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Background: Several recent studies have investigated the influence of family history on the progression of DCIS patients treated by tylectomy and radiation therapy. Since three treatment strategies have been used for DCIS at our institution, we evaluated the influence of family history and young age on outcome by treatment method. Methods: Between 1/1/82 and 12/31/92, 128 patients were treated for DCIS by mastectomy (n = 50, 39%), tylectomy alone (n = 43, 34%), and tylectomy with radiation therapy (n = 35, 27%). Median follow-up is 8.7 years. Thirty-nine patients had a positive family history of breast cancer; 26 in a mother, sister, or daughter (first-degree relative); and 26 in a grandmother, aunt, or cousin (second-degree relative). Thirteen patients had a positive family history in both first- and second-degree relatives. Results: Six women developed a recurrence in the treated breast; all of these were initially treated with tylectomy alone. There were no recurrences in the mastectomy group or the tylectomy patients treated with postoperative radiation therapy. Patients with a positive family history had a 10.3% local recurrence rate (LRR), vs. a 2.3% LRR in patients with a negative family history (p = 0.05). Four of 44 patients (9.1%) 50 years of age or younger recurred, compared to two of 84 patients (2.4%) over the age of 50 (p = 0.10). Fifteen patients had both a positive family history and were 50 years of age or younger. Among these women, the recurrence rate was 20%. Women in this group treated by lesionectomy alone had a LRR of 38% (3 of 8). Conclusion: The most important determinant of outcome was the selection of treatment modality, with all of the recurrences occurring in the tylectomy alone group. In addition to treatment method, a positive family history significantly influenced LRR in patients treated by tylectomy, especially in women 50 years of age or younger. These results suggest that DCIS patients, particularly premenopausal women with a positive family history, benefit from treatment of the entire breast, and raise concerns about treating patients with a possible genetic susceptibility to breast cancer with tylectomy alone.

There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin (ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p = 0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.

The role of systemic therapy in addition to irradiation for locoregional recurrence of breast cancer is controversial. In the absence of prospective randomized trials, treatment decisions must be based on retrospective studies. We retrospectively analyzed 230 patients treated for locoregionally recurrent breast cancer between 1964 and 1986. Forty-seven were premenopausal, 173 were postmenopausal, and the menopausal status was unknown in 10 patients. Each patient treated with radiotherapy (RT) and chemotherapy or with RT and hormonal therapy was matched with a control patient treated with RT alone. The addition of hormonal therapy to radiation therapy significantly improved the 5-year overall survival (50 versus 28%), disease-free survival (37 versus 26%), and distant metastases-free survival (45 versus 29%). No improvement in locoregional control was observed. In contrast, chemotherapy did not confer such survival benefits, but there was a trend towards improvement in 5-year locoregional control (68 versus 50%), p = 0.08. Our data support the use of hormonal therapy along with RT at the time of locoregional recurrence of breast cancer. Although our data suggest that chemotherapy is not routinely indicated, controlled clinical trials are needed to define which subsets of patients, if any, benefit from systemic therapy.

Forty-six cases of solitary plasmacytoma were reviewed for response to radiation and progression to multiple myeloma. Cases were classified as solitary plasmacytomas of bone (SPB) (32 cases) or extramedullary plasmacytomas (EP) (14 cases). There was an overall 93% response rate of the tumor to radiation therapy: 62% had a complete response after radiation therapy, whereas 31% had a partial response. Conversion to multiple myeloma was influenced by the type of plasmacytoma; 53% of the patients with SPB converting to myeloma versus 36% of the patients with EP. Time from diagnosis to conversion for patients with SPB showed no evidence of plateau, with conversion continuing to occur even after 17 years. The median survival time for patients after conversion to myeloma was 14.5 months and was not affected by time to conversion. Serum protein level, presence of monoclonal gammopathy, and size of primary lesion were of some prognostic significance in predicting conversion to myeloma. Adjuvant chemotherapy did not affect the incidence of conversion but did appear to delay conversion to myeloma. Seven patients in whom multiple sequential solitary plasmacytomas developed formed a distinct subset, with a median time to a second plasmacytoma of 63 months. In three of these patients, conversion to myeloma occurred subsequently. This study supports the idea of EP having a lower incidence of conversion to myeloma and a different natural history from SPB, with SPB likely to be multiple myeloma in evolution.

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.

