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BACKGROUND Despite the generally successful scintigraphic detection of endocrine tumors with [111In]-DTPA-D-[Phe1]-octreotide (OctreoScan®, Mallinckrodt Medical, Petten, The Netherlands), its intraoperative application awaits the development of suitable gamma detectors. This study describes a novel probe (H-probe2) and its ex vivo efficacy for the detection of midgut carcinoid tumors. METHODS The probe measures 180 mm × 24 mm, and contains a bismuth germinate crystal connected to a photomultiplicator tube, a lead shield, and a tantalum collimator with an angled, 3-mm wide opening. It was characterized in a test bench utilizing solublilized 111In and 99mTc, and 8 fresh operative specimens containing 26 histologically verified midgut carcinoid tumors (2-40 mm) from patients exposed to OctreoScan®. Measurements were made at 2.5-mm intervals over the entire specimens and presented three dimensionally. RESULTS The test bench analysis supported efficient shielding, and a total collimation of 27 ° for 111In and 20 ° for 99mTc. In addition to 18 palpable tumors, 4 of 6 surgically occult tumors (2-3 mm in dimension) could be discovered with H-probe2. Small tumors in close apposition to a large tumor could not be separated. Wellcounter examination showed that tumors detected with the H-probe2 exhibited 1.7-84.1 times higher radionuclide uptake than the surrounding normal tissue. CONCLUSION Ex vivo analysis of H-probe2 supported detection of tumors inaccessible to surgical palpation, but its clinical efficiency awaits intraoperative evaluation. Cancer 1997; 80:2495-500. © 1997 American Cancer Society.

Background. The aim of this study was to assess the effectiveness of full doses of reirradiation to salvage previously irradiated recurrent skin cancer of the face. Methods. As of December 1990, 17 patients at the Mallinckrodt Institute of Radiology were reirradiated for recurrent skin cancer in previously irradiated areas of the face. There were eight basal cell and nine squamous cell carcinomas. The interval between the two treatments ranged from 6 months to 15 years (median, 4 years). The dosimetry was reviewed, and the radiation doses were recomputed by the biologic effective dose (BED) formula. Results. The accumulated BED from the two irradiation regimens ranged from 48.78 to 143.5 Gy on the skin surface (median, 103 Gy) and 80.93 to 160.68 Gy at 5 mm depth (median, 108 Gy). Local control was achieved in ten patients ; two of them had skin defects that required reconstruction. Six of seven patients with persistent tumors had squamous cell carcinoma. Those patients with BED of previous treatment at 5 mm depth less than 55 Gy, and accumulated BED on skin surface of no more than 110 Gy had the best outcome. The residual damage of skin from previous treatment is a function of fraction size and total dose. Conclusions. Reirradiation is a feasible treatment alternative for recurrent skin cancer of the face when cosmesis is a concern. Cancer 1995 ;75 :2351-5.

Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure.

[(111)In]-diethylenetriamine pentaacetic acid (DTPA)-D-[Phe1]-octreotide (OctreoScan, Mallinckrodt Medical, Petten, The Netherlands), combined with single photon emission computed tomography (SPECT), has limited possibilities to detect small abdominal endocrine tumors. This study explores the efficacy of OctreoScan and a newly developed handheld gamma detector probe (H-probe2) for the localization of neuroendocrine abdominal tumors.Twenty-one patients with endocrine pancreatic or midgut carcinoid tumors were given 100-200 megabecquerels (MBq) [(111)In]-DTPA-D-[Phe1]-octreotide and underwent preoperative SPECT examination, after which time surgery was undertaken within 24-48 hours. Intraoperatively the radioactivity of tumors and normal tissues was measured with the H-probe2 connected to a portable personal computer. Resected intestinal specimens of ten patients with carcinoid tumors were examined by gamma camera ex vivo. Biopsies of all tumors subsequently were investigated in a wellcounter and by routine histopathology.Disregarding liver metastases, a total of 34 of 60 abdominal tumors were detected by SPECT; however, SPECT failed to visualize any tumor9 mm. The shielding of the manual probe allowed intraoperative examination despite the substantial radiation energy of (111)In. The H-probe2 detected 91% of the tumors investigated, and these included all those5 mm. In the wellcounter the H-probe2-detected tumors exhibited 4.7-157.7 times higher radionuclide uptake than the surrounding normal tissues. The gamma camera analysis detected 68% of tumors in the resected specimens.The intraoperative H-probe2 examination provided substantial improvement in the detection of small endocrine lesions accumulating [(111)In]-DTPA-D-[Phe1]-octreotide and all lesions with a size5 mm in greatest dimension could be identified.

