The enzymatic preparation of isolated intact parenchymal cells from rat liver.

Suspensions of isolated parenchymal cells were prepared from rat liver by incubation with collagenase and hyaluronidase followed by mechanical treatment. Utilization of 0.15% collagenase together with 0.15% hyaluronidase yielded adequate numbers of cells for experimental purposes. As shown by light and electron microscopy, approximately 75% of the isolated cells retain their structural integrity. The cell suspensions are capable of maintaining endogenous respiration in the presence of 1% albumin for periods of time up to 8 hr. These cell preparations consist almost entirely of parenchymal cells and offer a unique tissue preparation for the study of hepatic metabolism.

Regional hyperthermia: a clinical appraisal of noninvasive deep-heating methods.

The concentric single-turn self-resonant coil operated at 13.56 MHz (CC) and the annular array applicator (AA) operated at 55 to 100 MHz are the only regional heating devices the clinical use of which has been subjected to sufficient thermometric characterization to be evaluable. The clinical heating characteristics and toxicity of both devices are reviewed. When spatial temperature measurements have been made during clinical treatments with the CC, the observed temperatures have been consistent with theoretical predictions and phantom studies; temperatures fall with increasing radial depth, and potentially injurious heating in superficial normal tissues and ineffective heating in deep-seated tumor loci have been commonly observed. The CC is ineffective in heating central pelvic tumors due to inadequate penetration and power-limiting sacrococcygeal pain. The AA has been demonstrated to heat many deep pelvic tumors to maximum temperatures greater than 42-43 degrees without significant side effects, but further study is needed to determine the feasibility of achieving higher minimum tumor temperatures and longer treatment durations. In the upper abdomen, the AA appears to have a slight superiority in rapid tumor heating at depth, but both devices have major limitations with insufficient penetration (CC) or treatment limiting systemic heating (AA). There has been no adequately thermometrically documented experience with heating in the deep thorax with either device.

Abdominal regional hyperthermia with an annular phased array.

Twenty-eight patients with advanced upper-abdominal malignancy were treated at the University of Utah on a pilot protocol involving regional hyperthermia (HT) produced by the BSD-1000 HT system and the annular phased array applicator (AA), usually driven at 60 MHz. Eighty-two percent of the patients had widespread metastatic disease, and the mean tumor burden was 2,900 cc. Seventy-nine percent of the patients received concurrent radiotherapy. Acute toxicity consisted primarily of pain within the AA aperture (43%), systemic stress (43%), and nausea or vomiting (29%). Systemic stress was the most frequent power-limiting factor (46%). There were two treatment-related complications: sciatic neuritis from intramuscular injection (one) and pleural effusion from thermometry probe placement (one). Detailed thermal mapping and thermal dosimetry were performed on 26 patients. The mean thermal dosimetry parameters were quite low. Concurrent radiation doses were also quite low (mean, 1,500 rad) to avoid toxicity of sensitive organ systems within the abdomen. The objective response rate was only 18%, all partial, but 43% of the patients achieved effective symptomatic palliation. The five objective responders did survive significantly (P = .02) longer than the 23 nonresponders.

"Thermal mapping" in experimental cancer treatment with hyperthermia: description and use of a semi-automatic system.

The regions of tumor which are least adequately heated during experimental hyperthermia treatments will most likely determine the ultimate probability of tumor control. Temperature inhomogeneity during local or regional hyperthermia is often marked, and stationary temperature probes yield very little information about the adequacy or inadequacy of tumor heating. Fine catheters can be placed through the tumor bearing region and temperatures recorded at various points within these catheters, thus yielding valuable data about temperature variations within the volume of interest. The "thermal mapping system" (TMS) described herein provides a method for remotely sampling these temperature variations in a semi-automatic manner in several catheters simultaneously. Its application in conjunction with a commercial hyperthermia system is described and clinical examples of its use and importance are provided.

Measurement of mechanical accuracy of isocenter in conventional linear-accelerator-based radiosurgery.