Immediate or delayed reconstruction using implants or autologous tissue transfer is increasingly offered to women undergoing mastectomy for breast cancer. Some patients require radiotherapy for prevention of local/regional relapse, and some for post-surgical local/regional recurrence. Others with augmented breasts may opt for conservative surgery and irradiation. At Washington University, 70 breast cancers were irradiated in 66 patients following mastectomy with reconstruction (N = 61) or wide local excision of an augmented breast (N = 5). Two patients elected to have a second reconstruction after an unsatisfactory initial result. Thus, 72 breasts were evaluated after radiotherapy for tumor control, complications, cosmesis, and patient satisfaction. Locoregional failure occurred in only five patients, one following adjuvant radiotherapy after mastectomy with reconstruction and four following radiotherapy for recurrent breast cancer within a reconstructed breast. Grade 2 or 3 complications occurred in 34 patients (51%). The complication rate was highest in autologous tissue transfer reconstructions. Cosmetic results were evaluated good/excellent in 49% by physicians and 67% by patients. Immediate reconstructions had fewer good/excellent physician evaluations (32%) compared with reconstructions performed at least 6 weeks after radiotherapy (55%). Transverse rectus abdominis flaps had the best cosmesis scores, followed by permanent silicone prostheses, tissue expanders, latissimus dorsi, and gluteal flaps. Only 48% of patients would choose to have the same reconstructive procedure again. Phantom interface dosimetry with a parallel plate chamber and TLD measurements was performed. Radiotherapy and reconstruction are not incompatible, but careful consideration of their relative timing and technique appear to be important in optimizing cosmesis while minimizing complications.

From 1968–1987 237 women with Stage III, noninflammatory breast cancer were treated with various modalities. Ninety-three (39%) had Stage IIIA tumors, and 144 (61%) had Stage IIIB, noninflammatory tumors (AJC, 1983 staging). Median follow-up was 5.4 years (range 2 to 22 years). No patients were lost to follow-up. Thirty-five patients (15%) were treated with irradiation alone, 27 (11%) with irradiation and adjuvant systemic therapy, 80 (34%) with mastectomy and irradiation, and 95 (40%) with combined mastectomy, irradiation, and systemic therapy. Local/regional control by treatment at 5 and 10 years, respectively, was 31% and 31% for irradiation alone, 47% and 47% for irradiation and systemic therapy, 80% and 80% for irradiation and mastectomy, and 93% and 78% for irradiation, mastectomy, and systemic therapy (p ⩽ .0001). Actuarial disease-free survival by treatment was 19% and 12% for irradiation alone, 25% and 18% for irradiation and systemic therapy, 34% and 20% for irradiation and mastectomy, and 41% and 31% for irradiation, mastectomy, and systemic therapy, at 5 and 10 years, respectively ( p = .0001). Patients given systemic therapy and/or irradiation prior to mastectomy had a better local/regional control and DFS and actuarial survival, although not achieving statistical significance ( p = 0.10). Of the triple modality group of patients, there were no chest wall failures with chest wall doses greater than 5040 cGy ( p = 0.3). There were 40237 (17%) grade 2 or greater treatment sequelae. The administration of chemotherapy significantly increased complications.

Thirty-three patients with optic glioma seen over a 30-year period were reviewed. Five patients (15%) had tumor confined to the optic nerve, 8 patients (24%) had optic nerve and chiasmal involvement, and the remaining 20 patients (61%) had invasion of contiguous structures as well as chiasmal involvement. Eleven patients (33%) had a history of neurofibromatosis. Two-thirds of the patients had either a biopsy or a partial resection of the tumor, with the remaining one-third being clinically diagnosed. All patients received irradiation to local fields. The median dose was 5040 cGy in 160 cGy fractions. Of patients alive at last follow-up, the median time of follow-up was 12.3 years. The 5-, 10-, and 15-year overall actuarial survivals were 94, 81, and 74%, respectively. Univariate and multivariate analysis were performed on the following clinical variables: extent of primary tumor, extent of surgery, dose of radiation, gender, race, age, and presence or absence of neurofibromatosis. Extension of the primary lesion to the optic chiasm and age less. than or equal to 15 years were the only two variables to have statistically significantly inferior 15-year progression free survivals by multivariate analysis. Eighteen (55%) patients had treatment related complications with most involving the pituitary gland. We conclude that postoperative radiotherapy is beneficial in patients with chiasmal involvement and those with incomplete resections. A minimum tumor dose of 4000 cGy is recommended.

