Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group.

BACKGROUND: Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients. PURPOSE: We present an update of results from a randomized clinical trial designed to examine the efficacy of breast irradiation following conservation surgery in the treatment of women with axillary lymph node-negative breast cancer. The patients were enrolled from April 1984 through February 1989. Initial results were published in 1992 after a median follow-up time of 43 months. It was reported that recurrence of cancer in the breast occurred in 5.5% of the patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two treatment groups. Now that the median patient follow-up has reached 7.6 years, the trial end points have been re-examined and an attempt has again been made to identify a group of patients at low risk for recurrence of cancer in the breast. METHODS: Eight hundred thirty-seven patients with node-negative breast cancer were randomly assigned to receive either radiation therapy (n = 416) or no radiation therapy (n = 421) following lumpectomy and axillary lymph node dissection. The cumulative local recurrence rate as a first event, distant recurrence (i.e., occurrence of metastasis) rate, and overall mortality rate for the treatment groups were described by the Kaplan-Meier method and compared with the use of the logrank test. The Cox proportional hazards model was used to adjust the observed treatment effect for the influence of various prognostic factors (patient age, tumor size, estrogen receptor level, and tumor histology) at study entry on the outcomes of local breast recurrence, distant recurrence, and overall mortality. All P values resulted from the use of two-tailed statistical tests. RESULTS: One hundred forty eight (35%) of the nonirradiated patients and 47 (11%) of the irradiated patients developed recurrent cancer in the breast (relative risk for patients in the former versus the latter group = 4.0; 95% confidence interval = 2.83-5.65; P < .0001). Ninety-nine (24%) of the patients in the former group have died compared with 87 (21%) in the latter group. Age (< 50 years), tumor size (> 2 cm), and tumor nuclear grade (poor) continued to be important predictors for local breast relapse. On the basis of these factors, we were unable to identify a subgroup of patients with a very low risk for local breast cancer recurrence. Tumor nuclear grade, as previously reported, and tumor size were important predictors for mortality. CONCLUSIONS: Breast irradiation was shown to reduce cancer recurrence in the breast, but there was no statistically significant reduction in mortality. A subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy was not identified.

Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer.

BACKGROUND: Although the conservation management of breast cancer has become a routine method of treatment in most centers, there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control. PURPOSE: Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer. We attempted to define low-risk groups of women for breast and distant site relapse (i.e., recurrence outside the breast) who might be spared breast irradiation or adjuvant systemic therapy. METHODS: Eight hundred thirty-seven patients were randomly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer. RESULTS: Breast irradiation reduced relapse in the breast from 25.7% in the controls to 5.5% in the irradiated patients. There was no difference in survival between the two groups (median follow-up, 43 months). A low-risk group (less than 5% chance of relapse in the breast without irradiation) could not be defined. Tumor size (greater than 2 cm), age (less than 40 years), and poor nuclear grade were important predictors for breast relapse. Age (less than 50 years) and poor nuclear grade were important predictors for mortality. The presence of ductal carcinoma in situ did not predict breast relapse. CONCLUSIONS: Breast irradiation significantly reduces breast relapse, but it does not influence survival. Important predictors of breast relapse are age, tumor size, and nuclear grade, but not the presence of ductal carcinoma in situ. Age and, in particular, nuclear grade predict survival. IMPLICATIONS: Further follow-up may define an acceptable low-risk group for breast relapse. Until then, we recommend that all patients receive breast irradiation. Systemic adjuvant therapy should be considered for patients with poor nuclear grade tumors.

Weekly high-dose methotrexate and doxorubicin for osteosarcoma: the Dana-Farber Cancer Institute/the Children's Hospital--study III.

