Inflammatory breast cancer: integration of irradiation, surgery, and chemotherapy.

Between January 1983 and April 1987, 36 consecutive patients with nonmetastatic clinical (30 patients) or occult (6 patients) inflammatory breast cancer were treated with irradiation, mastectomy, and chemotherapy. In 29 patients, treatment consisted of preoperative once daily (16 patients) or twice daily (13 patients) irradiation with concurrent chemotherapy. In 27 (93%) of these 29 patients, this treatment was followed by mastectomy and additional chemotherapy. In 25 (86%) of these patients, major clinical response was attained, but an examination of the pathology of the operative specimen revealed complete tumor absence in only two patients (7%). The remaining seven patients underwent immediate mastectomy followed by once daily irradiation and chemotherapy. With a median follow-up of 30.4 months in all patients (59.2 months in surviving patients), the 5-year probability of relapse-free survival was 24% and of overall survival, 34%. Overall, the probability at 5 years of initial isolated local-regional tumor recurrence was 19%; in patients treated with once daily irradiation, the 5-year probability was 28%, whereas the probability was 8% with twice daily (accelerated) fractionated irradiation. Chemotherapy dose intensity did not appear to be adversely affected by the use of irradiation. The treatment approach described herein provides results comparable with those in other contemporary American series.

Resection for solitary brain metastasis. Role of adjuvant radiation and prognostic variables in 229 patients.

The authors reviewed 229 consecutive patients treated intramurally by resection of solitary cerebral metastasis. Patients were classified into four groups on the basis of whether a gross total resection or subtotal resection was performed and whether systemic disease was present or absent at the time of craniotomy. Group 1 had gross total resection and no systemic disease; Group 2 had subtotal resection and no systemic disease; Group 3 had subtotal resection and systemic disease; and Group 4 had gross total resection and systemic disease. All four groups were further subdivided into Subgroup A (adjuvant whole-brain radiation therapy) or Subgroup B (no adjuvant radiation). Data were collected regarding multiple patient and tumor variables for multivariate analysis. Survival data for the 46 patients in Group 1A (median 1.3 years, 2-year survival rate 41%, 5-year survival rate 21%) were markedly better than those for the 75 in Group 1B (median 0.7 year, 2-year survival rate 19%, 5-year survival rate 4%). The 20 patients in Group 2A also had superior survival data (median 1.1 years, 2-year survival rate 30%, 3-year survival rate 30%) when compared with the eight patients in Group 2B (median 3 months, 1-year survival rate 0%). However, the 16 and 22 patients in Groups 3A and 4A, respectively, had no discernible differences compared to the seven and 35 patients in their Group 3B and 4B counterparts. Multivariate analyses were performed to assess the association of survival with multiple patient, disease, and treatment variables. Poor neurological status and systemic disease were significantly associated with inferior survival, while longer (greater than 36 months) intervals between primary diagnosis and craniotomy were significantly associated with improved survival. After adjusting for the effects of other patient, disease, and treatment characteristics, adjuvant whole-brain radiotherapy was significantly associated with improved survival times. These data support the continued use of craniotomy followed by adjuvant whole-brain radiation therapy for treatment of solitary brain metastasis. However, this aggressive therapy appears relatively contraindicated in the face of either systemic disease or substantial neurological deficit.

Humoral hypercalcemia associated with a dysgerminoma.

A 16-year-old girl sought medical attention at the Mayo Clinic because of a 4.5-kg weight loss, hypercalcemia, and a pelvic mass. Preoperatively, the level of the beta-subunit of human chorionic gonadotropin was 147 IU/liter. After a brief period for observation and hydration, abdominal exploration revealed a stage III dysgerminoma; total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Within the dysgerminoma, syncytial giant cells expressed human chorionic gonadotropin-positive immunostaining in the cytoplasm. Postoperatively, the value of the beta-subunit of human chorionic gonadotropin decreased rapidly. The patient received whole-abdomen irradiation 4 weeks postoperatively, after which the level of calcium returned to normal. The patient has been free of disease for more than 7 years.

Soft tissue sarcoma. Integration of brachytherapy, resection, and external irradiation.