Between 1979 and 1987, 76 women with 77 ductal carcinomas in-situ of the breast were evaluated by The Radiation Oncology Center after breast conservation surgery.Seventy breasts (91%) had tylectomy and irradiation and seven breasts (9%) had tylectomy alone. Median follow-up was 4.0 years, with a range of 2-10 years. Fifty patients (65%) had occult lesions discovered by mammography with a median mammographic size of 0.9 cm. The twenty-six patients with presenting symptoms had a median clinical tumor size of 1.95 cm. All patients had local excision of the primary tumor. Of 15 patients who had axillary dissections, one had nodal metastasis. Seventy breasts were irradiated. Seven patients refused radiotherapy.Overall 5-year actuarial survival was 99%; 5-year actuarial disease-free survival was 89%; the 5-year actuarial intramammary tumor control rate for irradiated patients was 93% vs. 57% for patients not irradiated (p0.001). Comedocarcinoma had a 5-year actuarial tumor control rate of 75%, 88% in the irradiated group as compared to 98% for all other histologic subtypes of ductal carcinoma in situ (p0.03). All six patients with local failure were successfully salvaged by further surgery. Multivariate analysis revealed significant factors in local control to be (a) radiotherapy, (b) comedocarcinoma histology, and (c) menopausal status.Although the number of patients treated is small, and follow-up time is limited, these early results support the contention that the treatment of ductal carcinoma in situ by excision and irradiation is an acceptable alternative to mastectomy. We urge caution in treating patients with the comedocarcinoma subtype and counsel these patients to have more treatment than excision alone.

Although prognostic variables for locoregional recurrence of breast cancer have been evaluated by univariate analysis, multifactorial analysis has not been previously performed. In the present study, survival following chest wall and/or regional lymphatic recurrence was determined in 230 patients with locoregionally recurrent breast cancer without evidence of distant metastases treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology and affiliated hospitals. Multifactorial analysis demonstrated that the site of recurrences correlated most strongly with overall survival (p = 0.001). The 5-year actuarial overall survival was 44-49% for patients with isolated chest wall, axillary, and internal mammary lymph node recurrence. Patients with either supraclavicular, multiple lymphatic, or concomitant chest wall and lymphatic recurrence had an 21-24% 5-year overall survival. The 5-year disease-free survival was 28-37% for patients with chest wall, axillary, or internal mammary recurrences compared to 4-13% for those with supraclavicular, chest wall and lymphatic, or those with multiple sites of lymphatic recurrence. Disease-free interval from mastectomy to recurrence was also found to be a significant prognostic factor for overall survival (p = 0.005). Fifty percent of patients with a disease-free interval of at least 2 years survived 5 years following locoregional relapse, compared to 35% for those with disease-free interval of less than 2 years. In the subset of patients with small chest wall recurrences (excised or less than 3 cm) and a disease-free interval of at least 2 years, the 5-year overall and disease-free survivals were 67% and 54%, respectively. These results suggest that subsets of patients with locoregional recurrence of breast cancer can survive for long periods of time. The conventional wisdom that chest wall and/or regional nodal recurrence following mastectomy uniformly confers a dismal prognosis is not necessarily true.

The results of therapy are reported in 296 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 127 were treated with irradiation alone (5,500 to 7,000 cGy), 133 with preoperative radiotherapy (2,000 to 3,000 cGy) or were initially planned for preoperative irradiation but treated with radiotherapy alone, and 36 with postoperative irradiation (5,000 to 6,000 cGy). The operation in all but 4 patients consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. Actuarial 5-year no evidence of disease (NED) was as follows: survival rates for patients with T1 tumors, 76%; T2, 54%; T3, 45%; and T4, 20%. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better relapse-free survival (60% to 70% at 5 years) than those with large or fixed lymph nodes (30% to 40%). Primary tumor recurrence rate in the T1-T2 groups was about 20% in patients treated with irradiation and surgery and 30% for those treated with irradiation alone (difference not statistically significant), 30% in patients with stage T3 lesions in all treatment groups, and 33% in patients with T4 disease treated with surgery and postoperative irradiation compared to 52% with irradiation alone (p = 0.03). The overall recurrence rate in the neck was about 20% for the N0 patients, 25% for N1, and 30% for those with N2 and N3 cervical lymph nodes in the 4 treatment groups. The incidence of contralateral neck recurrences was about 8% with the various treatment modalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Three recent studies have investigated the influence of a positive family history (+FH) of breast cancer on the prognosis of DCIS patients treated by conservafive surgery end radiation therapy (CS+RT), with two studies showing a higher risk of locoregional relapse (LRR) in these patients (pts) and another showing no significant difference. Since three treatment strategies have been used for DCIS at our institotion, we evaluated the influence of +FH and young age on outcome by treatment method.