Weekly high-dose methotrexate with leucovorin rescue and vincristine (HDMTX) and doxorubicin was administered as adjuvant postoperative therapy to 46 patients with a diagnosis of conventional high-grade nonmetastatic osteosarcoma of an extremity between July 1976 and December 1981. The primary lesions were managed by wide or radical amputation (26 patients) or by limb-sparing resection in 20 selected patients. The margins of the resections were retrospectively classified as marginal in three, wide in 16, and radical in one. The 5-year relapse-free survival (RFS) for all patients is 59% (95% confidence interval [CI], 43%, 74%) and overall survival is 78% (95% CI, 65%, 91%). The RFS for patients initially having a limb resection procedure is 55% (95% CI, 32%, 77%) compared with 62% (95% CI, 43%, 81%) for those initially having amputations (P = .52). Using multivariate analysis, the only significant prognostic variables that predicted RFS of greater than or equal to 3 years, were the presence of moderate to marked lymphocytic infiltration of the primary tumor (P less than .002), primary site outside of the proximal humerus (P less than .005), and the absence of a predominance of osteoblastic pattern in the primary tumor (P less than .03).

Prospective analysis of strategies for diagnosing renovascular hypertension.

Renovascular hypertension is a potentially curable form of high blood pressure. However, it is unclear how best to select patients who are likely to have renovascular hypertension, what diagnostic strategy to use in these selected patients, and how to predict the hemodynamic significance of a renal artery stenosis. We determined the prevalence of renovascular hypertension in adults who exhibited suggestive clinical features. In these clinically selected patients, we then determined the test characteristics of various diagnostic and potential screening tests. Renovascular hypertension was diagnosed if correction of renal artery stenosis resulted in decreased blood pressure. Of the 66 hypertensive adults evaluated, 11 (16.7%) had renovascular hypertension. Captopril-stimulated peripheral renin activity detected renovascular hypertension with 73% sensitivity, 72% specificity, 38% positive predictive value, and 92% negative predictive value. Less optimal combinations of sensitivity and specificity were found for differential glomerular filtration rate renography, differential effective renal plasma flow renography, and selective renal vein renin ratios, each performed after a single dose of captopril. Intravenous digital subtraction renal angiography detected all patients with renovascular hypertension and was normal in 71% of patients with essential hypertension. To evaluate potential screening tests for renovascular hypertension, we calculated predictive values applied to a low prevalence population. If the observed sensitivities and specificities apply to a population with 5% prevalence of renovascular hypertension, captopril-stimulated peripheral renin would have a positive predictive value of 12% and a negative predictive value of 98%. In 16 patients with known renal artery stenosis, neither the captopril-stimulated renal vein renin ratio nor captopril-stimulated differential renography accurately predicted blood pressure response to correction of the stenosis. We conclude that clinical criteria can identify a subgroup with 16.7% prevalence of renovascular hypertension. In this high prevalence group, intravenous digital subtraction renal angiography will identify virtually all patients with renovascular hypertension, and a normal study will be sufficient to exclude renovascular hypertension. In unselected hypertensive patients, screening with captopril-stimulated peripheral renin activity may be the most useful and efficient procedure for identification of patients with renovascular hypertension. Functional tests do not accurately predict the hemodynamic significance of a renal artery stenosis.

Breast cancer: a 21 year experience with conservative surgery and radiation.

Evidence is presented from a study of 680 patients followed over a period of 21 years that conservative treatment of breast cancer by local excision of the primary tumor followed by breast irradiation yields results equivalent to the traditional radical approach, with the added benefit of an excellent cosmetic result and improved quality of life. The relative survivals were 8.3% at 5 years and 71% at 10 years. There was no difference in survival when radiation was given. Breast irradiation significantly reduced relapse in the breast, but axillary irradiation did not influence relapse at this site. Relapse in the breast alone was not detrimental to survival if treated appropriately. Axillary relapse indicated a much poorer prognosis as might be expected.

Comparison of intravenous digital subtraction angiography and conventional arteriography in defining renal anatomy.