The treatment of patients with locally advanced noninflammatory breast cancer has evolved substantially over the past 30 years. From 1968 to 1989, 281 women were treated at Mallinckrodt Radiation Oncology Center with four different treatment methods. Median follow-up was 6.2 years (range 3-22 years); no patient was lost to follow-up.Retrospective review of records and analysis of data on a computer file were carried out. Thirty-five patients were treated with irradiation alone, 33 with irradiation and adjuvant chemotherapy, 81 with mastectomy and irradiation, and 132 with mastectomy, irradiation, and chemotherapy (triple-modality).Actuarial 5- and 10-year disease free survival (DFS) rates were 45% and 36%, respectively, with triple-modality therapy, 31% and 10% with irradiation and chemotherapy, 32% and 19% with irradiation and mastectomy, and 19% and 11% with irradiation alone. Cause specific survival (CSS) paralleled DFS in the four groups. Locoregional tumor control at 5 years was 91% for irradiation, mastectomy, and chemotherapy, 80% for irradiation and mastectomy, 54% for irradiation and chemotherapy, and 31% for irradiation alone. Systemic therapy and/or irradiation given before mastectomy yielded better locoregional tumor control, DFS, and CSS (not statistically significant). No difference in results was noted with radical, modified radical, or total mastectomy. In the triple-modality group, no chest wall failures occurred with chest wall doses greater than 5040 cGy. Grade 2 or higher treatment sequelae were noted in 10-42% of patients, depending on treatment modality.Triple-modality therapy yielded improved locoregional tumor control, DFS, and CSS compared with other modalities. Patients treated with surgery had better locoregional tumor control than those who received irradiation alone or in combination with chemotherapy, but the impact on DFS and CSS was less impressive. Additional clinical trials are needed to define further the role and optimal use of the various therapeutic modalities in the management of locally advanced breast cancer.

