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Biomedical subjects

M M Kligerman

Publications and source records attributed to M M Kligerman.

At least 19 recordsLinked to original sources
PubMed2000

Variation in parotid gland size, configuration, and anatomic relations.

PURPOSE: To examine the variation in the anatomy of parotid glands discerned by magnetic resonance imaging. METHODS: Head and neck magnetic resonance scans of 16 patients (representing 32 glands) whose studies consisted of 5 mm contiguous sections were selected at random. The T1 weighted scans were thresholded and outlined to only encompass the parotid tissue. A volumetric analysis program (ISG Technologies, Inc.) was used to compute the parotid volume in cubic millimeters. Each of the 32 glands was measured independently by two observers. RESULTS: The difference between observers averaged 4.8%. The median volume was 25,262 mm3, range 9225-54,080 mm3. In four patients there were considerable differences in the volumes of the right and left parotid glands, with variations of 9, 10, 14 and 29%. In nine patients, (18 glands) the depth from the medial edge of the gland to the spinal cord ranged from 19-32 mm. However, the maximum variation between the two sides in a single patient was 4 mm. Observations made include: (1) parotid glands extending anterior to the masseter muscle, or posterior to the posterior margin of this muscle; (2) parotid glandular tissue extending above the zygoma and the external auditory canal; (3) parotid tissue extending posteriorly to overlap the spinal cord; (4) parotid glands extending below or remaining above the angle of the mandible; and (5) wide variation of the transverse dimension of the parotid glands, with one measuring 4.8 cm. DISCUSSION: To ensure that the entire parotid is or is not in a treatment field a computerized tomography or magnetic resonance scan is necessary. If a specific portion of the gland must be in the field a volume histiogram must be available.

Dose-Response Relationship, Radiation↗
PubMed1999

A phase I trial of 96-hour paclitaxel infusion plus accelerated radiotherapy of unrespectable head and neck cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of paclitaxel given as a 96-hour continuous infusion during Weeks 1 and 5 of an accelerated radiotherapy schedule for the definitive treatment of advanced (nonmetastatic) unresectable squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Thirteen patients with Stage IV SCCHN were enrolled. Radiotherapy consisted of 70-72 Gy over 6 weeks, with a fractionation scheme of 2 Gy q.d. for 4 weeks followed by 1.6 Gy b.i.d. for 2 weeks, with no planned interruptions. Paclitaxel was administered over a 96-hour continuous infusion during Weeks 1 and 5 of radiotherapy at the following dose levels: Dose Level 1: 40 mg/m(2)/96-hours (3 patients); Dose Level 2: 80 mg/m(2)/96-hrs (5 patients); Dose Level 3: 120 mg/m(2)/96-hours (2 patients); and Dose Level 2A: 100 mg/m(2)/96-hours (3 patients). RESULTS: The MTD of Paclitaxel was 100 mg/m(2)/96-hours. All but one patient (who experienced progressive disease after receiving 61 Gy and both cycles of paclitaxel) completed therapy as planned. Dose-limiting toxicity occurred in both patients enrolled at Dose Level 3, with one patient experiencing Grade 4 diffuse moist desquamation and the other patient experiencing Grade 4 mucositis and febrile neutropenia. Thus, Dose Level 2A was opened and no dose limiting toxicity was noted. Grade 3 non-dose limiting mucositis and dermatitis occurred at all paclitaxel dose levels. There were no treatment-related deaths. All Grade 3 and 4 toxicities were reversible. Complete responses were seen in 8 of 13 patients, 4 patients achieved partial responses, and 1 patient had no response/progressive disease. CONCLUSIONS: Infusional paclitaxel over 96 hours during Weeks 1 and 5 of this accelerated radiotherapy schedule is feasible. The MTD of paclitaxel in this protocol was 100 mg/m(2)/96-hours. Dose-limiting toxicities were primarily enhanced epithelial reactions, but febrile neutropenia also occurred. All patients develop non-dose limiting Grade 3 skin and mucosal reactions, reflecting the high treatment intensity. This regimen merits further investigation.

Aged↗
PubMed1996

Diagnostic imaging aids to head and neck radiation oncology.

Tumors of the head and neck are primary sites for radiation treatment. In combination with surgery, the role of radiation is further expanded; however, localization of the primary tumor and its metastases, actual or potential, and the relationship to critical structures are quintessential to the application of radiation. In this process, the information made available by appropriate imaging studies as interpreted by the diagnostic radiologist is a requirement for cancer management.

