Organ preservation therapy in stage T1 and T2 carcinoma of the breast.
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Breast Neoplasms↗
Biomedical subjects
J R Simpson
Publications and source records attributed to J R Simpson.
Survival following breast-conserving surgery and irradiation or modified radical mastectomy in patients with invasive breast cancers with a maximum diameter of 1 cm.
The reported relapse-free survival for women with invasive breast cancers measuring no more than 10 mm in dimension ranges from 75% to 95%, with axillary status an important prognostic factor in most series. Further study of prognostic variables in this most favorable subset is notably limited. We retrospectively reviewed the records of 168 women with invasive breast cancers < or = 10 mm treated with either breast conserving surgery+axillary dissection (AXD) and radiation therapy, or mastectomy+AXD. The actuarial survival and survival free of distant metastases (DMFS) at 7 years was 95% and 97%, respectively. Location and size of the primary tumor were most important in predicting outcome, although statistical significance was not achieved. The 5-year distant metastases-free survival (DMFS) was 100% for central and inner quadrant tumors, compared to 97% in those with outer quadrant tumors, p = 0.18. The 5-year DMFS was 100%, 95%, and 98% for patients with cancers 2-5 mm, 6-9 mm, and 10 mm, respectively, p = 0.15. Status of the axillary lymph nodes, type of breast surgery, clinical tumor status (palpable vs. nonpalpable), age, menopausal status, histologic grade, systemic therapy, or histologic type were not found to have a significant impact on prognosis.
Adult↗
Carcinoma of the hard palate.
Thirteen patients with primary carcinoma of the hard palate were seen over an 18-year period at the Mallinckrodt Institute of Radiology. Nine patients had adenoid cystic carcinoma, three had squamous cell carcinoma, and one patient had mucoepidermoid carcinoma. The median tumor size was 3 cm3. The patients were clinically staged: T = 1, T2 = 5, T3 = 3, T4 = 4. All were N0M0. Ten patients underwent excision and postoperative irradiation. The remaining three patients were treated definitively with radiotherapy. The 10-year disease-free survival is 77% with an actuarial local control rate of 92%. Patients with negative surgical margins had an improved local control and disease-free survival. Duration of radiation therapy, total tumor dose or histology had no impact on outcome. We conclude that combined surgery and irradiation gives good 10-year local control and disease-free survival rates in patients with this disease.
Aged↗
Postoperative radiotherapy for malignant fibrous histiocytoma.
Between 1974 and 1989, 49 patients with histologically confirmed malignant fibrous histiocytoma received postoperative radiotherapy at the Mallinckrodt Institute of Radiology for primary (41) or recurrent (8) disease. Median age of the patients was 63 years, and the median follow-up period was 41 months. Patients were grouped according to the 1988 AJC staging classification: stage IA (one patient), stage IIA (4 patients), stage IIB (9 patients), stage IIIA (15 patients), stage IIIB (18 patients), and stage IVA (2 patients). Eight tumors (16%) were in the pelvis, 8 (16%) in the trunk, 4 (8%) in the head and neck, and 29 (60%) in the extremities. Primary surgical procedures included incisional biopsy (4 patients), excisional biopsy (19), narrow margin excision (14), wide local excision (9), and removal of the entire compartment (3). Based on pathology reports, the margins of resection were classified as positive in 23 (5 gross, 18 microscopic), 5 close, 11 negative, and 10 unknown. Patients were irradiated with shrinking field technique; the median radiation dose was 6000 cGy, with more than 95% of patients receiving at least 4500 cGy. In addition, seven patients received postoperative chemotherapy. The 5-year overall survival rate was 62%, disease-free survival 64%, local control 68%, and freedom-from-distant metastasis 85%. Thirteen patients had local recurrences, with greater than 75% recurring within 3 years. Sites of local recurrence were as follows: trunk (3), pelvis (3), lower extremities (4), and head and neck (3). There appears to be a correlation of local failure with positive surgical margin: of 23 patients with positive margins, 9 (39%) had local recurrences, whereas 1 of 11 patients (9%) with negative margins had local recurrence. Three of 13 patients with persistent or recurrent disease were salvaged by additional treatment, rendering ultimate local control in 80% (39/49). Thirty-four of 36 patients with local control obtained good to excellent function. Two patients were found to have grade 3 complications: 1 patient had edema of the extremity, and the other developed necrotic skin ulcer that was successfully treated with hyperbaric oxygen. Five patients developed distant metastases, with 80% occurring within 2 years. In summary, adequate but conservative surgery with postoperative radiotherapy for malignant fibrous histiocytoma can achieve local tumor control as well as preservation of functional limbs with acceptable morbidity in a large proportion of patients.