PURPOSE: Five Varian linear accelerators were studied to determine whether their mechanical isocentric accuracies were sufficient for radiosurgery and, if not, if the observed errors were sufficiently consistent and predictable to be correctable by some form of secondary collimator steering device to maintain isocentric alignment. METHODS AND MATERIALS: A 0.3 mW 670 nm diode laser was mounted in the secondary collimator insert of a radiosurgery extended collimator assembly. A cylindrical lens was used to create a laser fan beam that passed through isocenter and could be oriented parallel or perpendicular to the plane of rotation. A position sensitive photo-diode having an electrical output that varied with the portion of its surface illuminated was mounted at isocenter in a rotational mount. This mount tracked the accelerator gantry such that the surface of the photo-diode remained perpendicular to the laser beam during gantry rotation. An X/Y recorder was connected to the gantry-angle potentiometer of the accelerator and to the photo-diode and plotted the positional variation from isocenter with gantry rotation. RESULTS: The root-mean-square error for the five machines was +/- 0.06 to +/- 0.08 mm in the plane of rotation and +/- 0.17 to +/- 0.35 mm out of (perpendicular to) the plane of rotation. The in-plane-of-rotation errors tended to be maximal near the diagonal gantry angles and the out-of-plane-of-rotation errors were maximal in the over and under vertical positions. CONCLUSIONS: Both types of errors were predictable but only the out-of-plane-of-rotation errors were considered large enough to warrant consideration of correction (although the need is debatable). On all the tested machines, the out-of-plane-of-rotation error curve was a relatively smooth bell-shaped function that would be readily amenable to correction. The diode laser/photo-detector system used should prove useful in accurately defining isocenter and facilitating the precise adjustment of the laser isocenter lights.

Practical thermal dosimetry.

A relatively simple means of thermal dose documentation is presented. It has the advantage of greatly condensing the vast amount of data collected during a course of hyperthermia treatments. The formulation incorporates both temporal and spatial temperature transients and is applicable when comparing hyperthermia devices and in quality control for prospective hyperthermia treatment protocols.

Heating patterns induced by a 13.56 MHz radiofrequency generator in large phantoms and pig abdomen and thorax.

Heating patterns generated by a commercially available 13.5 MHz radiofrequency generator and induction coil hyperthermia system in human size phantoms and a 230 pound pig were studied using a multichannel computer-monitored thermometry system that is noninteractive in electromagnetic fields. The phantom studies were composed of synthetic muscle equivalent material and fresh tissue. The pig was heated in the regions of the upper abdomen and the midthorax, both under anesthesia and dead. The temperature was measured along fine penetrating catheters at 1 cm intervals in all experiments. In a homogeneous cylindrical phantom, under our measurement conditions, the temperature profile across the diameter is parabolic with marked superficial heating and essentially no central heating. In nonhomogeneous phantoms and in the pig, the symmetry of this profile was distorted but the basic pattern of marked superficial heating and nearly absent deep central heating remained. Blood flow in the living animal produced some thermal smoothing. It is considered probable that substantial radial temperature gradients will exist within eccentrically located human tumors heated with this device and that certain deep central tumors will be difficult or impossible to heat. Determination of its ultimate value for investigational; clinical hyperthermia studies will require accurate temperature mapping of tumors and normal tissues in various anatomic sites in comparison with other approaches to deep heating.

Dynamic field shaping to optimize stereotactic radiosurgery.

A dynamic field shaping collimation system is evaluated for use in stereotactic radiosurgery of non-spherical lesions. The concept is as follows: (a) use the existing circular collimators to define a cone which encompasses the maximum dimensions of the target volume; (b) position two sets of independent rectangular photon collimators immediately upstream from the circular aperture and allow each collimator to have independent translational and rotational motion in order to define, for each increment of arc, a polygonal field shape having up to four straight and four curved edges which enscribe the beam's eye projection of the target; (c) modify the translational and rotational position of each independent collimator with each change in arc angle to continuously shape the instantaneous field to the target shape. A prototype device has been constructed and uses vane control technology developed in a related research project in electron arc therapy. The efficacy of this device is illustrated by dose calculations and measurement based on actual clinical data. Dose volume histograms are used to compare the dose received by three techniques: single isocenter treatment using a single circular aperture, dual isocenter treatment, and single isocenter treatment using dynamically shaped fields. Doses were calculated throughout the brain using a volume grid of 3 mm spacing. Dose volume histograms comparing dose within the target volume and brain volume excluding target volume, as well as computed isodose distributions, demonstrate the possible reduction in normal tissue dose burden while simultaneously preserving dose uniformity throughout the prescribed target volume. This simple four-vane collimation system may provide a viable alternate treatment technique for non-spherical lesions.

Electron arc therapy: physical measurement and treatment planning techniques.

