Molecular predictive factors for local recurrence and distant metastasis of breast cancer after lumpectomy with postoperative radiation therapy.

To determine the risk factors associated with the recurrence and metastasis of breast cancer after lumpectomy with postoperative radiation therapy, 112 cases were studied who had been treated during a period of 11 years at the University of Florida Health Science Center/Jacksonville. The patients were evaluated for their age, race, and clinical stage, as well as the tumor grade, stage, histological type, and node involvement. Among these cases, four (4%) recurred locally within a year of treatment; 10 (9%) cases presented with distant metastasis within three years. No obvious clinical risk factors were identified for local recurrence; however, positive-node status seemed to be associated with distant metastasis. The primary tumors of these cases were then studied using immunohistochemical staining to evaluate the potential prognostic value of tumor markers such as estrogen receptor (ER), progesterone receptor (PR), tumor suppressor gene p53, HER-2/neu oncogene, and multi-drug resistance gene (MDR). The expression of p53 was associated with all local recurrence cases as well as 50% of those who had metastasis. The expression of MDR was observed in 80% of the distant metastatic cases. This preliminary result may warrant further studies on larger number of cases to assess the predictive value of p53 and MDR in the outcome of breast cancers in patients treated with postoperative radiation therapy.

1;19 translocation in human meningioma.

BACKGROUND: Loss of chromosome 22 represents the most common chromosome abnormality (70%) in meningiomas. The remainder (30%) have a normal karyotype. Not only are the structural changes rare, they also occur simultaneously with various chromosome losses. METHODS: The authors identified and studied the meningiomas of two patients with standard tumor cell culture technique and chromosome preparation. RESULTS: Twenty karyotypes from each meningioma had a 46 modal chromosome number with t(1;19) (q21;p13) in all cells. CONCLUSIONS: The sole change of the (1;19) translocation in meningioma, without any other changes such as chromosome loss, as shown in this study, is unique and has never been reported before in the literature, to the knowledge of the authors. Additional study is needed to learn more about the rate of occurrence and the significant impact on meningeal tumor genesis.

Lipoma of cervical spinal cord and posterior fossa. Case report.

A case is reported of cervical spinal cord lipoma with extension into the posterior fossa and a leading symptom of apnea. A C1-C7 laminectomy and debulking of the medullary portion of the lipoma were performed with good results. The apneic spells were completely resolved. Intraspinal lipoma with posterior fossa extension is a rare condition and requires surgical intervention to relieve symptoms.

Fine needle aspiration cytology of papillary endometrioid carcinoma of the prostate. The grooved nucleus as a cytologic marker.

The fine needle aspiration (FNA) cytologic findings of an endometrioid carcinoma of the prostate are presented, along with the histologic, immunohistochemical and endoscopic features. Cystoscopy of an elderly male patient with hematuria and symptoms of bladder outlet obstruction showed the delicate papillary growths at the verumontanum that are characteristic of this lesion. Transrectal FNA of the prostate produced samples that included clusters of malignant cells with crowding and overlapping of hyperchromatic nuclei containing prominent nucleoli and a loss of polarization and cohesion. Many of the groups of tumor cells suggested papillary structures. A novel finding in the aspirate was a grooved nucleus in 10% of the tumor cells. Immunohistochemical staining of biopsy sections of the papillary growths for prostate-specific antigen was strongly positive. It is important to recognize this variant of prostatic carcinoma since its behavior and response to therapy are not yet established.

Malignant fibrous histiocytoma of the gingiva. A clinicopathological study.

A case is reported of malignant fibrous histiocytoma (MFH) of the gingiva. The 65-year-old female presented with a fast-growing mass originating from the left lower gingiva. The tumor measured 15 cm in diameter, occupying the entire oral cavity, protruding outside, and causing a mechanical airway obstruction. It appeared to respond to a 1000 rad single dose of preoperative radiation but recurred soon after composite resection with mandibulectomy, even though surgical margins were reportedly free from microscopic invasion. The patient expired from massive lung metastasis in spite of appreciable local response from treatment. This supports the thesis that MFH is a malignant disease and behaves like any soft-tissue sarcoma, which must be treated aggressively by a combined modality of surgery, radiation, and perhaps chemotherapy.

Long-term survival of lung cancer with brain metastasis.

Two patients presented with adenocarcinoma of the lung and subsequently brain metastasis. Lobectomies were performed initially. One patient had a lung recurrence and was treated effectively by irradiation, the other had primary lung cancer controlled by surgery. Solitary brain metastases developed in both of them and was surgically removed. They were given postoperative radiation to the brain. Both survived, one more than five years and the other more than four years. They are women in their early 40s and 50s and are in good general condition. Contrary to the accepted method of treatment for patients with brain metastasis, which is usually palliation, surgical treatment followed by radiation could achieve the most rewarding results.