Intravenous digital subtraction renal angiography (IV-DSRA) is frequently used in the preoperative evaluation of living-related (LR) kidney donors. However, the true accuracy of IV-DSRA in the donor population is difficult to assess since abnormalities of the kidney and its circulation are uncommon in this group. Therefore, we evaluated IV-DSRA in a group of patients more likely to have anomalies and abnormalities that would affect LR donor selection, donor nephrectomy, and subsequent transplantation. Hypertensive adults being evaluated for renovascular hypertension had IV-DSRA and conventional renal arteriograms, which were interpreted independently. We determined the accuracy of IV-DSRA, compared with conventional arteriography, in detecting multiple renal arteries, renal artery stenosis, fibromuscular dysplasia, and abnormal renal parenchyma. Technically unsatisfactory studies were excluded from analysis. Of 59 patients evaluated, 37 had abnormalities or anomalies. IV-DSRA failed to detect 28 of 50 findings in these 37 patients. In 21 patients with multiple renal arteries, IV-DSRA underestimated the number of main renal arteries in 8. Significant renal artery stenosis, present in 16 patients, was undetected by IV-DSRA in 3 of these patients. Mild fibromuscular dysplasia was not detected by IV-DSRA in any of the 5 patients with this condition, and abnormalities of renal parenchyma were not detected in 6 of the 8 patients with scarred or cystic kidneys. When compared with conventional renal arteriography in a hypertensive population, the IV-DSRA does not accurately detect abnormalities of the kidney and its circulation. If these data are confirmed in nonhypertensive subjects, preoperative evaluation of LR kidney donors using IV-DSRA alone may fail to detect potentially important anatomic abnormalities.

Osteomyelitis: early scintigraphic detection in children.

The value of scintigraphy in the early detection of osteomyelitis is demonstrated in children who had signs and symptoms suggestive of bone infection. Nine patients between 2 and 13 years of age were evaluated with technetium Tc 99m diphosphonate bone scintigrams and roentgenograms. Blood cultures were performed in all patients, and bone biopsy or drainage was obtained in six patients. The diagnosis of osteomyelitis was made in seven patients; one patient had a subperiosteal abscess surrounded by osteomyelitis, and one patient had cellulitis. The seven children with osteomyelitis had focal increase of radiopharmaceutical uptake in the bone. The child with the subperiosteal abscess had an area of decreased uptake in the center of the abscess surrounded by a zone of increased uptake of the radioactive bone-seeker. The patient with cellulitis had soft tissue changes by X-ray and a normal bone scintigram. In the seven patients with osteomyelitis, the bone scintigram was performed during the early phase of the disease and no bony changes were present on the roentgenogram. In one patient with subacute osteomyelitis, soft tissue changes were seen radiologically. Only three of the seven children with osteomyelitis developed radiological bony changes. Since bone scintigraphy can detect early local bone derangement, it is recommended in the initial evaluation of children in whom osteomyelitis is suspected.

Pleuroperitoneal migration of intraperitoneal phosphorus-32-chromic phosphate therapy for stage I ovarian carcinoma.

A patient with postoperative Stage I ovarian carcinoma received 15 mCi of 32P-chromic phosphate suspension in normal saline intraperitoneally as part of her therapy. The following day, a portion of the infused radiopharmaceutical and normal saline had passed transdiaphragmatically into the patient's right pleural cavity. Thoracentesis removed as much fluid as possible and this fluid contained radioactive material. In the ensuing 4 yr, the patient has not manifested any detectable pleural or pulmonary abnormalities attributable to the radioactivity. Retrospective review of 100 consecutive patients receiving 32P-chromic phosphate intraperitoneal therapy resulted in 43 patients in whom the hemithoraces could be evaluated scintigraphically. Three of the 43 patients (7%) had right pleural fluid radioactivity. This is similar to the percentages reported in patients with cirrhosis with ascites in whom hepatic hydrothorax is identified.

Bilateral urinothorax identified by technetium-99m DPTA renal imaging.

A case of unilateral urinary tract obstruction with extravasation resulting in bilateral pleural effusions is presented. The fluid within the pleural cavities was established to originate from the kidney using [99mTc]diethylenetriaminepentaacetic acid and scintillation camera imaging.

Concentration of Tc-99m methylenediphosphonate in hepatic metastases from squamous cell carcinoma.

A case is described in which Tc-99m methylene diphosphonate concentrated in a hepatic metastasis from esophageal squamous cell carcinoma. We observed radiopharmaceutical concentration in the hepatic metastases, which was probably related to the presence of necrosis with calcification.

Microfiche as a medium for the long-term storage of laboratory computer records.