Seventy-nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty-five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft-tissue or adjacent organ invasion, referred to in composite as grave signs. The median follow-up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease-free survival for all patients was 76% at 2 years and 71% at 3 years. The locoregional control rate for all patients was 70%. This study demonstrates that there is no difference in local recurrence or disease-free survival, or time to recurrence relative to the status of the surgical margins, which may be a benefit of the postoperative radiation therapy. This study also demonstrates that there is an increase in the number of patients with grave signs with increasing nodal stage. The rate of neck recurrence in patients with grave signs was substantially higher (54%) than in patients without grave signs (8%), even though these patients also had positive lymph nodes.more » Interestingly, there was also a higher rate of local recurrence among patients who had grave signs. Patients receiving doses higher than 6000 cGy to the primary site had fewer local failures, although within each group of patients with positive or negative surgical margins the differences in survival were minimal.« less

Obe hundred fifty-seven patients with local-regional recurrence of breast cancer but without co-existing distant metastases were reviewed. The incidence of failure to control the local-regional recurrence was essentially the same whether the recurrence was treated with radiotherapy alone (62% ), surgery alone (76% ), or with a combination of the two (60 % ). A detailed analysis of the failures occurring in the patients treated with radiotherapy, with or without surgery, showed that most of the failures were because of a) inadequate doses of irradiation, b) the use of fields that were too small, and c) the lack of elective irradiation to the chest wall and supraclavicular fossa. Of the 100 patients with uncontrolled local-regional disease, 62% developed clinical symptoms that markedly impaired the quality of life. All of these symptoms were directly caused by the uncontrolled local-regional disease. Specific recommendations for the treatment of isolated local-regional recurrence are made.

An important aspect of evaluating treatments aimed at local tumor control is to assess the effect of local control on survival. A common approach to this problem is to compare all patients who have failed locally with those who have not using a logrank test. However, this method of analysis does not take into account the effect of time on a patient's local disease status. Since patients in the local failure group must survive long enough to fail, this group may be biased in favor of longer survival times. The Mantel-Byar extension of the logrank test avoids this source of bias by utilizing the data on time to local failure in defining the local control and local failure groups. In this paper, the application of this technique is illustrated using data from recurrent breast cancer patients and contrasted with the results obtained using the standard logrank test.

A retrospective analysis of 70 pediatric patients (less than 16 years of age) with histologically proven or presumed primary neoplasms of the thalamus, hypothalamus, and brainstem, treated with combined surgery and postoperative radiotherapy or radiotherapy alone at the Washington University Medical Center from January 1950 through December 1983, is reported. Overall survival for all patients at 5 and 10 years was 34.9% and 32.7%, respectively. Follow-up of the 22 surviving patients ranged from 3.0 to 20.0 years (median, 10.6 years). Statistical analysis of multiple prognostic factors was performed. Prognostic factors found by single variate analysis to significantly influence survival were primary site of disease, extent of surgery, race, cranial nerve paresis at diagnosis, and dose of radiation. Factors evaluated but found to be insignificant were age at diagnosis, duration of symptoms before diagnosis, sex, and volume irradiated. Multivariate analysis revealed that only total radiation dose and race were of prognostic significance.

Twenty-six out of a total of 49 patients who were treated for Wilms' tumor at the Mallinckrodt Institute of Radiology between January 1960 and December 1975 have survived at least five years. The median follow-up time is 153 months (12 years, 9 months). One girl, who received pelvic irradiation, has not reached puberty at age 14, but the other 25 patients are currently in good health and have no major complaints or functional impairments at present. Twenty-one patients have, however, developed some complication at some time since treatment. Serious side-effects requiring hospitalization included one case of pericarditis and one of esophageal varices secondary to portal hypertension. Both these patients, however, had advanced tumors requiring aggressive treatment and their complications should be seen in perspective. There has also been one case of temporary low grade renal failure and one of transient hypertension. More common complications were 14 instances of scoliosis (only three have had any symptoms, however), five of osseous hypoplasia, three of soft tissue hypoplasia, three of liver damage and three of lung damage. There was one case of osteochondroma within a radiotherapy field. The factors pertaining to these complications and the anticancer therapy which preceded them are discussed in detail. We conclude that, whereas structural changes following modern radiotherapy for Wilms' tumor are very common, severe dysfunctions are infrequent. Even more extended periods of observation will he required before the total number of abnormalities is ascertained. However, the striking observation from this study is the lack of late functional effects.

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.