Adolescent↗
Carcinoma of the nasopharynx: factors affecting prognosis.
This is a retrospective analysis of 143 patients with histologically confirmed epidermoid carcinoma of the nasopharynx treated with definitive irradiation. Patients were treated with a combination of Cobalt-60, 4 to 6 MV X rays, and 18 to 25 MV X rays to the primary tumor and the upper necks, excluding the spinal cord at 4000 to 4500 cGy to total doses of 6000 to 7000 cGy. At 10 years the actuarial primary tumor failure rate was 15% in T1, 25% in T2, 33% in T3, and 60% in T4 lesions. The corresponding failure rate in the neck was 18% for N0, 14% for N1, and 33% for N2 and N3 lymphadenopathy. The incidence of distant metastasis was related to the stage of the cervical lymphadenopathy: 16% in patients with N0-N1 nodes compared with 40% in the N2-3 node group. The actuarial 10-year disease-free survival rate was 55% to 60% for T1-3N0-1 tumors, 45% for T1-3N2-3 tumors, 35% for T4N0-1, and 20% for T4N2-3 lesions. The overall 10-year survival rate was about 40% for patients with T1-2N0-1 tumors, 30% for those with T3 any N stage tumors, and only 10% for the patients with T4 lesions. Multivariate analysis showed that tumor stage and histological type, cranial nerve involvement, patient age, and doses of irradiation to the nasopharynx were significant prognostic factors for local/regional tumor control. Increasing doses of irradiation resulted in nasopharynx tumor control in 80% of the patients receiving 6600 to 7000 cGy and 100% of those receiving over 7000 cGy in the T1, T2, and T3 tumors. However, the tumor control rate did not rise above 55% even for doses over 7000 cGy in the T4 lesions. Local tumor control was higher in patients who had simulation (55/78 = 71%) compared with those on whom simulation was not performed (34/61 = 56%) (p = 0.10). Moreover, patients with more than 75% of the reviewed films judged as adequate had 69% primary tumor control (66/96) compared with 53% (23/43) for those with fewer than 75% adequate portal films (p = 0.07).
Carcinoma, Squamous Cell↗
Survival following locoregional recurrence of breast cancer: univariate and multivariate analysis.
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.
Adult↗
Clinical stage I endometrial cancer: prognostic factors for local control and distant metastasis and implications of the new FIGO surgical staging system.
A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) from January 1960 through December 1986. Most patients received a preoperative intracavitary insertion (3500-4000 mgh to the uterus and a 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 1-2 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when factors such as deep myometrial invasion were present. Occasionally patients were treated with a preoperative intracavitary insertion and preoperative external beam irradiation (2000 cGy whole pelvis). The 5-year progression-free survivals by FIGO (1988) surgical stage were 93% for IA, 90% for IB, and 91% for Stage IC. An analysis of multiple variables was performed to ascertain their prognostic significance. Factors that significantly affected the 5-year progression-free survivals by univariate analysis were grade (grade 1 = 95%, grade 2 = 88%, grade 3 = 73%; p less than 0.0001), histology (adenoacanthoma = 96%, clear cell = 89%, adenocarcinoma = 89%, papillary = 81%, adenosquamous = 80%; p = 0.04), lower uterine segment involvement (uninvolved = 89%, involved = 73%; p = 0.006), depth of myometrial invasion (no residual tumor = 91%, limited to the endometrium = 96%, less than 1/3 myometrial penetration = 92%, 1/3 - 2/3 = 100%, greater than 2/3 = 50%; p = 0.02), peritoneal cytology (negative = 92%, positive = 56%, p less than 0.0001), uterine serosal involvement (uninvolved = 89%, involved = 55%; p less than 0.0001), vascular space invasion (absent = 89%, present = 75%; p = 0.001), and the presence of extrauterine disease (absent = 90%, present = 64%; p less than 0.0001). A multivariate analysis of these prognostic variables showed that histological grade (p = 0.001), peritoneal cytology (p = 0.004), and uterine serosal involvement were prognostic for local failure and that peritoneal cytology (p less than 0.001), grade (p = 0.001), age (p = 0.002), and extrauterine disease (p = 0.02) were prognostic for the development of distant metastasis.
Brachytherapy↗
Locoregional recurrence of breast cancer: a retrospective comparison of irradiation alone versus irradiation and systemic therapy.
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.
Adult↗
Three-dimensional treatment planning considerations for prostate cancer.