The chemical pathology requests on 180 000 patients a year are stored on microfiche, occupying 72 mm of shelf space. They are produced by a sequence of three computer programs which remove data from disc on to magnetic tape using the laboratory's Digital Equipment Corporation PDP 11/34 minicomputer. Processing on to microfiche is performed by a bureau. The magnetic tape is available for retrospective research and management studies in one-month periods.

Assessment of fat malabsorption.

For the assessment of fat malabsorption, the standard method of measuring faecal fat excretion using a 5 day stool collection has been compared with the alternative methods: stool microscopy, a lipid tolerance test and a continuous marker technique for the estimation of fat content on a single stool sample. The lipid test, using an emulsion of arachis oil (Prosparol), was less reliable than had been expected with a sensitivity of 33% and a specificity of 45.4%. Stool microscopy using Oil Red O to stain fat globules had a sensitivity of 72.2% and a specificity of 95.4%. Fat estimation of a single stool sample using copper (1) thiocyanate showed a high correlation with that determined on a 5 day stool collection (p less than 0.001). It is concluded that lipid tolerance tests have little place in the estimation of fat absorption. In laboratories where faecal fats are not measured, microscopic examination of stool for fat globules provides a specific and relatively sensitive method for detecting steatorrhoea. The use of a continuous marker provides a method for assessing the degree of steatorrhoea on a single stool sample without the disadvantages of the conventional method of faecal fat analysis.

Nonobstructive dilatation of upper urinary tract may later convert to obstruction.

We report on 5 babies found to have pyelocaliectasis or hydroureteronephrosis antenatally who were evaluated soon after birth because of persistent mild or moderate upper urinary tract dilatation. In each instance, vesicoureteral reflux was absent and the technetium-99m diethylenetriaminepentaacetic acid renal scan revealed good function in the ipsilateral kidney. Renogram curves, after furosemide, did not show an obstructed pattern. Indeed, allowing for the dilatation, the drainage patterns were thought to be normal. In each instance the patient represented or was found on follow-up to have increased dilatation. Renograms were then repeated, using the same radiopharmaceutical and dose of diuretic. An obstructive pattern was seen in each instance. These significant observations demonstrate that nonobstructive hydronephrosis, diagnosed prenatally, may later convert to obstruction at the ureteropelvic junction (UPJ) or in the juxtavesical ureter (UVJ). Thus, careful follow-up, for a period yet to be determined, is desirable in patients in whom the initial postnatal evaluation does not demonstrate obstruction by current criteria.

Arthritis in children.

Arthritis in children may be caused by many diseases and disorders. Some processes may be aborted by early diagnosis and treatment. Others may not cause true arthritis until the adult years, with a variable latent period. The spectrum includes congenital malformations, neoplasia (benign and malignant), infection, trauma, hematologic/vascular disorders, and connective tissue diseases. In all instances, early diagnosis is important. The growing skeleton has great potential to remodel if it is given adequate time.

Osteoporotic sacral fractures: a clinical study.

Traumatic sacral fractures are most often due to motor vehicle or industrial accidents and are commonly associated with pelvic, urogenital, and neurological injuries. In recent years, a more subtle type of sacral fracture, not associated with major trauma, has been described. It is an osteoporotic insufficiency fracture that presents as low back pain in elderly patients, especially postmenopausal Caucasian women. It may escape detection unless radionuclide bone scans, tomograms, or computed tomograms are obtained. The radiographic features have been detailed in various publications, but little has been reported about the clinical features, treatment, or ultimate outcome of patients with osteoporotic sacral fractures. We have reviewed the charts and radiological studies of 13 women and 3 men who sustained this type of fracture between 1983 and 1986. All of these patients were Caucasian. The average age was 71 years. The most common presenting symptom complex was diffuse low back pain accompanied by hip, buttock, or thigh pain. Pertinent physical findings were limited to tenderness on palpation of the sacrum and a decreased range of low back motion. The osteoporotic fractures were seldom noted on plain roentgenograms of the sacrum, but were readily defined by sacral tomography or computed tomography. Radionuclide bone scanning also proved helpful in making the diagnosis by localizing the process. Treatment was medical and consisted of therapies designed to reduce pain and to combat the associated osteopenia. Of our 16 patients, 11 had complete pain relief, 2 had substantial pain relief, 2 noted decreasing pain before they died of other causes, and 1 was followed less than 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

Reactive sclerosis of a pedicle and spondylolysis in the lumbar spine.