From the *Department of Radiology, Jewish Hospital, and the tMusculoskeleta1 Section, Mallinckrodt Institute of Radiology, St. Louis, Missouri; the $Department of Radiation Oncology, Stanford University Medical Center, Stanford, California; the SPediatric Oncology Group Statistical Office, Gainesville, Florida; the 11 Department of Radiation Oncology, Roger Williams General Hospital, Providence, Rhode Island; and the #Pediatric Oncology Group Operations Office, St. Louis, Missouri. Supported in part by grants from the National Cancer Institute and the National Institutes of Health (CA-30969, CA-29139, CA05587, and CA-33603). Principal investigators and their participating parent institutions are as follows (with grant numbers in parentheses): J. Akabutu, Alberta Pediatric Oncology Consortium, Edmonton, Alberta, Canada; Y. Ravindranath, Children’s Hospital of Michigan, Detroit, Michigan (CA-29691); R. Ducos, Children’s Hospital of New Orleans, New Orleans, Louisiana (C-35272); J. Falletta, Duke University Medical Center, Durham, North Carolina (CA-15525); A. Ragab, Emory University Medical School, Atlanta, Georgia (CA-20549); J. Talbert, Florida Community Clinical Oncology, Gainesville, Florida (CA-35 157); B. Leventhal, Johns Hopkins School of Medicine, Baltimore, Maryland (CA-28476); V. M. Whitehead, McGill University, Montreal, Canada (CA-33587); H. Maurer, Medical College of Virginia, Richmond, Virginia (CA-28530); J. Laver, Medical University of South Carolina, Charleston, South Carolina; B. Camitta, Midwest Children’s Cancer Center, Milwaukee, Wisconsin (CA-32053); E. Forman, New England Pediatric Consortium, Providence, Rhode Island (CA-29293); R. Nitschke, Oklahoma University, Oklahoma City, Oklahoma (CA-I 1233); D. Maybee, Uniformed Services Oncology Consortium, Washington, DC; E. Douglass, St. Christopher’s Hospital, Philadelphia, Pennsylvania; M. Link, Stanford University Medical Center, Palo Alto, California (CA-33603); H. Wagner, Swiss Pediatric Oncology Group, Bern, Switzerland; R. Dubowy, State University of New York, Syracuse, New York (CA-41721); R. Castleberry, University of Alabama, Birmingham, Alabama (CA-25408); D. Berry, University of Arkansas, Little Rock, Arkansas (CA-41188); F. Kung, University of California at San Diego, San Diego, California (CA-28439); T. Vats, University of Kansas, Kansas City, Kansas (CA-28841); J. Pullen, University of Mississippi Medical Center, Jackson, Mississippi (CA015989); S. Toledano, University of Miami, Miami, Florida (CAphy (CT) appearance of Ewing sarcoma for indicators of decreased survival or future disease progression. Methods. The authors evaluated CT scans and plain radiographs of the primary tumor site from 105 patients with Ewing sarcoma at diagnosis (prebiopsy), after induction chemotherapy (13 weeks), and after radiation therapy (20 weeks). Results. Data suggest an association between postinduction CT findings of medullary involvement, cortical destruction, lysis, permeation, and unhealed pathologic fracture and decreased survival. On the postradiation scans, only medullary involvement was associated with worsened survival. No plain radiographic features were significant at any time. Absolute greatest tumor dimension was not significantly related to survival or tumor progression. The Cox model suggested that fractional change in greatest tumor dimension on CT at the time points studied relative to the prebiopsy CT was correlated to survival. Log-rank testing did not corroborate this finding. All significant associations appeared to result from adverse outcomes in small subgroups. Conclusions. Our data suggest that CT obtained immediately after induction chemotherapy and radiation may have some limited use in predicting the long-term prognosis of patients with Ewing sarcoma. Cancer 1993; 72: 2503-10.

We have reviewed the records of 76 patients with Stage I or II extranodal non-Hodgkin's lymphoma who were referred to the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, during the years 1964 through 1974. The histologic slides were reviewed in the 67 cases in which they were available. Forty-three percent of Ann Arbor Stage I and II patients relapsed after primary radiation treatment.Seventy-three percent of these failed in sites distant from the irradiated volume. Failures in the treated volume were infrequent (7%) except in those patients presenting with primary lesions of the brain (4/5). Those patients presenting with lesions of Waldeyer's ring experienced a decrease in survival with increasing tumor size. Because of the high rate of failure in distant sites with tumors in the lingual and palatine tonsils, we are recommending the study of adjuvant chemotherapy in these cases, after primary radiation treatment.

A retrospective analysis was performed on all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, St. Louis, Missouri. Of 210 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (RT), 121 received immediate postoperative RT (2 to 6 weeks), and 19 received RT following surgical failure. The mean follow-up time from the date of diagnosis for those patients alive at the time of last follow-up was 13.0 years (range, 3.0 to 30.0 years). Actuarial progression-free survival was analyzed up to 30 years. The 10-, 20-, and 30-year progression-free survival was 80.5%, 73.5%, and 73.5% for those patients treated with irradiation alone and 92.8%, 71.2%, and 44.0% for those treated with immediate postoperative irradiation. The median time to first failure from initial diagnosis by original treatment was 3.8 years for surgery alone, 4.2 years for RT only, and 10.2 years for surgery plus postoperative RT. Analysis for risk of recurrence per 5-year interval was performed using a hazard function analysis. The risk of recurrence after radiotherapy alone was greatest during the first 5-year interval after treatment and decreased to zero by 20 years. However, the risk of recurrence after primary surgery and postoperative radiotherapy revealed an increasing risk for recurrence up to 30 years after treatment. The concept of "cure" for pituitary adenomas requires extended follow-up.