Radiation therapy for transitional cell bladder carcinoma. A ten-year experience.

From 1969 to 1979, 185 patients with transitional cell bladder carcinoma were curatively irradiated; 147 were treated with radiation alone (RT) and 38 received a combined radiation + surgery (RT + S). At presentation, 40 percent of the patients had obstructive uropathy which yielded a much lower five-year survival (18%) than when it was absent (50%). The overall five-year disease-free survival was 30 percent and 53 percent for patients treated with radical RT and RT + S, respectively. Among patients subjected to preoperative irradiation, downstaging was seen in 40 percent of postsurgical specimens, with 27 percent of the specimens showing no evidence of tumor; these patients had excellent survival. Severe complications were seen in 3 percent, 10 percent, and 27 percent of patients in the radical RT, RT + S, and radical RT + salvage cystectomy groups. Survival results, pelvic controls, and patterns of failure are presented.

A therapeutic approach to primary adenocarcinoma of the cervix.

Retrospective study of 97 patients with primary adenocarcinoma of the uterine cervix was undertaken to evaluate the efficacy of two treatment methods, radiation alone and radiation plus surgery. Of 31 Stage I patients, 16 were treated with radiation alone and 15 with combined radiation plus surgery. There was no difference in 5-year disease-free survival of Stage I patients treated by either method. Of 44 Stage II patients, 30 were treated with radiation alone with 54% survival rate; while 14 were treated with a combined approach, with 86% survival rate. It is apparent from the results of this study that surgery in conjunction with radiation showed a significant improved survival rate from 54% to 86% in Stage II disease. Factors influencing the prognosis appear to be tumor volume, uterine size, and tumor grade. Furthermore, these data suggest that early primary adenocarcinoma of the cervix (Stage I, lesion smaller than 4 cm) can be treated effectively by radiation alone or radical hysterectomy with comparable results. Tumors larger than 4 cm, Stage II or beyond disease, uterine enlargement, a high-grade tumor or barrel-shaped lesion, would necessitate a combined therapy to improve the cure rate.

A therapeutic approach to early vocal cord carcinoma.

One hundred and twenty patients with early glottic carcinoma received radiation therapy at the University of Maryland Hospital from 1959 to 1977. The radiation dose ranged from 55 Gy in 4 weeks for small T1a lesions to 65 Gy in 61/2 weeks for T2 lesions. The local control rates by irradiation alone for stages T1a, T1b, and T2 were 92, 91 and 88 per cent, respectively, while 5-year determinate disease-free survival rates were 96 per cent for stage I disease and 88 per cent for stage II disease. Most of the local failures were salvaged by surgery, with a low complication rate. Regional metastases were uncommon, and occurred in 7 per cent in stage I and in 6 per cent in stage II disease. Factors increasing the risk of failures appeared to be bulky tumor, anterior commissure involvement and subglottic extension.

Radiation treatment of primary carcinoma of the vagina. Patterns of failures after definitive therapy.

Patterns of failures after definitive radiation therapy were analyzed in 88 patients with primary carcinoma of the vagina treated between 1957 and 1975. The majority of the local failures in early stages of the disease (I, II and a few III) were due to inadequate treatment either by external beam therapy or brachytherapy. In some cases the inadequate treatments were unavoidable (previous radiation treatment) and in a few they were due to poor brachytherapy technique. Distant failures are still a problem and need to be given further attention.

Retreatment of very late recurrent invasive squamous cell carcinoma of the cervix with irradiation. II. Criteria for patients' selection to achieve the success.

Very late recurrent invasive squamous cell carcinoma of the cervix (over 10 years) after successful initial radiation treatment is a very rare occurrence (approximately 0.5%). Even though the treatment of choice has been radical surgery, there are a number of patients in whom surgery was regarded as undesirable. Ten such patients were reirradiated for these late recurrences after the full course of irradiation some 10 or more years ago. Six patients (six of ten) survived disease-free several years, while the remainder experienced relief of their symptoms. Factors determining success and failure are: (1) the extent of the recurrence (clinical stage); (2) the degree of tumor necrosis; (3) status of normal surrounding tissues; and (4) radiation treatment and doses, integration and individualization of the external beam and brachytherapy. Criteria for patient selection and treatment technique are discussed.

Radiation treatment of recurrent carcinoma of the vulva.