This report is a retrospective analysis of 83 adults (greater than 16 years of age) with histologically proven or presumed primary neoplasms of the thalamus, hypothalamus, midbrain, pons, and medulla. Patients were treated with combined surgery and postoperative irradiation or with irradiation alone at the Washington University Medical Center (St. Louis, MO) from January 1950 through December 1984. Histologic analysis confirmed the diagnosis of tumor in 21, including nine with well-differentiated astrocytoma, four with astrocytoma with anaplasia, and eight with glioblastoma multiforme. Overall and disease-free survivals at 5 years were 28.7 and 23.2%, respectively. A statistical analysis was performed to ascertain the prognostic importance of the following variables: age, race, gender, duration of symptoms, cranial nerve paresis, primary site, extent of surgery, histology, and irradiation dose. The only factor identified by univariate analysis to be critical for survival was primary location of disease. Patients with supratentorial (thalamus/hypothalamus, midbrain) tumors had a 10-year disease-free survival of 15.4% compared to 29.6% for those with infratentorial (pons, medulla) tumors (P = 0.07). Patients with lesions of the pons had a 5-year disease-free survival of 35.8% compared to 13.8% for those with tumors of the thalamus (P = 0.05). Increasing irradiation dose was not correlated with superior survival. Factors evaluated but established to be insignificant were age (P = 0.27), race (P = 0.63), gender (P = 0.27), duration of symptoms (P = 0.19), cranial nerve paresis (P = 0.71), histologic type (P = 0.16), and extent of surgery (P = 0.94). Follow-up for 13 surviving patients ranged from 2.6 to 28.7 (mean, 12.0) years. Neurologic deficits in surviving patients were absent in 15% (two of 13), mild in 62% (eight of 23), and moderate in 23% (three of 13). One case of brain radionecrosis was identified (6000 cGy, 200 cGy daily).

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.

Between 1949 and 1978, 119 children with the diagnosis of neuroblastoma or ganglioneuroblastoma were treated at the Washington University Medical Center. Of these, 50 (41%) were alive and disease-free 3 or more years after diagnosis. Important prognostic variables included stage of tumor (Evans staging), histology, age at diagnosis, and site of primary tumor. A stepwise logistic regression analysis of these data has shown that, in order of significance, stage, histology and age at diagnosis are independent prognostic variables. Sex of the patient and nodal status at diagnosis (where known) were not significant prognostic variables. No effects of individual treatment modalities could be detected. This study confirms the overwhelming influence of factors unrelated to treatment in determining the prognosis of neuroblastoma.

A retrospective review was undertaken of 129 patients with isolated local-regional recurrence of breast cancer following radical or modified radical mastectomy. The overall survival and disease-free survival for these patients five years from the time of local-regional recurrence was 36 and 13%, respectively. The clinical stage at initial diagnosis, the number of histologically positive nodes at mastectomy, menopausal status, and the location of the recurrence (chest wall vs. nodal) were all found to have no significant effect on survival or disease-free survival. On the other hand, the number of recurrences, the size of the largest recurrence, and the time interval between mastectomy and recurrence (disease-free interval) had definite prognostic significance. A single recurrence, the size of the largest recurrence being less than or equal to 1 cm, and a disease-free interval of longer than 24 months predicted a good prognosis; on the other hand, multiple recurrences, the size of the largest recurrence being greater than 1 cm, and a disease-free interval of less than 24 months predicted a bad prognosis. Eighty-one percent of the patients ultimately developed distant metastases; the incidence of distant metastases was the same for patients with factors predicting a good prognosis as it was for those with factors predicting a bad prognosis. The time to appearance of distant metastases, however, was significantly longer in the former group of patients than in the latter. The information from this analysis should be useful in designing future clinical trials involving patients with isolated local-regional recurrence of breast cancer.

A retrospective analysis was performed on the clinical course of all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, Missouri. Of 212 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (XRT), 121 began immediate post-operative XRT (2-6 weeks) and 20 received XRT following surgical failure. Several sub-groups of adenomas were identified and analyzed, including secreting versus non-secreting adenomas (33.0% secreting) and by clinical syndrome; 27% with amenorrhea/galactorrhea, 18.4% acromegalic, Cushing's disease in 6.1% and 3.3% with Nelson's syndrome. The median follow-up time from the data of diagnosis for those patients alive at the time of last follow-up was 11.9 years (range 3.0 to 30.0 years). Actuarial overall and disease-free survival was analyzed up to 25 years. The 10-year overall and disease-free survival was 77.8 and 75.3% for those patients treated with XRT alone, 86.4 and 87.2% for those treated with immediate post-operative XRT and 100.0 and 87.5% for those who were irradiated after surgical failure. Complications related directly to XRT occurred in only five patients. One patient had documented central nervous system radionecrosis, two had visual complications, and tumor necrosis with hemorrhage occurred in the other two patients. In conclusion, overall survival for all patients did not significantly differ from an age, sex and race matched population. Control of local disease was greater for those patients receiving surgery and post-operative XRT than for those receiving XRT only. XRT salvage of surgical failures was possible. Treatment with XRT results in a low complication rate.

