Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors.

BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.

The use of lasers in the treatment of cholangiocarcinoma.

Six of seven patients were treated with external beam radiation, iridium-192 internal radiation and neodymium-YAG laser therapy via a percutaneous transhepatic tract for relief of biliary obstruction. After laser therapy, the transhepatic catheters were removed and patients remained tube-free and non-jaundiced for periods ranging from 1 to 20 months.

New surgical method to prevent pelvic radiation enteropathy.

Pelvic radiation doses exceeding 4,000-4,500 cGy are known to be associated with acute and chronic radiation enteropathy. This same radiation dose is, at the same time, only moderately effective in the elimination of microscopic malignancy, let alone gross clinical disease. Numerous medical and surgical attempts to minimize this complication have been uniformly unsuccessful. With the availability of a new synthetic, absorbable, polyglycolic acid mesh, an intestinal sling surgical procedure has been devised to exclude the small bowel from the pelvis and subsequent radiation fields. Twenty-five patients have been treated by this new technique with only one complication presenting as a fungal infection. Small-bowel barium contrast studies in 16 patients referred for postoperative radiation demonstrated 13 satisfactory exclusions of the small bowel from the translateral pelvic irradiation field. In 16 evaluable patients, three had unsatisfactory exclusion two of which were due to technical error. This has permitted high-dose (5,500-6,500 cGy) radiotherapy to the critical treatment volume without posttreatment complication. Mean follow-up time is 14.8 months. Several patients have been reexplored demonstrating complete absorption of the mesh without fibrinous adhesions or other foreign body reaction. It is concluded that this new technique of small bowel exclusion will permit the routine delivery of much higher doses of radiation in patients requiring improved local-regional control of their pelvic cancers and without morbidity from radiation-associated small bowel injury.

Adenocarcinoma of the cecum. Analysis of 106 cases.

The natural history of surgically treated adenocarcinoma of the cecum has not been well defined. This report is a retrospective study of 106 patients followed for a median time of 25 months after hemicolectomy. The overall median survival rate was 73 months and the median disease-free survival rate was 37 months; 22 of 106 patients failed locally (21%). In addition, 7 of these 22 patients had distal failure. Thus, there appears to exist a group of patients likely to benefit from adjuvant radiotherapy. Whether total abdominal irradiation or locoregional radiotherapy is the method of choice needs to be further defined.

Efficacy of polyglycolic acid mesh sling in keeping the small bowel in the upper abdomen after abdominal surgery: a 12-month study in baboons.

The purpose of this study was to determine if a "sling" made of polyglycolic acid (PGA) would be a reliable method of preventing small bowel descent into the pelvis following abdominal surgery. Baboons were used, as they respond to infection and ambulate similarly to humans. Animals had the small bowel mobilized to the upper abdomen and had the PGA "sling" sewn into place. Documentation of small bowel position was evaluated by upper gastrointestinal series over the 12-month study. Small bowel descent into the pelvis was prevented by utilization of the PGA "sling." Animals were sacrificed and autopsied, and sections of small bowel were taken. There was no evidence of mesh, obstruction, sepsis, fistulae, or herniation in animals at autopsy. Small bowel sections were considered normal histologically. Utilization of PGA sling appears to be a safe and reliable method of preventing small bowel descent into the pelvis after abdominal surgery.

New surgical approach to minimize radiation-associated small bowel injury in patients with pelvic malignancies requiring surgery and high-dose irradiation. A preliminary report.

Complications associated with small bowel intolerance to radiation therapy at doses higher than 4500 to 5000 cGy have been the limiting factor in delivering pelvic radiation either as an adjuvant to surgery or alone in the treatment of pelvic malignancies. Despite numerous surgical, medical, and radiation therapy technical measures to minimize small bowel injury, none have been uniformly successful in eliminating this problem. With the availability of a new synthetic absorbable mesh, a pelvic sling can be placed at the time of exploration or definitive surgery aimed at suspending the small bowel out of the pelvis. Preliminary work in animal models has shown the mesh sling to be well-tolerated and successful. Barium-contrast simulation studies of seven patients with pelvic malignancies requiring resectional surgery and postoperative radiation therapy in whom the mesh sling was placed at the time of surgery demonstrate total exclusion of the small bowel from the pelvic radiation treatment field. All patients have been followed for at least 4 months since mesh placement, and to date no complications have occurred. It is possible that this technique of bowel exclusion will permit the delivery of larger doses of radiation therapy in patients with pelvic malignancies aiming at more effective local and regional control of cancer without increased complications from radiation-associated small bowel injury.

Small bowel exclusion from the pelvis by a polyglycolic acid mesh sling.

Radiation enteritis is seen in patients receiving radiation therapy for various pelvic malignancies. Attempts to prevent this have included various surgical as well as nutritional approaches with little success. The use of a polyglycolic acid mesh sling sewn above the pelvic inlet has prevented small bowel descent into the true pelvis in rats and in humans. The technique has been successful in both with no attendant morbidity during an 11-month follow up. Several patients have received additional doses of radiation therapy that would not have been given if the small bowel were not removed from the area to be irradiated.

