Sucralfate for radiation mucositis: results of a double-blind randomized trial.

PURPOSE: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. METHODS AND MATERIALS: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The patients subjective evaluation of throat soreness and relief with medication was elicited as well as physician observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. RESULTS: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable for indicators including degree of soreness, dietary changes, and objective measures or mucosal irritation or infection. For the head and neck patients there was a significant worsening in soreness and in the ability to eat in both treatment groups, whereas patients treated to the chest had less nutritional change. Multivariate analysis including control for confounding factors did not detect treatment effects for any of the response measures. No patient had occult fungal infection detected by oral pathology evaluation of routine mucosal scrapings. CONCLUSIONS: A trend (that was not statistically significant) of less severe radiation mucositis was noted for patients receiving sucralfate in addition to the combination of viscous lidocaine, diphenhydramine, and antacid for nonulcerative radiation mucositis.

A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck.

Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high-dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day x 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies.

Treatment of recurrent head and neck cancer with 5-fluorouracil, hydroxyurea, and reirradiation.

Head and neck cancer locally recurrent after previous irradiation and surgery presents a difficult management problem. Conventional treatment alternatives include chemotherapy, reirradiation with interstitial implant, and hyperthermia. Reirradiation with external beam is generally not considered because of previous high radiation dose and limited tissue tolerance. In this study, 21 patients with recurrent and previously irradiated head and neck cancer were treated in a Phase I-II fashion. Patients received 5 days of 5-fluorouracil, 300 mg/m2/day IV bolus, Hydroxyurea 1.5 or 2 g/day by mouth and external beam radiation therapy every 2 weeks for up to four courses. Of 20 evaluable patients, 9 have attained a complete response (CR) and 6 a partial response (PR). Fifteen patients completed all planned therapy, eight on time, seven patients with delays. With a median follow-up of 7 months, 13 patients are alive, 7 disease-free (3 after salvage surgery) and 6 with recurrence. Eight patients have died. The 1-year survival is 56%. Treatment toxicity was mainly neutropenia. No major early or late radiation related side effects have been observed at a median follow-up of 7 months. Neither previous radiation dose, time since first radiation, prior chemotherapy, or site of recurrence was predictive of response or treatment tolerance. Patients with a performance status of at least 80 had a significant higher CR rate, with 7/10 patients in this group, as compared to 2/10 patients in patients with a performance status less than 80, achieving a CR. Reirradiation with 5-fluorouracil and hydroxyurea is a well tolerated outpatient treatment program for patients with recurrent and previous irradiated head and neck cancer that produces a high response rate and can provide significant palliation of symptoms.

Expedient set-up of tangential breast fields with a simple gantry attachment.

A novel technique for setting up tangential fields is described. The technique uses a simple device (Breast Aligner) which attaches to the collimator of the treatment unit. The function of the Breast Aligner is similar to conventional front and back pointers except that the beam edge rather than central ray is defined. By delineating beam entrance and exit points at the posterior field edge, the device greatly simplifies and expedites set-up, and enhances precision of port alignment. Additional advantageous features include: (a) the ability to compensate for small inadvertent variations from the initial set-up position or for patient movement between the set-up of opposing ports, (b) the ability to visually check port alignment in the treatment position immediately before irradiation, and (c) decreased chance of human and equipment error by eliminating the need for measurements and calculations at the time of treatment. Our method can be used for SSD or SAD techniques and, with minor adjustment, is applicable for establishment of coplanar cephalad field borders as required at the junction of a supraclavicular field.

Three-port perineal sparing technique.

The records were reviewed of 103 patients with low-lying pelvic malignancies irradiated with a skin-sparing technique involving use of a pair of anteroposterior-posteroanterior opposed ports and a direct perineal port. Patients had rectal, anal, cervical, vaginal, urethral, or vulvar cancer. Use of a special lead compensator allowed the three beams to be applied perpendicularly to the surface, while delivery of a homogeneous dose to the pelvis and perineum was maintained. Skin dose with this method was greatly reduced compared with that delivered with simple opposing or four-port techniques, in which irradiation is tangential to the surface at the perineum. Acute perineal skin irritation was assigned a grade between 0 and 3, with grade 0 representing the least amount of irritation. All patients were in the grade 0 or grade 1 category. Patients treated for low-lying rectal carcinoma showed no increase in perineal recurrences when compared with historic control subjects. Use of this approach allowed delivery of adequate doses to the pelvis and perineum and a definite decrease in local toxic effects, and local control was not compromised.

A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation therapy in patients with squamous cell cancer of the head and neck.