A retrospective review was performed of 11 children and adolescents (less than 19 years of age) with diagnosed pituitary adenomas. The patients were treated with subtotal resection and postoperative irradiation (S + R) or with irradiation alone (RT) at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, from January 1958 through December 1982. Patient conditions at diagnosis were acromegaly in one, Nelson's syndrome in one, prolactinoma in three, chromophobe adenoma in three, and Cushing's disease in three. Median follow-up was 15.6 years (range 6.3-29.5 years). Only two patients have had failure: one at 8.6 years and the other at 20.7 years following treatment. All four patients with visual field (VF) defects at diagnosis underwent S + R, with only one developing recurrent disease. The remaining seven patients, who did not have VF defects, received RT only, and there has been one failure in this group. None have suffered long-term visual complications. All have been able to continue school and/or work. Three of eight females have borne children. Hypopituitarism requiring medication occurred in all who received S + R and in four of seven who received RT only.

A review of 1048 patients with cancer of the cervix treated with radiation, either alone or combined with surgery, disclosed 32 cases of second primary malignancies occurring from 1 to 16 years subsequent to treatment. Using the person years approach, the incidence rate of second primaries was 5.49 per 1000 person years, which is not significantly different from population based rates. The anatomic locations of the new malignancies and the times from treatment of the cervix cancer to diagnosis of a new primary are presented; the possible carcinogenic effects of radiation are discussed. In this group of patients, it was concluded that under the period of observation irradiation administered at therapeutic doses did not increase the probability of second malignancy in the pelvis or at other sites.

One hundred forty-seven patients with non-inflammatory, Stage III and IV breast cancer were treated with irradiation alone (54 patients) or with a combination of irradiation and mastectomy (93 patients). In the T 3 category, the local failure rate was 45% ( 5 11 ) for the irradiation alone patients vs 12% ( 3 25 ) for the irradiation plus surgery patients; in the T 4 category these figures were 65% ( 28 43 ) vs 13% ( 9 68 ), respectively. Corresponding local failure rates by size of primary tumor were 50% ( 2 4 ) vs 15% ( 5 29 ) for tumors 0–5 cm, 43% ( 9 21 ) vs 14% ( 6 45 ) for 5–8 cm tumors, and 75% ( 22 29 ) vs 54% ( 1 20 ) for tumors ≥8 cm. The rates of regional failure for the two treatment methods were compared according to N stage; they were 9% ( 2 23 ) for irradiation alone vs 11% ( 8 76 ) for irradiation plus surgery in the N 0–1 category, and 58% ( 18 31 ) vs 18% ( 3 17 ), respectively, for the N 2–3 category. A dose response analysis for patients with tumors greater than 5 cm treated with irradiation alone did not show a decrease in local failure rate with increasing total tumor dose over a range of 4000 to 7000 rad, suggesting that doses in this range are too low for these large tumors. Since a significant late complication rate has been reported with doses higher than this, patients with non-inflammatory, but large (>5 cm) tumors, should be treated with a combination of surgery and irradiation whenever possible to achieve maximum local-regional control with a minimum probability of complications. In 36 patients with inflammatory carcinoma, the rates of local and regional failure were 52% ( 15 29 ) and 38% ( 11 29 ), respectively, for patients treated with irradiation alone, and 14% ( 1 7 ) and 29% ( 2 7 ), respectively, for patients receiving irradiation plus surgery. Since none of these differences were statistically significant, one cannot conclude that surgery should necessarily play a role in the treatment of inflammatory carcinoma.

A multivariate analysis of prognostic variables was performed on a retrospective review of 136 patients with presumed or histologically proven primary lesions of the thalamus and brainstem treated by combined surgery and post-operative irradiation or by irradiation alone from January 1950 through December 1983. Overall survival for all patients at 5 and 10 years was 34.4 and 27.8%, respectively. Follow-up of 33 living patients ranged from 3 to 22 years. Prognostic variables analyzed by univariate analysis and found to be of significance (p less than 0.05) were race, duration of symptoms, extent of surgery (i.e. subtotal excision), and dose of irradiation. Further evaluation by Cox regression analysis revealed these same factors to be of prognostic significance (p less than 0.05). It is of importance to note that age and tumor site were not significant prognostic variables in the multivariate analysis but were significant by univariate analysis. The 5-year overall survival for patients with thalamic tumors was 59.5 and 20.9% for children and adults, respectively (p = 0.006). The 5-year overall survival for patients with pontine lesions was 46.6 and 16.0% for adults and children, respectively (p = 0.01). Only one patient was known to have expired due to a complication of therapy. Neurologic deficits and functional ability was normal or mild in 57.6% of the surviving patients.