An electron beam arc therapy technique has been developed for the treatment of the post-mastectomy chest wall using a clinical linear accelerator modified for arc therapy. The effects on the dose distribution of primary X ray collimators, secondary cerrobend blocks attached to the accelerator accessory tray, and tertiary cerrobend casting of the treatment area on the patient's thorax have been investigated. Multiple electron energies within the same arc, variable rad per degree, and variable shaped secondary and tertiary applicators have been employed to optimize dose uniformity across the treated surface. A computerized treatment planning program has been developed to aid in visualization and optimization of dose distributions. A simple technique to estimate the width variation in the secondary collimator necessary to compensate for radial patient thickness changes in the cephalocaudad direction is described. Electron beam energies of 6 MeV, 9 MeV, 12 MeV, 15 MeV, and 18 MeV have been studied. The physical measurements needed to implement this technique are described, and a comparison of electron arc therapy dose distributions with other standard treatment techniques is presented.

A comparison of deep regional hyperthermia from an annular array and a concentric coil in the same patients.

Twenty-two patients with advanced pelvic or abdominal malignancy (or both) were treated on successive occasions with hyperthermia produced by an annular array (AA) (60-80 MHz, 500-1800 W forward power) and a concentric coil (CC) (13.56 MHz, 350-1000 W forward power). Both devices were compared with respect to acute toxicity and power limitations. There was no power limiting factor in pelvic heating in 7/14 patients treated with the AA, however 13/14 experienced power limiting sacrococcygeal pain with the CC. The 9 patients who underwent abdominal heating had a variety of power limitations with both devices. Thermal mapping was performed in 23 treatments with the AA and in 19 with the CC. Composite thermal maps of patients with similar thermometry sites show that heating patterns produced by the CC were predictable from theory and static phantom measurements. The AA achieved broader regional heating, particularly at depth, but heating patterns were less predictable. Spatial thermal dose (TD) analysis revealed higher minimum tumor TDs and more favorable mean tumor/normal tissue TD ratios with the AA than with the CC. We conclude that the AA is superior to the CC for pelvic treatment and that both devices have limitations in abdominal treatment.

Regional hyperthermia in the treatment of clinically advanced, deep seated malignancy: results of a pilot study employing an annular array applicator.

From October 1980 through December 1982, 46 patients were entered into a pilot study at the University of Utah Medical Center to assess the feasibility and safety of heating deep-seated, advanced, pelvic and abdominal malignancies with an annular array of electromagnetic wave (EMW) applicators. The patients, most of whom were heavily pretreated, were treated on a protocol in which most of the patients received combined hyperthermia and low dose X ray therapy. Discomforting local symptoms were the predominant treatment related acute side effects in 28 patients with pelvic disease, while systemic hyperthermia and associated symptoms were the predominant side effects in 18 patients with abdominal disease. Minor subacute toxicity was minimal and no serious treatment related, chronic toxicity was observed. The treatments of 22 patients with sufficiently detailed thermometry were analyzed at arbitrary index temperatures of 41 degrees C and 43 degrees C. Objective response rates in 22 evaluable patients were 67% and 9% for pelvic and abdominal sites respectively.

Electron arc therapy: clinical experience with chest wall irradiation.

In order to overcome the technical problems commonly encountered in fixed field photon and electron beam chest wall irradiation, we have treated the chest wall in 22 breast cancer patients with a moving electron beam that rotates about the patient's thorax. This paper discusses the clinical results of chest wall treatment by electron arc therapy. Twenty-one patients were treated following mastectomy, 16 electively because of high risk for local failure, and 5 because of local recurrence. One patient with advanced local-regional disease was treated primarily. During a median follow-up period of 24 months there has been one chest failure in one of the patients treated for local recurrence. No major complications were observed in skin, lung, soft tissue or esophagus, even in the 7 patients recently or concomitantly treated with multiagent cytotoxic chemotherapy. In 3 patients, small areas of telangiectasia developed in the region of abutment of the electron arc field to a photon field used to irradiate the supraclavicular nodal area. We conclude that the technique as applied to these patients is safe and efficacious. In certain clinical settings it has advantage over standard, fixed field approaches to treat the chest wall.

Change in the in vivo hyperthermic response resulting from the metabolic effects of temporary vascular occlusion.