Recurrent vulvar cancer after surgical treatment carries a poor prognosis and poses a clinical therapeutic problem. Retrospective analysis of 21 recurrent vulvar cancers treated by radiation alone over 20 years (1958-1977) is presented. Highly individualized interstitial brachytherapy was used alone in some selected cases and combined with external beam therapy in most cases. The results showed that limited disease in the introitus and introitus involving the vagina have the best prognosis (6/6; 100%). Small groin node has a good chance for cure (2/4; 50%), while all extensive recurrences have the worse prognosis as expected. Factors responsible for the success of radiation treatment appear to include size and depth of the recurrence (5 cm or less lesion has a high chance for cure); groin node (less than or equal to 2 cm has good prognosis); perineal skin involvement (the lesser, the better); degree of tumor tissue necrosis (the lesser, the better); and radiation dose (5500-8500 rad). Integration of the external beam and brachytherapy and individualization with good planning are essential to achieve a better cure rate. Attempts were made to recommend a criteria for patient selection for cure and method of treatment as well as a technical aspect of the treatment.

Radiation management of carcinoma of the tonsillar region.

This is a retrospective analysis of 185 patients with squamous cell carcinoma of the tonsillar region treated at the Department of Radiation Oncology, University of Maryland Hospital from 1956 to 1977. All patients were treated by one of the following: (1) external beam therapy alone; or (2) combined external beam and interstitial brachytherapy. Five-year disease-free survivals, for early Stages (I and II), are 100% and 73%, comparable to the other series published in the literature. However, in advanced Stages III and IV, survival data showed 52% and 21%, respectively, 5-year disease-free survival better than any other reports. It is thought that the special interest of the authors in interstitial brachytherapy and a well-integrated plan of external beam and brachytherapy is responsible for this success. The local control rate for T1, T2, T3, and T4 was 94%, 88%, 62%, and 19%, respectively, with the overall regional control rate of 83%. The prognostic factors appear to be related to the T-factor, N-factor, radiation dose, and method of treatment given, and the degree of tongue involvement. The detailed analysis of survivals and failures in the light of dosimetric study is presented along with some example cases of interstitial brachytherapy.

Radiation therapy in primary carcinoma of the female urethra. II. An update on results.

Analysis of 21 patients with primary carcinoma of the female urethra who were treated by radiation only, from 1961 to 1980, is presented. Of 21 patients studied, 14 were treated for curative intent, 6 for palliation, and 1 patient did not finish the treatment as planned. For the curative group, radiation treatment was highly individualized and integrated with a special interest in brachytherapy. The authors were able to obtain excellent local control and subsequent 5-year-disease-free survival in Stage I, II, IIIA, IIIB, IIIC, and IV. The overall local control was 11 of 14 (78%) while achieving 77% 5-year disease-free survival. The bladder neck involvement continues to be a therapeutic problem and represents the only failure site. Factors responsible for the prognosis of this cancer are the extent of the cancer (clinical stage), location, individualization, and integration of the external beam and brachytherapy. Involvement of the vulva or vagina did not alter the good outcome, but involvement of the bladder neck, bladder, parametrium, and inguinal node represented a poor prognosis. Palliative irradiation treatment for those whose diseases were beyond cure can only offer a short-term, symptom-free result in 70% (5 of 7) of cases treated. No major complications occurred as a consequence of radiation treatment. Sample cases, particularly with brachytherapy and dosimetric analysis, are discussed.

Carcinoma of the floor of the mouth: a 20-year experience.

From 1955 to 1975, 116 patients with squamous cell carcinoma of the floor of the mouth were primarily treated by irradiation in the Department of Radiation Oncology, University of Maryland at Baltimore. Of these, 93 evaluable patients yielded loco-regional control rates of 83, 85, 42 and 21% for Stages I-IV, respectively. A palisading technique of radium needle implants was used, either alone or combined with external beam therapy, for early tumors (Stages I-II). Similar control rates were achieved by these two techniques: 13/14 for interstitial irradiation alone and 16/24 for combined interstitial and external irradiation. In selected early cases (Stages I-II), errors in staging were minimized by the systematic use of a needle biopsy of the submaxillary triangle for suspicious submaxillary swellings. Patients with early lesions and truly negative nodes (N0) only received irradiation to the primary tumor bed. No subsequent nodal neck failures have occurred in 13 of such patients. The overall complication rate for the entire series was 17% with only 8 patients requiring surgery. No differences in complication rates were found among the treatment modalities employed. The distribution of lymph nodal involvement by anatomical level, correlation of histological differentiation or tumor aggressiveness at presentation, the dosimetric analysis of the palisading interstitial technique, the spread and failure patterns and other observations are discussed.

Radiation management of squamous cell carcinoma of the bladder.