Between December 1981 and August 1988, 63 patients with clinically localized nonretroperitoneal soft tissue sarcomas underwent 65 brachytherapy procedures in conjunction with conservative resection with (61 tumors) or without (four tumors) external beam irradiation. Implant doses of 1500 to 2000 cGy were combined with 4500 to 5000 cGy of external irradiation. External irradiation was given preoperatively for larger lesions near bone or neurovascular structures, whereas it was used postoperatively for smaller, more resectable lesions or those that had previously been inadequately excised. There were 47 high-grade tumors, 34 tumors greater than 5 cm, and nine patients with recurrent lesions (five with previous irradiation). With mean follow-up of 20 months, conclusions on local control are tentative, but only two of 56 tumors (4%) with brachytherapy as part of initial management had recurred locally and three of nine recurrent tumors had re-recurred locally. Only one of five local recurrences was within the implanted volume. Only two of 40 implantations (5%) performed at initial resection followed by postoperative external irradiation led to wound complications, whereas four of 16 implantations (25%) performed at resection after preoperative external irradiation were associated with wound problems. This technique does not increase local morbidity and may enhance local tumor control in comparison with either external radiation or brachytherapy alone as an adjuvant to conservative resection.

Chylous ascites after whole-abdomen irradiation for gynecologic malignancy.

From November 1981 through December 1987, 207 patients received whole-abdomen irradiation (WAI) for gynecologic malignancies at the Mayo Clinic. In seven (3%) of these patients, chylous ascites subsequently developed; one additional patient with chylous ascites after WAI for a gynecologic malignancy was referred to us from another institution. In these eight patients, irradiation was done either adjuvantly (five patients) or as salvage therapy after chemotherapy failure (three patients). Chylous ascites was confirmed by laboratory analysis in six cases and was presumed based on the clinical course in two cases. Mean cumulative radiation doses were 2,925 and 5,122 cGy to the abdomen and pelvis, respectively, with para-aortic boosts administered in six cases to a mean cumulative dose of approximately 4,200 cGy. The mean time from completion of WAI to development of ascites was 12 months (range, 6 to 18 months). In six patients, therapy was conservative-observation and diuretics. Two other patients required multiple paracenteses for relief of abdominal distention. Parenteral nutrition was given to two patients who had associated radiation enteritis. The ascites resolved in all eight cases at a mean of 18 months (range, 8 to 30 months) after development. At a mean follow-up of 57 months after initial diagnosis and 16 months after resolution of the ascites, seven patients are without evidence of disease and one patient died of recurrent carcinoma. Distinguishing this clinical entity from recurrent carcinoma is important because of its benign course and its resolution with conservative management.

A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia.

Anorexia, cachexia, and resultant weight loss are major clinical problems in a substantial proportion of patients with advanced cancer. Effective means of alleviating these problematic symptoms are lacking. Extensive clinical data demonstrate a weight enhancing effect for the serotonin antagonist, cyproheptadine, in several clinical situations. In addition, sound basic research suggests that cyproheptadine may be helpful in patients with cancer anorexia/cachexia. Because of this, the authors performed a randomized, placebo-controlled, double-blinded clinical trial using cyproheptadine, 8 mg orally three times a day in 295 patients with advanced malignant disease. Patients assigned to cyproheptadine had less nausea (P = 0.02), less emesis (P = 0.11), more sedation (P = 0.07), and more dizziness (P = 0.01) than placebo patients. Patients' appetites, measured by serial patient-completed questionnaires, appeared to be mildly enhanced by cyproheptadine. Unfortunately, cyproheptadine did not significantly abate progressive weight loss in these patients with advanced malignant disease; patients assigned to cyproheptadine lost an average of 4.5 pounds per month compared to 4.9 pounds per month for patients assigned to a placebo (P = 0.72).

Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix.

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P less than 0.0001), and number of nodal metastases (P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter less than 1 cm) and no more than two nodes with metastases fell into the low-risk category; those patients with large cervical lesions (diameter greater than 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.

Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early-stage squamous carcinoma of the cervix with pelvic nodal metastasis: a matched-control study.

In a retrospective study, 185 patients with previously untreated stage IB or IIA (International Federation of Gynecology and Obstetrics) squamous cell carcinoma of the cervix were found to have pelvic nodal metastasis at the time of Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Of these patients, 103 received adjuvant whole-pelvis irradiation and 82 received no adjuvant therapy. Median dose of pelvic irradiation was 5000 cGy. Among the irradiated patients, in 75% the dose was 5000 cGy or greater. Matching irradiated and nonirradiated patients according to stage, tumor size, and number and location of positive nodes yielded 60 pairs. Mean length of follow-up was 3.9 years for the 60 irradiated patients and 5.8 years for the non-irradiated patients. Kaplan-Meier overall and cancer-specific survival estimates for the two groups were not significantly different (P greater than 0.30). During the follow-up period, 21 surgery-only patients and 22 patients treated with adjuvant radiotherapy had recurrence, but adjuvant radiotherapy decreased the proportion of recurrences occurring in the pelvis alone--27% compared with 67% in the surgery-only group (P = 0.01).