One hundred eighty-three patients with Stage III and nonmetastatic Stage IV breast cancer, seen between 1960-1975 at the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, were retrospectively analyzed to determine the prognostic significance of the following clinical features: (1) "grave signs" (skin ulceration, skin fixation, chest wall fixation, and edema); (2) size of primary tumor; (3) nodal stage; and (4) inflammatory changes. Since therapy among 147 patients with noninflammatory cancer comprised of either irradiation alone (54 patients) or surgery plus irradiation (93 patients), all the above factors were analyzed also with respect to the method of treatment. In 147 patients with noninflammatory carcinoma, the local failure rate, regional failure rate, distant failure rate and five-year disease free survival were all unaffected by the presence or absence of "grave signs," whether treated by irradiation alone or surgery plus irradiation. The size of the primary tumor, in patients treated with irradiation alone, influenced the rate of local failure (44% for tumors 0-8 cm and 76% for tumors greater than or equal to 8 cm) and five-year disease-free survival (30 versus 4%, respectively). Such a statistically significant difference in local failure rate or disease-free survival was not noted when treated with combined modality. N stage also influenced the prognosis in patients treated with irradiation alone since the regional failure rate increased from 9% for N0, N1 to 58% for N2, N3 patients. This was reflected in a decreased disease-free survival (4 versus 30%) for patients with advanced nodal disease who were treated with irradiation alone. No such difference was noted when the nodal disease was treated with a combination of surgery and irradiation. The 36 patients with inflammatory carcinoma had essentially the same incidence of local, regional and distant failure as the 147 patients with noninflammatory carcinoma but the appearance of distant metastases occurred significantly earlier in patients with inflammatory carcinoma than in those with noninflammatory carcinoma. This earlier appearance of distant metastases was reflected in the significantly lower disease-free survival for the patients with inflammatory carcinoma (6 versus 28%). The data from this analysis suggests that consideration should be given to removing the presence of grave signs from the current AJC staging system and substituting in its place the size of the primary tumor (less than 8 cm versus greater than or equal to 8 cm). Further analysis on a large number of patients is needed to substantitate this recommendation.

Seventy-four patients with histologically confirmed diagnoses of Wilms' tumor were treated between 1949 and 1978 at the Mallinckrodt Institute of Radiology and St. Louis Children's Hospital. The results have been divided into two eras of therapy, i.e., before and after 1965, when chemotherapy became a major modality for Wilms' tumor therapy. Analysis at 5 years by era of therapy has shown similar disease-free survival results for Stage I ("prechemotherapy" era 67% versus "chemotherapy" era 75%), whereas the Stage II ("prechemotherapy" era 33% versus "chemotherapy" era 100%) and Stage III ("prechemotherapy" era 0% versus "chemotherapy" era 70%) are significantly different (P less than 0.001). This suggests that chemotherapy has substituted for postoperative irradiation in Stage I patients; whereas in Stage II and III, improved survival occurs as a result of the eradication of subclinical metastatic disease. The patterns of failure by era of treatment are presented and the literature is discussed.

Between 1958 and 1985, 107 patients with nonmetastatic inflammatory breast cancer (IBC) received radiotherapy as all or part of initial treatment at the Mallinckrodt Institute of Radiology. For this review, the diagnosis of IBC was made on the basis of either clinical or histopathologic criteria. Fifteen factors of potential prognostic significance were evaluated, by both univariate and multivariate analysis. For relapse-free survival, univariate analysis suggested prognostic value for initial tumor size, discrete versus diffuse tumor mass, adjuvant chemotherapy, and mastectomy. In the multivariate analysis, the independent prognostic factors, in order of significance, were mastectomy, diffuse versus discrete tumor mass, and race (marginal). For survival, univariate analysis suggested prognostic value for initial tumor size, diffuse versus discrete tumor mass, nodal stage, year of treatment, adjuvant chemotherapy, and mastectomy. In the multivariate analysis, the prognostic factors in order of significance were mastectomy and chemotherapy (marginal). The diagnostic selection group showed no prognostic value, suggesting that either clinical or histopathologic criteria justify the diagnosis of IBC. Our results appear to support a role for surgery as part of the combined modality approach to this disease.