This is a retrospective analysis of 52 patients with squamous cell carcinoma of the bladder treated by irradiation between 1958 and 1978. There were 28 males and 24 females with hematuria being the leading symptom. At the time of initial presentation, 2 patients were evaluated to be stage B1, 34 patients to be B2C and 16 patients stage D. Nineteen patients were treated by preoperative irradiation (50 Gy/5 weeks) plus cystectomy and 33 patients were treated by irradiation alone (60-65 Gy/6-6 1/2 weeks). From our study, it appears that in stage B2C , irradiation plus cystectomy offered a better disease-free survival (40%) than irradiation alone (16%). Local failures occurred less frequently in the group treated by preoperative irradiation and surgery than those treated by irradiation alone. However, the majority of failures occurring in the preoperative group were distant failures. Factors determining the success and failures appear to include: stage of the disease, type of treatment, tumor size, degree of tumor necrosis, depth of muscle involvement, and tumor grade. It is suggested that the treatment of choice for this disease be a combined approach--preoperative irradiation and cystectomy whenever possible to minimize the loco-regional failures. Chemotherapeutic agents or radiation sensitizers combined with radiation should be further studied to minimize the distant metastases and loco-regional failures in most advanced inoperable squamous cell carcinoma of the bladder.

Radium needles implant in the treatment of extensive vaginal involvement from cervical carcinoma. A dosimetry appraisal.

An appraisal of the dosimetry of a modified brachytherapy approach is presented for improving the local control of extensive vaginal involvement from carcinoma of the cervix. This approach incorporates radium needles implant to the vaginal disease in conjunction with the usual routine intracavitary radium application. The aim of the interstitial implant is specifically to supplement the dose to the vaginal disease from the intracavitary application. Our procedure for accomplishing this boost in the dose to the vagina depends on the location, extent and thickness of the vaginal lesion following external beam irradiation of the whole pelvis. An increase of greater than 50 per cent in the dose to the vaginal disease is gained by this combination intracavitary/implant approach which has been used in a variety of cases covering virtually all pertinent stages of cervical carcinoma. Discussion of the dosimetry of example cases is presented to demonstrate the value of combining interstitial and intracavitary therapy for this specific clinical application.

Radiation management of advanced nasopharyngeal cancer.

During the period from 1957-1976, 70 patients with advanced malignant tumors of nasopharynx were treated by irradiation in the Department of Radiation Therapy, University of Maryland Hospital. Forty-nine patients were treated with curative intent and 21 patients with palliative purpose. Of 49 patients treated for cure, 22 (45%) survived disease-free for at least 5 years. Local control was achieved best (92%) by combined treatment, external beam and brachytherapy. Factors responsible for local control and disease-free survival, appear to be related to clinical staging (primary and nodal disease), cell types and treatment used. In spite of aggressive radiation treatment for advanced cases (Stages III and IV), distant disease is still a major problem and will necessitate further trial by combined chemotherapeutic treatment with irradiation. This article highlights the results and failures of the technique of the irradiation, both external and brachytherapy. It is suggested that aggressive radiation treatment using a combined approach (external beam and brachytherapy, whenever possible) be done in all cases for cure. Palliative treatment can only offer a short-term symptom-free status in 72% of all cases treated.

Adenocarcinoma arising in female urethral diverticulum.

Cancer arising from a female urethral diverticulum is rare, and because of its rarity, a review of the medical literature reveals significant nonuniformity in its management. We report an additional 2 cases of this disease, one of which has an even rarer feature of being mucin-producing. The management of our 2 cases is presented in detail and in line with the management of female urethral cancer. From our extensive literature search, diverticulectomy alone showed poor results with the highest rate of recurrence (67%). Extensive surgery, either in the form of cystourethrectomy or anterior exenteration, offered results comparable with those of combined therapy (diverticulectomy and full course of irradiation for early cases; preoperative irradiation followed by cystourethrectomy for late cases). Individualization of radiation treatment and cooperative effort between urologist and radiation oncologist are essential if best results are to be achieved.

Parametrial implant in Stage III B cancer of the cervix. III. A five-year study.

Since 1975, the Department of Radiation Therapy, University of Maryland Hospital initiated a policy of supplementing the dose to the affected parametrium by using radium needles implants in conjunction with a protruding tandem preferably, or Manchester ovoid in the case of absence of the lower segment of the uterus. The authors have noted a remarkable improvement in local control as well as an improved three-year survival rate with minimal immediate complications. Additional Stage IIIB (FIGO) cases were collected and they were treated by the same technique and have a close follow-up since 1975. Forty-nine cases studied, 32 (65%) survived with disease-free status for a minimum of five years with no loss to follow-up. Local control was excellent, as expected, at the level of 84% (41/49). There were 8% major complications as a consequence of radiation treatment and the majority of them required surgical intervention with excellent success. Paraaortic metastasis remains a major problem and requires further study. The current plan will include retroperitoneal exploratory laparotomy and para-aortic node sampling with extension of the external beam portals to include the positive node region and followed by interstitial and intracavitary brachytherapy.