Chondrosarcoma of the spine.

Twenty patients were diagnosed as having chondrosarcoma of bone that originated in the spine and, except for one, were treated surgically at the Mayo Clinic. The patients' ages ranged from eighteen to seventy years. Pain in the area of involvement was the first symptom in nearly all patients. Nearly one-half of the patients had detected a mass before being diagnosed. In addition, nine patients had neurological symptoms and signs when they were first seen. All patients had a surgical biopsy of the lesion, often combined with decompressive laminectomy. Five patients received postoperative radiation therapy in various dosages. No patient received adjunctive chemotherapy. All but five patients died of local progression of the disease. The five-year survival rate was 55 per cent. The median length of survival was six years. Although it is rare, chondrosarcoma of the spine can usually be identified on radiographs. Preoperative assessment must include computed tomography, magnetic resonance imaging, and, possibly, arteriography to assess the precise extent of the disease. Although surgical ablation often is technically difficult, a wide excision should be attempted. If this is not obtainable, postoperative radiation therapy should be considered.

Toxicity of open-field whole abdominal irradiation as primary postoperative treatment in gynecologic malignancy.

Between June 1979 and March 1985, 77 patients received whole abdominal radiation as the sole postoperative treatment for gynecologic malignancy. With an open-field technique of irradiation, a median of 3,000 cGy was delivered to the entire abdominal contents with partial liver and kidney shielding; the total dose to the pelvis after boosts was 5,100 cGy, and that to the sub-diaphragmatic and para-aortic nodal regions was 4,200 cGy. The primary sites of malignancy were the endometrium in 41 patients, ovary in 25, uterus in 5, fallopian tube in 4, and cervix in 2. Seven patients (9%), all older than 60 years, experienced acute gastrointestinal toxicity that interrupted treatment, only one of whom failed to complete the prescribed course as a result. Hematologic toxicity was sufficient to interrupt therapy in 21 patients (27%), 1 of whom failed to complete therapy as a result. Hematologic toxicity was not increased in elderly patients. All patients were followed up for a minimum of 30 months (median, 43 months) or until death. Six patients experienced a treatment-related bowel obstruction (two of whom had concomitant progressive intra-abdominal disease); the 3-year actuarial risk for a treatment-related bowel obstruction was 9%. This risk was significantly increased by high-dose boosting for residual disease. Only one instance of clinical radiation pneumonitis occurred, and no cases of clinical hepatitis were noted; however, subclinical evidence of pulmonary and hepatic radiation effect was frequent. Whole abdominal irradiation as described has modest toxicity for patients with gynecologic cancer who are at high risk for intra-abdominal failure.

Solitary plasmacytoma of bone: Mayo Clinic experience.

A review of 46 cases of solitary plasmacytoma of bone was undertaken in an attempt to better define the clinical features and prognostic indicators associated with this disease. Criteria for inclusion in the study included the following: (a) solitary lytic bone lesion on skeletal survey; (b) histologic confirmation of the lesion; and (c) bone marrow plasmacytosis of less than 10 percent. Patients with extramedullary plasmacytomas and osteosclerotic lesions were excluded. All patients were evaluated with serum and urine protein studies at the time of diagnosis. The median follow-up was 90 months with a minimum of 30 months. Fifty-four percent of the lesions involved the vertebral column. The thoracic spine was the single most commonly involved site (13/46 patients). The initial lesion was treated with radiotherapy in all but three patients in whom complete surgical resection was achieved. Total doses ranged from less than 20 Gy to 70 Gy with a median of 39.75 Gy. Overall, 54% developed multiple myeloma, 2% failed with new bone lesions without multiple myeloma, and 11% developed local recurrences. No patient receiving 45 Gy or more to the solitary lesion had a local failure. While the median time to progression was 18 months, 23% of the failures occurred after 60 months. The five local failures occurred at 7, 12, 18, 40, and 114 months. The overall survival was 74% at 5 years and 45% at 10 years. The 5- and 10-year disease-free survivals, however, were 43 and 25%, respectively. Evidence of abnormal serum and/or urine protein was found in 25 of 46 patients. Neither survival nor disease-free survival was significantly influenced by the presence of abnormal proteins even if they persisted after irradiation.

Advanced epithelial ovarian cancer: salvage whole abdominal irradiation for patients with recurrent or persistent disease after combination chemotherapy.