Head and Neck Neoplasms↗
PubMed1995

Decreased acute toxicity by using midline mucosa-sparing blocks during radiation therapy for carcinoma of the oral cavity, oropharynx, and nasopharynx.

PURPOSE: To determine whether midline mucosa-sparing blocks (MSBs) protecting the aerodigestive tract can statistically significantly reduce acute toxicity during radiation therapy for carcinoma of the head and neck, without compromising tumor control. MATERIALS AND METHODS: Radiation records and simulation films were reviewed in 125 patients with carcinoma of the oral cavity, oropharynx, or nasopharynx. Patients with and without MSBs were compared. Measures of acute toxicity during radiation therapy were weight loss (> or = 5%), hospitalization for nutritional support, and unplanned treatment interruptions (> or = 5 days). Actuarial local-regional tumor control was compared. RESULTS: Patients with MSBs had significantly less weight loss (26 of 50 vs 37 of 47 patients, P = .006), fewer hospitalizations for nutritional support (one of 61 vs seven of 64 patients, P = .04), and a trend toward fewer treatment interruptions (10 of 61 vs 19 of 64 patients, P = .07) than patients without MSBs. The 3-year actuarial tumor control rates in the neck were similar. CONCLUSION: Midline MSBs decrease acute toxicity during radiation therapy for carcinoma of the oral cavity, oropharynx, and nasopharynx without compromising tumor control.

Actuarial Analysis↗
PubMed1993

Initiation of multi-leaf collimator conformal radiation therapy.

Clinical studies have been initiated in conformal radiotherapy using a computer controlled multi-leaf collimator. Quantitative dosimetry and treatment planning studies comparing field shaping by lead alloy blocks and the multi-leaf collimator demonstrate the clinical acceptability of the multi-leaf collimator. Sixteen patients with tumors in multiple sites have received some part of their treatments with both blocking systems. Studies of dosimetry and field shaping show that the multi-leaf collimator produces clinically acceptable blocking for most field shapes and disease sites. The 80-20% penumbra was characterized for a wide range of shaped beams. For straight edges perpendicular to the leaf travel, the penumbra of measured dose distributions from the multi-leaf collimator is equal to conventional divergent blocking. When the multi-leaf collimator leaves approach a contour at an angle, the penumbra increases. At forty-five degrees, the maximum angle of approach, the penumbra is approximately 4 mm wider than that for divergent blocks. Three-dimensional treatment planning demonstrates that equivalent dose distributions can be obtained from the two field shaping systems. The multi-leaf collimator can be used effectively and efficiently to treat a variety of disease sites. Its optimal utility may be in treating complex fields--five or more shaped coplanar or non-coplanar beams. It is well suited for conformal therapy applications.

Humans↗
PubMed1992

Use of radiation with or without WR-2721 in advanced rectal cancer.

One hundred patients with inoperable, unresectable, or recurrent adenocarcinoma of the rectum were stratified and randomized to WR-2721 plus radiation therapy (WR + RT) or radiation therapy (RT) only treatment arms. The protector, WR-2721, was administered at a dose of 340 mg/m2 15 minutes before RT, 4 days a week for 5 weeks. The entire pelvis received 225 cGy per fraction for a total of 4500 cGy. The RT only group received the same treatment schedule. After this, both groups received a conedown of 720 cGy in 4 fractions. Inoperable and unresectable cases received a second conedown of 720 cGy. No moderate or severe pelvic normal tissue late effects were seen in the 34 evaluable patients in the combination group. However, in the RT only group, 5 of 37 evaluable patients exhibited late effects of moderate or severe degree. This difference was statistically significant (P = 0.03). There was no evidence of tumor protection by WR-2721. Sixteen percent of patients randomized to the WR + RT group had a complete response compared with 10% in the RT only group. The conditions of 12 patients of 100 became operable and 8 were resected. Seven of these patients remain free of recurrence.

Adult↗
PubMed1992

Interim analysis of a randomized trial of radiation therapy of rectal cancer with/without WR-2721.