The radiosensitization properties of 5-FU are well documented, and clinical trials have suggested improved local control and survival in head and neck cancer. Clinical trials to date have used bolus injection or short term (less than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant with conventional radiation therapy, 18 patients with advanced inoperable head and neck cancers were treated with conventional irradiation and 100, 200, 250, or 300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum tolerated dose and is recommended for Phase II studies.

Extradural spinal cord compression: analysis of factors determining functional prognosis--prospective study.

The treatment results in 59 patients with extradural spinal cord compression (ESCC) who were treated with irradiation between April 1987 and December 1988 were analyzed prospectively. Eighty percent of the patients presented with back pain, which preceded ESCC by an average of 6 weeks. The most common primary tumor was lung cancer (27% of cases), followed by prostate cancer and breast cancer. The prognostic significance of pretreatment motor function, degree of spinal cord block, radiosensitivity of tumor, and radiation dose schedule was determined with multivariate analysis. Only pretreatment motor function was found to be a significant factor in determining functional prognosis (P = .0058). Even with the increasing clinical awareness of ESCC, 78% of the patients in the current series were nonambulatory at presentation. Therefore, computed tomographic myelography or magnetic resonance imaging is recommended for patients with back pain and bone destruction at the site of the complaint if local radiation treatment is not planned.

Hyperthermia of pet animal tumours with self-regulating ferromagnetic thermoseeds.

Investigations with thermally self-regulating ferromagnetic implants (thermoseeds) were done on healthy rats and pet animals with spontaneous and transmissible venereal tumours (TVT). The thermoseeds were produced from a nickel-copper alloy and electroplated with a gold-silver layer. Manufacturing conditions were varied to produce thermoseeds with various operating temperatures, the critical temperature above which heating power production sharply declines. To test for toxicity, thermoseeds were implanted into the liver of rats and left in place for up to 14 months. While atomic absorption spectroscopy showed increased nickel and copper levels in tissues near the implants, no clinical evidence of ill-effects was noted. For hyperthermia treatment, thermoseeds were implanted into tumours of pet animals, and these were placed into an induction coil which produced an 89 kHz frequency, 4000 A/m amplitude field. The highest recorded tumour temperature correlated with the nominal operating point of the thermoseeds, demonstrating their ability to regulate the temperature. Of the 15 evaluable animals with spontaneous tumours treated, 12 received concomitant 60Co radiation (two of them only after tumour recurrence following an initial treatment course of hyperthermia alone). Five of those treated with both modalities experienced complete response, five responded partially and two had no change. The treatment course of hyperthermia alone resulted in one animal achieving a complete response, and in three partial responders. Animals bearing TVT had a complete local response with hyperthermia alone. Massive tissue necrosis and seed migration caused the major treatment-related toxicity. Our findings suggest that self-regulating thermoseeds offer the possibility of predictable heat delivery to defined tissue volumes, and may be useful in the treatment of human tumours which are amenable to implantation. Until migration can be controlled, clinical trials should be limited to removable implants.

Management of early endometrial carcinoma.

Management of early endometrial carcinoma is controversial in regard to timing and indication of adjunctive radiation therapy. Two hundred eighty patients with stage I carcinoma of the endometrium are analyzed: 135 patients were treated with surgery only and 61 patients underwent preoperative and 83 patients postoperative radiation therapy. The overall survival was 94%. Recurrence rates in all three treatment arms were equal. Tumor grade was found to change from the diagnostic D&C specimen to the definite surgical specimen in 31% of all cases and in 50% of all grade 3 lesions. As only 39% of all patients required postoperative radiation therapy with equal survival, a primary surgical approach spares the majority of patient unnecessary treatment and preserves prognostically important histology.

Ferromagnetic thermoseeds: suitable for an afterloading interstitial implant.

Previous studies have shown implantable ferromagnetic thermoseeds to be a promising hyperthermia method. However, migration from the implant site and chemical toxicity caused by corrosion of the thermoseed alloy have proven to be potential hazards. These problems could be overcome by placing the thermoseeds into removable catheters similar to those used for afterloading interstitial brachytherapy. As an additional merit, the method would allow convenient combination of heat and radiation therapy. To test the clinical performance of this method, we compared temperature distributions and biologic effects in canine muscle and transmissible venereal tumors for bare thermoseeds and thermoseeds contained within catheters. We found no significant difference in the heating patterns and similar tissue changes when all implants were removed immediately after heating. More severe tissue changes were present around bare thermoseeds that were retained. This suggests that catheters provide a safe and reliable method for thermoseed hyperthermia which would allow convenient combination with interstitial radiation.

Primary lymphoma of bone: the use of MRI in pretreatment evaluation.