High-dose, large volume local-regional irradiation has been shown to be necessary in patients with local-regional recurrence of breast cancer without coexisting distant metastases; however, no studies exist that deal with the dose and volume of local-regional irradiation required for patients with both local-regional recurrence and distant metastases. This report is an analysis of 68 patients who presented with previously untreated local-regional recurrence and coexisting distant metastases. Thirty-five of these patients were treated with local-regional irradiation and systemic therapy; the remaining 33 patients received systemic therapy only. An analysis of the dose and volume in the 35 irradiated patients showed that if the irradiation was inadequate (dose less than 4500 rad and volume not large enough to encompass the entire involved site), the incidence of uncontrolled local-regional disease for the duration of life was 79%, similar to the 64% rate of uncontrolled local-regional disease in the 33 patients not receiving local-regional irradiation. On the other hand, if the dose to the recurrence was at least 4500 rad and if the field was large enough to encompass the entire site containing the recurrence, the incidence of uncontrolled local-regional disease for the duration of life was only 27%. The present study also suggestsmore » that local-regional irradiation may be indicated in patients with asymptomatic as well as symptomatic local-regional disease. In patients with distant metastases and initially asymptomatic local-regional disease, adequate irradiation resulted in a lower incidence of ultimate local-regional symptoms when compared to similar patients who were treated with inadequate or no local-regional irradiation. This difference was not quite statistically significant because of the small number of patients in each group.« less

A retrospective analysis was performed of 51 patients with locoregional recurrence of endometrial carcinoma, treated by radiotherapy between 1959 and 1986. There were 17 patients (33%) with isolated vaginal recurrence, 12 patients (24%) with vaginal recurrence with pelvic extension, 7 patients (14%) with pelvic recurrence only, and 15 patients (29%) with simultaneous locoregional and distant failure. Eighty percent of the recurrences occurred within 3.5 years from primary treatment; time to relapse was shorter in patients with advanced-stage, high-grade malignancy at original diagnosis. Locoregional control was achieved in 18 patients (35%). Complete tumor regression in the vagina, irrespective of extravaginal pelvic disease status or distant metastasis, occurred in 28 of 34 patients with vaginal involvement (82%). The 5- and 10-year overall actuarial survivals for all patients were 18 and 12.5%, respectively. The 5- and 10-year progression-free survivals of patients with isolated vaginal recurrences were 40% and 29%, respectively; the 5-year progression-free survival of patients with vaginal recurrence with pelvic extension was 20%. There were no survivors beyond 1.5 years among patients with pelvic recurrence (p = 0.02). All patients with simultaneous locoregional and distant failure were dead by 3.5 years. Stage at original diagnosis, time to relapse from primary treatment, histologic pattern, and grade of malignancy were prognosticators of survival. Five patients (10%) developed a total of ten radiation-related sequelae.

From 1958 to 1985, 107 patients with a clinical and/or histopathologic diagnosis of non-metastatic inflammatory breast cancer received radiotherapy as all or part of initial treatment. Therapy included definitive irradiation alone in 31 patients, irradiation with mastectomy in 16 patients, irradiation and combination chemotherapy in 23 patients, and irradiation with chemotherapy and surgery in 37 patients. Survivors have a median follow-up of 30 months. Overall median relapse-free survival (RFS) was 12 months (12% at 5 years). Local control and relapse-free survival were significantly improved for patients receiving surgery as part of initial treatment: 19% (10/52) of operated patients experienced locoregional failure vs. 70% (37/53) not operated (p less than 0.0001). The median overall actuarial survival was 24 months (17% at 5 years). Patients who received surgery showed improved survival (44 months vs. 18 months median; 37% vs. 7% at 5 years; p = 0.0004). Chemotherapy also was associated with improved relapse-free survival (18 months vs. 8 months median; 20% vs. 5% at 5 years; p = 0.02) and actuarial survival (32 months vs. 17 months median; 23% vs. 3% at 5 years; p less than 0.02). Patients treated with initial chemotherapy (usually 2-3 cycles of CAF), surgery, and postoperative irradiation followed by maintenance chemotherapy showed a 34 month median relapse-free survival (37% at 5 years RFS) and a 47 month median survival (48% at 5 years). Moderate to severe complications were seen in 25% of patients, the most frequent complication being fibrosis of the breast or chest wall. There were two fatalities secondary to Adriamycin-induced cardiomyopathy. This study suggests better local control, with fewer complications, when surgery and irradiation are combined with multiagent chemotherapy. Further prospective clinical trials are strongly recommended.