This report updates a previous publication describing the experience at the Mallinckrodt Institute of Radiology with irradiation and hyperthermia in the treatment of superficial metastatic and recurrent malignant tumors. In a dose-seeking Phase I-II clinical study, a total of 101 lesions have been treated. Twenty-two tumors were treated with doses of irradiation ranging from 1000 to 3000 rad and the rest with doses between 3000 and 4000 rad. Irradiation was delivered twice weekly (every 72 hours) in tumor doses of 400 rad, usually with electrons (9–16 MeV). Hyperthermia was initiated within 30 minutes following irradiation, most of the patients being treated with 915 MHz microwaves, 41–43°C, for 60–90 minutes every 72 hours. Adequate temperatures were reached in most lesions measuring less than 2 cm in thickness, 70% of those 2–4 cm and only in 30% of those thicker than 4 cm. Of 36 measurable lesions in the head and neck, 20 had a complete response and 12 a partial response. In 16 of the 20 patients (80%) showing a complete response the tumor was controlled from three to 36 months. Of 30 adenocarcinoma of the breast lesions, recurrent in the chest wall, 16 showed a complete response and 9 a partial regression. Twelve of the 16 lesions that regressed completely (71.4%) showed long-lasting tumor control. Of 22 metastatic or recurrent melanoma lesions, 16 had a complete regression and six a partial response. Of the 16 patients with complete response, 13 (81%) had no evidence of recurrence lasting from three to 36 months. Three sarcoma lesions responded well to the combination of irradiation and heat and did not recur after treatment. Patients treated with doses larger than 3000 rad in the head and neck or in the chest wall (epidermoid carcinoma or adenocarcinoma, respectively) showed better tumor response than those treated with lower doses. However, in melanoma satisfactory results (80% or higher response) were observed with doses as low as 2000 rad. This combined therapy has been well tolerated by the normal tissues. In 6% of the patients there was evidence of tumor necrosis with ulceration and in 5% thermal burns which healed after 2 to 3 months, with conservative management. Subcutaneous fibrosis and some skin atrophy developed in about one third of the patients, probably due to the additional doses of irradiation delivered after previous definitive radiotherapy. These preliminary observations suggest enhanced tumor response and control after moderate doses of irradiation and hyperthermia. Efforts must be intensified to develop adequate equipment to satisfactorily produce heat and to measure temperatures in clinical settings, thus paving the way for appropriately designed clinical trials to test the efficacy of hyperthermia in patients with deep seated lesions and advanced primary tumors.

Forty-nine cases of Wilms' tumor treated at the Mallinckrodt Institute of Radiology and Children's Hospital, Washington University Medical Center, between 1950 and December 1969, were retrospectively analyzed. The most important prognostic factors were the anatomical stage of the tumor and some pathologic findings such as invasion of the renal capsule, the renal vein or inferior vena cava, and metastases to the regional lymph nodes or to other organs. A histopathologic classification based on differentiation of the tumor is presented and correlated with cure rates. Stage I lesions had a very good prognosis (85% 3-year survival NED), even without high-dose irradiation or prolonged chemotherapy. Triple therapy, involving nephrectomy, irradiation, and prolonged chemotherapy yielded a 55% survival rate in patients with Stage II and 30% in Stage IV (patients with pulmonary metastases). Stage III tumors showed an unsatisfactory response to this comprehensive approach. Patients with bilateral tumors are potentially curable if aggresively treated. From this study it can be concluded that: 1. thorough analysis of the clinical and pathologic characteristics of the tumor should be made in every case and management should be individualized, to avoid excessive treatment in early lesions with favorable prognosis, and 2. carefully administered postoperative irradiation and prolonged chemotherapy may improve the poor results in extensive lesions, even in the presence of distant metastases, with relatively minor sequelae in the surviving children. The late effects of vigorous and prolonged chemotherapy on the bone marrow, the immunologic surveillance system, and the germinal cells of the gonads as well as the repercussion on normal growth of these children remain to be evaluated.

Recruitment of patients to clinical trials is a multi-stage process. To participate in a protocol, a patient must meet all the eligibility requirements; the physicians managing the patient must be amenable to enrolling the patient on protocol; and finally, the patient must consent to participate. In 1979, 64 clinical trials were open to patient accrual in the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, St. Louis, Missouri. A total of 1103 cases were reviewed. Two hundred sixty-three patients were eligible for one of the protocols, of whom 124 were successfully recruited. The reasons for ineligibility and nonparticipation are discussed.