Primary lymphoma of bone (PLB) is an uncommon neoplasm representing only 5% of all extranodal non-Hodgkin's lymphomas. The precise role of magnetic resonance imaging (MRI) scanning is unknown. A review of the literature and a recent case treated at the University of Alabama at Birmingham in which MRI unveiled other foci of disease undetected by routine staging studies is presented.

Analysis of treatment modalities and their failures in stage IB cancer of the cervix.

This is a retrospective analysis of 240 patients who had clinical Stage IB cancer of the cervix treated with radiation between 1969 and 1980. Of these, 186 patients were treated with a combination of external and intracavitary radiation therapy, and 54 patients received adjuvant postoperative radiation therapy. The minimum follow-up was 5 years. In the group who received only radiation therapy, the overall recurrence in 170 patients (excluding 16 patients found at laparotomy to have unresectable disease) was 17% (29 of 170); pelvic recurrence was 9% and distant metastases alone was 6%. In the group who received the adjuvant postoperative radiation therapy, 16 patients had a simple hysterectomy followed by vaginal ovoid and/or external pelvic irradiation for an unexpected Stage IB cancer of the cervix. Their overall recurrence was 37.5% (6 of 16). Pelvic recurrence was the most common treatment failure with a recurrence of 31%. Significant prognostic factors were depth of stromal invasion and status of surgical margins. Thirty-eight patients had a radical hysterectomy followed by postoperative radiation therapy because of positive pelvic lymph nodes and/or close surgical margins. In patients with positive pelvic lymph nodes, the overall recurrence was 39% (9 of 23); pelvic recurrence was 13%. Distant metastases, the most common treatment failure, was 26%. In seven patients with close surgical margins, five recurred in the pelvis. There was no distant metastases without pelvic failure. Five of eight patients with close paracervical margins recurred in the pelvis. All five of these patients were treated with vaginal ovoid irradiation alone. Whole pelvic irradiation plus vaginal ovoid irradiation is necessary in those with close paracervical margins. The vaginal ovoid irradiation alone should be limited to very selected patients with positive vaginal margins only.

Skeletal metastases from cancer of the uterine cervix: frequency, patterns, and radiotherapeutic significance.

The records of eight hundred two patients who received primary radiotherapy for invasive cervical cancer between 1969 and 1985 were reviewed. The incidence of bone metastasis was 1.9% (15/802). Lumbar spine involvement was the most common site, followed by the pelvic bones. Lumbar spine involvement was characterized by unilateral destruction of one or several contiguous vertebrae. All 10 patients with lumbar spine involvement were associated with a para-spinal mass. In seven of ten patients, this bone destruction due to direct extension from metastatic para-aortic tumor was the only recurrent cancer. In contrast, involvement of a long bone, a rib or the skull indicates hematogenous bone metastasis. When a spine X ray or bone scan is positive in the lumbar area in a cervical cancer patient with back pain, a CT scan should be performed to determine the extent of the underlying tumor. This will allow more accurate establishment of a radiation treatment plan, and will improve the chances for successful palliation.

The influence of prostaglandin antagonists on radiation therapy of carcinoma of the cervix.

In a random trial of 160 women undergoing radiation therapy for carcinoma of the cervix of all stages 76 individuals were treated with 3 X 100 mg oxyphenbutazone daily and 84 individuals served as controls. Reevaluation shows a significantly better 5- and 10-year-survival rate of 70 and 62% in the treatment group, compared to 55 and 44% in the control group. The mode of action of oxyphenbutazone consists of the inhibition of prostaglandin synthesis. Improvement of survival rates is explained by two theories: (1) slowing of tumor spread by inhibition of necessary prostaglandins; and (2) improvement of cell repair after radiation therapy.

[Platin-containing cytostatic combinations in the therapy of advanced gynecologic carcinomas]. / Erfahrungen mit platinhaltigen Zytostatikakombinationen bei der Therapie fortgeschrittener gynäkologischer Karzinome.

95 patients with advanced and recurred gynecological carcinomas (57 ovarian carcinoma, 22 cervical carcinoma) were treated by a platinum (CDDP) based polychemotherapy platinum, adriamycine, cyclophosphamide (PAC); platinum, adriamycine, bleomycine (PAB), 22 out of 48 patients with low differentiated epithelial carcinoma of the ovary stage III and IV achieved a remission (13 CR; 9 PR). Today 6 of the CR-patients survive 23 months without recurrence; 7 had a medium survival of 17 months. Medium survival of PR-patients was 15 months. 6 NED-patients survive 22 months without recurrence and 2 NED-patients died after 19,5 months. The overall response rate (CR, PR, NED) was 63%. A retrospective comparison with 78 patients (low differentiated ovarian carcinoma stage III and IV) treated by a cyclophosphamide monotherapy shows an elevated 2-year survival rate of the PAC treated patients. The other patients suffered from carcinoma of the mamma, the tubes, the corpus uteri, the vagina, and the vulva. The therapeutic effect of CDDP based polychemotherapy cannot be judged because of the small number of cases; but the side effects at these patients were registered thoroughly. Side effects of totally 514 therapeutic cycles (460 mg CDDP per patient, 78 mg CDDP per cycle) are presented.