Previous workers have reported that clamping of animal tumors in vivo enhanced the effect of hyperthermia; the enhancement has been attributed to pH and nutritional effects of vascular occlusion. It has not been clear, however, the degree to which improved heating patterns or effects on the tumor cells and vasculature from the clamping procedure itself might have contributed to the observed effect. In the experiments herein reported, care was taken to insure comparable heating of C3H mouse mammary tumors transplanted on the flank whether clamped or unclamped. Clamping for one hour with hyperthermia during the final 30 minutes caused a marked thermosensitization as measured by tumor control. The temperature at 30 minutes heating to control 50% of the tumors for 120 days (TCT 50-120) was reduced from 46.8 degrees C in controls to 43.5 degrees C in clamped tumors, a difference of 3.3 +/- 0.09 degrees C. No cytotoxicity from the clamping alone was evident by assessment of subsequent tumor growth and no lasting vascular effects could be detected by 133Xe washout and tumor growth. Since the techniques used produced essentially identical heating patterns, we conclude that the striking enhancement in hyperthermic response in clamped tumors can be attributed to the metabolic consequences of temporary vascular occlusion.

Electron arc irradiation of the postmastectomy chest wall with CT treatment planning: 20-year experience.

PURPOSE: Since 1980, electron arc irradiation of the postmastectomy chest wall has been the preferred radiotherapy technique at the University of Utah for patients with advanced breast cancer. We report the results of this technique in 156 consecutive Stage IIA-IIIB patients treated from 1980 to 1998. METHODS: CT treatment planning was used in all patients to identify chest wall thickness and internal mammary lymph node depth. Computerized dosimetry was used to deliver total doses of 50 Gy in 5-1/2 weeks to the chest wall and the internal mammary lymph nodes with electron arc therapy. Patients were assessed for local, regional, and distant control of disease and for survival. Univariate and multivariate proportional hazards were modeled using a hierarchical nonproportional semiparametric model testing the following prognostic factors: age, stage, tumor size, number of positive lymph nodes, estrogen receptor status, and dose. End points evaluated included disease-free survival, cause-specific survival, and overall survival. RESULTS: Eighty-one percent of patients were at high risk for local-regional failure because of > T2 primary tumor or > 3 positive axillary lymph nodes. The median number of positive lymph nodes was 5, and the median tumor size was 3.5 cm. Actuarial 10-year local-regional control and overall survival were 95% and 52%, respectively. In multivariate analysis, the only factor prognostic for disease-free survival, cause-specific survival, and overall survival was the number of positive lymph nodes (p < 0.001). The 10-year rates of local-regional control for patients with 0, 1-3, 4-9, and > or = 10 involved lymph nodes were 100%, 98%, 93%, and 89%, respectively. The only rates of acute and chronic radiotherapy toxicity > or = 2 by RTOG/EORTC criteria were skin related and observed in 44% and 10% for acute and late reactions, respectively. CONCLUSION: These data demonstrate excellent local-regional control rates with electron arc therapy of the postmastectomy chest wall in patients with advanced breast cancer. Our 20-year experience with electron arc radiotherapy has demonstrated the safety and efficacy of this technique. The advantage of this technique is that the internal mammary lymph node chain can be easily encompassed while the dose to heart and lung is minimized; it also obviates match lines in areas of high risk.

Regional hyperthermia for advanced tumors: a clinical study of 353 patients.

A Phase I study using deep regional hyperthermia (HT) with an annular phased array was conducted in 14 U.S. medical centers from 1980 through 1986. There were 353 patients whose average age was 57 years. All patients had advanced recurrent or persistent tumors. Prior frequently complex, multimodality anti-cancer therapy was received by 71% of the patients. Gastrointestinal adenocarcinoma was present in 146 (41%) patients, genitourinary tumors in 86 (24%), soft tissue sarcomas in 46 (13%), malignant melanoma in 21 (6%) and 15% had other tumors. The sites treated included: pelvis 55%, abdomen 21%, liver 14%, thorax 6%, and other sites 3%. All patients received deep regional HT with an average frequency of 55 MHz. A total of 1412 HT treatments was administered to these 353 patients with an aim to increase the temperature in the volume of interest to greater than 42 degrees C for greater than or equal to 30 minutes. Thermal dose (TD in equivalent minutes at 42.5 degrees C) was less than 50 in 104 (29%), greater than or equal to 50 less than 100 in 30 (11%), greater than or equal to 100 in 26 (7%), and greater than 200 in 34 (10%). The remaining 150 (42%) patients had TD = 0. In addition to HT, 260 (74%) received radiotherapy (RT). RT was given at 180 or 200 cGy daily with an average total dose of 33.4 Gy. A total of 42 (12%) patients were given chemotherapy (CT) with HT, and 15 (4%) CT + HT + RT/HT alone was given to 47 (13%) patients. Complete response (CR) was obtained in 35 (10%) and partial response (PR) in 59 (17%) patients. CR was 12% in patients who received RT, vs 2% in those who did not receive it, p = 0.003. Radiation dose was an important factor influencing response, p less than 0.001. Thermal dose was not an important parameter influencing tumor response. A duration of CR ranged from 4 to 73 weeks with an average duration of 31 weeks and the median duration of 28 weeks. The overall 2-year survival was 13% with the median survival of 42 weeks. Patients with CR and PR had a 2 year survival of 41%, and a median survival of 71 weeks. This compared with 8% 2-year survival and 24 weeks median survival in patients who did not have CR or PR, p less than 0.001. Of the patients presenting with significant pain, 62% had complete or partial pain relief.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanical assay of consequential and primary late radiation effects in murine small intestine: alpha/beta analysis.