Prognostic factors and results of therapy were analyzed in a retrospective examination of 121 patients with pituitary adenomas treated with surgery and postoperative irradiation (RT) from January 1954 through December 1982 at the Radiation Oncology Center, Mallinckrodt Institute of Radiology. The 10-year overall and disease-free survival for all patients was 85.1 and 89.4%. The expected survival for an age-, gender-, and race-matched population was not significantly distinct at 85.3% (p = 0.72). Follow-up of 94 surviving patients ranged from 3.4 to 29.5 years (mean, 11.7). Statistical analysis was performed for multiple prognostic factors including age, race, gender, disease bulk, visual field symptoms, disease type, surgical approach, and irradiation dose and volume. The only prognostic variable identified by univariate analysis to significantly alter disease-free survival was irradiation dose. Patients receiving 5000-5400 cGy had a tumor control rate of 94.1% (64/68) compared to 85.0% (17/20) for 4000-4999 cGy, 75.0% (18/24) for 3000-3999 cGy, and 28.6% (2/7) for less than 3000 cGy (p = 0.000059). Factors evaluated but established to be insignificant were age, race, gender, disease bulk, visual field symptoms, disease type, surgical approach, and irradiated volume. The 10-year disease-free survival by classification was 93.3% for patients with amenorrhea/galactorrhea, 89.9% for non-functioning adenomas, and 76.4% for acromegaly (p = 0.21). Overall improvement in visual field defects subsequent to treatment occurred in 48.4% (44/91) of those with visual field defects before RT and was significantly correlated with RT dose. The median time to progression of disease was 10.2 years with the last failure occurring at 25 years following the fulfillment of RT. Severe complications related to RT were apparent in 1.7% (2/121). None were known to have endured brain radionecrosis. Serious surgical complications occurred in 9.9% (12/121).

Tumour response and control (freedom from local relapse) were compared in two non-randomized groups of patients with recurrences from carcinoma of the breast (95 per cent in the chest wall and 5 per cent in the axillary or supraclavicular lymph nodes) receiving treatment at the Mallinckrodt Institute of Radiology. One group, comprising 48 patients treated between March 1978 and December 1984, received varying doses of irradiation (2000-4000 cGy in fractions of 400 cGy every 72 h) followed by local microwave hyperthermia (41-43 degrees C, 30-60 min). Irradiation was usually delivered with electrons ranging from 9 to 16 MeV. Hyperthermia was administered with 915 MHz external microwaves. The second group of 116 patients, with lesions similar to those treated with hyperthermia and irradiation, were treated with irradiation alone between January 1964 and December 1984. Doses of irradiation ranged from 2000 to 6000 cGy, usually delivered in daily fractions of 200-300 cGy TD. Irradiation was administered with Cobalt-60, 4 MeV photons or electrons (9-13 MeV) and occasionally with superficial X-rays. Patients with lesions 1-3 cm in diameter treated with irradiation and hyperthermia exhibited a complete tumour response rate of 80 per cent (12/15) while patients receiving irradiation alone had a complete response rate of 33 per cent (P = 0.04, Fisher exact test, two tail). The complete response rate for tumours larger than 3 cm treated with irradiation and heat was 65 per cent (13/20) compared to 42 per cent (18/43) for lesions receiving irradiation alone (P = 0.1, Fisher exact test, two tail).(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-six out of a total of 49 patients who were treated for Wilms' tumor at the Mallinckrodt Institute of Radiology between January 1960 and December 1975 have survived at least five years. The median follow-up time is 153 months (12 years, 9 months). One girl, who received pelvic irradiation, has not reached puberty at age 14, but the other 25 patients are currently in good health and have no major complaints or functional impairments at present. Twenty-one patients have, however, developed some complication at some time since treatment. Serious side-effects requiring hospitalization included one case of pericarditis and one of esophageal varices secondary to portal hypertension. Both these patients, however, had advanced tumors requiring aggressive treatment and their complications should be seen in perspective. There has also been one case of temporary low grade renal failure and one of transient hypertension. More common complications were 14 instances of scoliosis (only three have had any symptoms, however), five of osseous hypoplasia, three of soft tissue hypoplasia, three of liver damage and three of lung damage. There was one case of osteochondroma within a radiotherapy field. The factors pertaining to these complications and the anticancer therapy which preceded them are discussed in detail. We conclude that, whereas structural changes following modern radiotherapy for Wilms' tumor are very common, severe dysfunctions are infrequent. Even more extended periods of observation will he required before the total number of abnormalities is ascertained. However, the striking observation from this study is the lack of late functional effects.