Over 300 treatment plans for a total of eight disease sites based on 3-D treatment planning considerations utilizing serial CT delineated target volumes were generated by four institutions as part of an NCI supported contract to both assess the current state-of-the-art capabilities and point directions for future efforts. Two patients with stage C prostate cancer were evaluated with protocol plans which required treatment of the prostate to 70 Gy and the pelvic lymph nodes to 46 Gy. When full 3-D target definition and multiple beam arrangements were employed, all institutions were able to submit plans which scored higher on tumor coverage and had lower normal tissue complication scores compared to traditional plans. The 3-D plans using standard beam arrangements, however, were often rated as highly as the 3-D unconstrained plans due to the multiple beam arrangements already selected to optimize standard plans at most institutions. For this site, heterogeneity corrections, beam energy changes and changes in CT number did not substantially change plan scores.
Aged↗
Effects of treadmill exercise on weight cycling in female mice.
Weight cycling increases food efficiency and rate of weight regain. This study induced weight loss in adult female B6D2F1 mice via dietary energy restriction and exercise to determine whether the weight loss regimen influenced rate of weight regain. Four groups of animals were studied: RES, restricted (food restricted); EX, exercised (treadmill exercised); SC, sham control (treadmill exposure, not exercised); LC, lab chow control (appropriately aged control). Both EX and SC voluntarily reduced food intake to the level of the RES animals. The RES group showed increased food efficiency and rate of weight regain relative to the LC group; this effect was attenuated in both the EX and SC groups. These findings demonstrate that a) the cycling phenomenon occurs in mice, and b) stressors such as forced exercise or exposure to a novel environment can modify the pattern of food efficiency and rate of weight regain engendered by dietary restriction.
Animals↗
Impact of changes in housing condition on mouse natural killer cell activity.
Various psychosocial stressors, such as housing condition and rotation, have been reported to influence tumour growth. This study assessed the influence of housing condition and change in housing condition on natural killer (NK) cell activity, an important component of natural immune defense against cancer. Mice which were individually housed for four weeks did not differ from group-housed mice in NK cell cytolytic activity against tumour targets in vitro or in the frequency of NK cells in the spleen. Switching of housing condition (group to individual, individual to group) for one week did not change the splenic NK cytolytic capacity relative to mice which were not switched. The two groups of mice which experienced a change in housing condition were, however, significantly different from each other. These data suggest that an acute change in housing condition, rather than the housing condition per se, has differential effects on the capacity to kill tumours by NK cells.
Animals↗
Clinical stage I endometrial cancer: results of adjuvant irradiation and patterns of failure.
A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively from January 1960 through December 1986 with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). Most patients received a preoperative intracavitary insertion (2500-4000 mgh to the uterus with Heyman capsules and tandem and 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 6 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when deep myometrial invasion was present. Occasionally patients were treated with preoperative external beam irradiation (2000 cGy whole pelvis) and intracavitary insertion. The 5-year overall survival for all patients was 84.0% compared to an expected survival of 88.8%. The 5-year progression-free survivals were 92% for FIGO clinical Stage IA and 86% for stage IB (p = 0.12). The dose to the uterine fundus from the preoperative intracavitary insertion was found to have a significant correlation with progression-free survival in patients with grade 3 tumors. Those receiving less than 2500 mgh to the uterine cavity had a 48.9% 5-year progression-free survival compared to 62.7% for 2500-3500 mgh and 87.4% for those receiving greater than 3500 mgh. Analysis of sites of failure showed that less than 1% (7/858) failed in the pelvis alone, 3% (30/858) in the pelvis combined with distant sites, and 7% (60/858) developed distant metastasis only. The lateral pelvic sidewall was the most common site of failure within the pelvis (20/37) and intraperitoneal failures (28/90) and lung (21/90) were the most common sites of distant metastasis. The overall severe (grades 2, 3, and 4) complication rate was 2.7% (23/858).
Adenocarcinoma↗
Effects of organic matter on virus transport in unsaturated flow.