A portion of jejunum in C3H/HeJ mice was irradiated in situ with 250 kV X rays, and the resulting elastic stiffness increase was used as an assay of chronic fibrotic injury. With data from this assay dose-response curves were evaluated with early- and late-appearing chronic intestinal injuries in two experiments. (1) After split-dose treatment with an interfraction interval of 0.0, 0.25, 0.5, 1.0, 2, 4 or 24 h, the asymptotic dose-recovery ratios in assays at 2-3 weeks and at 4 months were statistically similar, R = 1.34 (95% confidence limits: 1.29-1.39) with t1/2 = 0.75 h (0.48-1.17), and R = 1.36 (1.31-1.42) with t1/2 = 0.49 h (0.21-0.86), respectively, although the slopes of the dose-response curves for the early and late assays differed significantly. (2) Mice received 2, 3, 4, 5, 10 or 15 equal X-ray fractions in 5 days with interfraction intervals of at least 5.5-6 h. The data from the dose responses were used in either of two analyses of variance for calculating alpha/beta values. Using slopes in transformed Fe plots, alpha/beta was 8.5 Gy (6.1-12.5) for the assay at 2-3 weeks and 3.6 Gy (2.4-5.4) at 4 months. Using these and other data we argue that assay at the two times measured separate fibrotic responses to injuries to the small intestine, namely, a rapidly appearing consequential late effect that had the same alpha/beta value as for crypt microcolony assays because it was a sequela of acute inflammation after transient loss of mucosal epithelial integrity after crypt sterilization, and a lower-threshold primary or true late effect with a lower alpha/beta value, which progressively masked the consequential injury.

Capillary blood flow in murine tumors, feet, and intestines during localized hyperthermia.

Changes in capillary blood flow were determined by serial measurements of xenon-133 (133Xe) washout rates from "Slow-line" C3H-mouse mammary carcinomas transplanted onto the flank or hindfoot, from non-tumor-bearing hindfeet, and from the lumen of a short portion of the proximal jejunum. The core temperature of the pentobarbital-anesthetized mice was externally controlled. Special techniques allowed selective rapid and uniform heating by water bath immersion of even the flank tumors and nonexteriorized jejunum. Immersion in a 44 degrees C bath immediately doubled washout rates not only from the immersed tumor, but also from a contralateral tumor that was not heated. This result and behavioral observations were consistent with an arousal-induced increase in cardiac output to the tumors that increased the capillary blood flow in them. In contrast, washout rates from the hindfeet or intestinal lumen did not increase unless the foot or intestine in question was itself heated, which is consistent with normal tissues having intrinsic mechanisms for regulating their own capillary blood flow that the Slow-line tumor lacks. This lack could complicate the design and interpretation of hyperthermia experiments in vivo. Immersion of Slow-line tumors in a 44 degrees C bath for 20 min did no microvascular damage detectable from 133Xe washout rates during the heating or for 1 hr subsequently. Washout rates from both foot and flank tumors had dropped by one-half after 41-43 min in the 44 degrees C bath. Equivalent declines had occurred after 60 min for the intestine and 100 min for the hindfeet.

Assay of premorbid murine jejunal fibrosis based on mechanical changes after X irradiation and hyperthermia.

