extent of new hair recovery when compared to untreated skin. TEMPOL was detected in treated skin specimens with electron paramagnetic resonance (EPR) spectroscopy. Similar measurements of blood samples failed to show any signal resulting from topical application, nor could TEMPOL be detected in brain tissue after application on the scalp. TEMPOL represents a new class of compounds with potential for selective cutaneous radioprotection without systemic absorption.

Administration, Topical↗
PubMed1991

Primary treatment of large and massive adult sarcomas with iododeoxyuridine and aggressive hyperfractionated irradiation.

For a decade, the authors have experimented with treatment for unresectable adult soft tissue and bony sarcomas. Over the last 6 years, they have combined hyperfractionated radiation therapy and intravenous iododeoxyuridine as a radiosensitizer, in regimens designed to minimize toxicity and permit delivery of aggressive radiation therapy. Patients with solitary lesions and those with metastasis (38%) were treated in the hope of both potential cure in some and durable palliation in others. The most formidable of these cancers have been those that are large or massive, often requiring five or more fields and extensive treatment planning. The authors report results from 36 patients with large unresectable sarcomas (tumors ranging from 5 to 35 cm; average 14 cm) treated with hyperfractionated radiation therapy, with a minimum follow-up of 1 year, follow-up of 4 or more years (in 50%), or follow-up until death. Overall local control has been 60%, with control of 66% of lesions from 5 to 9 cm, 63% of those from 10 to 14 cm, 63% of those from 15 to 19 cm, and 57% of those greater than 20 to 40 cm. Morbidity has been modest. This experience compares favorably with the authors' earlier trials with misonidazole, and toxicity has been reduced considerably.

Adult↗
PubMed1990

A staging of lymphomas: practical thoughts on impractical practices.

Staging of lymphomas represents a discipline different from the staging of other cancers. In lymphomas, the purpose of staging rests more on the establishment of consistent standards by which we can evaluate changes in treatment programs, rather than a means of deciding on an appropriate treatment for an individual patient. In comparing treatments from different times and centers, one should exercise care to ensure the true comparability of the study groups. Frequently, errors are encountered in the comparison of surgical versus clinical staging. Other pitfalls occur when new, more sensitive diagnostic tests result in the clinical upstaging of selected groups leading to the improvement in subgroups but not affecting the treatment results for the group as a whole.

Humans↗
PubMed1988

Stage IA and IIA supradiaphragmatic Hodgkin's disease: prognostic factors in surgically staged patients treated with mantle and paraaortic irradiation.

A total of 315 pathologically staged (PS) patients with IA and IIA Hodgkin's disease (HD) were treated with mantle and paraaortic irradiation, and evaluated for freedom-from-first relapse (FFR), survival, prognostic factors, and long-term complications. The 14-year actuarial FFR and survival were 82% and 93%, respectively, with a median follow-up time of 9 years. Mediastinal size was the only factor that predicted for a lower FFR, P less than .001. Forty-nine patients have developed recurrent HD. Thirty-six patients are disease-free following retreatment and only 13 patients have died of HD. Patients with mixed cellularity (MC) histology were more likely to relapse below the diaphragm (11%) as compared with patients with nodular sclerosis (NS) (5.1%) or lymphocyte predominant (LP) (3.6%) histology. These relapses were often associated with bulky pelvic nodal adenopathy and salvage treatment with chemotherapy alone often failed to control recurrent disease. Alternative diagnostic and therapeutic recommendations are presented for these patients. Thyroid abnormalities represented the most common long-term complication with an actuarial risk at 16 years of 37%. Major complications were rare. Mantle and paraaortic irradiation is associated with a high FFR and a low risk of complications and should remain standard treatment for early-stage HD.

Adolescent↗
PubMed1987

Treatment of patients with "minimal" stage IIIA Hodgkin's disease.

Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone.

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.

Actuarial Analysis↗
PubMed1981

Unexplained increase in serum creatine kinase isoenzyme MB activity in a lung cancer patient.

In this case of mixed small cell--large cell cancer of the lung in an elderly woman, creatine kinase (EC 2.7.3.2) isoenzymes were assayed serially because of chest pain. The proportions of serum CK-BB and CK-MB isoenzyme activities were persistently above normal (CK-MB 10-18%, normal less than 5%). Electrocardiograms revealed no signs of ischemia or infarction. At autopsy no gross or microscopic infarction or inflammation of the heart was seen. There was also no infarction of smooth or skeletal muscle. The tumor was the probable source of most of the circulating CK-MB isoenzyme. Future cases may pose a similar diagnostic dilemma: differentiating creatine kinase that is present as a result of myocardial infarction from tumor-related CK-MB. Whether or not CK-MB assay could be useful in detecting tumors remains to be investigated.

Aged↗
PubMedDate not supplied

Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment.

In the conventional linear-quadratic model of single-dose response, the alpha and beta terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with "unconventional" treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD. The expressions developed by Thames [Int. J. Radiat. Biol. 47, 319-339 (1987)] for fractionated treatment (the IR model) and by Dale [Br. J. Radiol. 58, 515-528 (1985); 59, 919-927 (1986)] for protracted and fractionated treatment are found to be similar to our results in the limiting case where the pool of SLD is very large (infinite).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