The neodymium:YAG laser in the treatment of gynecologic malignancies.

The Nd:YAG laser has been used for tumor volume reduction of recurrent gynecologic malignant tumors after previous radiation therapy. The localization of the tumor did not allow conventional surgical resection or surgery was contraindicated because of severe medical problems. Hemorrhage caused by recurrent tumor was controlled by tissue coagulation. The laser beam was delivered by means of a handpiece using the Model 8000 of the Molectron Medical Corporation. A power of 40 to 100 W was used with the maximal pulse duration of 9.9 sec and multiple pulse irradiation. The total energy ranged between 620 and 13.105 Ws. Good palliation was achieved in patients with hemorrhaging tumors of the cervix and ovary metastatic to the vagina.

[Carcino-embryonic antigen in cases of cervical carcinoma (author's transl)]. / Karzinoembryonales Antigen beim Zervixkarzinom.

Carcino-embryonic antigen (CEA) was determined by means of solid-phase radio-immuno-assay through one year in 83 patients with Groups I through IV cervical carcinoma. The intention was to test CEA diagnosis for its value as tumour marker in therapeutic monitoring and detection of recurrences. CEA values prior to treatment were above normal, that is in excess of 2.5 ng/ml, in 42.8 per cent of the cervical carcinoma patients. CEA values declined during therapeutic radium and cobalt 60 irradiation in 81 per cent of those patients in whom original values had been increased to more than 2.5 ng/ml. No substantive change was recordable from those patients in whom original values had been below 2.5 ng/ml. Recurrence diagnosis gave good agreement between CEA levels and clinical findings in 58 per cent of the cases, falsely negative data in 37 per cent and falsely positive values in four per cent. The development of recurrence was repeatedly sensed by means of CEA determination up to six months before clinical manifestation in 72 patients who had been under long-time monitoring. The usefulness of CEA determination in therapeutic monitoring and after-care of patients with cervical carcinoma was found to be limited to the effect that only increased values were of clinical relevance, whereas no conclusions whatever could be drawn from low values.

Plasma urate measurements and fetal outcome in preeclampsia.

The relation of fetal birth weight to plasma urate concentrations and blood pressure was studied in 71 pregnant women with hypertension. The tendency to low birth weight was markedly increased when maternal plasma urate concentrations were over the normal level, generally in association with preeclampsia. Plasma urate showed a better correlation than either edema or proteinuria by itself with low fetal birth weight. Hypertension in association with elevated levels of plasma urate showed the lowest birth weight. Hyperuricemia in normotensive pregnancies showed similar fetal birth weights as maternal hypertension without other preeclamptic symptoms. These findings suggest that, in terms of fetal development, changes in renal retention of urate may be an additional predicting factor for fetal development as important as hypertension alone.

Plasma levels of prostaglandin metabolites during spontaneous delivery.

1. The fetal contribution to PGFM levels is smaller than supposed. 2. The highest levels of PGFM found at placental separation seem to indicate the decidual origin of PGs which enter the maternal organism via the open uterine veins. This assumption is supported by low levels during the postpartum period when contractions are nearly as strong as during labor, but the uterine veins are closed. 3. There is no evidence that obstetrical factors are correlated to PGFM levels.

[Carcino-embryonic-antigen (CEA) in adenocarcinoma of uterine corpus (author's transl)]. / Karzinoembryonales Antigen beim Endometriumkarzinom.

Sandwich radio-immune assay was used before, parallel with as well as following surgical and radiation therapies on 73 patients in a follow-up check for an assessment of the clinical value of CEA im adenocarcinoma of the uterine corpus. CEA levels were increased in only 17 per cent of all cases. The strongest drops in CEA levels in correlation with patients' clinical response to therapy were recorded from those probands who had undergone surgery followed by Co60 irradiation. While CEA determination is, generally, recommended for monitoring of therapy and for the detection of recurrent corpus carcinomas, only pathological CEA levels should be considered as being relevant to clinical action, since the rate of false negative values has been as high as 34 per cent.