Eleven patients were seen with reactive sclerosis and hypertrophy of one pedicle and lamina of a lumbar vertebra and a contralateral spondylolysis in the same vertebral segment. Differentiating the reactive sclerosis in this condition from that associated with osteoid-osteoma is necessary since excision of a sclerotic pedicle associated with contralateral spondylolysis will create painful instability. In asymptomatic patients observation is sufficient, while in those with symptoms not relieved by external immobilization, spine fusion, usually of three levels, is indicated.

Femoral anteversion.

Biplane roentgenography, axial roentgenography, and fluoroscopy are the usual roentgenographic methods of measuring femoral anteversion. These methods use a strict geometrical definition of anteversion. The computerized tomography method of measuring anteversion that was developed recently, and is now widely used, does not adhere to the accepted definition of anteversion and has not been tested for accuracy in a large series. In the present study, the widely used computerized-tomography method of measuring anteversion was tested on thirty-two femoral specimens. With that method, anteversion was consistently underestimated by an average of 10 degrees compared with direct measurements and was reproducible only to within +/- 3.6 degrees. Therefore, a new method of measuring anteversion using computerized tomography was developed. It was shown to be accurate to +/- 1 degree, as tested on the same specimens. This study demonstrated geometrically why the currently practiced computerized-tomography method of selecting the points that are used to define the axis of the femoral neck is not consistent with geometrical definitions of anteversion. A more accurate method for both defining the axis of the femoral neck and measuring femoral anteversion is described and recommended for clinical use.

The association of femoral retroversion with slipped capital femoral epiphysis.

We examined twenty-five patients who had a unilateral or bilateral slip of the capital femoral epiphysis and determined the degree of anteversion of the thirty-nine involved hips with computerized axial tomography. Thirteen patients (eighteen hips) were seen at the time of the original diagnosis (Group I), and twelve patients (twenty-one hips) were seen one to seven years after operative treatment (Group II). The mean amount of anteversion for all of the involved hips was +1.0 +/- 8.2 degrees. The mean amount of anteversion for the Group-I hips was -0.7 +/- 7.4 degrees and the mean amount for the Group-II hips was 2.5 +/- 8.7 degrees. The mean amount of anteversion for the hips in both Groups I and II was less than the predicted mean amount for individuals of the same age. The mean amount of anteversion of the unaffected hips of our patients who had a unilateral slip was +6.3 +/- 8.2 degrees. The amount of internal rotation of the hip in extension exceeded the amount when it was in flexion in all of the patients. A decreased angle of femoral anteversion appears to be specifically associated with the development of slipped capital femoral epiphysis. The mechanical forces that act across the proximal femoral physis may be altered by this rotational abnormality, and this may lead to an increased shear stress that ultimately causes failure of the growth plate.

Breast cancer. Experiences with conservation therapy.

A series of 1,504 patients with clinically node-negative carcinoma of the breast treated by breast conservation has been followed for 26 years. The majority did not have an axillary dissection. A relative survival of 84% at 5 years and 72% at 10 years compares favorably with reported survival rates for radical surgery. Postoperative irradiation does not influence survival but breast irradiation reduces relapse in the breast. Irradiation of the regional nodes is unnecessary. Lumpectomy alone in clinically node-negative patients produces a survival rate equivalent to more radical treatment. Younger patients had larger tumors, an increased risk of breast relapse, and reduced survival. Local or distant relapse was not a function of estrogen receptor (ER) or progesterone receptor (PR) status.

Radiographs.

Physicians performing radiology for children should utilize modern equipment, expose children to the least amount of radiation possible, and avoid unnecessary examinations. Those interpreting radiographs must be familiar with the wide range of normal variations of the skeleton and/or be prepared to refer to texts and atlases dealing with these. Careful examination of soft tissues greatly increases the accuracy of diagnostic radiology in the search for trauma and infection.