The objectives of this randomized trial are to define the maximum tolerated dose of radiation therapy, at curative dose levels, that can be delivered following WR-2721, and to observe the anti-tumor effects and normal tissue responses. One hundred patients with inoperable, unresectable, or recurrent rectal cancer were stratified and randomized to radiation only, or WR-2721 and radiation. The entire pelvis is treated with 4 portals 4 times a week to a total of 4500 cGy (first level dose) in 5 weeks. WR-2721, 340 mg/m2 was given 15 minutes before radiation to the combination group. Subsequently, both groups received a conedown of 720 cGy in 4 days to 144(2) cm portals APPA, and if originally inoperable or unresectable 720 cGy in four days to second conedown of 64(2) cm. Patients were observed from 3 to 18 months (median = 12 months). No significant hypotension or hematologic toxicity occurred in the WR-2721 treated group. Mild to moderate emesis occurred in 80% of the courses. (No antiemetics were used.) Moderate or severe acute toxicities to normal tissues were observed less frequently in the WR-2721 arm. No moderate or severe late toxicities to the skin, mucous membrane, urinary bladder or intestine was observed in the WR-2721 group, however, 5 patients treated with radiation alone experienced moderate or severe late toxicity to these organs. No evidence of tumor protection was observed.

Adenocarcinoma↗
PubMed1988

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↗
PubMed1988

Factors influencing the oxidation of the radioprotector WR-1065.

N-(2-Mercaptoethyl)-1,3-diaminopropane (WR-1065) is the free thiol form of the radio- and chemoprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). Interest currently exists in the clinical use of WR-2721 and WR-1065 as radio- and chemoprotectors of normal tissues. However, measurement of plasma levels of WR-1065 has proven difficult, due to rapid drug oxidation. Therefore, we studied factors influencing the oxidation of WR-1065, in Hepes-buffered saline as well as in tissue culture media containing 10% fetal bovine serum. The rate of oxygen consumption by WR-1065, as determined using the Clark oxygen electrode system, was faster in medium plus serum than in Hepes-buffered saline. That this effect is largely due to the presence of trace metal ions in tissue culture media and serum was indicated by the observation that addition of Cu2+ or Fe3+ to buffer stimulated oxygen consumption. Addition of KCN inhibited the reaction of WR-1065 with oxygen, and this effect was dependent on KCN concentration. That KCN blocked WR-1065 oxidation to the disulfide was verified using Ellman's reagent to quantitate the free thiol form. The rate of oxygen consumption was shown to be affected by temperature as well as concentration of WR-1065. Catalase reduced the rate of oxygen consumption of WR-1065, indicating that peroxide is formed in this system. Superoxide dismutase had a stimulatory effect. WR-1065 was found to stimulate the hexose monophosphate shunt in A549 cells. Since this stimulation was prevented by the presence of catalase, it appeared to be due to the response of the cells to peroxide, formed as a result of WR-1065 autooxidation.

Mercaptoethylamines↗
PubMed1987

Radiation therapy of esophageal carcinoma: correlation of clinical and radiographic findings.

Seventeen patients with esophageal carcinoma treated by radiation therapy (RT) at our hospital between 1981 and 1984 had initial diagnostic esophagrams and 1 or more repeat esophagrams after completing RT. Total regression of the tumor was observed radiographically in 10 patients (59%) with a normal esophagus (24%) or benign-appearing residual stricture (35%) at the site of the previous lesion. Partial regression was observed in 4 patients, and progression of the tumor in 3. No correlation was found between the size, stage, or morphology of the lesion and its response to therapy. Although local recurrences were relatively uncommon, patient survival was often limited by the development of distant metastases. Fourteen of 15 patients with clinical follow-up initially had significant relief from dysphagia as the tumor regressed. However, 9 of those patients had recurrent or increased dysphagia over a subsequent 3-9-month period. Exacerbation of symptoms did not necessarily indicate recurrent carcinoma; it also resulted from benign radiation strictures, opportunistic esophagitis, or other complications of RT detected on esophagography.

Aged↗
PubMed1987

Long-term results of pion therapy at Los Alamos.

Two hundred twenty-eight patients were treated at the Los Alamos Meson Physics Facility (LAMPF) with negative pi-mesons (pions) between 1974 and 1981. Of these, 19 patients with metastatic disease were treated in pilot studies. Following the clinical determination of relative biological effectiveness (RBE) of pions, 209 patients were treated in site and dose searching studies beginning in 1977. Advanced but regionally localized cancers that were considered poorly responsive to conventional therapy were selected for treatment. A wide range of treatment fractions (22 to 45) and of total dose (1800 to 4200 cGy at the 80% isodose level) to the prescribed target volumes was explored. A follow-up observation period of between 4.5 and 9 years has been completed. The analysis focuses on 129 patients receiving pion therapy alone. Thirty-six (28%) had persisting local tumor control of which 12 (9%) suffered complications of treatment. The results varied among treatment sites, for example: prostate cancer, 18/21 (86%) locally controlled, 6/21 (29%) complications; head and neck, 8/31 (26%) locally controlled, 1/31 (3%) complications; and pancreas, none controlled and no complications. Analysis of dose-fraction response suggests a steep rising curve of complications beyond the dose level of 3750 cGy minimum, 4700 cGy maximum, in 38 fractions. The tumor control response has a broader and ill-defined curve possibly due to the heterogeneity of tumor types. The RBE for late effects in normal tissues appeared to be higher than that for acute effects although the mixture of tumor types, sites, dose, and fractionation made this estimate highly uncertain. No late secondary neoplastic changes in pion irradiated tissues were seen. It is concluded that pions can locally ablate some advanced cancers, often without significant sequelae, but that the optimum therapeutic range is critical. The Los Alamos data may be of use to ongoing pion studies in Canada and Switzerland.