Between 1979 and 1984, 53 patients received whole abdominal irradiation in a curative salvage effort for residual (32 patients) or recurrent (21 patients) epithelial ovarian cancer after combination chemotherapy (cisplatin-based in 48 patients). Residual cancer less than or equal to 2 cm in diameter was confirmed at operation in all patients before irradiation consisting of 2,550 to 3,000 rad to the whole abdomen with partial liver/kidney shielding and boosting of the dose to the diaphragmatic/paraaortic nodal regions and pelvis to approximately 4,000 and 5,000 rad, respectively. Twelve patients (23%) did not complete therapy as a result of hematologic intolerance. Actuarial overall and disease-free survival at 3 years are 35% and 30%, respectively, with follow-up for disease-free patients ranging from 30 to 79 months (median, 43 months). Twenty-seven of 36 relapses (75%) occurred within the irradiated abdomen alone. At 3 years, 70% of patients with well- or moderately-differentiated tumors were disease-free v 10% of those with poorly differentiated tumors (P less than .001). Among prognostic factors evaluated, including grade, initial residual disease before chemotherapy, residual disease at time of irradiation, age, chemotherapy response v progression, and completion of irradiation, only grade and initial residual disease before chemotherapy were statistically significant in multivariate analysis (both P less than .01). Patients with the combination of high-grade tumor, initial residual disease greater than 2 cm before chemotherapy, and macroscopic disease after "second-look" laparotomy do not benefit from irradiation. Eleven patients (21%) developed an apparent treatment-related bowel obstruction after completion of irradiation. Selected subsets of patients do well; however, the role of irradiation in this setting can be confirmed only with randomized clinical study.

Evaluation of treatment and survival after positive second-look laparotomy.

During the 9-year interval 1977 through 1985, of 250 patients undergoing second-look laparotomy, 116 (46%) were found to have clinically occult ovarian carcinoma. Salvage therapy consisted of external irradiation in 37, intraperitoneal 32P in 12, chemotherapy in 63, and no therapy in 3 or other therapy in 1. Eligible follow-up time ranged from 1 to 9 years. The Kaplan-Meier projected median time-to-progression and survival were 15 and 22.5 months, respectively, with 4-year progression-free and overall survival rates being 21 and 27%, respectively. Survival was independent of the original stage of disease but was significantly influenced by histologic grade and microscopic (55%) versus macroscopic (19%) residual tumor after the laparotomy. Projected 4-year salvage rates in patients with microscopic or residual disease less than or equal to 5 mm was 72, 39, and 19% for intraperitoneal 32P, external irradiation (33/37, whole abdominopelvic), and chemotherapy, respectively. However, multivariable analysis demonstrated that histologic grade and isotope therapy retained independent influence on survival, but no therapeutic advantage for external irradiation over chemotherapy was demonstrable. Furthermore, use of regimens that were identical to, partially altered from, or different from the first-trial agents did not affect chemotherapy salvage rates.

Isolated peripheral lymph node recurrence of endometrial carcinoma.

The natural history of endometrial carcinoma recurring first in an inguinal, axillary, or supraclavicular node as an isolated site is not well documented. Twenty-two patients with such a recurrence were examined between January 1963 and December 1986 at our institution. This event is associated with a higher initial surgical stage and tumor grade. Supraclavicular and inguinal recurrences occur with equal frequency. Axillary recurrences are rare. Overall, 15 patients achieved local control of the nodal recurrence, including all seven patients treated by excision and aggressive local irradiation. Of the seven patients with uncontrolled local disease, four experienced significant local morbidity. Initial supraclavicular recurrence seems to be associated with subsequent systemic progression, whereas initial inguinal recurrence seems to be associated with subsequent abdominal progression. Although the median survival after isolated peripheral lymph node recurrence is only 19 months, six patients are alive without evidence of cancer at a median follow-up of 27 months. Although an effective systemic adjuvant treatment for these patients is needed, aggressive local treatment after thorough restaging can provide long-term, disease-free survival.

Management of malignant airway compromise with laser and low dose rate brachytherapy. The Mayo Clinic experience.