The effects of natural humic material and sewage sludge organic matter (SSOM) derived from primary treated sewage sludge on virus transport by unsaturated flow through soil columns were evaluated. Bacteriophage MS-2 was applied to loamy fine sand columns 0.052 m in diameter and 1.05 m long. Virus concentrations in the influent and effluent were measured daily for 7 to 9 days. In the first experiment, virus transport through two fresh soil columns was compared with that through a column previously leached with more than four pore volumes (T) of well water. The soil water organic matter concentrations in the leachate of the fresh soil declined with time. Relative virus concentrations (C/Co) from one fresh soil column reached 0.82 in 0.9 T and then declined to 0.51 by 2.1 T. The other fresh soil column reached and maintained a steady-state relative virus concentration [(C/Co)s] of 0.47 from 1.5 to 2.5 T. The leached column reached and maintained a (C/Co)s of 0.05. Concentrations measured at 0.2-, 0.4-, 0.8-, and 1.05-m depths indicated that most virus particles were removed in the surface 0.2 m. In the second experiment, one leached column was pretreated with SSOM derived from primary treated sewage sludge and the other leached column was untreated. SSOM concentrations declined with depth. A suspension of virus and SSOM in well water was applied to both columns. Although the (C/Co)s values were similar (0.41 for the pretreated column and 0.47 for the untreated column), breakthrough was delayed for the untreated column. Both natural humic material and sewage sludge-derived SSOM increased the unsaturated-flow transport of MS-2.
Adsorption↗
Supraglottic carcinoma: impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease.
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. 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.
Adult↗
Use of an enzyme-linked immunosorbent assay to estimate prevalence of paratuberculosis in cattle of Florida.
A survey was conducted from 1986 through 1987, for which an ELISA was used to obtain information on the prevalence of Mycobacterium paratuberculosis infection in cattle of Florida. Results revealed prevalence of 8.6% in beef cattle and 17.1% in dairy cattle. In beef and dairy cattle, prevalence increased with increasing herd size. It was concluded that ELISA-detectable circulating antibodies to M paratuberculosis are widespread in cattle of Florida.
Animals↗
Isolated local-regional recurrence of breast cancer following mastectomy: radiotherapeutic management.
Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment. Although the majority of patients with local and/or regional recurrence of breast cancer will eventually develop distant metastases and succumb to their disease, a significant percentage will live 5 years. Therefore, aggressive radiotherapy should be used to provide optimal local-regional control.(ABSTRACT TRUNCATED AT 400 WORDS)
Breast Neoplasms↗
Cervical metastases from unknown primaries: radiotherapeutic management and appearance of subsequent primaries.
Between 1964 and 1986, 72 patients who presented with squamous or undifferentiated metastatic carcinoma to neck nodes, where the primary tumor could not be found by standard clinical procedures, were treated at the Mallinckrodt Institute of Radiology. These cases were managed in the following manner: biopsy and radiotherapy in 46 out of 72 patients, radiotherapy (RT) and a planned neck dissection in 14 out of 72, and neck dissection after failure to achieve a complete response (CR) with RT in 12 out of 72. Minimum follow-up was 2 years. The initial CR rates for stages N1, N2a, N2b, N3a, and N3b were 83%, 93%, 61%, 50%, and 33%, respectively. The long-term neck tumor control for the same stages was 83%, 71%, 67%, 44%, and 50%, respectively. One patient had soft tissue necrosis and two had carotid artery ruptures, one of which left no symptomatic sequelae. Twenty-one out of 72 patients developed subsequent primary tumor. Only one of these patients survived. This incidence was not affected significantly by prophylactic treatment of the mucosal areas except in patients with bilateral neck nodes, undifferentiated or poorly differentiated histologies, and/or posterior cervical node involvement. A multivariate analysis showed that prognosticators of an improved disease-free survival were: a complete clearance of tumor by the end of radiotherapy (p less than 0.0009) and no appearance of a subsequent primary tumor (p = 0.035). The only factor that correlated with an increased loco-regional control was having a complete response by the end of radiotherapy (p less than 0.00009). The recommended management and possible ways of preventing the appearance of subsequent primaries will be discussed.
Adult↗
Juvenile nasopharyngeal angiofibroma: efficacy of radiation therapy.
From 1962 to 1984, 13 patients with juvenile nasopharyngeal angiofibroma (JNA) were treated with megavoltage radiation therapy. Follow-up ranged from 40 to 255 months (median, 136 months). Two patients received radiation therapy as the initial treatment; the other 11 patients had undergone unsuccessful previous surgical treatment (median, three resections). Gross tumor was evident at the start of radiation therapy in seven patients, and orbital, sphenoid sinus, or intracranial extension was noted in eight of 13 (62%). Doses ranged from 3,600 to 5,200 cGy (median, 4,800 cGy in daily fractions of 180-200 cGy). Tumor was controlled in 11 patients (85%) after irradiation. Two patients were treated with embolization for residual mass; both remained asymptomatic and without evidence of tumor 134 and 83 months after embolization, respectively. With the exception of xerostomia and caries, no significant chronic morbidity was seen. This review and other studies demonstrate that megavoltage radiation therapy is an effective and appropriate treatment for advanced and recurrent JNA; its routine use for early tumors remains controversial.
Adolescent↗