Elementary Particles↗
PubMed1986

Human pharmacokinetics of WR-2721.

The pharmacokinetic properties of WR-2721 were investigated in 13 cancer patients given a 150 mg/M2 intravenous bolus dose of the drug. An average plasma clearance value of 2.17 L/min was obtained. Very little of the drug or the two metabolites, WR-1065 and WR-33278, were excreted in urine obtained after the blood collection schedule. Plasma concentrations of WR-2721 decreased by 94% within 6 minutes of drug administration. The mean value of 6.44 L obtained for the steady-state volume of distribution indicates that the extravascular space occupied by the drug is small. These observations suggest that in human cancer patients, WR-2721 is rapidly taken up by tissues and converted to metabolites.

Amifostine↗
PubMed1986

Phase I/II trials of WR-2721 and cis-platinum.

Renal dysfunction is a well-known dose-limiting toxicity of cis-platinum. Previous studies demonstrated a 32% incidence of nephrotoxicity following a 100 mg/M2 single dose of cis-platinum with mannitol diuresis. WR-2721 is an aminothiol which in the animal model improves renal tolerance to cis-platinum by factors of 1.3 to 1.7. Phase I trials were initiated to establish the toxicity when WR-2721 was given prior to escalating doses of cis-platinum. Fifty-two patients received 161 courses of WR-2721 prior to cis-platinum (60-150 mg/M2) with mannitol and hydration. Nephrotoxicity, measured by twice weekly serum creatinines and monthly creatinine clearances, occurred in only 10/97 (10%) courses with 120 mg/M2 of cis-platinum. No patient experienced a creatinine elevation after 135 mg/M2 of cis-platinum. With 150 mg/M2 of cis-platinum, 6/17 (35%) courses were associated with transient nephrotoxicity. Five patients who developed transient creatinine elevations following 150 gm/M2 of cis-platinum were subsequently retreated with WR-2721 and cis-platinum (100 mg/M2) without nephrotoxicity. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies were noted in seven patients following cumulative cis-platinum doses ranging from 460-1160 mg/M2. Objective partial responses were observed in 26/45 (58%) patients with measurable or evaluable disease. Thus, there is no evidence that WR-2721 protects against the antitumor efficacy of cis-platinum in man. Compared to retrospective series, our data suggest that WR-2721 may provide some protection against platinum-induced nephrotoxicity and neurotoxicity. Controlled trials will be required to define the potential clinical benefit of WR-2721 and cis-platinum.

Amifostine↗
PubMed1986

A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation.

The volume, distribution, and mobility of opacified pelvic small bowel (PSB) were determined by fluoroscopy and orthogonal radiographs in 150 consecutive patients undergoing pelvic irradiation. Various techniques including uteropexy, omental transposition, bladder distention, inclining the patient, and anterior abdominal wall compression in the supine and prone treatment position were studied for their effect on the volume and location of small bowel within the pelvis. Abdominal wall compression in the prone position combined with bladder distention was selected for further investigation because of its simplicity, reproducibility, patient comfort, and ability to displace the small bowel. Factors correlating with the volume of pelvic small bowel (PSB) included prior pelvic surgery, pelvic irradiation (XRT), and body mass index. After pelvic surgery, especially following abdominoperineal resection (APR), there was a greater volume of PSB which was also less mobile. The severity of acute gastrointestinal effects positively correlated with the volume of irradiated small bowel. Overall, 67% of patients experienced little or no diarrhea, 30% developed mild diarrhea, and no patient required treatment interruption. Late gastrointestinal effects correlated with the prior pelvic surgery and with the volume of small bowel receiving greater than 45 Gy. Small bowel obstruction was not observed in 75 patients who had no previous pelvic surgery. However, following pelvic surgery excluding APR, 2/50 patients and following APR, 3/25 patients developed small bowel obstruction.

Female↗