Preparative surgery immobilized 15 mm of functional jejunum against the peritoneal surface of the ventral abdominal wall in C3H/HeJ mice. The surgery allowed subsequent treatments with single fractions of 44 degrees C hyperthermia and X irradiation to be selective to this portion of small intestine. With each doubling of time since treatment, 1 through 70 weeks, a sample of mice was killed and specimens of their intestines were excised and radially stretched in a tensile-testing apparatus that measured tension as a continuous function of circumference. Preconditioning with repeated cycles of stretch and relaxation before specimens were irreversibly stretched enabled measurement of the limit collagen placed on the extensibility of the intestinal wall by physiologic forces and the stiffness of the intestinal collagen once that limit was exceeded. Both kinds of measurements made possible dose-response characterization of radiation fibrosis for treatments that killed no mice. Response increased linearly with X-ray dose above a threshold. After X rays alone the threshold remained constant at 9.7 +/- 0.6 Gy for the assays at 1 through 8 weeks and subsequently decreased to about 6 Gy by 35 weeks. With adjuvant hyperthermia of 15 min at 44 degrees C beginning 10 min after X irradiation, the threshold of approximately 5 Gy at 2-4 weeks decreased to about 2 Gy by 17 weeks; the thermal enhancement ratio as calculated from slope-ratio analysis of the dose-response curves was 1.50 +/- 0.08 at 2-4 weeks post-treatment and 1.96 +/- 0.05 at 17-70 weeks post-treatment. Up to 20 min at 44 degrees C by itself was without effect. From comparisons of these data with results of crypt microcolony assays, it was concluded that intestinal fibrosis was both a chronic sequela of acute mucosal injury and a late effect of X irradiation. Adjuvant hyperthermia both hastened the expression of the late effect and increased its severity beyond that predicted from the acute injury.

RIF-1 tumor treatment in anesthetized mice with minimal effects on blood flow and hypoxia.

The injectable anesthetic etomidate and a clip that facilitates hyperthermia by water bath immersion (the "Gibbs clip") were evaluated for their suitability with subcutaneous flank RIF-1 tumors in C3H/HeJ mice. For tumors between 100 and 250 mg (mean, 160 mg), etomidate at 40 mg kg-1 ip did not significantly increase the radiobiologic hypoxic fraction (RHF); as calculated from an in vitro assay after treatment in vivo the RHF increased from 0.06 (95% C.I.:0.03-0.13) to 0.08 (0.04-0.16). In contrast, for larger tumors (270-650 mg; mean, 400 mg) etomidate increased the RHF from 0.08 (0.04-0.17) to 0.28 (0.14-0.60). Holding 250-mg-or-less tumors 3-mm laterally away from the flank in an X-ray jig did not significantly reduce tumor blood flow as inferred from the clearance rates of Xe, but the RHF of 0.15 (0.08-0.26) was significantly (P less than 0.05) greater than the RHF in unanesthetized mice, although not the RHF in anesthetized mice. The Gibbs clip, which folded skin around a tumor to enhance thermal conduction from a water bath, did not impair the increase in tumor blood flow in response to the cardiovascular arousal associated with exposure to a hyperthermic stimulus. Intratumor temperature was within 0.25 degrees C of bath temperature 3 min after the tumor and clip were immersed, but only when rectal temperatures were at 37 degrees C or above; tumor blood flow increased intratumor temperature gradients by 0.10 degrees C for each 1.5 degrees C that the body temperature was below 37 degrees C.

Prognostic indicators in head and neck cancer patients receiving combined therapy.

In 1983 we initiated a prospective nonrandomized study of the value of preoperative chemotherapy in previously untreated patients with stages III and IV squamous cell carcinoma of the head and neck. In 1983 and 1984, 50 patients were entered in the study. Prior to therapy all patients were evaluated by a representative from the Medical Oncology, Radiation Therapy, and Head and Neck Surgery Divisions, University of Utah School of Medicine, Salt Lake City. In addition to the standard preoperative evaluation, pretreatment computed tomographic scans were performed on all patients. Follow-up computed tomographic scans were performed after the second cycle of chemotherapy and at the completion of treatment. Initial therapy in all patients consisted of induction chemotherapy with cisplatin (day 1, 100 mg/m2) and fluorouracil (days 1 through 5, 1000 mg/m2). Several factors were examined for their utility in predicting response to therapy and survival. Factors evaluated included: (1) extent and timing of chemotherapeutic response; (2) computed tomographic quantitated primary tumor size; (3) size of computed tomographic quantitated regional (neck) metastases; (4) performance status; (5) cancer stage; (6) total lymphocyte count; and (7) serum liver function tests. The factor found to be most useful in predicting improved survival was the extent of response to chemotherapy. The remaining factors, performance status, regional lymph node status, serum gamma-glutamyltransferase levels, and cancer stage, were also found to correlate with length of survival but were much less important than the response to chemotherapy.