Interstitial radiotherapy of the base of the tongue. Improved non-looping afterloading technique.

P6modification of the non-looping afterloading interstitial technique for tongue-cancer therapy is described. The subsequent risk of tearing or breaking of the tubes, resulting in radioactive sources left as foreign bodies in soft tissues, is reduced. In addition, evaluation of implant position is simplified by the use of radioopaque tubes.

Radiation-associated impotence. A clinical study of its mechanism.

External beam pelvic irradiation in men is frequently complicated by erectile dysfunction. We tested the erectile function in 23 patients (mean age, 65 years) who received radiation therapy for prostate cancer. Fifteen patients experienced changes in erectile potency following radiotherapy. Neurological, endocrine, and vascular testing revealed abnormalities in 0, 5, and 15 of these patients, respectively. In two, arteriography revealed bilateral occlusive disease in the distal internal pudendal and penile arteries overlying the pelvic radiation field. A significant difference with cigarette smoking was found among the 15 patients whose erectile capacity decreased and the four patients whose capacity remained unchanged. Vasculogenic impotence is the most consistent organic erectile abnormality in RAI.

Importance of myelography in early diagnosis of spinal epidural disease.

Epidural metastasis is potentially one of the most disabling complications encountered in oncology. Once paraplegia has been established, only one patient in ten responds to treatment. A series of 16 patients is presented in which early diagnosis and treatment led to improvement in 13 of 16 patients. Most patients present with pain for varying periods (mean 2.2 months) before neurological signs appear. Myelography alone establishes the diagnosis. Spinal radiography correlates well with the block level in two thirds of cases. Radiotherapy, alone or with steroids, increasingly is used in the management of this condition.

Mycosis fungoides in the maxillary sinus and oral cavity: report of two cases.

Two cases of biopsy-proven mycosis fungoides are described. Case 1 appears to be the first reported instance of mycosis fungoides in the maxillary sinus. Case 2 involves persistently recurring lesions within the oral cavity, which appear to have been placed in a long-term remission by a full course of cobalt irradiation therapy to the entire oral cavity.

A combined treatment program for the management of locally recurrent breast cancer following chest wall irradiation.

Locally recurrent breast cancer involving the previously irradiated chest wall and skin is a difficult but manageable problem. A detailed oncological evaluation is initially undertaken to determine the extent of local and systemic disease. Local infection, if present, is controlled by topical therapy with 0.5% silver nitrate in conjunction with well-planned, aggressive radiotherapy to the areas of tumor recurrence. Concomitant, hormonal, and/or cytotoxic chemotherapy is administered if evidence of systemic involvement is detected. Biopsies of the ulcer margin are performed with surgical excision and débridement as indicated, followed by sequential skin grafting. Seven patients are presented in whom circumferential ulcer biopsies, radiation therapy, skin grafting, and topical silver nitrate therapy were carried out with control and resolution of local symptoms in all cases. It is not essential to have initial tumor control in order to insure graft take. This program has particular application to the poor risk surgical patient, with or without evidence of systemic disease.

Improvement of in vitro mitogen proliferative responses in non-Hodgkin's lymphoma patients exposed to fractionated total body irradiation.

Patients with non-Hodgkin's lymphomas who failed to respond to chemotherapy were treated with low dose fractionated total body irradiation (TBI). Prior to during and after scheduled therapy, their clinical status was evaluated and peripheral blood studies were performed to enumerate EAC and E rosetting cells and to measure proliferative responses to mitogens. Peripheral blood abnormalities were present prior to TBI using these in vitro assays. Patients who obtained clinical remissions following therapy had restoration of mitogen progressive disease had no change in their ability to proliferate in response to mitogens. Normalization of EAC and E rosetting profiles often occurred regardless of clinical response. These data indicate that low dose fractionated TBI produces clinical and in vitro detectable immunological changes. Furthermore, they show that improvement in mitogen responsiveness correlates best with good clinical responses.

Arc technique for total-body irradiation by a 42-MV betatron.

An arc technique for total-body irradiation (TBI) has been developed using a Siemens 42-MV betatron. Dose is administered with the isocenter approximately one-third the distance from source to patient. A modified inverse-square function for a beam arcing isocentrically was derived and confirmed experimentally. Relationships between stationary and arcing beam equilibrium and depth doses have been established theoretically and experimentally. Depth doses for TBI by 42-MV beams are compared with those for 60Co and 4-MV beams. The simplicity of setup and short treatment times are comparable to setup and treatment times of 60Co and linear accelerator TBI techniques.

Single port technique of mantle field treatment in Hodgkin's disease using very high energy x-ray beams.

Treatment pd irradiation of Hodgkin's disease is described indicating the advantage of this energy range and the appropriate dose build-up modifications necessary to achieve a single port irradiation technique.