Between January 1983 and October 1985, 65 patients with malignant airway compromise have had 93 flexible bronchoscopic placements of a nylon afterloading catheter for low dose rate iridium-192 temporary intraluminal brachytherapy. All patients received prior (59 patients) and/or concurrent (13 patients) external beam irradiation to "tolerance" and were not candidates for surgery. Forty of these patients also received neodymium-YAG laser treatment prior to brachytherapy in a planned combined approach to provide immediate symptomatic relief and facilitate catheter placement. A dose of 3,000 cGy is prescribed to 5 mm and 10 mm radii over 20-40 hours in the bronchus and trachea, respectively. Of 59 patients treated with palliative intent, 40 patients (68 percent) have had follow-up bronchoscopy, 18 patients have had clinical follow-up only, and one patient was lost to follow-up. Of 40 patients examined by bronchoscope in follow-up, 24 (60 percent) responded, eight were stable, and eight progressed. Lack of progression after prior external beam radiation for periods of greater than 12 months, six-12 months and less than six months yielded response rates to brachytherapy in 83 percent, 50 percent and 31 percent, respectively. Most patients with clinical follow-up only expired at early intervals with airway palliation from extra-airway disease progression. Four of five patients treated with curative intent are disease-free at a median of 16 months. Eleven patients have experienced fistula and/or hemorrhage, of which seven instances (11 percent of all patients) appear to be treatment-induced. This brachytherapy technique is simple, well tolerated, and convenient for the patient providing airway palliation in the significant majority of patients with acceptable risk.

Soft-tissue sarcoma: Mayo Clinic experience.

Soft-tissue tumors encompass a wide variety of lesions and continue to pose a difficult treatment problem. The outlook, however, is improving, and there have been recent advances in pretreatment assessment, clinicopathologic correlation, and adjuvant treatment programs. We retrospectively reviewed our experience in a large series of soft-tissue tumors treated at the Mayo Clinic as well as recent experience using chemotherapy and radiation treatment.

Ovarian dysgerminoma: a retrospective analysis of results of treatment, sites of treatment failure, and radiosensitivity.

Thirty-five patients with a diagnosis of pure ovarian dysgerminoma underwent assessment at our institution between 1950 and 1984. The median age of these patients was 21 years (range, 8 to 41 years). The surgical pathologic stages of the tumors were as follows: stage IA1 in 18 patients, stage IA2 in 2, stage IB1 in 2, stage IC in 1, stage IIB in 2, stage III in 9, and stage IV in 1. The overall survival at 5, 10, and 20 years was 94.3%, 82.9%, and 82.9%, respectively, for all 35 patients and 100%, 83.9%, and 83.9%, respectively, for the 18 patients with stage IA1 lesions. The maximum interval from diagnosis to relapse was 3.7 years. All patients were under surveillance for a minimum of 2 years (median follow-up, 15.9 years). Of the 18 patients with stage IA1 disease, 16 did not receive prophylactic radiation therapy to the para-aortic lymph nodes, and in 6 of the 16 (38%) recurrent disease developed in this region. Five of these patients were salvaged with radiation therapy and one with radiation therapy and subsequent chemotherapy. No definite correlation was noted between the size or mass of the resected unilateral encapsulated tumor and the risk of development of recurrent disease. For patients with stage IA1 dysgerminoma who have undergone unilateral oophorectomy, two treatment options seem reasonable: (1) observation, with radiation therapy reserved for subsequent recurrence, or (2) prophylactic radiation therapy (2,000 cGy) to para-aortic and ipsilateral common iliac lymph nodes, which would preserve fertility.

Fallopian tube cancer: the role of radiation therapy.

Thirty-four patients with fallopian tube cancer were evaluated at the Mayo Clinic between 1964 and 1985 and received radiation therapy postoperatively. Employing a system analogous to FIGO ovarian cancer staging, there were 9 patients with stage I disease, 13 with stage II, and 12 with stage III/IV. Residual disease was present in 15 patients and absent in 19. Nodal metastases were documented in 12 patients or 35% (10 at presentation, two at relapse), with para-aortic nodes most commonly involved (67%) and 7 of the 12 having disease otherwise limited to the pelvis at presentation. Fifteen of 34 (44%) patients survived disease-free until intercurrent death or to a median follow-up of 70 months. Seven patients were treated with palliative intent for massive disease, and 27 patients were treated with curative intent (21 radiation alone, six radiation plus chemotherapy). Of those treated with curative intent, 15 patients received pelvic irradiation (with or without para-aortic nodal irradiation), 10 received whole abdominal irradiation, and 2 received intraperitoneal radiophosphorus. In the potentially curative group, seven of nine (78%) patients with stage I disease, five of 12 (42%) with stage II, and 2 of 6 (33%) with stage III have remained disease-free. Among the 21 patients with stage I or II disease, only four of the 11 (36%) patients who received pelvic irradiation alone were disease-free, but four patients had an isolated upper abdominal failure. In contrast, eight of 10 (80%) patients receiving treatment to the entire abdomen (including two patients who received 32P) were disease-free.(ABSTRACT TRUNCATED AT 250 WORDS)